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Role of ALDH2 in Hepatic Disorders: Gene Polymorphism and Disease Pathogenesis

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 90-98页

作者： Qiaoling Wang Binxia Chang Xiaoyan Li zhengsheng zou Peking University 302 Clinical Medical SchoolBeijingChina Diagnosis and Treatment Center for Non-Infectious Liver Diseases Fifth Medical Center of Chinese PLA General HospitalBeijingChina Anhui Medical University HefeiAnhuiChina

Aldehyde dehydrogenase 2(ALDH2)is a key enzyme of alcohol metabolism and it is involved in the cellular mechanism of alcohol liver ***2 gene mutations exist in about 8%of the world’s population,with the incidence reaching 45%in East *** mutations will result in impairment of enzyme activity and accumulation of acetaldehyde,facilitating the progression of other liver diseases,including non-alcoholic fatty liver diseases,viral hepatitis and hepatocellular carcinoma,through adduct formation and inflammatory *** this review,we seek to summarize recent research progress on the correlation between ALDH2 gene polymorphism and multiple liver diseases,with an attempt to provide clues for better understanding of the disease mechanism and for strategy making.

关键词： Aldehyde dehydrogenase 2 Gene polymorphisms Alcoholic liver disease Non-alcoholic fatty liver disease Viral hepatitis Hepatocellular carcinoma

Study on the Deformation Mechanism of a Soft Rock Tunnel

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Fluid Dynamics & Materials Processing 2022年第2期18卷 243-255页

作者： Jianhui Yang Kai Shen Shoudong Pan Shuren Wang zhengsheng zou School of Civil Engineering and Architecture Zhejiang University of Science and TechnologyHangzhou310023China China Railway 16 Bureau Group Co. Ltd.Beijing100018China School of Civil Engineering Henan Polytechnic UniversityJiaozuo454003China

The large deformation of soft rock tunnel is one of the key problems to be overcome in the tunnel construction *** the present study,the deformation mechanism of a representative tunnel and some related countermeasures are investigated using field tests and engineering geological *** to the scarce performances of methods based on other criteria such as small pipe spacing,anchor bolt length and steel frame spacing,a new support scheme is implemented and *** show that shear failure and bedding sliding are produced under high horizontal stress *** low strength of the surrounding rock results in the uneven convergence of both sides of the *** the aforementioned new support scheme,however,most of such problems can be mitigated leading to good stability properties and ensuing economic advantages.

关键词： Soft rock tunnel high stress deformation mechanism supporting countermeasure

终末期肝病食谱APP改善肝硬化患者并发营养不良及衰弱的研究

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胃肠病学和肝病学杂志 2024年第3期33卷 265-271页

作者：杨萍王晶宁会赵雅娟邹正升内蒙古科技大学包头医学院第二附属医院消化科内蒙古包头014000 中国人民解放军总医院第五医学中心非感染性肝病诊疗与研究中心

目的探讨终末期肝病食谱应用程序(end-stage liver disease recipe application,ESLDR APP)对肝硬化患者并发营养不良及衰弱的治疗效果。方法选取2022年3月至2022年8月在内蒙古科技大学包头医学院第二附属医院住院的60例肝硬化并发营养... 详细信息

目的探讨终末期肝病食谱应用程序(end-stage liver disease recipe application,ESLDR APP)对肝硬化患者并发营养不良及衰弱的治疗效果。方法选取2022年3月至2022年8月在内蒙古科技大学包头医学院第二附属医院住院的60例肝硬化并发营养不良及衰弱患者,通过ESLDR APP为上述患者提供3个周期的治疗(每30 d为1个治疗周期),于每个周期结束到院复查,以排除依从性较差的患者,并检查有无食物过敏或出现其他并发症。比较患者使用ESLDR APP治疗3个周期前后的BMI、上臂围(arm circumference,AC)、三头肌皮褶厚度(triceps skin-fold thickness,TSF)及上臂肌围(arm muscle circumference,AMC)的差异,总蛋白、白蛋白、胆碱酯酶及胆汁酸的差异,优势手握力的差异,衰弱表型评估(frailty phenotype,FP)结果的差异。并于3个治疗周期结束后通过调查问卷的形式收集上述患者对ESLDR APP的评价。结果最终共入组53例患者,男28例,女25例。患者使用ESLDR APP治疗3个周期前后BMI、AC、TSF、AMC、总蛋白、白蛋白及胆碱酯酶水平均显著升高,胆汁酸水平、FP结果显著降低,差异均有统计学意义(P均0.05);说明达到了一定程度的干预效果。通过调查问卷方式收集53例肝硬化患者对ESLDR APP的评价,37例(69.81%)认为本APP对改善营养不良及衰弱非常有效;10例(18.87%)认为一般有效;6例(11.32%)认为无效。结论ESLDR APP通过为患者制定科学营养的食谱,达到了改善肝硬化并发营养不良及衰弱的目的,提升了蛋白水平及营养状况,使患者受益。

关键词：肝硬化营养不良衰弱

Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injury Issued by China Food and Drug Administration

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Acta Pharmaceutica Sinica B 2019年第3期9卷 648-658页

作者： Xiaohe Xiao Jianyuan Tang Yimin Mao Xiuhui Li Jiabo Wang Chenghai Liu Kewei Sun Yong’an Ye zhengsheng zou Cheng Peng Ling Yang Yuming Guo Zhaofang Bai Tingting He Jing Jing Fengyi Li Na An China Military Institute of Chinese Medicine Beijing302Hospital of ChinaBeijing100039China Center for Drug Evaluation China Food and Drug AdministrationBeijing100022China Renji Hospital of Shanghai Jiaotong University Shanghai200127China Beijing Youan Hospital of Capital Medical University Beijing100069China Shuguang Hospital of Shanghai University of Traditional Chinese Medicine Shanghai200127China First Affiliated Hospital of Hunan University of Traditional Chinese Medicine Changsha410007China Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine Beijing100700China Center for Non-infectious Liver Diseases Beijing302Hospital of ChinaBeijing100039China College of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu610075China College of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai201203China Center for Infectious Liver Diseases Beijing302Hospital of ChinaBeijing100039China

1. Introduction Drug-induced liver injury (DILI), defined as liver injury caused by a drug and/or its metabolites, is a common clinical adverse drug reaction1–4. This type of injury can cause acute liver failure and ... 详细信息

关键词： TCM PTA Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injury Issued by China Food and Drug Administration China

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酒精性肝炎临床诊断的再思考

临床肝胆病杂志 2019年第3期35卷 476-477页

作者：邹正升解放军总医院第五医学中心非感染性肝病诊疗与研究中心北京100039

根据酒精性肝炎(AH)和重症AH的概念、临床特征、预后等的明显差异,建议将AH明确区分为轻症AH和重症AH。住院的酒精性肝病(ALD)患者的疾病谱,肝硬化占绝大多数,同时轻症AH和重症AH共占比15%左右。重症AH包含酒精性肝衰竭;重症AH是临床诊... 详细信息

根据酒精性肝炎(AH)和重症AH的概念、临床特征、预后等的明显差异,建议将AH明确区分为轻症AH和重症AH。住院的酒精性肝病(ALD)患者的疾病谱,肝硬化占绝大多数,同时轻症AH和重症AH共占比15%左右。重症AH包含酒精性肝衰竭;重症AH是临床诊断,而酒精性脂肪性肝炎是病理诊断。重症AH欧美国家的临床诊断标准趋于一致,而2018年中国指南与欧美国家不一致。

关键词：肝炎,酒精性诊断

Increased IL-22-producing cells contribute to the progression of liver fibrosis in hepatitis B virus infection

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Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb,Polygonum multiflorum

第八届全国免疫学学术大会

作者： Zheng Zhang Juanjuan Zhao zhengsheng zou Fu-Sheng Wang Institute of Translational Hepatology Research Center for Biological Therapy Beijing 302 Hospital

背景:Interleukin(IL)-22 has been found to be up-regulated in the liver in patients with chronic hepatitis B and C virus infection.目的:The present study aims to identify the characteristics of IL-22 and its correlation with liver fibrosis in HBV-infected subjects.方法:Intrahepatic and peripheral IL-22-producing cells were comprehensively investigated in 50 patients with chronic hepatitis B(CHB) and 27 patients with liver cirrhosis, as well as 30 healthy *** impacts on liver fibrosis were analyzed in vitro assays.结果:IL-22 was mainly produced by CD4 T cells in peripheral blood, but its production shifted to innate immune cells in livers of enrolled *** particular, IL-22 was preferentially produced by intrahepatic NK and γδ T cells and IL-22+IL-17a+IFN-γ- Th17 cells in LC patients, compared with CHB patients and HC subjects, and was positively associated with liver fibrosis severity in CHB *** importantly, high levels of IL-22 R expression were identified on human *** vitro IL-22 exposure largely activated HSCs, as indicated by increased p STAT3 expression and fibrotic protein production, and also prevented soluble TRAILmediated HSC apoptosis through reducing caspase 3 activity and increasing bcl-2 *** examine the essential role of the cytokine, a T cell-mediated liver fibrosis model was established, and blockade of IL-22 in HBV-transgenic mice with liver fibrosis induced by activated T cells significantly reduced α-SMA expression and restricted liver fibrosis progression.结论:IL-22-producing cells were enriched in the livers, preferentially in the activated hepatic stellate cells and may prevent their apoptosis in situ in HBV-infected *** findings may facilitate the rational development of immunotherapeutic strategies targeting IL-22 for the blockade of liver fibrosis.

关键词： IL-22 liver fibrosis HBV hepatic stellate cell

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Frontiers of Medicine 2021年第2期15卷 330-332页

作者： Chunyu Li Ming Niu Zhaofang Bai Congen Zhang Yanling Zhao Ruiyu Li Can Tu Huifang Li Jing Jing Yakun Meng Zhijie Ma Wuwen Feng Jinfa Tang Yun Zhu Jinjie Li Xiaoya Shang zhengsheng zou Xiaohe Xiao Jiabo Wang China Military Institute of Chinese Medicine 302 Military HospitalBeijing 100039China Institute of Medicinal Plant Development Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China Integrative Medical Center 302 Military HospitalBeijing 100039China Beijing Friendship Hospital Capital Medical UniversityBeijing 100050China Diagnosis and Treatment Center for Non-infectious Diseases 302 Military HospitalBeijing 100039China Beijing Union University Beijing 100101China Shanxi University of Traditional Chinese Medicine Taiyuan 030619China

Erratum to Frontiers of Medicine 201711(2):253–265 https://***/10.1007/s11684-017-0508-9 The original version of this article unfortunately contained some *** panel of“LPS–/drug–”in Fig.3B(Page 259),the panels of“LPS–/EtoAc+”and“LPS–/Residue+”in Supplementary Fig.3(Page 7 in the online supplementary materials)should be *** authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.

关键词： Medicine hepato corrected

Evidence chain-based causality identification in herb-induced liver injury： exemplification of a well-known liver-restorative herb Polygonum multiflorum

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Frontiers of Medicine 2015年第4期9卷 457-467页

作者： Jiabo Wang Zhijie Ma Ming Niu Yun Zhu Qingsheng Liang Yanling Zhao Jingyuan Song Zhaofang Bai Yaming Zhang Ping Zhang Na Li Yakun Meng Qi Li Lushan Qin Guangju Teng Junling Cao Baosen Li Shilin Chen Yonggang Li zhengsheng zou Honghao Zhou Xiaohe Xiao China Military Institute of Chinese Medicine 302 Military Hospital Beijing 100039 China Beijing Friendship Hospital Capital Medical University Beijing 100050 China Diagnosis and Treatment Center for Non-infectious Diseases 302 Military Hospital Beijing 100039 China Institate of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100193 China Integrative Medical Center 302 Military Hospital Beijing 100039 China Dongzhimen Hospital Beijing University of Chinese Medicine Beijing 100700 China Diagnosis and Treatment Center of Western and Chinese Medicine for Liver Diseases 302 Military Hospital Beijing 100039 China Institute of Clinical Pharmacology Central South University Changsha 410008 China

Herbal medicines have recently been recognized as the second most common cause of drug-induced liver injury （DILI） in the United States. However, reliable methods to identify the DILl causality of some herbs, such as Heshouwu （dried root ofPolygonum multiflorum）, remain lacking. In this study, a total of 12 307 inpatients with liver dysfunction and 147 literature-reported cases of Heshouwu DILI were screened. A general algorithm indicated that only 22.5% （9/40） and 30.6% （45/147） of all hospitalization and literature case reports, respectively, demonstrate the high probability of DILI causality of Heshouwu. By contrast, 95% （19/20） of all cases prospectively investigated by pharmacognosy, phytochemistry, and metabolomic tests exhibited highly probable causality, including a patient who was previously incorrectly attributed and a case that was excluded from Heshouwu causality by pharmacognostic evidence. Toxin （heavy metals, pesticides, and mycotoxins） contamination was also excluded from Heshouwu DILI causality. The objectivity of these screening methods for Heshouwu DILI diagnosis addresses safety concerns regarding stilbene-containing herbal medicines and dietary supplements.

关键词： Polygonum multiflorum Chinese herbal medicine drug-induced liver injury pharmacognosy metabolomics stilbene

细胞色素P450基因多态性与药物性肝损伤的关系

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临床肝胆病杂志 2020年第5期36卷 1150-1153页

作者：王巧玲邹正升北京大学医学部北京100071 解放军总医院第五医学中心非感染性肝病诊疗与研究中心北京100039

随着药物性肝损伤患病率的逐年上升,药物性肝损伤发病机制成为了关注的焦点。CYP450酶作为一个庞大的家族,参与了药物在人体肝脏内的几乎所有氧化代谢反应。近年来发现CYP450酶的基因多态性导致了药效动力学在不同个体中的代谢差异性,... 详细信息

随着药物性肝损伤患病率的逐年上升,药物性肝损伤发病机制成为了关注的焦点。CYP450酶作为一个庞大的家族,参与了药物在人体肝脏内的几乎所有氧化代谢反应。近年来发现CYP450酶的基因多态性导致了药效动力学在不同个体中的代谢差异性,故探索CYP450酶基因多态性在药物性肝损伤中的作用,可促进对药物性肝损伤发病机制的了解。对已发现与药物性肝损伤相关的CYP450酶基因多态性进行综述。

关键词：细胞色素P450酶系统多态现象,遗传化学性与药物性肝损伤