Hypermethylated RASAL1's promotive role in chemoresistance and tumorigenesis of choriocarcinoma was regulated by TET2 but not DNMTs.

BACKGROUND: Patients with choriocarcinoma (CC) accompanying chemoresistance conventionally present a poor prognosis. Whether ras protein activator like-1 (RASAL1) functions as a tumor promoter or suppressor depends on tumor types. However, the role of RASAL1 in process of chemoresistance of CC and underlying molecular mechanism remain elusive. METHODS: The expression pattern of RASAL1 in CC cells and tissues was measured using Western blotting, immunohistochemistry and qRT-PCR. Cell viability and proliferative ability were assessed by MTT assay, Tunnel assay and flow cytometric analysis. Additionally, the stemness was evaluated by the colony formation and tumor sphere formation. Methotrexate (MTX) was applied to exam the chemosensitivity of CC cells. RESULTS: The expression of RASAL1 was reduced both at the protein and mRNA levels in CC tissues and cells compared to hydatidiform mole (HM) and invasive mole (IM). Loss of RASAL1 was attributed to its promoter hypermethylation and could be restored by 5-Aza. Knock-down of RASAL1 promoted the viability, proliferative potential, stemness and EMT phenotype of JEG-3 cells. However, induced overexpression of RASAL1 by 5-Aza significantly prohibited cell proliferation and stemness potential of the JAR cell. Additionally, the xenograft model indicated that knockdown of RASAL1 led to a remarkable increase of tumor volume and weight in comparison with its counterpart. Moreover, the stimulatory activity brought by decrease of RASAL1 could be deprived by ß-catenin inhibitor XAV 939, yet the suppressive activity resulted from its promoter demethylation could be rescued by ß-catenin activator BML-284, indicating that function of RASAL1 depends on ß-catenin. Besides, the co-immunoprecipitation assay confirmed the physical binding between RASAL1 and ß-catenin. Further investigations showed hypermethylated RASAL1 was regulated by TET2 but not DNMTs. CONCLUSION: Taken together, the present data elucidated that reduced RASAL1 through its promoter hypermethylation regulated by TET2 promoted the tumorigenicity and chemoresistance of CC via modulating ß-catenin both in vitro and in vivo.

Clinical characteristics and outcomes of extrauterine epithelioid trophoblastic tumors.

BACKGROUND: Epithelioid trophoblastic tumor (ETT) derived from intermediate trophoblasts is one type of gestational trophoblastic neoplasia (GTN), and it accounts for less than 2% of all gestational trophoblastic diseases (GTD). Extrauterine ETT is extremely rare, and there is currently no consistent strategy for its treatment and management. Therefore, the aim of the study is to analyze and summarize the clinicopathologic features of extrauterine ETT with or without metastasis. METHOD: The Web of Knowledge, Google Scholar, EMbase, congress of library, and PubMed were searched for extrauterine ETT without primary uterine lesions. All available data were extracted from published case reports or serial case reports, and then, the clinical and pathological characteristics were analyzed. RESULTS: Twenty-two clinical studies consisting of 27 patients diagnosed with extrauterine ETT, according to the given inclusion and exclusion criteria, were included in the study. A total of 27 cases of extrauterine ETT were identified. Of these cases, four (14.81%) were located in the lungs, three (11.11%) in the ovaries, two (7.41%) in the vagina, and eight (29.63%) patients had other primary lesions. The patients originated from different continents, with 59% located in Asia and 26% in North America. Among 23 patients, the antecedent pregnancy prior to the diagnosis was full-term in 12 cases, abortion in 6 cases, hydatidiform mole in 3 cases, and invasive mole in 1 case. From the available antecedent information on pregnancy, the median interval from pregnancy to diagnosis of extrauterine ETT was 4 years. Additionally, the median gravidity and para of the patients was three times and two times, respectively. The median hCG titer was 14,374 mIU/mL in 5 patients, and the mean ß-HCG titer was 3,724,805 mIU/mL in 14 patients. For all patients, the disease was confined to extrauterine ETT at diagnosis. From the available information, 20 cases were successfully treated by extraction of local lesions, and 12 cases received chemotherapy. Diagnosis was confirmed by histological tests. The Ki-67 staining ranged from 8.7 to 80%, and tumors were positive for hCG, PLAP, EMA, and p63. CONCLUSION: In this study, we observed that abnormal levels of serum hCG titers and the local presentation of lesions with varying intervals after antecedent term pregnancy were the most common presenting features of extrauterine ETT. In addition, we found that the extraction of extrauterine lesions was needed for the treatment of extrauterine ETT. Of course, the follow-up was also important.

Secreted Frizzled Related Protein 2 Modulates Epithelial-Mesenchymal Transition and Stemness via Wnt/ß-Catenin Signaling in Choriocarcinoma.

BACKGROUND/AIMS: Choriocarcinoma (CC) is a highly aggressive gestational trophoblastic neoplasia; however, the underlying molecular mechanisms of its invasiveness and metastasis remain poorly understood. Human secreted frizzled-related protein 2 (SFRP2) could function as a tumor promoter or suppressor in different tumors, yet the role it plays in CC's invasion and metastasis is thoroughly unclear. The current study was aimed to explore the function and underlying mechanism of SFRP2 in CC. METHODS: The expression of SFRP2 in CC tissues was examined via immunohistochemistry. The methylation level and expression of SFRP2 in CC cell lines, JEG-3 and JAR were examined via bisulfite sequencing PCR (BSP), western blotting and quantitative RT-PCR. The biological role of increasing expressed SFRP2 through its promoter demethylation with 5-Aza-2'-deoxycytidine (5-Aza) was examined by a series of in vitro functional studies. Furthermore, lentivirus transfection technology was adopted to investigate the biological roles of SFRP2 knockdown in JEG-3 and JAR cells in vitro and in vivo. Moreover, its downstream signaling pathway was investigated. RESULTS: SFRP2 was downregulated in CC tissues, and its expression was inversely related to its promoter hypermethylation frequency in JEG-3 and JAR cells. Increased SFRP2 through its promoter demethylation inhibited cell migration, invasion and colony formation in JEG-3 and JAR cells, whereas decreased SFRP2 reversed the epithelial-mesenchymal transition (EMT) process and stemness in JEG-3 and JAR cells both in vitro and vivo. Mechanistically, SFRP2 regulated the EMT and stemness of CC cell lines via canonical Wnt/ß-catenin signaling, validated by the usage of a Wnt activator and inhibitor. CONCLUSION: The current study indicates that downregulated SFRP2 has potent tumor-promotive effects in CC through the modulation of cancer stemness and the EMT phenotype via activation of Wnt/ß-catenin signaling in vitro and in vivo.

Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study.

The aim of this study was to explore risk factors of recurrent bacterial vaginosis (RBV) among women of reproductive age. This cross-sectional study was carried out in real-world conditions. Women with RBV were selected, and simultaneously uncomplicated bacterial vaginosis (UBV) and those who underwent routine gynecological examination and had normal vaginal microflora were also recruited as the control. Totally, 316 participants were enrolled. Univariate analysis showed that unemployment, desserts, and wiping were related to UBV, while there was no definite relationship between education, high body mass index, smoking, sedentary lifestyle, and RBV or UBV. History of human papillomavirus infection, contraceptive methods, age at first sexual intercourse, and not cleaning vulva during sexual activity were connected with UBV, while the history of other vaginitis and number of sexual partners in the previous year were related to both RBV and UBV. Multivariate logistic regression analysis revealed that lower educational level increased the risk of suffering RBV. Interestingly, no smoking was a protective factor. Moreover, the absence of other vaginitis and an exclusive sexual partner could also weaken the risk of incurring RBV. These various adverse factors alter endocrine function and vaginal immunity, further leading to the recurrence of BV. It is necessary to take corresponding measures to avoid risk factors and to help lessening the prevalence of RBV among women of reproductive age.

Improved treatment of vulvovaginal candidiasis with Clotrimazole plus probiotic Lacidophilin Vaginal Capsules: A prospective, real-world study.

BACKGROUND: Clotrimazole has long been used to treat vulvovaginal candidiasis (VVC), yet the antibiotic resistance, adverse effects and recurrences still bring about a great challenge for the clinicians. To explore the effect of probiotic Lacidophilin Vaginal Capsules plus Clotrimazole Vaginal Tablets (500mg) in the treatment of uncomplicated VVC, a self-controlled real-world study was conducted. METHODS: Twenty-seven women with a normal vaginal flora and 15 women with uncomplicated VVC were recruited. The patients were treated with the single dose of Clotrimazole Vaginal Tablets (500mg) supplemented with 2 Lacidophilin Vaginal Capsules for the following 7 days. The patients were prospectively examined 4 times and the time points were at m0 (the first visit), m1 (8-10 days after the first visit), m2 (30 days after the second visit) and m3 (30 days after the third visit). However, women in the healthy normal control group were examined just once at the first visit. The obtained vaginal secretions were examined by high-throughput sequencing. RESULTS: The mean age in healthy control group and case group was 28.63 ± 5.40y and 27.67 ± 3.33y, respectively. Finally, 46.67% (7/15) of patients were cured at the second visit, 61.54% (8/13) were cured at the third visit and eventually 72.73% (8/11) were cured. A total of 81 samples were sequenced, generating 1668 operation taxonomy units among all the samples. The bacterial composition of women in the healthy control group was exceedingly abundant and dominated by Lactobacillus, especially by Lactobacillus. crispatus, and followed by Lactobacillus. iners, Lactobacillus. jensenii and Gardneralla. On the contrary, the bacterial composition of women with VVC was relatively few and dominated by Lactobacillus. iners. During the process of treatment, the bacterial abundance of VVC patients was increased gradually. At the final visit, the abundance of vaginal flora was augmented further with the dominant bacteria being Lactobacillus. crispatus, followed by Lactobacillus. iners. CONCLUSION: Clotrimazole Vaginal Tablets plus probiotic Lacidophilin Vaginal Capsules could improve the effect in treating uncomplicated VVC. This improved effect was achieved perhaps through improving the composition of vaginal flora and restoring vaginal microecology.

Biocompatible carbon-doped MoSe2 nanoparticles as a highly efficient targeted agent for human renal cell carcinoma.

MoSe2 is a typical transition-metal dichalcogenide material, and many researches have been focused on using its property of near infrared strong absorption for laser mediated photothermal cancer treatment. However, the anti-canter effect of MoSe2 and its possible mechanism in renal cell carcinoma (RCC) is still unclear. RCC has high incidence of metastasis, which is known as one of the most lethal malignancies in the urological system. This study revealed that the carbon-doped MoSe2 particles can obviously inhibit proliferation for 786-O and ACHN cells. Meanwhile, the carbon-doped MoSe2 nanoparticles have little impact on the viability of KH-2 cells in vitro. The mechanism analysis revealed that the carbon-doped MoSe2 particles have hydrogen bond effect in aqueous solution, and the particle aggregation effect caused the KH-2 cells to have high viability. The carbon-doped MoSe2 nanoparticles with minimal toxicity may be a potential therapeutic candidate against RCC.

Risk Factors of Vulvovaginal Candidiasis among Women of Reproductive Age in Xi'an: A Cross-Sectional Study.

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.

Association between RAD51 135 G/C polymorphism and risk of 3 common gynecological cancers: A meta-analysis.

AIM: Available data concerning the association between RAD51 135G/C (rs1801320) polymorphism and the risk of 3 common gynecological cancers still could not reach a consensus. Thus, we conducted a meta-analysis to explore the relationship. METHODS: Several electronic databases and bibliographies of relevant articles were screened to identify the studies up to July 2017. Then a meta-analysis was performed to evaluate the connection between 3 common gynecological tumors' susceptibility and RAD51 135G/C polymorphism in different inheritance models. Simultaneously, we did subgroup analysis and sensitivity analysis if necessary. RESULTS: A total of 11 articles including 14 studies involving 4097 cases and 5890 controls were included in this meta-analysis. Overall, RAD51 135G/C polymorphism increased the risk of 3 common gynecological tumors. The subgroup analysis stratified by cancer types- endometrial carcinoma (EC) and ovarian cancer (OC)-showed that RAD51 135G/C polymorphism increased the risk of EC: allele model (C vs G: odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.63-7.10, P < .00001), dominant model (CC + GC vs GG: OR = 2.28, 95% CI = 1.44-3.60, P = .004), recessive model (CC vs GC + GG: OR = 10.27, 95% CI = 14.71-22.38, P < .00001), and homozygous model (CC vs GG: OR = 7.26, 95% CI = 3.59-14.68, P < .00001), but there was no significant association between RAD51 135G/C polymorphism and OC. In the subgroup analysis stratified by source of controls, a significantly increased risk was observed in hospital-based studies. Nevertheless, the data showed RAD51 135G/C polymorphism had no link in population-based studies. CONCLUSIONS: This meta-analysis suggested that RAD51 135G/C polymorphism was a risk factor for the three common gynecological tumors, especially for EC among hospital-based populations.

Postoperative adjuvant chemo (embolization) therapy for hepatocellular carcinoma with portal vein tumor thrombosis.

BACKGROUND: The present meta-analysis was aimed to evaluate the effects of postoperative adjuvant chemotherapy/transarterial chemoembolization (TACE) on the survival/disease-free survival (DFS) rate in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). METHODS: The relevant trials were collected using a database search of MEDLINE, Embase, Cochrane Library, Web of Science, ScienceDirect, the China Journal Full-text Database, and the National Institute of Health Clinical Trials Database. The 1-, 3-, and 5-year survival/DFS rates were considered to be the primary end points. A sensitivity analysis was conducted by reanalyzing the data using different statistical approaches. RESULTS: Eight studies met the inclusion criteria. When compared with surgery alone, the pooled OR showed that the postoperative adjuvant therapy significantly increased the 1-, 3-, and 5-year survival rates for HCC patients with PVTT (the pooled OR and 95% CI of the 1-, 3-, and 5-year survival rates, respectively, were as follows: 2.72, 1.98-3.74; 1.62, 1.13-2.33; 1.99, 1.20-3.29). In addition, when compared with surgery alone, subgroup analysis showed that the postoperative chemotherapy improved the 1-, 3-, and 5-year survival rates of HCC patients with PVTT. CONCLUSION: Compared with surgery alone, postoperative adjuvant chemotherapy can improve the 1-, 3- and 5-year survival rates of HCC patients with PVTT. However, postoperative TACE can only increase the 1-year survival rate. However, due to the limitations of this meta-analysis, additional relevant trials are required to confirm these findings.

Association between KIF1B (rs17401966) polymorphism and hepatocellular carcinoma susceptibility: a meta-analysis.

INTRODUCTION: The results of the earlier published studies on the association between KIF1B (rs17401966) polymorphism and hepatocellular carcinoma (HCC) risk are inconclusive. Hence, we performed this meta-analysis to evaluate the relationship between KIF1B (rs17401966) polymorphism and HCC risk. METHODS: Databases including PubMed, Web of Science and the Cochrane Library and bibliographies of relevant papers were screened to identify relevant studies published up to March 25, 2018. Pooled ORs and 95% CIs were calculated to evaluate the association. The subgroup analysis was conducted based on ethnicity, age, region and environment. A total of 19 studies from 11 eligible articles published from 2010 to 2016, with 8,741 cases and 10,812 controls, were included. RESULTS: The pooled results indicated that the association between KIF1B (rs17401966) polymorphism and the decreased HCC risk was significant. Subgroup analysis stratified by ethnicity showed the same association in Chinese, but not in non-Chinese population. When stratified by age, both old and young patients showed a decrease in HCC risk. When stratified by region, we detected the same association in Chinese in southern China. Similarly when stratified by environment, we observed the same association in Chinese in inland areas; however, no statistically significant association was observed in those in coastal areas. CONCLUSION: This meta-analysis suggested that KIF1B (rs17401966) polymorphism could decrease HCC risk in Chinese and in overall population, but not in non-Chinese. This association remained significant in Chinese in southern China and inland areas, but not in those in northern and central China and coastal areas. Further large-scale multicenter studies are warranted to confirm these findings.

Daidzein inhibits choriocarcinoma proliferation by arresting cell cycle at G1 phase through suppressing ERK pathway in vitro and in vivo.

Choriocarcinoma is a highly malignant tumor arising from abnormal gestational trophoblast proliferation. Although chemotherapy has dramatically improved the prognosis, there are still some patients who become drug-resistant or relapse. Daidzein has garnered interest in its antitumor activity especially in proliferation inhibition. However, few reports exist on daidzein effect in growth of choriocarcinoma. Therefore, in this study, we performed in vitro and in vivo experiment in JAR and JEG­3 to investigate the effect of daidzein in proliferation of choriocarcinoma. Daidzein inhibited cell growth in a time- and dose-dependent way. Cell cycle was arrested at G1 phase and expression of cyclin D1, c-myc, PCNA was reduced while p21 was upregulated during daidzein treatment. At the same time, the expression of p-ERK was downregulated and translocation into nuclear afterwards was also inhibited. Moreover, ERK agonist ceramide C6 abolished daidzein's effects on cell proliferation. Besides, in vivo experiment also showed daidzein's anti-proliferation function as xenografts growth was inhibited and expressions of c-myc, PCNA and p-ERK were suppressed. In conclusion, results in our study demonstrate daidzein can inhibit choriocarcinoma cell proliferation in vitro and in vivo; underlying mechanism behind the inhibitory effects may probably be suppressing ERK pathway and afterwards arresting cell cycle at G1 phase.

Association between XRCC1 polymorphisms and the risk of cervical cancer: a meta-analysis based on 4895 subjects.

The present meta-analysis was intended to explore the relationship between the X-ray repair cross complementing 1 (XRCC1) polymorphisms (Arg194Trp, Arg280His and Arg399Gln) and cervical cancer risk. Several electronic databases were searched systematically and bibliographies of relevant papers were identified carefully. Then, a meta-analysis was performed based on eligible studies in various genetic models. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were employed to evaluate the strength of associations between the XRCC1 polymorphisms and cervical cancer risk. Additionally, heterogeneity analysis and sensitivity analysis were done if necessary. Totally, 11 articles involving 2092 cases and 2803 controls were included. Taken together, there was no obvious association between the Arg194Trp or Arg280His polymorphism and cervical cancer risk. Considering the great heterogeneity, subgroup analysis was done, but the pooled result remained stable. Nevertheless, the association between the Arg399Gln polymorphism and cervical cancer risk showed distinct statistic significance in the allele model, dominant model, homozygous model and heterozygous model. In view of the exiting heterogeneity, we did subgroup analysis stratified by ethnicity, resulting in the fact that the Arg399Gln polymorphism was related to the decreased risk of cervical cancer. The Begg's test and Egger's test were used to find no publication bias. To conclude, the current meta-analysis indicated that the XRCC1 Arg399Gln polymorphism decreased the risk of cervical cancer, while the Arg194Trp and Arg280His polymorphisms were not associated with cervical caner risk. Certainly, a well-designed large-scale multicenter study is warranted to confirm the finding.

Association between FGFR2 (rs2981582, rs2420946 and rs2981578) polymorphism and breast cancer susceptibility: a meta-analysis.

The association between fibroblast growth factor receptor 2 (FGFR2) polymorphism and breast cancer (BC) susceptibility remains inconclusive. The purpose of this systematic review was to evaluate the relationship between FGFR2 (rs2981582, rs2420946 and rs2981578) polymorphism and BC risk. PubMed, Web of science and the Cochrane Library databases were searched before October 11, 2015 to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Sensitivity and subgroup analyses were conducted. Thirty-five studies published from 2007 to 2015 were included in this meta-analysis. The pooled results showed that there was significant association between all the 3 variants and BC risk in any genetic model. Subgroup analysis was performed on rs2981582 and rs2420946 by ethnicity and Source of controls, the effects remained in Asians, Caucasians, population-based and hospital-based groups. We did not carryout subgroup analysis on rs2981578 for the variant included only 3 articles. This meta-analysis of case-control studies provides strong evidence that FGFR2 (rs2981582, rs2420946 and rs2981578) polymorphisms were significantly associated with the BC risk. For rs2981582 and rs2420946, the association remained significant in Asians, Caucasians, general populations and hospital populations. However, further large scale multicenter epidemiological studies are warranted to confirm this finding and the molecular mechanism for the association need to be elucidated further.

Association between cyclin D1 (CCND1) G870A polymorphism and gastric cancer risk: a meta-analysis.

Published data on the association between cyclin D1 (CCND1) G870A polymorphism and gastric cancer (GC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between CCND1 G870A polymorphism and GC risk. We searched PubMed, EMBASE, Web of science and the Cochrane Library up to June 12, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Nine studies published from 2003 to 2014, with a total of 1813 cases and 2173 controls, were included in this meta-analysis. The pooled results showed that there was no association between CCND1 G870A polymorphism and GC risk in any genetic model. The subgroup analysis stratified by ethnicity showed an increased breast cancer risk in Caucasian based on heterozygote comparison (GA vs. GG: OR=1.49, 95% CI=1.06-2.10, P=0.02). We found the same association in population based (PB) stratified analyses by Source of controls (AA vs. GG: OR=1.39, 95% CI=1.01-1.93, 0.05). When stratifying by the type, Sex and H. pylori infection in dominant model, Interestingly, we found the opposite result in Male (AA + GA vs. GG: OR=0.5, 95% CI=0.33-0.76, P=0.001), there were no association between CCND1 G870A polymorphism and GC risk in any other subgroup. This meta-analysis suggests that CCND1 G870A polymorphism is a risk factor for susceptibility to GC in Caucasians and in general populations. While, CCND1 G870A polymorphism plays a possible protective effect in GC in Male. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

Association between 8q24 (rs13281615 and rs6983267) polymorphism and breast cancer susceptibility: a meta-analysis involving 117,355 subjects.

Published data on the association between 8q24 polymorphism and breast cancer (BC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between 8q24 (rs13281615 and rs6983267) polymorphism and BC risk. We searched PubMed, EMBASE, Web of science and the Cochrane Library up to August 13, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Twenty-six studies published from 2008 to 2014, with a total of 52,683 cases and 64,672 controls, were included in this meta-analysis. The pooled results showed that there was significant association between 8q24 rs13281615 polymorphism and BC risk in any genetic model. In the subgroup analysis by ethnicity, the effects remained in Asians and Caucasians. However, no genetic models reached statistical association in Africans. There was no association in any genetic model in rs6983267. This meta-analysis suggests that 8q24 rs13281615 polymorphism is a risk factor for susceptibility to BC in Asians, Caucasians and in overall population, While, there was no association in Africans. The rs6983267 polymorphism has no association with BC risk in any genetic model. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

Effects and Safety of Magnesium Sulfate on Neuroprotection: A Meta-analysis Based on PRISMA Guidelines.

To evaluate the evidence of effects and safety of magnesium sulfate on neuroprotection for preterm infants who had exposure in uteri. We searched electronic databases and bibliographies of relevant papers to identify studies comparing magnesium sulfate (MgSO4) with placebo or other treatments in patients at high risk of preterm labor and reporting effects and safety of MgSO4 for antenatal infants. Then, we did this meta-analysis based on PRISMA guideline. The primary outcomes included fatal death, cerebral palsy (CP), intraventricular hemorrhage, and periventricular leukomalacia. Secondary outcomes included various neonatal and maternal outcomes. Ten studies including 6 randomized controlled trials and 5 cohort studies, and involving 18,655 preterm infants were analyzed. For the rate of moderate to severe CP, MgSO4 showed the ability to reduce the risk and achieved statistically significant difference (odd ratio [OR] 0.61, 95% confidence interval [CI] 0.42-0.89, P = 0.01). The comparison of mortality rate between the MgSO4 group and the placebo group only presented small difference clinically, but reached no statistical significance (OR 0.92, 95% CI 0.77-1.11, P = 0.39). Summarily, the analysis of adverse effects on babies showed no margin (P > 0.05). Yet for mothers, MgSO4 exhibited obvious side-effects, such as respiratory depression, nausea and so forth, but there exited great heterogeneity. MgSO4 administered to women at high risk of preterm labor could reduce the risk of moderate to severe CP, without obvious adverse effects on babies. Although there exit many unfavorable effects on mothers, yet they may be lessened through reduction of the dose of MgSO4 and could be tolerable for mothers. So MgSO4 is both beneficial and safety to be used as a neuroprotective agent for premature infants before a valid alternative was discovered.

Effects of metformin on pregnancy outcomes in women with polycystic ovary syndrome: A meta-analysis.

AIM: The aim of the study is to evaluate the effects of metformin on pregnancy outcomes in women with polycystic ovary syndrome (PCOS). METHODS: We searched electronic databases and bibliographies of relevant papers to identify studies comparing the pregnancy outcomes in the metformin group with those in the placebo or blank control group. Then, we did this meta-analysis based on the PRISMA guidelines. The primary outcomes included early pregnancy loss (EPL), preterm delivery, term delivery, and gestational diabetes mellitus (GDM). Secondary outcomes included pregnancy-induced hypertension (PIH), intrauterine growth restriction (IUGR), fetal malformation, vaginal delivery (VD), cesarean section (CS), and metformin's side effects, such as nausea or gastrointestinal discomfort. Certainly, data about neonatal death and macrosomia were analyzed if data available. RESULTS: Finally, 13 studies including 5 randomized controlled trials (RCT) and 8 cohort studies involving 1606 pregnant women with PCOS were analyzed. The pooled OR of EPL was 0.19 with obvious statistical significance, manifesting that metformin help to lower the rate of EPL (95% CI 0.12-0.28, P < 0.00001). Simultaneously, metformin showed the advantage of reducing the prevalence of preterm delivery (OR 0.37, 95% CI 0.20-0.68, P = 0.002). In addition, metformin could promote term delivery greatly and the pooled OR was 5.23 with sharp statistical difference (95% CI 3.12-8.75, P < 0.00001). CONCLUSION: Metformin treatment in women with PCOS throughout pregnancy could increase the possibility of term delivery, VD and reduce the risk of EPL, preterm labor, pregnancy complications such as GDM and PIH, with no serious side effects. Moreover, metformin was not teratogenic based on the limited data. So we may recommend metformin treatment for women with PCOS during the whole pregnancy period for it is quite beneficial and safe for both mothers and babies.

Association between maternal diabetes mellitus and the risk of congenital malformations: A meta-analysis of cohort studies.

Increasing studies suggest that gestational diabetes mellitus (GDM) and pre-gestational diabetes mellitus (PGDM) may be associated with an increased risk of major congenital malformations (MCM) in the offspring. To determine whether GDM or PGDM is associated with an increased risk of congenital malformations, we performed a meta-analysis of cohort studies. We systematically searched the PubMed, Web of Science and Cochrane Library (from January, 1990 to October, 2014) and reviewed the reference lists of included papers to search for additional studies. Meta-analysis tools were used to summarize results. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random-effects models or fixed-effects models. Study quality was assessed using the Newcastle-Ottawa scale. A total of 21 cohort studies were included in the meta-analysis. Analysis of all studies showed that both PGDM and GDM were associated with an increased risk of MCM (RR=2.44, 95% CI=1.92-3.10, I2=78.3%, p=0.342; RR=1.11, 95% CI=1.11-1.27, I2=9.9%, p<0.001, respectively). There is a slightly higher risk of major congenital malformations in women with GDM than in the reference group. However, this risk is much lower than in women with PGDM. Further large-scale prospective cohort studies are needed to test the effect of PGDM and GDM on specific congenital malformations risk.

Association between Interleukin-8-251A/T polymorphism and gastric cancer susceptibility: a meta-analysis based on 5286 cases and 8000 controls.

OBJECTIVES: Published data on the association between Interleukin-8-251A/T polymorphism and gastric cancer (GC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between cyclin D1 G870A polymorphism and GC risk. METHODS: We searched PubMed, EMBASE, Web of science and the Cochrane Library up to July 12, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. RESULTS: Twenty-six studies published from 2004 to 2015, with a total of 5286 cases and 8000 controls, were included in this meta-analysis. The pooled results showed that there was significant association between Interleukin-8-251A/T polymorphism and GC risk in any genetic model. In the subgroup analysis by ethnicity, the effects remained in Asians. However, no genetic models reached statistical association in Europeans. The subgroup analysis stratified by Source of controls showed an increased breast cancer risk in hospital-based (HB) studies in any genetic model except recessive model. However, there was no association in any genetic model in population based (PB) studies. When stratifying by Genotyping method, we found statistical association in Non-RFLP (restriction fragment length polymorphism) in any genetic model except heterozygote comparison, the effect was remain in PCR-RFLP in dominant model and heterozygote comparison. CONCLUSIONS: This meta-analysis suggests that Interleukin-8-251A/T polymorphism is a risk factor for susceptibility to GC in overall population, especially in Asians, in hospital populations and in Non-RFLP. While, there was no association in Europeans and in general population. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

Placental site trophoblastic tumor: A case report and literature review.

Here, we report a case of a placental site trophoblastic tumor (PSTT) in a 36-year-old Chinese woman 10 months after a normal pregnancy. Two months postpartum, the woman presented with abnormal vaginal discharge and her condition was overlooked by her local hospital. The woman did not receive further attention until a mass with a heterogeneous echo was found in an ultrasound examination eight months postpartum. The final diagnosis was confirmed by histological examinations in conjunction with immunohistochemical studies. Since the patient had potential risk factors, she was successfully treated with a hysterectomy and peri- and post-operative chemotherapy. The latest follow-up (16 months after diagnosis) was uneventful, and the patient exhibited no signs of recurrence or metastasis.