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Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese medicine and Western medicine

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Military Medical Research 2024年第3期11卷 313-322页

作者： Ying-Hui Jin Yan-Ping Wang Ying-Lan Xie Gui-Hua Tian Xiao-Yu Zhang Nan-Nan Shi Ke-Hu Yang Xin Sun Yao-Long Chen Da-Rong Wu Xin-Feng Guo Long Ge Chen Zhao Cheng Lu Yin Jiang Jing Guo Si-Yu Yan Yong-Bo Wang Qiao Huang Xiang-Ying Ren Ying-Yue Rao Yun-Yun Wang Meng-Qian Yuan Xian-Tao Zeng Hong-Cai Shang center for Evidence-Based and translational medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Institute of Basic Research in Clinical medicine China Academy of Chinese Medical SciencesBeijing 100700China China center for Evidence Based Traditional Chinese medicine Beijing 100029China Hubei Provincial Hospital of Traditional Chinese medicine Wuhan 430074China Key Laboratory of Chinese Internal medicine of Ministry of Education and Beijing Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China Evidence-Based medicine center School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China China center for Evidence-Based medicine West China Hospital of Sichuan UniversityChengdu 610041China State Key Laboratory of Dampness Syndrome of Chinese medicine the Second Affliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Evidence-based medicine Team Guangdong Provincial Hospital of Traditional Chinese MedicineGuangzhou 510120China Nanjing University of Chinese medicine Nanjing 210023China Jiangsu Province Hospital of Chinese medicine Nanjing 210029China

Integrated traditional Chinese medicine(TCM)and Western medicine(WM)is a new medical science grounded in the knowledge bases of both TCM and WM,which then forms a unique modern medical system in China.Integrated TCM and WM has a long history in China,and has made important achievements in the process of clinical diagnosis and treatment.However,the methodological defects in currently published clinical practice guidelines(CPGs)limit its development.The organic integration of TCM and WM is a deeper integration of TCM and WM.To realize the progression of"integration"to"organic integration",a targeted and standardized guideline development methodology is needed.Therefore,the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

关键词： Methodology Traditional Chinese medicine Western medicine Organic integration Clinical practice guidelines(CPGs)

Neuroprotective effects of chaperone-mediated autophagy in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1291-1298页

作者： Qi Jia Jin Li Xiaofeng Guo Yi Li You Wu Yuliang Peng Zongping Fang Xijing Zhang Department of Anesthesiology and Perioperative medicine and Department of Intensive Care Unit Xijing Hospital The Fourth Military Medical University Department of Critical Care medicine translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People's Hospital School of Medicine Tongji University

Chaperone-mediated autophagy is one of three types of autophagy and is characterized by the selective degradation of proteins. Chaperone-mediated autophagy contributes to energy balance and helps maintain cellular homeostasis, while providing nutrients and support for cell survival. Chaperone-mediated autophagy activity can be detected in almost all cells, including neurons. Owing to the extreme sensitivity of neurons to their environmental changes, maintaining neuronal homeostasis is critical for neuronal growth and survival. Chaperone-mediated autophagy dysfunction is closely related to central nervous system diseases. It has been shown that neuronal damage and cell death are accompanied by chaperone-mediated autophagy dysfunction. Under certain conditions, regulation of chaperone-mediated autophagy activity attenuates neurotoxicity. In this paper, we review the changes in chaperone-mediated autophagy in neurodegenerative diseases, brain injury, glioma, and autoimmune diseases. We also summarize the most recent research progress on chaperone-mediated autophagy regulation and discuss the potential of chaperone-mediated autophagy as a therapeutic target for central nervous system diseases.

关键词： chaperone-mediated autophagy neurodegenerative disease neuronal homeostasis neuroprotection

Deficiency of Trp53 and Rb1 in myeloid cell lineage spontaneously develops acute myeloid leukemia in a mouse model

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Genes & Diseases 2024年第1期11卷 4-6页

作者： Yang Li Shu-ting Yang Shuying Yang Department of Basic&translational Sciences School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Orthopaedic Surgery School of MedicineJohns Hopkins University BaltimoreMD 21205USA center for Innovation&Precision Dentistry School of Dental MedicineSchool of Engineering and Applied SciencesUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Penn center for Musculoskeletal Disorders School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Acute myeloid leukemia(AML)is a rapidly lethal blood cancer characterized by aberrant proliferation and differentiation of myeloid progenitors in the hematopoietic tissue.In recent decades,AML patients are significantly increased.In 2019 alone,21,450 new AML cases were diagnosed in the United States,with an estimated 10,920 deaths due to AML.What’s worse,AML occurs with an increasing incidence with advanced age,and the survival rate remains dismal with a median overall survival of only 5e10 months.Notwithstanding great advances in allogenic transplant and chemotherapy,the therapeutic outcomes are unfavorable due to the disease relapse and mortality rates.More importantly,the development of more specific and effective therapies was hampered in part by the lack of proper animal models for AML.Thus,management and elucidation of the pathological mechanism of AML remain an ongoing challenge,and the development of effective AML mouse models and treatment options are urgently needed.

关键词： myeloid Acute leukemia

Hodgkin's lymphoma:2023 update on treatment

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Cancer Biology & medicine 2024年第4期21卷 269-273页

作者： Sicong Zhang Xianming Liu Lanfang Li Lihua Qiu Zhengzi Qian Shiyong Zhou Xianhuo Wang Huilai Zhang Department of Lymphoma Tianjin Medical University Cancer Institute&HospitalNational Key Laboratory of Druggability Evaluation and Systematic Translational MedicineNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinThe Sino-US Center for Lymphoma and Leukemia ResearchTianjin 300060China

Hodgkin's lymphoma(HL)is a common,malignant hematological tumor of the lymph nodes and lymphatic system,accounting for 10%of all lymphomas.HL comprises 2 main subtypes:classical HL(cHL)and nodular lymphocyte predomina... 详细信息

关键词： lymphoma treatment predominant

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

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Acta Pharmaceutica Sinica B 2024年第2期14卷 579-601页

作者： Jing Yan Hao Zhang Guangfeng Li Jiacan Su Yan Wei Can Xu Institute of translational medicine Shanghai UniversityShanghai 200444China Institute of medicine Shanghai UniversityShanghai 200444China Department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China Organoid Research center Shanghai UniversityShanghai 200444China Department of Gastroenterology Changhai HospitalShanghai 200433China

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in 2018.To illuminate the unique superiority of lipid nanovehicles in RNA delivery,in this review,we first introduce various RNA therapeutics,describe systemic delivery barriers,and explain the lipid components and methods used for lipid nanovehicle preparation.Then,we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery.Finally,the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed.Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery,inspiring the development of more high-performance RNA lipid nanovesicles in the future.

关键词： Lipid nanovehicles RNAtherapeutics Barriers to systemicRNA delivery Lipid components Fabricationmethods Lipid nanovehicledesign Extrahepatictissue targeting Organ tropism

EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1187-1203页

作者： Yongyun Li Tianyu Zhu Jie Yang Qianqian Zhang Shiqiong Xu Shengfang Ge Renbing Jia Jianming Zhang Xianqun Fan Department of Ophthalmology Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology Shanghai 200001China National Research center for translational medicine(Shanghai) State Key Laboratory of Medical GenomicsShanghai Institute of HematologyRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of translational medicine Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai 200240China

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma(UM).Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular functions.In search of genetic vulnerability for UM,we found that inhibition of euchromatic histone lysine methyltransferase 2(EHMT2)expression or activity significantly reduced the proliferation and migration capacity of cancer cells.Notably,elevated expression of EHMT2 had been validated in UM samples.Furthermore,Kaplan-Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T stage.Chromatin immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of EHMT2.Its transcription was suppressed by EHMT2 in a methyltransferasedependent pattern in GNAQ/11-mutant UM cells,leading to elevated RhoA activity.Rescuing constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic phenotypes.Simultaneously blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth,suggesting the driver role of these two key molecules.In summary,our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

关键词： Uveal melanoma EHMT2 RhoA pathway ARHGAP29 G protein GNAQ GNA11

Efficacy and safety of extracorporeal shock wave therapy combined with sodium hyaluronate in treatment of knee osteoarthritis:a systematic review and Meta-analysis

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Journal of Traditional Chinese medicine 2024年第2期44卷 243-250页

作者： ZHOU Mingwang DONG Zhuanli WEI Changhao FENG Lufang WANG Xiaoping LIU Haiping JI Xing YANG Kehu LI Shenghua Department of Orthopaedics Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050China Department of Quality Management Lanzhou Petrochemical General HospitalLanzhou 730050China Department of Orthopaedics Lanzhou Petrochemical General HospitalLanzhou 730050China Evidence-Based Social Science Research center School of Public HealthLanzhou UniversityLanzhou730000China Evidence-Based medicine center School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China Key Laboratory of Evidence Based medicine and Knowledge Translation of Gansu Province Lanzhou 730000China center for translational medicine Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050China Department of Orthopaedics Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730000China

OBJECTIVE:To assess the efficacy and safety of extracorporeal shockwave therapy(ESWT)combined with sodium hyaluronate(HA)for the treatment of knee osteoarthritis(KOA).METHODS:PubM ed,Embase,the Cochrane Library,Web of Science,China National Knowledge Infrastructure,Wanfang database,China Science and Technology Journal Database,and SinoMed were searched from inception to July 2020.The quality of the randomized controlled trials was evaluated independently by two reviewers according to the criteria in the Cochrane Collaboration for Systematic Reviews.The identified articles were then screened individually using EndnoteX9 for eligibility in this Meta-analysis.The heterogeneity among the articles was evaluated using I2.RESULTS:A total of 17 studies,comprising 2000 individuals,were included in this Meta-analysis.The results showed that a significant improvement was observed in knee pain and function based on the clinical efficacy of ESWT combined with HA.Statistical analysis of clinical efficacy showed that[relative risk(RR)=1.21,95%confidence interval(CI)(1.12,1.30),Pcenter trials are warranted to validate the current findings.

关键词： osteoarthritis knee randomized controlled trial extracorporeal shockwave therapy hyaluronic acid Meta-analysis

Metal nanoparticles for cancer therapy:Precision targeting of DNA damage

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1132-1149页

作者： Qian Chen Chunyan Fang Fan Xia Qiyue Wang Fangyuan Li Daishun Ling Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Frontiers Science center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China World Laureates Association(WLA)Laboratories Shanghai 201203China Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province Hangzhou 310009China

Cancer,a complex and heterogeneous disease,arises from genomic instability.Currently,DNA damage-based cancer treatments,including radiotherapy and chemotherapy,are employed in clinical practice.However,the efficacy and safety of these therapies are constrained by various factors,limiting their ability to meet current clinical demands.Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy.Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms.In this review,we delve into the design principles and optimization strategies of metal nanoparticles.We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles.These encompass targeted drug delivery,inhibition of DNA repair mechanisms,induction of cell death,and the cascading immune response.Moreover,we explore the pivotal role of physicochemical factors such as nanoparticle size,stimuli-responsiveness,and surface modification in shaping metal nanoparticle platforms.Finally,we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy,paving the way for novel treatment paradigms.

关键词： DNA damage Metal nanoparticles Nucleus-targeting DNA repair inhibition Immune response Size optimization Stimuli-responsiveness Surface modification

High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National center for Advancing translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles.Previous studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein adducts.The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes.In the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers.Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,respectively.Mechanistically,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against AILI.We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists.Among these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in mice.In conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2