Introduction: Osteoarthritis (OA) is a highly prevalent degenerative disease worldwide, and tumor necrosis factor (TNF-a) is closely associated with its development. Growth differentiation factor 11 (GDF11) has demonstrated anti-injury and anti-aging abilities in certain tissues; however, its regulatory role in OA remains unclear and requires further investigation. Objectives: To identify whether GDF11 can attenuate osteoarthritis. To exploring the the potential mech-anism of GDF11 in alleviating osteoarthritis. Methods: In this study, we cultured and stimulated mouse primary chondrocytes with or without TNF-a, analyzing the resulting damage phenotype through microarray analysis. Additionally, we employed GDF11 conditional knockout mice OA model to examine the relationship between GDF11 and OA. To investigate the target of GDF11's function, we utilized NLRP3 knockout mice and its inhibitor to verify the potential involvement of the NLRP3 inflammasome. Results: Our in vitro experiments demonstrated that endogenous overexpression of GDF11 significantly inhibited TNF-a-induced cartilage matrix degradation and inflammatory expression in chondrocytes. Furthermore, loss of GDF11 led to NLRP3 inflammasome activation, inflammation, and metabolic dys-function. In an in vivo surgically induced mouse model, intraarticular administration of recombinant human GDF11 alleviated OA pathogenesis, whereas GDF11 conditional knockout reversed this effect. Additionally, findings from the NLRP3-knockout DMM mouse model revealed that GDF11 exerted its pro-tective effect by inhibiting NLRP3. Conclusion: These findings demonstrate the ability of GDF11 to suppress TNF-a-induced inflammation and cartilage degeneration by preventing mitochondrial dysfunction and inhibiting NLRP3 inflamma-some activation, suggesting its potential as a promising therapeutic drug for osteoarthritis. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Ovarian cancer ranks among prevalent malignancies affecting the female reproductive system with an escalating incidence of drug resistance necessitating intensified efforts in drug discovery research for enhanced patient outcomes. Through rigorous screening within a small molecule compound library, we have pinpointed compound GNE-317 as a robust dual inhibitor targeting PI3K-mTOR via anticancer metabolic library screening methods. Our findings demonstrate that GNE-317 efficaciously impedes ovarian cancer cell proliferation while augmenting cellular demise relative to control groups. Notably, ferroptosis inhibitors exhibit potential in reversing GNE-317-induced cell death without impacting apoptosis or necrosis pathways. Further studies revealed that GNE-317 promoted the accumulation of lipid reactive oxygen species (ROS) and malondialdehyde (MDA). Mechanistically, GNE-317 directly binds to the GPX4, and the GNE-317-mediated increase in lipid ROS and MDA in OC were significantly reversed after GPX4 overexpression in ovarian cancer cells. Thus, GNE-317 can effectively inhibit ovarian cancer development, which may be achieved by increasing GPX4-mediated ferroptosis. These results suggest that GNE-317 has the potential to be a potential drug for targeted treatment of ovarian cancer.

With the increasing incidence of breast lesions, the differential diagnosis between benign lesions and breast cancer (BCa) has become a big challenge. Host peripheral blood mononuclear cells (PBMCs) could undergo changes in DNA methylation upon disease progression. However, the clinical value of DNA methylation of PBMCs in differentiating benign lesions and BCa is still unclear. DNA of PBMCs was isolated and the methylation status of PBMCs in patients with BCa and benign breast nodules was detected by using Illumina Infinium methylation EPIC array. The specific methylation targets were validated by pyrosequencing, Targeted Bisulfite Sequencing Assay, and Multiplex Methylation PCR Assay(MMPA). cg26977936, cg23351954, and cg27209741 were validated as differentially methylated and showed the potential diagnostic values (sensitivity and specificity were 90.0

The pathogenesis of adenomyosis is closely related to the epithelial-mesenchymal transition and macrophages. MicroRNAs have been extensively investigated in relation to the epithelial-mesenchymal transition in a range of malignancies. However, there is a paucity of research on extracellular vesicles derived from the eutopic endometrium of adenomyosis and their encapsulated microRNAs. In this study, we investigated the role of microRNA-25-3p derived from extracellular vesicles in inducing macrophage polarization and promoting the epithelial-mesenchymal transition in endometrial epithelial cells of patients with adenomyosis and controls. We obtained eutopic endometrial samples and isolated extracellular vesicles from the culture supernatant of primary endometrial cells. Real-time quantitative PCR analysis demonstrated that microRNA-25-3p was highly expressed in extracellular vesicles, as well as in macrophages stimulated by extracellular vesicles from eutopic endometrium of adenomyosis; and macrophages transfected with microRNA-25-3p exhibited elevated levels of M2 markers, while displaying reduced levels of M1 markers. After co-culture with the above polarized macrophages, endometrial epithelial cells expressed higher levels of N-cadherin and Vimentin, and lower protein levels of E-cadherin and Cytokeratin 7. It was revealed that microRNA-25-3p encapsulated in extracellular vesicles from eutopic endometrial cells could induce macrophage polarization toward M2, and the polarized macrophages promote epithelial-mesenchymal transition in epithelial cells. However, in vitro experiments revealed no significant disparity in the migratory capacity of endometrial epithelial cells between the adenomyosis group and the control group. Furthermore, it was observed that microRNA-25-3p-stimulated polarized macrophages also facilitated the epithelial-mesenchymal transition and migration of endometrial epithelial cells within the control group. Thus, the significance of microRNA-25-3p-induced polarized macrophages in promoting the development of adenomyosis is unclear, and macrophage infiltration alone may be adequate for this process. We emphasize the specificity of the local eutopic endometrial microenvironment and postulate its potential significance in the pathogenesis of adenomyosis.

We reported a case of ovarian teratoma-associated Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with recurrent epileptic seizures and disturbance of consciousness. Although surgical excision of the tumor remains the established standard of care, unlike other reported cases, the patient exhibited limited response to early oophorocystectomy, as well as IVIG and steroid therapy; however, a favorable response was observed with Plasma exchange (PE) initiated on postoperative day 12. Literature review revealed no definite recommended surgical extent for ovarian teratomas, and outstanding improvement in patients with anti-NMDAR encephalitis following PE. Our case raises the question regarding the optimal surgical extent for tumor resection, necessitating careful consideration when deciding between oophorectomy and adnexectomy as the preferred surgical procedure for anti-NMDAR encephalitis in female teens and adults. Furthermore, for refractory patients who fail to respond following tumor resection, PE can be performed early instead of immediately initiating second-line therapy.

Adenomyosis is a benign disease, but it exhibits a metastatic property similar to tumors. Its pathogenesis is still unclear. One theory is that adenomyosis is the result of epithelial-mesenchymal transition (EMT) in displaced embryonic Muller cells. Macrophages accumulate in the eutopic endometrium of adenomyosis and play an important role in EMT and the pathogenesis of adenomyosis. Extracellular vesicles (EVs) are considered an important mechanism of intercellular communication, but few studies have shown the role of EVs between endometrial epithelial cells and macrophages. In this study, we collected the eutopic endometrium of adenomyosis, and acquired the primary endometrial cells, then isolated EVs from the culture supernatants. We identified the characteristics of EVs by transmission electron microscopy, nanoparticle tracking, and western blot, and then detected the mRNA expression levels of CD163, IL-10, iNOS, and TNF-α in macrophages by qRT-PCR after co-cultured with EVs; the expression levels of E-cadherin, CK7, N-cadherin, and Vimentin by Western blot, and the migration abilities of epithelial cells by Transwell assay. The results showed that macrophages were highly expressed in the mRNA levels of CD163, IL10, and TNF-α after treated by EVs from adenomyosis patients; endometrial epithelial cells expressed lower protein levels of E-cadherin and CK7, higher levels of N-cadherin and Vimentin after co-cultured with the above polarized macrophages; and the migration abilities of epithelial cells were enhanced. In conclusion, EVs derived from adenomyosis can induce macrophages to polarize toward M2b, and the polarized macrophages could, in turn, induce EMT process in endometrial epithelial cells.

PURPOSE:The aim of this study was to investigate the expression of stathmin 1 (STMN1) in ovarian cancer and its effect on prognosis. The effect and mechanism of STMN1 on the proliferation and migration of ovarian cancer cells were also investigated.METHODS:Expression of STMN1 was measured by immunohistochemical staining in ovarian cancer tissues. The effects of STMN1 on the proliferation and migration capacity of ovarian cancer were evaluated using Cell Counting Kit-8 (CCK-8) assays, colony formation assays, immunofluorescence staining, wound healing assays, and Transwell assays. Transcription factors were predicted by bioinformatic analysis of TCGA database.RESULTS:STMN1 was upregulated in ovarian cancer tissues as compared to paracancerous tissues and associated with shorter overall survival. STMN1 expression significantly correlated with FIGO staging and tumor differentiation (P < 0.05). Furthermore, STMN1 promoted proliferation and migration in ovarian cancer cell lines. Bioinformatic analysis revealed that STMN1 was potentially regulated by E2F transcription factors. Then, we found that E2F1 regulated the expression of STMN1 and affected proliferation.CONCLUSION:STMN1 is overexpressed in ovarian cancer, and its high expression suggests a poor prognosis. STMN1 promotes the proliferation and migration of ovarian cancer and is regulated by E2F1. Thus, STMN1 may serve as a negative prognostic factor and possible target for the treatment of ovarian cancer patients.

ObjectiveThe aim of this study was to investigate the effect of antibiotic treatment for chronic endometritis (CE) on reproductive outcomes.DesignSystematic review and meta-analysis.PatientsWomen with reproductive failures, including recurrent implantation failure (RIF), and recurrent pregnancy loss (RPL).InterventionsLiterature searches were performed using three electronic databases (PubMed, Embase, and Web of Science) until 1 December 2021 (without date restriction). The following comparators were included: women with CE receiving antibiotics vs. untreated controls; women with cured CE vs. women with normal endometrial histology (negative for CE); and women with cured CE vs. women with persistent CE (PCE). The summary measures were indicated as odds ratio (OR) with a 95% confidence interval (CI).Main outcome measuresThese include on-going pregnancy rate/live birth rate (OPR/LBR), clinical pregnancy rate (CPR), and miscarriage rate/pregnancy loss rate (MR/PLR).ResultsA total of 2,154 women (from twelve studies) were enrolled. Compared with the control group, women with CE receiving antibiotics did not show a statistically significant difference in OPR/LBR (P = 0.09) and CPR (P = 0.36), although there was a lower MR (P = 0.03). Women with cured CE have higher OPR/LBR (OR 1.57) and CPR (OR 1.56) in comparison with those with non-CE. There was a statistically significantly higher OPR/LBR (OR 6.82, P < 0.00001) and CPR (OR 9.75, P < 0.00001) in women with cured CE vs. those with persistent CE.ConclusionWhile antibiotic treatment is a sensible option to cure CE, more well-designed prospective studies are needed to evaluate the reproductive impact of antibiotic treatment. Cured CE provides high-quality maternal conditions for subsequent embryo transfer and successful pregnancy.

Background Uterocutaneous fistula (UCF) is an uncommon clinical entity. The aetiology and optimal treatment strategy of UCF are still not clear. GnRHa (gonadotropin-releasing hormone agonist) treatment as an option for conservative hormone therapy for UCF has diverse clinical outcomes. The true status of hormone receptors in UCF lesions and its relationship with the therapeutic effect of GnRHa treatment have not yet been studied. Case presentation and review of the literature A 39-year-old woman underwent an uneventful myomectomy during her initial visit to our centre. The patient returned to our centre with complaints of fluid oozing from her abdominal wound. Misdiagnosed with poor wound healing, the patient received a secondary closure. Consequent blood-stained drainage from the wound during menstruation and imaging tests confirmed the diagnosis of UCF. Surgical repair and excision of the fistula tract were performed. Histopathological analysis revealed fistulization and a negative status of hormone receptors in the fistula. Considering the controversial role of GnRHa treatment in UCF and the negative oestrogen receptor (ER) and progesterone receptor (PR) status in the current case, we further systematically reviewed the literature for GnRHa treatment for UCF, with the results showing that GnRHa manipulation as a conservative hormone therapeutic schedule is effective in 2 (50%) of the 4 patients in which it was attempted. Conclusion UCF is a rare entity and tends to be misdiagnosed. GnRHa as a conservative therapy for UCF has different clinical outcomes. The current finding of a negative hormone receptor status in the fistula may provide new clues for further exploration of the mechanisms of the diverse therapeutic effects of GnRHa on UCF.

Chemoresistance is one of the major obstacles that lead to poor prognosis in cervical cancer. linc00958 was reported to be an oncogene in cervical cancer. However, its role in mediating chemoresistance remains to be revealed. To explore the regulatory mechanisms of linc00958 in cisplatin-resistant cervical cancer cells and further validate in xenograft mice. Online bioinformatic tools were used to conduct the pre-investigation of linc00958/miR-185-5p/RSF-1 and predict the associations between RSF-1 and AKT1/GSK3β/VEGFA in cervical cancer. RT-qPCR measured the RNA expression levels of linc00958/miR-185-5p/RSF-1 in SiHa and SiHa/DDP. Cell survival rates were evaluated by CCK8 methods after cells were exposed to differential concentrations of DDP. Dual-luciferase reporter methods were used to measure luciferase activity. Western blot measured RSF-1 protein and phosphorylated changes of AKT1/GSK3β. Immunofluorescence was employed to observe VEGFA secretion in vitro. Tube formation was applied to evaluate the in-vitro changes of angiogenesis. The SiHa/DDP cells stably transfected with pLKO-sh-NC or pLKO-sh-linc00958 plasmids, were injected into mice, establishing xenograft models. The changes in mice weight and tumor volumes were recorded. H&E staining and Immunohistochemistry (IHC) method was further performed. linc00958 expression was higher in SiHa/DDP cells. High linc00958 expression was associated with low overall survival. In SiHa/DDP cells linc00958/miR-185-5p/RSF-1 axis inhibited the cellular resistance to cisplatin and suppressed VEGFA and the tube formation through AKT1/GSK3β/VEGFA pathway. The knockdown of linc00958 inhibited RSF-1 and Ki67, curbing tumor growth; it also inhibited VEGFA and CD34, decreasing angiogenesis in mice. linc00958/miR-185-5p/RSF-1 modulates cisplatin resistance and angiogenesis through AKT1/GSK3β/VEGFA pathway in cervical cancer.

Adenomyosis is a common disease that affects many premenopausal women. Two patients with adenomyosis, aged 51 and 42 years, presented with dysmenorrhea and increased menstrual volume. They refused laparoscopy or laparotomy surgery and were not eligible for the levonorgestrel-releasing intrauterine system (LNG-IUS). The first patient underwent endometrial ablation and subcutaneous etonogestrel (ENG)-releasing implant placement at the same time. Her symptoms of dysmenorrhea and heavy menstruation improved significantly. When serum follicle-stimulating hormone (FSH) and estradiol (E2) levels suggested menopause, the ENG-releasing implant was removed. However, her abdominal pain recurred and was relieved by medication. For the second patient, an ENG-releasing implant was placed first, and her dysmenorrhea and heavy menstrual volume were relieved. However, the bleeding pattern changed from regular bleeding to prolonged bleeding, which troubled the patient. Endometrial ablation was performed 4 months later to solve the problem. Both patients had improved symptoms and were satisfied with the treatment. For patients with adenomyosis who refuse surgery and are not candidates for the use of LNG-IUS, an ENG-releasing implant combined with endometrial ablation may be an effective alternative.

Introduction: Activin A has been widely regarded as an important promoter of trophoblast invasion during the first trimester of pregnancy. However, whether integrin 83 is involved in activin A-upregulated trophoblast in-vasion and the underlying molecular mechanisms remain largely unknown.Methods: We utilized immortalized (HTR8/SVneo) and primary human extravillous trophoblast (EVT) cells, as well as first-trimester chorionic villous explants as study models to investigate the function and underlying molecular mechanisms of integrin 83 in activin A-promoted human trophoblast invasion.Results: We found that activin A increased integrin 83 mRNA and protein levels in both HTR8/SVneo and primary EVT cells, and knockdown of integrin 83 significantly decreased basal and activin A-upregulated trophoblast invasion. Moreover, SB431542 (a specific inhibitor of TGF-8 type CYRILLIC CAPITAL LETTER BYELORUSSIAN-UKRAINIAN I receptor kinase) abolished activin A-upre-gulated integrin 83 expression and SMAD2/3 phosphorylation. In addition, siRNA-mediated knockdown of ALK4 or SMAD4 both abolished activin A-upregulated integrin 83 expression in HTR8/SVneo cells, while knockdown of ALK4 or SMAD4 attenuated activin A-upregulated integrin 83 expression in primary EVTs. Discussion: Our findings reveal the mediation role of integrin 83 in activin A-upregulated human trophoblast invasion and that activin An upregulates integrin 83 expression in an ALK4-SMAD4 signaling-dependent manner.

Objective: To evaluate the efficacy of subcutaneous etonogestrel implants for adenomyosis.Methods: We conducted a clinical observational study of 20 patients suffering from adenomyosis treated with subcutaneous etonogestrel implants from August 2015 to July 2017 and followed up for 36 months. We evaluated the efficacy of subcutaneous etonogestrel implants primarily based on the following indicators: the pictorial blood loss assessment chart (PBAC) for menstrual blood volume, changes in bleeding patterns, the visual analog scale (VAS) pain score for dysmenorrhea, uterine volume, serum cancer antigen 125 (CA125) levels, hemoglobin levels and side effects.Results: During the 3 years of follow-up, subcutaneous etonogestrel implants were removed from six patients, among whom one was diagnosed with endometrial cancer, four had an increased menstrual blood volume, and one entered menopause. In total, 14 patients were treated with subcutaneous etonogestrel implants for 3 years. Among these patients, the number of patients with heavy menstrual bleeding and high PBAC and VAS scores and serum CA125 levels was significantly decreased after implantation compared with that before implantation. In the eight patients with anemia, hemoglobin levels increased gradually. However, the uterine volumes did not significantly change. Bleeding patterns were changed but were tolerable.Conclusion: Subcutaneous etonogestrel implants represent a new option for the clinical treatment of adenomyosis for patients who refuse surgery.

Background: Qishenyiqi dripping pill for chronic heart failure (CHF) remains controversial due to lack of high-quality trials. Therefore, we conduct this pooled-analysis to evaluate the efficacy and safety of Qishenyiqi in CHF patients. Methods: We searched for randomized clinical trials for Qishenyiqi dripping pill in treating CHF up to August 2018 through China National Knowledge Infrastructure (CNKI), the PubMed Database, the Wanfang Database, the China Scientific Journal Database (VIP), and the Chinese Biomedicine Literature Service System. RevMan 5.3 was used for pooled analyses. Based on the New York Heart Association (NYHA) classification, the clinical therapeutic effect was collected as the primary endpoint. Results: The efficacy and safety of Qishenyiqi combined with routine treatment significantly increased NYHA functional classification, left ventricular ejection fraction, cardiac index, and 6-minute walking test and decreased brain natriuretic peptide, left ventricular end-diastolic, and end-systolic dimensions with no obvious side effects in comparison with routine therapy alone. Conclusions: Together these results provide important insights into Qishenyiqi is effective and safe in improving ventricular remodeling and function of CHF patients. PROSPERO registration number: PROSPERO106695.

Patients with diabetes mellitus were often accompanied with hyperlipidemia. ATP-binding cassette sub-family A member1 (ABCA1) promotes the efflux of lipids and thereby mediates the metabolism of cholesterol. The aim of our study was to determine the associations of ABCA1 gene polymorphisms with the risks of diabetes mellitus and dyslipidemia in diabetic patients. We retrieved literature about the relationship between ABCA1 gene polymorphisms (C69T and R230C) and the risk of diabetes through PubMed, Web of Science, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Cochrane database. Weighted mean difference (WMD) and odds ratio (OR) were used to compare continuous and dichotomous variables, respectively, accompanied by their 95% confidence interval (CI). A total of 1746 diabetic patients and 1292 non-diabetic controls were enrolled. All subjects were Caucasians. ABCA1 R230C T allele was significantly associated with reduced the risk of diabetes (OR = 0.75, 95% CI = 0.57–0.98, P = 0.04). There was no association of ABCA1 C69T gene polymorphisms with the risk of diabetes. However, subgroup analyses showed that the ABCA1 C69T gene mutation significantly reduced the risk of hypertriglyceridemia in diabetic patients as compared with that in non-diabetic subjects (dominant model: WMD =0.66, 95% CI = 0.52–0.8, P < 0.0001; recessive model: WMD = 0.47, 95%CI = 0.11–0.83, P = 0.01). ABCA1 R230C T allele gene mutation is a protective in decreasing the risk of diabetes in Caucasians and ABCA1 C69T gene mutation markedly influences the level of lipid metabolism in diabetic patients.

Objective: To evaluate the clinical significance of preoperative ultrasound diagnosis and classification of ovarian pregnancy (OP). Methods: The ultrasonographic reports, medical records, and operative summaries were reviewed for twelve women with a confirmed diagnosis of OP. According to the ultrasonographic appearance, OP was classified into two types. For every type, we analyzed the possibility and clinical significance of preoperative ultrasound diagnosis, combining with its clinical manifestations and treatments. Results: According to sonographic features, twelve cases of OP can be classified into ruptured type (n = 6) and unruptured type (n = 6), the latter was subclassified into embryo sac type (n = 2) and non-homogeneous mass type (n = 4). All the unruptured OP have the characteristic solid hyperechoic rings or masses, and 66.7% (4/6) were correctvly diagnosed by preoperative ultrasound. No characteristic ultrasonogram was detected in ruptured OP which were all diagnosed as ruptured ectopic pregnancy (EP) or corpus luteum by preoperative ultrasound. The diagnostic and surgical procedures of four cases diagnosed by preoperative ultrasound were all laparoscopy and removal of the gestational products, and their average hemoperitoneum, operation time, hospital days was 313 +/- 278 ml, 57 +/- 9 min, and 4.25 +/- 0.5days, respectively. While ruptured OP cases (6 cases diagnosed at first visit and 1 underdiagnosed but ruptured after 6 days), the diagnostic procedures was laparoscopy(3/7) or laparotomy(4/7), the surgical procedure was removal of the gestational products (2/7), wedge resection(3/7), or adenexectomy(2/7), and their average hemoperitoneum, operation time, and hospital days was 1914 +/- 1059 ml, 93 +/- 17 min, and 5.9 +/- 1.3days, respectively. Conclusions: Ultrasound plays a significant role in diagnosis of OP, and part of the unruptured OP based on the typical sonographic characteristics could be correctly diagnosed by an experienced sonographer, this is beneficial and effective in terms of the risk of patient's operation and life. Whereas ruptured OP were generally diagnosed as ruptured EP or corpus luteum because there were no characteristic ultrasound manifestations. (C) 2019 The Authors. Published by Elsevier Masson SAS.

Copeptin has been identified as a biomarker of disease severity and is associated with mortality risk in several common diseases. This study sought to determine the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. PubMed, Web of Science, and Wanfang Medicine Database were searched for studies assessing the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. The pooled hazard ratio (HR) of mortality was calculated and presented with 95 % confidence interval (95 % CI). Data from 1332 intracerebral hemorrhage patients were derived from 9 studies. Meta-analysis showed that intracerebral hemorrhage patients with poor prognosis had much higher copeptin levels than those survivors (standardized mean difference = 1.68, 95 % CI 1.26–2.11, P < 0.00001). Meta-analysis of 8 studies with HRs showed that high circulating copeptin level was associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 2.42, 95 % CI 1.60–3.65, P < 0.0001). Meta-analysis of 6 studies with adjusted HRs showed that high circulating copeptin level was independently associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 1.67, 95 % CI 1.26–2.22, P = 0.0003). Our study suggests that there is an obvious association between circulating copeptin level and mortality in patients with intracerebral hemorrhage. High circulating copeptin level is independently associated with higher risk of mortality in patients with intracerebral hemorrhage.

It is unclear how microRNA (miR)-494 inhibits the proliferation of cervical cancer cells by altering the expression of SOCS6. Therefore, the present study aimed to investigate the molecular mechanism underlying miR-494 regulation of suppressor of cytokine signaling 6 (SOCS6) in human cervical cancer samples and the human cervical cancer HeLa cell line. The expression of miR-494 was determined using reverse transcription-quantitative polymerase chain reaction. In addition, TargetScan was used to predict miR-494 target genes and the luciferase reporter assay was used to determine whether SOCS6 was a direct target of miR-494. The results of the present study demonstrated that compared with the cervical intraepithelial neoplasia and normal cervical tissues, the miR-494 expression level in cervical cancer samples was significantly decreased (P<0.01). In addition, compared with normal cervical tissue, miR-494 expression level was significantly decreased in cervical intraepithelial lesions (P<0.05). Furthermore, the expression of miR-494 was associated with patients with or without lymph node metastasis, clinical stage and depth of stromal invasion (P<0.01); however, miR-494 expression was not identified to be associated with age, tumor size and menopausal status (P>0.05). Transfection of a miR-494 mimic significantly increased the expression level of miR-494 in HeLa cells (P<0.01), and anti-miR-494 transfection decreased the expression of miR-494 (P<0.01). An MTT proliferation assay and Boyden chamber invasion ability assay revealed that miR-494 mimic transfection significantly inhibited the proliferation, and invasion ability of HeLa cells (P<0.01), whereas anti-miR-494 transfection significantly increased the proliferation and invasion ability (P<0.05). SOCS6 was predicted, using bioinformatics, to be the target gene of miR-494 and this was validated using a luciferase reporter assay. Western blot analysis revealed that transfection of miR-494 significantly increased the expression of SOCS6 in HeLa cells, and transfection of anti-miR-494 significantly decreased the expression of SOCS6. Therefore, the results of the present study demonstrated that miR-494 expression in cervical cancer was significantly decreased. Exhibiting a decreased expression level of miR-494 may result in enhanced proliferative and invasive abilities of HeLa cell, thus contributing to the occurrence, and development of cervical cancer.

Context:Premature ovarian insufficiency (POI) is highly heterogeneous, both in phenotype and etiology. They are not yet clearly stated and correlated.Objective:To characterize clinical presentations of a large, well-phenotyped cohort of women with POI, and correlate phenotypes with etiologies to draw a comprehensive clinical picture of POI.Design, Patients, Interventions, and Main Outcome Measures:In this retrospective study, a total of 955 Chinese women with overt POI between 2006 and 2015 were systemically evaluated and analyzed. The phenotypic features, including menstrual characteristics, hormone profiles, ovarian ultrasonography/biopsy, pregnancy/family history, and genetic/autoimmune/iatrogenic etiologies were assessed and further compared within different subgroups.Results:Among 955 women with POI, 85.97% presented with secondary amenorrhea (SA) and 14.03% with primary amenorrhea (PA). PA represented the most severe ovarian dysfunction and more chromosomal aberrations than SA. The decline of ovarian function in patients with SA progressed quickly. They had shortened reproductive periods (approximately 10 years) and developed amenorrhea within 1 to 2 years after menstrual irregularity. The ovaries were invisible or small, and the presence of follicles (28.43%) was correlated with other good reproductive indicators. Familial patients (12.25%) manifested better ovarian status and fewer chromosomal aberrations than sporadic patients. The etiologies consisted of genetic (13.15%), autoimmune (12.04%), and iatrogenic (7.29%), approximately 68% remaining idiopathic. There were significant differences among different etiologies, with the genetic group representing the most severe phenotype.Conclusion:Our results regarding distinct phenotypic characteristics and association with different etiologies further confirmed the high heterogeneity of POI. Additional longitudinal clinical studies and pathogenesis research are warranted.

Objective: To detect ZP (zona pellucida) gene (ZP1-ZP4) mutations in patients with oocyte anomalies.Design: Case-control genetic study.Setting: University-based reproductive medicine center.Patient(s): A total of 92 infertile patients with repeated cycles of oocyte maturation arrest (group I, n = 49) or oocyte morphologic defect (group II, n = 43) as well as 373 healthy controls.Intervention(s): Genomic DNA extracted from peripheral blood and coding regions of ZP genes amplified by polymerase chain reaction and sequenced by a DNA analyzer.Main Outcome Measure(s): Variant prediction of ZP genes with software.Result(s): In group I with oocyte maturation arrest, no novel variants were found. In group II with oocyte morphologic defects, four novel variants, two in the ZP1 gene [c.247T>C (p.W83R) and c.1413G>A (p.W471X)] and two in the ZP2 gene [c.1599G>T (p.R533S) and c. 1696T>C (p.C566R)] were detected in 4 of 43 patients (approximately 9%) but were absent from the controls. Protein alignments showed that the four variants were highly conserved among different species, and all four variants were predicted to be deleterious by gene software predictions.Conclusion(s): ZP gene variants may account for patients with oocyte morphologic abnormalities but not for those with oocyte maturation arrest. (C) 2017 by American Society for Reproductive Medicine.