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Association of TCF7L2 rs7903146 Gene Polymorphism with the Risk of NAFLD and CAD in the Chinese Han Population

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Journal of Clinical and Translational Hepatology 2020年第4期8卷 371-376页

作者： xin Yan Wenwen Jin Jie Zhang Mengke Wang Shousheng Liu yongning xin Department of Infectious Disease Qingdao Municipal HospitalQingdaoShandongChina Clinical Research Center Qingdao Municipal HospitalQingdaoShandongChina Digestive Disease Key Laboratory of Qingdao QingdaoShandongChina Dalian Medical University DalianLiaoningChina

Background and Aims:Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that TCF7L2 rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association be-tween TCF7L2 rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population. Methods: TCF7L2 rs7903146 genotypes were measured by the MALDI-TOF-MS from 143 NAFLD patients, 159 CAD patients, 131 NAFLD+ CAD patients, and 212 healthy controls. The demographic data and serum lipid profiles of all subjects were collected. The distributions of genotype and allele frequency in each group were also tested. Logistic regression was used to inves-tigate the risk of TCF7L2 rs7903146 with NAFLD and CAD. All statistical analyses were conducted using SPSS 23.0. Results: There were no significant differences in the distri-butions of TCF7L2 rs7903146 genotype and allele frequency in each of the two groups, and the TCF7L2 rs7903146 CT+TT genotype did not increase the risk of developing NAFLD, CAD, and NAFLD+CAD. Except for body mass index in the control group, the differences of clinical parameters between the TCF7L2 rs7903146 T allele carriers and non-carriers in each group were not significant. In the non-obese group, the TCF7L2 rs7903146 CT+TT genotype was a protective factor for the development of NAFLD in the non-obese subjects (odds ratio=0.359, 95% confidence interval: 0.134-0.961, p = 0.041). Conclusions: TCF7L2 rs7903146 was not associated with the risk of developing NAFLD, CAD, and NAFLD + CAD in the Chinese Han population. In the non-obese population, the TCF7L2 rs7903146 CT + TT genotype was a protective factor against the development of NAFLD.

关键词： Nonalcoholic fatty liver disease Coronary artery disease TCF7L2 Single nucleotide polymorphism

TM6SF2 E167K Variant Overexpression Promotes Expression of Inflammatory Cytokines in the HCC Cell Line HEPA 1-6

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Journal of Clinical and Translational Hepatology 2019年第1期7卷 27-31页

作者： Shuixian Du Songling Liao Shousheng Liu yongning xin Department of Infectious Disease Qingdao Municipal HospitalQingdaoChina Department of Gastroenterology Dalian Medical UniversityDalianChina Central Laboratories Qingdao Municipal HospitalQingdaoChina Department of Gastroenterology Qingdao Municipal HospitalQingdaoChina Digestive Disease Key Laboratory of Qingdao QingdaoChina

Background and Aims:Accumulated evidence has shown that chronic liver inflammation is one of the main risks of hepatocellular carcinoma(HCC),and E167K variant of the transmembrane 6 superfamily member 2(TM6SF2)plays an important role in the progression of chronic liver diseases and *** aim of this study was to explore effects of the TM6SF2 E167K variant on expression of the inflammatory cytokines TNF-cα,IL-2,IL-6 and IL-8 in the HCC cell line HEPA ***:HEPA 1-6 cells were infected with lentivirus containing either the TM6SF2 E167K variant or TM6SF2 wildtype,or control *** real-time polymerase chain reaction(qRT-PCR)and western blotting were conducted to analyze the expression of the inflammatory cytokines TNF-α,IL-2,IL-6 and IL-8.A t-test was used for statistical ***:Compared with the control group and TM6SF2 overexpression group,the relative expression of IL-2 and IL-6 mRNAs were significantly elevated in the TM6SF2 E167K overexpression group(p<0.05).The relative mRNA expression of IL-8 in theTM6SF2 and TM6SF2 E167K overexpression groups were increased compared to the control group(p<0.05).No obvious differences were observed for the expression of TNF-αin each *** expression of TNF-α,IL-2,IL-6 and IL-8 that was tested by western blotting showed the same trends as the qRT-PCR ***:In conclusion,the E167K variant of theTM6SF2 gene could promote the expression of inflammatory cytokines IL-2 and IL-6 in HEPA 1-6 cells,suggesting that the TM6SF2 E167K variant may accelerate the progression of HCC.

关键词： Hepatocellular carcinoma TM6SF2 E167K variant Inflammatory

The Genetics of Clinical Liver Diseases: Insight into the TM6SF2 E167K Variant

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Journal of Clinical and Translational Hepatology 2018年第3期6卷 326-331页

作者： Xiaoyu Zhang Shousheng Liu Quanjiang Dong yongning xin Shiying Xuan Department of Gastroenterology Taishan Medical UniversityTaianChina Department of Infectious Disease Qingdao Municipal HospitalQingdaoChina Department of Gastroenterology Qingdao Municipal HospitalQingdaoChina Digestive Disease Key Laboratory of Qingdao QingdaoChina Central Laboratories Qingdao Municipal HospitalQingdaoChina

The transmembrane 6 superfamily member 2(TM6SF2)gene E167K variant(rs58542926)was identified by exome-wide as-sociation study as a nonsynonymous single nucleotide poly-morphism associated with nonalcoholic fatty liver *** TM6SF2 E167K variant features a C-to-T substitution at nucleotide 499,encoding a glutamate with lysine change at codon 167(E167K).TM6SF2 is markedly expressed in the liver,small intestine and kidney,and has been proposed as an im-portant risk factor for diseases associated with lipid ***,multifunctional studies of the TM6SF2 E167K variant have been carried out in a spectrum of liver dis-eases,such as nonalcoholic fatty liver disease,nonalcoholic steatohepatitis,fibrosis,cirrhosis,and viral *** re-view summarizes the research status of the TM6SF2 E167K variant in different liver diseases and specific populations,and discusses the potential mechanisms of the TM6SF2 E167K var-iant's role in the progression of various liver diseases.

关键词： TM6SF2 SNP NAFLD Fibrosis Cirrhosis Virus hepatitis

Systematic Review and Meta-analysis of Circulating Fetuin-A Levels in Nonalcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 3-14页

作者： Shousheng Liu Jianhan Xiao Zhenzhen Zhao Mengke Wang Yifen Wang yongning xin Clinical Research Center Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Digestive Disease Key Laboratory of Qingdao QingdaoShandongChina Department of Infectious Disease Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina

Background and Aims:Accumulated studies have reported the key role of circulating fetuin-A in the development and progression of nonalcoholic fatty liver disease(NAFLD)but the results have not been *** this study,we performed a systematic review and meta-analysis to explore the relationship between circulating fetuin-A level and the development and classification of ***:The PubMed,EMBASE,and Cochrane Library databases were searched to obtain the potentially relevant studies up to May *** mean differences(SMD)and 95%confidence intervals of circulating fetuin-A levels were extracted and ***,subgroup analysis and meta-regression analysis were performed to investigate the potential *** of circulating fetuin-A level with classification of NAFLD was also ***:A total of 17 studies were included,composed of 1,755 NAFLD patients and 2,010 healthy ***-analysis results showed that NAFLD patients had higher circulating fetuin-A level(SMD=0.43,95%confidence interval[CI]:0.22-0.63,p<0.001)than *** analysis indicated that circulating fetuin-A level was markedly increased in adult NAFLD patients(SMD=0.48,95%CI:0.24-0.72,p<0.001)and not in pediatric/adolescent patients compared to *** fetuin-A level was markedly increased in ultrasound-proven NAFLD pediatric/adolescent patients(SMD=0.42,95%CI:0.12-0.72,p=0.007),other than in the liver biopsy-proven NAFLD pediatric/adolescent *** mass index might be the influencing factor to the heterogeneity in adult *** fetuin-A level was not associated with the classification of NAFL *** steatohepatitis(NASH).Whether the circulating fetuin-A level was associated with the development of fibrosis remains controversial.

关键词： Nonalcoholic fatty liver disease Fetuin-A Meta-analysis Fibrosis

Association of LDLR rs1433099 with the Risk of NAFLD and CVD in Chinese Han Population

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 203-209页

作者： Yi Han Yongshuo Zhang Shousheng Liu Guangxia Chen Linlin Cao yongning xin Department of Infectious Disease Qingdao Municipal HospitalQingdaoShandongChina Department of Gastroenterology The First People’s Hospital of XuzhouXuzhou Municipal Hospital Affiliated to Xuzhou Medical UniversityXuzhouJiangsuChina Administrative Management Office The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsuChina Clinical Research Center Qingdao Municipal HospitalQingdaoShandongChina

Background and Aims:Recent genome-wide association studies have shown that low-density lipoprotein receptor(LDLR)rs1433099 polymorphism is associated with cardiovascular disease(CVD)risk in many ***,the association of LDLR rs1433099 with CVD in China has not been reported *** are no studies on LDLR rs1433099 and non-alcoholic fatty liver disease(NAFLD)as *** purpose of this study was to investigate whether LDLR rs1433099 is related to CVD or NAFLD in the Chinese ***:LDLR rs1433099 polymorphism was genotyped in 507 individuals,including 140 healthy controls,79 NAFLD patients,185 CVD patients,and 103 patients with NAFLD combined with *** expression of LDLR was tested by the sequence detection system,and clinical parameters were assessed by biochemical tests and physical ***:The genotype distribution of LDLR rs1433099 was not statistically different among the NAFLD group,the CVD group,the combined group,and the healthy control group(p>0.05).There was no significant correlation of LDLR rs1433099 genotypic distribution or allele frequency and the risk of NAFLD,CVD or NAFLD combined with CVD(p>0.05).In the CVD group,T allele carriers had higher alkaline phosphatase and gamma-glutamyl transpeptidase than non-carriers(p<0.05).Conclusions:Our study demonstrated that the LDLR rs1433099 polymorphism is not a risk factor of *** LDLR rs1433099 polymorphism may increase the risk of CVD through a mechanism involving alkaline phosphatase and gamma-glutamyl transpeptidase.

关键词： LDLR rs1433099 C44857T CVD NAFLD Gene polymorphism

Antiviral Effects of Stichopus japonicus Acid Mucopolysaccharide on Hepatitis B Virus Transgenic Mice

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Journal of Ocean University of China 2016年第4期15卷 719-725页

作者： xin yongning LI Wei LU Linlin ZHOU Li David W Victor XUAN Shiying Qingdao Municipal Hospital Qingdao 266071 P. R. China Department of Gasteroenterology Qingdao No.6 People's Hospital Qingdao 266033 P. R. China Taiyuan Infectious Diseases Hospital Taiyuan 030000 P. R. China Hepatology & Transplant Medicine Department of Medicine Houston Methodist Hospital Houston USA

Hepatitis B virus(HBV) is a significant global pathogen and efficient cure for HBV patients is still a challenging goal. We previously reported that acidic mucopolysaccharide from stichopus japonicus selenka(SJAMP) could inhibit HBs Ag and HBe Ag expression in vitro. However, the potential anti-HBV effects of SJAMP in vivo have not yet been explored. In this study, we show that SJAMP exhibits potent anti-HBV activity in HBV transgenic mice in a dose-dependent manner. Specifically, sixty HBV transgenic male BALB/c mice were randomly selected to receive the treatment of PBS, low dose SJAMP(30 mg kg^(-1)), middle dose SJAMP(40 mg kg^(-1)), high dose SJAMP(50 mg kg^(-1)) and IFN(45 IU kg^(-1)) for 30 d. SJAMP treatment suppressed serum HBV-DNA, and liver HBs Ag and HBc Ag levels in HBV-transgenic mice. The present study highlights the potential application of SJAMP in HBV therapy.

关键词： Transgenic transgenic pathogen challenging suppressed potent highlights brown manner inhibit

Noninvasive Quantitative Detection Methods of Liver Fat Content in Nonalcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2018年第2期6卷 217-221页

作者： Shujing Lv Sushan Jiang Shousheng Liu Quanjiang Dong yongning xin Shiying Xuan Medical College of Qingdao University QingdaoShandongChina Digestive Disease Key Laboratory of Qingdao QingdaoShandongChina Central Laboratories Qingdao Municipal HospitalQingdaoShandongChina Department of Gastroenterology Qingdao Municipal HospitalQingdaoShandongChina Department of Infectious Disease Qingdao Municipal HospitalQingdaoShandongChina

Nonalcoholic fatty liver disease(NAFLD)ranges from simple steatosis to NAFLD-related liver cirrhosis and is a main cause of chronic liver *** with nonalcoholic steatohe-patitis and fibrosis are at a great risk of the progression to cirrhosis or hepatocellular carcinoma,both of which are tightly associated with liver-related *** biopsy is still the gold standard for the diagnosis of NAFLD,but some defects,such as serious complications,sampling error and variability in histologic evaluation among pathologists,remain ***,noninvasive,repeatable and accurate diagnostic methods are urgently *** is a well-established and lower-cost imaging technique for the diagnosis of hepatic steatosis,especially suitable for population census,but limited by its low sensitivity to diagnose mild steatosis and being highly *** tomography also lacks the sensitivity to detect mild steatosis and small changes in fat content,and presents a potential radiation *** attenuation parameter based on the FibroScan?technology is a promising tool for noninvasive semiquantita-tive assessment of liver fat content,but the accuracy rate de-pends on the operator's expertise and is affected by age,width of the intercostal space,skin capsular distance and body mass *** resonance imaging and magnetic resonance spectroscopy are regarded as the most accurate quantitative methods for measuring liver fat content in clinical practice,especially for longitudinal follow up of NAFLD *** this review,we mainly introduce the current imaging methods that are in use for evaluation of liver fat content and we discuss the advantages and disadvantages of each method.

关键词： Nonalcoholic fatty liver disease Hydrogen-1 magnetic resonance spectroscopy Noninvasive Liver fat content

Serum Resistin Levels in Adult Patients with Nonalcoholic Fatty Liver Disease:A Systematic Review and Meta-analysis

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Journal of Clinical and Translational Hepatology 2021年第4期9卷 484-493页

作者： Dongli Han Jie Chen Shousheng Liu Zengzhi Zhang Zhenzhen Zhao Wenwen Jin yongning xin Department of Infectious Disease Qingdao Municipal HospitalDalian Medical UniversityDalianLiaoningChina Qingdao City Shinan District Centers for Disease Control and Prevention QingdaoShandongChina Clinical Research Center Qingdao Municipal HospitalQingdaoShandongChina Digestive Disease Key Laboratory of Qingdao QingdaoShandongChina

Background and Aims:Previous studies reported that serum resistin levels were remarkably changed in patients with nonalcoholic fatty liver disease(NAFLD)but the conclusions were *** aim of this study was to investigate accurate serum resistin levels in adult patients with ***:A complete literature research was conducted in the PubMed,Embase,and Cochrane Library databases,and all the available studies up to 7 May 2020 were *** pooled standardized mean difference(SMD)values were calculated to investigate the serum resistin levels in patients with NAFLD and healthy ***:A total of 28 studies were included to investigate the serum resistin levels in patients with *** with NAFLD had higher serum resistin levels than controls(SMD=0.522,95%confidence interval[CI]:0.004–1.040,I2=95.9%).Patients with nonalcoholic steatohepatitis(NASH)had lower serum resistin levels than the healthy controls(SMD=−0.44,95%CI:−0.83–0.55,I2=74.5%).In addition,no significant difference of serum resistin levels was observed between patients with NAFL and healthy controls(SMD=−0.34,95%CI:−0.91–0.23,I2=79.6%)and between patients with NAFL and NASH(SMD=0.15,95%CI:−0.06–0.36,I2=0.00%).Furthermore,subgroup and sensitivity analyses suggested that heterogeneity did not affect the results of ***:This meta-analysis investigated the serum resistin levels in adult patients with NAFLD *** with NAFLD had higher serum resistin levels and patients with NASH had lower serum resistin levels than healthy *** resistin could serve as a potential biomarker to predict the development risk of NAFLD.

关键词： Resistin Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Biomarker

Tenofovir Alafenamide Fumarate,Tenofovir Disoproxil Fumarate and Entecavir:Which is the Most Effective Drug for Chronic Hepatitis B?A Systematic Review and Meta-analysis

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 335-344页

作者： Xuefeng Ma Shousheng Liu Mengke Wang Yifen Wang Shuixian Du yongning xin Shiying Xuan Department of Infectious Disease Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Clinical Research Center Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Digestive Disease Key Laboratory of Qingdao QingdaoShandongChina

Background and Aims:The therapeutic effect of tenofovir alafenamide fumarate(TAF),tenofovir disoproxil fumarate(TDF)and entecavir(ETV)on chronic hepatitis B(CHB)patients remains *** aim of this study was to explore the differences in virological responses to TAF,TDF and ETV in patients with ***:Literature searches were conducted of the PubMed,EMBASE,and the Cochrane Library databases to identify randomized controlled trials and observational studies published up to July 21,*** comparisons of virological response between TDF,ETV,and TAF were carried out with pooled odds ratio(OR)***:The virological response in TDF-treated CHB patients was notably superior to that of the ETV-treated CHB patients after 12-weeks[OR=1.12,95%confidence interval(CI):0.89–1.41],24-weeks(OR=1.33,95%CI:1.11–1.61),48-weeks(OR=1.62,95%CI:1.16–2.25),72-weeks(OR=1.43,95%CI:0.78–2.62),and 96-weeks(OR=1.56,95%CI:0.87–2.81)*** significant difference was observed for the virological responses in CHB patients after 48-weeks treatment with TAF or *** virological response in TDF+ETV-treated CHB patients was superior to that of TDF-treated CHB patients after 24-weeks,48-weeks(OR=1.54,95%CI:1.17–2.02),96-weeks,and ***:The virological response in TDF-treated CHB patients was superior to that in ETV-treated CHB patients,but there was no significant difference between TAF and *** addition,the therapeutic effect of TDF+ETV was superior to TDF alone.

关键词： Tenofovir alafenamide Entecavir Tenofovir disoprox Chronic hepatitis B Virological response