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Effects of NLRP3 Inflammasome Mediated Pyroptosis on Cardiovascular Diseases and Intervention Mechanism of Chinese medicine

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Chinese Journal of Integrative medicine 2024年第5期30卷 468-479页

作者： ZHONG Yi LI Xin-yue LIANG Tian-jun DING Bao-zhu MA Ke-xin REN Wen-xuan LIANG Wen-jie College of integrated traditional Chinese and western medicine Hebei University of Chinese MedicineHebei Key Laboratory of Integrated Traditional Chinese and Western Medicine in Liver and Kidney DiseasesInstitute of Integrated Traditional Chinese and Western MedicineShijiazhuang 050200China Department of Cardiovascular Internal medicine the Second Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi Province 332000China Graduate School Hebei Medical UniversityShijiazhuang 050017China Rural Physician College Hebei Medical UniversityShijazhuang 050017China medical Department the First Hospital of Hebei Medical UniversityShijiazhuang 050030China

Activation of the NOD-like receptor protein 3(NLRP3)inflammasome signaling pathway is an important mechanism underlying myocardial pyroptosis and plays an important role in inflammatory damage to myocardial tissue in patients with cardiovascular diseases(CVDs),such as diabetic cardiomyopathy,ischemia/reperfusion injury,myocardial infarction,heart failure and *** RNAs(nc RNAs)are important regulatory *** Chinese medicine(CM)compounds,including their effective components,can regulate pyroptosis and exert myocardium-protecting *** mechanisms underlying this protection include inhibition of inflammasome protein expression,Toll-like receptor 4–NF-κB signal pathway activation,oxidative stress,endoplasmic reticulum stress(ERS),and mixed lineage kinase 3 expression and the regulation of silent information regulator *** NLRP3 protein is an important regulatory target for CVD prevention and treatment with *** the effects of the interventions mediated by CM and the related mechanisms provides new ideas and perspectives for CVD prevention and treatment.

关键词： pyroptosis cardiovascular diseases Chinese medicine NOD-like receptor protein 3 mechanisms

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Flurbiprofen microneedle patches for the management of acute postoperative pain

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Nano research 2024年第8期17卷 7493-7503页

作者： Huaqing Chu Yanyan Zhang Yuan Yang Jiangtao Xue Cong Li Wei Zhang Zhou Li Hui Zheng National Cancer Center/National Clinical research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Beijing institute of Nanoenergy and Nanosystems Chinese Academy of SciencesBeijing 101400China Key Laboratory of Hunan Province for integrated traditional Chinese and western medicine on Prevention and Treatment of Cardio-Cerebral Diseases School of Integrated Chinese and Western MedicineHunan University of Chinese MedicineChangsha 410208China School of Life Science Institute of Engineering MedicineBeijing Institute of TechnologyBeijing 100081China institute of Process Engineering Chinese Academy of SciencesBeijing 100190China

Acute postoperative pain is commonly treated with flurbiprofen(FBP),but conventional delivery methods are *** study prepared a new non-burst release microneedles(MNs)using genipin cross-linked gelatin(cGel).By adding varying amounts of genipin to modulate the crosslinking degree of cGel,the drug release behavior of the drug-loaded MNs in the skin can be *** crosslinking parameters that meet therapeutic requirements are selected,thus providing rapid and longlasting analgesic *** solutions were successfully cross-linked,altering matrix material microstructure,confirmed by scanning electron microscope imaging and fourier transform infrared *** demonstrated increasing mechanical strength with higher *** release rates were rapid initially,then slowed,exhibiting a characteristic of decreased release rates with increasing degrees of *** vivo,FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery,with the greatest effect observed at 2–3 h post-surgery,and can maintain analgesia for up to 6 *** tests confirmed good ***/cGel MNs effectively penetrate the stratum corneum,safely delivering drugs with significant analgesic effects,excellent mechanical properties,and good biocompatibility,representing a promising strategy for managing acute postoperative pain.

关键词： microneedle postoperative pain flurbiprofen non-steroid anti-inflammatory drug cross-linked gelatin

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Efficacy and safety of Huzhang Granule,a compound Chinese herbal medicine,for acute gouty arthritis:A double-blind,randomized controlled trial

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Journal of Integrative medicine 2024年第3期22卷 270-278页

作者： Hao Wang Si-ting Chen Xiao-jie Ding Le Kuai Liang Hua Xin Li Yi-fei Wang Ming Zhang Bin Li Rui-ping Wang Mi Zhou Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China institute of Dermatology Shanghai Academy of Traditional Chinese MedicineShanghai 201203China Department of Dermatology the Affiliated Hospital of Jiangxi University of Chinese MedicineNanchang 330000Jiangxi ProvinceChina Shanghai Skin Disease Hospital School of MedicineTongji UniversityShanghai 200443China institute of Dermatology School of MedicineTongji UniversityShanghai 200443China

Background:Acute gouty arthritis(AGA)is an inflammatory joint disease with a high *** medical interventions,including nonsteroidal anti-inflammatory drugs,colchicine and glucocorticoids,can have serious adverse *** Granule(HZG),a compound Chinese herbal medicine,has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse ***,the efficacy and safety of HZG in AGA patients remains ***:The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA ***,setting,participants and interventions:The current study was conducted as a noninferiority,randomized controlled clinical trial on 180 eligible enrolled *** were randomly assigned into the HZG and etoricoxib *** were administered for 5 d,during which the HZG group received HZG and placebo etoricoxib,while the etoricoxib group received etoricoxib and placebo HZG in the same ratio(1:1).Main outcome measures:The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment *** pain level was measured via a visual analogue scale,ranging from 0 mm to 100 *** secondary outcomes comprised joint tenderness and swelling,reduction of inflammatory biomarkers,and the patient’s and investigator’s global evaluations of therapeutic ***:The mean reduction in pain was-51.22 mm(95%confidence interval[CI],[-53.42,-49.03]mm)for the HZG and-52.00 mm(95%CI,[-54.06,-49.94]mm)for the etoricoxib *** mean difference between the two groups was 0.78 mm(95%CI,[-2.25,3.81]mm).All additional efficacy endpoints,covering decreased inflammation and pain relief,yielded compelling proof of *** in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group(4.44%vs 13.33%;P≤0.05).Conclusion:HZG and etoricoxib groups demons

关键词： Acute gouty arthritis Huzhang Granule Randomized controlled trial Blind

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Cortical Organoid-on-a-Chip with Physiological Hypoxia for Investigating Tanshinone IIA-Induced Neural Differentiation

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research 2024年第3期2023卷 457-468页

作者： Yue Zhi Yujuan Zhu Jinglin Wang Junqi Zhao Yuanjin Zhao Department of Rheumatology and Immunology Nanjing Drum Tower HospitalClinical Medical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing210023China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Shenzhen research institute Southeast UniversityShenzhen518038China

Cortical organoids represent cutting-edge models for mimic human brain development during the early and even middle stage of pregnancy, while they often fail to recreate the complex microenvironmental factors, such as physiological hypoxia. Herein, to recapitulate fetal brain development, we propose a novel cortical organoid-on-a-chip with physiological hypoxia and further explore the effects of tanshinone IIA (Tan IIA) in neural differentiation. The microfluidic chip was designed with a micropillar array for the controlled and efficient generation of cortical organoids. With low oxygen, the generated cortical organoids could recapitulate key aspects of early-gestational human brain development. Compared to organoids in normoxic culturing condition, the promoted neurogenesis, synaptogenesis and neuronal maturation were observed in the present microsystem, suggesting the significance of physiological hypoxia in cortical development. Based on this model, we have found that Chinese herbal drug Tan IIA could promote neural differentiation and maturation, indicating its potential therapeutic effects on neurodevelopmental disorders as well as congenital neuropsychiatric diseases. These results indicate that the proposed biomimetic cortical organoid-on-a-chip model with physiological hypoxia can offer a promising platform to simulate prenatal environment, explore brain development, and screen natural neuroactive components.

关键词： promoted herbal cutting

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Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

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Journal of Pharmaceutical Analysis 2024年第2期14卷 177-195页

作者： Haochen Hui Zhuoya Wang Xuerong Zhao Lina Xu Lianhong Yin Feifei Wang Liping Qu Jinyong Peng Department of Pharmaceutical Analysis College of PharmacyDalian Medical UniversityDalianLiaoning116044China Innovation Materials research and Development Center Botanee Research InstituteYunnan Botanee Bio-technology Group Co.Ltd.Kunming650106China Department of traditional Chinese medicine Pharmacology School of PharmacyAnhui University of Chinese MedicineHefei230012China

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is *** acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and *** results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism *** transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model *** conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against *** is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

关键词： Gut microbiota Inflammatory bowel disease Polysaccharide Selaginella uncinata(Desv.)Spring Thiamine metabolism

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Tongqiao Yizhi granule(通窍益智颗粒) repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats

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Journal of traditional Chinese medicine 2024年第4期44卷 680-687页

作者： LI Yanjiao HAO Linyao LI Shuangyang LUO Yanqi WANG Juan WANG Raoqiong BAI Xue College of Integrative medicine Southwest Medical UniversityLuzhou 646600China Department of Neurology and National traditional Chinese medicine Clinical research Base the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhou 646000China institute of integrated Chinese and western medicine Southwest Medical UniversityLuzhou 646000China

OBJECTIVE:To explore the mechanism by which Tongqiao Yizhi granule(通窍益智颗粒,TQYZKL)intervenes pyroptosis to treat vascular dementia(VaD)in a rat ***:The rat model of VaD was established by two-vessel occlusion(2VO).The rats were randomly divided into Sham group,Model group,Nimodipine group,TQYZKL(6.2 g·kg^(-1)·d^(-1)),TQYZKL(12.4 g·kg^(-1)·d^(-1)),TQYZKL(24.8 g·kg^(-1)·d^(-1)).The Morris water maze(MWM)test was carried out to test the learning and memory function;Hematoxylin-eosin staining and transmission electron microscopy(TEM)to observe the pathological damage in the hippocampus;Tunel fluorescence staining to detect neuronal pyroptosis in the *** expression levels of pyroptosis-related proteins,namely Golgi peripheral membrane protein p65(P65),nucleotide oligomerization domain-like receptors 3(NLRP3),caspase-1 and Gasdermin D(GSDMD),were detected using western blotting and reverse transcription polymerase chain ***,the serum levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)were determined through the enzyme-linked immunosorbent ***:The study revealed that TQYZKL effectively improved the ability of VaD ratsto learn and memorize,relieved the pathological damage in the hippocampus,restored neuronal morphology,and reduced the expression of pyroptosis-related proteins P65,NLRP3,caspase-1,GSDMD-N,IL-18 and IL-1β(P<0.05).CONCLUSION:TQYZKL inhibits neuronal pyroptosis in the hippocampus of VaD rats by regulating nuclear factor kappa-B/NLRP3/caspase-1 signaling pathway,thus exerting a therapeutic effect on VaD in the rats.

关键词： NLRP3 rats kappa

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Discovery and characterization of naturally occurring covalent inhibitors of SARS-CoV-2 M^(pro)from the antiviral herb Ephedra

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Chinese Journal of Natural medicines 2024年第9期22卷 797-807页

作者： HU Qing ZHANG Yiwen CHEN Pengcheng ZHANG Yani ZHU Guanghao LIU Wei WANG Chaoran ZHENG Shuilian SHEN Nonger WANG Haonan HUANG Ping GE Guangbo Center for Clinical Pharmacy Cancer CenterDepartment of PharmacyZhejiang Provincial People’s Hospital(Affiliated People’s Hospital)Hangzhou Medical CollegeHangzhou 310014China Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghai 201203China Shuguang Hospital Affiliated to Shanghai university of traditional Chinese medicine Shanghai 200021China dalian institute of Chemical Physics Chinese Academy of SciencesDalian 116023China

The Chinese herb Ephedra(also known as Mahuang)has been extensively utilized for the prevention and treatment of coronavirus-induced diseases,including coronavirus disease 2019(COVID-19).However,the specific anti-SARS-CoV-2 compounds and mechanisms have not been fully *** main protease(M^(pro))of SARS-CoV-2 is a highly conserved enzyme responsible for proteolytic processing during the viral life cycle,making it a critical target for the development of antiviral *** study aimed to identify naturally occurring covalent inhibitors of SARS-CoV-2 M^(pro)from Ephedra and to investigate their covalent binding *** results demonstrated that the non-alkaloid fraction of Ephedra(ENA)exhibited a potent inhibitory effect against the SARS-CoV-2 M^(pro)effect,whereas the alkaloid fraction did ***,the chemical constituents in ENA were identified,and the major constituents'anti-SARS-CoV-2 M^(pro)effects were *** the tested constituents,herbacetin(HE)and gallic acid(GA)were found to inhibit SARS-CoV-2 M^(pro)in a time-and dose-dependent *** combination displayed a significant synergistic effect on this key ***,various techniques,including inhibition kinetic assays,chemoproteomic methods,and molecular dynamics simulations,were employed to further elucidate the synergistic anti-M^(pro)mechanisms of the combination of HE and ***,this study deciphers the naturally occurring covalent inhibitors of SARS-CoV-2 M^(pro)from Ephedra and characterizes their synergistic anti-M^(pro)synergistic effect,providing robust evidence to support the anti-coronavirus efficacy of Ephedra.

关键词： Main protease Ephedra Ephedra non-alkaloid fraction Covalent inhibitors Synergistic effect

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A novel FGFR1 inhibitor CYY292 suppresses tumor progression,invasion,and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis

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Genes & Diseases 2024年第1期11卷 479-494页

作者： Yanran Bi Ruiling Zheng Jiahao Hu Ruiqing Shi Junfeng Shi Yutao Wang Peng Wang Wenyi Jiang Gyudong Kim Zhiguo Liu Xiaokun Li Li Lin School of Pharmaceutical Science Wenzhou Medical UniversityWenzhouZhejiang 325035China College of Pharmacy and research institute of Drug Development Chonnam National UniversityGwangju 61186Republic of Korea Department of Dermatology Wenzhou Hospital of Integrated Traditional Chinese and Western MedicineWenzhouZhejiang 325000China Zhejiang Lab for Regenerative medicine Oujiang LaboratoryWenzhouZhejiang 325035China

Glioblastoma(GBM)is a malignant brain tumor that grows quickly,spreads widely,and is resistant to *** growth factor receptor(FGFR)1 is a receptor tyrosine kinase that regulates cellular processes,including proliferation,survival,migration,and ***1 was predominantly expressed in GBM tissues,and FGFR1 expression was negatively correlated with overall *** rationally designed a novel small molecule CYY292,which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in ***292 also exerted an effect on the conserved Ser777 residue of ***292 dose-depen-dently inhibited cell proliferation,epithelial-mesenchymal transition,stemness,invasion,and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells,and this effect was prevented by pharmacological inhibitors and critical gene *** vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than ***292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM *** study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292,which targets FGFR1,on downstream signaling pathways directly reducing GBM cell growth,invasion,and metastasis and thus impairing the recruitment,activation,and function of immune cells.

关键词： Blood-brain barrier EMT FGFR1 FGFR1 inhibitor Glioblastoma

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin Xing Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering research Center of traditional Chinese medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Department of Rehabilitation medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence(Fudan university) Ministry of EducationShanghaiChina Human Phenome institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

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Organic Integration of traditional Chinese and western medicines—Future of Clinical Practice Guidelines of integrated traditional Chinese and western medicines

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Chinese Journal of Integrative medicine 2024年第4期30卷 359-365页

作者： XIE Ying-lan HAN Fei JIN Ying-hui DING Yan-bing GUO Jing JI Dong-xiao ZHANG Teng CHENXiao-min SHANG Hong-cai Department of traditional Chinese medicine Encephalopathy Hubei Provincial Hospital of Traditional Chinese MedicineWuhan(430074)China Department of traditional Chinese medicine Encephalopathy Hubei Province Traditional Chinese Medicine Research InstituteWuhan(430074)China Xuanwu Hospital of traditional Chinese medicine Beijing(100000)China Center for Evidence-Based and Translational medicine Zhongnan Hospital of Wuhan UniversityWuhan(430074)China College of Acupuncture and Massage College of Health and RehabilitationNanjing University of Chinese MedicineNanjing(210023)China Department of Ophthalmology Huaihe Hospital of Henan UniversityKaifengHenan Province(475000)China Ministry of Education and Beijing Key Laboratory of Internal medicine of traditional Chinese medicine Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine/Ministry of Education and Beijing Key Laboratory of Internal Medicine of Traditional Chinese MedicineBeijing(100700)China

The transformation and implementation of clinical practice guidelines for integrated traditional Chinese medicine(TCM)and western medicine(WM)is crucial to the adoption of medical science and technological findings and is an important way for TCM to be made available to the ***,clinical practice guidelines(CPGs)of TCM and WM integration in recent years was analyzed to clarify the current situation and problems in the existing guidelines according to the following four perspectives:(1)perspective of TCM and WM integration in guidelines,(2)diagnosis Using integrated TCM and WM,(3)integration of TCM and WM treatment,(4)promoting TCM and WM ***,the information and quality evaluation of CPGs for integrated Chinese and western medicine in 2020–2022 were analyzed to explore the degree and methods of integration of Chinese and western medicine *** last this study aimed to lay a foundation for the further establishment of Chinese characteristic,repeatable,and calculable clinical practice guidelines of TCM and WM integration.

关键词： clinical practice guidelines integrated traditional Chinese and western medicine organic integration

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