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孟德尔随机化研究溃疡性结肠炎与甲状腺功能减退发生风险的因果关系

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实用医学杂志 2024年第6期40卷 827-832页

作者：花胤王晓燕王振辛永宁刘守胜南京医科大学青岛临床医学院(青岛市市立医院) 山东青岛266011 青岛市市立医院国际门诊山东青岛266011 青岛市市立医院感染性疾病科山东青岛266011 青岛市市立医院临床研究中心山东青岛266011

目的运用两样本孟德尔随机化(two sample mendelian randomization, TSMR)评估溃疡性结肠炎(ulcerative colitis, UC)与甲状腺功能减退(hypothyroidism, HT)之间的双向因果关系。方法 UC与HT相关的单核苷酸多态性位点(single nucleotide polymorphism, SNP)数据分别来自芬兰生物银行和IEU数据库,提取出与UC强相关的独立SNP作为工具变量,采用逆方差加权法(inverse variance weighted,IVW)、Egger回归法(MR-Egger)、中位数加权法(weighted median)评估UC与HT之间的因果关联,同时采用MR-PRESSO评估水平多效性及离群的SNP,Cochran′s Q检测及漏斗图(funnel test)评估SNPs中的异质性,留一法分析(leave one out)是否存在单个SNP能够影响因果评估的结果。结果筛选出4个与UC强相关关联的工具变量,IVW法提示UC和HT之间存在因果关系(OR=0.975,95%CI:0.924~0.990,P=0.011),Cochran Q检验Q=2.566,P=0.463,提示SNP之间不存在异质性。MR-Egger法(P=0.523)和MR-PRESSO法(P=0.548)均提示不存在水平多效性,反向TSMR的结果不支持反向因果关系。结论 TSMR发现UC与HT之间存在负向因果关系。

关键词：溃疡性结肠炎甲状腺功能减退孟德尔随机化

HBV cccDNA:The Stumbling Block for Treatment of HBV Infection

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Journal of Clinical and Translational Hepatology 2019年第3期7卷 195-196页

作者： shousheng liu Yongning Xin Central Laboratories Qingdao Municipal HospitalQingdaoChina Department of Infectious Disease Qingdao Municipal HospitalQingdaoShandong 266011China

Hepatitis B virus(HBV)infection leads to severe liver disease and is one of the main causes of hepatocellular carcinomarelated *** the prevalence of HBV infection has decreased markedly with the effective application of vaccines,it's still an arduous task to clear the hepatitis B surface antigen after routine antiviral therapy,as the viral rebound often occurs after therapy ***,the situation of dealing with HBV infection is still *** such,eliminating HBV infection has become an important task for governments all over the *** 2016,the Global Health Sector Strategy on Viral Hepatitis was approved by the World Health Assembly to eliminate the HBV infection by 2030.

关键词： routine infection markedly

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

Administration of Yeast Glucan on Immunity of Offspring in Turbot Scophthalmus maximus: A Trans-Generational Immune-Enhancing Effect

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Journal of Ocean University of China 2019年第4期18卷 997-1003页

作者： JIANG Chengyan WANG Peng liu shousheng WANG Yanfeng LI Jun JI Guangdong College of Life Science and Technology Hong He University Mengzi 661100 China Laboratory for Evolution & Development Institute of Evolution & Marine Biodiversity and Department of Marine Biology Ocean University of China Qingdao 266003 China Center of Biotechnology R&D Institute of Oceanology Chinese Academy of Sciences Qingdao 266071 China

β-glucan has been shown to increase immunity and survival in various juvenile and adult fish both in freshwater and marine aquaculture species as well as in marine fish larvae. However, information about the trans-generational immune-enhancing effects of β-glucan remains rather limited. Here we clearly show that dietary intake of β-glucan enhanced the levels of C3, Bf and lysozyme in the serum of turbot as well as in their eggs released. We also show that yeast glucan induced a significant increase in lysozyme activity in both the serum and eggs. Moreover, the embryos derived from yeast glucan-treated turbot were more resistant to bacterial challenge than control embryos. By contrast, the administration of yeast glucan on female turbots had little influence on the egg development and embryonic development. Collectively, these data indicate that yeast glucan can be safely used to promote the non-specific trans-generational immunity in offspring of turbot.

关键词： turbot Scophthalmus glucan trans-generational immunity

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

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

Association of GCKR Gene Polymorphisms with the Risk of Nonalcoholic Fatty Liver Disease and Coronary Artery Disease in a Chinese Northern Han Population

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Journal of Clinical and Translational Hepatology 2019年第4期7卷 297-303页

作者： Hui Gao shousheng liu Zhenzhen Zhao Xinjuan Yu Qun liu Yongning Xin Shiying Xuan Department of Infectious Disease Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Central Laboratories Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Department of Gastroenterology Qingdao Municipal HospitalQingdao UniversityQingdaoShandongChina Digestive Disease Key Laboratory of Qingdao QingdaoShandongChina

Background and Aims: Accumulated studies have eval-uated the effects of glucokinase regulatory protein(GCKR)gene polymorphisms on the risk of nonalcoholic fatty liver disease(NAFLD)and coronary artery disease(CAD),but the association of GCKR polymorphisms with the risk of NAFLD and CAD in the Chinese Han population have remained *** aim of this study was to investigate the association between GCKR gene polymorphisms(rs780094 and rs1260326)and the risk of NAFLD and CAD in NAFLD patients in a Chinese Northern Han ***: GCKR rs780094 and rs1260326 gene polymorphisms were geno-typed by polymerase chain reaction sequencing for B-type ultrasonography-proven NAFLD patients with(n = 82)or without(n = 142)CAD,and in healthy controls(n = 152).Serum lipid profiles'levels were determined using biochemi-cal *** analyses were conducted using SPSS 22.0 statistical ***: As the results showed,sig-nificant differences in the serum lipid profiles existed between each *** significant differences were observed in the distributions of genotypes and alleles of GCKR rs780094 and rs1260326 in each *** GCKR rs780094 T and rs1260326 T allele carriers possessed decreased body mass index value,and serum fasting plasma glucose and TG levels in the overall subjects,*** addition,the GCKR rs780094 T allele carriers possessed decreased serum fasting plasma glucose level in the controls and NAFLD+CAD ***: GCKR rs780094 and rs1260326 poly-morphisms were found to be not associated with the risk of NAFLD nor of CAD in NAFLD patients in this Chinese Northern Han *** rs780094 T and rs1260326 T alleles could affect the body mass index value and serum fasting plasma glucose and triglyceride levels.

关键词： Non-alcoholic fatty liver disease Glucokinase regulatory protein gene Polymorphism Coronary artery disease