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Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

Animal Models and Experimental Medicine 2023年第2期6卷 92-102页

作者： Xiaochen Gai Fangming Liu Yuting Wu Baohui Zhang Bufu Tang Kezhuo Shang lianmei wang Haihong Zhang Yixin Chen Shuhui Yang Weiwei Deng Peng Li Jing wang Hongbing Zhang State Key Laboratory of Medical Molecular Biology Department of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Physiology School of Life ScienceChina Medical UniversityShenyangChina Department of Radiology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouChina Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijingChina Department of Cardiac Surgery Fuwai HospitalStata Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular Diseases of ChinaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of Life Sciences Westlake UniversityHangzhouChina State Key Laboratory of Medical Molecular Biology Department of PathophysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global and myeloid cell-specific PKM2 knock-in mice with ApoE^(-/-)background(ApoE^(-/-),PKM2^(KI/KI)and Lyz2-cre,ApoE^(-/-),and PKM2^(flox/flox))were produced to evaluate the clinical significance of PKM2 in atherosclerosis development.Wild-type and PKM2 knock-in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis.Atherosclerotic mice were treated with PKM2 inhibitor shikonin(SKN)to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis.Results:Oxidized low-density lipoprotein(oxLDL)upregulated PKM2 in macrophages.PKM2 in return promoted the uptake of oxLDL by macrophages.Overexpressed PKM2 accelerated atherosclerosis in mice.SKN blocked the progress of mouse atherosclerosis.Conclusions:PKM2 accelerates macrophage phagocytosis and atherosclerosis.Targeting PKM2 is a potential therapy for atherosclerosis.

关键词： atherosclerosis low-density lipoprotein macrophage pyruvate kinase muscle 2

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Deficient Rnf43 potentiates hyperactive Kras-mediated pancreatic preneoplasia initiation and malignant transformation

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Animal Models and Experimental Medicine 2022年第1期5卷 61-71页

作者： Xian Zhou Zhichao Sun Mengdi Zhang Xiaoyu Qu Shuhui Yang lianmei wang Yanling Jing Li Li Weiwei Deng Fangming Liu Jin Di Jie Chen Jian Wu Hongbing Zhang State Key Laboratory of Medical Molecular Biology Department of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Institute of Cancer Stem Cell Dalian Medical UniversityDalianChina Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijingChina Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina MyGenostics Inc. BeijingChina

Background:Largely due to incidental detection,asymptomatic pancreatic cystic le-sions(PCLs)have become prevalent in recent years.Among them,intraductal papillary mucinous neoplasm(IPMN)infrequently advances to pancreatic ductal adenocarcinoma(PDAC).Conservative surveillance versus surgical intervention is a difficult clinical decision for both caregivers and PCL patients.Because RNF43 loss-of-function mutations and KRAS gain-of-function mutations concur in a subset of IPMN and PDAC,their biological significance and therapeutic potential should be elucidated.Methods:Pancreatic Rnf43 knockout and Kras activated mice(Rnf43^(−/−);Kras^(G12D))were generated to evaluate their clinical significance in pancreatic pre-neoplastic initiation and malignant transformation.Results:Loss of Rnf43 potentiated the occurrence and severity of IPMN and PDAC in oncogenic Kras mice.The Wnt/β-catenin signaling pathway was activated in pan-creatic Kras^(G12D)and Rnf43 knockout mice and the PORCN inhibitor LGK974 blocked pancreatic IPMN initiation and progression to PDAC accordingly.Conclusions:Rnf43 is a tumor suppressor in the prevention of pancreatic malignant transformation.This genetically reconstituted autochthonous pancreatic Rnf43^(−/−);Kras^(G12D)preclinical cancer model recapitulates the pathological process from pancreatic cyst to cancer in humans and can be treated with inhibitors of Wnt/β-catenin signaling.Since the presence of RNF43 and KRAS mutations in IPMNs predicts future development of advanced neoplasia from PCLs,patients with these genetic anomalies warrant surveillance,surgery,and/or targeted therapeutics such as Wnt/β-catenin inhibitors.

关键词： intraductal papillary mucinous neoplasms KRAS pancreatic ductal adenocarcinoma RNF43 Wnt

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Acquired Cardiomyopathy Caused by Cardiac Tsc1 Deficiency

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Journal of Genetics and Genomics 2014年第2期41卷 73-77页

作者： Yi Chena Fang wang Chunjia Li lianmei wang Hongbing Zhang Hongbing Yan Department of Cardiology Beijing An Zhen HospitalCapital Medical University Department of Physiology Institute of Basic Medical Sciences and School of Basic MedicinePeking Union Medical College and Chinese Academy of Medical Sciences Center for Coronary Heart Disease Cardiovascular Institute & Fu Wai HospitalPeking Union Medical College and Chinese Academy of Medical Sciences

Cardiomyopathies are myocardial disorders with enlarged, thick, or rigid cardiac muscles. Because no effective treatment is available to prevent the deterioration of the myocardium function, the prognosis of cardiomyopathy is usually poor. Cardiomyopathies can be inherited or acquired. A number of genes associated with inherited cardiomyopathy, such as the genes encoding for sarcomeric, cytoskeletal,

关键词： than Acquired Cardiomyopathy Caused by Cardiac Tsc1 Deficiency mTOR BNP MyHC

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腹膜透析相关性腹膜炎预防知信行量表的构建及信效度检验

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长治医学院学报 2024年第2期38卷 96-100页

作者：焦敏陶秀彬王连梅武仪冉韩雅婷朱敏皖南医学院研究生学院安徽芜湖241001 皖南医学院附属第一医院弋矶山医院

目的:构建适用于腹膜透析患者的腹膜透析相关性腹膜炎预防知信行量表,并检验信效度。方法:以知信行理论为指导,采用文献回顾、质性访谈和德尔菲专家函询法并在预调查的基础上形成初始量表。采取便利抽样法选取安徽省3所三级甲等医院腹... 详细信息

目的:构建适用于腹膜透析患者的腹膜透析相关性腹膜炎预防知信行量表,并检验信效度。方法:以知信行理论为指导,采用文献回顾、质性访谈和德尔菲专家函询法并在预调查的基础上形成初始量表。采取便利抽样法选取安徽省3所三级甲等医院腹透中心随访的268名腹膜透析患者进行调查。采用临界比值法、相关系数法、Cronbach′s α系数法和因子分析法进行条目筛选,采用内部一致性和重测信度进行信度检验,采用内容效度和结构效度进行效度检验。结果:形成的腹膜透析相关性腹膜炎预防知信行量表包括知识、信念和行为3个维度,共34个条目;总问卷和各维度的Cronbach′s α系数分别是0.972、0.971、0.968、0.949;分半信度分别是0.825、0.983、0.981、0.905,重测信度分别是0.830、0.710、0.800、0.635;条目水平内容效度指数介于0.95~1之间,量表水平的内容效度指数为0.976;探索性因子分析结果显示提取3因子模型,累计方差贡献率74.143%;验证性因子分析结果显示量表拟合度良好。结论:本问卷具有良好的信效度,可为医护人员开展腹膜透析患者腹膜透析相关性腹膜炎预防现状评估提供参考。

关键词：腹膜透析腹膜炎预防知信行问卷编制信效度

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Toxicity study of ethanol extract from Oroxylumindicum(L.) Vent in rats

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Journal of Traditional Chinese Medicine 2018年第5期38卷 714-725页

作者： Yi Yan Zhao Yong Li Chunying Zhang Yushi Bin Yang Yuan Yalan wang lianmei Pan Chen Liang Aihua Institute of Chinese Materia Medica China Academy of Chinese Medical Science

OBJECTIVE: To evaluate the safety of Oroxylumindicum(L.) Vent extract administered for 26 weeks in Wistar rats.METHODS: Oroxylumindicum(L.) Vent extract was administrated to male and female rats by gavage once daily at doses of 54, 225, and450 mg·kg-1·d-1.The rats were sacrificed after administration for13 weeks and 26 weeks. Part of the rats in each group were allowed to recover for 4 weeks after 26-week administration. Systematic examinations including haematology, urology, blood biochemistry and histomorphology were performed at the end of13, 26 weeks of administration and 4 weeks of recovery.RESULTS: No treatment related adverse effect shappened on rats' general status, body weight, food consumption, urinary index and histomorphologyexamination. Although during the administration,in some rats of extract's groups, the value of Red blood cell count(RBC), white blood cell counts(WBC), hemoglobin(HGB), haematocrit(HCT) and K iron were decreased, and biochemistry index,such as glucose(GLU), triglyceride(TG), alanine transaminase(ALT) and blood urea nitrogen(BUN)were increased, the above parameters were within the normal ranges and all returned to baseline after the drug stopping for 4 weeks.CONCLUSION: The administration of Oroxylumindicum(L.) Vent extractat levers up to 450 mg/kg(equals to 75 times of clinical dose) is well toleratedfor both genders without significant toxicity within the administration duration in this study.

关键词： Oroxylumindicum (L.)Vent Safety Chronic toxicity Rats

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Potential chronic liver toxicity in rats orally administered an ethanol extract of Huangqin(Radix Scutellariae Baicalensis)

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Journal of Traditional Chinese Medicine 2018年第2期38卷 242-256页

作者： Yi Yan Zhao Yong Li Chunying Zhang Yushi Bin Yang Yuan Yalan Pan Chen wang lianmei Liang Aihua Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences

OBJECTIVE: To investigate the potential chronic liver toxicity of oral administration of ethanol extract of Huangqin(Radix Scutellariae Baicalensis)(SBE) in Wistar rats.METHODS: SBE was administered to rats by gavage for 26 weeks, at doses of 300, 1250, or 2500 mg·kg-1·d-1 respectively. The rats were euthanized at the end of 13 and 26 weeks daily oral dosing and following 4 weeks of recovery time. The changes of hematology, urinary, blood biochemistry and histomorphology were examined at each time point and focus on liver function and histological changes.RESULTS: When SBE at a dose of up to 2500 mgkg-1 d-1 was fed to male and female rats for 2··6 weeks, the liver tissue showed some inflammatory change that predominated by leukocyte infiltrationbut returned to normal after withdrawal. In addition, high-dose SBE treatment of 26 weeks in rats,glucose, electrolyte and lipid levels also have some changes. In addition, there are no other functional or organic lesions related to SBE treatment.CONCLUSIONS: Long-term and high-dose SBE may cause liver damage, however, the structural damage of the liver can be restored after the ethanol extract stopping. SBE will be well-tolerated for long-term use as a drug or health food, but in order to ensure drug safety, liver function, and serum glucose, electrolyte and lipid levels should be monitored when using SBE long term.

关键词：肝毒性老鼠乙醇管理类脂化合物 Wistar 高剂量恢复时间

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细辛的化学成分、药理及毒理研究进展

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中国实验方剂学杂志 2023年第10期29卷 224-234页

作者：刘美婷王连嵋孟晶郑宝鑫秦莎莎梁爱华天津中医药大学天津301617 中国中医科学院中药研究所中药鉴定与安全性检测评估北京市重点实验室北京100700

细辛是我国的一味传统中药,已有2000多年的用药历史,历代本草多有收录,具有解表散寒、祛风止痛、通窍、温肺化饮的功效,至今仍在临床上广泛用于治疗感冒、新型冠状病毒肺炎、哮喘、过敏性鼻炎、目痛、头痛、牙痛、口腔溃疡、湿疹等病证... 详细信息

细辛是我国的一味传统中药,已有2000多年的用药历史,历代本草多有收录,具有解表散寒、祛风止痛、通窍、温肺化饮的功效,至今仍在临床上广泛用于治疗感冒、新型冠状病毒肺炎、哮喘、过敏性鼻炎、目痛、头痛、牙痛、口腔溃疡、湿疹等病证。现代药理研究显示细辛具有解热、抗炎、止痛、抗菌、抗病毒、止咳平喘、抗过敏等多种作用。细辛具有多种化学成分,其中挥发油,既与散寒解热、止痛抗炎、抗过敏等功效相关,也是其毒性成分。细辛中还含有木脂素类、黄酮类、酰胺类、生物碱、菲类等非挥发油类成分在调节免疫、抗炎止痛、强心扩血管等方面发挥重要作用。其中的菲类化合物主要为马兜铃酸类物质,如马兜铃酸Ⅳa和马兜铃内酰胺Ⅰ,马兜铃酸Ⅳa具有显著抗炎作用。细辛的毒性和黄樟醚和马兜铃酸类成分有关,还受制备方法、剂量、产地、采集时间、药用部位、煎煮时间等多种因素影响,临床应用时应综合考虑。笔者通过检索国内外相关文献,针对细辛的化学成分-药理作用-毒理作用相关性,马兜铃酸、黄樟醚等成分的安全性研究进行了综述,旨在探究细辛的化学成分、药理毒理作用,提供客观认识细辛安全性的新视角,为细辛的临床合理用药、产品风险防控、药品科学监管等提供参考。

关键词：细辛马兜铃酸化学成分挥发油毒理学研究药理作用

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优质护理干预在中老年慢性阻塞性肺疾病患者护理中的效果分析

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科技与健康 2024年第11期3卷 117-120页

作者：廖连梅遵义市中医院肺病科贵州遵义563000

评估优质护理干预对改善老年慢性阻塞性肺疾病患者护理效果的作用.选取2022年1月-2023年4月遵义市中医院收治的66例老年慢性阻塞性肺疾病患者作为研究对象,随机将其分为观察组和对照组,每组各33例.对照组患者接受常规护理,观察组患者接... 详细信息

评估优质护理干预对改善老年慢性阻塞性肺疾病患者护理效果的作用.选取2022年1月-2023年4月遵义市中医院收治的66例老年慢性阻塞性肺疾病患者作为研究对象,随机将其分为观察组和对照组,每组各33例.对照组患者接受常规护理,观察组患者接受优质护理干预,比较两组患者护理效果.结果显示,干预后,两组患者肺功能指标均优于干预前,且观察组优于对照组,差异具有统计学意义(P<0.05).观察组患者的住院时间短于对照组,差异具有统计学意义(P<0.05);观察组患者的护理总满意率高于对照组,差异具有统计学意义(P<0.05).研究发现,给予老年慢性阻塞性肺疾病患者优质护理干预,有利于优化患者的治疗效果,改善患者的肺功能,缩短患者的住院时间,具有推广价值.

关键词：老年慢性阻塞性肺疾病优质护理肺功能

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Dynamic scheduling model of computing resource based on MAS cooperation mechanism

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Science in China(Series F) 2009年第8期52卷 1302-1320页

作者： JIANG WeiJin1,2, ZHANG lianmei3 & wang Pu4 1 School of Computer and Electronic Engineering, Hunan University of Commerce, Changsha 410205, China 2 School of Information Engineering, Xiangtan University, Xiangtan 411000, China 3 Electrical Engineering College, Wuhan University, Wuhan 430072, China 4 School of Commerce, Central South University, Changsha 410083, China School of Computer and Electronic Engineering Hunan University of Commerce Changsha China School of Information Engineering Xiangtan University Xiangtan China Electrical Engineering College Wuhan University Wuhan China School of Commerce Central South University Changsha China

Allocation of grid resources aims at improving resource utility and grid application performance. Currently, the algorithms proposed for this purpose do not fit well the autonomic, dynamic, distributive and heterogeneous features of the grid environment. According to MAS （multi-agent system） cooperation mechanism and market bidding game rules, a model of allocating allocation of grid resources based on market economy is introduced to reveal the relationship between supply and demand. This model can make good use of the studying and negotiating ability of consumers＇ agent and takes full consideration of the consumer＇s behavior, thus rendering the application and allocation of resource of the consumers rational and valid. In the meantime, the utility function of consumer is given; the existence and the uniqueness of Nash equilibrium point in the resource allocation game and the Nash equilibrium solution are discussed. A dynamic game algorithm of allocating grid resources is designed. Experimental results demonstrate that this algorithm diminishes effectively the unnecessary latency, improves significantly the smoothness of response time, the ratio of throughput and resource utility, thus rendering the supply and demand of the whole grid resource reasonable and the overall grid load balanceable.

关键词： multi-agent system （MAS） resource scheduling model evolutionary game cooperation mechanism utility function

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酿酒酵母转化半乳糖醇的工程菌株构建及优化

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生物工程学报 2024年第6期40卷 1909-1923页

作者：邓连妹李娇门燕孙媛霞贾士儒朱玥明天津科技大学生物工程学院天津300457 中国科学院天津工业生物技术研究所工业酶国家重点实验室天津300308

半乳糖醇是一种稀少糖醇,广泛应用于食品工业与医药领域。工业上一般通过化学氢化法生产半乳糖醇,但反应条件苛刻、生产成本高、对环境不友好,亟须开发更有效的“绿色”生物合成技术。本研究挖掘了来源于黑曲霉(Aspergillus niger)CBS 5... 详细信息

半乳糖醇是一种稀少糖醇,广泛应用于食品工业与医药领域。工业上一般通过化学氢化法生产半乳糖醇,但反应条件苛刻、生产成本高、对环境不友好,亟须开发更有效的“绿色”生物合成技术。本研究挖掘了来源于黑曲霉(Aspergillus niger)CBS 513.88的木糖还原酶(Aspergillus niger xylose reductase,AnXR),该酶属于NADPH依赖的醛酮还原酶家族。对AnXR的酶学性质进行研究,发现其最适温度和pH分别为25℃和8.0。以酿酒酵母(Saccharomyces cerevisiae)为底盘细胞,利用基因重组技术敲除半乳糖激酶(galactokinase,GAL1)基因,使得宿主细胞对半乳糖的分解代谢利用大幅降低,并在此底盘菌株中引入AnXR基因构建了催化D-半乳糖生成半乳糖醇的工程菌株。对工程菌株全细胞转化的条件进行优化,半乳糖醇的最高产量达到12.10g/L。同时,该菌株对其他单糖的还原能力也进行了测试,可生成木糖醇、阿拉伯糖醇等功能性糖醇。利用本研究构建的工程菌株可以实现半乳糖醇等多种功能糖醇的高效生物转化,对稀少糖醇的绿色制造具有借鉴意义。

关键词：半乳糖醇木糖还原酶酿酒酵母工程菌株全细胞转化

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