BACKGROUND Since non-alcoholic fatty liver disease(NAFLD)is associated with abnormal liver function tests,treatment recommendations aim to reduce the level of known markers of liver inflammation,such as alanine transa...BACKGROUND Since non-alcoholic fatty liver disease(NAFLD)is associated with abnormal liver function tests,treatment recommendations aim to reduce the level of known markers of liver inflammation,such as alanine transaminase(ALT),aspartate transaminase(AST)and gamma-glutamyl transferase(GGT).Essential phospholipids(EPLs)have been shown to reduce levels of these liver enzymes and improve ultrasonographic features.While non-invasive diagnostic tests have been developed to stage inflammation,these tests were not specifically designed to evaluate patients with NAFLD.This highlights the need to describe the liver enzyme profile across the different levels of NAFLD severity for improved grading and staging of NAFLD.AIM To describe liver enzyme profiles across NAFLD severity to inform a diagnostic staging algorithm and identify who may benefit from EPLs.METHODS This post-hoc analysis of the observational MANPOWER study included 2843 adult patients with newly diagnosed NAFLD.The primary endpoint was assessment of baseline liver enzyme profiles.Secondary endpoints were effectiveness of Essentiale®(an EPL)on liver enzyme levels and ultrasonography findings across three definitions of NAFLD:(1)Statistical distribution of liver enzyme levels;(2)MANPOWER cut-offs;and(3)Presence of physiciandiagnosed non-alcoholic steatohepatitis.The best performing algorithm was used to describe the risk factors and profiles associated with increased liver enzyme levels.RESULTS Of the 2843 patients included in this post-hoc analysis,most were female(62.2%),with a mean age of 48.4 years(SD 8.59 years).Overall,mean levels of ALT,AST and GGT increased with NAFLD severity for all three subgroups,with the rate of chronic comorbidities correlated with NAFLD severity.Across each subgroup of interest,Essentiale significantly reduced average liver enzyme levels and improved ultrasonography features,including diffuse liver hyperechogenicity and heterogeneous liver structure(P<0.05),with greater benefit associated with increased severity.Compared with all algorithms tested,the algorithm based on the statistical distribution of liver enzymes displayed the highest accuracy,sensitivity and specificity for the grading and staging of NAFLD and could form the basis of a diagnostic algorithm.CONCLUSION Liver enzyme profiles may identify NAFLD severity and allow monitoring of therapeutic response.Essentiale may improve liver enzyme levels and ultrasonography features.An algorithm could aid in the diagnosis/staging of NAFLD.展开更多
Biotherapeutic's higher order structure(HOS)is a critical determinant of its functional properties and conformational relevance.Here,we evaluated two covalent labeling methods:diethylpyrocarbonate(DEPC)-labeling a...Biotherapeutic's higher order structure(HOS)is a critical determinant of its functional properties and conformational relevance.Here,we evaluated two covalent labeling methods:diethylpyrocarbonate(DEPC)-labeling and fast photooxidation of proteins(FPOP),in conjunction with mass spectrometry(MS),to investigate structural modifications for the new class of immuno-oncological therapy known as bispecific antigen-binding biotherapeutics(BABB).The evaluated techniques unveiled subtle structural changes occurring at the amino acid residue level within the antigen-binding domain under both native and thermal stress conditions,which cannot be detected by conventional biophysical techniques,e.g.,near-ultraviolet circular dichroism(NUV-CD).The determined variations in labeling uptake under native and stress conditions,corroborated by binding assays,shed light on the binding effect,and highlighted the potential of covalent-labeling methods to effectively monitor conformational changes that ultimately influence the product quality.Our study provides a foundation for implementing the developed techniques in elucidating the inherent structural characteristics of novel therapeutics and their conformational stability.展开更多
目的调查全国已开展和有意向开展流感疫苗接种公费项目地区的基本情况,分析流感公费项目实施的关键要点,为制订政策措施提供依据。方法通过定性访谈和线上调查,对2018年已开展流感公费项目地区以及拟在未来3年开展流感公费项目地区的疾...目的调查全国已开展和有意向开展流感疫苗接种公费项目地区的基本情况,分析流感公费项目实施的关键要点,为制订政策措施提供依据。方法通过定性访谈和线上调查,对2018年已开展流感公费项目地区以及拟在未来3年开展流感公费项目地区的疾病预防控制中心负责流感公费项目的业务骨干进行调查。采用SPSS 20.0软件进行统计分析。结果共调查11个已开展和54个有意向开展流感公费项目的地区疾控中心。在已开展流感公费项目地区,老年人是最主要的目标人群,其次是在校中小学生和医护人员。有意向开展流感公费项目地区,城市老龄化是影响项目开展进度的因素之一,其中"已与行政部门确认完毕,今年实施"的地区的老年人口比例(20.66%)高于其它地区(17.59%);此外,"与行政部门协调,获得行政部门支持"被认为是最主要实施瓶颈(81.48%);其次依次是"流感疫苗的管理和分配"(44.44%)、"公费人群流感疫苗的接种宣传"(33.33%)、"疫苗预防接种不良事件(adverse events following immumization,AEFI)的处理预案制定"(27.78%)和"社区卫生服务中心接种人员的培训和调配"(18.52%)。结论老年人是流感公费项目最主要的目标人群,而城市老龄化是影响项目进度的因素之一。疾控中心是流感公费项目发起的关键,对于有意向开展流感公费的地区,疾控机构应积极主动去倡导项目的发起,用专业能力去影响政府部门决策实施。展开更多
中国合格评定国家认可委员会(China National Accreditation Service for Conformity Assessment,CNAS)实验动物机构认可是我国实验动物管理的重要制度,是致力于保障我国实验动物质量和福利的一项具有中国特色的第三方评价制度。美国实...中国合格评定国家认可委员会(China National Accreditation Service for Conformity Assessment,CNAS)实验动物机构认可是我国实验动物管理的重要制度,是致力于保障我国实验动物质量和福利的一项具有中国特色的第三方评价制度。美国实验动物饲养管理评估认证协会(Association for Assessment and Accreditation of Laboratory Animal Care,AAALAC)认证是为全球实验动物管理和使用机构提供动物福利和伦理认证服务的一种评价活动。本文从CNAS与AAALAC的性质、CNAS认可和AAALAC认证本质、评价依据和文件、评审流程、评审人员管理、结果采信等方面进行了比较分析,探讨两项实验动物机构评价制度的差异与特点。展开更多
文摘BACKGROUND Since non-alcoholic fatty liver disease(NAFLD)is associated with abnormal liver function tests,treatment recommendations aim to reduce the level of known markers of liver inflammation,such as alanine transaminase(ALT),aspartate transaminase(AST)and gamma-glutamyl transferase(GGT).Essential phospholipids(EPLs)have been shown to reduce levels of these liver enzymes and improve ultrasonographic features.While non-invasive diagnostic tests have been developed to stage inflammation,these tests were not specifically designed to evaluate patients with NAFLD.This highlights the need to describe the liver enzyme profile across the different levels of NAFLD severity for improved grading and staging of NAFLD.AIM To describe liver enzyme profiles across NAFLD severity to inform a diagnostic staging algorithm and identify who may benefit from EPLs.METHODS This post-hoc analysis of the observational MANPOWER study included 2843 adult patients with newly diagnosed NAFLD.The primary endpoint was assessment of baseline liver enzyme profiles.Secondary endpoints were effectiveness of Essentiale®(an EPL)on liver enzyme levels and ultrasonography findings across three definitions of NAFLD:(1)Statistical distribution of liver enzyme levels;(2)MANPOWER cut-offs;and(3)Presence of physiciandiagnosed non-alcoholic steatohepatitis.The best performing algorithm was used to describe the risk factors and profiles associated with increased liver enzyme levels.RESULTS Of the 2843 patients included in this post-hoc analysis,most were female(62.2%),with a mean age of 48.4 years(SD 8.59 years).Overall,mean levels of ALT,AST and GGT increased with NAFLD severity for all three subgroups,with the rate of chronic comorbidities correlated with NAFLD severity.Across each subgroup of interest,Essentiale significantly reduced average liver enzyme levels and improved ultrasonography features,including diffuse liver hyperechogenicity and heterogeneous liver structure(P<0.05),with greater benefit associated with increased severity.Compared with all algorithms tested,the algorithm based on the statistical distribution of liver enzymes displayed the highest accuracy,sensitivity and specificity for the grading and staging of NAFLD and could form the basis of a diagnostic algorithm.CONCLUSION Liver enzyme profiles may identify NAFLD severity and allow monitoring of therapeutic response.Essentiale may improve liver enzyme levels and ultrasonography features.An algorithm could aid in the diagnosis/staging of NAFLD.
基金supported by Amgen Inc.,USA and the National Institutes of Health,USA(Grant Nos.:R01CA218500(ARI)and R35GM136421(ARI))。
文摘Biotherapeutic's higher order structure(HOS)is a critical determinant of its functional properties and conformational relevance.Here,we evaluated two covalent labeling methods:diethylpyrocarbonate(DEPC)-labeling and fast photooxidation of proteins(FPOP),in conjunction with mass spectrometry(MS),to investigate structural modifications for the new class of immuno-oncological therapy known as bispecific antigen-binding biotherapeutics(BABB).The evaluated techniques unveiled subtle structural changes occurring at the amino acid residue level within the antigen-binding domain under both native and thermal stress conditions,which cannot be detected by conventional biophysical techniques,e.g.,near-ultraviolet circular dichroism(NUV-CD).The determined variations in labeling uptake under native and stress conditions,corroborated by binding assays,shed light on the binding effect,and highlighted the potential of covalent-labeling methods to effectively monitor conformational changes that ultimately influence the product quality.Our study provides a foundation for implementing the developed techniques in elucidating the inherent structural characteristics of novel therapeutics and their conformational stability.
文摘目的调查全国已开展和有意向开展流感疫苗接种公费项目地区的基本情况,分析流感公费项目实施的关键要点,为制订政策措施提供依据。方法通过定性访谈和线上调查,对2018年已开展流感公费项目地区以及拟在未来3年开展流感公费项目地区的疾病预防控制中心负责流感公费项目的业务骨干进行调查。采用SPSS 20.0软件进行统计分析。结果共调查11个已开展和54个有意向开展流感公费项目的地区疾控中心。在已开展流感公费项目地区,老年人是最主要的目标人群,其次是在校中小学生和医护人员。有意向开展流感公费项目地区,城市老龄化是影响项目开展进度的因素之一,其中"已与行政部门确认完毕,今年实施"的地区的老年人口比例(20.66%)高于其它地区(17.59%);此外,"与行政部门协调,获得行政部门支持"被认为是最主要实施瓶颈(81.48%);其次依次是"流感疫苗的管理和分配"(44.44%)、"公费人群流感疫苗的接种宣传"(33.33%)、"疫苗预防接种不良事件(adverse events following immumization,AEFI)的处理预案制定"(27.78%)和"社区卫生服务中心接种人员的培训和调配"(18.52%)。结论老年人是流感公费项目最主要的目标人群,而城市老龄化是影响项目进度的因素之一。疾控中心是流感公费项目发起的关键,对于有意向开展流感公费的地区,疾控机构应积极主动去倡导项目的发起,用专业能力去影响政府部门决策实施。
文摘中国合格评定国家认可委员会(China National Accreditation Service for Conformity Assessment,CNAS)实验动物机构认可是我国实验动物管理的重要制度,是致力于保障我国实验动物质量和福利的一项具有中国特色的第三方评价制度。美国实验动物饲养管理评估认证协会(Association for Assessment and Accreditation of Laboratory Animal Care,AAALAC)认证是为全球实验动物管理和使用机构提供动物福利和伦理认证服务的一种评价活动。本文从CNAS与AAALAC的性质、CNAS认可和AAALAC认证本质、评价依据和文件、评审流程、评审人员管理、结果采信等方面进行了比较分析,探讨两项实验动物机构评价制度的差异与特点。
