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Aim and Objective: To assess the relationship between serum folate and schizophrenia (SZ) risk in the Chinese Han adult population in different papers, a systematic review and metaanalysis were conducted. Materials and Methods: We searched for this meta-analysis on three English databases (PubMed, Embase, and Web of science) and four Chinese databases (CNKI, SinoMed, Wanfang, and CQVIP) on March 27, 2021. Inclusion criteria: studies provided folate levels in serum of cases and controls as mean and standard deviation. Exclusion criteria: subjects were not Chinese Han adult population. The Newcastle-Ottawa Scale score was used to assess the risk of bias in the included studies. Standard mean difference (SMD) was used to measure the difference between SZ patients and healthy controls. Subgroup analyses by measurement time, duration, and age were performed, respectively. Results: This meta-analysis included 19 publications involving 1571 SZ cases and 1283 healthy controls. In total studies, the pooled result showed that SZ patients had decreased serum folate levels compared with healthy controls (SMD [95%CI] = -1.37[-1.83,-0.90], PSMD Conclusion: Dose-response analysis and subgroup analyses by gender were not performed due to the lack of data. Folate deficiency is associated with the patients, and antipsychotic drugs might have positive effects on improving serum folate levels in Chinese Han adult SZ.

The burden of non-communicable diseases (NCDs) has increased in China. However, the contribution of dietary risks to the NCD burden has not been evaluated. This study aimed to estimate the burden of ischemic heart disease (IHD) and colorectal cancer (CRC) attributable to a diet low in fiber in China from 1990 to 2017. China data from the Global Burden of Disease Study (GBD) 2017 were used to assess the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of IHD and CRC related to a diet low in fiber. In 2017, a diet low in fiber contributed 170,143 [95% uncertainty interval (UI): 99,623–256,806] IHD deaths and 25,561 (95% UI: 13,726–39,215) CRC deaths, with the population attributable fractions (PAFs) were 9.7 and 13.7%, respectively. Males had higher risk-attributable mortality and DALY rates for IHD and CRC than females. An upward trend with age in rates of mortality and DALY was observed. All-age risk-attributable mortality and DALY rates increased significantly by 111.4 and 53.2% for IHD, and 94.4 and 59.6% for CRC from 1990 to 2017, respectively; however, the corresponding age-standardized rates for IHD and CRC showed relatively stable trends. Heilongjiang, Xinjiang, and Inner Mongolia were ranked as the top three provinces in terms of total risk-attributable NCD burden in 2017. China has a large and growing NCD burden attributable to a diet low in fiber. Greater priority in disease prevention and control should be given to male and older adults throughout China, particularly in some western provinces.

Epithelial-mesenchymal transition (EMT) plays an important role in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We hypothesized that germline variants in the major EMT regulatory genes (SNAIL1, ZEB1, ZEB2, TWIST1) may influence the development of HBV-related HCC. We included 421 cases of HBsAg-positive patients with HCC, 1371 cases of HBsAg-positive subjects without HCC [patients with chronic hepatitis B (CHB) or liver cirrhosis (LC)] and 618 cases of healthy controls in the case-control study. Genotype, allele, and haplotype associations in the major EMT regulatory genes were tested. Environment-gene and gene-gene interactions were analysed using the non-parametric model-free multifactor dimensionality reduction (MDR) method. The SNAIL1rs4647958T>C was associated with a significantly increased risk of both HCC (CT+CC vs. TT: OR=1.559; 95% confidence interval [CI], 1.073-2.264; P=0.020) and CHB+LC (CT+CC vs. TT: OR=1.509; 95% CI, 1.145-1.988; P=0.003). Carriers of the TWIST1rs2285681G>C (genotypes CT+CC) had an increased risk of HCC (CG+CC vs. GG: OR=1.407; 95% CI, 1.065-1.858; P=0.016). The ZEB2rs3806475T>C was associated with significantly increased risk of both HCC (Precessive =0.001) and CHB+LC (PrecessiveP=0.0347). Meanwhile, the CT haplotype of the rs2285681/rs2285682 haplotype block was associated with significant differences between CHB+LC and HCC patients (P=0.0123). In MDR analysis, the combination of TWIST1rs2285681, ZEB2rs3806475, SNAIL1rs4647958 exhibited the most significant association with CHB+LC and Health control in the three-locus model. Our results suggest significant single-gene associations and environment-gene/gene-gene interactions of EMT-related genes with HBV-related HCC.

HBV infection is recognized as a serious global health problem, and hepatitis B virus infection is a complicated chronic disease leading to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). New biochemical serum markers could be used to advance the diagnosis and prognosis of HBV-associated liver diseases during the progression of chronic hepatitis B into cirrhosis and HCC. We determined whether the 4210 Da and 1866 Da polypeptides are serum metabolite biomarkers of hepatopathy with hepatitis B virus. A total of 570 subjects were divided into five groups: healthy controls, those with natural clearance, and patients with CHB, LC, and HCC. The 1866 Da and 4210 Da polypeptides were measured by Clin-ToF II MALDI-TOF–MS. There were significant differences in 4210 Da and 1866 Da levels among the five groups (P P P

The burden of non-communicable diseases (NCDs) has increased in China. However, the contribution of dietary risks to the NCD burden has not been evaluated. This study aimed to estimate the burden of ischemic heart disease (IHD) and colorectal cancer (CRC) attributable to a diet low in fiber in China from 1990 to 2017.China data from the Global Burden of Disease Study (GBD) 2017 were used to assess the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of IHD and CRC related to a diet low in fiber.In 2017, a diet low in fiber contributed 170,143 [95% uncertainty interval (UI): 99,623-256,806] IHD deaths and 25,561 (95% UI: 13,726-39,215) CRC deaths, with the population attributable fractions (PAFs) were 9.7 and 13.7%, respectively. Males had higher risk-attributable mortality and DALY rates for IHD and CRC than females. An upward trend with age in rates of mortality and DALY was observed. All-age risk-attributable mortality and DALY rates increased significantly by 111.4 and 53.2% for IHD, and 94.4 and 59.6% for CRC from 1990 to 2017, respectively; however, the corresponding age-standardized rates for IHD and CRC showed relatively stable trends. Heilongjiang, Xinjiang, and Inner Mongolia were ranked as the top three provinces in terms of total risk-attributable NCD burden in 2017.China has a large and growing NCD burden attributable to a diet low in fiber. Greater priority in disease prevention and control should be given to male and older adults throughout China, particularly in some western provinces.

A meta-analysis.To update the current knowledge about the association between overweight, obesity, and low back pain (LBP) risk, we conducted a meta-analysis of published cohort studies.The association between obesity and LBP risk has been the research focus in the past decade. However, available data from studies on the association between obesity and LBP remains debatable.An extensive English language literature retrieval regarding the association between overweight, obesity, and the risk of LBP incidence was conducted on PubMed and EMBASE databases through December 2015. Meta-analysis for all the included literature was performed by STATA 12.0 to summarize test performance with Forest plots after a heterogeneity test. Moreover, subgroup and sensitivity analyses were performed to examine the potential candidate-effect factors.A total of 10 cohort studies including 29,748 subjects satisfied the predefined eligibility criteria. The pooled odds ratio (OR) for overweight and obesity compared with normal weight was 1.15 [95% confidence interval (CI), 1.08-1.21) and 1.36 (95% CI, 1.18-1.57), respectively. Moreover, subgroup analysis proved that increased body mass index was associated with an increased incidence of LBP in both men (overweight: pooled OR=1.16, 95% CI, 1.04-1.31; obesity: pooled OR=1.36, 95% CI, 1.15-1.61) and women (overweight: pooled OR=1.24, 95% CI, 1.04-1.50; obesity: pooled OR=1.40, 95% CI, 1.08-1.82). There was no evidence of publication bias.Our findings consistently show that overweight and obesity are risk factors for LBP in men and women. Maintaining a healthy body weight may be one of the factors preventing the occurrence of LBP.Level 1.

Introduction Previous studies indicate that the IL-33/ST2 pathway is involved in hepatitis B virus (HBV) -related liver diseases. This study aimed to determine the relationship between genetic variants in IL-33/ST2 pathway with susceptibility to liver cirrhosis. Materials and methods A total of 2632 Han Chinese samples met the inclusion and exclusion criteria, including 840 negative controls (NeC), 691 chronic hepatitis B (CHB), 680 HBV-related liver cirrhosis (LC) and 421 HBV-related hepatocellular carcinoma (HCC) (without LC) patients. Four polymorphisms (IL33-rs4742170, rs1048274, rs10975519 and IL1RL1-rs1041973) were selected and genotyping was performed. All statistical analyses were performed by SPSS21.0, mainly using the Hardy-Weinberg equilibrium test, Pearson chi-square, unconditional Logistic regression and haplotype analysis. Results After adjusting for age, sex, smoking and drinking, significant associations were observed between IL33-rs4742170, rs1048274 and rs10975519 polymorphisms with LC risk. NeC with IL33-rs4742170 CC genotype was 1.80 times more likely to develop LC compared with TT genotype, while NeC with rs10975519(TC + CC) genotype was 1.32 times more likely to develop LC when compared with the TT genotype. CHB cases with rs4742170(CC + TC) genotype had 1.30 times higher susceptibility to develop LC compared with the TT genotype. The IL33-rs1048274G allele occurred more frequently in the LC group compared with the HCC group in codominant model (AG/AA: P = 0.001, OR = 1.66, 95%CI = 1.22–2.25; GG/AA: P = 0.018, OR = 1.54, 95%CI = 1.08–2.20). The IL33 haplotype CG conformed by rs10975519C and rs1048274G was more frequent in the LC group than in the NeC group and CHB group. Moreover, the IL33 haplotype CCG conformed by rs4742170C, rs10975519C and rs1048274G was found to be more frequent in the LC group than the HCC group. However, there was no association between IL1RL1-rs1041973 and LC risk. Conclusion Our findings demonstrate the association between genetic variants in IL33 with susceptibility to liver cirrhosis. IL33-rs4742170C, rs1048274G and rs10975519C could serve as biomarkers of LC.

Recent studies show that variants in some interferon genes together with interferon receptor genes are associated with the outcome of infectious diseases. We examined the association between the risk of hepatitis B virus (HBV)-related liver disease and the functional polymorphisms within IFNL4, IFNLR1, IFNA1, IFNA2, IFNA5 and IFNAR2 genes (14 loci in all) in a Han Chinese population. A total of 3128 people participated and were divided into 5 groups: healthy controls, natural clearance, chronic hepatitis B(CHB), liver cirrhosis and hepatocellular carcinoma (HCC). Significant associations were observed for 4 variants in IFNAR2, IFNLR1 with HBV infection, and IFNLR1-rs4649203 was associated with HBV recovery. Moreover, we demonstrated the clear relevance of 5 polymorphisms in IFNA1, IFNA2, IFNL4 with HCC. Three SNPs in IFNL4 gene may be important susceptible factors for the progression of HBV-related liver disease by trend chi-square test. The IFNL4 haplotype conformed by rs12971396_G, rs8113007_T and rs7248668A was more frequent in HCC than CHB and LC group. Three polymorphisms in the 5' region of the IFNL4 gene are associated with the progression of HBV-related liver disease. IFNA1- rs1831583 and IFNA2- rs649053 are associated with the development of HCC. IFNLR1- rs4649203, rs7525481 are predictors for HBV infection, and rs4649203 is a predictor of spontaneous clearance. IFNAR2 -rs1051393, rs12233338 may be predictive markers of HBV infection in the Chinese population.

Several recent studies showed that the genetic polymorphisms in the PNPLA3 region (rs738408, rs738409, rs2294918, rs2294919 and rs2281135) were with related to various kinds of liver diseases. We analyzed the five single-nucleotide polymorphisms (SNPs) for major HBV outcomes in Han Chinese.A total of 2410 samples were involved and peripheral blood samples were collected in this study. The SNPs in the PNPLA3 region were genotyped by using Matrix-assisted laser desorption/ionization time of flight mass spectrometry.Our study indicated the clear relationship between the PNPLA3 rs2294918, rs2294919 and HBV-related HCC after control for the effects of sex, drinking and smoking. Health subjects with the PNPLA3 rs2294919 TC genotype would have a 0.605 (95% CI: 0.413, 0.886; p = .010) times lower odds of having HCC, and those with the rs2294918 AG genotype would have a 1.872 (95% CI: 1.256, 2.792; p = .002) times higher odds of having HCC, whereas the values of sex, age, drinking and smoking were fixed. In addition, CA haplotype of the haplotype block of rs738409 and rs2281135 was also associated with HBV-related HCC.Our study suggested that PNPLA3 loci (rs2294918, rs2294919) were associated with HBV-related HCC in Han Chinese.

Background The prevalence of abdominal obesity is increasing dramatically worldwide. This study aimed to estimate the current prevalence of abdominal obesity from the 2011 China Health and Nutrition Survey (CHNS) and compare the data with other countries. Methods Waist circumference (WC) of 12,326 Chinese adults (aged 20 years or older) from the 2011 CHNS were analyzed by age group and region. Abdominal obesity was defined as a WC ≥90 cm for men and WC ≥80 cm for women based on World Health Organization (WHO) recommendations for Asians. Results In 2011, the age-adjusted mean WC was 85.9 cm (95% confidence interval [CI], 85.6–86.2 cm) for men and 80.7 cm (95% CI, 80.4–80.9 cm) for women. Based on the WHO recommendations, the age-adjusted prevalence of abdominal obesity was 44.0% (95% CI, 43.1%–44.8%) overall, 35.3% (95% CI, 34.1%–36.6%) in men, and 51.7% (95% CI, 50.5%–52.9%) in women. Moreover, the age-adjusted prevalence was 44.0% (95% CI, 42.7%–45.2%) in rural populations, 42.5% (95% CI, 40.7%–44.2%) in urban populations, and 45.2% (95% CI, 43.5%–46.9%) in megacity populations. The prevalence in China (35.3% for men and 51.7% for women) was lower than in Japan (50.8% for men) and the United States (43.5% for men and 64.7% for women). Similar results were observed when applying the criteria suggested by the Working Group on Obesity in China. Conclusions In 2011, the age-adjusted prevalence of abdominal obesity in China was 35.3% in men and 51.7% in women., Highlights • In 2011, the mean waist circumference in China was 85.9 cm (men) and 80.7 cm (women). • In 2011, the prevalence of abdominal obesity was 35.3% in men and 51.7% in women. • The prevalence in China was lower than in Japan and the United States.

The present study aimed to identify candidate substrates of ubiquitin-specific protease (USP)13 using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). USP13 is a well-characterized member of the USP family, which regulates diverse cellular functions by cleaving ubiquitin from ubiquitinated protein substrates. However, existing studies indicate that USP13 has no detectable hydrolytic activity in vitro. This finding implies that USP13 likely has different substrate specificity. In this study, a USP cleavage assay was performed using two different types of model substrates (glutathione S-transferase-Ub52 and ubiquitin-β-galactosidase) to detect the deubiquitinating enzyme (DUB) activity of USP13. In addition, a proteomic approach was taken by using 2D-DIGE to detect cellular proteins whose expressoin is significantly altered in 293T cell lines following the overexpression of USP13 or its C345S mutant (the catalytically inactive form). The data indicated that USP13 still has no detectable DUB activity in vitro nor does C345S. The results of 2D-DIGE demonstrated that the expression of several proteins increased or decreased significantly in 293T cells following the overexpression of USP13. Mass spec-troscopy analysis of gel spots identified 7 proteins, including 4 proteins with an increased expression, namely vinculin, thimet oligopeptidase, cleavage and polyadenylation specific factor 3, and methylosome protein 50, and 3 proteins with a decreased expression, namely adenylosuccinate synthetase, annexin and phosphoglycerate mutase. In addition, in the samples of 293T cell lines after the overexpression of USP13 and USP13 C345S, vinculin exhibited an increased expression, suggesting that it may be a candidate substrate of USP13. However, sufficient follow-up validation studies are required in order to determine whether vinculin protein directly interacts with USP13.

The association between serum folate and vitamin B12 levels and the risk of diabetic peripheral neuropathy (DPN) remains unclear. This meta-analysis included 16 studies of serum folate levels (1190 cases and 1501 controls) and 18 studies of serum vitamin B12 levels (1239 cases and 1562 controls) in patients with type 2 diabetes mellitus (T2DM). Reduced serum levels of folate and vitamin B12 were found in patients with T2DM and DPN compared with patients with T2DM but without DPN; weighted mean difference (WMD) = −1.64 (95% confidence interval [CI] = −2.46, −0.81) and WMD = −70.86 (95% CI = −101.55, −40.17), respectively. A subgroup analysis confirmed these associations in the Chinese population, but not in the Caucasian and mixed populations. In conclusion, these findings support the need for further controlled studies in defined patient populations and the importance of monitoring serum folate and vitamin B12 levels in patients with T2DM.

Background: Oxidative stress is closely related to the occurrence and development of various diseases such as cancer, diabetes, and cardiovascular and infectious diseases. We identified six critical genetic variants related to oxidative stress, and evaluated their main effects and their interaction effects on hepatitis B virus (HBV)-induced liver diseases. Methods: We enrolled 3128 Han Chinese subjects into five groups: healthy controls, chronic hepatitis B (CHB), liver cirrhosis (LC), hepatocellular carcinoma (HCC), and natural clearance. We then determined the genotypes in each group for CYBA-rs4673, NCF4-rs1883112, NOX4-rs1836882, rs3017887, SOD2-rs4880, and GCLM-rs41303970, and evaluated the association between these variants and HBV-induced liver diseases. Gene-gene interactions were evaluated using generalized multifactor dimensionality reduction, logistic regression, and four-by-two tables. Results: Significant associations were observed between healthy controls and the CIB group (CHB+LC+HCC). The CYBA-rs4673AG genotype was associated with a 1.356 rate of persistent HBV infection compared to the wild type GG genotype. The NCF4-rs1883112G allele occurred more frequently in healthy controls than in the CIB group in all three models (dominant, codominant, and recessive). Nox4-rs1836882 TC showed a protective association, being more frequent in healthy controls compared to the wild type TT genotype. GCLM-rs41303970A was associated with persistent HBV persistent infection. The overall best model by multifactor dimensionality reduction was a five factor interaction model that had the highest cross validation consistency (10/10) and test accuracy (0.5669), p = 0.001. Conclusions: Oxidative stress-related gene polymorphisms are likely to be associated with persistent HBV infection, suggesting that information on these variations is useful for risk assessment of HBV infection.

Background The aim of this study is to quantify the burden caused by viral hepatitis in China from 1990 to 2016. Methods Data from the GBD 2016 study were extracted to calculate incidence, prevalence and disability-adjusted life years (DALYs). Trends in DALYs were assessed in 33 provinces/regions. Results From 1990 to 2016, the total incidence of hepatitis decreased by 88.5%. However, the prevalence of hepatitis (counts in thousands), increased by 37.6% from 153,856 (95% UI: 136,047-172,319) in 1990 to 211,721 (95% UI: 179,776-240,981) in 2016, with age-standardized prevalence rates changing slightly. The number and age-standardized rates of prevalence increased by 35.9 and 1.6% for hepatitis B, respectively, and by 81.8 and 30.4% for hepatitis C. Guangxi, Guangdong and Hainan had the highest age-standardized prevalence rates (≥16,500 per 100,000). Tibet, Qinghai and Gansu had the highest age-standardized DALYs rates (≥40 per 100,000). The largest absolute number of DALYs was observed in the 15–49 year age group in 2016. The highest rate of DALYs occurred in males aged 50–69 years and in females aged ≧70 years. Conclusion The incidence and DALYs of viral hepatitis decreased dramatically from 1990 to 2016. However, the prevalence still remains at a high level, which may result in heavy burdens in the future.

Summary Introduction HBV and/or HCV infection is the main cause of hepatocellular carcinoma (HCC), but the molecular mechanisms by which HBV promotes HCC are not clear. In 2011, the result of a GWAS revealed a common variant of DEPDC5 affected HCC susceptibility in patient with chronic HCV infection in Japan. This study investigated the correlation between DEPDC5 polymorphism and HBV-related HCC. Materials and methods 1289 samples of Han population were involved in northern China and peripheral blood samples were obtained, including 506 healthy controls, 217 Hepatitis B chronic (CHB) and 258 liver cirrhosis (LC), and 308 HBV-related HCC patients. SNPs in the DEPDC5 rs1012068 were detected by MALDI-TOF-MS. Results After controlling for the influence of sex, smoking and drinking, this study showed a significant relationship between the polymorphism of DEPDC5 rs1012068 and HBV-related HCC. Healthy participants with CC genotype showed 2.008 (95% CI = 1.145, 3.520; P = 0.015) times more likely to develop HCC; CHB cases with CC genotype showed 2.241 (95% CI = 1.226, 4.461; P = 0.022) times more likely to develop HCC; LC cases with CC genotype showed 2.706 (95% CI = 1.371, 5.340; P = 0.004) times more likely to develop HCC; and individuals with AC genotype showed 1.615 (95% CI = 1.110, 2.352; P = 0.012) times more likely to develop HCC. Conclusions There was a significant correlation between DEPDC5 rs1012068A/C and HBV-related HCC in the Han Chinese population. A to C mutation increased the risk of the developing of HBV-related HCC.

Background Several epidemiological studies have evaluated the association between the NAD(P)H oxidase p22 phox gene C242T polymorphism and the risk of type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN), and carotid atherosclerosis with T2DM (CA), but the results are inconclusive. This meta-analysis was therefore designed to clarify these controversies. Methods Systematic searches were performed using electronic databases such as MEDLINE, PubMed, EMBASE, and China National Knowledge Infrastructure, as well as through manual searching of the references of identified articles. A total of 11 publications were eligible for this meta-analysis after running a search on the NAD(P)H oxidase p22 phox gene C242T polymorphism, including 7 with outcomes for T2DM, 7 with outcomes for DN, and 3 with outcomes for CA. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using a fixed effects model (FEM) or a random effects model (REM). Publication bias was tested by Begg's funnel plot analysis. Sensitivity analysis was also performed. Results The results showed a significant association between the NAD(P)H oxidase p22 phox gene C242T polymorphism and T2DM risk in the allelic model (REM: OR = 1.23, 95% CI = 1.06–1.43), additive model (FEM: OR = 1.61, 95% CI = 1.14–2.26), and recessive model (FEM: OR = 1.50, 95% CI = 1.10–2.05). A significant association was also observed for DN in the allelic model (REM: OR = 1.25, 95% CI = 1.06–1.47), additive model (FEM: OR = 1.61, 95% CI = 1.08–2.38), and dominant model (REM: OR = 1.26, 95% CI = 1.03–1.54). However, no association was observed for CA. Similar results were obtained in subgroup analysis based on ethnicity. Conclusions Results of this meta-analysis suggest that the NAD(P)H oxidase p22 phox gene 242T allele might be associated with an increased risk of T2DM and DN, but not CA., Graphical abstract, Highlights • There are significant association between P22 phox gene C242T polymorphism with T2DM DN risk but no significant association with CA.

It is common knowledge that soils irrigated with wastewater accumulate heavy metals more than those irrigated with cleaner water sources. However, little is known on metal concentrations in soils and cultivars after the cessation of wastewater use. This study assessed the accumulation and health risk of heavy metals 3 years post-wastewater irrigation in soils, vegetables, and farmers’ hair. Soils, vegetables, and hair samples were collected from villages previously irrigating with wastewater (experimental villages) and villages with no history of wastewater irrigation (control villages). Soil samples were digested in a mixture of HCL/HNO3/HCLO4/HF. Plants and hair samples were digested in HNO3/HCLO4 mixture. Inductive coupled plasma-optical emission spectrometer (ICP-OES) was used to determine metal concentrations of digested extracts. Study results indicate a persistence of heavy metal concentration in soils and plants from farms previously irrigated with wastewater. In addition, soils previously irrigated with wastewater were severely contaminated with cadmium. Hair metal concentrations of farmers previously irrigating with wastewater were significantly higher (P < 0.05) than farmers irrigating with clean water, but metal concentrations in hair samples of farmers previously irrigating with wastewater were not associated with current soil metal concentrations. The study concludes that there is a persistence of heavy metals in soils and plants previously irrigated with wastewater, but high metal concentrations in hair samples of farmers cannot be associated with current soil metal concentrations.

The nuclear transcription factor Krüppel-like factor 4 (KLF4) has an important role in cellular biological processes. However, the influence of KLF4 on collagen metabolism remains to be elucidated. In the present study, the effects and underlying mechanism of action of KLF4 on collagen metabolism was investigated in human hepatic stellate cells (HSC), by downregulating KLF4 expression using small interfering RNA (siRNA). The effects of KLF4 silencing by three predesigned siRNAs (siRNA1‑3) were evaluated using both reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting in the human LX2 HSC line. The mRNA expression levels of KLF4 were decreased by ~34, 40, and 69% in the siRNA1, siRNA2, and siRNA3 groups, respectively, as compared with the control group. These results were concordant with the protein expression levels of KLF4, as determined by western blot analysis. In the siRNA3 group, the quantity of type Ⅰ and type III collagen, and the expression levels of collagen metabolism proteins including matrix metalloproteinase‑1 (MMP‑1) and tissue inhibitors of metalloproteinases‑1 (TIMP‑1), were determined using both RT‑qPCR and western blotting. Both the mRNA and protein expression levels of type I and type III collagen were significantly decreased in the siRNA3 group, as compared with the control group. The mRNA and protein expression levels of TIMP‑1 were also significantly reduced in the siRNA3‑treated cells, whereas the mRNA and protein expression levels of MMP‑1 were significantly upregulated. Furthermore, KLF4 gene silencing significantly decreased the expression levels of numerous cytokines, including transforming grow factor‑β1, tumor necrosis factor‑α, and interleukin‑1β. The results of the present study provide evidence of siRNA‑mediated silencing of KLF4 expression, which may promote extracellular matrix (ECM) degradation, and inhibition of ECM synthesis. Therefore, KLF4 may be a promising target for the development of novel antifibrotic therapies.

The therapeutic management of liver fibrosis remains an unresolved clinical problem. The activation of hepatic stellate cells (HSCs) serves a pivotal role in the formation of liver fibrosis. In our previous study, matrix‑assisted laser desorption/ionization time‑of‑flight mass spectrometry (MALDI‑TOF MS) was employed to identify potential serum markers for liver cirrhosis, such as eukaryotic peptide chain releasing factor 3b polypeptide (eRF3b‑37), which was initially confirmed by our group to serve a protective role in liver tissues in a C‑C motif chemokine ligand 4‑induced liver cirrhosis mouse model. Therefore, eRF3b‑37 was hypothesized to affect the activation state of HSCs, which was determined by the expression of pro‑fibrogenic associated factors in HSCs. In the present study, peptide synthesis technology was employed to elucidate the role of eRF3b‑37 in the expression of pro‑fibrogenic factors induced by transforming growth factor‑β1 (TGF‑β1) in LX‑2 cells that were treated with either control, TGF‑β1 and TGF‑β1+eRF3b‑37. 3‑(4,5‑Dimethyl‑2‑thiazolyl)‑2,5‑diphenyltetrazolium bromide and flow cytometric assays, and fluorescent microscope examinations were performed to evaluate the effects of eRF3b‑37 on proliferation viability, G0/G1 arrest, apoptosis and cell migration. The results of the present study indicated that eRF3b‑37 inhibited the activation of HSCs. The increased mRNA and protein expression of the pro‑fibrogenic factors collagen I, connective tissue growth factor and α‑smooth muscle actin (SMA) stimulated by TGF‑β1 were reduced by eRF3b‑37 via the following mechanisms: i) Inhibiting LX‑2 cell proliferation, leading to G0/G1 cell cycle arrest and inhibition of DNA synthesis by downregulating the mRNA expressions of Cyclin D1 and cyclin dependent kinase‑4, and upregulating the levels of P21; ii) increasing cell apoptosis by upregulating the mRNA level of B‑cell lymphoma-2 (Bcl‑2)‑associated X protein (Bax) and Fas, and downregulating the expression of Bcl‑2; and iii) reducing cell migration by downregulating the mRNA and protein expression of α‑SMA. In addition, eRF3b‑37 is thought to serve a role in HSCs by inhibiting TGF‑β signaling. Therefore, eRF3b‑37 may be a novel therapeutic agent for targeting HSCs for hepatic fibrosis.

It has been reported that single nucleotide polymorphisms (SNPs) of Alpha-synuclein (SNCA) are associated with Parkinson's disease (PD). Some researchers have attempted to validate this finding in various ethnic populations. The results of studies concerning SNCA polymorphisms and PD susceptibility remain conflicting. To evaluate the association between these SNPs and PD, the authors conducted a series of meta-analyses using a predefined protocol. Databases including PubMed, MEDLINE and PD gene were searched to identify relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. All analyses were calculated using STATA11.0. A total of 19 studies on the SNPS rs181489, rs356186, rs356219, rs894278, rs2583988, rs2619363, rs2619364, rs2737029, rs10005233 and rs11931074 were included. This meta-analysis showed that eight out of these 10 candidate SNPs may be associated with PD risk. Significant association was found between PD and the following SNPs: rs181489, rs356186, rs356219, rs894278 rs2583988, rs2619364, rs10005233 and rs11931074. Among these SNPs, rs356186 was found to be the only SNP that may play a protective role in Parkinson's disease. These results suggest that the SNCA gene may be associated with PD.

Chronic hepatitis B virus (HBV) infection is a global health problem and the outcome are associated with both viral factors and host genetic factors. High Throughput Sequencing (HTS) technology were used to identify variants associated with liver disease.Fifty-five Chronic hepatitis B (CHB) patients, fifty-three self-healing HBV (SH) patients and 53 healthy controls (HC) were recruited, 404 cytokine and cytokine receptor related genes were captured and sequenced at high depth (900X), both variant (Fischer's exact test, P value 0.05) and gene (SKAT-O gene level test, adjust P value 0.05) level association were used to identify variants and genes associated with CHB.Total 5083 variants have been detected, fifty-four variants were found associated with CHB, most (29/32) variants were located in HLA region, including HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DQB2, HLA-DRB1 and HLA-DRB5. Several missense variants were found associated with CHB, including p.E226K in PVR (poliovirus receptor), p.E400A and p.C431R in IL4R (interleukin 4 receptor). Four variants located in 3'UTR (untranslated region) have also been found associated with CHB.Our study revealed that high through target region sequencing, combined with association analysis at variant and gene level, would be a good way to found variants and genes associated with CHB even at small sample size. Our data implied that chronic hepatitis B patients who carry these variants need intensive monitoring.

Host genotype may be closely related to the different outcomes of Hepatitis B virus (HBV) infection. To identify the association of variants and HBV infection, we comprehensively investigated the cytokine- and immune-related gene mutations in patients with HBV associated hepatocellular carcinoma (HBV-HCC). Fifty-three HBV-HCC patients, 53 self-healing cases (SH) with HBV infection history and 53 healthy controls (HCs) were recruited, the whole exon region of 404 genes were sequenced at >900× depth. Comprehensive variants and gene levels were compared between HCC and HC, and HCC and SH. Thirty-nine variants (adjusted PTT) from three genes (REAT1E, NOD-like receptor (NLR) protein 11 (NLRP11), hydroxy-carboxylic acid receptor 2 (HCAR2)) were found strongly associated with HBV-HCC. We found 39 different variants in 11 genes that were significantly related to HBV-HCC. Five of them were new findings. Our data implied that chronic hepatitis B patients who carry these variants are at a high risk of developing HCC.

Conflicting results in previous case–control studies on the association between Glutathione S-transferase T1 (GSTT1) gene polymorphism and Parkinson’s disease (PD) risk have been reported, so we conducted this meta-analysis. We searched and extracted data from 3 Chinese and 3 English web-based electronic databases to evaluate the associations by odds ratio (OR) and its 95 % confidence interval (CI) under the recessive genetic comparison model (null genotype vs. present genotype). We also conducted subgroup analyses by ethnicity and adjusted status of OR, respectively. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also reanalyzed. When 18 eligible studies (3,963 PD cases and 5,472 controls) were pooled to analyze the association, we found no statistically significant result (OR 1.24, 95 % CI 0.96–1.60). In the subgroup analyses by ethnicity, there was statistically significant association between the null genotype of GSTT1 and PD risk among Caucasians, while the associations were not found among Asians and Latinos. In the subgroup analyses by adjusted status of OR, there were no significant associations both in studies with crude OR and adjusted OR. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also confirmed the associations mentioned above. Power analysis indicated only meta-analysis of Caucasians had enough evidence to claim the association. In conclusion, the meta-analysis suggests that the null genotype of GSTT1 contributes to PD risk in Caucasians, and no association in Asians is needed more studies to confirm.

The study investigated the age-adjusted mortality rate and disease odds among deceased residents living in areas exposed to wastewater and cleanwater from 2007 to 2011, in Shijiazhuang, China. Mortality data for eight villages exposed to wastewater and 16 villages not exposed to wastewater were collected and crosschecked from multiple sources. Overall mean age-adjusted mortality rate for wastewater areas was 798/105 (95% Confidence Interval (CI) = ± 68), insignificantly higher than the mean mortality rate for cleanwater area, 726/105 (95% CI = ± 46), p0.05. Malignant neoplasms and respiratory mortality and disease odds were higher in wastewater areas than in cleanwater areas, OR = 1.7 (95% CI = 1.3-2.2, p0.01) and OR = 1.9 (95% CI = 1.1-3.4, p0.05), respectively. Wastewater area mortality and disease odds for Lung and Stomach cancers after adjustments were OR = 1.6 (95% CI = 1.1-2.4, p0.05) and OR = 1.8 (95% CI = 1.2-2.7, p0.01), respectively, significantly higher than those of cleanwater areas. There is a possibility that exposure to wastewater might be associated with cancer and respiratory disease mortality. The study recommends that the use of wastewater be limited, discouraged, or discontinued.

Summary Recent studies have associated genetic variation near the interleukin 28B (IL28B/IFN-λ3) gene with natural clearance of the hepatitis C virus (HCV) infection, and a common variant in the DEP domain containing 5 (DEPDC5) locus on chromosome 22 has been shown to affect susceptibility to hepatocellular carcinoma (HCC) in Japanese individuals with chronic HCV infection. This study was conducted to determine whether polymorphisms near or in interferon-lambda (IFN-λs) genes and their receptor genes such as interleukin 28 receptor, alpha (IL28RA) and interleukin 10 receptor, beta (IL10RB) as well as p21_activated kinases 4 (PAK4) and iron/zinc purple acid phosphatase-like protein (PAPL), which are locate upstream of IFN-λs, and lastly the DEPDC5 gene are associated with hepatitis B virus-related liver disease in Han Chinese. The study subjects included 507 normal healthy controls, 350 individuals with natural clearance of HBV and 792 HBV-infected patients. The patients were categorized into 157 inactive carriers (Case I), 216 active carriers (Case II), 111 cirrhotics (Case III) and 308 HCC patients (Case IV) subgroups. Seven single nucleotide polymorphisms (SNPs) were genotyped using the Matrix-assisted Laser Desorption/Ionisation mass spectrometric (MALDI-TOF MS) SNP genotyping assay. Rs423058 upstream of PAPL, rs2834167 in IL10RB and rs1012068 in DEPDC5 were associated with chronic HBV status, HBV natural clearance and the presence of HCC (P = 0.0004–0.024), respectively. PAPL, IL10RB and DEPDC5 polymorphisms have an impact on progression of HBV-related liver disease. However, IFN-λs genes as a tool to differentiate between different clinical courses of HBV infection were not useful in the Han Chinese population.

Two recent genome-wide studies showed that the single-nucleotide polymorphisms in the HLA-DQ region (rs2856718 and rs9275572) were associated with chronic hepatitis B virus infection and chronic hepatitis C virus-associated hepatocellular carcinoma in Japanese patients. We tested the effects of the two single-nucleotide polymorphisms for all major HBV outcomes and lamivudine treatment in Han Chinese. A total of 1649 samples were enrolled, and peripheral blood samples were collected in this study. The single-nucleotide polymorphisms in the HLA-DQ region were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Our study demonstrated the clear relevance of HLA-DQ rs2856718 and rs9275572 with HBV susceptibility, natural clearance and HBV-associated HCC. HLA-DQ rs2856718G and rs9275572A were strongly associated with decreased risk of chronic HBV infection (odds ratio = 0.641; P = 2.64 × 10(-4) ; odds ratio = 0.627, P = 7.22 × 10(-5) ) and HBV natural clearance (odds ratio = 0.610; P = 4.80 × 10(-4) ; odds ratio = 0.714, P = 0.013). Moreover, rs9275572A was also associated with development of cirrhosis and hepatocellular carcinoma (odds ratio = 0.632, P = 0.008). In addition, we showed for the first time to our knowledge that rs9275572 was a predictor for lamivudine therapy (viral response: odds ratio = 2.599, P = 4.43 × 10(-4) ; biochemical response: odds ratio = 2.279, P = 4.23 × 10(-4) ). Our study suggested that HLA-DQ loci were associated with both HBV clearance and HBV-related diseases and outcomes of lamivudine treatment in Han Chinese.

To assess the association between gene polymorphisms (single nucleotide polymorphisms [SNPs]) of rs8099917 and rs12980602 in the IL-28 gene and the response to lamivudine treatment in naïve of Chinese rural patients.Three hundred and fifty-four naïve chronic hepatitis B (CHB) patients treated with lamivudine were enrolled in this study. Rs8099917 and rs12980602 SNPs were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Baseline characteristics and genotypes were compared between 181 patients with treatment response and 173 without response.The IL-28 genotypes were independently associated with responses at 1 year post-treatment with lamivudine in CHB patients (OR for rs8099917 GT/GG vs. TT, 4.097 [95% CI, 1.342-12.512; p = 0.015]; OR for rs12980602CT/CC vs. TT, 2.27 [95% CI, 1.202-4.284; p =0.014]). When adjusting for age, gender, smoking, drinking, and levels of hepatitis B virus (HBV) DNA, alanine aminotransferase, and HBV genotype, the rs8099917 genotype GT (OR, 4.025 [95% CI, 1.316-12.354; p = 0.013] and fibrosis stage (OR, 0.716 [95% CI, 0.432-0.986; p = 0.036] appeared to be associated with a higher probability of response to lamivudine treatment.The genotype G/T for rs8099917 of IL-28 gene and early fibrosis stage may be predictive of treatment success.

Background and Aim: Several epidemiological studies have reported the association between obesity and multiple sclerosis (MS). Methods: A literature search of the observational studies, published as original articles in English before December 2015, was performed using electronic databases. Results: Five observational studies were included, of which 3 were case-control studies and 2 were cohort studies. The pooled relative risk (RR) for overweight and obesity during childhood and adolescence compared with normal weight (body mass index = 18.5-24.9 kg/m2) was 1.44 (95% CI 1.22-1.70) and 2.01 (95% CI 1.63-2.48), respectively. In subgroup analyses, we found that excess body weight during childhood and adolescence increased the risk of MS in the female group (overweight: pooled RR = 1.62, 95% CI 1.35-1.94; obesity: pooled RR = 2.25, 95% CI 1.77-2.85), but not in the male group (overweight: pooled RR = 1.19, 95% CI 0.91-1.55; obesity: pooled RR = 1.22, 95% CI 0.79-1.90). Conclusions: Excess body weight during childhood and adolescence was associated with an increased risk of MS; severe obesity demonstrated a stronger risk. A statistically significant association was found in the female group, but not in the male group.

Objectives: Studies examining whether glutathione S-transferase M1 (GSTM1) polymorphisms are associated with Parkinson’s disease (PD) have reported inconsistent results. To clarify those inconsistencies, a meta-analysis was performed. Methods: The electronic databases were searched for all publications regarding the association. Studies were included if they met the eligibility criteria. The strength of the association between GSTM1 polymorphisms and PD risk was measured by odds ratios (ORs) and 95% confidence intervals (CIs) in the recessive genetic model (null genotype vs. present genotype). Subgroup analyses by ethnicity and OR type were performed. Results: A total of 22 publications (23 studies) were included. There were 14, 7 and 2 studies with Caucasians, Asians and Latinos, respectively. OR types were 15 and 8 studies with crude and adjusted ORs, respectively. The combined results of the overall analysis showed that the GSTM1 null genotype was not significantly associated with PD risk (ORrandom-effects = 1.06, 95% CI = 0.95–1.19). In subgroup analyses by ethnicity, no significant associations were found in Caucasians, Asians or Latinos individually. Similarly, there were no associations in the subgroup analyses by OR type. There were no obvious publication biases in any of the comparisons. Discussion: The results of this meta-analysis suggest that the GSTM1 null genotype is not significantly associated with PD risk.

Background and Aim: The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed on activated and regulatory T lymphocytes. Polymorphisms could have remarkable effects on susceptibility to autoimmunity. However, the associations between CTLA-4 polymorphisms and primary biliary cirrhosis (PBC) remain ambiguous. The aim of this meta-analysis is to determine more precise estimations of the relationship. Methods: From literature retrieval from PubMed, Web of Science, Science Direct, and the Chinese National Knowledge Infrastructure (CNKI) Database, the publications on the associations between rs231775, rs3087243, rs5742909, rs231725 and rs11571317 polymorphisms of CTLA4 and PBC through June 2011 were collected. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in fixed or random model, I2 was calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects with Revman 5.1 and Stata 11. Results: Overall, a significantly increased risk was found for G versus A allele for rs231775 (OR = 1.28, 95% CI = 1.17–1.41). For rs3087243, a significant association was found for AA versus GG genotype (OR = 0.66; 95% CI = 0.55–0.80). When subgroup analysis by ethnicity was performed, the same association was only found in Caucasians. For rs231725, the OR values (95% CI) for GG versus AA, GA versus AA and G versus A allele were 0.52 (0.40–0.68), 0.74 (0.60–0.92) and 0.73 (0.61–0.88). No significant associations were found for other polymorphisms. Conclusion: The G allele of rs231775 is a risk factor for PBC, while AA genotype of rs3087243 and GG, GA and G allele of rs231725 show negative associations with PBC.

Studies investigating the associations between GSTM1 and GSTT1 polymorphisms and colorectal cancer (CRC) risk in Chinese population have reported controversial results. Thus, a meta-analysis was performed.Four hundred and seven relevant records were identified through a literature search up to September 7, 2011, and 19 studies were finally included, involving a total of 3,130 CRC cases and 6,423 controls. Subgroup analyses were performed by language and study design. Statistical analysis was performed with the software programs Review Manager (version 5.1.2) and STATA (version 11.0).For the GSTM1 polymorphism, the null genotype of GSTM1 was not associated with CRC risk in Chinese population (OR = 1.12, 95% CI = 0.97-1.28). Similar associations were found for GSTT1 polymorphism (OR = 1.10, 95% CI = 0.94-1.29) and the dual null genotype of GSTM1/GSTT1 (OR = 1.26, 95% CI = 0.93-1.71). For subgroup analyses, studies published in English and population-based studies further identified these associations for the three aspects above in Chinese population.This meta-analysis suggests that the null genotypes of GSTM1 and GSTT1 and the dual null genotype of GSTM1/GSTT1 were all not risk factors in CRC in Chinese population.

Serum markers are needed to be developed to specifically diagnose Hepatocellular carcinoma (HCC). Des-γ-carboxy prothrombin (DCP) is a promising tool with limited expense and widely accessibility, but the reported results have been controversial. In order to review the performance of DCP for the diagnosis of HCC, the meta-analysis was performed. After a systematic review of relevant studies, the sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively) were pooled using a bivariate meta-analysis. Potential between-study heterogeneity was explored by meta-regression model. The post-test probability and the likelihood ratio scattergram to evaluate clinical usefulness were calculated. Based on literature review of 20 publications, the overall sensitivity, specificity, PLR and NLR of DCP for the detection of HCC were 67% (95%CI, 58%-74%), 92% (95%CI, 88%-94%), 7.9 (95%CI, 5.6-11.2) and 0.36 (95%CI, 0.29-0.46), respectively. The area under the bivariate summary receiving operating characteristics curve was 0.89 (95%CI, 0.85-0.92). Significant heterogeneity was present. In conclusion, the major role of DCP is the moderate confirmation of HCC. More prospective studies of DCP are needed in future.

There is a dearth of information on the temporal changes in polychlorinated dibenzodioxin/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) contamination, in both environmental and biological specimens, in China. We compared the concentrations of PCDD/Fs and dl-PCBs in human milk collected in Shijiazhuang, Hebei Province, in northern China in 2002 (n = 30) and 2007 (n = 20). The level of PCDD/Fs and dl-PCBs showed an increasing trend. The mean concentrations of PCDD/Fs plus dl-PCBs were 4.47 TEQ pg g−1 fat and 6.24 TEQ pg g−1 fat in human milk from Shijiazhuang in 2002 and in 2007, respectively. Based on statistical analysis of questionnaire data collected by in-person interviews with mothers, we found positive correlations between consumption of sea fish and PCDFs. The PCDDs, PCDFs, PCDD/Fs, and PCDD/Fs plus dl-PCBs levels in individuals consuming greater amounts of sea fish were higher than those consuming less sea fish, both with and without adjustments for potential confounding factors. Among 17 congeners of PCDD/Fs, the 2,3,7,8-TCDF, 1,2,3,7,8-PeCDF, 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 2,3,4,6,7,8-HxCDF congener concentrations in 2007 increased 134%, 55%, 53%, 57%, 65% and 130% when compared to 2002 levels, respectively. The 2007 dl-PCB congener levels were greater than those of the 2002 samples, with the exception of PCB81 and PCB77. Specifically, PCB105, PCB114, PCB118, PCB123 and PCB156 had increased greater than twofold from 2002 to 2007. Continuous surveillance of PCDD/F and dl-PCB levels in human milk is needed to accurately evaluate both environmental contamination and the human health risk to neonates in China.

There were some studies on the associations between Glutathione S-transferase M1 (GSTM1) and Glutathione S-transferase T1 (GSTT1) polymorphisms and cervical cancer (CC) risk, but the results were inconsistent. Thus, a meta-analysis was performed. The electronic databases PubMed, Science Direct, CBM, and CNKI were searched for possible studies. Finally, 16 studies (1,627 cases and 2,161 controls) were included. For the GSTM1 and GSTT1 polymorphisms, the unadjusted odds ratios (OR) and 95% confidence intervals (95% CI) from each study were used to estimate summary OR. Subgroup analyses by ethnicity and histological type of CC were also performed. For the GSTM1 polymorphism, the null genotype of GSTM1 was associated with an increased CC risk in total population (OR=1.32, 95% CI=1.06-1.66). Similar association was found in Asians (OR=1.47, 95% CI=1.11-1.94), but not in Caucasians (OR=0.96, 95% CI=0.73-1.27). For the GSTT1 polymorphism, the null genotype of GSTT1 was not statistically significantly associated with CC risk in total population (OR=1.36, 95% CI=0.97-1.90). This result was also found in Asians (OR=1.27, 95% CI=0.87-1.85) and Caucasians (OR=1.09, 95% CI= 0.66-1.79), but not in Latinos (OR=4.58, 95% CI= 2.04-10.28). For the GSTM1/GSTT1 interaction analysis, the dual null genotypes of GSTM1/GSTT1 were significantly associated with increased CC risk in total population (OR=1.77, 95% CI= 1.14-2.75), and all the six studies were from Asia. For subgroup analyses by histological type of CC, the three aspects of the analyses above were all not significantly associated with CC risk in squamous cell carcinoma and adenocarcinoma, respectively. The null genotype of GSTM1 and the dual null genotypes of GSTM1/GSTT1 were risk factors in CC, and the null genotype of GSTT1 was not associated with CC risk.

Hydrogen sulfide (H(2)S) is a gaseous messenger and serves as an important neuromodulator in the central nervous system. The current study was undertaken to investigate whether H(2)S attenuates the neuronal injury induced by vascular dementia (VD). Rats were subjected to bilateral common carotid artery and vertebral artery occlusion for 5 min three times in an interval of 5 min to induce VD. An H(2)S donor, sodium hydrosulfide (NaHS) or an inhibitor of cystathionine-beta-synthase, hydroxylamine (HA) was administered intraperitoneally. The number of neurons in the hippocampus was determined by hematoxylin and eosin staining, and the performance of learning and memory was tested by the Morris water maze. H(2)S content in plasma was evaluated. Apoptosis in the hippocampus was assessed by flow cytometry. In addition, Bcl-2 and Bax expression was analyzed by immunohistochemical staining. The neuronal injury occurred gradually with a decreased number of neurons and increased apoptosis ratio in the hippocampus over 720 h after VD. The H(2)S level was also gradually decreased in plasma over 720 h after VD, which negatively correlated with the apoptosis ratio in the hippocampus after VD. In addition, NaHS treatment significantly attenuated neuronal injury and improved neural functional performance, whereas HA exaggerated the neuronal injury and exacerbated learning and memory at 720 h after VD. Furthermore, NaHS treatment markedly improved the ratio of Bcl-2 over Bax with increased Bcl-2 expression and decreased Bax expression. In contrast, HA reduced the ratio of Bcl-2 over Bax. It is suggested that H(2)S attenuates VD injury via inhibiting apoptosis and may have potential therapeutic value for VD.

In the present study, the wastewater sample collected from the Dongming discharging river in Shijiazhuang city was analysed using both chemical analysis and biological assays including the Salmonella mutagenicity test, micronucleus test and single-cell gel electrophoresis. Chemical analysis of the sample was performed using gas chromatography mass spectrometry and inductively coupled plasma mass spectrometry. The Salmonella mutagenicity test was performed on Salmonella typhimurium TA97, TA98, TA100 and TA102 strains with and without S9 mixture. The mice received the wastewater in natura through drinking water at concentrations of 25%, 50%, and 100%. One group of mice was exposed for 2 consecutive days, and the other group of mice was exposed for 15 consecutive days. To establish the levels of primary DNA damage, single-cell gel electrophoresis was performed on treated mouse liver cell. The concentrations of chromium and lead in the sample exceeded the national standard (GB20922-2007) by 0.78 and 0.43-fold, respectively. More than 30 organic compounds were detected, and some of the detected compounds were mutagens, carcinogens and environmental endocrine disrupters. A positive response for Salmonella typhimurium TA98 strain was observed. Mouse exposure via drinking water containing 50% and 100% of wastewater for 15 consecutive days caused a significant increase of MN frequencies in a dose-response manner. Mouse exposure via drinking water containing 50% and 100% of wastewater for 15 consecutive days caused a significant increase of the Olive tail moments in a dose-response manner. All the results indicated that the sample from the Dongming discharging river in Shijiazhuang city exhibited genotoxicity and might pose harmful effects on the local residents.

Several recent genome-wide studies showed that the genetic polymorphisms in the HLA-DQ region (rs9275572 and rs2856718) were related to chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). We analyzed the two single-nucleotide polymorphisms for major HBV outcomes in Han Chinese. A total of 1291 samples were involved and peripheral blood samples were collected in this study. Matrix-assisted laser desorption/ionization time of flight mass spectrometry were used to genotype the single-nucleotide polymorphisms in the HLA-DQ region. Our study indicated the clear relationship between the HLA-DQ rs9275572 and HBV-related HCC after control for the effects of sex, drinking, and smoking. Health subjects with the HLA-DQ rs9275572 GA genotype would have a 0.641 (95 % CI 0.416, 0.985; P = 0.043) times lower odds of having HCC, and those with the AA genotype would have a 0.256 (95 % CI 0.106, 0.618; P = 0.002) times lower odds of having HCC, whereas the values of the other covariates were fixed. Whereas there was no significant difference found for the HLA-DQ rs2856718 AG and GG genotype. Our study suggested that HLA-DQ loci (rs9275572) were associated with HBV-related HCC as a protective factor in Han Chinese.

OBJECTIVES. We seek to investigate the joint effects of age and body mass index (BMI) on the incident hypertension subtypes among Chinese adults during 1989–2011. METHODS. We investigated the Incidence rates (IRs, per 100 person-years) of hypertension subtypes, adjusted relative risks (RRs) and population attributable risk percent (PAR%) of BMI for hypertension, and clarified the age-specific effect of BMI on incident hypertension utilizing a dynamic cohort study from the China Health and Nutrition Survey (CHNS) 1989–2011. RESULTS. Normotensive participants (n=53,028) at baseline were included, with mean age was 41.7 (95% CI, 41.6–41.7) years old. During a total of 118,694 person years (average was 6.38 years) of follow-up, a total of 5,208 incident cases of hypertension were documented. The IRs of hypertension were 4.4 (95% CI, 4.3–4.5), which increased gradually by age and BMI (P(trend)22 vs BMI =140/90/or treatment for BMI >22 vs. IR for BMI

Objective Epidemiological studies have reported an inconsistent association between obesity and ovarian cancer. To update the current knowledge of and further qualify the association between overweight, obesity and ovarian cancer risk, we conducted a meta-analysis of published observational studies. Methods Using the PubMed, MEDLINE and EMBASE databases, we performed a literature search of all of the case-control and cohort studies published as original articles in English before March 2015. We included 26 observational studies, of which 13 were case-control studies (7782 cases and 21 854 controls) and 13 were cohort studies (5181 cases). Fixed- and random-effects models were used to compute summary estimates and the corresponding 95% confidence intervals. Subgroup analyses were also performed. Results The pooled relative risk for overweight and obesity compared with normal weight (body mass index = 18.5-24.9 kg/m(2)) was 1.07 (95% confidence interval: 1.02-1.12) and 1.28 (95% confidence interval: 1.16-1.41), respectively. In subgroup analyses, we found that overweight/obesity increased the risk of ovarian cancer in most groups, except for the postmenopausal group (overweight: pooled relative risk = 0.97, 95% confidence interval: 0.76-1.24; obesity: pooled relative risk = 0.93, 95% confidence interval: 0.61-1.42). There was no evidence of publication bias. Conclusions Increased body weight was associated with an increased risk of ovarian cancer; in particular, severe obesity demonstrated a stronger risk effect. No statistically significant association was observed in the postmenopausal period, but was in the premenopausal period.

This study investigated correlations between polymorphisms in DNA mismatch repair (MMR) genes and the risk of primary hepatocellular carcinoma (PHC).Single nucleotide polymorphisms (SNPs) in the DNA MMR genes MLH3 (rs175080), PMS1 (rs5742933), PMS2 (rs1059060), MSH3 (rs26279), MSH5 (rs1150793, rs2075789) and MSH6 (rs1042821) were detected using the SNaPshot method in 250 PHC cases and in 308 patients without PHC in the Han population in northern China.The AA genotype in MLH3 (rs175080) increased the risk of PHC (odds ratio [OR] = 3.424; 95% confidence interval [CI]: 1.097-10.689). The AG and GG genotypes in MSH3 (rs26279) increased the risk of PHC (OR: 1.644 and 3.300; 95% CI: 1.112-2.428 and 1.765-6.168, respectively). The AA genotype in MSH5 (rs2075789) increased the risk of PHC (OR: 9.229; 95% CI: 1.174-72.535). The CT genotype in MSH6 (rs1042821) reduced the risk of PHC (OR: 0.629; 95% CI: 0.428-0.924).Our study suggests that polymorphisms in MLH3 (rs175080), MSH3 (rs26279), MSH5 (rs2075789) and MSH6 (rs1042821) may be independent risk factors for PHC.

To clarify the relationship between serum folate and schizophrenia (SZ) risk, the meta-analysis was conducted. PubMed, Embase, and Web of Science were searched without language restrictions. Weighted mean difference (WMD) as a summary statistic was used in this meta-analysis. Subgroup analyses by publication language (English and non-English), ethnicity (Caucasian, Asian, African, Latino, and mixed population), duration (acute, chronic, patients including both acute and chronic SZ, and not mentioned about either chronic or acute), measurement time (before drugs using and after drugs using), gender (male and female) and age (50 years old and50 years old) were performed. Power analysis was also conducted to detect the reliability of the meta-analyses' results. In summary, the subgroups which failed to detect significant decreased associations were always with lower statistic power and could not be confirmed. The results supported that decreased serum folate was associated with SZ risk in total studies and subgroups of English publications, Caucasians, Asians, acute SZ patients, measurement after drugs using in SZ patients, and age50 with the great enough powers, respectively. In conclusion, the present meta-analysis found that folate deficiency is associated to SZ, and subgroups which did not reach enough statistical power need further investigation in the future.

Human milk specimens from 55 women in Shijiazhuang urban and Tangshan rural areas in Hebei Province in northern China were collected and analyzed for persistent organic pollutants, such as p,p′ -dichlorodiphenyldichloroethylene ( p,p′ -DDE), hexachlorobenzene (HCB), β -hexachlorocyclohexane ( β- HCH), and dioxins. We administered a questionnaire to milk donors at collection time, asking about lifestyle factors that potentially influence organochlorine pesticide (OCP) levels in human milk. We found that the concentrations of p,p′ -DDE and β -HCH in human milk from the primiparous mothers in Shijiazhuang (3330 and 108.8 ng/g fat, respectively) were higher than in samples from mothers from Tangshan (1916 and 21.2 ng/g fat, respectively). In addition, we found the level of p,p′ -DDE correlated positively with a dietary history of meat consumption or consumption of internal organs of pigs and sheep ( r = 0.38 and r = 0.52 , respectively), but not with intake frequencies of vegetables and fruits in primiparous mothers. The higher level for p,p′ -DDE may be due to a greater intake of contaminated fatty foods in the industrialized areas. We also showed that the body burden of p,p′ -DDE was higher in the urban group compared to the values in other regions in China after 1998. However, there was no difference in dioxin levels between the two regions. Comprehensive monitoring of persistent organic pollutants in human milk and food is needed in China.

Ubiquitin-specific protease 22 (USP22) can regulate the cell cycle and apoptosis in many cancer cell types, while it is still unclear whether the deubiquitinating enzyme activity of USP22 is necessary for these processes. As little is known about the impact of USP22 on the growth of HeLa cell, we observed whether USP22 can effectively regulate HeLa cell growth as well as the necessity of deubiquitinating enzyme activity for these processes in HeLa cell. In this study, we demonstrate that USP22 can regulate cell cycle but not apoptosis in HeLa cell. The deubiquitinating enzyme activity of USP22 is necessary for this process as confirmed by an activity-deleted mutant (C185S) and an activity-decreased mutant (Y513C). In addition, the deubiquitinating enzyme activity of USP22 is related to the levels of BMI-1, c-Myc, cyclin D2 and p53. Our findings indicate that the deubiquitinating enzyme activity of USP22 is necessary for regulating HeLa cell growth, and it promotes cell proliferation via the c-Myc/cyclin D2, BMI-1 and p53 pathways in HeLa cell.

Aberrant expression and structural alterations of microRNAs (miRNAs) play important roles in tumorigenesis. The miRNA-196a2 polymorphism is associated with tumorigenesis, but its association with non-Hodgkin lymphoma (NHL) remains unexplored. We evaluated the association between the miRNA-196a2 T>C polymorphism (rs11614913) and NHL risk in a case–control study of 318 NHL cases and 320 healthy controls. We also examined miRNA-196a expression in tissue samples from NHL patients (n = 59). The TC and CC genotypes were associated with cancer risk in NHL [odds ratio (OR) = 1.384, confidence interval (CI) = 1.010–1.898 for TC vs. TT, and OR = 1.822, 95 % CI = 1.163–2.853 for CC vs. TT]. Analysis of the association between this polymorphism and the clinicopathology of NHL showed that the combined TC/CC genotypes were associated with Ann Arbor stage (OR = 1.852, 95 % CI = 1.139–3.010), bone marrow invasion (OR = 1.850, 95 % CI = 1.062–3.223), and B symptoms (OR = 1.852, 95 % CI = 1.154–2.972), but not with immunohistological subtype, lymph node size, age, or gender. In addition, the CC or CC/TC genotypes were associated with significantly higher levels of mature miR-196a (p = 0.002 or 0.008) in a genotype–phenotype correlation analysis. Our findings suggest that the miR-196a2 polymorphism may increase the risk of NHL by altering the expression of mature miR-196a.