Purpose. To explore risk factors of vulvovaginal candidiasis (VVC) among women of reproductive age in Xi'an district and then to offer reference for clinical prevention and treatment of VVC. Methods. Patients from the outpatient department of gynecology and obstetrics in the First Affiliated Hospital of Xi'an Jiaotong University from June 2016 to May 2017 were recruited strictly according to the inclusion and exclusion criteria. Participants diagnosed as simple VVC were assigned to the case group, while women who underwent routine gynecological examination and had normal vaginal microflora were assigned to the control group. Then we conducted a questionnaire survey of the two groups and used the logistic regression model to explore the related risk factors of VVC. Results. In the present study, ninety-seven cases were sample VVC patients and eighty-seven cases were healthy women. This cross-sectional study showed that occasionally or never drinking sweet drinks (odds ratio [OR] =0.161, 95% confidence interval [CI] =0.056-0.462, P=0.001), occasionally or never eating sweet foods (OR=0.158, 95%CI=0.054-0.460, P=0.001), and the use of condom (OR=0.265, 95%CI=0.243-0.526, P=0.001) were regarded as protective factors for VVC. In addition, sedentary life style (OR=7.876, 95%CI=1.818-34.109, P=0.006), frequently wearing tights (OR=6.613, 95%CI=1.369-27.751, P=0.018), frequent intravaginal douching (OR=3.493, 95%CI=1.379-8.847, P=0.008), having the first sexual encounter when under 20 years old (OR=2.364, 95%CI=1.181-7.758, P=0.006), the number of sexual partners being over two (OR=3.222, 95%CI=1.042-9.960, P=0.042), history of curettage (OR=3.471, 95%CI=1.317-9.148, P=0.012), history of vaginitis (OR=8.999, 95%CI=2.816-28.760, P<0.001), and not cleaning the vulva before or after sexual encounters (OR=13.684, 95%CI=2.843-65.874, P=0.001) were considered to be risk factors of VVC. Conclusion. In conclusion, risk factors of VVC are various, involving ages, hygienic habits, disease history, and other aspects.

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.

Abstract. Choriocarcinoma (CC) is the highest malignant gestational trophoblastic tumor which causes high mortality without timely treatment. HIF-1α is a very important molecule promoting neoplasm aggressiveness, metastasis through the induction of the epithelial to mesenchymal transition (EMT). Several researches have shown that Notch signaling is necessary for coupling hypoxia to the EMT. However, the pathway in choriocarcinoma remains undetermined. In this study, overexpression of HIF-1α inhibited epithelial index E-cadherin, cytokeratin 18 (CK18) and cytokeratin 19 (CK19) in two choriocarcinoma cell lines (JAR and JEG-3, respectively). The reciprocal changes associated with the EMT phenotypic transformation. The migration and invasive capability was significantly enhanced. HIF-1α overexpression was positively correlated with Notch1 and Hes1 (P<0.01; respectively). Using DAPT (Notch1 inhibitor) to knock down Notch1 expression, morphological and molecular typical changes of the EMT were detected in vitro. Knockdown of Notch1 prominently reduced MMP2 and MMP9 activities, and increased E-cadherin, CK18 and CK19 expression in JAR and JEG-3 cells (P<0.01). In vivo, serum-free suspension containing 5x10 6 JAR cells (lv-HIF-1α and lv-NC, respecticely) were implanted subcutaneously or injected intravenously into female NOD SCID mice, which were injected with DAPT or DMSO six times at 3-day intervals. Mice with subcutaneous nodules were injected i.v. fluorine-18 fluorodeoxyglucose ( 18 F-FDG) and then scanned in small animal PET/CT (SA-PET/ CT), and mice with lung metastasis were monitored by using the in vivo imaging system (IVIS). The in vivo data showed that inhibition of Notch signaling by DAPT treatment effectively suppressed metastatic tumor growth, metabolic activity and invasion. In summary, overexpression of HIF-1α promotes choriocarcinoma cell aggressiveness and metastasis through the regulation of the EMT dependenting on Notch signaling pathway.

Intravesical chemotherapy is often used to prevent the recurrence of superficial bladder cancer after transurethral resection. A search for more effective and less toxic intravesical agents is urgently needed. We previously found the in vitro apoptotic effects of silibinin, a natural flavonoid, on high-risk bladder carcinoma cells. Here, we further explored the underlying mechanisms and examined the intravesical efficacy in the prevention and treatment of bladder cancer. Human bladder carcinoma cell line 5637, which has the same molecular features of high-risk superficial bladder cancer, was used as the model system in vitro and in vivo. Autochthonous rat model of bladder cancer induced by intravesical N-methyl-N-nitrosourea (MNU) was used to investigate its intravesical efficacy. Exposure of 5637 cells to silibinin resulted in growth inhibition and induction of caspase-dependent and -independent apoptosis, which was associated with disruption of mitochondrial membrane potential and selective release of cytochrome c, Omi/HtrA2, and apoptosisinducing factor (AIF) from mitochondria. Silibinin also downregulated survivin and caused nuclear translocation of AIF. Oral silibinin suppressed the growth of 5637 xenografts, which was accompanied with the activation of caspase-3, downregulation of survivin, and increased translocation of AIF. Furthermore, intravesical silibinin effectively inhibited the carcinogenesis and progression of bladder cancer in rats initiated by MNU by reducing the incidence of superficial and invasive bladder lesions without any side effects, which was accompanied with proapoptotic effects. These findings identify the in vitro and in vivo antitumor efficacy of silibinin, and suggest silibinin as an effective and novel intravesical agent for bladder cancer.

In the present study, we investigated the effect of reduced enolase-1 expression in human umbilical vein endothelial cells (HUVECs)/MDA-MB-231 cells on the response to hypoxia and the possible mechanisms involved. Breast cancer cells transfected with enolase-1 siRNA were injected into mice to establish a tumor-bearing mouse model, and the correlation between enolase-1 expression and breast cancer angiogenesis, as well as its effect on the efficacy of radiation therapy were assessed. HUVECs were cultured in vitro, and transfected with enolase-1 siRNA. Following stable passage, 1.0% O2 was used to induce hypoxia. The growth, proliferation, division and angiogenesis of HUVECs were observed using MTT assay, flow cytometry (FCM) and time-lapse video microscopy. The key regulatory molecules were detected using western blot analysis, two-dimensional (2-D) electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The breast cancer cell line, MDA-MB-231, was cultured in vitro, and transfected with enolase-1 siRNA. The cells were injected into nude mice, and radiation therapy was administered. Tumor growth, angiogenesis in tumor tissues and apoptosis were observed, and the expression of the endogenous hypoxia marker, hypoxia inducible factor-1α (HIF-1α), was detected using immunohistochemistry after the mice were sacrificed. A significant reduction in the hypoxia-induced apoptosis of HUVECs was observed in the control group compared with the endothelial cells transfected with enolase-1 siRNA. After the enolase-1 transfected breast cancer cells were injected into nude mice, tumor growth significantly declined, and the tumor volume and weight were reduced. Following treatment with radiation therapy, tumor size significantly decreased in both groups, and the highest reduction was observed in the transfected group. The reduction in enolase-1 expression significantly decreases the response to hypoxia and enhances the sensitivity of the cells to radiation therapy; therefore, enolase-1 may be a drug target for the treatment of breast cancer.

Oral administration of indigo naturalis (IN) can induce remission in ulcerative colitis (UC); however, the underlying mechanism remains unknown. The main active components and targets of IN were obtained by searching three traditional Chinese medicine network databases such as TCMSP and five Targets fishing databases such as PharmMapper. UC disease targets were obtained from three disease databases such as DrugBank,combined with four GEO gene chips. IN-UC targets were identified by matching the two. A protein–protein interaction network was constructed, and the core targets were screened according to the topological structure. GO and KEGG enrichment analysis and bioGPS localization were performed,and an Herbs-Components-Targets network, a Compound Targets-Organs location network, and a Core Targets-Signal Pathways network were established. Molecular docking technology was used to verify the main compounds-targets. Ten core active components and 184 compound targets of IN-UC, of which 43 were core targets, were enriched and analyzed by bioGPS, GO, and KEGG. The therapeutic effect of IN on UC may involve activation of systemic immunity, which is involved in the regulation of nuclear transcription, protein phosphorylation, cytokine activity, reactive oxygen metabolism, epithelial cell proliferation, and cell apoptosis through Th17 cell differentiation, the Jak-STAT and IL-17 signaling pathways, toll-like and NOD-like receptors, and other cellular and innate immune signaling pathways. The molecular mechanism underlying the effect of IN on inducing UC remission was predicted using a network pharmacology method, thereby providing a theoretical basis for further study of the effective components and mechanism of IN in the treatment of UC.

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Background: Tumor-infiltrating lymphocytes (TILs) are involved in the antitumor immune response. The association between prognosis in patients with TILs and high-grade serous ovarian cancer (HGSOC) remains obscure, with some studies reporting conflicting results. Methods: We conducted an extensive literature search of electronic databases and retrieved prognostic data of each selected subtype of TILs, including CD3+, CD4+, CD8+, CD103+, and PD-1+ TILs. The fixed-effects model was applied to derive the pooled hazard ratio (HR) and 95% confidence interval (CI) of these markers. Results: The systematic review process yielded 19 eligible studies comprising 6004 patients with HGSOC. We compared TIL-positive and TIL-negative patients, and the pooled HRs from the multivariate analysis revealed that intraepithelial CD8+ TILs were positively correlated with progression-free survival (PFS, HR 0.46, 95% CI 0.25–0.67) and overall survival (OS, HR 0.90, 95% CI 0.86–0.9); stromal CD8+ TILs were positively correlated with OS (HR 0.61, 95% CI 0.36–0.87). Furthermore, the pooled HRs from univariate analysis demonstrated that intraepithelial CD3+, CD4+, CD8+, and CD103+ TILs were positively associated with OS (HR 0.58, 95% CI 0.44–0.72; HR 0.37, 95% CI 0.16–0.59; HR 0.51, 95% CI 0.42–0.60, and HR 0.59, 95% CI 0.44–0.74, respectively); stromal CD4+ and CD8+ TILs were significantly associated with OS (HR 0.63, 95% CI 0.32–0.94 and HR 0.78, 95% CI 0.58–0.97, respectively). However, the pooled HR from the multivariate analysis revealed that PD-1+ TILs were not associated with the OS of patients with HGSOC (HR 0.97, 95% CI 0.90–1.04). Conclusion: This meta-analysis provided evidence of the association of CD3+, CD4+, CD8+, and CD103+ TILs with the survival benefits (OS and PFS) of patients with HGSOC.