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World journal of Hepatology 2017年第7期9卷 385-390页

作者： Kathleen E Corey Samer Gawrieh Andrew S deLemos Hui Zheng Andrew E Scanga jennifer W Haglund jorge Sanchez Christopher j Danford Megan Comerford Krista Bossi Samina Munir Naga Chalasani julia Wattacheril Department of Medicine Gastrointestinal UnitMassachusetts General HospitalHarvard Medical School Department of Medicine Division of GastroenterologyIndiana University School of Medicine Department of Medicine Division of GastroenterologyCarolinas Medical Center Department of Medicine Division of GastroenterologyVanderbilt University School of Medicine Department of Medicine Division of GastroenterologyColumbia University College of Physicians and SurgeonsNew York Presbyterian Hospital

AIM To identify risk factors associated with hepatocellular carcinoma(HCC), describe tumor characteristics and treatments pursed for a cohort of individuals with nonalcoholic steatohepatitis(nash) cirrhosis. METHODS We conducted a retrospective case-control study of a well-characterized cohort of patients among five liver transplant centers with nash cirrhosis with(cases) and without HCC(controls).RESULTS Ninety-four cases and 150 controls were included. Cases were significantly more likely to be male than controls(67% vs 45%, P nash cirrhosis. nash cirrhosis associated HCC in this cohort was characterized by early stage disease at diagnosis and treatment with locoregional therapy and transplant.

关键词： Hepatocellular carcinoma Nonalcoholic fatty liver disease Cirrhosis Gender Ethnicity

ATHYS模型及其在巢湖流域丰乐河水文过程模拟中的应用

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安徽农业大学学报 2014年第6期41卷 1061-1069页

作者：郑珊珊 Perrin j L 储茵马友华 Salles C Tournoud M G 安徽农业大学资源与环境学院合肥230036 Université Montpellier 2. HydroSciences Montpellier(UMR 5569) France

以巢湖典型支流丰乐河流域为例,利用分布式水文模型ATHYS对流域降雨—径流过程进行模拟,以期为丰乐河流域水土保持、防洪、水资源利用和非点源污染防治等提供科学依据。ATHYS模型将流域分为大小相同的空间小单元,以库模型进行产流计算,... 详细信息

以巢湖典型支流丰乐河流域为例,利用分布式水文模型ATHYS对流域降雨—径流过程进行模拟,以期为丰乐河流域水土保持、防洪、水资源利用和非点源污染防治等提供科学依据。ATHYS模型将流域分为大小相同的空间小单元,以库模型进行产流计算,以滞后演算法(lag and route)方法进行汇流计算,并以nash.and Sutcliffe指数作为检验模拟结果的标准,模拟流域出口断面日径流量,初步分析流域径流实测值与模拟值的年际变化。模型模拟结果表明,在率定期和验证期模拟与实测径流量的总nash.and Sutcliffe值(nash值)都可以达到0.80以上,相关系数均可达0.89以上。除了部分峰值和基流,模型能较好地模拟丰乐河的径流过程。模型模拟径流总量的相对误差在率定期为23.1%,验证期为34.6%。流域降雨量、径流量的年内、年际变化均比较明显,径流实测值和模拟值的年际变化也都比较大。综合来看,模型比较适用于所研究流域的日径流模拟。

关键词：降雨径流水文模拟 ATHYS模型丰乐河流域

Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries

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World journal of Hepatology 2015年第9期7卷 1192-1208页

作者： Hilmar K Lückhoff Frederik C Kruger Maritha j Kotze Division of Anatomical Pathology Department of Pathology Faculty of Medicine and Health Sciences Stellenbosch University Gastroenterology Unit Durbanville MediClinic

Heterogeneity in clinical presentation, histological severity, prognosis and therapeutic outcomes characteristic of non-alcoholic fatty liver disease(NAFLD) necessitates the development of scientifically sound classification schemes to assist clinicians in stratifying patients into meaningful prognostic subgroups. The need for replacement of invasive liver biopsies as the standard method whereby NAFLD is diagnosed, graded and staged with biomarkers of histological severity injury led to the development of composite prognostic models as potentially viable surrogate alternatives. In the present article, we review existing scoring systems used to(1) confirm the presence of undiagnosed hepatosteatosis;(2) distinguish between simple steatosis and nash; and(3) predict advanced hepatic fibrosis, with particular emphasis on the role of NAFLD as an independent cardio-metabolic risk factor. In addition, the incorporation of functional genomic markers and application of emerging imaging technologies are discussed as a means to improve the diagnostic accuracy and predictive performance of promising composite models found to be most appropriate for widespread clinical adoption.

关键词： Liver biopsy Genomics Steatohepatitis Non-invasive biomarkers Histological severity Nonalcoholicfatty liver disease

Effect of Vitamin E and Alpha Lipoic Acid in Nonalcoholic Fatty Liver Disease: A Randomized, Placebo-Controlled, Open-Label, Prospective Clinical Trial (VAIN Trial)

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Open journal of Gastroenterology 2014年第5期4卷 199-207页

作者： Patrick P. Basu Niraj j. Shah Mark M. Aloysius Robert S. Brown jr. Columbia University College of Physicians and Surgeons New York USA james j. Peters VA Medical Center Mount Sinai School of Medicine New York USA King’s County Hospital New York USA

Objective: Antioxidants, including alpha lipoic acid (ALA) and vitamin E, are efficacious for the treatment of nonalcoholic fatty liver disease (NAFLD). The objective was to evaluate the effects of ALA and vitamin E alone or combined as therapy for patients with NAFLD and nonalcoholic steatohepatitis (nash). Design: Placebo-controlled, open-label, prospective study in which patients with NAFLD and nash were randomized to treatment with ALA 300 mg (n = 40), vitamin E 700 IU (n = 40), ALA 300 mg plus vitamin E 700 IU (n = 40), or placebo (n = 35) daily for 6 months. Body mass index, homeostasis model assessment scores, fibrosis and steatosis markers, and diagnostic laboratory tests were assessed at baseline and at the end of the study. Results: Treatment with ALA and vitamin E alone or in combination, improved inflammatory cytokine levels, steatosis scores, homeostasis model assessment scores, and triglyceride levels after 6 months relative to baseline. Conclusion: Alpha lipoic acid and vitamin E, either alone or in combination, were effective treatments for patients with NAFLD and nash.

关键词： Antioxidant Liver Disease Vitamin E Alphalipoic Acid

Herbal drug discovery for the treatment of nonalcoholic fatty liver disease

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Acta Pharmaceutica Sinica B 2020年第1期10卷 3-18页

作者： Tingting Yan Nana Yan Ping Wang Yangliu Xia Haiping Hao Guangji Wang Frank jGonzalez Laboratory of Metabolism Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA State Key Laboratory of Natural Medicines Key Laboratory of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai 201203China School of Life Science and Medicine Dalian University of TechnologyPanjin 124221China

Few medications are available for meeting the increasing disease burden of nonalcoholic fatty liver disease(NAFLD)and its progressive stage,nonalcoholic steatohepatitis(nash).Traditional herbal medicines(THM)have been used for centuries to treat indigenous people with various symptoms but without clarified modern-defined disease types and *** modern times,NAFLD was defined as a common chronic disease leading to more studies to understand NAFLD/nash pathology and *** have garnered increased attention for providing therapeutic candidates for treating *** this review,a new model called"multiple organs-multiple hits"is proposed to explain mechanisms of nash *** this proposed model,the effects and mechanisms of the frequentlystudied THM-yielded single anti-NAFLD drug candidates and multiple herb medicines are reviewed,among which silymarin and berberine are already under ***-sanctioned phase 4 clinical ***,experimental designs for anti-NAFLD drug discovery from THM in treating NAFLD are *** opportunities and challenges of reverse pharmacology and reverse pharmacokinetic concepts-guided strategies for THM modernization and its global recognition to treat NAFLD are *** mechanistic evidence is being generated to support the beneficial role of THM in treating NAFLD and anti-NAFLD drug discovery.

关键词： Natural products Fatty liver Metabolic syndrome TCM NAFLD

An Automatic Optimization Technique for the Calibration of a Physically Based Hydrological Rainfall-Runoff Model

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journal of Geoscience and Environment Protection 2021年第3期9卷 1-20页

作者： Zohou Pierre jérôme Alamou Adéchina Eric Obada Ezéchiel Biao Iboukoun Eliézer Eugène C. Ezin Université d’Abomey-Calavi (UAC) Abomey-Calavi Bénin Laboratoire de Recherche en Sciences Informatiques et Applications (LRSIA) UAC Abomey-Calavi Bénin Laboratoire d’Hydrologie Appliquée (LHA) UAC Abomey-Calavi Bénin Université Nationale des Sciences Technologies Ingénierie et Mathématiques (UNSTIM) Abomey Bénin

Models are tools widely used in the prediction of hydrological phenomena. The present study aims to contribute to the implementation of an automatic optimization strategy of parameters for the calibration of a hydrological model based on the least action principle (HyMoLAP). The Downhill Simplex method is also known as the Nelder-Mead algorithm, which is a heuristic research method, is used to optimize the cost function on a given domain. The performance of the model is evaluated by the nash Stucliffe Efficiency Index (NSE), the Root Mean Square Error (RMSE), the coefficient of determination (R2), the Mean Absolute Error (MAE). A comparative estimation is conducted using the nash-Sutcliffe Modeling Efficiency Index and the mean relative error to evaluate the performance of the optimization method. It appears that the variation in water balance parameter values is acceptable. The simulated optimization method appears to be the best in terms of lower variability of parameter values during successive tests. The quality of the parameter sets obtained is good enough to impact the performance of the objective functions in a minimum number of iterations. We have analyzed the algorithm from a technical point of view, and we have carried out an experimental comparison between specific factors such as the model structure and the parameter’s values. The results obtained confirm the quality of the model (NSE = 0.90 and 0.75 respectively in calibration and validation) and allow us to evaluate the efficiency of the Nelder-Mead algorithm in the automatic calibration of the HyMoLAP model. The developed hybrid automatic calibration approach is therefore one of the promising ways to reduce computational time in rainfall-runoff modeling.

关键词： Optimization HyMoLAP Automatic Calibration Validation Nelder-Mead Algorithm

Alteration in immune function in patients with fatty liver disease

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Hepatoma Research 2022年第1期8卷 363-375页

作者： Stephanie N.Gregory Shruthi R.Perati Zachary j.Brown Department of Surgery Rutgers Robert Wood Johnson Medical SchoolNew BrunswickNJ 08901USA Division of Surgical Oncology Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusOH 43210USA

Nonalcoholic fatty liver disease(NAFLD)is a disease spectrum that spans simple steatosis,fibrosis,and ultimately cirrhosis,and is a leading cause of chronic liver disease *** severe variant of NAFLD,non-alcoholic steatohepatitis(nash),is characterized by triglyceride accumulation within hepatocytes and the subsequent inflammatory pathway activation,ultimately progressing to cirrhosis in 10%-20%of *** is a known major risk factor for the development of hepatocellular carcinoma(HCC),and there is emerging data demonstrating the impact of nash on immune subsets and the tumor microenvironment that may influence therapeutic *** review describes the various ways in which the immune system is altered in patients with *** innate immune system in nash shows alterations in dendritic and Kupffer cells,impaired cytotoxicity of Natural Killer cells,and an accumulation of ***,there is emerging evidence emphasizing the role of the adaptive immune system in the development and progression of nash,seen in the alteration of B-cells,T-cells,and NKT *** to the complex interplay of the immune system in NAFLD/nash.and its progression to HCC,many current treatments focus on targeting immune cells for HCC ***,immune checkpoint inhibitors such as atezolizumab and bevacizumab have been approved as first-line therapy for unresectable *** an emerging field of research,further studies and clinical trials are needed to understand the complex interface of nash,HCC and the immune response.

关键词： Non-alcoholic steatohepatitis nonalcoholic fatty liver disease steatohepatitis immunology hepatocellular carcinoma

券商研报信度的监管研究——分析师、利益机构和监管机构的三方博弈分析

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安徽大学学报（自然科学版） 2014年第6期38卷 9-15页

作者：王家军杨健中国人民大学信息资源管理学院北京100872 中国人民大学金融信息中心北京100872

"研报门"事件引发了证券市场对券商研报信度问题的关注.以往的研究基于二元、静态的模型,论文提出了研报信度是分析师、利益机构和监管机构三方动态博弈结果的论点,构建了三方博弈模型,通过数学公式的推演,求得了模型的纳什均衡解.研究... 详细信息

"研报门"事件引发了证券市场对券商研报信度问题的关注.以往的研究基于二元、静态的模型,论文提出了研报信度是分析师、利益机构和监管机构三方动态博弈结果的论点,构建了三方博弈模型,通过数学公式的推演,求得了模型的纳什均衡解.研究结论指出:券商研报信度高低与违规合作行为的发生概率成反比;分析师和利益机构采取违规合作策略的最优概率与监管机构的稽查成本成正比,与违规合作的成本成反比;监管机构采取稽查策略的最优概率与监管机构查证违规合作的概率以及违规合作的成本系数成反比,与违规合作后的收入大小无关.

关键词：研报门信度博弈论证券监管策略分析

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儿童非酒精性脂肪肝的组织病理学

世界核心医学期刊文摘（胃肠病学分册） 2006年第2期2卷 46-47页

作者： Schwimmer j.B. Behling C. Newbury R. j.E. Lavine 王铮 University of California San Diego 200 West Arbor Drive San Diego CA 92103- 8450 United States Dr.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (nash) are common in children and adolescents. However, standard histological criteria for pediatric NAFLD and nash are undeveloped. We reviewed consecutive patients ages 2 to 18 years with biopsy-proven NAFLD diagnosed between 1997 and 2003. Biopsies were evaluated by two pathologists for individual features of steatohepatitis. Agglomerative hierarchical cluster analysis demonstrated two different forms of steatohepatitis. Type 1 was characterized by steatosis, ballooning degeneration, and perisinusoidal fibrosis; type 2 was characterized by steatosis, portal inflammation, and portal fibrosis. The study included 100 children with NAFLD. Simple steatosis was present in 16% of subjects, and advanced fibrosis was present in 8% . Type 1 nash was present in 17% of subjects, and type 2 nash was present in 51% . Boys were significantly (P nash.and less likely to have type 1 nash than girls. The nash type differed significantly (P nash was more common in white children, whereas type 2 nash was more common in children of Asian, Native American, and Hispanic ethnicity. In cases of advanced fibrosis, the pattern was generally that of type 2 nash. In conclusion, type 1 and type 2 nash are distinct subtypes of pediatric NAFLD, and type 2 is the most common pattern in children. nash subtypes should be considered when interpreting liver biopsies and planning studies of the pathophysiology, genetics, natural history, or response to treatment in pediatric NAFLD.

关键词：组织病理学门静脉纤维化脂肪性肝炎脂肪变性酒精性脂肪肝组织学诊断退行性变肝组织病理聚类

MR弹性成像早期诊断非酒精性脂肪肝病中的非酒精性脂肪性肝炎

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国际医学放射学杂志 2011年第4期 384-385页

作者： j.A.Talwalkar K.j.Glaser S.O.Sanderson R.L.Ehman 马可云 Department of Radiology Mayo Clinic

目的探讨MR弹性成像对发现早期非酒精性脂肪性肝病(NAFLD)中的非酒精性脂肪性肝炎(nash)的诊断准确性[受试者操作特征曲线下面积(AUROC)]。材料与方法符合HIPAA并无需病人知情同意,回顾分析了58例NAFLD

关键词：非酒精性脂肪性肝病人 NAFLD 炎症病理肝硬度弹性成像 MR