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Background: Uterine adenomyosis is associated with chronic pelvic pain, abnormal uterine bleeding, and infertility. The pathogenesis of adenomyosis is still unclear. Circular RNAs (circRNAs) have been implicated in several benign diseases and malignant tumors. We aimed to explore the co-dysregulated circular RNA profile in the eutopic endometrium and endometrial-myometrial interface (EMI) of adenomyosis.Methods: Total RNA was extracted from the eutopic endometrium and EMI of 5 patients with adenomyosis and 3 patients without adenomyosis. Next-generation sequencing was performed to identify the circRNA expression profile of the two tissue types. Bioinformatics analysis was performed to predict circRNA-binding miRNAs and miRNA-binding mRNAs and construct ceRNA networks, and functional enrichment analysis was performed to predict the biological functions of circRNAs.Results: Among the adenomyosis patients, 760 circRNAs were significantly upregulated and 119 circRNAs were significantly downregulated in the EMI of adenomyosis, while 47 circRNAs were significantly upregulated and 17 circRNAs were significantly downregulated in the eutopic endometrium of adenomyosis. We identified hsa_circ_0002144 and hsa_circ_0005806 as co-upregulated and hsa_circ_0079536 and hsa_circ_0024766 as co-downregulated in the eutopic endometrium and EMI. Bioinformatics analysis was performed to construct a ceRNA network of codifferentially expressed circRNAs. The MAPK signaling pathway is the most important signaling pathway involved in the function of the ceRNA network.Conclusions: Co-dysregulated circRNAs were present in the eutopic endometrium and EMI of adenomyosis. MiRNA binding sites were observed for all of these circRNAs and found to regulate gene expression. Co-dysregulated circRNAs may induce the eutopic endometrial invagination process through the MAPK signaling pathway and promote the progression of adenomyosis. [ABSTRACT FROM AUTHOR]

Purpose: To study the predictive value of the DNA methylation levels of JAM3, SOX1, SLIT2, C13ORF18, and TERT in the cervical intraepithelial neoplasia prognosis.Method: In the present study, 139 cases were collected and followed up for 24 months. The DNA methylation levels of JAM3, SOX1, SLIT2, C13ORF18, and TERT were tested from their exfoliated cells. One-way ANOVA, receiver operating characteristic (ROC) curve analyses were conducted to analyze the data.Results: The DNA methylation of the five genes was associated with prognosis of CIN. The levels of methylation increased as the progression of lesion for the prognosis. For CIN1, difference between DNA methylation of JAM3, SOX1, SLIT2, and C13ORF18 had significance statistically (P < 0.001). Sensitivity (95.2%) and specificity (93.1%) of JAM3 were the highest compared with other genes for the prognosis of CIN1. In addition, for CIN2/3, DNA methylation of JAM3, SOX1, SLIT2, TERT, and C13ORF18 had difference statistically (P < 0.001). JAM3 were also the highest in sensitivity (95.2%) and specificity (93.1%) compared with other genes for the prognosis of CIN2/3.Conclusions: Our data suggest for the first time that DNA methylation levels are associated with prognosis of CIN significantly. DNA methylation levels of some genes, especially JAM3, may serve as markers for the prediction of the CIN prognosis, including CIN1 nature prognosis and CIN2/3 after treatment. [ABSTRACT FROM AUTHOR]

Adenomyosis (ADS) is a common benign gynecological disease. Abnormal proliferation at the endometrial-myometrial interface (EMI) plays a crucial role in the occurrence and progression of ADS. miR-141-3p is associated with cell proliferation and apoptosis. However, the specific mechanism of miR-141-3p in the etiology of ADS is still unknown. In this study, we explored the effects of miR-141-3p on the proliferation and apoptosis of ADS EMI smooth muscle cells (SMCs). We collected EMI tissues for the primary culture of SMCs from 25 patients diagnosed with ADS and 20 without ADS. Real-time quantitative polymerase chain reaction and western blot were used to measure the mRNA and protein expression levels of miR-141-3p, JAK2, STAT3, phospho-JAK2, and phospho-STAT3 in ADS EMI SMCs. The cell counting kit 8 assay and flow cytometry analysis were used to evaluate the proliferation and apoptosis of EMI SMCs. The miR-141-3p mimic/inhibitor was used to increase or decrease the expression level of miR-141-3p. We added WP1066 to block the phosphorylation of JAK2/STAT3 pathway components. The miR-141-3p levels were decreased, while JAK2 and STAT3 levels were increased in ADS EMI SMCs. miR-141-3p overexpression significantly inhibited the proliferation and enhanced the apoptosis of EMI SMCs, whereas a decrease in miR-141-3p expression level was connected to the opposite results. Meanwhile, inactivated JAK2/STAT3 pathway decreased proliferation and enhanced apoptosis of EMI SMCs after WP1066 treatment. Furthermore, rescue experiments confirmed that the JAK2/STAT3 pathway was the downstream pathway of miR-141-3p and reduced the effect of miR-141-3p on the proliferation and apoptosis of EMI SMCs. These results demonstrate that miR-141-3p regulates the proliferation and apoptosis of ADS EMI SMCs by modulating the JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Background: The denomyotic junctional zone (JZ) plays an important role in the pathogenesis of adenomyosis. Proliferating cell nuclear antigen (PCNA) is an important nuclear marker of cell proliferation. This study aimed to evaluate the effects of the cannabinoid receptor CB1 on proliferation and apoptosis in the JZ in women with and without adenomyosis. Methods: JZ smooth muscle cells (JZSMCs) of the adenomyosis and control groups were collected and cultivated. Immunohistochemistry and immunoblotting were used for protein localization and expression detection of CB1 and PCNA. Additionally, qRT-PCR was used to quantitatively analyse the mRNA expression of the two. AM251 and ACEA were used to regulate the function of CB1 receptors, and CCK-8 assay and flow cytometry assay were used to verify the proliferation and apoptosis of JZSMCs after regulation. Results: We demonstrated that in normal JZSMCs CB1 and PCNA messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. CB1 and PCNA expression in JZSMCs from women with ADS was significantly higher than that in control women and did not significantly differ across the menstrual cycle. CB1 receptor antagonist AM251 inhibited the proliferation of adenomyotic JZSMCs in a dose-dependent manner. The CB1 receptor agonist ACEA significantly promoted the proliferation of adenomyotic JZSMCs. The apoptosis rate of adenomyotic JZSMCs treated with AM251 was significantly higher than that of JZSMCs from the untreated control group. The apoptosis rate was significantly decreased in the ACEA group compared with that in the untreated control group. Furthermore, AM251 suppressed the phosphorylation of AKT and Erk1/2 in adenomyotic JZSMCs. The CB1 agonist ACEA significantly promoted the phosphorylation of AKT and Erk1/2. Conclusions: Our results indicated that the levels of CB1 and PCNA were increased in patients with adenomyosis and that cyclic changes were lost. CB1 may affect uterine JZ proliferation and apoptosis in adenomyosis by enhancing AKT and MAPK/Erk signalling. [ABSTRACT FROM AUTHOR]

• The found gene module associates with the ubiquitin-mediated proteolysis pathway. • This gene module drives the proliferation of endometriosis endometrial cells. • GWES of 142 patients and 71 control subjects were analysed in this study. • WGCNA enabled the analysis of co-expression gene clusters rather than single-gene. • The NNET model discovered the clinical value of hub genes for endometriosis. Is abnormal gene module expression in the eutopic endometrium related to the occurrence of endometriosis? Nine datasets of normal and eutopic endometrium were searched and collected through the National Center for Biotechnology Information Gene Expression Omnibus, which included genome-wide expression studies of 71 normal cases and 142 endometriosis cases. Surrogate variable analysis was used for dataset integration. The network module and hub genes were selected by weighted gene co-expression network analysis. Machine learning was used to establish a diagnostic model of endometriosis. A gene module that was most relevant to endometriosis was selected through weighted gene co-expression network analysis. After further analysis of this module, four hub genes that represent the function of this module were selected: SCAF11, KRAS, MDM2 and KIF3A. Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the four hub genes revealed that all of them were most highly correlated with genes enriched in the ubiquitin-mediated proteolysis pathway. Moreover, in the correlation analysis between hub genes and Jab1, SCAF11 was found to be closely related to Jab1. Furthermore, hub genes were effective indicators for clinical diagnosis. The deep machine learning diagnostic model based on hub genes was highly sensitive. The gene module identified is highly correlated with endometriosis. The four hub genes in this module degrade p27kip1 through the ubiquitin-mediated proteolysis pathway to regulate the endometrium cell cycle and affect the development of endometriosis. The hub genes and the deep learning model based on them are valuable for clinical diagnosis. [ABSTRACT FROM AUTHOR]

• Preoperative estrogen therapy may improve the short-term prognosis of IUAs. • There was no sufficient evidence of the effect on reproductive outcomes. • More well-designed, randomized controlled trials are needed. The aim of this systematic review and meta-analysis was to assess the effect of oestrogen therapy as a preoperative intervention for improving clinical outcomes and fertility outcomes in women with intrauterine adhesions (IUA). A systematic search of PubMed, Embase, The Cochrane Library, clinicaltrials.gov, OVID and Chinese databases was carried out to identify relevant studies published before December 2019. Outcomes were expressed as odds ratios and 95% confidence intervals. Five cohort studies with moderate to high methodological quality were included in the meta-analysis. Preoperative oestrogen therapy was strongly associated with better clinical outcome at second-look hysteroscopy (OR 2.72; 95% CI 1.49 to 4.96; P = 0.001); whereas no significant difference was found in menstruation improvement and conception rate (OR 1.45; 95% CI, 0.95 to 2.23; P = 0.09; and OR 0.96; 95% CI 0.60 to 1.54; P = 0.87, respectively). The overall quality of the evidence ranged from moderate to very low. Preoperative oestrogen therapy may improve the short-term prognosis of IUA at second-look hysteroscopy, whereas the long-term prognosis-fertility outcome was similar to the control group. More strictly designed research studies are needed to assess the effectiveness of oestrogen administration before hysteroscopic adhesiolysis. [ABSTRACT FROM AUTHOR]

Objectives: To determine the feasibility and performance of sentinel lymph-node (SLN) mapping among women with high-risk endometrial cancer (EC).Materials and Methods: Ninety-eight patients at high-risk EC were enrolled in this retrospective surgical trial from August 2016 to August 2018. All patients underwent intraoperative SLN biopsy, with ICG injection for laparoscopic staging; this was followed by pelvic and paraaortic lymphadenectomy (LAD). Outcomes included SLN detection rate, false-negative SLN algorithm rate, and the negative predictive value (NPV) of the SLN algorithm. The Chi-square test was used to analyze the relationship between SLN mapping and the risk factors. Then, we performed Kappa consistency check (P < 0.05 with Meaning), to estimate the consistency of SLN and lymph-node metastasis.Results: Successful biopsy occurred in 94 patients (170 sides) among 98 patients (196 sides). At least 1 SLN was identified in 86.7% (170/196). Overall, the false-negative rate (FNR) was 11.8% (2/17), NPV was 97.3% (72/74), and sensitivity was 88.2% (15/17). 22/98 patients (22.4%) with high-risk EC had at least one metastatic lymph node identified. When the SLN algorithm was retrospectively applied, the FNR was 9.1% (2/22) and sensitivity was 90.9% (20/22). Considering the surgeon's experience, 68 cases of EC (except for 30 patients), the detection rate was 89.7% (122/136), NPV was 98.1% (50/51), and the FNR was 5.6% (1/18). The factor significantly affecting the detection rate of SLNs was lymphovascular space invasion (LVSI) (P = 0.016). SLN metastasis of EC was associated with depth of myometrial invasion (P = 0.034). The analysis result of SLN and the consistency of pelvic lymph-node metastasis status. As detected by Kappa coefficient was 0.939 (P < 0.001), suggests highly consistency.Conclusions: Our SLN detection rate for high-risk EC was the same as previously reported. When SLN is not detected, better after 30 patients' experience, is a reasonable alternative to complete LAD in high-risk EC. In addition, SLN shows high co-occurrence with pelvic lymph nodes. Therefore, SLN biopsy can be used to diagnose high-risk EC. [ABSTRACT FROM AUTHOR]