Genetically predicted serum testosterone and risk of gynecological disorders: a Mendelian randomization study.

Background: Testosterone plays a key role in women, but the associations of serum testosterone level with gynecological disorders risk are inconclusive in observational studies. Methods: We leveraged public genome-wide association studies to analyze the effects of four testosterone related exposure factors on nine gynecological diseases. Causal estimates were calculated by inverse variance-weighted (IVW), MR-Egger and weighted median methods. The heterogeneity test was performed on the obtained data through Cochrane's Q value, and the horizontal pleiotropy test was performed on the data through MR-Egger intercept and MR-PRESSO methods. "mRnd" online analysis tool was used to evaluate the statistical power of MR estimates. Results: The results showed that total testosterone and bioavailable testosterone were protective factors for ovarian cancer (odds ratio (OR) = 0.885, P = 0.012; OR = 0.871, P = 0.005) and endometriosis (OR = 0.805, P = 0.020; OR = 0.842, P = 0.028) but were risk factors for endometrial cancer (OR = 1.549, P < 0.001; OR = 1.499, P < 0.001) and polycystic ovary syndrome (PCOS) (OR = 1.606, P = 0.019; OR = 1.637, P = 0.017). dehydroepiandrosterone sulfate (DHEAS) is a protective factor against endometriosis (OR = 0.840, P = 0.016) and premature ovarian failure (POF) (OR = 0.461, P = 0.046) and a risk factor for endometrial cancer (OR= 1.788, P < 0.001) and PCOS (OR= 1.970, P = 0.014). sex hormone-binding globulin (SHBG) is a protective factor against endometrial cancer (OR = 0.823, P < 0.001) and PCOS (OR = 0.715, P = 0.031). Conclusion: Our analysis suggested causal associations between serum testosterone level and ovarian cancer, endometrial cancer, endometriosis, PCOS, POF.

Metastasis from small cell lung cancer to ovary: A case report.

Small cell lung cancer (SCLC) rarely metastasizes to the ovary, and is difficult to diagnose given its overlapping clinical features and histological characteristics with primary ovarian cancer. Since therapies for SCLC and primary ovarian cancer differ, it is important to determine the original site of ovarian lesions. This report describes the differential diagnosis of metastatic from primary ovarian cancer. A 46-year-old Chinese woman with a history of SCLC, confirmed by transbronchial lung biopsy in August 2018, presented with abdominal distension in December 2018. Ultrasound examination and whole abdomen computed tomography showed one mass in each ovary. A provisional diagnosis of ovarian tumor was given. A palliative total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed; and three postoperative courses of chemotherapies. The patient died from multiple organ failure in May 2019. Metastatic ovarian cancer from SCLC was determined based on characteristic histological and immunohistochemical staining.

FGFR3 phosphorylates EGFR to promote cisplatin-resistance in ovarian cancer.

Ovarian cancer is a deadly gynecologic cancer, and the majority of patients with ovarian cancer experience relapse after traditional treatment. Cisplatin (DDP) is a common chemotherapeutic drug for ovarian cancer, but many patients acquire DDP-resistance after treatment with long-term chemotherapy. The mechanisms of drug-resistance in ovarian cancer are not clear, and we thus aim to investigate novel targets for DDP-resistant ovarian cancer. Differential analysis, KEGG pathway enrichment and protein interaction networks were employed to identify the key genes related to DDP-resistance in ovarian cancer. Subsequently, cell viability, apoptosis and migration were measured to assess the effect of fibroblast growth factor receptor 3 (FGFR3) on DDP-resistance. Further, Pearson correlation analysis and co-expression analysis were used to explore the downstream pathways of FGFR3, and the function of FGFR3 and its downstream targets were further demonstrated by in vitro and nude mice experiments. FGFR3 were expressed at high levels in DDP-resistant ovarian cancer cells. FGFR3 silencing suppressed the activation of PI3K/AKT pathway and impeded the drug-resistance and development of tumor cells. Afterwards, we found that FGFR3 was co-expressed with epidermal growth factor receptor (EGFR). FGFR3 overexpression elevated EGFR phosphorylation and activated PI3K/AKT signaling. Furthermore, in nude mice, silencing FGFR3 and inhibiting EGFR phosphorylation were observed to promote the therapeutic effect of DDP. In conclusion, FGFR3 overexpression enhances DDP-resistance of ovarian cancer by promoting EGFR phosphorylation and further activating PI3K/AKT pathway. This study may offer promising targets for DDP-resistant ovarian cancer.

Effects of Morphologies of Thermosensitive Electrospun Nanofibers on Controllable Drug Release.

Electrospun nanofibers is a promising and versatile avenue for building controlled drug release system because of the facile fabrication and the broad range of polymer materials. This research systematically studied the morphological effect of thermosensitive electrospun nanofibers, including porous and coaxial structures, on controllable drug release. Three types of drugs, nicotinamide, paracetamol, and ibuprofen, with different hydrophilicity were applied in this study. The data of drug release were all fitted to the first-order kinetic model regardless of the drug properties, and the release rates paralleled with their hydrophilicity. Sol-gel phase transition of the thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel led to slower drug release at 37°C compared with those at 25°C. Regarding morphology, coaxial nanofibers could provide higher loading efficiency and slower drug release rather than porous nanofibers. Our research highlighted the overall effects of compound property, temperature, and the morphological structures of thermosensitive electrospun nanofibers on the controlled drug release. Our results concluded that hydrophobic drug encapsulated in the core-shell PNIPAAm nanofibers could perform excellent sustained release and also controllable release under temperature stumuli. Impact statement The behaviors for the controlled release of drugs loaded in the thermosensitive electrospun nanofibers could be affected by various factors including the properties of loaded drug, morphologies of nanofibrous, and lower critical solution temperatures of thermosensitive hydrogels. However, few systematical investigations have been performed in this area. In this article, we designed and fabricated porous and coaxial thermosensitive poly(N-isopropylacrylamide) electrospun nanofibers with different drug loading to study the comprehensive effect. This study suggested when adopting thermosensitive electrospun hydrogel nanofibers as the controllable drug release carrier, the hydrophilicity of loaded compounds and the morphologies of nanofibers are necessary to be optimized.

Spontaneous rupture of an unscarred uterus with an intact amniotic sac extrusion and fetal leg entrapment at 28 gestational weeks: a case report.

The spontaneous rupture of an unscarred uterus at 28 gestational weeks is an extremely rare event, particularly when associated with an intact amniotic sac extrusion and fetal leg entrapment, which has not been previously reported. A 27-year-old primigravid woman was referred to our department, due to perpetual abdominal pain, at 28 weeks and 5 days of gestation. The patient, G3p0, had previously undergone two induced abortions. At the time of admission, abdominal ultrasonography suggested a defect in the left uterine horn. An emergency laparotomy was subsequently performed and revealed an intact amniotic sac extrusion and fetal leg entrapment. Considering the risk of placental abruption, and the possibility of a secondary rupture if the gestation was not terminated, an emergency Cesarean section was recommended. Uterine rupture may be suspected whenever a patient complains of durative abdominal pain at 28 weeks and 5 days of gestation, even in the absence of an intra-abdominal hemorrhage or vaginal bleeding.

Dioscin improves postmenopausal osteoporosis through inducing bone formation and inhibiting apoptosis in ovariectomized rats.

Postmenopausal osteoporosis (PMO) has become a public health problem worldwide. Hormonal replacement therapy (HRT) is the most popular treatment for PMO at present, but the side effects, including increased risk of endometrial cancer and breast cancer, limit its clinical use. Therefore, finding a new medication with high efficiency and less side-effects is urgently required. Dioscin is the main ingredient of some medicinal plants such as Dioscorea nipponica Makino and Dioscorea zingiberensis Wrigh. It is reported that dioscin has anti-tumoral and anti-atherosclerotic activity as well as an inhibitory effect on hepatic fibrosis. In this study, the effects of dioscin on PMO were examined and the mechanisms were analyzed. The results indicated that the bone mineral density and ultimate load of PMO rats were increased after being treated with dioscin. H&E staining and immunohistochemical staining showed the bone trabeculae formation and bone differentiation of PMO rats were promoted by dioscin. Western blots revealed that dioscin could activate the PI3K/P38/AKT signaling pathway and inhibit the apoptosis signaling pathway in bone tissue cells of PMO rats. In addition, MTT assays showed that MC3T3-E1 cell viability could be improved by dioscin. These results suggest dioscin is a potential therapeutic reagent for osteoporosis and deserves further investigation.

Atrazine exposure improves the proliferation of H22 cells in vitro and in vivo.

Atrazine (ATZ), a widely used triazine herbicide, has been detected in the surface and ground water even far from where it is applied. Recently, the biotoxicity of atrazine to the immune, reproductive and endocrine systems has been preliminarily observed in laboratory experiments and epidemiological research studies. In order to further comprehend the carcinogenic nature of ATZ, in vitro and in vivo models were established in this study to explore the effects of ATZ exposure on hepatocellular carcinoma. The results showed that after being treated with ATZ, the proliferation of H22 cells increased, and the tumor volume and amount of ascites were significantly increased in an in situ transplantation tumor model established in C57BL/6 mice compared to the control group. The expression of p53 was down-regulated, while the expression of cyclin-D1, VEGF, MMP2, Stat3 and C-myc was up-regulated in the ATZ-treated groups compared to the control group. These results indicate that ATZ might activate the Stat3 signaling pathway and promote the proliferation and invasion of hepatocellular carcinoma cells.