ERß-activated LINC01018 promotes endometriosis development by regulating the CDC25C/CDK1/CyclinB1 pathway.

Endometriosis refers to as an estrogen-dependent disease. Estrogen receptor ß (ERß), the main estrogen receptor subtype which is encoded by the estrogen receptor 2 (ESR2) gene, can mediate the action of estrogen in endometriosis. Although selective estrogen receptor modulators can target the ERß, they are not specific due to the wide distribution of ERß. Recently, long noncoding RNAs have been implicated in endometriosis. Therefore, we aim to explore and validate the downstream regulatory mechanism of ERß, and to investigate the potential role of long intergenic noncoding RNA 1018 (LINC01018) as a nonhormonal treatment for endometriosis. Our study demonstrates that the expression levels of ESR2 and LINC01018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINC01018 expression. Mechanistically, ERß directly binds to an estrogen response element located in the LINC01018 promoter region and activates LINC01018 transcription. Functionally, ERß can regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro. Consistent with these findings, the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo. In summary, our study demonstrates that the ERß/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.

Rapidly growing extensive polypoid endometriosis after gonadotropin-releasing hormone agonist discontinuation: A case report.

BACKGROUND: Polypoid endometriosis (PEM) is a rare and unique type of endometriosis. To date, no article has provided a systematic report of this disease. The current article provides a complete report on rare PEM based on ultrasound, magnetic resonance imaging, intraoperative findings and postoperative pathology data. CASE SUMMARY: A 38-year-old female patient was admitted to our hospital after complaining of "vague pain in the right lower quadrant with an aggravated menstrual period for 8 mo". The patient underwent laparoscopic exploratory surgery on January 7, 2022. The postoperative pathology revealed extensive PEM. CONCLUSION: PEM is a type of endometriosis that is a benign disease but has biological properties similar to malignant tumours.

Metabolomic and Transcriptomic Analysis of Effects of Three MUFA-Rich Oils on Hepatic Glucose and Lipid Metabolism in Mice.

SCOPE: Olive oil, rapeseed oil, and lard are dietary fats rich in monounsaturated fatty acids, but the effects of dietary oils enriched in monounsaturated fatty acids on hepatic lipid deposition have seldom been compared. METHODS AND RESULTS: Ninety 8-week-old C57BL/6J male mice are randomly divided into six groups and fed diets containing lard, rapeseed oil, or olive oil with a 10% or 45% fat energy supply for 16 weeks. Under high-fat conditions, serum total cholesterol levels in the lard and olive oil groups are significantly higher than those in the rapeseed oil group. Hepatic lipid content in the olive oil group is higher than that in the other two groups. Compared with rapeseed oil, lard increases the liver levels of arachidonic, palmitic, and myristic acids and decreases the levels of eicosapentaenoic linolenic acid and linoleic acid. Olive oil increases the liver levels of docosatrienoic, arachidonic, oleic, and myristic acids; maltose; and fructose and decreases the levels of eicosapentaenoic, linolenic, and linoleic acids. CONCLUSION: Olive oil probably causes hepatic lipid deposition in mice, which may enhance hepatic lipid synthesis by activating the starch and sucrose metabolic pathways. By contrast, rapeseed oil shows a significant anti-lipid deposition effect on the liver.

MicroRNA-92a-3p Inhibits Cell Proliferation and Invasion by Regulating the Transcription Factor 21/Steroidogenic Factor 1 Axis in Endometriosis.

Endometriosis (EMS) is an estrogen-dependent disease. However, little is known about the regulation of estrogen, a potential therapeutic target, in EMS, which remains very poorly managed in the clinic. We hypothesized that microRNAs (miRNAs) can be exploited therapeutically to regulate transcription factor 21 (TCF21) and steroidogenic factor-1 (SF-1) gene expression. In our study, paired eutopic and ectopic endometrial samples were obtained from women with EMS and processed by a standard protocol to obtain human endometrial stromal cells (EMs) for in vitro studies. We found that miR-92a-3p levels were decreased in ectopic endometrium and ectopic stromal cells (ESCs) compared with paired eutopic lesions. miR-92a-3p overexpression significantly suppressed the proliferation and migration of ESCs, whereas a decreased level of miR-92a-3p generated the opposite results. Next, we identified TCF21 as a candidate target gene of miR-92a-3p. In vitro cell experiments showed that miR-92a-3p negatively regulated the expression of TCF21 and its downstream target gene SF-1. Moreover, cell proliferation and invasion ability decreased after the silencing of SF-1 and increased after SF-1 overexpression. We also observed that silencing SF-1 while inhibiting miR-92a-3p partially blocked the increase in cell proliferation and invasion ability caused by miR-92a-3p knockdown while overexpressing both SF-1 and miR-92a-3p mitigated the impairment in cell proliferation and invasion ability caused by miR-92a-3p overexpression. Our results may provide a novel potential therapeutic target for the treatment of EMS.

Assessment of Two Formulations of Triptorelin in Chinese Patients with Endometriosis: A Phase 3, Randomized Controlled Trial.

INTRODUCTION: This phase 3, randomized, open-label, active-controlled, multicenter study investigated the efficacy of triptorelin pamoate prolonged-release (PR) 3-month in Chinese patients with endometriosis by demonstrating the noninferiority of the 3-month formulation to the standard of care, triptorelin acetate PR 1-month. METHODS: The trial was conducted in 24 clinical centers in China, and included 300 Chinese women (18-45 years) with endometriosis and regular menstrual cycles who required treatment with a gonadotropin-releasing hormone agonist for 6 months. One group of patients (n = 150) was treated with triptorelin pamoate PR 3-month (15 mg per injection, once every 12 weeks), and the other (n = 150) with triptorelin acetate PR 1-month (3.75 mg per injection, once every 4 weeks). The primary outcome measure was the proportion of patients with estradiol (E2) concentrations suppressed to castration levels (≤ 184 pmol/L, or 50 pg/mL) after 12 weeks of treatment. RESULTS: Triptorelin pamoate PR 3-month was noninferior to triptorelin acetate PR 1-month for the treatment of endometriosis: over 98% of patients in both groups were chemically castrated at week 12. Both formulations were also equally efficacious in reducing endometriosis-associated pelvic pain, and reducing serum concentrations of E2, luteinizing hormone, and follicle-stimulating hormone over time. No new safety concerns were identified. CONCLUSION: Triptorelin pamoate PR 3-month is a valid alternative to triptorelin acetate PR 1-month for the treatment of Chinese women with endometriosis, with fewer injections and a potentially lower burden of care. TRIAL REGISTRATION: NCT03232281.

Long Intergenic Non-Protein Coding RNA 02381 Promotes the Proliferation and Invasion of Ovarian Endometrial Stromal Cells through the miR-27b-3p/CTNNB1 Axis.

PURPOSE: Catenin Beta 1 (CTNNB1) is a key regulator of cell proliferation and invasion in endometriosis; however, its upstream factor is not clear. Long noncoding RNAs may participate in endometriosis. The aim of this study was to investigate the mechanism of interaction between LINC02381 and CTNNB1 in endometriosis. METHOD: Screening and validation of RNAs were completed by whole transcriptional sequencing and qRT-PCR. The subcellular localization of LINC02381 was determined by RNA in situ hybridization and nucleo-cytoplasmic separation. Plasmids were transfected for functional experiments. Luciferase assay was used to verify the binding relationship. RESULTS: The expression of LINC02381 and CTNNB1 was significantly increased in ovarian ectopic endometrial tissues (OSAs) and ectopic endometrial stromal cells (ESCs). When LINC02381 was downregulated in ESCs, the expression of CTNNB1, metallopeptidase 9 (MMP9) and cyclinD1, as well as ESCs invasion and proliferation, decreased. LINC02381 was mainly present in the cytoplasm of ESCs, indicating that it may act as a competitive endogenous RNA. Bioinformatic analysis revealed that microRNA-27b-3p (miR-27b-3p) is a downstream target of LINC02381. miR-27b-3p decreased in OSAs and ESCs. Moreover, when miR-27b-3p was upregulated in ESCs, the expression of CTNNB1, MMP9 and cyclinD1, as well as the invasion and proliferation ability of ESCs, were reduced. Additionally, rescue experiments demonstrated that the expression of CTNNB1, MMP9 and cyclinD1, as well as the invasion and proliferation ability, were significantly increased in the group transfected with both sh-LINC02381 and a miR-27b-3p inhibitor. CONCLUSION: LINC02381 upregulated CTNNB1 by adsorbing miR-27b-3p, causing increased proliferation and invasion of ESCs.

Molecular Characterization and Phylogenetic Analysis of Spirometra Tapeworms from Snakes in Hunan Province.

Sparganosis is a neglected zoonotic parasitic disease that poses huge threats to humans worldwide. Snakes play an important role in sparganosis transmission because they are the most common second intermediate hosts for Spirometra parasites. However, the population genetics of Spirometra isolates from snakes is currently not well studied in China. The present study was performed to explore the molecular characteristics and phylogenetic analysis of Spirometra tapeworms from different species of snakes in Hunan Province. This study obtained 49 Spirometra isolates from 15 geographical areas in Hunan Province, Central China. Subsequently, the 18S and 28S ribosomal DNA (rDNA) fragments were amplified from the isolated parasites, and their sequences were analyzed to assess their genetic diversity. Phylogenetic analyses were performed using the maximum likelihood algorithm. The results showed that sequence variations among these isolates were 0-2.3% and 0-0.1% for 18S and 28S rDNA, respectively. The phylogenetic analysis showed that all Spirometra isolates from Hunan Province were clustered into the same branch with Spirometra erinaceieuropaei isolated from other areas (China, Vietnam, Australia). Moreover, the phylogenetic trees revealed that Spirometra is closely related to Adenocephalus, Pyramicocephalus, Ligula, Dibothriocephalus, Schistocephalus, and Diphyllobothrium. The Spirometra isolates of different hosts/regions in Hunan Province are not host segregated or geographically isolated, and support for the taxonomic status of Spirometra tapeworms in China has been added. These results provide reference values for future accurate identification and taxonomic status of Spirometra tapeworms in China.

Comparison of the Efficacy of Two Laparoscopic Surgical Procedures Combined with Hysteroscopic Incision in the Treatment of Cesarean Scar Diverticulum.

Objective: To investigate the efficacy of two different surgical procedures in combined hysteroscopic and laparoscopic surgery-the "folding suture method" and the "muscle flap filling suture method"-in the treatment of cesarean scar diverticulum (CSD).Methods: The clinical data of 24 patients with CSD who underwent surgery in the Peking University First Hospital from August 2016 to December 2018 were retrospectively analyzed.Results: There was no difference in age, vaginal bleeding time, thickness of the lower uterine segment, operative time and intraoperative bleeding between the two groups. At three months after the operation, the patients of the folding suture and muscle flap groups had an average menstrual period of 6.9 ± 1.8 days and 7.5 ± 3.0 days, respectively, which was 5.8 ± 4.2 days and 4.4 ± 3.8 days, respectively, shorter than that before the operation, as well as a lower segment thickness of the uterus of 6.7 ± 1.8 mm and 6.3 ± 1.7 mm, respectively. Among the patients in the folding suture and muscle flap groups, 8 and 6 cases were cured, and 3 and 6 cases were improved, respectively, resulting in an effective rate of 100%. There was no significant difference in any indicator between the two groups.Conclusion: As two new surgical methods that preserve uterine integrity, the laparoscopic "muscle flap filling suture method" and "folding suture method" combined with hysteroscopic incision are safe and effective treatments for repairing CSD.

Uterine cervical Müllerian adenosarcoma possibly arising from ovarian cystadenofibroma: A case report and review of the literature.

Uterine cervical Müllerian adenosarcoma (MA), a rare malignant tumor of the female reproductive organs, is composed of a benign epithelium and a low-grade malignant stromal component. Because few studies have investigated the clinical management of MA, misdiagnosis often occur. Therefore, we proposed an optimal course of clinical management for patients with MA. MA is possibly a malignant transformation of the cystadenofibroma. In this study, we present a case of a 46-year-old woman who presented with symptoms of MA of the uterine cervix, such as metrorrhagia and a cyst in the cervical canals, after transvaginal excision of the left ovarian mucinous cystadenofibroma.

Extracellular Vesicles Inhibit Proliferation and Invasion of Ovarian Endometrial Stromal Cells and Their Expression of SF-1, ERß, and Aromatase.

Objective: Endometriosis is an estrogen-dependent chronic disease. The abnormal proliferation and invasion of ectopic stromal cells (ESCs) are important manifestations of endometriosis, and it is necessary to find safer and more effective treatments. Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (UC-MSCs) have been shown to be promising for the treatment of many diseases, except endometriosis. The main purpose of this study was to explore the effect of EVs derived from UC-MSCs on ESCs and evaluate the therapeutic value of EVs on endometriosis. Study Design: Following the successful culture and identification of UC-MSCs, we collected the medium of UC-MSCs and extracted EVs by ultracentrifugation. Then, 120 µg/mL EVs were used to stimulate ESCs, which were collected to evaluate cell proliferation and invasion and expression of the estrogen-related proteins steroidogenic factor-1 (SF-1), estrogen receptors ß (ERß), and aromatase. Results: Compared with the control group treated with isodose phosphate buffered saline (PBS), 120 µg/mL EVs exposure significantly decreased the expression of cyclin D1 (mRNA: n = 6, P = 0.02; protein: n = 6, P = 0.000) and matrix metalloproteinase (MMP) 9 (mRNA: n = 6, P = 0.04; protein: n = 6, P = 0.000) of ESCs, which were consistent with Cell Counting Kit-8(CCK-8) results (day 0: NC: 0.29 ± 0.04, 120 µg/mL EVs: 0.28 ± 0.04; day 1: NC: 0.42 ± 0.08, 120 µg/mL EVs: 0.32 ± 0.01; day 2: NC: 0.64 ± 0.07, 120 µg/mL EVs: 0.50 ± 0.05, P = 0.000; day 3: NC: 0.82 ± 0.09, 120 µg/mL EVs: 0.65 ± 0.07, P = 0.000; day 4: NC: 0.95 ± 0.11, 120 µg/mL EVs: 0.76 ± 0.07, P = 0.012; n = 6) and Transwell experiments (n = 6, P = 0.000). In addition, the expression of SF-1 (encoded by NR5A1; mRNA: n = 6, P = 0.000; protein: n = 6, P = 0.000), ERß (encoded by ESR2; mRNA: n = 6, P = 0.000; protein: n = 6, P = 0.000), and aromatase (encoded by CYP19A1; mRNA: n = 6, P = 0.04; protein: n = 6, P = 0.000) in ESCs decreased significantly. Conclusion: Taken together, the results show that 120 µg/mL EVs derived from UC-MSCs can effectively inhibit the proliferation and invasion of ESCs, as well as their expression of SF-1, ERß and aromatase, and thus may lead to the alleviation of endometriosis.

Sirtuin 3 Restores Synthesis and Secretion of Very Low-Density Lipoproteins in Cow Hepatocytes Challenged with Nonesterified Fatty Acids In Vitro.

Fatty liver is closely associated with elevated concentrations of nonesterified fatty acids (NEFA) and a low level of very low-density lipoproteins (VLDL) in blood of dairy cows. High NEFA inhibit the VLDL synthesis and assembly, and cause hepatic triacylglycerol (TAG) deposition. Sirtuin 3 (SIRT3), a mitochondrial deacetylase, antagonizes NEFA-induced TAG accumulation through modulating expressions of fatty acid synthesis and oxidation genes in cow hepatocytes. However, the role of SIRT3 in the VLDL synthesis and assembly was largely unknown. Here we aimed to test whether SIRT3 would recover the synthesis and assembly of VLDL in cow hepatocytes induced by high NEFA. Primary cow hepatocytes were isolated from 3 Holstein cows. Hepatocytes were infected with SIRT3 overexpression adenovirus (Ad-SIRT3), SIRT3-short interfering (si) RNA, or first infected with Ad-SIRT3 and then incubated with 1.0 mM NEFA (Ad-SIRT3 + NEFA). Expressions of key genes in VLDL synthesis and the VLDL contents in cell culture supernatants were measured. SIRT3 overexpression significantly increased the mRNA abundance of microsomal triglyceride transfer protein (MTP), apolipoprotein B100 (ApoB100) and ApoE (p < 0.01), and raised VLDL contents in the supernatants (p < 0.01). However, SIRT3 silencing displayed a reverse effect in comparison to SIRT3 overexpression. Compared with NEFA treatment alone, the Ad-SIRT3 + NEFA significantly upregulated the mRNA abundance of MTP, ApoB100 and ApoE (p < 0.01), and increased VLDL contents in the supernatants (p < 0.01). Our data demonstrated that SIRT3 restored the synthesis and assembly of VLDL in cow hepatocytes challenged with NEFA, providing an in vitro basis for further investigations testing its feasibility against hepatic TAG accumulation in dairy cows during the perinatal period.

Menstrual patterns and disorders among Chinese women of reproductive age: A cross-sectional study based on mobile application data.

ABSTRACT: Menstruation is an important indicator of women's health. Identification of abnormal menstrual patterns in adolescence may improve early diagnosis of potential health concerns in adulthood. This study aimed to evaluate menstrual patterns and disorders of Chinese women of reproductive age based on an APP.From December 2015 to January 2016, a cross-sectional study was conducted. We utilized a mobile application (APP) to collect information about participants' age at menarche, length of menstruation, duration of menstruation, amount of menstrual flow, regularity of menstrual cycle, prevalence of abnormal uterine bleeding and dysmenorrhoea.A total of 156,055 women (25,716 from the questionnaire survey and 130,000 from the mobile APP users) participated in the study. The average age of the subjects was 26.32 ±â€Š6.97 years (median age, 25 years). Mean age at menarche was 13.08 ±â€Š1.87 years; average length of menstrual cycle, 30.9 ±â€Š4.28 days (median 30 days); and average duration of menstruation, 5.01 ±â€Š1.13 days (median 5 days). Women with irregular menstrual cycles accounted for 36.41%. Women aged < 18 years and > 30 years were more likely to experience irregular menstrual cycles. The prevalence of secondary amenorrhoea was 4.07%. More than 20% of women reported abnormal menstrual flow. About 20.11% of women had abnormal uterine bleeding, and 77.65% had dysmenorrhoea. A hot compress was the most commonly used approach to ameliorate dysmenorrhoea. Women with low education and low income and those with high education and high income tended to have menstrual problems.A mobile APP as a survey tool has the advantages of large sample size, low cost, and high efficiency. The use of a mobile APP is an emerging approach for collecting big data in the field of health research. The results showed that the prevalence of menstrual disorders among Chinese reproductive women was high. Healthcare providers should educate girls and their caregivers about menstrual physiology, normal menstrual pattern, and reproductive health to prevent long-term diseases.

The safety and efficacy of a novel method for treatment of HSIL.

PURPOSE: To investigate the efficacy and safety of Nr-CWS on treatment of cervical HSIL. METHOD: In this observational study, 16 patients were treated with Nr-CWS 1 time every 2 days for 6 times as one-course group (OC group), the other 184 patients were treated with Nr-CWS 1 time every 2 days for 12 times between 2 menstruations as two-course group (TC group). The medical information including age, HPV assay, vaginal-cervical cytology, and the pathological result of biopsy before and after treatment was collected. All patients were followed up at least twice after treatment. The LEEP was performed once the patients with persistent HR-HPV infection and/or abnormal TCT after the second follow-up. RESULTS: The cytology remission rate of cervical HSIL in OC and TC group was 100.0% and 87.8%, respectively, which were significant higher than the control (25.0%) with the P value of 2.00 × 10-3 and 2.06 × 10-4. Furthermore, HPV clearance rate was 87.5% and 70.2% in OC and TC group, respectively, which were significant higher than control (32.4%) with the P value of 2.74 × 10-4 and 2.18 × 10-5, respectively. Moreover, the more severe of cytology, the worse effect of HPV clearance for the HPV remission was 75.4%, 68.3%, 67.4%, 65.6% and 64.3% in the negative, LSIL, ASC-US, ASC-H, and HSIL group. 12 patients underwent LEEP after Nr-CWS treatment, 9 (75%) had persistent HSIL and 44.4% cases were found HSIL lesion in the cervical canal. There was no serious adverse reaction observed during treatment and follow-up, four patients were pregnant after treatment and no adverse pregnancy outcomes were observed. CONCLUSION: Nr-CWS is an effective and safe drug for treatment of cervical HSIL for Chinese women, especially for cases without lesions in cervical canal.

Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis.

PURPOSE: Endometriosis is a common, chronic gynecological disease that affects women's fertility potential. Dydrogesterone is an effective and safe drug that is under-utilized due to limited clinical research. The purpose of this evidence mapping is to identify, describe, and analyze the current available evidence regarding dydrogesterone for the treatment of endometriosis. MATERIALS AND METHODS: We performed a search in electronic databases: Medline, The Cochrane Library, EMBASE, PubMed, CNKI, Wanfang, VIP, and CBM. We also hand-searched google for relevant studies. Our primary outcomes included changes in pain relief including pelvic pain, dysmenorrhea, and dyspareunia. Secondary outcomes included pregnancy rate, frequency of analgesic use, and other reported outcomes according to specific settings in the studies. RESULTS: Of 377 references screened, 19 studies were included in the data synthesis involving 1709 female participants. Nearly three-quarters were either randomized control trials or clinical control trials. Compared with gestrinone, dydrogesterone relieved dysmenorrhea, increased the pregnancy rate, and reduced the risk of certain adverse events. Compared with GnRH-a, dydrogesterone also lowered the risk of endometriosis recurrence and elevated transaminase levels. Whether there was any difference in efficacy between dydrogesterone and leuprolide acetate, letrozole or traditional Chinese medicine remains unclear due to insufficient data. CONCLUSIONS: The amount and quality of evidence evaluating the effects of dydrogesterone for the treatment of endometriosis is generally very low. Limited evidence suggests that dydrogesterone may have some advantages over gestrinone, GnRH agonists, and other therapeutic interventions in treating endometriosis. However, this conclusion should be interpreted with caution.

YAP1 inhibits ovarian endometriosis stromal cell invasion through ESR2.

Endometriosis is an estrogen-dependent disease, and estrogen receptor 2 (ESR2) plays a critical role in the pathogenesis of ovarian endometriosis by promoting cell invasion. Yes-associated protein 1 (YAP1) plays suppressive roles in several types of tumors. However, the relationship between YAP1 and ESR2 is not fully understood. The aim of this study was to investigate the regulatory mechanism of YAP1 in terms of ESR2 and YAP1 regulation of endometriotic stromal cell (ECSC) invasion in ovarian endometriosis. Our results demonstrated that YAP1 mRNA and protein levels in eutopic endometrium (EU) tissues were higher than those in paired ectopic endometrium (EC) tissues. ECSCs transfected with siYAP1 exhibited a significant increase in both ESR2 mRNA levels and protein expression. Simultaneously, YAP1 overexpression in ECSCs yielded the opposite results. Co-IP assays demonstrated YAP1-NuRD complex formation by YAP1, CHD4 and MTA1 in ECSCs. YAP1 bound to two sites, (-539, -533) and (-158, -152), upstream of the ESR2 transcription initiation site. YAP1 binding to the two sites of the ESR2 promoter in ECSCs was significantly lower than that in eutopic endometrial stromal cells (EUSCs) from EU tissues. ECSCs transfected with siYAP1 exhibited increased invasion activity, while ECSCs transfected with siESR2 showed inhibition of invasion. However, transfection with siYAP1 and siESR2 together decreased the number of invading cells compared with transfection with siYAP1 alone. Therefore, we conclude that decreased levels of YAP1 in ovarian endometriomas enhance ESR2 expression via formation of a YAP1-NuRD complex, which further binds to the ESR2 promoters. Furthermore, YAP1 inhibits ECSCs invasion.

Postoperative delirium after hysteroscopy in young woman: A case report.

RATIONALE: Postoperative delirium is extremely rare in young women and in minimally invasive endoscopic surgeries in gynecology and obstetrics. It greatly affects both physicians and patients. This report presents a special case of postoperative delirium after hysteroscopy in a young woman and a literature review of the associated etiology, diagnosis, and treatment. PATIENT CONCERNS: A 39-year-old woman was admitted to the gynecology ward following irregular vaginal bleeding for 3 months and an intrauterine space-occupying lesion for 1 week. Hysteroscopy, endometrial polypectomy, and fractional curettage procedures were successfully performed; however, the patient became unresponsive after surgery. DIAGNOSIS: Postoperative delirium. INTERVENTIONS: Sedatives and vasoactive medicines, such as dexmedetomidine, midazolam, and dopamine were administered for maintenance treatment. OUTCOMES: The patients gradually regained consciousness. LESSONS: Physicians should attach importance and improvise effective clinical management strategies for postoperative delirium based on clinical specialty characteristics and related guidelines.

Mitofusin2 regulates the proliferation and function of fibroblasts: The possible mechanisms underlying pelvic organ prolapse development.

The present study aimed to investigate the effects of Mitofusin2 (Mfn2) on the proliferation of human uterosacral ligament fibroblasts and on the expression of procollagen. We also aimed to identify the possible signal transduction pathway involved in the development of pelvic organ prolapse (POP). For this purpose, uterosacral ligaments were harvested from POP and non­pelvic organ prolapse (NPOP) patients for fibroblast culture. Cellular proliferation and the cell cycle were assessed following transduction with lentiviral vectors for the overexpression and suppression of Mfn2. The expression levels of the proteins Mfn2, procollagens, phosphoprotein 21 wild­type p53 activating fragment (p21Waf1), cyclin­dependent kinase 2 (CDK2), extracellular signal­regulated kinase1/2 (ERK1/2) and rapidly accelerated fibrosarcoma­1 (Raf­1) were examined. Overexpression of Mfn2 resulted in the decreased proliferation of cells and the induction of G0/G1 phase arrest. Concomitantly, the relative expression levels of procollagen proteins, CDK2 and the phosphorylation levels of ERK1/2 and Raf­1 proteins were notably decreased, while the levels of the p21waf1 protein were increased in the Mfn2 overexpressing group. Opposing results were reported cells following Mfn2 silencing via RNA interference. The results of the present study indicated that the cell cycle of the fibroblasts, their cellular proliferation and the levels of the procollagen proteins could be inhibited via the Ras­Raf­ERK axis as a result of the increased levels of Mfn2 during the development of POP.

Not Having Been Breastfed May Protect Chinese Women From Developing Deep Infiltrating Endometriosis: Results From Subgroup Analyses of the FEELING Study.

BACKGROUND: This study aimed to investigate potential factors, especially early-life exposures, associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) in Chinese women. METHODS: This is a subgroup analyses of the FEELING study, which was a case-control study that investigated the clinical, lifestyle, and environmental factors associated with OMA and/or DIE in China, Russia, and France. In this subgroup analysis, the data for the Chinese participants were further analyzed using logistic regression model. RESULTS: All women (N = 546) had fully completed the questionnaire. The mean age of the participants was 31.8 (range: 18-41) years. Univariable analysis showed that noncyclic chronic pelvic pain, dysmenorrhea intensity class, and whether breastfed during infancy were distributed differently between patients with OMA or DIE and those with no endometriosis (non-EM) or superficial peritoneal endometriosis (SUP; P < .05). Multivariable analysis revealed that not having been breastfed was a protective factor against OMA and DIE (odds ratio [OR] = 0.33, 95% confidence interval [CI]: 0.16-0.69). Further analysis indicated not having been breastfed was a protective factor for DIE compared with non-EM (OR = 0.13, 95% CI: 0.02-0.88) and with OMA + SUP (OR = 0.19, 95% CI: 0.04-0.85) but was not a protective factor for OMA compared with non-EM (OR = 0.66, 95% CI: 0.32-1.36) and with SUP (OR = 0.63, 95% CI: 0.31-1.30). CONCLUSION: This is the first study suggesting that not having been breastfed might protect against DIE in Chinese women.

Farnesoid X Receptor Agonist GW4064 Inhibits Aromatase and ERß Expression in Human Endometriotic Stromal Cells.

Endometriosis is an estrogen-dependent disease. Farnesoid X receptor (FXR) activation has been shown to inhibit estrogen signaling in breast cancer and testicular tumors. However, the role of FXR in endometriosis is still poorly understood. Here, we aimed to investigate whether FXR activation by its synthetic agonist GW4064 has a therapeutic effect on endometriosis and the underlying molecular mechanisms. We found that the expression of FXR (encoded by the NR1H4 gene) in endometriotic tissues and stromal cells (ESCs) was higher than that in eutopic endometrial tissues and stromal cells. The GW4064 treatment led to a dose-dependent decrease in aromatase and estrogen receptor ß (ERß) expression and induced ERK1/2, p38, AMPK, and Stat3 activation in ESCs. In contrast, ERK1/2 inhibitor reversed the GW4064-induced reduction in aromatase expression. In addition, treatment with p38, AMPK, and Stat3 inhibitors or small interfering RNAs could also reverse the GW4064-induced reduction of ERß expression in ESCs. The GW4064 treatment markedly increased Stat3 phosphorylation, enhancing the binding of Stat3 to the ESR2 promoter, which resulted in the downregulation of ERß. Coimmunoprecipitation assay and chromatin immunoprecipitation analysis revealed that FXR was able to compete with cyclic AMP response element-binding (CREB) protein for binding to a common sequence on the aromatase promoter region after GW4064 treatment in ESCs. Moreover, treatment of endometriosis xenografts with GW4064 suppressed aromatase and ERß expression in nude mice. Our results suggest that FXR may represent a potential therapeutic target for future therapy.

Antifibrotic Effects of Decellularized and Lyophilized Human Amniotic Membrane Transplant on the Formation of Intrauterine Adhesion.

OBJECTIVES: Intrauterine adhesion is a disease involving endometrial fibrosis that arises from injury to the basal layer of the endometrium. Here, we aimed to explore the preventive effects of decellularized and lyophilized amniotic membrane on endometrial fibrosis in a rat model of intrauterine adhesion. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 2 groups. For the intrauterine adhesion group, endometria of left uteri were scraped without treatment. For the intrauterine adhesion plus decellularized and lyophilized amniotic membrane transplant group, decellularized and lyophilized amniotic membrane was sutured onto the scraped wound of left uteri. Right uteri were kept as the control group. At 3, 7, 14, and 28 days after transplant, uteri were sampled for histologic and immunohistochemical evaluation. RESULTS: Histology examination revealed extensive fibrosis with significantly reduced numbers of endometrial glands in uteri in the intrauterine adhesion group. Immunohistochemical staining showed a remarked increase in expression of transforming growth factor ß1 (P < .01) and decreased expression of matrix metalloproteinase-9 (P < .01) in the intrauterine adhesion group. In rats with transplant of decellularized and lyophilized amniotic membrane, endometrial fibrosis apparently improved (P < .05) with reduced expression of transforming growth factor ß1 and increased matrix metalloproteinase-9 expression (P < .05). However, there were no significant differences in the number of endometrial glands or endometrial thickness between the 2 groups (P > .05). CONCLUSIONS: Development of intrauterine adhesion was prevented with transplant of decellularized and lyophilized amniotic membrane via suppression of transforming growth factor ß1 and increased production of matrix metalloproteinase-9 in a rat model.