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Myofascial pelvic pain (MFPP) caused by myofascial trigger points (MTrPs) is a major contributor to chronic pelvic pain in women. However, the effect of the patient's self-myofascial release (SMFR) is unclear. This study aimed to investigate the effect of SMFR combined with biofeedback and electrical stimulation (BES) therapy in comparison with BES alone in patients with MFPP.A prospective randomized controlled study was conducted. Sixty-eight patients were randomly allocated into BES-SMFR group (n = 34) and BES group (n = 34). Every patient received 4 weeks of treatment, evaluated at baseline (T0), 4 weeks post-intervention (T4) and 12-week follow-up (T12). The primary outcome was pain intensity. The secondary outcomes were degree of activation of MTrPs, surface electromyography (sEMG) levels and Patient Global Impression of Improvement (PGI-I).Compared with the effect of BES, BES-SMFR treatment significantly decreased pain intensity and the degree of activation of MTrPs in the levator ani (p = 0.02) and obturator internus (p = 0.03), as well as the sEMG levels of the pre-test resting baseline and post-test resting baseline (all p 0.01). The degree of activation of MTrPs in the piriformis and coccygeus (all p 0.05) and the sEMG levels of the quick flicks and endurance contraction were not significantly different. The BES-SMFR treatment improved the PGI-I scale at T4 (p = 0.02) but not at T12 (p = 0.40).This study confirmed that the addition of SMFR to BES treatment resulted in superior outcomes compared with those with BES alone in patients with MFPP.Myofascial pelvic pain (MFPP) is a major contributor of female chronic pelvic pain. Myofascial release has been used commonly for better pain release; however, poor therapeutic effect due to poor patient compliance is common in clinical practice. Therefore, in future research, there is a need to investigate the effect of patient's self-myofascial release (SMFR) technique, which can eliminate the need for frequent office visits and improve patient compliance to some extent, in patients with MFPP.

Objective The study aimed to recognize potential molecular targets and signal pathways whereby phenolic environmental estrogen promotes the proliferation of uterine leiomyoma cells. Methods Primary cultured cell lines of uterine leiomyoma were treated with 0.1% DMSO, 10.0 μmol/L Bisphenol A (BPA), and 32.0 μmol/L Nonylphenol (NP) for 48 h before RNA-seq was performed. Those genes affected by BPA and NP were identified. Then, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and Protein-protein Interaction (PPI) analysis were performed. Quantitative real-time polymerase chain reaction (q-PCR) and western blot were used to verify the differentially expressed gene and protein. Results Compared to with the control group, 739 differentially expressed genes were identified in both the BPA group and the NP group. GO enrichment analysis showed that the most enriched GO terms were connective tissue development and G1/S transition of mitotic cell cycle, and extracellular matrix. The results of KEGG enrichment analysis showed that differentially expressed mRNA were enriched mainly in three primary pathways, including environmental information processing, human diseases, and cellular processes. The cell cycle, PI3K-Akt signaling pathway are significantly enriched. The q-PCR and western blot verified the cell cycle associated genes and proteins were upregulated in both BPA group and NP group. Both BPA and NP activated the PI3K-AKT signaling pathway. Conclusion Phenolic environmental estrogens may promote the proliferation and cell cycle progression of uterine leiomyoma cells through rapid non-genomic ER signaling, which leads to disordered cell cycle regulation and accelerates the transition of the cell cycle from G0/G1 phase to S phase. In addition, as an external stimulant, phenolic estrogen promotes the upregulation of inflammatory factors in uterine leiomyomas.

BACKGROUND This study aimed to investigate the value of CA125 dynamic change in PFS prediction for patients with epithelial ovarian carcinoma (EOC). MATERIAL AND METHODS Data analysis was performed using SPSS 24.0 statistical software with progression-free survival (PFS) as an outcome measure. Kaplan-Meier method was used to analyze the relationship between PFS and preoperative and postoperative NLR, PLR and CA125 levels, CA125 half-life, CA125-negative time, age, FIGO stage, histopathology, differentiation, vessel carcinoma embolus, and ascites. The survival curves were compared by the log-rank test. Based on the results of single-factor analysis, the Cox model was used for multifactor analysis to analyze independent risk factors affecting the PFS of epithelial ovarian carcinoma. RESULTS A total of 117 patients with EOC were selected from January 2012 to January 2019 to carry out a retrospective study. Univariate analyses showed that PFS of the patients with EOC was associated with differentiation, vessel carcinoma embolus, FIGO stage, CA125 half-life, CA12- negative time, and preoperative NLR (P

Background Cervical cancer is the most common malignancy from the female reproductive tract, and usually develops from low-grade or high-grade squamous intraepithelial lesions (LSIL or HSIL). Detecting the precancerous lesion during the LSIL-HSIL-invasive cancer sequelae can effectively interrupt the oncogenesis and decrease the incidence of invasive carcinoma. The aim of this study is to evaluate the performance of P16/Ki67 dual staining in triaging hr-HPV-positive population. Methods Conventional gynecological examination, cervical cytology and hr-HPV testing were given to all patients. Specimens were collected for cytology examination and HPV genotyping. According to cytology results, patients were divided into cervical cancer group, HSIL group, LSIL group and benign lesion group. Sensitivity and specificity of the dual staining method in each histopathologic group was obtained and compared. Results Among the108 patients participated in the study, 65 were diagnosed as normal, 15 as LSIL, 20 as HSIL and 8 as CC, by histopathologic examination. Dual staining of p16/Ki67 on cytology specimen provided a positive predictive value of 86% and the negative predictive value of 96%. The sensitivity approached 96.43% when combining ThinPrep cytological test (TCT) with the dual staining, with a specificity of 60% in detecting HSIL. Joint detection of TCT and p16/Ki67 dual staining displayed the highest specificity among all the attempted combinations of detection methods. Conclusions This study demonstrated that p16/Ki-67 dual staining represents an effective method for cervical cancer screening. Application of this method could lead to a reduction of unnecessary colposcopy referrals and misdiagnosis.

Uterine tumors resembling ovarian sex-cord tumor (UTROSCT) are a rare, multi-phenotype sex-cord tumors, containing a structure which is characteristic with the trabecular, cord, nests, and false adenoid arrangement. In addition, CD99-positive was a basis for diagnosis of the disease. With uncertain malignant potential and relapse, these patients should be closely followed up. This article is to summarize clinical and pathological features, diagnosis and differential diagnosis, treatment, and prognosis of UTROSCT.

Aim: Although routine screening contributes to substantial reductions in cervical cancer morbidity and mortality, the low specificity of HPV detection and limited sensitivity of cervical cytology necessitates the application of more optimized markers, such as the newly-introduced p16/Ki-67 dual-staining method. Here we reviewed several studies to evaluate the performance of this method in cervical cancer screening. Methods: An electronic database search was performed on PubMed, Web of Science, CNKI and Wanfang Database for studies assessing p16/Ki-67 dual immunostaining in the diagnosis of high-grade cervical intraepithelial neoplasm (HGCIN) with abnormal cytological morphologies. Two reviewers screened literatures, extracted data and assessed the quality of the included studies independently. Meta-analysis was performed using ReV. Man 5.2 and Meta-DiSc 1.2 software packages. Results: The absolute sensitivity of p16/Ki-67 dual staining for diagnosing HGCIN ranged from 80% to 94%, while the sensitivity of triage method with hrHPV testing ranged from 78% to 96%. The specificity of p16/Ki-67 testing and hrHPV detection for predicting absence of CIN2+ ranged from 39% to 79% and 15% to 44%, respectively. Quantitative meta-analysis showed that the pooled sensitivity of p16/ki-67 dual staining is 0.88 [95'CI (0.86-0.90)], the pooled specificity is 0.58 [95'CI (0.56-0.60)]. For hrHPV testing, the pooled sensitivity and pooled specificity is 0.94 [95'CI (0.93-0.96)] and 0.32 [95'CI (0.29-0.34)], respectively. Conclusions: p16/Ki-67 dual immunostaining had comparable sensitivity and improved specificity in screening HGCIN or CC when compared with hrHPV detection. Further studies may be beneficial to assess the efficacy of this novel biomarker, which can be potentially used as one of the initial screening assays.

Objective The objective was to evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approximately 8 μg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population. Study design An open-label, single-arm phase III study conducted at 25 centers in China, Australia and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women ( N =1114) aged 18–40 years with regular menstrual cycles (21–35 days). Primary outcome was pregnancy rate, expressed as the Pearl Index. Secondary outcomes included 3-year cumulative failure rate, treatment-emergent adverse events (TEAEs), discontinuation rate, bleeding profile and placement pain. Results The full analysis set comprised 925 women (mean age 31.6 years, 6.4% nulliparous). Overall unadjusted Pearl Index was 0.35 (95% confidence interval 0.15–0.70); the 3-year cumulative failure rate was 0.9% (95% confidence interval 0.4–1.9). TEAEs and study drug-related TEAEs were reported in 70.1% and 31.2% of women, respectively. Overall, 27.9% of women discontinued the study, 16.9% due to adverse events. Frequent or prolonged bleeding (World Health Organization criteria) decreased from the first to the twelfth 90-day reference intervals (from 5.0% to 0.7% and from 44.1% to 3.0%, respectively), and the percentage of women with amenorrhea increased over time (from 0.4% to 10.8%). Pain on placement was reported as “none” or “mild” in 91.9% of women. Conclusions LNG-IUS 8 was an effective and well-tolerated contraceptive method, providing another option for women in the Asia-Pacific region. Implications In this phase III study, LNG-IUS 8 was shown to be highly effective and well tolerated in an Asia-Pacific population and was not associated with any new or unexpected safety events. LNG-IUS 8 provides another contraceptive option for women in the Asia-Pacific region.

Tumor vaccines offer a number of advantages for cancer treatment. In the study, the vaccination with cancer stem cells (CSCs) with high expression of the type I receptor tyrosine kinase-like orphan receptor (ROR1) was evaluated in a murine model for the vaccine’s immunogenicity and protective efficacy against epithelial ovarian carcinoma (EOC). CD117+CD44+ CSCs were isolated from human EOC HO8910 cell line using a magnetic-activated cell sorting system; murine ID8 EOC suspension sphere cells, which are collectively known as cancer stem-like cells, were acquired from serum-free suspension sphere-forming culture. Mice were subcutaneously immunized with the repeat cycles of freezing and thawing whole HO8910 CD117+CD44+ CSCs and ID8 cancer stem-like cells, respectively, followed by a challenge with HO8910 or ID8 cells at one week after final vaccination. The results showed that the CSC vaccination significantly induced immunity against EOC growth and markedly prolonged the survival of EOC-bearing mice in the prophylactic setting compared with non-CSC vaccination. Flow cytometry showed significantly increased immunocyte cytotoxicities and remarkably reduced CSC counts in the CSC-vaccinated mice. Moreover, the protective efficacy against EOC was decreased when the ROR1 expression was downregulated by shRNA in CSC vaccines. The findings from the study suggest that CSC vaccines with high ROR1 expression were highly effective in triggering immunity against EOC in vaccinated mice and may serve as an effective vaccine for EOC immunoprophylaxis.

The high mortality of ovarian cancer is partly due to the frequent resistance of ovarian cancer to current chemotherapy agents such as paclitaxel and platinum. Somatostatin analogue (SSTA) has been shown to inhibit the proliferation of some tumors through binding to somatostatin receptor (SSTR) and activation of Ras-, Rapl- and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2). It was reported that paclitaxel-octreotide conjugate (POC) exhibited enhanced tumor growth inhibition with reduced toxicity. In the present study, we prepared the POC and investigated its effects and mechanism for the reversal of drug resistance in paclitaxel-resistant ovarian cancer cell line. We demonstrated that treatment with POC led to more cell apoptosis than either paclitaxel or octreotide (OCT) alone. Moreover, the expression of multidrug resistance 1 (MDR1) and vascular endothelial growth factor (VEGF) mRNA, and protein decreased in a dose-dependent manner while the expression of SSTR remained stable following treatment with POC. Although the exact action, in vivo effects and pharmacologic kinetics of POC remain to be investigated, we have demonstrated the feasibility for the synthesis of POC, and more significantly, provided a potential approach to overcome the resistance of ovarian cancer against taxol. The findings also shed some new light on the mechanisms underlying the development of resistance to taxol by ovarian cancer cells.

Peptide hormone-based targeted therapy to tumors has been studied extensively. Our previous study shows that somatostatin receptor expresses high level on drug-resistant human ovarian cancer. The paclitaxel-octreotide conjugate (POC) exhibits enhanced growth inhibition, as well as reduced toxicity, in paclitaxel-resistant human ovarian cancer cells. The aim of this study was to investigate the effect of targeted cytotoxicity and potential reversal mechanism of resistance in paclitaxel-resistant human ovarian cancer cells xenografted into nude mice. The SSTR2 shows higher expression levels in tumor tissue. Moreover, fluorescein-labeled POC displays favorable targeting in tumor cells. POC presents the perfect efficacy in inhibiting tumor growth and exerts lower or no toxic effects on normal tissues. Real-time PCR and Western Blotting has demonstrated that the mRNA and protein expressions of SSTR2 in POC group were significantly higher, while MDR1, α-tubulin, βIII-tubulin, VEGF and MMP-9 were significantly lower than in the other treatment groups and controls. Combined with the previous study in vitro, this study evaluates an effective approach on the treatment of paclitaxel-resistant ovarian cancer which expresses somatostatin receptor SSTR. Our investigation has also revealed the possible molecular mechanism of POC in treating the ovarian cancer, and therefore, provided a theoretical basis for the clinical application of this newly-invented compound.

Aim To explore the effect of phenolic environmental estrogens (EE) on women with uterine leiomyoma (UL). Methods Urine and blood plasma samples were collected from 300 patients diagnosed with UL at the Affiliated Zhongda Hospital of Southeast University between December 2013 and December 2014. Control urine and blood plasma samples were collected from 300 women who are either patients without UL or healthy volunteers presenting to the same hospital for physical examination during the same period. Bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) concentration in these samples was measured using solid phase extraction (SPE) coupled with liquid chromatography–tandem mass spectrometry. Results The OP concentration in urine and blood plasma was significantly higher in the UL group compared with the control group (r = 0.224, P = 0.001). Urine BPA concentration was not significantly different between the UL group and the control group (r = 0.009, P = 0.896). There was also no statistically significant difference in urine NP concentration between the two groups (r = 0.057, P = 0.419). On logistic regression, exposure concentration of urine BPA (OR, 1.129; 95%CI: 1.081–1.179) and NP (OR, 1.165; 95%CI: 1.025–1.324) was associated with UL genesis (P 0.05). Conclusion Urine and blood plasma EE exposure levels in women, especially the urine level, was related to the incidence of UL.

Qi Yu,1 Zirong R Huang,2 Mulan Ren,3 Qing Chang,4 Zhongqi Zhang,5 Susanne Parke61Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China; 2Department of Family Planning, Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China; 3Department of Obstetrics and Gynecology, Zhongda Hospital, Southeast University, Nanjing, China; 4Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing, China; 5Bayer Healthcare Co., Ltd., Beijing, China; 6Bayer Pharmaceuticals, AG, Berlin, Germany Background: To investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women.Methods: In this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study.Results: A total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG.Conclusion: EV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population.Clinical trials registry: ClinicalTrial.gov identifier: NCT01638910.Keywords: Asian, bleeding pattern, combined oral contraceptive, cycle control, estradiol valerate/dienogest, women

Yunxia Zhang,1,2 Jing Wang,2 Di Wu,1 Miao Li,1 Fenshu Zhao,1 Mulan Ren,2 Yunlong Cai,2 Jun Dou1 1Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China Background: Epithelial ovarian cancer (EOC) with insidious characteristic manifests no symptoms in its early onset but most patients have advanced and distant cancer metastasis at diagnosis. Innovative early diagnosis and effective treatment of EOC are urgently needed. Methods: In the study, we developed a novel agent of IL-21-secreting human umbilical cord mesenchymal stem cells (hUCMSCs) combined with miR-200c to evaluate its effects on SKOV3 EOC in vitro and in vivo.Results: hUCMSCs-LV-IL-21 combined with miR-200c significantly inhibited the SKOV3 cell mobility and tumorigenesis compared with hUCMSCs-LV-IL-21, hUCMSCs- LV-vector, and hUCMSCs, respectively. These were reflected in decreasing the tumor sizes and elongating the tumor bearing nude mouse survival, accompanied with increasing the serum cytokine levels of IFN-γ, IL-21 and TNF-α as well as the splenocyte cytotoxicity. In addition, the expression of β-catenin, cyclin-D1, Gli1, Gli2, and ZEB1 was decreased but the E-cadherin expression was increased in tumor tissues of mice treated with hUCMSCs-LV-IL-21 plus miR-200c.Conclusion: We demonstrated that the synergistic effect of fighting SKOV3 EOC is attributable to repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in SKOV3 EOC. The findings may provide a new strategy for therapy of EOC. Keywords: epithelial ovarian cancer, umbilical cord mesenchymal stem cells, IL-21, miR-200c, Wnt/β-catenin signaling, epithelial–mesenchymal transition

Objective: This meta-analysis aims to examine whether the MspI and Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer risk. Methods: Eligible case–control studies were identified dated until July 2017. Pooled odds ratios (ORs) were used to assess the strength of the association between the two variants and cervical cancer risk. Results: Thirteen studies were eligible (2148 cases and 2252 controls) concerning MspI polymorphism and 8 studies were eligible (1466 cases and 1690 controls) for Ile462Val polymorphism. MspI polymorphism seemed to result in cervical cancer risk in any genetic model (C allele vs T allele: OR = 1.44, 95% confidence interval [CI] = 1.16–1.79; heterozygous model: OR = 1.40, 95% CI = 1.08–1.82; homozygous model: OR = 2.22, 95% CI = 1.48–3.33, dominant model: OR = 1.50, 95% CI = 1.14–1.98 and recessive model: OR = 1.80, 95% CI = 1.35–2.41); similar significantly increased risk was found among Caucasians and Asians. Ile462Val polymorphism was associated with elevated cervical cancer risk (Val allele vs Ile allele: OR = 1.85, 95% CI = 1.27–2.67; heterozygous model: OR = 1.42, 95% CI = 1.28–1.61; homozygous model: OR = 2.94, 95% CI = 1.15–7.54; dominant model: OR = 2.00, 95% CI = 1.33–3.00); this finding was replicated upon Caucasian population. Conclusion: This meta-analysis demonstrated that polymorphisms in MspI and Ile462Val of CYP1A1 were risk factors for developing cervical cancer.

Aim The aim of this study was to investigate whether a vegetarian diet correlates with a potential reduced risk of uterine fibroids. Material and Methods We used data from a case–control study conducted in Southeast University Zhongda Hospital between February 2010 and December 2014. Cases included 600 Chinese Han women with uterine fibroids (case group) whose clinical diagnosis dated back no more than 1 year. Controls were 600 patients without uterine fibroids as well as healthy volunteers (control group). All of the information gathered through the questionnaire survey was analyzed for the risk factors of the uterine fibroids pathogenesis. Results The multifactor analysis showed that women with uterine fibroids reported a less frequent consumption of broccoli (odds ratio [OR]: 0.552; 95% confidence interval [CI]: 0.316–0.964), cabbage (OR: 0.446; 95%CI: 0.211–0.943), Chinese cabbage (OR: 0.311; 95%CI: 0.102–0.946), tomato (OR: 0.453; 95%CI: 0.241–0.853), and apple (OR: 0.416; 95%CI: 0.213–0.814) (P < 0.05). Conclusion The original evidence from this epidemiological investigation shows that a high consumption of broccoli, cabbage, Chinese cabbage, tomato and apple seems to be a protective factor for uterine fibroids. We suggest that greater intake of fresh fruits and cruciferous vegetables may be able to reduce the incidence of uterine fibroids.

Objective To study the effect and mechanism of environmental estrogens bisphenol A (BPA) on uterine leiomyoma (UL) cells. Methods Primary cultures and subcultures of human UL cells, which were identified by immunocytochemical staining with a monoclonal anti-α-smooth muscle actin antibody, were performed. The viability of cells in different concentration of bisphenol A of 24 h, 48 h and 72 h were analyzed by CCK-8. The expressions of mRNA of ERα, IGF-1 and VEGF in all groups were detected by real-time quantitative PCR assay, and then the expressions of proteins detected by Western blot assay. Results BPA promoted the growth of UL cells and the expressions of ERα, IGF-1 and VEGF, which had positive correlation with the concentration and action time of BPA treatment. Conclusion BPA promotes the growth of leiomyoma cells. The expressions of IGF-1, VEGF can be up-regulated by ERα, which may be possible mechanism of BPA promote the growth of leiomyoma cells.

Objective: The aim of this study is to investigate whether certain combination of maternal killer cell immunoglobulin-like receptors (KIR) and fetal human leukocyte antigen-C (HLA-C) is risk for preeclampsia in the Chinese Han population. Methods: A case–control study was conducted in 47 pregnant women with preeclampsia and 54 normal pregnant women. Twelve KIR genes were genotyped by PCR-sequence-specific primer in mothers. High-resolution HLA-C genotyping was performed in couples and fetuses by a routine sequencing-based typing method. Results: The frequency of KIR2DS1 was decreased (p = 0.028) and AA genotype was increased (p = 0.017) in preeclampsia compared with controls. More women with KIR AA genotype have fewer C2 genes than their fetuses in preeclampsia than controls. Conclusion: Women with KIR AA genotype and fewer C2 genes than their fetuses were at risk for preeclampsia in the Chinese Han population, supporting that maternal–fetal KIR-HLA-C interaction plays an important role in preeclampsia de...

Specific blocking of interactions between ligands and receptors along the angiogenic pathways represents an effective approach for enhancing the efficacy as well as reducing adverse effects of chemotherapy. Over the past decade, there was a rapid progression in the application of this therapeutic strategy in cancer treatment. Anti-angiogenic therapy is the most promising targeted therapy for ovarian cancer. The addition of bevacizumab to conventional chemotherapy, either in the first-line setting or at disease relapse, may improve overall survival (OS) of ovarian cancer patients, at least in a subset of patients with poor prognosis. In this article, we summarize published data on the major agents used for anti-angiogenic therapy in ovarian cancers. We will review the molecular mechanisms, results of clinical trial of existing agents and describe the development of new agents. The limitations and side effects of angiogenesis inhibitor are also discussed.

Aim To explore the relationship between estrogen metabolism enzyme gene polymorphism and susceptibility to uterine fibroids, and to seek the screening molecular markers for genetic traits in uterine fibroid populations. Methods A total of 300 female Han Chinese patients and 300 healthy female Han Chinese volunteers in Nanjing (age range, 30–50 years) were recruited from Zhongda Hospital, Southeast University from February 2011 to March 2012. The single nucleotide polymorphisms (SNP) of estrogen-metabolizing enzyme genes from the two groups of women were examined by polymerase chain reaction denaturing high-performance liquid chromatography, which were four COMT gene loci including rs3087869, rs165774, rs165599 and rs4680, three CYP1A1 gene loci including rs1048943, rs4646421 and rs4646422, and three CYP1B1 gene loci including rs1056827, rs1056836 and rs1056837. Genotype frequencies among cases and controls were calculated and analyzed by binary logistic regression. Results Regression analysis of SNP showed that COMT IVS1+2329C>T (odds ratio [OR], 2.872; 95% CI, 1.690–4.882) and Val158Met (OR, 2.593; 95% CI, 1.546–4.350), CYP1A1 Ile462Val (OR, 2.383; 95% CI, 1.418–4.005) and Gly45Asp (OR, 2.489; 95% CI, 1.49–4.159), and CYP1B1 Ala119Ser (OR, 3.361; 95% CI, 2.035–5.552) and Leu432Val (OR, 0.164; 95% CI, 0.061–0.441) influenced uterine fibroids significantly (P T and Val158Met loci in COMT, Ile462Val and Gly45Asp loci in CYP1A1 and Ala119Ser loci in CYP1B1 were risk factors for uterine leiomyoma development, and Leu432Val locus in CYB1B1 may be a protective factor. The results provide a theoretical basis for genetic screening and early intervention for uterine leiomyoma-susceptible populations.

To explore the major risk factors and early prediction methods in the pathogenesis of early onset preeclampsia through combining prenatal screening markers and epidemiological characteristics.Prenatal screening was performed in second trimester using enzyme-linked immunosorbent assay in 1,011 gravidas and epidemiological correlation factors were got by telephone with prospective cohort study. Predictive model of early onset preeclampsia was established and evaluated by single and multiple factor logistic analysis in 30 cases of preeclampsia and 867 cases of normal gravidas.As compared with the control group, the maternal serum level of human chorionic gonadotropin (hCG) in second trimester of patients with early onset preeclampsia elevated significantly (P 0.001). Pregestational BMI ≥ 24 kg/m(2) (OR = 3.649, 95 % CI 1.600-8.321, P = 0.002), history of hypertension, diabetes and nephritis (OR = 55.724, 95 % CI 8.223-377.614, P 0.001), family history of hypertension (OR = 6.777, 95 % CI 2.917-15.742, P 0.001), and risk coefficient for trisomy 21 (OR = 3.688, 95 % CI 1.013-13.429, P = 0.048) were major risk factors of early onset preeclampsia. The sensitivity and specificity of predictive model were 70.0 and 75.1 %, when cutoff point was 0.249. The diagnostic accuracy of the logistic model was better than hCG.In order to early prevent the onset and development of EOPE, it is necessary to strengthen pregestational and prenatal care for women in these aspects including pregestational BMI ≥ 24 kg/m(2), history of hypertension, diabetes, nephritis, family history of hypertension, and high risk for trisomy 21 syndrom.

The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 μg ethinylestradiol [EE] and 120 μg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 μg EE and 3 mg drospirenone in healthy Chinese women aged 18-40 years.This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study.Participants were randomised either to the NuvaRing (n = 732) or to the COC (n = 214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result.Once-monthly NuvaRing is efficacious and safe for use in Chinese women.

The present study aimed to investigate the effects of octreotide (OCT) on the reversal of resistance of cisplatin-resistant cancer cells and on enhancement of the cisplatin sensitivity of cancer cells. The 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide method and flow cytometry were used to investigate the effect of cisplatin, OCT or the combination of these two compounds on the proliferation and apoptosis of SKOV3/DDP cells. Real-time, quantitative RT-PCR was used to detect the mRNA expression of SSTR2, MDR1, MRP2, GST-π and EGFR in SKOV3/DDP cells following OCT treatment. At the concentration of 2.5–20 μg/ml, OCT significantly reduced the IC50 value (P0.05). It is suggested that OCT inhibits ovarian cancer proliferation and promotes apoptosis, via the cell surface expression of SSRT2, and reverses cisplatin resistance through the inhibition of MRP2 and EGFR expression.

Objectives: To study the transforming growth factor beta (TGF-β) signaling pathway in interactions with estrogen receptor alpha (ERα) signaling pathway mediating the growth of human uterine leiomyoma (UL) activated by phenolic environmental estrogens (EEs). Methods: The subcultured UL cells were used to determine the validation of TGF-β3 for the viability of human UL cells using CCK-8 assay, mRNA expressions of ERα, and c-fos by quantitative reverse transcription polymerase chain reaction method, and expressions of p-Smad3, SnoN, and c-fos proteins by Western blot assay in each treatment group. Results: Compared with each of EEs or TGF-β3 treatment, slightly decrease in the proliferation rate of UL was detected in the coexistence of each EE with TGF-β3. Interestingly, mRNA expressions of ERα and c-fos reduced in the setting of coexistence of TGF-β3 and EEs. Somehow, the expression of p-Smad3 and c-fos proteins significantly decreased in each of E2, bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) group, as well as the expression of SnoN protein significantly reduced only in BPA and NP groups, followed by TGF-β3 treatment. With the overlaid action of ICI 182,780, the expression of p-Smad3 protein significantly increased in OP group, but slightly increased in E2, BPA, NP, and OP groups. However, compared with the control group, the expression of SnoN and c-fos proteins significantly decreased in the same setting. Conclusion: Both ERα signaling pathway and TGF-β signaling pathway have different roles in governing UL cell proliferation. The phenolic EEs can be a promoter to the proliferation of UL cells, which is mediated by ERα signaling pathway and cross-talked with TGF-β signaling pathway.

Background Accumulating evidence has shown that different immunotherapies for ovarian cancer might overcome barriers to resistance to standard chemotherapy. The vaccine immunotherapy may be a useful one addition to conditional chemotherapy regimens. The present study investigated the use of vaccine of ovarian cancer stem cells (CSCs) to inhibit ovarian cancer growth. Methods CD117+CD44+CSCs were isolated from human epithelial ovarian cancer (EOC) SKOV3 cell line by using a magnetic-activated cell sorting system. Pre-inactivated CD117+CD44+CSC vaccine was vacccinated into athymic nude mice three times, and then the mice were challenged subcutaneously with SKOV3 cells. The anti-tumor efficacy of CSC vaccine was envaluated by in vivo tumorigenicity, immune efficient analysis by flow cytometer, and enzyme-linked immunosorbent assays, respectively. Results The CD117+ CD44+CSC vaccine increased anti-ovarian cancer efficacy in that it depressed ovarian cancer growth in the athymic nude mice. Vaccination resulted in enhanced serum IFN-γ, decreased TGF-β levels, and increased cytotoxic activity of natural killer cells in the CD117+ CD44+CSC vaccine immunized mice. Moreover, the CSC-based vaccine significantly reduced the CD117+CD44+CSC as well as the aldehyde dehydrogenase 1 positive cell populations in the ovarian cancer tissues in the xenograft mice. Conclusion The present study provided the first evidence that human SKOV3 CD117+ CD44+CSC-based vaccine may induce the anti-ovarian cancer immunity against tumor growth by reducing the CD117+CD44+CSC population.

To assess the efficacy and safety of mifepristone combined with oral or vaginal misoprostol for termination of pregnancy between 8 and 16 weeks of gestation.This was a randomized, multi-center, open clinical trial. A total of 625 women at 8-16 weeks of gestation were randomized to receive 200 mg oral mifepristone followed by either oral misoprostol 400 µg every 3 hours or vaginal misoprostol 400 µg every 6 hours for a maximum of 4 doses 36-48 hours later. There were 417 women in oral group with 198 at 8-9 weeks and 219 at 10-16 weeks, while 208 women in vaginal group with 99 at 8-9 weeks and 109 at 10-16 weeks. The outcome measures were the success abortion rate, induction to abortion interval, the amount of bleeding, reoccurrence of menstruation and adverse events.Abortion rate was significantly higher in vaginal group [98.1% (202/206)] than that in oral group [94.0% (390/415), P = 0.023]; concerning termination of pregnancy at 8-9 weeks and 10-16 weeks respectively, there were no significant differences between oral and vaginal groups (P = 0.156, P = 0.073). The induction to abortion interval was no significant difference in oral and vaginal group in different gestational weeks (P = 0.238, P = 0.273). The average induction to abortion interval was (4.1 ± 6.6) hours and (6.0 ± 4.5) hours respectively in terminating 8-9 weeks and 10-16 weeks of gestation. Concerning the amount of bleeding within 2 hours of placenta expulsion, there was significant difference between oral group [(63 ± 46) ml] and vaginal group [(55 ± 45) ml] in terminating 8-9 weeks of gestation (P = 0.047), while there was no significant difference between groups in terminating 10-16 weeks of gestation [oral group (76 ± 52) ml versus vaginal group (76 ± 61) ml, P = 0.507]. The reoccurrence of menstruation was about 37 days in both oral and vaginal groups. Two cases of incomplete abortion were serious adverse events (SAE) relating to treatment. The common adverse events (AE) of nausea and vomiting were significantly higher in oral group [57.2% (239/417), 36.3% (151/417)] than those in vaginal group [45.4% (94/208), 26.1% (54/208); P = 0.005, 0.011].Oral or vaginal misoprostol combined with mifepristone, is effective and safe for termination of pregnancy between 8 and 16 weeks of gestation.

The aim of this paper is to study the participation of transforming growth factor-β (TGF-β) signaling pathway in mediating the growth of human uterine leiomyoma (UL) activated by phenolic environmental estrogens (EEs), via the interaction between TGF-β and ER signaling pathways. The UL cells were prepared by primary culture and subculture methods. To validate the role of TGF-β3 (5 ng/ml) for the viability of human uterine leiomyoma cells, CCK-8 assay was performed in each of five treatment groups including E2 group (E2 10(9) mol/l), BPA group (bisphenol A 10 μmol/l), NP group (nonylphenol 32 μmol/l), OP group (octylphenol 8 μmol/l), or control group (DMSO only). Subsequently, qRT-PCR was applied to detect mRNA expressions of ERα and c-fos, while western blot assay was used to test the expressions of p-Smad3, SnoN, and c-fos proteins in all settings mentioned above; the expressions were compared among different groups, and also in settings with and without synchronous treatment of ICI 182,780. Primarily cultured UL cells were successfully established. Compared with the control group, there were statistically significant increases in the proliferation rate of the UL cells in all EE groups or treated with TGF-β3 only (p 0.05). Nevertheless, a slight decrease in proliferation rate of UL was detected in coexistence with TGF-β3 in all EE groups (p 0.05). Interestingly, mRNA expressions of ERα and c-fos reduced in the setting of coexistence of TGF-β3 and EEs compared to isolated EE treatment (p 0.05). Compared with the control group, the expression of p-Smad3 and c-fos proteins significantly decreased (p 0.05) in each of E2, BPA, NP, and OP group, and the expression of SnoN protein also significantly reduced only in BPA and NP groups (p 0.05), followed by TGF-β3 treatment. When adding ICI 182,780, the expression of p-Smad3 protein significantly increased in OP group (p 0.05), but slightly increased in E2, BPA, NP, and OP groups (p 0.05). However, compared with the control group, the expressions of SnoN and c-fos proteins significantly decreased (p 0.05) after adding ICI182,780. Moreover, there was a significant statistical difference in the expression of p-Smad3, SnoN, and c-fos proteins between pre- and post-treatment of ICI 182,780 in all groups (p 0.05). The ERα signaling pathway and TGF-β signaling pathway have different roles in the control of UL cell proliferation. The phenolic EEs can be a promoter of UL cell proliferation, which is mediated by ERα signaling pathway and its cross-talking with TGF-β signaling pathway. Both less exposure to EEs and blockade of TGF signaling pathway are necessary strategies to prevent UL.

The present study was designed to explore the cross talk between fatty acid synthase (FASN) and HER2 (ErbB2) in ovarian cancer. A total of 60 ovarian cancer patients and 15 normal ovarian tissues were enrolled. Tissue array was conducted by using a tissue microarray instrument. Immunohistochemistry was performed to quantify the expressions of HER2 and FASN. The FASN was detected to be distributed in the cell cytoplasm and was significantly correlated with cancer grade (p = 0.000) and FIGO staging (p = 0.000). Patients with FASN overexpression in ovarian cancer tend to have a worse overall survival rate (p = 0.000). HER2 was also stained to be distributed in the cell cytoplasm associated with higher expression in high-grade cancer. It was also disclosed that FASN expression level is not correlated with HER2 status in ovarian cancer. These results for the first time indicated that a cross talk in FASN and HER2 expressions might be associated with prognosis in malignant ovarian cancer.

Published data on the association between the glutathione S-transferases (GSTs) gene polymorphisms and endometriosis risk are inconclusive. We performed a meta-analysis to clarify the association of GSTM1 and GSTT1 polymorphisms and endometriosis risk. A comprehensive search was conducted to examine all the eligible studies of GSTM1 and GSTT1 polymorphisms and endometriosis risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 18 case–control studies were included in the meta-analysis of GSTM1 (2593 cases and 2732 controls) and GSTT1 (2520 cases and 2508 controls) genotypes. The overall results showed that the GSTM1 null genotype was related to an increased risk of endometriosis (OR = 1.55, 95% CI = 1.38–1.73). Similarly, for GSTT1 null polymorphism, moderate significantly increased risk was found (OR = 1.30, 95% CI = 1.13–1.50). In the subgroup analysis by ethnicity, significantly increased risks were also found among Caucasians and Asians for null GSTM1 genotype, and Asians for null GSTT1 genotype, but no correlation was noted in Caucasian populations for GSTT1 polymorphism. This meta-analysis provides strong evidence that the GSTM1 and GSTT1 polymorphisms are associated with the development of endometriosis.

To investigate the effect of estrogen replacement therapy applied in different periods to ovariectomized rats and to evaluate the cognitive function of the rats.Totally 40 rats were ovariectomized to be postmenopausal models. They were divided into early hormone replacement therapy group (n = 10, managed by estradiol valerate at day 3 after surgery), early control group (n = 10, managed by saline at day 3 after surgery), late hormone replacement therapy (n = 10, managed by estradiol valerate at day 90 after surgery for 30 days) and late control group (n = 10, managed by saline at day 90 after surgery for 30 days). The behavior indicators of the rats were evaluated by Morris watermaze and hippocampal metabolite was detected by proton magnetic resonance spectroscopy, including N-acetylaspartate (NAA), choline containing compounds (Cho), creatine (Cr), myoinositol (mI), NAA/Cr, Cho/Cr and mI/Cr.(1)Navigation test: escape latency were (43 ± 13) s at the early control group, (28 ± 9) s at the early HRT group, (82 ± 26) s at the late control group and (48 ± 18) s at late HRT group. Swimming distance were (1 404 ± 238) cm at the early control group, (878 ± 354) cm at the early HRT group, (2 411 ± 818) cm at the late control group and (1 310 ± 434) cm at the late HRT group. The escape latency and swimming distance of the early and late HRT groups were significantly shorter than those at the control groups (P0.05). (2) Spatial probe test: the swimming time in the target quadrant of rats in the early HRT group (34.0 ± 3.0) s were longer than those in other groups (P0.05). (3) Proton magnetic resonance spectroscopy: NAA/Cr were 1.12 ± 0.17 at the early control group, 1.26 ± 0.12 at the early HRT group, 1.57 ± 0.21 at the late control group and 1.38 ± 0.28 at the late HRT group. The late HRT group and the late control group were higher than their early groups (F = 6.05, P = 0.040). There was no significant difference between the HRT groups and the control groups (F = 0.04, P = 0.860). mI/Cr were 0.69 ± 0.04 at the early control group, 0.46 ± 0.12 at the early HRT group, 0.70 ± 0.03 at the late control group and 0.75 ± 0.08 at the late HRT group. There were statistically significant differences of the experimental time between the early and late groups(F = 16.45, P = 0.004). The differences between the early HRT group and the early control group, and the late HRT group and the late control group were significant (F = 6.01, P = 0.040). And there was an interaction with the experimental time and HRT measures (F = 13.79, P = 0.006); early HRT can reduce the average level of mI/Cr. Cho/Cr were 0.95 ± 0.09 at the early control group, 0.80 ± 0.12 at the early HRT group, 0.87 ± 0.09 at the late control group and 0.85 ± 0.12 at the late HRT group. There was no significant difference among those groups (P0.05). NAA/mI: there was an interaction with the experimental time and HRT measures (F = 12.95, P = 0.007). Early HRT can elevated levels of NAA/mI, while the late results were reversed.Earlier estrogen replacement therapy may play a positive role in improving cognitive function of the ovariectomized rats.

Objective To study the effect and mechanism of action of nonylphenol (NP), an environmental oestrogen, on uterine leiomyoma (UL) cells. Methods Primary culture and subculture of human UL cells, identified as smooth muscle cells by immunocytochemical staining with a monoclonal anti-α-smooth muscle actin antibody, were performed. The viability of cells treated with various concentrations of NP for 24, 48 and 72 h was determined by CCK-8 assay. mRNA expression of oestrogen receptor α (ERα), insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) was detected using real-time quantitative polymerase chain reaction, and protein expression was detected using Western blot analysis for all groups. Results NP promoted the growth of UL cells and expression of ERα, IGF-1 and VEGF; this was positively correlated with the concentration and duration of NP treatment. Conclusion NP promotes the growth of UL cells. The mechanism of action appears to be over-expression of IGF-1 and VEGF, up-regulated by ERα, resulting in the growth of UL cells.

Uterine leiomyoma (UL) is an estrogen-responsive benign tumor in the female reproductive system and the main risk of hysterectomy for women. However, gene polymorphism of estrogen-metabolizing enzymes may lead to the different susceptibility to UL. We detected 10 single mucleotide polymorphisms in three key estrogen metabolite enzymes (COMT, CYP1A1, CYP1B1) in a Chinese Han population consisting of 800 patients and 800 healthy women from five different medical centers. The genetic polymorphism of rs3087869 (IVS1+2329C>T) (OR 3.200, 95% CI 1.614-6.345) and rs4680 (Val158Met) (OR 5.675, 95% CI 2.696-11.942) loci on COMT, rs1048943 (Ile462Val) (OR 4.629, 95% CI 2.216-9.672) and rs4646422 (Gly45Asp) (OR 3.240, 95% CI 1.624-6.461) loci on CYP1A1 and rs1065827 (Ala119Ser) (OR 5.635, 95% CI 2.990-10.619) locus on CYP1B1 were the risk factors to UL development and rs1056836 (Leu432Val) (OR 0.188, 95% CI 0.061-0.575) locus on CYB1B1 may be the protective factor to UL. The results provide a theoretical basis for genetic screening and early intervention to UL-susceptible populations.

Various studies examined the relationship between human epidermal growth factor receptor 2 (HER-2/neu) overexpression and the clinical outcome in patients with ovarian cancer, but yielded conflicting results. Electronic databases updated in May 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between HER-2/neu overexpression and survival of patients with ovarian cancer. Survival data were aggregated and quantitatively analyzed. We conducted a final analysis of 3,055 patients from 20 eligible studies and evaluated the correlation between HER-2/neu overexpression and survival in patients with ovarian cancer. Combined hazard ratios suggested that HER-2/neu overexpression was not associated with a significant impact on survival, with the hazard ratio (HR) and 95 % confidence interval (CI) being 1.05 and 0.92–1.19, respectively, overall. When grouped according to the study design type, a statistically significant combined HR was found in retrospective studies (HR = 1.44, 95 % CI 1.14–1.75) and no statistically significant combined HR was found (HR = 0.96, 95 % CI 0.81–1.11) for prospective studies. HER-2/neu overexpression seems to have no significant impact on survival of ovarian cancer patients. However, a statistically significant combined HR was found in retrospective studies, but not in prospective studies.

To explore the relationship between estrogen metabolism enzyme gene polymorphism and susceptibility to uterine fibroids, and to seek the screening molecular markers for genetic traits in uterine fibroid populations.A total of 300 female Han Chinese patients and 300 healthy female Han Chinese volunteers in Nanjing (age range, 30-50 years) were recruited from Zhongda Hospital, Southeast University from February 2011 to March 2012. The single nucleotide polymorphisms (SNP) of estrogen-metabolizing enzyme genes from the two groups of women were examined by polymerase chain reaction denaturing high-performance liquid chromatography, which were four COMT gene loci including rs3087869, rs165774, rs165599 and rs4680, three CYP1A1 gene loci including rs1048943, rs4646421 and rs4646422, and three CYP1B1 gene loci including rs1056827, rs1056836 and rs1056837. Genotype frequencies among cases and controls were calculated and analyzed by binary logistic regression.Regression analysis of SNP showed that COMT IVS1+2329CT (odds ratio [OR], 2.872; 95% CI, 1.690-4.882) and Val158Met (OR, 2.593; 95% CI, 1.546-4.350), CYP1A1 Ile462Val (OR, 2.383; 95% CI, 1.418-4.005) and Gly45Asp (OR, 2.489; 95% CI, 1.49-4.159), and CYP1B1 Ala119Ser (OR, 3.361; 95% CI, 2.035-5.552) and Leu432Val (OR, 0.164; 95% CI, 0.061-0.441) influenced uterine fibroids significantly (P 0.05). Allele and genotype frequencies among cases and control were calculated and examined to match the Hardy-Weinberg equilibrium with the χ²-test.The genetic polymorphisms of IVS1+2329CT and Val158Met loci in COMT, Ile462Val and Gly45Asp loci in CYP1A1 and Ala119Ser loci in CYP1B1 were risk factors for uterine leiomyoma development, and Leu432Val locus in CYB1B1 may be a protective factor. The results provide a theoretical basis for genetic screening and early intervention for uterine leiomyoma-susceptible populations.

The aim of this study was to determine whether the increased serum cell-free fetal DNA (cffDNA) level of gravidas developed into early-onset preeclampsia (EOPE) subsequently in the early second trimesters is related to prenatal screening markers. Serum was collected from 1011 gravidas. The level of cffDNA and prenatal screening markers were analyzed in 20 cases with EOPE and 20 controls. All fetuses were male. The maternal serum cffDNA level was assessed by amplification of the Y chromosome specific gene. Correlations between the variables were examined. (Logged) cffDNA in EOPE (median, 3.08; interquartile range, 2.93–3.68) was higher than controls (median, 1.79; interquartile range, 1.46–2.53). The increased level of (logged) cffDNA was correlated significantly with the increased human chorionic gonadotropin (HCG) level (r = 0.628, p < 0.001). Significant reciprocal correlations between cffDNA and babies’ birth weight as well as gestation weeks at delivery were noted (r = −0.516, p = 0.001; r = −0.623, p < 0.001, respectively). The sensitivity and specificity of cffDNA to discriminate between the EOPE cases and the controls were 90% and 85%, respectively. CffDNA is a potential marker for EOPE, which had a significant reciprocal correlation with babies’ birth weight and gestation weeks at delivery. Moreover, it may help in indicating the underlying hypoxic condition in the placenta.

Objective: To study the anti-tumor effects of octreotide on A2780/Taxol ovarian cancer cells in vitro, and further explore its potential molecular mechanism. Materials and Methods: Immunocytochemistry was performed to determine the expression of SSTR2 on A2780/Taxol cells. Octreotide at different concentrations (0, 1.25, 2.5, 5.0, 10.0, and 20.0 nmol/ml) were administrated to A2780/Taxol cells in vitro. CCK-8 assay was used to measure the effects on cell proliferation, and the cytometry of octreotide determined the cell apoptosis. The expressions of SSTR2 MDR1, and vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) were investigated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay and the expressions of the above protein were investigated after A2780/Taxol was treated with octreotide for 48 hours by western blot in vitro. Results: Positive expression of SSTR2 was observed on the membrane of A2780/Taxol cells. The proliferation of A2780/Taxol cells was gradually inhibited with increasing octreotide concentration in a concentration-dependent and time-dependent manner. Meanwhile, flow cytometry data demonstrated the octreotide-induced cell apoptosis. The results of SSTR2 mRNA suggested that there was no significant difference between each concentration group of octreotide (P > 0.05). Compared with the control group, both the MDR1 and VEGF mRNA decreased in a dose-dependent manner following 48 hours of treatment of octreotide (P < 0.05). The results of western blot showed that octreotide decreased the expressions of SSTR2, MDR1, and VEGF protein in a dose-dependent manner (P < 0.05). Conclusions: Octreotide significantly inhibits ovarian cancer's proliferation and promotes its apoptosis via the cell surface expression of SSTR2. It could be used as a new targeted drug for treatment of ovarian cancer.

Objectives The development of preeclampsia is considered to be related to maternal immune and genetic factors. HLA-C is one of the major histocompatibility antigens that plays an important role in regulating maternal fetal interface. However, epidemiological studies show that paternal risk factors can play a role in the development of preeclampsia. The aim of this study is to explore the relationship between paternal and fetal HLA-C allelic polymorphisms and preeclampsia in Chinese Han population. Methods 34 spouses and fetuses of women with preeclampsia and 37 spouses and fetuses of healthy pregnant women were included in the case-control study. All pregnant women were at the third trimester of gestation. The HLA-C genes from blood genomic DNA were genotyped by polymerase chain reaction–sequencing-based typing (PCR-SBT) genotyping method. The associations of HLA-C alleles with the disease were expressed as P and odds ratios (ORs). Results No differences were observed in the spouses’ age, body mass index, contraception method or previous history of hypertension and cardiovascular disease. Gestational age was shorter (36.39 ± 3.15 vs. 39.31 ± 1.14, p p ∗ 08:01:01G was significantly higher in the spouses of preeclamptic women, compared with that in the spouses of normotensive women (14.7 vs. 2.7%, P = 0.010, OR = 6.207, 95%CI (1.308, 29.451)). There was no statistical difference in the frequency of fetal HLA-C alleles ( p > 0.05). Conclusions Pregnant women with spouses carrying HLA-C ∗ 08:01:01G have a greater risk for the developing of preeclampsia in Chinese Han population. Disclosures H. Yu: None. N. Pan: None. Y. Shen: None. S. Jin: None. J. Zhai: None. D. Qiao: None. L. Chen: None. W. Xu: None. F. Miao: None. Y. He: None. M. Ren: None. J. Zhang: None.

Objectives To investigate the effect of phenolic environmental estrogens on uterine leiomyoma from the perspective of clinical epidemiology. Methods Urine and blood samples were collected from Han women with uterine leiomyoma and women without uterine leiomyoma, living in Nanjing, China, between September 2011 and February 2013. A total of 156 urine samples and 214 blood samples were collected from the uterine leiomyoma group and 106 urine samples and 126 blood plasma samples from the control group. Bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) concentrations were determined by solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results Phenolic environmental estrogens in the uterine leiomyoma and control groups were compared based on: gravida>3 and gravida ≤ 3. In participants with gravida>3, urine OP concentration was significantly (P0.05) different between gravida>3 and gravida ≤ 3 patients. There was no significant (P>0.05) difference in plasma concentrations of BPA, OP and NP between the leiomyoma group and control group. Mean exposure concentration and range of distribution of BPA, OP and NP plasma concentration differed between the uterine leiomyoma and control group. Conclusion Exposure level of phenolic environmental estrogens in human was related with leiomyoma tumorigenesis.