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Chinese Medical Journal 2022年第19期135卷 2380-2382页

作者： Yuhao Sun Xiaoyu Wen Zhuoxian Li lijing Xu Meng Xia School of Basic Medicine Guangxi University of Chinese MedicineNanningGuangxi 530200China.

To the Editor:Vascular dementia(VD)is a clinical disease characterized_by cognitive dysfunction and intellectual decline caused byvarious cerebrovascularfactors.The high incidence of VD in middle-aged and elderly people has become a major medical and social problem worldwide.li Since its specific pathogenesis has not been fully elucidated,clinical practice is stillfocused on improving cognition and sAylmteprntoamtivaetilcy,t rweiathtm heignht,seuffcehc taivse pnierascse atanmd faenwd sdidoen eepffeezcitl.s2,i traditional Chinese medicine has drawn medical attention and become a hotspot in the medical research field.

关键词： decoction clinical pathogenesis

CDK11 negatively regulates Wnt/β-catenin signaling in the endosomal compartment by affecting microtubule stability

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Cancer Biology & Medicine 2020年第2期17卷 328-342页

作者： Danmin Ou lin Chen Jiang He zhuoxian Rong Jie Gao liyu liu Feiyu Tang Jiang li Yuezhen Deng Lunquan Sun Department of Oncology Center for Molecular MedicineXiangya HospitalCentral South UniversityChangsha 410008China international Cooperation Base of Cancer Precision Therapy Department of Science and Technology of Hunan ProvinceChangsha 410008China Key Laboratory of Molecular Radiation Oncology of Hunan Province Changsha 410008China National Clinical Research Center for Geriatric Disorders Changsha 410008China

Objectives:Improper activation of Wnt/β-catenin signaling has been implicated in human diseases.Beyond the well-studied glycogen synthase kinase 3p(GSK3p)and casein kinase 1(CK1),other kinases affecting Wnt/β-catenin signaling remain to be defined.Methods:To identify the kinases that modulate Wnt/β-catenin signaling,we applied a kinase small interfering RNA(siRNA)library screen approach.Luciferase assays,immunoblotting,and real-time polymerase chain reaction(PCR)were performed to confirm the regulation o f the Wnt/β-catenin signaling pathway by cyclin-dependent kinase 11(CDK11)and to investigate the underlying mechanism.Confocal immunofluorescence,coimmunoprecipitation(co-IP),and scratch wound assays were used to demonstrate colocalization,detect protein interactions,and explore the function of CDK11.Results:CDK11 was found to be a significant candidate kinase participating in the negative control of Wnt/P-catenin signaling.Down-regulation of CDK11 led to the accumulation of Wnt/β-catenin signaling receptor complexes,in a manner dependent on intact adenomatosis polyposis coli(APC)protein.Further analysis showed that CDK11 modulation of Wnt/P-catenin signaling engaged the endolysosomal machinery,and CDK11 knockdown enhanced the colocalization of Wnt/β-catenin signaling receptor complexes with early endosomes and decreased colocalization with lysosomes.Mechanistically,CDK11 was found to function in Wnt/β-catenin signaling by regulating microtubule stability.Depletion of CDK11 down-regulated acetyl-a-tubulin.Moreover,co-IP assays demonstrated that CDK11 interacts with the a-tubulin deacetylase SIRT2,whereas SIRT2 down-regulation in CDK11-depleted cells reversed the accumulation of Wnt/(3-catenin signaling receptor complexes.CDK11 was found to suppress cell migration through altered W nt/β-catenin signaling.Conclusions:CDK11 is a negative modulator of Wnt/β-catenin signaling that stabilizes microtubules,thus resulting in the dysregulation of receptor complex trafficking from early endosomes to lysosomes.

关键词： Wnt/β-catenin signaling CDK11 endosome microtubule SIRT2

对项目整个生命周期PHSER方法的探究与借鉴

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化工学报 2021年第3期72卷 1634-1642页

作者：李婧怡匡卓贤美国斯坦福大学化工学院美国加利福尼亚斯坦福94305 中国寰球工程有限公司北京100012

针对“我国企业HSE管理重在施工现场和运行装置,基本上没有深入到对项目前期和设计过程”的现状,以及在重大事故中所暴露出来的本质安全问题,本研究探讨了国外先进石化企业已经成熟使用多年的涵盖项目整个生命周期的项目HSE审查方法(PHS... 详细信息

针对“我国企业HSE管理重在施工现场和运行装置,基本上没有深入到对项目前期和设计过程”的现状,以及在重大事故中所暴露出来的本质安全问题,本研究探讨了国外先进石化企业已经成熟使用多年的涵盖项目整个生命周期的项目HSE审查方法(PHSER)。国外先进公司特别重视对项目前期和设计阶段的审查,确保重大HSE问题得到识别、本质安全得到保证和设计危害得到控制,这恰是我国绝大多数企业项目安全管理的薄弱之处。因此,提出“学习和借鉴PHSER方法,使HSE管理向项目前端和设计阶段延伸,向技术HSE扩展”的建议。PHSER审查是以企业为主的项目HSE审查,是企业自主地追求项目本质安全或本质HSE设计活动、保障项目全过程HSE管理,从而达到全面管控项目风险的目的。

关键词：项目HSE审查 PHSER 整个生命周期本质安全全过程风险先进管理

The Revelation of Foreign Disabled People Basic Public Service System to China

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International English Education Research 2015年第7期 94-96页

作者： li zhuoxian Luo Juan Gao Kai Shanghai University of Engineering Science Shanghai 201620 China

Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3454-3470页

作者： Yao Yang Zimu li Ping Huang Jiachan lin Jinyuan li Kexin Shi Jiahui lin Jingwen Hu zhuoxian Zhao Yongkang Yu Hongzhong Chen Xiaowei Zeng lin Mei Institute of Pharmaceutics School of Pharmaceutical Sciences(Shenzhen)Sun Yat-sen UniversityShenzhen 518107China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yatsen University Cancer CenterGuangzhou 510060China Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical SciencesPeking Union Medical CollegeTianjin300192China

Despite growing prevalence and incidence,the management of gout remains suboptimal.The intermittent nature of the gout makes the long-term urate-lowering therapy(ULT)particularly important for gout management.However,patients are reluctant to take medication day after day to manage incurable occasional gout flares,and suffer from possible long-term toxicity.Therefore,a safe and easy-tooperate drug delivery system with simple preparation for the long-term management of gout is very necessary.Here,a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal.This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention.Furthermore,its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models.Besides,the drug co-delivery system could help avoid long-term daily oral colchicine,a drug with a narrow therapeutic index.This system also avoids mass injection of uricase by improving its stability,enhancing the clinical application value of uricase.In general,this two-drug system reduces the dosage of uricase and colchicine and improves the patient’s compliance,which has a strong clinical translation.

关键词： Microneedles Colchicine Sustained-release Uricase liposome Transdermal administration Gout management Long-term urate-lowering therapy

过程安全管理体系对BP Texas事故探析

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炼油技术与工程 2021年第6期51卷 68-72页

作者：李婧怡匡卓贤斯坦福大学化工学院美国加利福尼亚州斯坦福94305 中国寰球工程有限公司北京市100012

危化品生产过程的安全事故所造成的经济损失和社会影响均较大,必须从根源上消除,至少也要极大程度地减缓。BP Texas炼油厂爆炸和火灾事故是美国近40年来最严重的工厂灾难之一,也是一起典型的过程安全事故。以过程安全管理(PSM)体系要素... 详细信息

危化品生产过程的安全事故所造成的经济损失和社会影响均较大,必须从根源上消除,至少也要极大程度地减缓。BP Texas炼油厂爆炸和火灾事故是美国近40年来最严重的工厂灾难之一,也是一起典型的过程安全事故。以过程安全管理(PSM)体系要素分析方法对该事故进行研究,系统地探讨该事故的原因。可以看出,多个要素严重违反体系要求为该事故发生的关键原因。同时以实例证明PSM体系的重要性,通过控制其中要素的严重偏离,实现从根源上和管理体系上消除重大安全事故风险的目标。

关键词： BP Texas炼油厂异构化装置爆炸火灾过程安全管理体系要素符合性矩阵评估

The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1- and Pgc-1α-mediated regulation of Glut2

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Protein & Cell 2019年第6期10卷 436-449页

作者： Xinhui Wang Hong Gao Wenhui Wu Enjun Xie Yingying Yu Xuyan He Jin li Wanru Zheng Xudong Wang Xizhi Cao zhuoxian Meng ligong Chen Junxia Min Fudi Wang School of Public Health The First Affiliated Hospital Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou 310058 China School of Pharmaceutical Sciences State Key Laboratory of Membrane Biology Tsinghua-Peking Center for Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China Department of Pathology and Pathophysiology Key Laboratory of Disease Proteomics of Zhejiang Province Zhejiang University School of Medicine Hangzhou 310058 China

Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly downregulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover,β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.

关键词： zinc zinc transporter pancreatic islets β-cells insulin secretion

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不同硒累积型水稻耐高硒毒害差异特征研究

核农学报 2023年第8期37卷 1681-1689页

作者：卜少腾李衍亮李玉义谭卓贤张木东莞理工学院生态环境与建筑工程学院广东东莞523808 广东省农业科学院农业资源与环境研究所/农业农村部南方植物营养与肥料重点实验室/广东省养分资源循环利用与耕地保育重点实验室广东广州510640 中国农业科学院农业资源与农业区划研究所北京100081 仲恺农业工程学院资源与环境学院广东广州510225

为探究不同硒累积水稻品种耐高硒毒害能力差异特征,本研究设置盆栽试验,以硒高、低累积水稻(Oryza sativa L.)品种为试验材料,研究了不同硒累积水稻品种在不同硒水平处理(0、0.5、25 mg·kg-1)下生长、生理特性及硒结合蛋白基因表达量... 详细信息

为探究不同硒累积水稻品种耐高硒毒害能力差异特征,本研究设置盆栽试验,以硒高、低累积水稻(Oryza sativa L.)品种为试验材料,研究了不同硒累积水稻品种在不同硒水平处理(0、0.5、25 mg·kg-1)下生长、生理特性及硒结合蛋白基因表达量的差异变化特征。结果表明,施用低浓度硒(0.5 mg·kg-1)能显著提升硒高累积水稻产量和地上部干物质量,但对硒低累积水稻提升不明显。高硒水平(25 mg·kg-1)下两个水稻品种产量和地上部干物质量均显著降低,但硒低累积水稻降幅更大。施硒显著提高了硒高累积水稻的抗氧化能力,其超氧化物歧化酶(SOD)、过氧化物酶(POD)、过氧化氢酶(CAT)活性和抗坏血酸(ASA)、谷胱甘肽(GSH)、类胡萝卜素(CAR)含量较不施硒处理分别增加了45.10%、10.30%、35.30%、68.10%、28.90%和26.00%。各施硒处理下,硒高累积水稻丙二醛(MDA)含量均显著低于硒低累积水稻。低浓度硒对两个水稻品种碳氮代谢产物含量均有提升作用,与不施硒处理相比,硒高累积水稻的可溶性糖含量显著增加了0.02个百分点,可溶性蛋白含量显著增加了15.10%,并且高硒水平下硒高累积水稻碳氮代谢产物含量均显著高于硒低累积水稻。两种施硒处理对硒高累积水稻硒结合蛋白基因的相对表达量均有显著提升作用且均高于硒低累积水稻。综上,硒高累积水稻在硒胁迫下拥有更强的抗氧化及碳氮代谢能力,同时能将更多的硒与硒结合蛋白结合而减轻其毒害作用,具有更强的耐高硒毒害能力。本研究结果为生产富硒水稻提供了技术和理论参考。

关键词：硒水稻抗氧化酶抗氧化物质碳氮代谢

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逍遥散类方治疗肝癌的研究进展

环球中医药 2022年第8期15卷 1491-1496页

作者：李卓娴徐丽静夏猛广西中医药大学基础医学院南宁530200

逍遥散类方是指黑逍遥散、加味逍遥散、四逆散、加味四逆散、肝积方、丹栀逍遥丸、柴胡疏肝散、逍遥丸等以逍遥散为核心方或类似方化裁而来的各种方剂。近年来多有研究表明逍遥散类方在临床上可用于肝癌的治疗,对肝癌治疗表现出多靶点... 详细信息

逍遥散类方是指黑逍遥散、加味逍遥散、四逆散、加味四逆散、肝积方、丹栀逍遥丸、柴胡疏肝散、逍遥丸等以逍遥散为核心方或类似方化裁而来的各种方剂。近年来多有研究表明逍遥散类方在临床上可用于肝癌的治疗,对肝癌治疗表现出多靶点、多层次的治疗效果。本文通过收集相关文献发现,逍遥散类方可以通过阻滞细胞周期、调控Ca信号、调控Bcl-2与TP53以及血管生成因子来抑制肿瘤细胞的增殖,诱导肿瘤细胞的凋亡,抗肿瘤血管生成并抑制肿瘤细胞的侵袭,从而影响肝癌肿瘤细胞,发挥治疗肝癌的作用。逍遥散类方还可通过调控炎性细胞因子与淋巴细胞亚群以调节免疫机制,调节单胺类神经递质与神经营养因子以调节神经系统,调节抗氧化酶、激活Nrf2信号通路、抑制一氧化氮水平而抗氧化应激并控制炎症反应以保护肝功能,调节益生菌的丰度、恢复肠道菌群的构成,即通过整体调节发挥治疗肝癌的作用。本文对逍遥散类方治疗肝癌的相关文献进行了综述,总结了逍遥散类方的作用机制,以期为逍遥散类方运用于临床提供参考与指导。

关键词：逍遥散肝癌肝细胞癌作用机制综述中医药

思政教育融入专业课程的教学实践研究——以中医基础理论为例

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中国中医药现代远程教育 2023年第15期21卷 3-5页

作者：徐丽静李卓娴夏猛广西中医药大学基础医学院广西南宁530200

中医基础理论是中医学专业的入门课程,是大学生进行思政建设的有效途径之一。此文从中医基础理论课程着手,设计了课程思政案例,深入挖掘该门课程的德育元素,从教学内容、教学方法、教学反馈等层面进行了课程思政的教学设计与尝试。实践... 详细信息

中医基础理论是中医学专业的入门课程,是大学生进行思政建设的有效途径之一。此文从中医基础理论课程着手,设计了课程思政案例,深入挖掘该门课程的德育元素,从教学内容、教学方法、教学反馈等层面进行了课程思政的教学设计与尝试。实践表明,通过梳理专业课程的教学内容,结合中华传统文化、辨证思维方法和社会主义价值观,嵌入思政教育元素,将中医基础理论内容与思想政治教育二者有机融合,能够使学生更容易接受并学习专业知识,进而丰富课程思政的内涵,达到润物无声的育人效果,以期培养一代又一代有理想、有文化、有道德的中医人。

关键词：思政教育中医基础理论课程思政