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Background: The World Health Organization (WHO) in 2015 stated that every effort should be made to provide cesarean delivery (CD) for women in need. In China, the two-child policy largely prompts the number of advanced age childbirth, which raises the possibility of an increasing number of women who need a c-section. The aim of this study was to assess the trends in the overall and medical indication-classified CD rates in the era of the two-child policy in Jiangsu, China.Methods: A retrospective cross-sectional study of 291,448 women who delivered in 11 hospitals in Jiangsu province between 2012 and 2019 was conducted. Medical cesarean indication for each woman was ascertained by manually reviewing the medical records. The 291,448 women were divided into two subgroups according to the presence of the indications: the indicated group (7.80%) and the non-indicated group (92.20%). We then fitted joinpoint regression and log-binomial regression models to estimate trends in the CD rates across the study period.Results: The overall CD rate was observed with a declining trend from 52.51% in 2012-2015 to 49.76% in 2016-2019 (adjusted RR, 0.92; 95% CI, 0.91-0.93; P < 0.001), along with an annual percentage change (APC) to be - 1.0 (95% CI, - 2.1 to 0.0) across the period. The participants were then divided into two subgroups according to the presence of medical CD indications: the indicated group (7.80%) and the non-indicated group (92.20%).We found the declining trend was most pronounced in the non-indicated group, with the CD rates decreased from 50.02% in 2012-2015 to 46.27% in 2016-2019 (adjusted RR, 0.90; 95% CI, 0.89-0.90; P < 0.001). By contrast, we observed a steady trend in the CD rate of the indicated group, which maintained from 87.47% in 2012-2015 to 86.57% in 2016-2019 (P = 0.448). In the indicated group, a higher risk of adverse pregnancy outcomes was revealed for those women who delivered vaginally as compared with those who received c-section. We further investigated that women with following specific indications had a higher proportion of vaginal delivery, i.e., pregnancy complications, fetal macrosomia, and pregnancy complicated with tumor (34.70%, 10.84%, and 16.34%, respectively). Women with the above 3 indications were observed with a higher risk of adverse pregnancy outcomes if delivered vaginally. The incidence rates of the medical indications among the general population increased considerably over the 8-year period (P < 0.001).Conclusions: Although the overall CD rate apparently decreased in the recent years, along with the decline of the unnecessary CD rate, a considerable proportion of indicated women were not provided with CD service in Jiangsu, China. Instead of targeting the overall CD rate, we need to take actions to reduce unnecessary CD rate and provide adequate c-section service for women with indications, particularly for those with underlying diseases and suspected fetal macrosomia. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) of the miR-30 family are closely linked with tumor metastasis and play key roles in the complex malignant phenotypes of cancers by targeting many tumor-related genes. Deregulated expression of miR-30 family members has been commonly observed in breast cancer. However, associations between the genetic variants in the regulatory region of miR-30 family and the risk of breast cancer are still limited, especially in the Chinese Han population. In the present study, we conducted a case-control analysis wherein 1064 breast cancer patients and 1073 healthy controls underwent genotyping of 10 SNPs in the regulatory region of miR-30 family members. Multivariate logistic regression analyses illustrated that the rs763354 variant in the miR-30a regulatory region was linked with a significant decrease in breast cancer risk in an additive model (adjusted OR = 0.86 , 95% CI: 0.75-0.98, P = 0.022). Further, eQTL analyses also indicated that this SNP was associated with miR-30a expression levels in breast cancer samples compiled in the TCGA database (P = 0.020). The Kaplan-Meier plotter showed that breast cancer patients with higher miR-30a expression have significantly better outcomes than do patients expressing low levels of this miRNA (HR = 0.75 , 95% CI: 0.61-0.91, P = 0.0041). Together, these findings suggest that the miR-30a rs763354 SNP is an important regulator of breast cancer risk, thus making it a potentially viable prognostic biomarker and one that can be used to guide therapeutic treatment in affected patients. [ABSTRACT FROM AUTHOR]

Background. Interleukin 1 receptor associated kinases (IRAKs) play a central role in TLR signaling pathway. Scarce literature has investigated the association of potential functional genetic variants of IRAKs with Hepatitis B Virus- (HBV-) related hepatocellular carcinoma (HCC). Methods. A case-control study with 1,538 HBV-positive HCC patients and 1,465 chronic HBV carriers was conducted to evaluate the effects of common missense variants of IRAK family members on HCC. Proliferation assays and real-time polymerase chain reactions were carried out to evaluate the functions. Multivariable adjusted logistic regression was adopted to estimate effect size and identify risk factors. Results. Association analysis indicated that rs4251545 A allele of IRAK4 (p.Ala428Thr) was positively associated with HBV-related HCC risk (OR = 1.30, 95% CI: 1.09–1.54, P=0.003). Functional annotation indicated that rs4251545 reduced its own expression in liver (P=0.031). Further molecular functional analysis detected that rs4251545 increased the proliferation rate of L02 cells (P<0.05). Meanwhile, rs4251545 reduced mRNA expressions of IL-6, IL-8, CXCL-1, and CXCL-2 in L02 cells (P<0.01). Conclusion. rs4251545 of IRAK4 (p.Ala428Thr) modified the susceptibility to HBV-related HCC via increased proliferation rate and reduced production of inflammatory cytokines and chemokines. Further well-designed experiments are warranted to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Metabolomics studies in Caucasians have identified a number of novel metabolites in association with the risk of type 2 diabetes (T2D). However, few prospective metabolomic studies are available in Chinese populations. In the present study, we sought to identify novel metabolites consistently associated with incident T2D in two independent cohorts of Chinese adults.Methods: We performed targeted metabolomics (52 metabolites) of fasting plasma samples by liquid chromatography-mass spectrometry in two prospective case-control studies nested within the Dongfeng-Tongji (DFTJ) cohort and Jiangsu Non-communicable Disease (JSNCD) cohort. After following for 4.61 ± 0.15 and 7.57 ± 1.13 years, respectively, 1039 and 520 eligible participants developed incident T2D in these two cohorts, and controls were 1:1 matched with cases by age (± 5 years) and sex. Multivariate conditional logistic regression models were constructed to identify metabolites associated with future T2D risk in both cohorts.Results: We identified four metabolites consistently associated with an increased risk of developing T2D in the two cohorts, including alanine, phenylalanine, tyrosine and palmitoylcarnitine. In the meta-analysis of two cohorts, the odds ratios (95% confidence intervals, CIs) comparing extreme quartiles were 1.79 (1.32-2.42) for alanine, 1.91 (1.41-2.60) for phenylalanine, 1.85 (1.37-2.48) for tyrosine and 1.63 (1.21-2.20) for palmitoylcarnitine (all Ptrend ≤ 0.01).Conclusions: We confirmed the association of alanine, phenylalanine and tyrosine with future T2D risk and further identified palmitoylcarnitine as a novel metabolic marker of incident T2D in two prospective cohorts of Chinese adults. Our findings might provide new aetiological insight into the development of T2D. [ABSTRACT FROM AUTHOR]

Previous epidemiological studies have reported that prenatal exposure to metals might have influence on fetal growth. Most studies assessed the effect of individual metals, while the investigation on the relationship between multiple metal exposure and fetal growth is sparse. The objective of the present study is to assess the joint impact of metal mixtures on fetal growth during pregnancy. A total of 1275 maternal-infant pairs from the Jiangsu Birth Cohort (JBC) Study were included to investigate the effect of maternal metal exposure on fetal biometry measures at 22–24, 30–32, and 34–36 weeks of gestation. Lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg), chromium (Cr), vanadium(V), thallium (Tl) and barium (Ba) were measured by inductively coupled plasma mass spectrometry (ICP-MS) in maternal urine samples collected in the first trimester. We used general linear models and restricted cubic splines to test dose-response relationships between single metals and fetal growth. The weighted quantile sum (WQS) models were then applied to evaluate the overall effect of all these metals. We observed inverse associations of exposure to Pb, V and Cr with estimated fetal weight (EFW) at 34–36 weeks of gestation. Notably, maternal exposure to metal mixtures was significantly associated with reduced EFW at 34–36 weeks of gestation after adjusting for some covariates and confounders (aβ −0.05 [95% CI: 0.09, −0.01], P = 0.023), and this association was mainly driven by Cr (30.41%), Pb (23.92%), and Tl (15.60%). These findings indicated that prenatal exposure to metal mixtures might impose adverse effects on fetal growth. • Prenatal exposure to metal mixtures showed inverse relationships with fetal growth at 34–36 weeks of gestation. • The negative effects were mostly driven by Cr, Pb, and Tl. • V and As might had sex specific toxicity of on fetal size. [ABSTRACT FROM AUTHOR]

POU5F1 is a key regulator of self-renewal and differentiation in embryonic stem cells and may be associated with initiation, promotion, and progression in cancer. We hypothesized that functional polymorphisms in POU5F1 may play an important role in modifying the lung cancer risk. To test this hypothesis, we conducted a case-control study to explore the association between 17 potentially functional SNPs in POU5F1 gene and the lung cancer risk in 1,341 incident lung cancer cases and 1,982 healthy controls in a Chinese population. We found that variant alleles of rs887468 and rs3130457 were significantly associated with increased risk of lung cancer after multiple comparison (OR = 1.29, 95% CI: 1.11–1.51, Pfdr=0.017 for rs887468; OR = 1.29, 95% CI: 1.10–1.51, Pfdr=0.034 for rs3130457, resp.). In addition, we detected a significant interaction between rs887468 genotypes and smoking status on lung cancer risk (P=0.017). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and increased risk of lung cancer (Ptrend<0.001). These findings indicate that potentially functional polymorphisms in POU5F1 gene may contribute to lung cancer susceptibility in a Chinese population. [ABSTRACT FROM AUTHOR]

Aminoacyl-tRNA synthetases (ARSs) are in charge of cellular protein synthesis and have additional domains that function in a versatile manner beyond translation. Eight core ARSs (EPRS, MRS, QRS, RRS, IRS, LRS, KRS, DRS) combined with three nonenzymatic components form a complex known as multisynthetase complex (MSC).We hypothesize that the single-nucleotide polymorphisms (SNPs) of the eight core ARS coding genes might influence the susceptibility of sporadic congenital heart disease (CHD). Thus, we conducted a case-control study of 984 CHD cases and 2953 non-CHD controls in the Chinese Han population to evaluate the associations of 16 potentially functional SNPs within the eight ARS coding genes with the risk of CHD. We observed significant associations with the risk of CHD for rs1061248 [G/A; odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.81–0.99; P = 3.81×10−2], rs2230301 [A/C; OR = 0.73, 95%CI = 0.60–0.90, P = 3.81×10−2], rs1061160 [G/A; OR = 1.18, 95%CI = 1.06–1.31; P = 3.53×10−3] and rs5030754 [G/A; OR = 1.39, 95%CI = 1.11–1.75; P = 4.47×10−3] of EPRS gene. After multiple comparisons, rs1061248 conferred no predisposition to CHD. Additionally, a combined analysis showed a significant dosage-response effect of CHD risk among individuals carrying the different number of risk alleles (Ptrend = 5.00×10−4). Compared with individuals with “0–2” risk allele, those carrying “3”, “4” or “5 or more” risk alleles had a 0.97-, 1.25- or 1.38-fold increased risk of CHD, respectively. These findings indicate that genetic variants of the EPRS gene may influence the individual susceptibility to CHD in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Abstract: We sought to determine risk factors associated with fetal macrosomia and to explore the long-term consequence of infant macrosomia at the age of 7 years. A prospective population based cohort study was designed to examine the associations between maternal and perinatal characteristics and the risk of macrosomia. A nested case-control study was conducted to explore the long-term health consequence of infant macrosomia. The mean maternal age of the macrosomia group was 24.74±3.32 years, which is slightly older than that in the control group (24.35±3.14 years, P = 0.000). The mean maternal body mass index (BMI) at early pregnancy was 22.75±2.81 kg/m2, which was also higher than that in the control group (21.76±2.59 kg/m2, P = 0.000). About 64.6% of macrosomic ne-onates were males, compared with 51.0% in the control group (P = 0.000). Compared with women with normal weight (BMI: 18.5-23.9 kg/m2), women who were overweight (BMI: 24-27.9 kg/m2) or obese (BMI≥28 kg/m2), respectively, had a 1.69-fold (P = 0.000) and a 1.49-fold (P = 0.000) increased risks of having a neonate with macrosomia, while light weight (BMI<18.5 kg/m2) women had an approximately 50% reduction of the risk. Fur-thermore, macrosomia infant had a 1.52-fold and 1.50-fold risk, respectively, of developing overweight or obesity at the age of 7 years (P = 0.001 and P = 0.000). Older maternal age, higher maternal BMI at early pregnancy and male gender were independent risk factors of macrosomia. Macrosomic infant was associated with an increased predisposition to develop overweight or obesity at the beginning of their childhood. [Copyright &y& Elsevier]

Abstract: Objective: Inflammation induced by H.pylori colonization in the stomach is related to the development of gastric cancer and the genetic variations of the genes involved in the immune responses modify the host response to the infection. The aim of this study was to evaluate whether polymorphisms in the toll-like receptor 4 (TLR4) gene, a key regulator of both innate and adaptive immunity, were related to the susceptibility to gastric cancer in a Chinese population. Methods: Two variations in the 5′-flanking region of TLR4 (rs1927914 T > C and rs10759932 T > C) were genotyped by using the PCR-restriction fragment length polymorphism (RFLP) assay in a case-control study of 1,053 incident gastric cancer cases and 1,100 cancer-free controls in a Chinese population. Results: Individuals carrying the C allele of rs10759932 had a significantly reduced risk of gastric cancer (adjusted OR = 0.81; 95%CI = 0.67-0.96), compared with the wild-type homozygote (TT), and the protective effect was not significantly different among subgroups stratified by age, sex, smoking, drinking and H.pylori infection status (P for heterogeneity > 0.05). No significant association was observed between rs1927914 and gastric cancer risk in this study population. Conclusion: The T to C allele substitution of rs10759932 may play a protective role in gastric carcinogenesis in a Chinese population. Large studies with different ethnic populations are warranted to confirm these findings. [Copyright &y& Elsevier]

Background: Successful implantation and delivery require both the functional embryo and receptive endometrium in assisted reproductive technology (ART) cycles. However, little is known about embryo-endometrial interaction on live-birth. We aimed to investigate the independent effect and interaction of endometrial thickness (EMT) and embryo quality on live-birth in fresh embryo transfer (ET) cycles. Methods: We conducted a retrospective cohort study including 15,012 ART cycles between 2013 and 2016 in three centers in China. Poisson regression with generalized estimating equations was employed to calculate relative risks (RRs) and 95% confidence intervals (CIs). We estimated the interaction of embryo quality and EMT on live-birth rate (LBR). Results: The LBR per cycle was 42.8% overall. LBR increased with increasing EMT and reached a plateau (50.6 to 54.2%) when EMT was 11 mm or thicker. Embryo quality represented by cumulative score was associated with LBR independently of number of embryos transferred and EMT. LBR was not increased with thicker EMT when only Q1 cleavage-stage embryo transferred (aRR 0.95, 95%CI 0.61–1.46). LBR was not increased significantly with thicker EMT with transfer of two good-quality cleavage-stage embryos and any blastocyst combination except Q1 group. There was significant interaction between EMT and embryo quality on LBR for cleavage-stage ETs (P=0.023). Conclusions: This study demonstrated the nonlinear EMT-LBR association and the EMT cut-off value of 11 mm which may be of more clinical significance for predicting live-birth. Embryo quality is an independent prognostic tool for LBR. Our finding of significant embryo-endometrial interaction indicates combination of EMT and embryos quality might improve the prognostic value in clinical practice for live-birth in patients undergoing transfer of 1–2 fresh cleavage-stage embryos. [ABSTRACT FROM AUTHOR]

Objective: To investigate the associations between genetically cis-regulated gene expression levels and nonobstructive azoospermia (NOA) susceptibility.Design: Transcriptome-wide association study (TWAS).Setting: Medical university.Interventions: None.Main Outcome Measure(s): The cis-hg2 values for each gene were estimated with GCTA software. The effect sizes of cis-single-nucleotide polymorphisms (SNPs) on gene expression were measured using GEMMA software. Gene expression levels were entered into our existing NOA GWAS cohort using GEMMA software. The TWAS P-values were calculated using logistic regression models.Result(s): Expression levels of 1,296 cis-heritable genes were entered into our existing NOA GWAS data. The TWAS results identified two novel genes as statistically significantly associated with NOA susceptibility: PILRA and ZNF676. In addition, 6p21.32, previously reported in NOA GWAS, was further validated to be a susceptible region to NOA risk.Conclusion(s): Analysis with TWAS provides fruitful targets for follow-up functional studies. [ABSTRACT FROM AUTHOR]