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Background: Histological chorioamnionitis (HCA) is a serious threat to fetal health during pregnancy, which is not easily detected due to the lack of clinical symptoms, and there is still a lack of effective predictors and diagnostic indicators. Heparin-binding protein (HBP), an antimicrobial protein secreted by neutrophils, is highly valuable in predicting a variety of infectious diseases and is expected to be an effective predictor of histological chorioamnionitis.Methods: A total of 100 full-term healthy pregnant women delivered by cesarean section (control group) and 51 randomly enrolled pregnant women (pathology group) were included in this study. Amniotic fluid was extracted at delivery for HBP concentration, and postpartum placental pathology was performed in the pathology group to clarify the diagnosis of HCA. The predictive value of HBP in amniotic fluid for HCA was determined by establishing the reference interval for HBP in normal population and the receiver operating characteristic (ROC) curve.Results: The 95% confidence interval (95% CI) for HBP concentration in the amniotic fluid of normal pregnant women was 0- 87.08 ng/ml, with a median of 6.41 ng/ml; HBP concentration in the amniotic fluid of pregnant women with HCA was significantly higher than that of controls (P < 0.001) and non-HCA pregnant women (P < 0.001). The ROC curve showed that when the cut-off value of HBP in amniotic fluid was 82.67 ng/ml, the corresponding sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) were 84.20%, 96.90%, 94.12%, 91.18% and 0.86 (P < 0.001, 95% CI 0.715-1.000), respectively. Discussion: HBP in amniotic fluid is a potential, good predictor of HCA. We will further to explore its clinical application value.

Objective: This meta-analysis comprehensively evaluated the association between ABO blood group and the risk of preeclampsia (PE).Design: Systematic review and meta-analysis.Data sources: PubMed, Web of Science, and ScienceDirect databases from their inception to September 23, 2020.Methods: Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were obtained through random-effects and fixed-effects models according to heterogeneity. Meta-regression analysis was applied to explore the source of heterogeneity. We conducted a subgroup analysis by the publication year, study design, state, and Newcastle-Ottawa Scale (NOS) score. In addition, we calculated the rate of each ABO blood group in PE by total pooled effects.Results: A total of 12 articles with 714,153 patients were included in our analysis. Compared with people without PE (control group), the O blood group presented a lower risk of PE (OR 0.95, 95% CI 0.93–0.97). The AB (OR 1.46, 95% CI 1.12–1.91) blood group presented a higher risk. However, the total pooled OR and 95% CI for the A (OR 1.02, 95% CI 0.90–1.16) and B (OR 1.02, 95% CI 0.98–1.05) blood groups were not significant. The funnel plot and linear regression equation showed that there was no publication bias for the O, A, or B blood groups (all P > 0.05). However, the funnel plot and linear regression equation for the AB blood group were obviously asymmetric (P < 0.05), and the publication bias persisted even after the trim-and-fill method was applied (P < 0.05). Multivariable meta-regression analysis did not find a specific source of heterogeneity. The A blood group showed an association with early-onset PE (OR 0.53, 95% CI 0.33–0.83), and the other blood groups showed no significant differences. In PE, the rates of the O, A, B, and AB blood groups decreased gradually (0.39, 0.33, 0.19, 0.07).Conclusion: These findings suggest that pregnant women with AB blood group are more likely to develop PE, and more attention should be paid to AB blood group whose blood pressure is high but not sufficient to diagnose PE.Systematic Review Registration: Prospero CRD42021227930.

Background: Increased fetal umbilical artery resistance can cause fetal hypoxia, redistribute fetal blood flow, dilate the middle cerebral artery, and reduce the cerebroplacental rate (CPR). CPRMethods: A total of 114 pregnant women with CPR < 1 who gave birth at Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University from January 2015 to December 2019 were analyzed retrospectively. The age, height, and weight of the aforementioned pregnant women, as well as the gestational age when CPRResults: ① the pregnant women in the continued pregnancy group waited for an average period of 3 weeks prior to the termination of pregnancy beyond 32 weeks. The average weight of the newborn was 1429 g, which was significantly lower than that of the average newborn at the corresponding gestational age. In the continued pregnancy group, intrauterine death was reported in 18 cases (40.9%) and intrauterine death of one fetus in a twin pregnancy was reported in 2 cases. Intrauterine death occurred 2–33 day after CPRConclusion: Intrauterine hypoxia is considered severe when CPR

Background and Objective: Fetal growth restriction (FGR) is a pathological condition in which the fetus cannot reach its expected growth potential. When it is diagnosed as a suspected FGR, it remains an unsolved problem whether to direct induction or continue expectant management. To effectively reduce the incidence of neonatal adverse outcomes, we aimed to evaluate whether either method was associated with a lower incidence of neonatal adverse outcomes.Methods: We searched the relevant literature through the PubMed, Web of Science, and Cochrane Library from inception to January 10, 2020. We defined induction as the experimental group and expectant management as the control group. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models owing to heterogeneity. Furthermore, we conducted a sensitivity analysis to explore the robustness of the included literature. We used the Newcastle-Ottawa scale (NOS) to evaluate the quality of the available studies. We applied the funnel plot to describe the publication bias. Additionally, subgroup analysis based on the study method, sample size, area, NOS score, Apgar score 0.05).Conclusion: Regardless of induction or expectant management of a suspected FGR, the neonatal adverse outcomes showed no obvious differences. More studies should be conducted and confounding factors should be taken into consideration to elucidate the differential outcomes of the two approaches for suspected FGR.

To compare conservative management and cesarean hysterectomy in patients with placenta increta or percreta.In this multicenter retrospective study, we recorded data on 2219 patients with placenta increta or percreta from 20 tertiary care centers in China from 1 January 2011 to 31 December 2015. Propensity score analysis was used to control for baseline characteristics. We divided patients into conservative management (C) and hysterectomy (H) groups. The primary outcome was operative/postoperative maternal morbidity; secondary outcomes were maternal-neonatal outcomes.In total, 17.9% (398/2219) of patients had placenta increta and percreta; 82.1% (1821/2219) of the patients were in group C. After propensity score matching, 140 pairs of patients from the two groups underwent one-to-one matching. Group C showed less average blood loss within 24 h of surgery (1518 ± 1275 vs. 4309 ± 2550 ml in group H,Either conservative management or hysterectomy should be considered after thorough evaluation and detailed discussion of risks and benefits. A balance between bleeding control and fertility can be achieved.

Study question What is the role of insulin-like growth factor 2 (IGF2)-derived miR-483-3p in macrosomia? Summary answer IGF2-derived intronic miR-483-3p is overexpressed in macrosomia placentas, and miR-483-3p prompts HTR-8/SVneo extravillous trophoblast cell line proliferation through down-regulation of its target RB1 inducible coiled-coil 1 (RB1CC1). What is known already Macrosomia is a common pregnancy-associated disease and causes a number of adverse maternal and perinatal outcomes. The development of macrosomia is reportedly attributable to over proliferation of the placental cells. MicroRNAs (miRNAs) play an important role in the development of fetal and placenta by regulating their target genes. Here, we investigated the role of IGF2-derived intronic miR-483-3p in macrosomia. Study design, size, duration The expression of IGF2, miR-483-3p and its target gene in placental tissues from 30 pregnant women who had macrosomia was compared to those of 30 gestation-matched healthy pregnant controls. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR-8/SVneo cell was used. Participants/materials, setting, methods Placenta tissues were collected from pregnant women who had macrosomia without diabetes or other complications (n = 30) and healthy pregnant controls (n = 30). HTR-8/SVneo cells were transfected with specific miRNA mimics or inhibitors. MiRNA and mRNA isolated from placenta tissues or cells were measured by quantitative real-time PCR. Protein was measured by western blot. Cell proliferation was assayed using a colorimetric proliferation assay method. Cell cycle and apoptosis were analyzed by flow cytometry. The putative targets of miR-483-3p were predicted using the TargetScan, miRanda, miRDB and DIANA algorithms. Dual luciferase reporter assay was used to measure the relationship of miR-483-3p and RB1CC1. Main results and the role of chance IGF2-derived miR-483-3p was overexpressed in macrosomia placentas. miR-483-3p promoted proliferation in HTR-8/SVneo cells and had a positive relationship with its host gene IGF2. Subsequently, RB1CC1 was confirmed as a direct target of miR-483-3p, which may be an important mediator of cell growth regulation for miR-483-3p. Large scale data N/A. Limitations, reasons for caution The level of IGF2 and its intronic miR-483-3p in the serum of these participants was not investigated. Further studies are required to understand the mechanisms underlying the cause of the increase of IGF2 and miR-483-3p in macrosomia. Wider implications of the findings These findings give a new insight into the role of intronic miRNA and its host gene in the development of macrosomia. Furthermore, it may offer a new target for prognostic and therapeutic intervention for macrosomia. Study funding/competing interest(s) This work was supported by awards from National Natural Science Foundation of China (Nos. 81401213, 81673217, 81703260), Jiangsu Provincial Medical Youth Talent (No. QNRC2016110), Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents, the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine), the Education Department of Jiangsu Province (No. 16KJB330010), the Science and Technology Department of Jiangsu Province (No. BK20160227), the China Postdoctoral Science Foundation funded project (No. 2016M601892). The authors declare no competing financial interests.

The objective of this study is to identify the maternal and neonatal outcomes in women with placenta increta or placenta percreta in China.We retrospectively analyzed 2219 cases from 20 tertiary care centers in China between January 2011 and December 2015. All cases were diagnosed of placenta increta or placenta percreta, based on either intraoperative findings or histopathological findings.The incidence of placenta increta and placenta percreta progressively increased from 0.18% in 2011 to 0.78% in 2015. Compared with the placenta increta, placenta percreta was strongly related to serious adverse outcomes: postpartum hemorrhage (65.9% versus 38.6%, p = .003), blood transfusion (86.2% versus 46.5%, p .001), hysterectomy (43.3% versus 11.2%, p .001), preterm birth (65.7% versus 49.9%, p .001), and the need for neonatal intensive care unit (NICU) admission (54.5% versus 36.7%, p .001).The incidence of placenta increta and placenta percreta is likely to increase in China. The depth of placenta implantation is associated with the severity of outcomes. Placenta percreta tends to have worse maternal and neonatal outcomes.

There is an urgent need in China to better predict vaginal birth after cesarean (VBAC) to face the challenge of the second child policy. We aimed to validate a widely used VBAC prediction model (Grobman’s model) and a modified version of this model in a Chinese population. In this retrospective cohort study, 444 women with one cesarean delivery and at least one subsequent attempt for a trial of labor in Nanjing, China were included. The considered potential VBAC predictors included Grobman’s background variables and five new variables. Overall, a total of 370 women had VBAC, with a success rate of 83.3%. The new background variables “maternal height” and “estimated fetal weight” were considered as two additional predictors for VBAC. The AUC of Grobman’s model was 0.831 (95%CI = 0.775–0.886) while the AUC of our modified model with two new variables added was 0.857 (sensitivity = 72.2%, specificity = 83.8%). However, the difference between the AUC of the two models was not significant (Z = −1.69, P = 0.091). We confirmed that Grobman’s model was accepted in the Chinese population. A modified model that is supplemented with maternal height and estimated fetal weight needs to be further studied in the Chinese population.

// Xuejing Song 1, 2, * , Can Rui 1, * , Li Meng 3 , Rui Zhang 1 , Rong Shen 3 , Hongjuan Ding 1 , Jun Li 4 , Jingyun Li 4 , Wei Long 1 1 Department of Obstetrics, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China 2 Fourth Clinical Medicine College, Nanjing Medical University, Nanjing, China 3 Nanjing Maternity and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China 4 State key Laboratory of Reproductive Medicine, Department of Plastic and Cosmetic Surgery, Maternal and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China * These authors contributed equally to this work Correspondence to: Wei Long, email: wlong@njmu.edu.cn Jingyun Li, email: dagumahao@163.com Keywords: lncRNA, RPAIN, early onset preeclampsia, complement protein C1q Received: October 09, 2016 Accepted: December 01, 2016 Published: December 09, 2016 ABSTRACT Long non-coding RNAs (lncRNAs) are key regulatory molecules that are involved in a variety of biological processes and human diseases. Their impact on early onset preeclampsia remains unclear. In this study, we tested the expression of RPAIN (transcript variant 12 of RPA interacting protein, a non-coding RNA, NR_027683.1) in placenta tissues derived from 25 pregnant women with PE and 15 healthy pregnant women using quantitative real-time PCR. The effect of RPAIN on trophoblast proliferation, invasion, and apoptosis and the underlying mechanisms were examined in trophoblast cell lines (HTR-8/SVneo). The results showed that RPAIN expression levels were significantly increased in early onset preeclamptic placentas compared to normal controls. The proliferation and invasive abilities of the trophoblast cells were significantly inhibited, and the apoptosis abilities of the trophoblast cells were significantly promoted when RPAIN was overexpressed. In addition, the overexpression of RPAIN inhibited the expression of complement protein C1q. Furthermore, C1q overexpression rescued the decreased cell invasion and enhanced cell apoptosis in RPAIN-overexpressing trophoblast cells. Our results suggest that increased RPAIN levels may contribute to the development of preeclampsia through regulating trophoblast invasion and apoptosis via C1q. Therefore, we proposed RPAIN as a novel lncRNA molecule, which might contribute to the development of PE (preeclampsia) and might compose a potential diagnostic and therapeutic target for this disease.

Purpose : Offspring obesity is one of long-term complications of Gestational diabetes mellitus (GDM). The aim of this study is to identify proteins differentially expressed in the umbilical vein blood plasma, which could become markers for early diagnosis of childhood obesity. Experimental design : Umbilical vein plasma samples were collected from 30 control and 30 GDM patients in 2007–8 whose offspring were suffering from obesity at 6–7 years old. Multiplexed isobaric tandem mass tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed proteins. Ingenuity Pathway Analysis (IPA) was performed to identify canonical pathways, biological functions and networks of interacting proteins. Western blotting was used to verify the expression of three selected proteins. Results : A total of 318 proteins were identified, of which 12 proteins were up-regulated in GDM group while 24 down-regulated. Lipid metabolism was the top category identified by IPA. Three randomly chosen proteins were validated by Western blotting, which were consistent with LC-MS. Conclusion : There are significant differences of protein profile in the umbilical vein blood plasma between normal and GDM patients with obese offspring. The results indicate that a variety of proteins and biological mechanisms may contribute to childhood obesity. This article is protected by copyright. All rights reserved

Background/Aims: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26μM) (P

Background/Aims: FOXC2 has been reported to play a role in tumor progression, but the correlations of FOXC2 with the cisplatin (CDDP) resistance of ovarian cancer cells are still unclear. The purpose of the present study is to investigate the roles of FOXC2 in the CDDP resistance of ovarian cancer cells and its possible mechanisms. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of FOXC2 mRNA in CDDP-resistant or sensitive ovarian cancer tissues and cell lines (SKOV3/CDDP and SKOV3). Gain- and loss-of-function assays were performed to analyze the effects of FOXC2 knockdown or overexpression on the in vitro and in vivo sensitivity of ovarian cancer cells to CDDP and its possible molecular mechanisms. Results: The relative expression level of FOXC2 mRNA in CDDP-resistant ovarian cancer tissues was higher than that in CDDP-sensitive tissues. Also, the expression of FOXC2 mRNA and protein in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) cell line was higher than that in its parental cell line (SOKV3). Small hairpin RNA (shRNA)-mediated FOXC2 knockdown significantly increased the in vitro and in vive sensitivity of SKOV3/CDDP cells to CDDP by enhancing apoptosis, while upregulation of FOXC2 significantly decreased the in vitro and in vivo sensitivity of SKOV3 cells to CDDP by reducing apoptosis. Furthermore, FOXC2 activates the Akt and MAPK signaling pathways, and then induced the decreased expression of Bcl-2 protein and the increased expression of Bax and cleaved caspase-3 proteins. Conclusions: FOXC2 mediates the CDDP resistance of ovarian cancer cells by activation of the Akt and MAPK signaling pathways, and may be a potential novel therapeutic target for overcoming CDDP resistance in human ovarian cancer.

Preterm birth is the most important cause of neonatal mortality and morbidity worldwide. The aim of this study was to identify factors associated with preterm birth and examine the heterogeneity and interactions between these factors. We collected data from 1607 pregnant women treated at Nanjing Maternity and Child Health Care Hospital in China. The women included in the study were divided into the full-term group and the preterm-birth group. We used t-tests to compare the characteristics of age and body mass index, Chi-square tests for the other variables, and we used the Wald test to calculate the interaction between factors that may affect preterm birth. The heterogeneity test was used to study the relationship between subgroups. Multivariable logistic regression analysis was used to explore the associations between risk factors and preterm birth, which included all risk factors. All tests were 2-tailed, P < 0.05 was considered significant, and 95% confidence intervals were estimated for percentages. There was no statistical difference in basic characteristics such as age between the full-term and preterm groups. We found 6 independent risk factors that were associated with preterm birth (P

To identify the 24-h proteinuria value with quantitative analysis and how it correlates with the severity of preeclampsia and subsequent adverse maternal outcomes in the Chinese population.Eleven hospitals in 10 provinces across China were chosen, in which 1,738 pregnant women complicated by hypertensive disorders of pregnancy (HDP) with the records of 24 h proteinuria were enrolled. They were allocated into four groups: patients with maximal quantified proteinuria 0.3 g/24 h (Group 1, n = 328); patients with maximal quantified proteinuria ≥ 0.3 g/24 h and 2.0 g/24 h (Group 2, n = 638); patients with maximal quantified proteinuria ≥ 2.0 g/24 h and 5.0 g/24 h (Group 3, n = 353); and patients with maximal quantified proteinuria ≥ 5.0 g/24 h (Group 4, n = 419). Logistic regression analysis were conducted to assess the differences in maternal outcomes between different subgroups of 24-h proteinuria and to identify independent risk factors of adverse maternal outcomes in preeclampsia. The multivariable risk prediction model of adverse maternal outcome for HDP was established with receiver operating characteristic curve (ROC) curve and its predicted value was assessed.Thrombocytopenia and cerebral or visual symptoms were more frequent in Groups 3 and 4 than Groups 1 and 2 but no differences were found between Groups 3 and 4 or Groups 1 and 2. Maternal complications were more frequent in Groups 3 and 4 than in Groups 1 and 2 [Group 3 vs. Group 1, odds ratios (ORs) = 3.359 (1.067-10.571); Group 4 vs. Group 1, OR = 3.628 (1.189-11.086); Group 3 vs. Group 2, OR = 2.845 (1.155-7.003); Group 4 vs. Group 2, OR = 3.082 (1.304-7.288)]. However, no significant difference was found between Groups 4 and 3 or between Groups 2 and 1. The proteinuria ≥ 2 g/24 h had an area under the receiver operating characteristic curve (AUC ROC) of 0.668 (95% confidence interval (CI) 0.632-0.705) for predicting adverse maternal outcome. After adjusting for the effects of other symptoms, signs, and laboratory tests, it was the independent risk factor and predictor factor of the adverse maternal outcome (OR = 3.683, 95% CI 2.439-5.562, P0.001). The final risk prediction model had an AUC ROC of 0.800 (95% CI 0.769-0.830, P0.001).The proteinuria ≥ 2 g/24 h is an independent predictive factor of adverse maternal outcomes in preeclampsia, but its individual predictive value is limited. The risk prediction model is effective in assessing the risk of adverse maternal outcomes in patients with HDP.

Omental adipose tissue plays a central role in insulin resistance in gestational diabetes mellitus (GDM), and the molecular mechanisms leading to GDM remains vague. Evidence demonstrates that maternal hormones, such as estradiol, contribute to insulin resistance in GDM. In this study we determined the differential expression patterns of microRNAs (miRNAs) in omental adipose tissues from GDM patients and pregnant women with normal glucose tolerance using AFFX miRNA expression chips. MiR-222, 1 of 17 identified differentially expressed miRNAs, was found to be significantly up-regulated in GDM by quantitative real-time PCR (P < .01), and its expression was closely related with serum estradiol level (P < .05). Furthermore, miR-222 expression was significantly increased in 3T3-L1 adipocytes with a high concentration of 17β-estradiol stimulation (P < .01), whereas the expressions of estrogen receptor (ER)-α protein and insulin-sensitive membrane transporter glucose transporter 4 (GLUT4) protein (P < .01) were markedly reduced. In addition, ERα was shown to be a direct target of miR-222 in 3T3-L1 adipocytes by using the luciferase assay. Finally, antisense oligonucleotides of miR-222 transfection was used to silence miR-222 in 3T3-L1 adipocytes. The results showed that the expressions of ERα and GLUT4, the insulin-stimulated translocation of GLUT4 from the cytoplasm to the cell membrane and glucose uptake in mature adipocytes were dramatically increased (P < .01). In conclusion, miR-222 is a potential regulator of ERα expression in estrogen-induced insulin resistance in GDM and might be a candidate biomarker and therapeutic target for GDM.

To evaluate the maternal serum 25(OH)D concentrations and its association with gestational diabetes and other pregnancy outcomes.zMethods:In our nested case-control study, 4718 pregnancy women were included, who were attending second- and third-trimester screening in Nanjing, China. Serum 25(OH)D concentrations were tested by enzyme-linked immunoassay, and the pregnancy and birth outcomes were obtained via electronic medical record collection and information extraction. The associations of 25(OH)D concentrations with gestational diabetes and other pregnancy outcomes were assessed by logistic regression analysis. And receiver-operator characteristic curve analysis was also conducted.For the total population, the median (IQR) concentrations of 25(OH)D was 43.7 (35.5-57.9) nmol lLow 25(OH)D concentrations (50.0 nmol l

Supplemental Digital Content is available in the text, The association between polymorphism of androgen receptor gene CAG (AR-CAG) and male infertility in several studies was controversial. Based on studies on association between AR-CAG repeat length and male infertility in recent years, an updated meta-analysis is needed. We aimed to evaluate the association between AR-CAG repeat length and male infertility in advantage of the data in all published reports. We searched for reports published before August 2015 using PubMed, CNKI, VIP, and WanFang. Data on sample size, mean, and standard deviation (SD) of AR-CAG repeat length were extracted independently by 3 investigators. Forty-four reports were selected based on criteria. The overall infertile patients and azoospermic patients were found to have longer AR-CAG repeat length (standard mean difference (SMD) = 0.19, 95% confidence interval (CI): 0.10–0.28, P

In this study, we sought to investigate the effects of a continuous glucose monitoring system (CGMS) on maternal and neonatal outcomes. A total of 106 women with gestational diabetes mellitus (GDM) in gestational weeks 24–28 were randomly allocated to the antenatal care plus CGMS group or the self-monitoring blood glucose (SMBG) group. The CGMS group was subdivided into early and late subgroups. There were no significant differences in prenatal or obstetric outcomes, e.g., caesarean delivery rate, Apgar score at 5 min, macrosomia or neonatal hypoglycaemia, between the CGMS and SMBG groups. The CGMS group had lower glycated haemoglobin (HbA1C) levels than the SMBG group; however, the difference was not statistically significant. The proportion of GDM women with excessive gestational weight gain was lower in the CGMS group than in the SMBG group (33.3% vs. 56.4%, P = 0.039) and women who initiated CGMS earlier gained less weight (P = 0.017). The mode of blood glucose monitoring (adjusted OR 2.40; 95% CI 1.030–5.588; P = 0.042) and pre-pregnancy BMI (adjusted OR 0.578; 95% CI 0.419–0.798; P = 0.001) were independent factors for weight gain. In conclusion, early CGMS for GDM mothers reduces gestational weight gain. A follow-up study with a large cohort is needed.

MicroRNA plays an important role in spermatogenesis. Whether pre-miRNAs polymorphisms are associated with idiopathic male infertility remains obscure. In this study, 1378 idiopathic infertile males and 486 fertile controls were included between 2006 and 2014. Genotype of three polymorphisms (hsa-mir-146a rs2910164, hsa-mir-196a-2 rs11614913 and hsa-mir-499 rs3746444) and expression of miRNA in seminal plasma were examined by TaqMan method. The role of hsa-miR-196a-5p in cell proliferation, apoptosis and cell cycle were also examined in GC-2 cells. Our results demonstrated that rs11614913 of hsa-miR-196a-2 was significantly associated with idiopathic infertility (TT vs. CT: P = 0.014; TT vs. CC: P = 0.005; TT vs. CT + CC: P = 0.003). In following stratified analysis, we found that rs11614913 exhibited a significantly higher risk of asthenospermia, oligozoospermia and azoospermia. However, no significant association was observed between the other two polymorphisms and idiopathic male infertility risk. In a genotype-expression correlation analysis, rs11614913 CC was significantly associated with elevated expression of hsa-miR-196a-5p (P hsa-miR-196a-2 polymorphism and idiopathic male infertility.

Macrosomia is one of the most common perinatal complications of pregnancy and has life-long health implications for the infant. microRNAs (miRNAs) have been identified to regulate placental development, yet the role of miRNAs in macrosomia remains poorly understood. Here we investigated the role of miR-17-92 cluster in macrosomia. The expression levels of five miRNAs in miR-17-92 cluster were significantly elevated in placentas of macrosomia, which may due to the up-regulation of miRNA-processing enzyme Drosha and Dicer. Cell cycle pathway was identified to be the most relevant pathways regulated by miR-17-92 cluster miRNAs. Importantly, miR-17-92 cluster increased proliferation, attenuated cell apoptosis and accelerated cells entering S phase by targeting SMAD4 and RB1 in HTR8/SVneo cells. Furthermore, we found that expression of miR-17-92 cluster in serum had a high diagnostic sensitivity and specificity for macrosomia (AUC: 80.53%; sensitivity: 82.61%; specificity: 69.57%). Our results suggested that miR-17-92 cluster contribute to macrosomia development by targeting regulators of cell cycle pathway. Our findings not only provide a novel insight into the molecular mechanisms of macrosomia, but also the clinical value of miR-17-92 cluster as a predictive biomarker for macrosomia.

Fetal macrosomia, defined as a birth weight ≥ 4000 g, may affect 15–45% of newborns of women with gestational diabetes mellitus (GDM). The associations between endogenous peptides and gestational diabetes-induced macrosomia have not been investigated extensively by peptidome analysis. Here, we analyzed the umbilical cord plasma by combining ultrafiltration using molecular weight cut-off filters and liquid chromatography–tandem mass spectrometry (LC–MS/MS) to investigate potential associations of GDM with macrosomia. As macrosomic babies have increased susceptibility to obesity, diabetes and cardiovascular diseases in later life, we also aimed to identify specific biomarkers to detect these future diseases. Thirty pairs of GDM mothers and controls were randomly divided into three subgroups. We identified 235 peptides of around 1000–3000 Da, originating from 115 proteins. Analyzing the cleavage sites revealed that these peptides were cleaved in regulation, which may reflect the protease activity and distribution in umbilical cord plasma. Four identified peptides, of 2471.7, 1077.2, 1446.5 and 2372.7 Da, were significantly differentially expressed in the GDM macrosomia groups compared with controls, whose precursors may play a critical role in developing GDM macrosomia. We provide for the first time a validated GDM macrosomia peptidome profile and identify potential biomarkers linking the effects of macrosomia to later-life diseases. Biological significance Fetal macrosomia is the predominant adverse outcome of gestational diabetes mellitus (GDM), which is a frequent medical condition during pregnancy. Till now, the detailed molecular mechanisms underlying gestational diabetes-induced macrosomia are still not elucidated. With high detection sensitivity and high throughput of peptidome technology, it is now possible to systemically identify peptides possibly involved in the umbilical cord plasma of GDM induced macrosomia cases. With LC–MS/MS based quantification, totally, we identified 235 peptides originated from 115 precursor proteins. And four peptides of 2471.7, 1077.2, 1446.5 and 2372.7 Da differentially expressed between GDM cases and compared controls. A precursor protein of 1077.2 Da was fibrinogen alpha chain (FGA), which was also identified in the Ai et al. [29] study with a downregulated manner in the serum samples of GDM cases. And further analysis the cleavage pattern of the identified peptides revealed that the enzymes in tissues cleaved the protein according to their rules. Thus, this quantitative peptidome approach can identify related peptides that may play a role in the gestational diabetes-induced macrosomia, and give candidate biomarkers contributing to the development of later-life diseases in macrosomic babies.

Peroxisome proliferator-activated receptor delta (Ppard) activation has been implicated in regulating a multitude of biological processes in placental development. In this study, we employed the UPLC-ESI-TOFMS approach to investigate the metabolic traits in placenta from GW501516-treated mice at Embryonic Day 10.5. By analyzing the mass spectrum data, ions with the most significant differences between control and GW501516-treated groups were identified. Among these metabolites, the fatty acids, phospholipids, and sterol lipids were dramatically increased. Ingenuity Pathway Analysis (IPA) showed that phosphatidylethanolamine biosynthesis and glycolysis were the top two altered metabolic pathways involved in carbohydrate metabolism, energy production, and lipid metabolism. Subsequent immunoblotting experiments provided evidence for positive correlation of PPARD level and AKT and ERK signaling pathways upon GW501516 treatment. Furthermore, the stimulation of GW501516 increased trophoblast cell fusion gene syncytin-A (Syna), but not syncytin-B (Synb), expression, suggesting a potential role of Ppard activation in promoting cytotrophoblast differentiation. Our results reveal that Ppard activation elicits dramatic changes of the metabolic activities in placenta, which is correlated to AKT and ERK signaling.

Several studies have investigated the association between polymorphisms in the Deleted in AZoospermia-Like (DAZL) gene and male infertility risk, but with inconsistent results. We aimed to derive a more precise estimation of the relationship, therefore a meta-analysis was performed. A total of 13 case-control studies, including 2556 cases and 1997 controls, were selected. Two polymorphisms in DAZL were investigated, namely T12A (Thr12 → Ala) and T54A (Thr54 → Ala). Our meta-analysis showed that A > G is a risk factor for male infertility (P = 0.047, OR = 1.262, 95%CI = 1.003–1.587). However, when using trial sequential analysis (TSA) to confirm, we found that A > G risk effect turned out to be false positive. In addition, significant association was found between the T54A polymorphism and male infertility under co-dominant model (AG vs. AA: OR = 4.364, 95%CI = 2.207–8.630, P < 0.001) and dominant model (OR = 4.584, 95%CI = 2.320–9.058, P < 0.001). Stratified analysis showed that significantly strong association between T54A polymorphism and male infertility was present only in Asians, but not in Caucasians. Further studies of T12A and T54A with their biological functions are needed to understand the role of these polymorphisms in the development of male infertility.

The placenta is thought to have a critical role in the pathogenesis of gestational diabetes mellitus (GDM), as GDM‑associated complications resolve following delivery. Placenta-specific microRNAs (miRNAs) may contribute to the pathology of the development of GDM. The aim of the present study was to evaluate whether the placenta-specific miR-518d contributes to the development of GDM. It was revealed that miR-518d expression was higher in placentas taken from patients with GDM compared with control placentas, whereas the protein levels of the predicted miR-518d target gene, peroxisome proliferator-activated receptor-α (PPARα), were lower in placentas from patients with GDM compared with those from control subjects. It was also demonstrated that PPARα was a direct target of miR-518d with a specific binding site at the seed sequence, which determines target specificity. In the placentas of females with GDM increased levels of miR-518d were negatively correlated with the levels of PPARα protein. As PPARα dysregulation may be related to the development of GDM, it is suggested that upregulation of miR-518d may be associated with the pathogenesis of GDM via an effect on the regulation of PPARα expression.

Several molecular epidemiological studies have been conducted to examine the association between glutathione S-transferase mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) null polymorphisms and childhood acute leukemia; however, the conclusions remain controversial. We performed an extensive meta-analysis on 26 published case-control studies with a total of 3252 cases and 5024 controls. Crude odds ratios (ORs) with 95% confidence interval were used to assess the strength of association between childhood acute leukemia risk and polymorphisms of GSTM1 and GSTT1. With respect to GSTM1 polymorphism, significantly increased risk of childhood acute leukemia was observed in the overall analysis (OR = 1.30; 95%CI, 1.11-1.51). Furthermore, a stratification analysis showed that the risk of GSTM1 polymorphism are associated with childhood acute leukemia in group of Asians (OR = 1.94; 95%CI, 1.53-2.46), Blacks (OR = 1.76; 95%CI, 1.07-2.91), ALL (OR = 1.33; 95%CI, 1.13-1.58), ‘< 100 cases and

Summary The association between polymorphism of eNOS and male infertility in several studies was controversial. To explore a more precise estimation of the association, a meta-analysis of eight case–control studies, including 1,968 cases and 1,539 controls, were selected. The meta-analysis was conducted by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Overall, the association between T786C and risk of male infertility was obvious (TC vs. TT: OR, 1.20; 95% CI, 1.01–1.42; CC vs. TT: OR, 3.37; 95% CI, 1.65–6.87; TC/CC vs. TT: OR, 1.47; 95% CI, 1.25–1.73; CC vs. TT/TC: OR, 3.18; 95% CI, 1.54–6.56; TC vs. TT: OR, 1.65; 95% CI, 1.27–2.03). However, no overall association was observed between the other two polymorphisms of eNOS (G894T and 4a4b) and male infertility. Stratified analysis showed that significantly strong association between T786C polymorphism and semen quality was present in all three types of male infertility (azoospermia, oligozoospermia and asthenozoospermia). In the subgroup analysis based on ethnicity, both T786C and 4a4b could influence the risk of male infertility in Asian and Caucasian. Further studies of polymorphisms of eNOS with their biological functions are needed to understand the role in the development of male infertility.