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39057685_p6
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|
2.1. Ethics Statement
| 2.123047 |
biomedical
|
Study
|
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Twenty Yangzhou geese raised at the Liuhe experimental farm were used in this study. The animals were allowed access to feed and water ad libitum under normal conditions and were executed by jugular vein bleeding to minimize suffering. The experimental procedures were approved by the Research Committee of Jiangsu Academy of Agricultural Sciences and conducted with adherence to the Regulations for the Administration of Affairs Concerning Experimental Animals .
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p7
|
39057685
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sec[1]/sec[1]/p[0]
|
2.2. Animals and Treatments
| 4.023438 |
biomedical
|
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Yangzhou geese of about 360 days (bodyweight 7.5–8 kg) at peak laying period were raised under natural photoperiod to eat and drink ad libitum. The behavior of laying is monitored by computer video. Twenty geese were exposed to LPS from E. coli 055: B5 (Sigma, Shanghai, China) for 0 h, 24 h, and 36 h by wing intravenous injection: ten animals in the control group and five animals in each of the treatment groups. Based on preliminary laboratory studies and pre-experiments , the LPS treatment concentration was determined to be 1.5 mg/kg BW. The egg-laying time of each goose was recorded, and LPS was treated at −28 h, −16 h, and 8 h relative to egg-laying time to ensure that LPS was applied to the ovulation period. Geese were slaughtered and sampled promptly 8 h after laying.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p8
|
39057685
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sec[1]/sec[2]/p[0]
|
2.3. Sample Collection and RNA Isolation
| 4.089844 |
biomedical
|
Study
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Before slaughter, blood samples (2 mL) were collected by wing vein puncture. The serum was separated by centrifugation at 4 °C and stored at −20 °C until assay. The preovulatory follicles of the hierarchy are identified according to size, with the F1 follicle being the largest follicle and the next follicle to ovulate, followed by the F2 follicle, the second-largest follicle, etc. The granulosa layer of the hierarchical follicles (F1–F5) was isolated and snap-frozen in liquid nitrogen. Both the GCs of hierarchical follicles of normal appearance and the GCs of the denatured hierarchical follicles were collected and snap-frozen in liquid nitrogen, then stored at −80 °C for further experiments. TRIzol reagent was used to extract total RNA from follicles tissues and GCs, according to the manufacturer’s instructions.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057685_p9
|
39057685
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sec[1]/sec[3]/p[0]
|
2.4. miRNA and mRNA Sequencing
| 4.226563 |
biomedical
|
Study
|
[
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cDNA libraries were constructed using the NEB Next Ultra-small RNA Sample Library Prep Kit for Illumina (New England Biolabs, Ipswich, MA, USA). The concentration of RNA samples was accurately quantified by Qubit 2.0, the purity of RNA samples was checked by Nanodrop (Thermo Fisher, Waltham, MA, USA), and RNA sequencing of mRNA and miRNA was performed by Illumina HiSeq X Ten (Illumina, San Diego, CA, USA). The reference genome sequence was Goose V1.0 . Differential expression analysis was performed using the edgeR R package. EdgeR (v3.8.6) provides statistical routines for determining differential expression in digital miRNA expression data using a model based on the negative binomial distribution. miRNA with a p < 0.01 found by DESeq (v1.18.0) were assigned as differentially expressed. The target genes of miRNAs were filtered using miRanda (v3.3a) with the parameters Score ≥ 140, Energy ≤ −1.0. The expression of miRNA was counted and normalized using the TPM method. T P M = R e a d c o u n t ∗ 1,000,000 M a p p e d R e a d s
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p10
|
39057685
|
sec[1]/sec[4]/p[0]
|
2.5. Cell Culture and Transfection
| 4.144531 |
biomedical
|
Study
|
[
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Goose hierarchical follicle granulosa cells were used in this experiment. After the ovaries were taken out, the F1–F5 follicles were separated and placed in 4 °C saline, the vascular and basement membrane layers were stripped, the follicles were cut open so that the yolk was released into saline, and the white translucent granular layer floating on the yolk was carefully stripped. Cells were cultured in a humidified atmosphere containing 5% CO 2 and 95% air at 37 °C in complete medium consisting of 89% M199 cell culture medium, 10% fetal bovine serum, and 1% penicillin-streptomycin. Primary GCs (4 × 10 5 cells/well in 1 mL of medium) were cultured in 12-well plates. When the cell density reached 70%, GCs were treated with LPS (1 μg/mL) for 12 h. Cells were collected by TRIzol, and the concentration of P4 was detected using an ELISA kit. To further explore the mechanism of miR-21-involved LPS-induced P4 secretion decrease, transfection experiments were performed in GCs.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057685_p11
|
39057685
|
sec[1]/sec[4]/p[1]
|
2.5. Cell Culture and Transfection
| 3.990234 |
biomedical
|
Study
|
[
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The RNA oligonucleotides were designed according to the sequences of miR-21 . Among them, miR-21 inhibitor, miR-21 mimics, siSMAD2, and Negative Control were constructed by GenePharma (Shanghai, China). Cells were transfected with 50 nM of miR-21 inhibitor, miR-21 mimics, and siRNA targeting goose SMAD2 using Lipofectamine 3000 (Invitrogen, Shanghai, China). The non-targeting pool Negative Control was used as transfection control.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057685_p12
|
39057685
|
sec[1]/sec[5]/p[0]
|
2.6. Quantitative Real-Time PCR
| 3.806641 |
biomedical
|
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After treatments, total RNA was extracted. The mRNA was reverse-transcribed using Prime Script RT Master Mix Perfect Real Time, whereas miRNA was reverse-transcribed using the one-step miRNA cDNA synthesis kit. The real-time qPCR was performed in triplicate per sample.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057685_p13
|
39057685
|
sec[1]/sec[5]/p[1]
|
2.6. Quantitative Real-Time PCR
| 4.078125 |
biomedical
|
Study
|
[
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] |
[
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] |
qRT-PCR was performed on an ABI 7500 system (Applied Biosystems, Shanghai, China) using FastStARt Universal SYBR Green Master Mix. The β-actin gene was used as the reference gene; all qRT-PCR gene-specific primers were designed using Oligo 7.0. The primer sequences are presented in Table S1 . Relative gene expression levels were calculated using the 2 −∆∆CT method with a significance level of p ≤ 0.05.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p14
|
39057685
|
sec[1]/sec[6]/p[0]
|
2.7. ELISA
| 4.085938 |
biomedical
|
Study
|
[
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Following the treatments, the cell culture medium was immediately assayed for P4 levels using a competitive enzyme immunoassay kit (Beijing North Institute of Biological Technology, Beijing, China) according to the manufacturer’s instructions. After treatment, culture medium was collected for P4 ELISA analysis, and the cells were collected for DNA extraction. The final P4 levels were analyzed using the following equation, as described by Silva et al. : P4 levels ng/mL/ng DNA = P4 concentration in culture medium/total amount of DNA. Each sample was measured three times, and three separate experiments were conducted.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p15
|
39057685
|
sec[1]/sec[7]/p[0]
|
2.8. Statistical Analysis
| 3.892578 |
biomedical
|
Study
|
[
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[
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Statistical analyses were performed using the IBM SPSS Statistics program (version 26). Normality of the data was tested using the Shapiro–Wilk normality test. Nonparametric data with multiple comparisons were analyzed by Kruskal–Wallis test (including Dunn–Bonferroni post hoc correction). The Mann–Whitney U test was used for comparison between two groups. Data with normal distribution were analyzed by one-way ANOVA with Tukey’s correction for multiple comparisons, and the Student t test was used for comparison between two groups. Values are presented as the Mean ± Standard Error of the Mean (Mean ± SEM). All tests were two-sided, and data were considered statistically significant if p values ≤ 0.05. Graphs were prepared in GraphPad Prism (version 8.2.1). *, p < 0.05; **, p < 0.01. Ns, not significant.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057685_p16
|
39057685
|
sec[2]/sec[0]/p[0]
|
3.1. Morphological Observation and Reproductive Hormone Levels
| 4.179688 |
biomedical
|
Study
|
[
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Ovarian morphology was observed and photographed, and it was found that follicles at different stages of development were present in the ovaries of geese; the morphology of hierarchical follicles changed considerably with increasing LPS treatment time. No significant changes in the morphology of the hierarchical follicles were observed after LPS treatment for 0 h. After LPS treatment for 24 h, the hierarchical follicles in some geese (3/5) became deep yellow in appearance and irregular ellipses or were round. After LPS treatment for 36 h, the hierarchical follicles of all geese (5/5) turned dark yellow and were irregularly elliptical in appearance, and the yolk became gelatinous . This resulted in difficulty in separating the follicular membrane layer from the granular layer. Interestingly, there was no significant change in the appearance of pre-hierarchical follicles during this process, indicating that the response of hierarchical follicles to LPS stimulation was much higher than that of pre-hierarchical follicles. In addition, serum P4 concentrations were significantly higher in geese with normal follicular appearance than in geese with degenerated follicles and negatively correlated with the time of LPS treatment .
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p17
|
39057685
|
sec[2]/sec[0]/p[1]
|
3.1. Morphological Observation and Reproductive Hormone Levels
| 3.53125 |
biomedical
|
Study
|
[
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[
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] |
Based on the above findings, the GCs of normal appearance (LPS treatment for 0 h, HF) and the GCs of the denatured hierarchical follicles (LPS treatment for 36 h, DF) were collected for miRNA sequencing with three biological replicates per group.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057685_p18
|
39057685
|
sec[2]/sec[1]/p[0]
|
3.2. miRNA RNA-Seq Profiling
| 4.183594 |
biomedical
|
Study
|
[
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] |
All the miRNA sequencing data are deposited in the SRA database with the accession number PRJNA 916249. Small RNA sequencing yielded between 17 M and 30 M raw reads in the six samples. The sequencing quality values Q30 were all greater than 98%. After the low-quality reads with connectors were removed, the clean reads obtained were greater than 79% (s). Most of the clean reads were between 21 and 23 nt in length, and read counts with 22 nt were the most abundant. Of note, 834 known miRNAs were obtained by comparison, and 1016 unknown miRNAs were discovered. Based on the Transcripts Per Kilobase of exon model per Million mapped reads (TPM), miRNA expression levels were divided into different intervals. Most miRNAs were distributed between 1 and 10 TPM, and only a few miRNAs were of high abundance . In general, the number of miRNAs was negatively correlated with the value of TPM, indicating that that only a few miRNAs could affect follicular P4 secretion. Analysis of the transcriptome sequencing quality data from the control group (HF) and LPS-treated group (DF) revealed that the Q30 of each group of samples was higher than 98.56% ( Table S2 ).
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p19
|
39057685
|
sec[2]/sec[2]/p[0]
|
3.3. Differentially Expressed miRNAs between HF and DF
| 4.164063 |
biomedical
|
Study
|
[
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A total of 51 differentially expressed miRNAs (DEMs) were identified among the known miRNAs, of which 31 miRNAs were highly expressed in the healthy follicles compared to the atretic follicles, whereas the other 20 miRNAs were down-regulated in the healthy follicles compared to the atretic follicles . Cluster analysis showed that miRNA expression patterns were different in HFs and DFs . To better understand the biological functions of the 51 DEMs identified, the potential target genes of miRNAs were predicted. This returned 3782 terms related to target genes, including 2444 unique genes. Subsequent miRNA-targeted pathway union analysis revealed 60 KEGG pathways significantly ( p < 0.05) related to genes targeted by up-regulated or down-regulated miRNAs. Several pathways were involved in follicle and corpus luteum development, including the PI3K-Akt signaling pathway, steroid biosynthesis, apoptosis, and the Hippo signaling pathway .
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p20
|
39057685
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sec[2]/sec[2]/p[1]
|
3.3. Differentially Expressed miRNAs between HF and DF
| 3.541016 |
biomedical
|
Study
|
[
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The results of GO enrichment analysis showed that the enrichment of DEM target genes in biological process mainly involves cellular processes, developmental processes, reproductive process, and reproduction .
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057685_p21
|
39057685
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sec[2]/sec[3]/p[0]
|
3.4. Functional Analysis of DEMs
| 4.15625 |
biomedical
|
Study
|
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] |
To investigate the mechanism of miRNA involvement of LPS on P4 secretion in GCs, ten highly expressed DEMs were selected as candidate genes for biological function validation ( Table 1 ). Target gene prediction was performed using the bioinformatics prediction software miRDB and miRanda ( Table S3 ). In addition, mRNA transcriptome sequencing was performed, and the target genes were predicted. The miRNA–mRNA interaction networks were constructed to identify their specific biological functions . The findings indicated that miR-21 initial sequences is a widely conserved aspect in human, mouse, rat, chicken, and pig , and miR-21 has a 7mer-m8 conserved binding site with goose SMAD2 . miRNA and mRNA sequencing results showed that miR-21 expression was higher in HF than DF, while the target genes SMAD2 showed a contrasting trend with higher miR-21 expression. This result is consistent with the expression pattern of miRNAs. Combined with KEGG in Figure 2 D, the steroid hormone synthesis-related pathway was enriched. Therefore, miR-21 was selected for functional validation.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
39057685_p22
|
39057685
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sec[2]/sec[4]/p[0]
|
3.5. LPS Up-Regulated miR-21 Expression and P4 Synthesis in GCs
| 4.136719 |
biomedical
|
Study
|
[
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In animal experiments, the expression of P4-related genes in ovarian function were determined. The experimental results showed that LPS significantly down-regulated the expression of SMAD2 and P4 production-related genes STAR, CYP11A1, and HSD3B1 . Next, primary GCs were treated with 1 μg/mL of LPS, and gene expression was reduced after 12 h of LPS treatment, showing the same results as in vitro experiments . Accordingly, the secretion of P4 was significantly decreased after LPS treatment, and the concentration of P4 in the supernatant of the cell culture medium was significantly decreased by ELISA . Meanwhile, LPS significantly increased the expression of miR-21 in vitro, further confirming the sequencing results .
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057685_p23
|
39057685
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sec[2]/sec[5]/p[0]
|
3.6. miR-21 Was Involved in LPS Regulation of P4 Synthesis in GCs
| 4.167969 |
biomedical
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Study
|
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0.00007069110870361328
] |
To further confirm the involvement of miR-21 in LPS-induced down-regulation of P4 production, a transfection was performed to suppress and overexpress miR-21. In general, the negative control (NC) had no effect on miR-21 expression, whereas there was significant inhibition and overexpression of miR-21 . Transfected GCs with 50 nM of miR-21 inhibitor significantly up-regulated SMAD2 mRNA levels, and transfected GCs with 50 nM of miR-21 mimics significantly down-regulated SMAD2 mRNA levels . Overexpression of miR-21 inhibited SMAD2 expression in LPS-treated GCs; inhibition of miR-21 effectively antagonized LPS treatment and restored SMAD2 to normal expression. Subsequently, the expression of steroid hormone production pathways STAR, CYP11A1, and HSD3B1 was examined. The expression of miR-21 was negatively correlated with STAR and CYP11A1 mRNA levels, but the expression of HSD3B1 was not affected . The P4 concentration was significantly increased after the use of miR-21 inhibitor, while overexpression of miR-21 showed the opposite effect .
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057685_p24
|
39057685
|
sec[2]/sec[6]/p[0]
|
3.7. miR-21 Was Involved in LPS Regulation of P4 Synthesis in GCs by Down-Regulating SMAD2
| 4.121094 |
biomedical
|
Study
|
[
0.99951171875,
0.0002448558807373047,
0.0002429485321044922
] |
[
0.99951171875,
0.00018405914306640625,
0.000232696533203125,
0.00005549192428588867
] |
Given the important role of STAR in the regulation of P4 production, the effect of SMAD2 on P4 production in GCs was next examined. A siRNA-mediated knockdown approach was used to knock down the endogenous expression of SMAD2. To figure out the role of SMAD2 in regulating P4 synthesis, siRNAs of SMAD2 were transfected into GCs. siSMAD2-3 was selected as the siRNA for this experiment by verifying the transfection efficiency of different siRNAs as the highest silencing efficiency siRNA . Silencing of SMAD2 had a significant effect on STAR and CYP11A1, but the expression of HSD3B1 was not affected . In LPS-treated GCs, HSD3B1 was decreased by LPS, and silencing SMAD2 did not affect HSD3B1 expression . The P4 concentration was detected by ELISA, and there was no significant decrease in P4 concentration after silencing SMAD2 under LPS treatment .
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057685_p25
|
39057685
|
sec[2]/sec[6]/p[1]
|
3.7. miR-21 Was Involved in LPS Regulation of P4 Synthesis in GCs by Down-Regulating SMAD2
| 4.183594 |
biomedical
|
Study
|
[
0.99951171875,
0.0002605915069580078,
0.0002281665802001953
] |
[
0.99951171875,
0.00019824504852294922,
0.0003466606140136719,
0.00006300210952758789
] |
GCs were treated for 12 h with 1 μg/mL of LPS after 36 h of transfection with miR-21 mimics (50 nM), miR-21 inhibitors (50 nM), and siSMAD2 (50 nM). After transfection with miR-21 inhibitor and siSMAD2, the expression level of miR-21 was not further decreased, while SMAD2 mRNA levels were not increased by miR-21 inhibitor, indicating that SMAD2 plays a role in the downstream of miR-21 . Additionally, after transfection with miR-21 mimics and siSMAD2, the expression of miR-21 increased while SMAD2 mRNA levels decreased, which was the same as the previous experimental results . Meanwhile, HSD3B1 mRNA level was not affected . In LPS-treated GCs, the miR-21 mimics and siSMAD2 group caused a significant decrease in CYP11A1 . Finally, miR-21 inhibitors could restore the decrease in P4 concentration caused by LPS, while siSMAD2 had a negative effect on the P4 production . Collectively, miR-21 was involved in the process of LPS inhibiting P4 production .
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057685_p26
|
39057685
|
sec[3]/p[0]
|
4. Discussion
| 4.203125 |
biomedical
|
Study
|
[
0.99951171875,
0.00031185150146484375,
0.00028514862060546875
] |
[
0.99951171875,
0.00012242794036865234,
0.00039124488830566406,
0.0000705718994140625
] |
The quality of the water has a direct impact on the reproductive performance of geese. Research has shown that plasma LPS concentration can significantly depress reproductive performance . LPS impairs ovarian function, granulosa cells (GCs) necrosis and apoptosis, and steroid hormone secretion through the p38, NF-κB, and MAPK pathways . Plasma LPS will be higher in women with polycystic ovary syndrome (PCOS) . miR-873-5p/HO-1 is involved in oxidative stress induced by LPS in PCOS . In addition, ROS inhibits STAR expression through the GATA4/6 pathway in LPS-treated porcine granulosa-lutein cells . The above results prove that the study of LPS in mammals is a comprehensive explanation of the role of LPS. In this research, geese follicles underwent gelatinous degeneration after LPS injection, the follicle shape became irregularly rounded, and it was difficult to separate the membranous layer, granulosa layer, and yolk, proving that the degenerated follicles had lost the follicular function and entered the stage of follicular atresia in early. Further, LPS-treated degenerated follicles from Yangzhou geese at the peak of egg-laying were selected as the sequencing model, and healthy follicles were used as the control group. The obtained sequencing data were analyzed and filtered, and the targeting relationship of highly differentially expressed miRNAs and mRNAs was further predicted by bioinformatics methods. In brief, miR-21 and its targeted gene SMAD2 were predicted in an attempt to investigate its molecular mechanism.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p27
|
39057685
|
sec[3]/p[1]
|
4. Discussion
| 4.230469 |
biomedical
|
Study
|
[
0.99951171875,
0.00030231475830078125,
0.00019562244415283203
] |
[
0.99951171875,
0.00020575523376464844,
0.0002827644348144531,
0.00009077787399291992
] |
P4 is the major steroid that plays a critical role in regulating ovulation in hierarchical follicles . STAR is a key gene in the secretion of all follicular steroid hormones. GCs of hierarchical follicles are stimulated by follicle-stimulating hormone (FSH) to synthesize P4 in response to STAR, CYP11A1, and HSD3B1 . Furthermore, P4 serves as a precursor for estradiol (E2) synthesis in Theca cells (TCs) of hierarchical follicles, which confidently regulates steroid production and secretion in TCs . Therefore, in this experiment, ELISA was used to detect P4 secretion, while qPCR was used to measure the expression of STAR, CYP11A1, and HSD3B1. The effect of LPS exposure on P4 production was verified by in vivo and in vitro experiments. In animal experiments, a decrease in serum P4 concentration was detected in Yangzhou geese at breeding stage after LPS injection. The P4 level decreased significantly after injection of 1.5 mg/kg of LPS for 24 h, and P4 decreased further after 36 h LPS injected. To further verify the effect of LPS on progesterone secretion in granulosa cells, primary GCs were treated with LPS, and the assay revealed that treatment of GCs with 1 μg/mL of LPS for 12 h inhibited progesterone production and down-regulated the STAR, CYP11A1, and HSD3B1 mRNA levels. The experimental results indicated that LPS had a negative effect on P4 and P4-related genes.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057685_p28
|
39057685
|
sec[3]/p[2]
|
4. Discussion
| 2.998047 |
biomedical
|
Other
|
[
0.99853515625,
0.0003044605255126953,
0.0009489059448242188
] |
[
0.2294921875,
0.7314453125,
0.037445068359375,
0.0016508102416992188
] |
As a non-coding RNA, miR-21 has an initial sequence that is conserved across multiple species, and existing studies have shown that miR-21 is extensively involved in physiological and pathological processes of the reproductive system.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057685_p29
|
39057685
|
sec[3]/p[3]
|
4. Discussion
| 4.515625 |
biomedical
|
Study
|
[
0.9990234375,
0.0005121231079101562,
0.000225067138671875
] |
[
0.998046875,
0.00036978721618652344,
0.0013227462768554688,
0.00021791458129882812
] |
miR-21 has a known regulatory function in human reproduction-related diseases such as breast cancer, ovarian cancer, and endometriosis. miR-21 may inhibit the growth and metastasis of luminal-like breast cancer by inhibiting the NF-κB/PDCD4 axis . The exosome miR-21 promotes ovarian cancer progression by regulating CDK6 . Up-regulation of YAP1/miR-21-5p decreases PGR expression and plays a negative role in the development of endometriosis . In addition, another report found that miR-21 in GCs regulates the expression of STAR through down-regulation of LATS1, which ultimately promotes the secretion of estrogen in GCs . Duan et al. found that miR-21 down-regulation is involved in infection-induced preterm birth (PTB), contributing to LPS through the NF-κB pathway, which is the only study on the modulation of miR-21 by LPS resulting in reproduction-related system diseases . The above findings suggest a potential role for miR-21 in ovarian function regulation, but the role in avian GCs requires further exploration. In this study, transcriptome analysis showed that 51 miRNAs were abnormally expressed in the follicular granulosa layer exposed to LPS, including 20 down-regulated miRNAs and 31 up-regulated miRNAs. Through bioinformatics prediction and in vitro analysis, it was found that the down-regulation of SMAD2 mediated by miR-21 inhibited P4 synthesis in GCs and affected the ovulation process under the action of LPS. As miR-21 was confirmed to be enriched in steroid synthesis pathways, this study explored the specific role of miR-21 in steroid synthesis in GCs. The findings indicated that transfection with miR-21 mimics or inhibitors had a significant effect on P4 synthesis. Overexpression of miR-21 inhibited sex steroid biosynthesis by suppressing the expression of SMAD2 and decreasing the expression of STAR and CYP11A1, decreasing P4 secretion while having no effect on the expression of HSD3B1. Up-regulation of miR-21 exacerbated the LPS-induced decline in P4 synthesis and vice versa. These findings are consistent with previous studies that have validated the crucial role of miRNAs in the synthesis of steroidal GCs .
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
39057685_p30
|
39057685
|
sec[3]/p[4]
|
4. Discussion
| 4.546875 |
biomedical
|
Study
|
[
0.9990234375,
0.0005793571472167969,
0.0002810955047607422
] |
[
0.9990234375,
0.0003833770751953125,
0.0005936622619628906,
0.0002092123031616211
] |
The SMAD (mothers against decapentaplegic homolog) family is an important new gene family in the transforming growth factor beta (TGF-β) superfamily. Multiple studies have shown that the TGF-β/SMAD pathway is involved in mammalian follicular development and hormone secretion . LPS/TLR4 is also involved in a number of pathological processes by affecting the TGF-β pathway . TGF-β/SMAD2/KLF8 axis regulates epithelial–mesenchymal transition (EMT) and contributes to ovarian cancer progression. The TGFBR2/Smad2 signaling pathway has a critical role in LPS-induced sepsis . SMAD2 was shown to function as a transcription factor for STAR. Activation of SMAD1/5/8 and SMAD2/3 signaling pathways was found to down-regulate the expression of STAR and inhibit P4 synthesis in human GCs . TGF-1 affects estradiol and P4 synthesis in goat GCs through the SMAD/SP1 pathway . These results suggest that SMAD2 may play a regulatory role in animal ovarian function. Our study further investigated the effects of silencing SMAD2 on GCs. Silencing SMAD2 has a synergistic effect in LPS-treated GCs. Furthermore, SMAD2 also inhibits P4 secretion in GCs by decreasing the expression of STAR and CYP11A1. At the same time, after the appropriate concentration was determined through pre-experiments, miR-21 mimics, inhibitors, and siRNA of SMAD2 were transfected into GCs together. It was found that silencing SMAD2 had no significant effect on the expression of miR-21, indicating that SMAD2 mainly plays a regulatory role in the downstream of miR-21. In addition, HSD3B1 was not affected by changes in miR-21 but was decreased by LPS, suggesting that it may be regulated by other undiscovered pathways. Interestingly, it was found that miR-21 targets STARD9 (steroid transport protein domain 9), which has been shown to be involved in cholesterol transport. This indicates that miR-21 may be the key miRNA of various sex hormones in GCs. It should be noted that the functions of P4 in mammals and birds are not the same; further studies are needed on the regulatory pathway of granulosa cell P4 production in birds and the effects of miRNA on follicle hormone secretion at other developmental stages. These data indicated that up-regulated miR-21 inhibits SMAD2 expression and was involved in the LPS-induced reduction of P4 production in GCs.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057685_p31
|
39057685
|
sec[4]/p[0]
|
5. Conclusions
| 4.152344 |
biomedical
|
Study
|
[
0.99951171875,
0.0002123117446899414,
0.0004405975341796875
] |
[
0.99951171875,
0.00015628337860107422,
0.0003006458282470703,
0.00004661083221435547
] |
In summary, in this study, miRNA-seq was performed in LPS-exposed Yangzhou geese at peak egg-laying period, and then an LPS injury model of primary GCs was established. miR-21 was found to inhibit P4 secretion in LPS-injured GCs of Yangzhou geese by suppressing SMAD2 expression. At the miRNA level, it was further verified that miR-21 regulates SMAD2 and participates in the important mechanism of LPS injury reproduction function by gene knockdown. The results of this research will be used as a tool for understanding the miRNA regulatory network, to clarify the molecular mechanism of LPS regulation of hierarchical follicle development and hormone secretion, and to provide a more in-depth solution to LPS pollution. Our results may provide future scientific insights into miRNA regulation in LPS-damaged GCs in the future.
|
[
"Xinyi Guo",
"Shijia Ying",
"Huiping Xiao",
"Hao An",
"Rihong Guo",
"Zichun Dai",
"Wenda Wu"
] |
https://doi.org/10.3390/metabo14070362
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p0
|
PMC11278949
|
sec[0]/p[0]
|
1. Introduction
| 4.0625 |
biomedical
|
Study
|
[
0.68359375,
0.0007548332214355469,
0.315673828125
] |
[
0.98974609375,
0.00872039794921875,
0.0013980865478515625,
0.00009399652481079102
] |
Steam generators are key components of nuclear power plants, as their reliability affects the overall operation of the plant. A common operational problem that occurs in steam generators is the corrosion of the structural material and the build-up and deposition of unwanted solids on its internal surfaces. Steel is chosen for most applications because of its properties such as strength, durability, ease of fabrication and cost. Iron alloys have the property of resisting corrosion by forming a thin layer of oxide . The area of focus in this research is magnetite Fe 3 O 4 that approximates the protective layer on low-carbon steel. Notwithstanding the fact that the real structure of such a layer could be amorphous, strongly clustered and with bound surface hydroxyls, understanding the characteristics, formation and transformation of Fe 3 O 4 can contribute to a reduction in material damage and waste, as well as the development of new products with improved qualities for various applications. The crystal structure of magnetite follows an inverse spinel lattice with alternating octahedral and tetrahedral–octahedral layers . A detailed atomistic understanding of magnetite in complex nanostructures and of surface interactions is essential for many fundamental and technological processes.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278949_p1
|
PMC11278949
|
sec[0]/p[1]
|
1. Introduction
| 4.285156 |
biomedical
|
Study
|
[
0.98876953125,
0.0005125999450683594,
0.01079559326171875
] |
[
0.9990234375,
0.0003070831298828125,
0.000518798828125,
0.00005060434341430664
] |
Ammonia (NH 3 ) is one of the principal components of secondary circuit water chemistry which ensures that the pH of the coolant remains sufficiently alkaline to minimize the uniform corrosion of steel. Recently, it has been reported that whereas at low concentrations (<10 −4 mol dm −3 ) it acts as a blocking inhibitor on carbon steel, at high concentrations (>10 −3 mol dm −3 ), inhibiting ammonia is removed via the formation of an ammoniated Fe(II) complex and the surface is activated . In recent years, the interaction of ammonia with various iron oxides was studied in the context of using its catalytic oxidation as a promising method for its removal from the atmosphere . The adsorption behavior of NH 4 + on a magnetite–montmorillonite composite was well expressed by pseudo-second-order kinetics and a Temkin isotherm model . On γ-Fe 2 O 3 , NH 3 was preferably adsorbed on the octahedral Fe site, with the N atom bonding to that site . A Mars−van Krevelen-type surface NH 3 oxidation mechanism was proposed for Fe oxide supported on Al 2 O 3 : the lattice oxygen of Fe oxide was used to oxidize adsorbed NH 3 to −NH 2 , which dimerized into N 2 H 4 intermediate species and was then desorbed as N 2 .
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p2
|
PMC11278949
|
sec[0]/p[2]
|
1. Introduction
| 4.320313 |
biomedical
|
Study
|
[
0.9990234375,
0.0002777576446533203,
0.0009288787841796875
] |
[
0.97412109375,
0.0008463859558105469,
0.024658203125,
0.0001405477523803711
] |
An accurate description of iron oxide/water electrostatic interactions depends on the correct selection of a force field (FF) and the parameters used to describe the bond between surface iron and oxygen atoms from water molecules. It is still challenging to model magnetite with empirical force fields using fixed point charges due to the lack of accurate approximations of the electronic structure and the complex oxidation state of magnetite. Using volume charge values for surface atoms results in an “unphysical” surface . An accurate approximation of the charge distribution is necessary to obtain realistic surface structures and to model the correct mechanical behavior of magnetite. Thanks to advances in computational algorithms and the accuracy of empirical force fields, atomistic-scale simulations have now provided a deeper insight into many other iron oxide-based materials that are not magnetite-based . Studying oxidations from an atomistic point of view can offer new insights into the behavior of atoms and the influencing factors in oxidation mechanisms . The number of atomistic molecular dynamics models of a magnetite surface is rather small, given the difficulties in describing the spin distribution. Also, the possibilities of adsorption on this type of surface are not sufficiently well studied.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p3
|
PMC11278949
|
sec[0]/p[3]
|
1. Introduction
| 4.207031 |
biomedical
|
Study
|
[
0.99609375,
0.00020110607147216797,
0.0035648345947265625
] |
[
0.9990234375,
0.00067901611328125,
0.00026726722717285156,
0.0000388026237487793
] |
The Clay FF is a force field suitable for the simulation of hydrated and multicomponent mineral systems and their surfaces with aqueous solutions. The approach in this field is to treat most interatomic interactions as nonbonding. This allows the use of the force field for a wide variety of phases and correctly accounts for energy and momentum transfer between the liquid phase and the solid, while keeping the number of parameters small enough to allow the modeling of relatively large systems. Simulating bulk magnetite requires adapting the parameters for the short-range repulsive interactions that represent the hematite–water interatomic potentials. There are a number of developments that propose parameters for bulk magnetite and its surface . In the present work, another method was applied to determine the iron atoms with octahedra and tetrahedra without separating them according to their place in the crystal (in the volume or on the surface). In the transferable intermolecular potential with 3 points (TIP3P) solid water model , the molecule is divided into three force centers corresponding to the three atoms of the water molecule and is implemented in the Clay FF .
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278949_p4
|
PMC11278949
|
sec[0]/p[4]
|
1. Introduction
| 3.017578 |
biomedical
|
Study
|
[
0.884765625,
0.001132965087890625,
0.11419677734375
] |
[
0.99755859375,
0.001995086669921875,
0.00027751922607421875,
0.0000909566879272461
] |
The main goal of the present work is the construction of a model surface of magnetite Fe 3 O 4 , considering the {111} plane. It is essential to track the basic characteristics of the systems within the simulation time. Another important part of this study is the characterization of the behavior of ammonia molecules placed in an aqueous phase near the magnetite surface. The possibility of adsorption of these molecules on the surface of magnetite was evaluated.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278949_p5
|
PMC11278949
|
sec[1]/p[0]
|
2. Results and Discussion
| 4.125 |
biomedical
|
Study
|
[
0.99853515625,
0.00029397010803222656,
0.0009775161743164062
] |
[
0.99951171875,
0.00011408329010009766,
0.0003218650817871094,
0.000044405460357666016
] |
From the atomistic molecular dynamic simulations of the system performed at the investigated temperatures, the trajectories with the coordinates and velocities of each atom were taken. The basic parameters related to the adequacy of the composite structure of magnetite under the imposed conditions were determined, information was obtained on the interaction of water molecules with the surface of the oxide, and the initial movement of some of the NH 3 molecules was described. The radial distribution functions between the atoms involved in the interactions were calculated. The data presented were averaged from parallel simulations performed for each temperature. Also, the analyses were averaged by the number of particles and by time for the entire length of the trajectory or for a given period. The obtained results were compared with similar simulations and the experimental data.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p6
|
PMC11278949
|
sec[1]/sec[0]/p[0]
|
2.1. Layer Properties
| 2.277344 |
biomedical
|
Study
|
[
0.58203125,
0.0014734268188476562,
0.416748046875
] |
[
0.962890625,
0.03558349609375,
0.000942230224609375,
0.00040531158447265625
] |
A main criterion for the correctness of the simulations and the behavior of the magnetite layer is the root mean square deviation (RMSD) profile. Figure 1 a shows the profiles at 343 and 473 K. For the other investigated temperatures, the shape of the curve is analogous with small differences in intensity.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278949_p7
|
PMC11278949
|
sec[1]/sec[0]/p[1]
|
2.1. Layer Properties
| 4.113281 |
biomedical
|
Study
|
[
0.99755859375,
0.00031256675720214844,
0.0022945404052734375
] |
[
0.99951171875,
0.0002732276916503906,
0.0001914501190185547,
0.00004690885543823242
] |
At the beginning of the display period, there is a slight increase in the values characteristic of the relaxation system. A reduction in fluctuations is also observed, again related to the stabilization of the system. There is no distinct transition or distinct fragments, indicating that no energy transition is observed in the layer. This is an expected result given the periodic structure of the nanolayer and the significantly strong bonds within it. As expected, there are no clearly defined substructures at different temperatures. A slight increase in the movement of atoms with increasing temperature is observed, which does not affect the stability of the layer. The presence of dissolved molecules in the aqueous phase does not affect the overall RMSD profile given the length of the trajectories. These results are completely satisfactory and enable the continuation of the atomistic molecular dynamics simulations with the confirmed geometries of the demonstration systems.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p8
|
PMC11278949
|
sec[1]/sec[0]/p[2]
|
2.1. Layer Properties
| 4.210938 |
biomedical
|
Study
|
[
0.99853515625,
0.0003490447998046875,
0.0008931159973144531
] |
[
0.99951171875,
0.00016307830810546875,
0.0002732276916503906,
0.00005561113357543945
] |
In order to determine possible deformations in the structure of the crystal system, it is appropriate to consider the radial distribution functions (RDFs). The determination was made for both types of iron ions by obtaining the most probable distance between iron atoms with the same charge. Figure 1 b shows the RDF profile for the productive part of the 50 ns long simulation before adding ammonia to the aqueous phase. Statistical analysis was conducted on the last 10 ns. The distributions of Fe 2+ and Fe 3+ are typical of a close-range ordered structure. There is no distinct second or third peak, indicating that at this stage the structure remains unchanged within the simulation time. Like the RMSD curves, there is no significant difference in shape with respect to temperature, and again there is a slight increase in peak intensity and width. An exchange of iron atoms is possible with the tetrahedral sites being more occupied by Fe 2+ . The preferred distance between the iron atoms differs slightly from that of an ideal crystal . Due to differences in the imposed temperature and pressure, the results obtained are in good compliance with the applied methodology . From the reasoning made, it is clear that the constructed layer of magnetite is adequate; there is no interaction of the bulk crystal with water and the system can be used in combination with ammonia.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p9
|
PMC11278949
|
sec[1]/sec[1]/p[0]
|
2.2. Surface Interaction
| 4.132813 |
biomedical
|
Study
|
[
0.99462890625,
0.0004551410675048828,
0.00476837158203125
] |
[
0.99951171875,
0.0001990795135498047,
0.00017702579498291016,
0.000040411949157714844
] |
A more accurate picture of the state of water and surface interactions can be made by calculating the mass density profile of water molecules relative to the z direction in the periodic box. The simulation box is divided into sub-volumes (20) in the direction parallel to the Fe 3 O 4 magnetite surface. In these sub-volumes, the atoms of the corresponding type of molecule are counted and referred to the entire volume. The end result is a mass density profile for a given component of the investigated systems in the periodic box. The data for the considered surface at the beginning of the simulation period are shown in Figure 2 a at 298 K. All simulations started from the same initial coordinates of the atoms and accordingly there are no differences in the state of the system at the initial stage regarding the surface. The dashed line corresponds to the boundary surface of magnetite determined at a solid phase density of 0 kg m −3 . The correct density of water in the bulk phase is reached and there is no intrusion of molecules into the crystal. At this stage of the simulations, there is no pronounced increase in the mass density of the water phase near the surface.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p10
|
PMC11278949
|
sec[1]/sec[1]/p[1]
|
2.2. Surface Interaction
| 4.164063 |
biomedical
|
Study
|
[
0.998046875,
0.0003719329833984375,
0.0017070770263671875
] |
[
0.99951171875,
0.0001481771469116211,
0.0001819133758544922,
0.00004470348358154297
] |
The atoms in the same sub-volumes at the end of the simulation were counted in the manner described above. The results are shown in Figure 2 b, but showing the number of molecules rather than the density. Here, the equimolecular dividing surface (EDS) determined at a water phase density of 500 kg m −3 is represented by a dashed line. The indicative data are at a temperature of 293 K, and there are no significant differences in the other values. In all systems near the surface of the magnetite, there is a peak formed corresponding to the ammonia molecules approaching its surface. Their number is the same (~11) at all temperatures except 433 K and 473 K. At lower temperatures, only one non-adsorbed molecule remains. One of the possible reasons for this is the too-large distance to the surface of the oxide, and another is the cut of the nitrogen atom in the molecule. At the two higher temperatures, fewer molecules (respectively, ~10 and ~8) reach the surface in all four runs. The attraction of ammonia molecules to the magnetite surface is unambiguous, due to the distribution of surface charges on the iron atoms. The number of molecules approaching the surface is largely influenced by the state of the water phase and the ability of the particles to move.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p11
|
PMC11278949
|
sec[1]/sec[1]/p[2]
|
2.2. Surface Interaction
| 2.873047 |
biomedical
|
Study
|
[
0.990234375,
0.0006403923034667969,
0.008941650390625
] |
[
0.99462890625,
0.004547119140625,
0.0003948211669921875,
0.00022363662719726562
] |
This necessitates a more careful study of the reported phenomenon. The RMSD profile of ammonia was calculated and the position of molecules relative to magnetite within the entire trajectory was determined. The data are illustrated in Figure 3 a.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278949_p12
|
PMC11278949
|
sec[1]/sec[1]/p[3]
|
2.2. Surface Interaction
| 4.128906 |
biomedical
|
Study
|
[
0.99560546875,
0.00039577484130859375,
0.004077911376953125
] |
[
0.99951171875,
0.00019180774688720703,
0.00015437602996826172,
0.00003981590270996094
] |
An analysis for NH 3 was carried out for all molecules placed in the system. The reason for this is the clear approach to the magnetite surface of most ammonia molecules. The profile in Figure 3 a shows temperatures of 293 K, 433 K, and 473 K. Similar to the analyses made so far, the general behavior of ammonia does not seem to vary significantly with temperature. From the RMSD plot, at 293 K, a change in motion, or more precisely a change in configuration, is observed between 100 and 140 ns. At 473 K, there is a change in their profile of 180 ns, which also corresponds to the moment of adsorption of ammonia molecules. At the end of the simulation time for all systems, there is a decrease in fluctuations, indicating that there is no transition in the structures. This indicates that there is a change in the orientation of ammonia, which remains relatively constant within the simulations. Again, there is an increase in intensity with time and the fluctuations generally subside because of the relaxation of the system.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p13
|
PMC11278949
|
sec[1]/sec[1]/p[4]
|
2.2. Surface Interaction
| 4.183594 |
biomedical
|
Study
|
[
0.99755859375,
0.0005121231079101562,
0.002140045166015625
] |
[
0.99951171875,
0.00011658668518066406,
0.0002410411834716797,
0.00004589557647705078
] |
The approach of ammonia NH 3 was also tracked by determining the minimum distances between the center of mass of the molecules and the position of the magnetite surface relative to the z axis in the periodic box. The resulting distances are presented in Figure 3 b. From the calculated trajectories, small distances between the surface and the considered ammonia molecules are estimated, which is a good indication of the contact between them, and it is possible that adsorption occurred. It is once again important to note that the initial coordinates at all temperatures are the same, but after heating in the NVT ensemble to the corresponding temperature there are differences in the position of the ammonia molecules. This is also due to the different distances of the ammonia molecules from the surface at the beginning of the trajectories. At all temperatures, ammonia reaches the magnetite. Particles within the simulation time remain on the surface and this is a clear indication of adsorption. The approach of ammonia is affected by the temperature and with growth this phenomenon takes place at an earlier stage. The exception is the system at the highest temperature . There, the average distance between ammonia and magnetite is smaller, but a sharp approach occurs after 150 ns. In this system, the ammonia molecules that reached the surface are fewer, in agreement with the analysis presented in Figure 2 b. The considered profiles show a clear tendency for the NH3 molecules to come closer together and the desire to stay permanently in the surface area. Additional information about ammonia adsorption can be obtained from the number of contacts of the molecule with the surface within the simulation. The calculated data are shown in Figure 4 . The numbers of contacts between ammonia molecules and the magnetite surface at two of the investigated temperatures are shown in Figure 4 .
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278949_p14
|
PMC11278949
|
sec[1]/sec[1]/p[5]
|
2.2. Surface Interaction
| 4.148438 |
biomedical
|
Study
|
[
0.99755859375,
0.00040841102600097656,
0.0018739700317382812
] |
[
0.99951171875,
0.0002524852752685547,
0.0001914501190185547,
0.00004839897155761719
] |
The data show a relatively rapid increase in the number of contacts as the molecules approach the oxide. Although the average distance at the highest temperature (473 K) increases more slowly compared to the others, after a certain time (160 ns) it rises sharply. In general, the total number of contacts is smaller compared to 293 K, which is in good agreement with the smaller number of adsorbed molecules. The time taken for the number of contacts to grow at both temperatures is relatively the same. At 293 K, an increase from single contacts to over 100 is reached in 14.6 ns; at 473 K, the contact development period is 16.8 ns. This shows that after the ammonia molecules reach a certain distance from the surface, the effect of temperature is not so significant, and the adsorption depends on the electrostatic interaction between the atoms.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278949_p15
|
PMC11278949
|
sec[1]/sec[2]/p[0]
|
2.3. Radial Distribution Functions
| 3.208984 |
biomedical
|
Study
|
[
0.9287109375,
0.0007472038269042969,
0.07061767578125
] |
[
0.94384765625,
0.05499267578125,
0.0009250640869140625,
0.00023305416107177734
] |
It is important to mention that with surface phenomena in general, it is of particular importance with which functional group of the molecule the surface is attacked. At this stage, visual observations show that most of the ammonia reacts with its nitrogen atom . A similar phenomenon has been observed for a single molecule of hydrazine adsorbed on an Fe(110) surface . This necessitates a more detailed examination of the interactions between specific atoms.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278949_p16
|
PMC11278949
|
sec[1]/sec[2]/p[1]
|
2.3. Radial Distribution Functions
| 4.179688 |
biomedical
|
Study
|
[
0.99755859375,
0.00038504600524902344,
0.00213623046875
] |
[
0.99951171875,
0.0002002716064453125,
0.0002263784408569336,
0.00004869699478149414
] |
Based on this, the most probable distance between the nitrogen atom of the ammonia molecule and the iron atoms of the two types of tetrahedral and octahedral sites (regardless of the charge) was calculated. The distance to the oxygen atoms was also determined. The function profiles overlap at different temperatures, which is not a completely expected result . With an increase in temperature, there is a slight decrease in the intensity of the peaks, but there is no shift in their place. Once they have reached the surface of the magnetite, the attraction of the molecules is more influenced by the charge of the atoms than the current by the temperature. Both types of magnetite target atoms show strong fluctuations related to the possible movement of ammonia molecules on the surface. One cannot speak of an adsorbed layer, but the presence of a peak is a clear indication of such a phenomenon. Tetrahedral sites are largely preferred, as there is a distribution of both charges. The interaction with the iron atoms in the octahedral positions is also significant, but not as intense. The interaction with oxygen atoms from the magnetite surface is weakest.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p17
|
PMC11278949
|
sec[1]/sec[2]/p[2]
|
2.3. Radial Distribution Functions
| 4.230469 |
biomedical
|
Study
|
[
0.95947265625,
0.001010894775390625,
0.0394287109375
] |
[
0.99951171875,
0.00033855438232421875,
0.0003261566162109375,
0.00005078315734863281
] |
To put the obtained modeling results into perspective in relation to the corrosion of carbon steel in steam generator coolant, the impedance spectra measured after 70 h of exposure in a de-oxygenated ammonia solution (pH 9.8 at room temperature) at temperatures in the range of 373–473 K are presented in Figure 6 a. As already reported for similar steel in ammonia–ethanolamine (AMETA) coolant , the low-frequency limit of the impedance that can be correlated with the inverse of the corrosion rate behaves non-monotonously with temperature, exhibiting a minimum at 160–180 °C. The complete interpretation of the spectra using the Mixed-Conduction Model for Oxide films will be reported in a companion paper. Here, we focus our attention on the parameters characterizing the magnetite (oxide formed on steel)/coolant (ammonia + water) interface—the interfacial capacitance (C int ) and charge transfer resistance (R t ). The temperature dependence of these parameters is illustrated in Figure 6 b. The order of values of C int (0.4–2.0 mF cm −2 ) is typical for an adsorption pseudo-capacitance at the oxide/water interface and is relatively constant in the interval 373–433 K, indicating no change in the adsorption mechanism. At higher temperatures, the capacitance decreases, suggesting a mode compact adsorption layer or a smaller coverage of the adsorbed species, which is in line with the modeling findings of an alteration of ammonia adsorption when the temperature approaches 473 K. The maximum of the inverse of the charge transfer resistance at 433–453 K, indicating the maximum rate of the cathodic coupled reaction of corrosion (water reduction), can also be tentatively ascribed to the modification of the adsorption layer leading to an alteration of the mechanism of water reduction. Further investigations are in progress to elucidate the influence of ammonia on the thickness and composition of the oxide and corrosion release rates of carbon steel in simulated steam generator conditions.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278949_p18
|
PMC11278949
|
sec[2]/p[0]
|
3. Systems and Methods
| 2.25 |
biomedical
|
Study
|
[
0.56494140625,
0.0011129379272460938,
0.433837890625
] |
[
0.69384765625,
0.3037109375,
0.001720428466796875,
0.0005888938903808594
] |
Magnetite has a spinel structure and crystallizes in the cubic space group Fd̅3m. In the present study, a structure at high pressures was used for the unit cell, keeping all the basic parameters of the crystal lattice. A detailed description of the structure and mode of replication of the unit cell is given below.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p19
|
PMC11278949
|
sec[2]/p[1]
|
3. Systems and Methods
| 4.34375 |
biomedical
|
Study
|
[
0.99853515625,
0.0004930496215820312,
0.0009140968322753906
] |
[
0.99853515625,
0.0008301734924316406,
0.0003204345703125,
0.00010943412780761719
] |
The system contained a total of 56 atoms with a side length of 8.44 Å, which was the lattice constant of 16 Fe 3+ atoms, 8 Fe 2+ atoms and 32 O 2− atoms. The Fe 2+ atoms were bonded to four equivalent O 2− atoms to form FeO 4 tetrahedra, which shared angles with twelve equivalent FeO 6 octahedra, the angles being 57°. All Fe 2 ⁺/O bond lengths were 1.92 Å. The Fe³⁺ atoms were bonded to six equivalent O 2− atoms to form FeO 6 octahedra, which shared corners with six equivalent FeO 4 tetrahedra and edges with six equivalent FeO 6 octahedra. All Fe 3+ /O bond lengths were 2.06 Å. The O 2− atoms were bonded in a distorted rectangular cradle-like geometry to one Fe²⁺ and three equivalent Fe 3 ⁺ atoms. A major challenge in modeling was the clear distinction between the charges of the iron atoms and their spatial orientation.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278949_p20
|
PMC11278949
|
sec[2]/p[2]
|
3. Systems and Methods
| 4.269531 |
biomedical
|
Study
|
[
0.9990234375,
0.0003933906555175781,
0.0007534027099609375
] |
[
0.99951171875,
0.0001537799835205078,
0.00027251243591308594,
0.00006449222564697266
] |
The resulting Fe 3 O 4 unit cell structure was multiplied in the three directions in such a way as to reproduce the {111} plane. The number of elementary units was 48 and the system contained a total of 2688 atoms. The size of the layer along the x and y axis is 3.39 nm and the thickness was 2.50 nm. With the layer thus constructed, it was possible to perform atomistic molecular dynamics simulations with the Clay force field. Simulating bulk magnetite requires adapting the parameters for the short-range repulsive interactions that represent the hematite–water interatomic potentials . It was proposed to divide the atoms into octahedral and tetrahedral atoms only, with the partial charges being distributed equally for the entire system. It turned out to be a reasonable choice to choose the opposite partial atomic charge of O 2− for Fe 2+ , as this provided a neutral charge on the bulk magnetite unit cell. Moreover, using this partial atomic charge for Fe 2+ led to a good description of bulk magnetite, and of magnetite surfaces. The approach presented here ultimately allowed the simulation of a realistic and much larger system. It is also suitable for studying the mechanical and structural properties of functionalized magnetite surfaces and nanoparticles. This opens the door to a more fundamental understanding of the oxidation state ordering of inverse spinel structures. As can be seen, understanding the chemical activity of Fe 3 O 4 is challenging due to the complex chemical behavior of magnetite on the surface. In the present study, the Clay FF was applied with charge and bond modifications . Periodic boundary conditions (PBCs) with changed dimensions along the z coordinate of 10 nm were imposed on the already built layer of Fe 3 O 4 . In this empty volume, there were 12 ammonia molecules, and the concentration reached was 1.8 10 −4 mol dm −3 . In the next step, the model system was saturated with water molecules until the correct density was reached for the given conditions. The number of water molecules was 3437, so the atoms in the system exceeded 13,000. The thickness of the water layer was large enough that there was no interaction with the periodic image. The initial coordinates of the system are shown in Figure 7 (left).
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278949_p21
|
PMC11278949
|
sec[2]/p[3]
|
3. Systems and Methods
| 4.335938 |
biomedical
|
Study
|
[
0.9990234375,
0.0004253387451171875,
0.0004801750183105469
] |
[
0.9990234375,
0.00023174285888671875,
0.0004978179931640625,
0.00009274482727050781
] |
The calculations were performed with the Clay force field , which was chosen as the most suitable for describing periodic structures and at the same time containing parameters for different functional groups for possible solvents. A leap-frog integrator of the equations of motion was used in combination with the PME (Particle mesh Ewald) method for the electrostatic interactions at a switched cut-off of 1.2/1.4 nm. The same cut-off was imposed for the van der Waals interactions, which were evaluated with the Lennard-Jones potential. The water model was TIP3P . All simulations were performed in the NPT ensemble at several temperatures (293 K; 323 K; 343 K; 373 K; 473 K) and a pressure of 90 bar was held constant with a Nose–Hoover’s thermostat and a Parrinello–Rahman’s barostat . NPT pressure scaling was applied—dependent on all coordinates (x,y,z) for all models in PBCs. The behavior of water at different temperatures was tailored to the viscosity according to damp = m/(3 × pi × μ × d), where the dynamic viscosity of water varies with respect to the temperature . The systems underwent energy minimization, heating and relaxation, the latter being verified by reaching a constant average of the total energy, temperature and pressure. The root mean square deviation of the coordinates of the two types of iron ions and the dissolved molecules in the aqueous phase was also monitored. The trajectory length was 200 ns, with some results presented for the last 50 ns. The time step was ∆t = 0.5 fs, and each frame in the trajectories was saved for 10 ps. For each temperature, four independent runs were made with different configurations for the ammonia and water molecules and with different velocities for the magnetite atoms, but the same initial coordinates in the model system. In order to follow the evolution of the systems in more detail, some of the statistical analyses were made for simulation intervals of 10 ns. Molecular dynamics (MD) calculations were performed with the LAMMPS 2Aug2023 (Large-scale Atomic/Molecular Massively Parallel Simulator) software package with a focus on the modeling of inorganic materials . A demo version of the source script is attached in the Supplementary Material . The program VMD 1.9.4a (Visual Molecular Dynamics) was used to visualize the results. The final coordinates (state) of the system are shown in Figure 7 (center) with a top view of the surface with ammonia molecules near the magnetite Figure 7 (right).
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278949_p22
|
PMC11278949
|
sec[2]/p[4]
|
3. Systems and Methods
| 3.998047 |
biomedical
|
Study
|
[
0.8115234375,
0.0005831718444824219,
0.1881103515625
] |
[
0.99560546875,
0.004100799560546875,
0.00038051605224609375,
0.00006031990051269531
] |
The electrochemical impedance spectra of low-carbon steel (22 K type) were measured in an NH 3 solution (pH 9.8) at the corrosion potential in the temperature interval 373–513 K and a pressure of 90 bar in a high-temperature re-circulation loop using a Compactstat 10030 potentiostat equipped with a frequency response analyzer module (Ivium, Eindhoven, The Netherlands). The spectra were measured in a frequency range of 0.5 mHz to 11 kHz with an ac signal of 40 mV (rms).
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278949_p23
|
PMC11278949
|
sec[3]/p[0]
|
4. Conclusions
| 4.195313 |
biomedical
|
Study
|
[
0.998046875,
0.0004093647003173828,
0.0015268325805664062
] |
[
0.99951171875,
0.00010633468627929688,
0.0002300739288330078,
0.00004476308822631836
] |
The main goal of the present work was the construction of a model system resembling the {111} plane of magnetite Fe 3 O 4 . The construction of this surface is at the molecular level, for which the methods of molecular mechanics were used. Given the spinel structure of this crystal, there are a number of difficulties in the selection of a force field and its modifications. For the present study, the Clay FF, also used in thee molecular dynamics simulations of a large number of long-range structures, was imposed. Atomistic systems containing magnetite, aqueous phase and ammonia molecules at different temperatures were built with the selected parameters and simulations using molecular dynamics were carried out. Statistical analyses were performed on the obtained trajectories, proving the stability of the developed systems. The root mean square deviation profile (RMSD), radial distribution functions (RDFs) and mass density profile for the aqueous phase were determined, and the movement of ammonia was analyzed. The constructed model structures are stable and there is no clearly pronounced energy transition in the systems. There is a definite approach of part of the dissolved ammonia molecules to the magnetite surface. The time for the observed phenomenon depends on the temperature, but not the interaction itself. The influence of temperature on the extent of the adsorption of ammonia is tentatively correlated with the interfacial parameters of the electrochemical impedance spectra of carbon steel measured in an ammonia–water solution in a similar temperature interval.
|
[
"Nikoleta Ivanova",
"Vasil Karastoyanov",
"Iva Betova",
"Martin Bojinov"
] |
https://doi.org/10.3390/molecules29143276
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p0
|
PMC11278961
|
sec[0]/p[0]
|
1. Introduction
| 3.898438 |
biomedical
|
Review
|
[
0.9990234375,
0.0004162788391113281,
0.0006780624389648438
] |
[
0.279541015625,
0.1610107421875,
0.55810546875,
0.0011262893676757812
] |
Cervical cancer (CC) is the fourth-most-frequent cancer in women worldwide, with around 660,000 new cases in 2022 . Furthermore, in the United States, it ranks as the second cause of cancer-related death among women aged 20 to 39 years . Squamous cell carcinoma is the most prevalent histological type globally, accounting for approximately 80% of CC cases. Adenocarcinoma follows closely behind, representing roughly 12% of all CC diagnoses .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p1
|
PMC11278961
|
sec[0]/p[1]
|
1. Introduction
| 3.925781 |
biomedical
|
Review
|
[
0.9990234375,
0.00044918060302734375,
0.00038123130798339844
] |
[
0.284912109375,
0.00954437255859375,
0.705078125,
0.0007314682006835938
] |
Since human papillomavirus (HPV) has been identified as a CC causative agent and the progression from precancerous lesions to invasive cancer is usually slow, CC is one of the most preventable cancers . The implementation of widespread screening programs in recent years has demonstrably improved early-detection rates, leading to a rise in the number of CC survivors. This success is reflected in the declining prevalence of the locally advanced disease and a slight increase in the diagnosis of early-stage cancers. Moreover, it is noteworthy that an estimated 40% of early-stage CC patients are younger than 40 years old .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p2
|
PMC11278961
|
sec[0]/p[2]
|
1. Introduction
| 2.419922 |
biomedical
|
Other
|
[
0.9794921875,
0.0173797607421875,
0.0033245086669921875
] |
[
0.003223419189453125,
0.9912109375,
0.003917694091796875,
0.0016717910766601562
] |
Radical hysterectomy is considered the standard treatment for early-stage CC, but it results in permanent infertility. In young women with childbearing desire, fertility preservation acquires a paramount importance .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p3
|
PMC11278961
|
sec[0]/p[3]
|
1. Introduction
| 3.679688 |
biomedical
|
Study
|
[
0.9990234375,
0.0006046295166015625,
0.0005178451538085938
] |
[
0.99609375,
0.0019683837890625,
0.0019626617431640625,
0.00015056133270263672
] |
Cervical conization is a standard surgical procedure that allows the removal of cervical lesions, and it has been widely accepted for treating FIGO stage IA1 CC . A study by the U.S. Surveillance, Epidemiology and End Results (SEER) program specifically analyzed women under 40 with stage IA1 CC. The study found no significant difference in the 5-year survival rates between those who received conization alone and those who underwent demolitive treatment .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278961_p4
|
PMC11278961
|
sec[0]/p[4]
|
1. Introduction
| 3.964844 |
biomedical
|
Study
|
[
0.99853515625,
0.0012302398681640625,
0.00026869773864746094
] |
[
0.66943359375,
0.0216522216796875,
0.307373046875,
0.001476287841796875
] |
While colposcopic-directed cervical biopsy remains a crucial diagnostic tool for cervical intraepithelial neoplasia (CIN), a phenomenon known as pathological upgrading can occur in clinical practice. This situation refers to cases in which the definitive diagnosis from a conization specimen reveals a more severe lesion compared to the initial biopsy. This discrepancy is more prevalent in postmenopausal women, due to lower estrogen levels, squamocolumnar junction recession and cervical atrophy. The overall incidence of pathological upgrading is estimated to be around 10% in women diagnosed with CIN 2 or 3 .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p5
|
PMC11278961
|
sec[0]/p[5]
|
1. Introduction
| 2.367188 |
biomedical
|
Other
|
[
0.99560546875,
0.0014934539794921875,
0.002941131591796875
] |
[
0.09979248046875,
0.80810546875,
0.08984375,
0.002468109130859375
] |
Several techniques exist for performing cervical conization, with cold knife (CK) conization, carbon dioxide (CO 2 ) laser conization, and loop electrosurgical excision procedure (LEEP) being the most common. However, there is a scarcity of high-quality comparative studies on these methods.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278961_p6
|
PMC11278961
|
sec[0]/p[6]
|
1. Introduction
| 3.925781 |
biomedical
|
Review
|
[
0.99755859375,
0.0012655258178710938,
0.0011587142944335938
] |
[
0.1094970703125,
0.0017213821411132812,
0.888671875,
0.00035262107849121094
] |
Although the LEEP remains the first-line treatment recommended by the major international societies , CO 2 laser conization seems to be a viable alternative for treating CIN, demonstrating favorable outcomes regarding specimen resection margins and the obstetric prognosis . Retrospective studies comparing conservative treatments for adenocarcinoma in situ (AIS) using CK conization or LEEP have shown a potential advantage for CK conization, with lower margin positivity rates .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p7
|
PMC11278961
|
sec[0]/p[7]
|
1. Introduction
| 3.474609 |
biomedical
|
Study
|
[
0.99658203125,
0.0025081634521484375,
0.0009598731994628906
] |
[
0.99853515625,
0.0009036064147949219,
0.0002624988555908203,
0.00017452239990234375
] |
Given the limited recent data comparing CK and CO 2 laser conization, our present study aims to assess the comparative effects of these two techniques on clinical implications and pathological outcomes.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p8
|
PMC11278961
|
sec[1]/p[0]
|
2. Materials and Methods
| 2.935547 |
biomedical
|
Study
|
[
0.9873046875,
0.0117645263671875,
0.0009889602661132812
] |
[
0.99658203125,
0.0021381378173828125,
0.00034165382385253906,
0.0008373260498046875
] |
This is a single-center retrospective study conducted at our tertiary care center associated with the University of Brescia, Italy. We retrospectively enrolled patients who underwent CK or CO 2 laser conization at our Division of Obstetrics and Gynecology at ASST Spedali Civili of Brescia between January 2010 and December 2022.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p9
|
PMC11278961
|
sec[1]/p[1]
|
2. Materials and Methods
| 1.768555 |
biomedical
|
Other
|
[
0.9833984375,
0.00372314453125,
0.0129852294921875
] |
[
0.47802734375,
0.515625,
0.004451751708984375,
0.0018243789672851562
] |
All data used in this article derive from an auditing of the databases used in the service of evaluations for cervical cancer and is hence already anonymized at the moment of data analysis. The design, analyses and interpretations of data, and the drafting and revisions conform to the Helsinki Declaration, the Committee on Publication Ethics guidelines and the Reporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD) Statement, as validated by the Enhancing the Quality and Transparency of Health Research Network . No personal data that could lead to actual identification of a patient were stored in the databases. The study was not advertised.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p10
|
PMC11278961
|
sec[1]/p[2]
|
2. Materials and Methods
| 3.933594 |
biomedical
|
Study
|
[
0.96484375,
0.034515380859375,
0.0007510185241699219
] |
[
0.98095703125,
0.01690673828125,
0.000713348388671875,
0.0015096664428710938
] |
The inclusion criteria consisted of the following: (i) age ≥ 18 years and treatment naive; (ii) newly diagnosed CIN2 or higher and AIS or higher, obtained by colposcopic biopsy; and (iii) surgical excision performed with either CO 2 laser or CK conization, the decision of the technique being left to the discretion of the surgeon. Exclusion criteria were: (i) CIN1 or negative colposcopic biopsy; and (ii) any case of invasive cancer.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p11
|
PMC11278961
|
sec[1]/p[3]
|
2. Materials and Methods
| 3.75 |
biomedical
|
Study
|
[
0.966796875,
0.03289794921875,
0.0004718303680419922
] |
[
0.9931640625,
0.003936767578125,
0.0008444786071777344,
0.0018367767333984375
] |
Patient demographics and medical history were collected, including the age at the time of conization, parity (number of term pregnancies), menopausal status, and preoperative histological biopsy (CIN2 of higher, CIS and AIS). Surgical data were also retrieved, including date of the surgical procedure, type of conization (CO 2 laser or CK conization), and type of anesthesia (local or general).
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p12
|
PMC11278961
|
sec[1]/p[4]
|
2. Materials and Methods
| 4.089844 |
biomedical
|
Study
|
[
0.99267578125,
0.00698089599609375,
0.0003008842468261719
] |
[
0.99755859375,
0.0013980865478515625,
0.0005183219909667969,
0.0004165172576904297
] |
The definitive histological results from the conization specimen were collected, including the following: postoperative histological report (negative, CIN 1, CIN2, CIN3, CIS, squamous cell cancer, AIS or adenocarcinoma); presence of stromal invasion; exocervical margin status (negative or positive); endocervical/deep margin status (negative or positive); and, eventually, FIGO stage for cases diagnosed with cervical cancer. Negative or positive margins were defined according to our institutional technique, which has been already published . In fact, further ablative treatment with CO 2 or monopolar was adopted for exocervical and endocervical margins for at least 5–8 mm to ensure the radicality of the treatment, determining a cylindrical footprint in the cervix. We reported treatment or follow-up modality in cases of incidental diagnosis of CC. Since most CC diagnoses in our study predated the implementation of the 2018 FIGO staging system revision, we restaged all the cases according to the most recent staging system.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p13
|
PMC11278961
|
sec[1]/p[5]
|
2. Materials and Methods
| 1.953125 |
biomedical
|
Study
|
[
0.98046875,
0.01416015625,
0.0055389404296875
] |
[
0.92236328125,
0.07208251953125,
0.00295257568359375,
0.0026874542236328125
] |
Although different surgeons performed the procedures, the quality of care remained consistent throughout the study period, as previously described in a published work .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11278961_p14
|
PMC11278961
|
sec[1]/p[6]
|
2. Materials and Methods
| 3.003906 |
clinical
|
Study
|
[
0.4208984375,
0.57373046875,
0.0055694580078125
] |
[
0.52685546875,
0.451904296875,
0.00275421142578125,
0.0184326171875
] |
For women diagnosed with invasive CC who chose follow-up instead of immediate treatment, we assessed clinical endpoints based on established safety criteria, including recurrence rates and obstetrics outcomes .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p15
|
PMC11278961
|
sec[1]/p[7]
|
2. Materials and Methods
| 2.505859 |
biomedical
|
Study
|
[
0.94189453125,
0.0552978515625,
0.002979278564453125
] |
[
0.978515625,
0.0183868408203125,
0.0009045600891113281,
0.0023593902587890625
] |
We considered a follow-up period of up to 5 years. Follow-up included a Pap smear, a colposcopy if indicated by the Pap smear results, and a comprehensive gynecological examination. We classified patients as lost to follow-up if we lacked documented follow-up data after their surgical procedure.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p16
|
PMC11278961
|
sec[1]/p[8]
|
2. Materials and Methods
| 4.023438 |
biomedical
|
Study
|
[
0.99072265625,
0.0087738037109375,
0.0003826618194580078
] |
[
0.99755859375,
0.0013484954833984375,
0.0005016326904296875,
0.0004134178161621094
] |
To assess obstetric outcomes, we investigated the following data points: childbearing desire (yes or no); pregnancy rate (number of pregnancies achieved after the procedure); delivery mode (vaginal delivery or cesarean section); and obstetric complications, including need for prophylactic cerclage (yes or no), preterm delivery (yes or no), and preterm premature rupture of membranes (yes or no). Spontaneous miscarriages in the first trimester were excluded from the analysis due to the lack of association with conization procedures .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p17
|
PMC11278961
|
sec[1]/p[9]
|
2. Materials and Methods
| 2.541016 |
biomedical
|
Study
|
[
0.99560546875,
0.0030117034912109375,
0.0014791488647460938
] |
[
0.990234375,
0.00901031494140625,
0.0004417896270751953,
0.00045228004455566406
] |
Given the low prevalence of obstetric complications in our population, we opted to analyze them as composite adverse obstetric outcomes. This measure comprehensively included the presence of any of the aforementioned obstetric complications.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p18
|
PMC11278961
|
sec[1]/p[10]
|
2. Materials and Methods
| 3.871094 |
biomedical
|
Study
|
[
0.984375,
0.014984130859375,
0.0007891654968261719
] |
[
0.9921875,
0.006855010986328125,
0.0004451274871826172,
0.0006146430969238281
] |
Our primary objective was to compare the surgical margin positivity rates between CO 2 laser and CK conization for all types of cervical lesions.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p19
|
PMC11278961
|
sec[1]/p[11]
|
2. Materials and Methods
| 3.978516 |
biomedical
|
Study
|
[
0.98974609375,
0.00981903076171875,
0.0005950927734375
] |
[
0.99658203125,
0.0027179718017578125,
0.0004143714904785156,
0.0003476142883300781
] |
The secondary objectives were to investigate, in women with incidental diagnosis of CC, the impacts of the two conization techniques on surgical margin status, recurrence rates and clinical implication, and to evaluate the composite rate of adverse obstetric outcomes in women who opted for follow-up after treatment.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p20
|
PMC11278961
|
sec[1]/sec[0]/p[0]
|
Statistical Methods
| 3.953125 |
biomedical
|
Study
|
[
0.99951171875,
0.00031495094299316406,
0.0002053976058959961
] |
[
0.99853515625,
0.000896453857421875,
0.00030493736267089844,
0.00007301568984985352
] |
The selected population was described using median and interquartile range (IQR) for data which exhibited a non-normal distribution. Absolute and relative frequencies were used for other categorical variables. The Mann–Whitney U test was performed to compare the median between subgroups, as the data showed a non-normal distribution. The existence of any association between categorical variables was investigated using chi-squared tests or Fisher’s exact test, if necessary.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p21
|
PMC11278961
|
sec[1]/sec[0]/p[1]
|
Statistical Methods
| 4.089844 |
biomedical
|
Study
|
[
0.99951171875,
0.000362396240234375,
0.00022113323211669922
] |
[
0.9990234375,
0.0003216266632080078,
0.000354766845703125,
0.0000655055046081543
] |
A multivariate analysis was conducted through a binomial logistic regression, considering as the dependent variable the presence of a positive deep margin (dichotomous) and as independent variables the presence of a preoperative CC diagnosis (dichotomous), the presence of a postoperative CC squamous histology (dichotomous), the presence of a postoperative CC adenocarcinoma histology (dichotomous), and conization type (CK vs. CO 2 laser conization); these were all categorical variables. Logistic regression allows the ascertainment of the simultaneous effects of the independent variables on the likelihood that patients show positive deep margins. Predictive effects for all independent variables are obtained from logistic regression coefficients in terms of odds ratios, and statistical significance for all tests was set at p = 0.05, while statistical analysis was conducted using IBM SPSS Statistics (version 26) software.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11278961_p22
|
PMC11278961
|
sec[2]/p[0]
|
3. Results
| 2.828125 |
biomedical
|
Study
|
[
0.98974609375,
0.0088958740234375,
0.0013761520385742188
] |
[
0.99609375,
0.003116607666015625,
0.00016379356384277344,
0.0004048347473144531
] |
A total of 1270 patients met the inclusion criteria and were enrolled in this study. The study population consisted of 1225 patients (96.5%) who underwent CO 2 laser conization and 45 patients (3.5%) who underwent CK conization.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p23
|
PMC11278961
|
sec[2]/sec[0]/p[0]
|
3.1. Patient Characteristics
| 1.852539 |
biomedical
|
Study
|
[
0.98828125,
0.0089569091796875,
0.002960205078125
] |
[
0.9775390625,
0.01885986328125,
0.002117156982421875,
0.0015916824340820312
] |
Table 1 summarizes the characteristics of the patients included in the study, classified according to the conization technique.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p24
|
PMC11278961
|
sec[2]/sec[0]/p[1]
|
3.1. Patient Characteristics
| 3.974609 |
biomedical
|
Study
|
[
0.98828125,
0.0114593505859375,
0.00047659873962402344
] |
[
0.9970703125,
0.001987457275390625,
0.0004429817199707031,
0.0005559921264648438
] |
The median age at surgery was similar between two groups, 38 years (IQR 31–46) for CO 2 laser and 38.6 years (IQR 33.5–48) for CK conization ( p = 0.321). Local anesthesia was most commonly adopted for CO 2 laser (92.4%), while general anesthesia was more frequent for CK conization (97.8%).
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p25
|
PMC11278961
|
sec[2]/sec[1]/p[0]
|
3.2. Primary Objective
| 4.128906 |
biomedical
|
Study
|
[
0.9970703125,
0.00269317626953125,
0.0002968311309814453
] |
[
0.99853515625,
0.0007734298706054688,
0.00042438507080078125,
0.00017309188842773438
] |
Our primary objective was to assess the rate of positive endocervical or deep margins between the CO 2 laser and CK conization groups for all types of cervical lesions, and the analysis revealed a statistically significant difference ( p = 0.015), with a lower rate of positive margins in the CO 2 laser group (4.3%) compared to CK group (13.3%), as can be seen in Table 1 . Overall, the rates of positive exocervical margins were not statistically significant ( p > 0.05). Interestingly, a strong association ( p < 0.001) between the type of preoperative histology and the positivity of the endocervical or deep margins ( Table 2 ) was noted.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p26
|
PMC11278961
|
sec[2]/sec[1]/p[1]
|
3.2. Primary Objective
| 4.085938 |
biomedical
|
Study
|
[
0.99853515625,
0.0013561248779296875,
0.00027060508728027344
] |
[
0.9990234375,
0.0004448890686035156,
0.0003504753112792969,
0.00010836124420166016
] |
The distribution of preoperative diagnoses also differed significantly between the two conization groups ( p < 0.001). In the CO 2 laser group, the most frequent preoperative diagnosis was cervical intraepithelial neoplasia of grade 3 or lower (≤CIN3), at 93.1%. Conversely, the CK group showed a higher prevalence of adenocarcinoma in situ (AIS).
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p27
|
PMC11278961
|
sec[2]/sec[2]/p[0]
|
3.3. Secondary Objectives
| 3.972656 |
biomedical
|
Study
|
[
0.9912109375,
0.00847625732421875,
0.0004074573516845703
] |
[
0.99609375,
0.0029048919677734375,
0.0003025531768798828,
0.0004742145538330078
] |
According to planned secondary aims, of 1270 cases, we identified 56 cases (4.4%) diagnosed with invasive CC after the conization procedure. Of them, 35 (62.5%) were squamous cell carcinomas and 21 (37.5%) adenocarcinomas. Overall, 34 underwent CO 2 laser conization and 22 underwent CK conization, as detailed in Table 3 and Table 4 .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p28
|
PMC11278961
|
sec[2]/sec[2]/p[1]
|
3.3. Secondary Objectives
| 3.929688 |
biomedical
|
Study
|
[
0.9990234375,
0.0007219314575195312,
0.0003609657287597656
] |
[
0.9990234375,
0.0004930496215820312,
0.0002448558807373047,
0.0000776052474975586
] |
The diagnosis of adenocarcinoma was significantly less frequent in the CO 2 laser conization group when compared to CK conization (17.6% vs. 54.5%; p < 0.01).
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p29
|
PMC11278961
|
sec[2]/sec[2]/p[2]
|
3.3. Secondary Objectives
| 4.09375 |
biomedical
|
Study
|
[
0.9990234375,
0.0004589557647705078,
0.0003211498260498047
] |
[
0.99951171875,
0.0002720355987548828,
0.0001653432846069336,
0.00005990266799926758
] |
The maximum size of CC showed a non-normal distribution for cases treated with both types of conizations. The median for CO 2 laser was 1.5 mm (IQR 0.5–11) and for CK 2.5 mm (IQR 0.5–11), with no significant difference observed using the Mann–Whitney U test ( p = 0.60).
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p30
|
PMC11278961
|
sec[2]/sec[2]/p[3]
|
3.3. Secondary Objectives
| 2.455078 |
biomedical
|
Study
|
[
0.9873046875,
0.010528564453125,
0.0019893646240234375
] |
[
0.9912109375,
0.0070648193359375,
0.0007901191711425781,
0.0008540153503417969
] |
FIGO 2018 staging is shown in Table 5 . The distribution of stages between the two procedures did not differ significantly ( p = 0.19).
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p31
|
PMC11278961
|
sec[2]/sec[2]/p[4]
|
3.3. Secondary Objectives
| 4.066406 |
biomedical
|
Study
|
[
0.998046875,
0.0014801025390625,
0.0004000663757324219
] |
[
0.9990234375,
0.0003895759582519531,
0.0003352165222167969,
0.00010061264038085938
] |
The rate of positive endocervical or deep margins is shown in Table 6 . In this analysis, the conization technique significantly affected the margin positivity, with a higher rate observed in the CO 2 laser group when compared to the CK group (58.8% vs. 22.7%, with p < 0.01).
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p32
|
PMC11278961
|
sec[2]/sec[2]/p[5]
|
3.3. Secondary Objectives
| 4.046875 |
biomedical
|
Study
|
[
0.9990234375,
0.0007448196411132812,
0.00024187564849853516
] |
[
0.99951171875,
0.00024771690368652344,
0.00032806396484375,
0.00008779764175415039
] |
Instead, with multivariate analysis ( Table 7 ), we found that regardless of the surgical technique, postoperative incidental diagnoses of CC for both squamous and adenocarcinoma histology were independent predictors of positive endocervical or deep positive margins, while the type of lesion reported in the preoperative setting was not statistically significant.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p33
|
PMC11278961
|
sec[2]/sec[2]/p[6]
|
3.3. Secondary Objectives
| 3.882813 |
biomedical
|
Study
|
[
0.998046875,
0.0015239715576171875,
0.00041675567626953125
] |
[
0.9990234375,
0.0007352828979492188,
0.0003135204315185547,
0.00012111663818359375
] |
Patients treated with CK conization had an odds ratio of 0.28 for positive endocervical/deep margins compared to those treated with CO 2 laser conization, although statistical significance was not achieved ( p = 0.06).
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p34
|
PMC11278961
|
sec[2]/sec[2]/p[7]
|
3.3. Secondary Objectives
| 3.486328 |
biomedical
|
Study
|
[
0.92333984375,
0.07550048828125,
0.0010709762573242188
] |
[
0.9814453125,
0.013336181640625,
0.0013971328735351562,
0.00406646728515625
] |
After a median follow-up of 53 months (IQR 32–76), no recurrences of cervical cancer were recorded in patients treated with either CO 2 laser or CK conization, regardless of FIGO 2018 stage.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p35
|
PMC11278961
|
sec[2]/sec[2]/p[8]
|
3.3. Secondary Objectives
| 3.857422 |
biomedical
|
Study
|
[
0.888671875,
0.1102294921875,
0.0011997222900390625
] |
[
0.9873046875,
0.00775146484375,
0.001361846923828125,
0.003673553466796875
] |
Of the 56 patients diagnosed with invasive carcinoma, 42 (75%) underwent radical treatment and 14 (25%) opted for exclusive follow-up, due to their desire for pregnancies. This latter subgroup included seven patients who underwent CO 2 laser conization and seven who underwent CK conization. The prevalence of composite adverse obstetric outcomes was very low, with only one case (7.1%) observed, in a patient who underwent CK conization.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p36
|
PMC11278961
|
sec[3]/p[0]
|
4. Discussion
| 4.082031 |
biomedical
|
Study
|
[
0.99853515625,
0.0014047622680664062,
0.00021970272064208984
] |
[
0.99853515625,
0.0005340576171875,
0.0007834434509277344,
0.00014317035675048828
] |
In our retrospective analysis, the cervical conization using CO 2 laser offers, overall, a lower rate of positive endocervical or deep margins when compared to CK conization. In cases of incidental diagnosis of CC, we found that the probability of having either positive endocervical or deep margins after CO 2 laser or CK conization is the same. There is a higher risk of having positive endocervical or deep margins in incidental adenocarcinoma when compared to squamous carcinoma, regardless of the conization technique.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p37
|
PMC11278961
|
sec[3]/p[1]
|
4. Discussion
| 4.105469 |
biomedical
|
Study
|
[
0.9990234375,
0.0008344650268554688,
0.0002206563949584961
] |
[
0.99853515625,
0.00039386749267578125,
0.0011587142944335938,
0.00010335445404052734
] |
Incomplete excision of cervical lesions, defined by positive endocervical or deep surgical margins, is a concern, since it can lead to residual disease and impact future treatment decisions . Therefore, our primary objective was to evaluate margin status. While no significant difference emerged in exocervical margin positivity between the techniques, the CO 2 laser conization showed a lower rate of positive endocervical or deep margins, compared to CK conization, for all types of cervical lesions (4.3% vs. 13.3%). This finding aligns with a 2017 meta-analysis by Arbyn et al. which considered the margin status for three methods (LEEP, CO 2 laser and CK conization), demonstrating a lower positive margin rate for CO 2 laser (17.8%) compared to CK (20.2%) across both endo- and exocervical margins. They also observed no significant change in positive margin rates for either technique over a considerable time frame .
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999994 |
PMC11278961_p38
|
PMC11278961
|
sec[3]/p[2]
|
4. Discussion
| 3.957031 |
biomedical
|
Study
|
[
0.99951171875,
0.0002410411834716797,
0.00027751922607421875
] |
[
0.978515625,
0.0005173683166503906,
0.0208282470703125,
0.0001456737518310547
] |
These results are further supported by Bogani et al. who investigated LEEP and CO 2 laser in relation to positive margins and reported a higher prevalence with LEEP (11.2%) compared to CO 2 laser (4.2%), particularly for endocervical margins (6% vs. 2.2%). However, a recent study by Mosseri et al. found no association between surgical method (LEEP vs. laser excision) and margin positivity.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p39
|
PMC11278961
|
sec[3]/p[3]
|
4. Discussion
| 4.054688 |
biomedical
|
Study
|
[
0.9990234375,
0.0006165504455566406,
0.0002073049545288086
] |
[
0.99951171875,
0.0002570152282714844,
0.0002856254577636719,
0.00008744001388549805
] |
Interestingly, our study revealed a significant association between preoperative diagnosis and margin positivity. In fact, 91.7% of patients with negative margins had a preoperative histological diagnosis of CIN3 or lower. This suggests that the risk of positive margins might be lower for cervical intraepithelial neoplasia compared to more advanced lesions (namely, CIS and AIS). Of course, conversely, the difference in preoperative diagnoses may explain the observed higher rate of positive margins in the CK group with a higher rate of AIS lesions.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p40
|
PMC11278961
|
sec[3]/p[4]
|
4. Discussion
| 3.685547 |
biomedical
|
Review
|
[
0.998046875,
0.0006012916564941406,
0.0015392303466796875
] |
[
0.432373046875,
0.00736236572265625,
0.5595703125,
0.0005164146423339844
] |
However, the relationship between disease severity and margin involvement is inconsistent in the literature. While Shin et al. reported no such association , Costa et al. found disease severity to be the most significant factor . Similarly, Arbyn et al. observed a rising rate of incomplete excision with increasing lesion severity . These contrasting findings suggest the need for further investigation into the factors influencing margin positivity.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p41
|
PMC11278961
|
sec[3]/p[5]
|
4. Discussion
| 4.175781 |
biomedical
|
Study
|
[
0.99853515625,
0.0011968612670898438,
0.00020563602447509766
] |
[
0.99853515625,
0.000492095947265625,
0.000743865966796875,
0.00015735626220703125
] |
Interestingly, among the identified incidental cases of CC, no recurrences were observed, regardless of the conization technique. However, the type of conization significantly impacted margin involvement ( p < 0.01), with a higher rate of positive margins observed in the CO 2 laser group compared to the CK group, contrasting with our results across the whole population. The diagnosis of adenocarcinoma was significantly more frequent ( p < 0.01) in the CK conization group (68.2%) compared to CO 2 laser conization (17.6%), but this discrepancy can reflect the preoperative histological selection bias. The postoperative incidental diagnosis of CC (either squamous or adenocarcinoma) significantly increased the odds of having positive endocervical or deep margin rates, regardless of the surgical technique. This result can be interpreted in the context of a missed diagnosis of CC in the preoperative setting, potentially with a lesion inside the endocervical canal. Interestingly, patients treated with CK conization had a lower odds ratio for positive endocervical/deep margins, compared to those treated with CO 2 laser conization. Colposcopy plays a crucial role in diagnosing cervical diseases. Biopsy guided by colposcopy provides a histological diagnosis, which is essential for assessing the most appropriate treatment. However, a key limitation of colposcopy is the biopsy area, which depends on whether the entire lesion is visible and accessible. As the transformation zone migrates deeper into the cervical canal with age and menopause, complete removal of the entire lesion becomes more challenging. Consequently, a negative preoperative biopsy may miss a deeper CC component within the canal.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p42
|
PMC11278961
|
sec[3]/p[6]
|
4. Discussion
| 2.992188 |
biomedical
|
Other
|
[
0.841796875,
0.1544189453125,
0.0039215087890625
] |
[
0.00888824462890625,
0.982421875,
0.00171661376953125,
0.006805419921875
] |
In our clinical practice, CO 2 laser conization is the most frequently employed technique due to its several advantages. First, it can be performed in an outpatient setting, without the need for general anesthesia. Additionally, the CO 2 laser offers advantages in terms of pain reduction and superior hemostasis due to its tissue-coagulating properties.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p43
|
PMC11278961
|
sec[3]/p[7]
|
4. Discussion
| 4.105469 |
biomedical
|
Study
|
[
0.9951171875,
0.004428863525390625,
0.00035190582275390625
] |
[
0.9951171875,
0.002178192138671875,
0.0023345947265625,
0.0004074573516845703
] |
According to our findings, it seems that surgeons prefer reserving the use of CK conization for specific cases, particularly those with a preoperative diagnosis of AIS, as can be seen in Table 1 . This preference can arise because of the well-known deeper location of AIS lesions within the cervical canal and because, with the use of CK conization, the surgeon can remove completely the endocervical part of the cervix. Based on our findings regarding the lower odds of overall positive endocervical or deep margins with CK conization, further studies specifically investigating the broader application and long-term outcomes of CK conization are warranted, and we cannot now conclude that CK conization might be preferable when colposcopy cannot explore the cervical canal even if the cranial margin of the lesion is not visible.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p44
|
PMC11278961
|
sec[3]/p[8]
|
4. Discussion
| 3.916016 |
biomedical
|
Study
|
[
0.99951171875,
0.00028133392333984375,
0.00024008750915527344
] |
[
0.9990234375,
0.00043964385986328125,
0.0006756782531738281,
0.00007474422454833984
] |
Importantly, we must consider the impact of conization on reproductive potential. Studies suggest that CK conization may be associated with higher rates of obstetric complications, such as preterm delivery, premature rupture of membranes and lower birth weight . However, due to the limited sample size in our study, including only one case of CK conization with a composite adverse obstetric outcome, further research with a larger cohort of women is necessary to definitively assess the association between CK conization and these obstetric complications.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11278961_p45
|
PMC11278961
|
sec[3]/p[9]
|
4. Discussion
| 4.054688 |
biomedical
|
Study
|
[
0.99755859375,
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0.0002307891845703125
] |
[
0.99853515625,
0.0006394386291503906,
0.0004687309265136719,
0.00025844573974609375
] |
The limitations of our study include its retrospective and single-center design, introducing potential selection bias and limiting the generalizability of our findings; in fact, this is not a randomized clinical trial. Another substantial limitation is the unbalanced proportion of women undergoing CO 2 laser vs. CK conization, and hence, generalization to the overall population can suffer by this selection bias. Additionally, the analysis did not evaluate lesion depth, multifocality or HPV testing status, and long-term obstetrical outcomes were unavailable, as well as records of pap smear status at the moment of colposcopy.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11278961_p46
|
PMC11278961
|
sec[3]/p[10]
|
4. Discussion
| 4.003906 |
biomedical
|
Study
|
[
0.9990234375,
0.0007729530334472656,
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] |
[
0.8466796875,
0.07000732421875,
0.08233642578125,
0.001007080078125
] |
Future studies employing prospective, multicenter, randomized controlled trials are needed to address these limitations and assess more robustly the impacts of conization technique on clinical and obstetrical outcomes. These future studies should also take into account the triaging pap smear and HPV testing status obtained before colposcopy and use these elements of data to build a decisional algorithm or score to select the most appropriate excisional treatment.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11278961_p47
|
PMC11278961
|
sec[4]/p[0]
|
5. Conclusions
| 4.097656 |
biomedical
|
Study
|
[
0.9990234375,
0.0008244514465332031,
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] |
[
0.9990234375,
0.00040984153747558594,
0.000377655029296875,
0.00010967254638671875
] |
To our knowledge, this is the first study comparing CO 2 laser and CK conization in preinvasive lesions of the cervix. A lower rate of positive endocervical or deep margins when using CO 2 laser conization is observed, as compared to CK conization. In cases of incidental diagnosis of CC, we found that the probability of having either positive endocervical or deep margins after CO 2 laser or CK conization is the same. A higher risk of having positive endocervical or deep margins in incidental adenocarcinoma was seen when compared to squamous carcinoma, regardless of the conization technique.
|
[
"Federico Ferrari",
"Emma Bonetti",
"Giulia Oliveri",
"Andrea Giannini",
"Elisa Gozzini",
"Jacopo Conforti",
"Filippo Alberto Ferrari",
"Federica Salinaro",
"Giancarlo Tisi",
"Giuseppe Ciravolo",
"Alessandro Favilli",
"Franco Odicino"
] |
https://doi.org/10.3390/medicina60071056
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
38960143_p0
|
38960143
|
sec[1]/p[0]
|
Introduction
| 3.615234 |
biomedical
|
Other
|
[
0.9990234375,
0.0003070831298828125,
0.0004887580871582031
] |
[
0.28271484375,
0.397216796875,
0.318359375,
0.0015707015991210938
] |
Cervical cancer is caused by a persistent infection of hrHPV. The vast majority of new cases (87%) and deaths (91%) occur in low and middle-income countries (LMICs) . Recent advances in cervical screening include the switch to objective molecular testing for the detection of hrHPV types in many national screening programs and the development of new strategies such as a self-sampling to attract more women into screening .
|
[
"Monica Molano",
"Dorothy A. Machalek",
"Samuel Phillips",
"Grace Tan",
"Suzanne M. Garland",
"David Hawkes",
"Prisha Balgovind",
"Reza Haqshenas",
"Steve G. Badman",
"John Bolnga",
"Josephine Gabuzzi",
"Zure Kombati",
"Gloria M. Munnull",
"Julia ML. Brotherton",
"Marion Saville",
"John M. Kaldor",
"Pamela J. Toliman",
"Andrew J. Vallely",
"Gerald L. Murray"
] |
https://doi.org/10.1016/j.tvr.2024.200288
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
38960143_p1
|
38960143
|
sec[1]/p[1]
|
Introduction
| 3.941406 |
biomedical
|
Review
|
[
0.9990234375,
0.0006070137023925781,
0.0004153251647949219
] |
[
0.3369140625,
0.006626129150390625,
0.65576171875,
0.0006632804870605469
] |
HPV testing is more sensitive than cytology for the detection of cervical abnormalities and of cancer. However, as most infections spontaneously resolve, not all persistently hrHPV+ women will have underlying disease. As such, referral of all positive women for treatment will result in many unnecessary procedures. In fact, first evaluations of the primary HPV screening in Europe and Australia with triage by cytology and/or HPV16/18 genotyping showed a substantial increase in colposcopy referrals compared with cytology-based screening .
|
[
"Monica Molano",
"Dorothy A. Machalek",
"Samuel Phillips",
"Grace Tan",
"Suzanne M. Garland",
"David Hawkes",
"Prisha Balgovind",
"Reza Haqshenas",
"Steve G. Badman",
"John Bolnga",
"Josephine Gabuzzi",
"Zure Kombati",
"Gloria M. Munnull",
"Julia ML. Brotherton",
"Marion Saville",
"John M. Kaldor",
"Pamela J. Toliman",
"Andrew J. Vallely",
"Gerald L. Murray"
] |
https://doi.org/10.1016/j.tvr.2024.200288
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |