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Inhibition of hepatitis B virus via selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet

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World Journal of Gastroenterology 2024年第13期30卷 1911-1925页

作者： Fei-Lin Ge Yan Yang Lan-Lan Si Yuan-Hua Li Meng-Zhen Cao Jun Wang Zhao-fang bai Zhi-Gang Ren Xiao-He Xiao Yan Liu Department of Chinese Medicine State Key Laboratory of Antiviral DrugsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina The Fifth Medical Center of Chinese PLA General Hospital Beijing 100039China College of Traditional Chinese Medicine Chongqing Medical UniversityChongqing 400010China Beijing Key Laboratory of Emerging Infectious Diseases Peking University Ditan Teaching HospitalBeijing 100015China Department of Infectious Diseases State Key Laboratory of Antiviral Drugsthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)*** studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains *** To investigate the potential mechanism of action of LWWL against *** In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell *** in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV *** and metabolomics were used to investigate the underlying mechanisms of action of *** In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,*** inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,*** of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups

关键词： Hepatitis B virus Chinese patent medicine Antiviral activity Antiviral mechanism Selective apoptosis

Compatibility with Fructus Ligustri Lucidi Effectively Mitigates Idiosyncratic Liver Injury of Epimedii Folium by Modulating NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 159-170页

作者： Xiao-Mei Zhao Zhi-Xin Wu Yan Wang Ying-Jie Xu Ye Xiu Xu Dong Jun-Jie Li Gui-Ji Lv Si-Hao Wang Yu-Rong Li Zhao-fang bai Xiao-He Xiao Department of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina Department of Military Patient Management The Fifth Medical Center of PLA General HospitalBeijingChina Department of Hepatology China Military Institute of Chinese Materia The Fifth Medical Center of PLA General HospitalBeijingChina Departmentof Hepatology National Key Laboratory of Kidney DiseasesBeijingChina

Background: Idiosyncratic drug-induced liver injury(IDILI) is a serious side effect of drugs, Epimedii Folium(EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome. Fructus Ligustri Lucidi(FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Aims and Objectives: Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Results: Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. Conclusions: FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.

关键词： Epimedii Folium Fructus Ligustri Lucidi idiosyncratic drug-induced liver injury NOD-like receptor family pyrin domain containing 3 inflammasome traditional Chinese medicine

多模态数据融合技术及其在眼科领域的应用研究进展

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眼科新进展 2024年第3期44卷 248-252页

作者：陈铭海白芳陶海解放军总医院第三医学中心眼科医学部北京市100039 安徽医科大学第五临床学院安徽省合肥市230032

多模态数据融合技术(MDF)是人工智能领域中的一种数据处理技术,是指利用计算机对多模态数据,如图片、文字、音频与视频等进行综合处理的技术。与传统单模态数据处理相比,MDF对描述对象的分析有更高的准确性与可靠性。近年来,该技术在眼... 详细信息

多模态数据融合技术(MDF)是人工智能领域中的一种数据处理技术,是指利用计算机对多模态数据,如图片、文字、音频与视频等进行综合处理的技术。与传统单模态数据处理相比,MDF对描述对象的分析有更高的准确性与可靠性。近年来,该技术在眼科领域的应用研究取得了较大进展,研究表明该技术能提高人工智能辅助诊断的准确性。本文综述了MDF的原理与优势、发展简况、架构与主要技术难点、MDF在眼科临床的应用现况以及目前存在的尚待解决的问题。

关键词：人工智能多模态数据融合技术眼科学研究进展文献综述

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数字时代职教学生数字素养:内涵与框架

中国职业技术教育 2024年第23期 42-49,85页

作者：周自波张丽娟白芳华中师范大学终身教育研究所福建省厦门第二中学华中师范大学教育学院

厘清职业教育学生数字素养的内涵并构建其数字素养框架,对数字时代职业院校人才培养具有重要意义。依据布鲁姆教育目标分类理论及ASK模型,结合职教学生“身份”和“类型”特征,构建了一个包括数字知识、数字技能、数字态度3个一级维度、... 详细信息

厘清职业教育学生数字素养的内涵并构建其数字素养框架,对数字时代职业院校人才培养具有重要意义。依据布鲁姆教育目标分类理论及ASK模型,结合职教学生“身份”和“类型”特征,构建了一个包括数字知识、数字技能、数字态度3个一级维度、8个二级维度以及21个三级维度能力指标的职教学生数字素养框架,以期为职业院校培养学生的数字素养提供理论参考。

关键词：职业教育数字素养职教学生内涵框架

综采工作面安撤作业乳化液节约技术研究与应用

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煤矿机械 2024年第3期45卷 141-143页

作者：房白兖矿能源集团股份有限公司山东济宁272000

煤矿综采(放)工作面安撤作业经常存在乳化液浪费现象,不仅增加了生产成本,还给后续矿井水处理带来压力。为减少乳化液的浪费,煤矿制定了严格的考核措施,但相关措施仅停留在管理层面,对乳化液节约措施的技术研究还存在缺失。对相关技术... 详细信息

煤矿综采(放)工作面安撤作业经常存在乳化液浪费现象,不仅增加了生产成本,还给后续矿井水处理带来压力。为减少乳化液的浪费,煤矿制定了严格的考核措施,但相关措施仅停留在管理层面,对乳化液节约措施的技术研究还存在缺失。对相关技术进行研究,并在济宁三号煤矿成功应用。

关键词：乳化液浓度自动配液回液降阻

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4种眼科继续医学教育培训形式的调查研究

中国继续医学教育 2024年第9期16卷 121-126页

作者：白芳陶海解放军总医院第三医学中心眼科学部北京100039

目的了解眼科医生对当下眼科继续医学教育的看法,探讨其中存在的问题和提出改善意见。方法2023年5月22日—6月6日,选取某全国性眼科微信学术讨论群为调查单位,以眼科医生为调查对象,发放调查问卷,最终纳入110份问卷。结果研究对象中,男4... 详细信息

目的了解眼科医生对当下眼科继续医学教育的看法,探讨其中存在的问题和提出改善意见。方法2023年5月22日—6月6日,选取某全国性眼科微信学术讨论群为调查单位,以眼科医生为调查对象,发放调查问卷,最终纳入110份问卷。结果研究对象中,男43名(39.09%),女67名(60.91%);医师21名(19.09%),主治医师39名(35.45%),副主任医师38名(34.55%),主任医师12名(10.91%)。82名(74.55%)接受过外院进修学习,99名(90.00%)接受过线下短期学习班,108名(98.18%)接受过线上培训课程,106名(96.36%)参加过各种学术会议。培训效果和受欢迎程度综合评分最高的是短期线下培训班和外院进修学习。最受欢迎的教学形式是手术视频教学。最受欢迎的教学内容是最新前沿知识和手术操作及技巧相关内容。研究对象反馈,外院进修学习培训内容全面,但时间成本高;短期线下学习班适合进行手术培训,但培训内容不够深入,经济成本高;线上课程的时间成本合适,但没有动手机会;学术会议能了解最新前沿知识,但动手机会少。当前存在的主要问题包括会议和培训班多,而精品课程少。结论不同继续医学教育形式有各自的优势和劣势,结合多种途径和形式,根据教学内容选择合理的教学形式,能够更加贴合临床医生的需求,最终提升培训效果。

关键词：眼科医生继续医学教育医学培训医生观点调查研究培训形式

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1651-1664页

作者： Xiong Xie Qiaoshuai Lan Jinyi Zhao Sulin Zhang Lu Liu Yumin Zhang Wei Xu Maolin Shao Jingjing Peng Shuai Xia Yan Zhu Keke Zhang Xianglei Zhang Ruxue Zhang jian Li Wenhao Dai Zhen Ge Shulei Hu Changyue Yu Jiang Wang Dakota Ma Mingyue Zheng Haitao Yang Gengfu Xiao Zihe Rao Lu Lu Leike Zhang fang bai Yao Zhao Shibo Jiang Hong Liu Drug Discovery and Design Center State Key Laboratory of Drug ResearchCAS Key Laboratory of Receptor ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Institute of Infectious Disease and BiosecurityFudan UniversityShanghai 200032China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China School of Chinese Materia Medica Nanjing University of Chinese Medicine138 Xian Lin RoadJiangsu 210023 NanjingChina School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China National Clinical Research Center for Infectious Disease Shenzhen Third People's HospitalShenzhen 518112China

Respiratory disease caused by coronavirus infection remains a global health *** several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be ***-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging *** L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune ***,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and *** X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of *** showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various *** mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral ***,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in *** addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse *** 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute *** together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with anti

关键词： calpain overcome entrance

Kernel Estimators of the ROC Curve with Censored Data

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Acta Mathematicae Applicatae Sinica 2013年第1期29卷 43-54页

作者： fang-fang bai Yong Zhou Academy of Mathematics and Systems Science Chinese Academy of Sciences School of Statistics and Management Shanghai University of Finance and Economics

Receiver operating characteristic （ROC） curves are often used to study the two sample problem in medical studies. However, most data in medical studies are censored. Usually a natural estimator is based on the Kaplan-Meier estimator. In this paper we propose a smoothed estimator based on kernel techniques for the ROC curve with censored data. The large sample properties of the smoothed estimator are established. Moreover, deficiency is considered in order to compare the proposed smoothed estimator of the ROC curve with the empirical one based on Kaplan-Meier estimator. It is shown that the smoothed estimator outperforms the direct empirical estimator based on the Kaplan-Meier estimator under the criterion of deficiency. A simulation study is also conducted and a real data is analyzed.

关键词： ROC curve smoothed estimator censored data Kaplan-Meier estimator deficiency

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大数据背景下财务管理模式的创新研究

商业观察 2024年第16期10卷 85-88,92页

作者：白芳张嘉斌山西开放大学经管学院山西太原030024 山西省成本调查监审局山西太原030021

大数据时代,财务管理模式的创新变得至关重要。通过阐述大数据的概念、特性及其对传统财务管理模式的影响,分析大数据时代背景下财务管理模式创新的需求和趋势,具有突出的重要性和紧迫性。为了应对挑战、把握机遇,文章提出基于大数据的... 详细信息

大数据时代,财务管理模式的创新变得至关重要。通过阐述大数据的概念、特性及其对传统财务管理模式的影响,分析大数据时代背景下财务管理模式创新的需求和趋势,具有突出的重要性和紧迫性。为了应对挑战、把握机遇,文章提出基于大数据的财务管理模式创新策略,涵盖财务决策、风险管理、财务报告和信息系统等核心领域的创新,并通过深入剖析国内外企业创新的成功案例,揭示大数据背景下财务管理模式创新的实践路径和效果评估方法。同时,针对创新过程中可能遇到的挑战,文章提出相应的对策和建议,以期帮助企业更好地利用大数据技术,提升财务管理水平,为企业创造更大的价值。

关键词：大数据财务管理模式创新策略实践路径挑战与对策