Circular RNA hsa_circ_0098181 inhibits metastasis in hepatocellular carcinoma by activating the Hippo signaling pathway via interaction with eEF2.

INTRODUCTION AND OBJECTIVES: The development of hepatocellular carcinoma (HCC) is a multi-step process that accumulates genetic and epigenetic alterations, including changes in circular RNA (circRNA). This study aimed to understand the alterations in circRNA expression in HCC development and metastasis and to explore the biological functions of circRNA. MATERIALS AND METHODS: Ten pairs of adjacent chronic hepatitis tissues and HCC tissues from patients without venous metastases, and ten HCC tissues from patients with venous metastases were analyzed using human circRNA microarrays. Differentially expressed circRNAs were then validated by quantitative real-time PCR. In vitro and in vivo assays were performed to assess the roles of the circRNA in HCC progression. RNA pull-down assay, mass spectrometry analysis, and RNA-binding protein immunoprecipitation were conducted to explore the protein partners of the circRNA. RESULTS: CircRNA microarrays revealed that the expression patterns of circRNAs across the three groups were significantly different. Among these, hsa_circ_0098181 was validated to be lowly expressed and associated with poor prognosis in HCC patients. Ectopic expression of hsa_circ_0098181 delayed HCC metastasis in vitro and in vivo. Mechanistically, hsa_circ_0098181 sequestered eukaryotic translation elongation factor 2 (eEF2) and dissociated eEF2 from filamentous actin (F-actin) to prevent F-actin formation, which blocked activation of the Hippo signaling pathway. In addition, the RNA binding protein Quaking-5 bound directly to hsa_circ_0098181 and induced its biogenesis. CONCLUSIONS: Our study reveals changes in circRNA expression from chronic hepatitis, primary HCC, to metastatic HCC. Further, the QKI5-hsa_circ_0098181-eEF2-Hippo signaling pathway exerts a regulatory role in HCC.

Comprehensive investigating of mismatch repair genes (MMR) polymorphisms in participants with chronic hepatitis B virus infection.

Background and aim: In this study, we focused on the relationship between single nucleotide polymorphisms in MMR genes and the occurrence and development of HBV infection. Materials and methods: A total of 3,128 participants were divided into five groups: negative control group (NeC), spontaneous clearance group (SC), chronic hepatitis B group (CHB), liver cirrhosis group (LC) and hepatocellular carcinoma group (HCC), CHB, liver cirrhosis and hepatocellular carcinoma constitute HLD. We conducted three case-control studies: NeC (840 cases) vs. HLD (1792 cases), SC (486 cases) vs. HLD (1792 cases) and CHB + LC (1,371 cases) vs. HCC (421 cases). 11 polymorphic loci in MLH1, MLH3, MSH5, PMS1 and PMS2 were involved in genotyping by Sequenom MassArray. The SNPStats performed Hardy-Weinberg equilibrium test. Linkage disequilibrium patterns were visualized using Haploview4.2. The GMDR (v0.9) was conducted to generalized multifactor dimension reduction analysis. The correlation, multiplicative interaction and additive interaction analyses were calculated by Logistic Regression through SPSS21.0. Matrix and programmed excel were also involved in the calculation of additive interaction. Results: In NeC vs. HLD group, MSH5-rs1150793(G) was a risk base to HBV susceptibility (nominal p = 0.002, OR = 1.346). We found multiplicative interaction between MLH1-rs1540354 (AA + AT) and PMS1-rs1233255 (AA) (nominal p = 0.024, OR = 1.240). There was additive interaction between PMS1-rs1233255 (AA) and PMS1-rs256554(CA + CC). In SC vs. HLD group, MLH1-rs1540354 (TT) was a risk genotype (nominal p < 0.05, OR>1). Through haplotype analysis, we found the linkage disequilibrium of three loci in MLH1. The results of GMDR showed the optimal five-locus model about the spontaneous clearance of HBV. In CHB + LC vs. HCC group, PMS2-rs12112229(A) was related to the cancerization of liver. Conclusion: We found rs1150793(G), rs1540354(T) and rs12112229(A) were significantly related to HBV susceptibility, spontaneous clearance of HBV and cancerization after infection, respectively.

Comparison of Serum Folate between Schizophrenic Patients and Healthy Controls in Chinese Han Adult Population: A Systematic Review and Meta-Analysis.

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<0.001), and in most of the subgroups, the associations reached decreased significantly; while in the subgroup of drugs use, the association was not reached significantly. 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.

4210 Da and 1866 Da polypeptides as potential biomarkers of liver disease progression in hepatitis B virus patients.

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 < 0.001). For the differential diagnosis of CHB from normal liver, the areas under the receiver operating characteristic (ROC) curve of 4210 Da and 1866 Da and their combination via logistic regression were 0.961, 0.849 and 0.967. For the differential diagnosis of LC from CHB, the areas under the ROC curve were 0.695, 0.841 and 0.826. For the differential diagnosis of HCC from CHB, the areas under the ROC curve were 0.744, 0.710 and 0.761, respectively. For the differential diagnosis of HCC from LC, the areas under the ROC curve of 4210 Da and 1866 Da were 0.580 and 0.654. The positive rate of 1866 Da was 45.5% and 69.0% in AFP-negative HCC patients and that of 4210 Da was 60.6% 58.6% in AFP-negative HCC patients of the study HCC vs. CHB and HCC vs. LC. The 4210 Da and 1866 Da polypeptide levels were positively correlated with HBV DNA levels (P < 0.001, r = 0.269; P < 0.001, r = 0.285). The 4210 Da and 1866 Da polypeptides had good diagnostic value for the occurrence and progression of HBV-related chronic hepatitis, liver cirrhosis and hepatocellular carcinoma and could serve to accurately guide treatment management and predict clinical outcomes.

Genetic variants in IL33 and IL1RL1 genes confer susceptibility to HBV-related liver cirrhosis in Chinese Han population.

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.

Germline Variants and Genetic Interactions of Several EMT Regulatory Genes Increase the Risk of HBV-Related Hepatocellular Carcinoma.

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 (P recessive =0.001) and CHB+LC (P recessive<0.001). The CG haplotype of the rs4647958/rs1543442 haplotype block was associated with significant differences between healthy subjects and HCC patients (P=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.

Burden and trend of ischemic heart disease and colorectal cancer attributable to a diet low in fiber in China, 1990-2017: findings from the Global Burden of Disease Study 2017.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Repeat Induced Abortion among Chinese Women Seeking Abortion: Two Cross Sectional Studies.

BACKGROUND: In China, there were about 9.76 million induced abortions in 2019, 50% of which were repeat abortions. Understanding the tendency of repeat induced abortion and identifying its related factors is needed to develop prevention strategies. METHODS: Two hospital-based cross-sectional surveys were conducted from 2005-2007 and 2013-2016 in 24 and 90 hospitals, respectively. The survey included women who sought an induced abortion within 12 weeks of pregnancy. The proportion of repeat induced abortions by adjusting the covariates through propensity score matching was compared between the two surveys, and the zero-inflated negative binomial regression model was established to identify independent factors of repeat induced abortion. RESULTS: Adjusting the age, occupation, education, marital status and number of children, the proportion of repeat induced abortions in the second survey was found to be low (60.28% vs. 11.11%), however the unadjusted proportion was high in the second survey (44.97% vs. 51.54%). The risk of repeat induced abortion was higher among married women and women with children [ORadj and 95% CI: 0.31 (0.20, 0.49) and 0.08 (0.05, 0.13)]; the risk among service industry staff was higher when compared with unemployed women [ORadj and 95% CI: 0.19 (0.07, 0.54)]; women with a lower education level were at a higher risk of a repeat induced abortion (ORadj < 1). Compared with women under the age of 20, women in other higher age groups had a higher frequency of repeat induced abortions (IRadj: 1.78, 2.55, 3.27, 4.01, and 3.93, separately); the frequency of women with lower education levels was higher than those with a university or higher education level (IRadj > 1); the repeat induced abortion frequency of married women was 0.93 (0.90, 0.98) when compared to the frequency of unmarried women, while the frequency of women with children was 1.17 (1.10, 1.25) of childless women; the induced abortion frequency of working women was about 60-95% with that of unemployed women. CONCLUSIONS: The repeat induced abortion proportion was lower than 10 years ago. Induced abortion seekers who were married, aged 20 to 30 years and with a lower education level were more likely to repeat induced abortions.

Burden of viral hepatitis caused by specific aetiologies in China, 1990-2016: findings from the GBD 2016.

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.

Correlation between the DEPDC5 rs1012068 polymorphism and the risk of HBV-related hepatocellular carcinoma.

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.

Oxidative Stress-Related Gene Polymorphisms Are Associated With Hepatitis B Virus-Induced Liver Disease in the Northern Chinese Han Population.

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. We enrolled 3,128 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. 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 susceptibility of HBV-induced liver disease 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 HBV-induced liver disease. 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. Oxidative stress-related gene polymorphisms are likely to be associated with HBV-induced liver disease, suggesting that information on these variations is useful for risk assessment of HBV-induced liver disease.

eRF3b-37 inhibits the TGF-ß1-induced activation of hepatic stellate cells by regulating cell proliferation, G0/G1 arrest, apoptosis and migration.

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, matrix­assisted laser desorption/ionization time­of­flight mass spectrometry (MALDI­TOF MS) was employed to identify potential serum markers for liver cirrhosis, such as eukaryotic peptide chain releasing factor 3b polypeptide (eRF3b­37), which was initially confirmed by our group to serve a protective role in liver tissues in a C­C motif chemokine ligand 4­induced liver cirrhosis mouse model. Therefore, eRF3b­37 was hypothesized to affect the activation state of HSCs, which was determined by the expression of pro­fibrogenic associated factors in HSCs. In the present study, peptide synthesis technology was employed to elucidate the role of eRF3b­37 in the expression of pro­fibrogenic factors induced by transforming growth factor­ß1 (TGF­ß1) in LX­2 cells that were treated with either control, TGF­ß1 and TGF­ß1+eRF3b­37. 3­(4,5­Dimethyl­2­thiazolyl)­2,5­diphenyltetrazolium bromide and flow cytometric assays, and fluorescent microscope examinations were performed to evaluate the effects of eRF3b­37 on proliferation viability, G0/G1 arrest, apoptosis and cell migration. The results of the present study indicated that eRF3b­37 inhibited the activation of HSCs. The increased mRNA and protein expression of the pro­fibrogenic factors collagen I, connective tissue growth factor and α­smooth muscle actin (SMA) stimulated by TGF­ß1 were reduced by eRF3b­37 via the following mechanisms: i) Inhibiting LX­2 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 kinase­4, and upregulating the levels of P21; ii) increasing cell apoptosis by upregulating the mRNA level of B­cell lymphoma-2 (Bcl­2)­associated X protein (Bax) and Fas, and downregulating the expression of Bcl­2; and iii) reducing cell migration by downregulating the mRNA and protein expression of α­SMA. In addition, eRF3b­37 is thought to serve a role in HSCs by inhibiting TGF­ß signaling. Therefore, eRF3b­37 may be a novel therapeutic agent for targeting HSCs for hepatic fibrosis.

Decreased frequency of circulating Th9 cells in patients with chronic hepatitis B infection.

BACKGROUND: Chronic hepatitis B (CHB) is one of the major infectious diseases in which CD4+ T helper (Th) cells play a crucial role. Th9 cells are a distinct subset of CD4+ Th cells with important physiological functions. OBJECTIVE: The study aimed to assess the potential involvement of Th9 cells in the inadequate immune response leading to chronic HBV infection. PATIENTS AND METHODS: Peripheral blood samples were collected from 22 CHB patients and 16 healthy controls (HC). The frequencies of circulating Th9, Tc9, Th1, and Tc1 cells were determined by flow cytometry. Serum levels of IL-9 and IL-10 were analyzed by ELISA. Serum biochemical indices of liver function were measured using an automated analyzers. Serum HBV DNA loads were analyzed by real-time PCR. The potential association of the frequency of Th9, Tc9, Th1 or Tc1 cells with clinical parameters was assessed. RESULTS: The frequency of circulating Th9 cells was significantly lower in CHB patients than those in HC. However, no significant differences in the frequency of Tc9, Th1 or Tc1 cells were observed between the two groups. The percentages of Th9 cells, but not Tc9 cells, were negatively correlated with HBV DNA loads, whereas the percentages of Tc1 cells were positively correlated with viral loads in CHB patients. Moreover, there was a positive correlation between serum levels of IL-9 and IL-10 and HBV DNA loads in patients with chronic HBV infection. CONCLUSION: The depletion of Th9 cells is associated with the development of chronic HBV infection.

Obesity as a Risk Factor for Low Back Pain: A Meta-Analysis.

STUDY DESIGN: A meta-analysis. OBJECTIVE: 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. SUMMARY OF BACKGROUND DATA: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 OF EVIDENCE: Level 1.

Comprehensive investigating of cytokine and receptor related genes variants in patients with chronic hepatitis B virus infection.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Comprehensive investigation of cytokine- and immune-related gene variants in HBV-associated hepatocellular carcinoma patients.

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 P<0.0001, Fisher's exact test) and 11 genes (adjusted P<0.0001, optimal unified approach for rare variant association test (SKAT-O) gene level test) were strongly associated with HBV-HCC. Thirty-four variants were from eight human leukocyte antigen (HLA) genes that were previously reported to be associated with HBV-HCC. The novelties of our study are: five variants (rs579876, rs579877, rs368692979, NM_145007:c.*131_*130delTG, NM_139165:exon5:c.623-2->TT) 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.

Association between PNPLA3 gene polymorphisms and risk of hepatitis B virus-related hepatocellular carcinoma in Han population in China:a case-control study.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our study suggested that PNPLA3 loci (rs2294918, rs2294919) were associated with HBV-related HCC in Han Chinese.

Identification of candidate substrates of ubiquitin-specific protease 13 using 2D-DIGE.

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-ß-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.

Prevalence of abdominal obesity among Chinese adults in 2011.

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.

Serum folate, vitamin B12 levels and diabetic peripheral neuropathy in type 2 diabetes: A meta-analysis.

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.