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Isorhamnetin Downregulates MMP2 and MMP9 to Inhibit Development of Rheumatoid Arthritis through SRC/ERK/CREB Pathway

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chinese Journal of Integrative medicine 2024年第4期30卷 299-310页

作者： LIU Xiao-rong LI Shuo-fu MEI Wen-ya LIU Xiang-dan ZHOU Ri-bao College of Pharmacy Hunan University of Chinese MedicineChangsha(410208)China Department of Orthopaedics The First Hospital of Hunan University of Chinese MedicineChangsha(410007)China

Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis(RA).Methods Tumor necrosis factor(TNF)-α-induced fibroblast-like synoviocytes(FLS)was exposed to additional isorhamnetin(10,20 and 40µmol/L).Overexpression vectors for matrix metalloproteinase-2(MMP2)or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS ***-FLS viability,migration,and invasion were ***,a collagen-induced arthritis(CIA)rat model was *** were randomly divided to sham,CIA,low-,medium-,and high-dosage groups using a random number table(n=5 in each group)and administed with normal saline or additional isorhamnetin[2,10,and 20 mg/(kg·day)]for 4 weeks,*** index was calculated and synovial tissue inflammation was determined in CIA *** levels of MMP2,MMP9,TNF-α,interleukin-6(IL-6),and IL-1β,as well as the phosphorylation levels of SRC,extracellular regulated kinase(ERK),and cyclic adenosine monophosphate response element-binding(CREB),were detected in RA-FLS and synovial *** docking was also used to analyze the binding of isorhamnetin to *** In in vitro studies,isorhamnetin inhibited RA-FLS viability,migration and invasion(P<0.05).Isorhamnetin downregulated the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1βin RA-FLS(P<0.05).The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion,as well as the levels of TNF-α,IL-6,and IL-1β(P<0.05).Furthermore,isorhamnetin bound to SRC and reduced the phosphorylation of SRC,ERK,and CREB(P<0.05).SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability,migration and invasion,as well as the negative regulation of MMP2 and MMP9(P<0.05).In in vivo studies,isorhamnetin decreased arthritis index scores(P<0.05)and alleviated synovial *** reduced the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1β,as well as the phosphorylation of SRC,ERK,and CRE

关键词： rheumatoid arthritis isorhamnetin SRC/ERK/CREB matrix metalloproteinase

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Reconstruction of Postinfarcted Cardiac Functions Through Injection of Tanshinone IIA@ Reactive Oxygen Species-Sensitive Microspheres Encapsulated in a Thermoreversible Hydrogel

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Energy & Environmental Materials 2024年第2期7卷 191-203页

作者： Ling Yu Yubin Liang Lei Gao Peipei Chen Zhiqiang Yu Minzhou Zhang Aleksander Hinek Shuai Mao Second Clinical College Guangzhou University of Chinese Medicine Department of Critical Care medicine Guangdong Provincial Hospital of Chinese Medicine Guangdong Provincial Branch of National Clinical Research Centre for chinese medicine Cardiology Department of Radiation medicine and Applied Sciences University of California San Diego Department of Laboratory medicine Dongguan Institute of Clinical Cancer Research Affiliated Dongguan Hospital Southern Medical University Translational medicine Hospital for Sick Children

Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death, highlighting the urgent clinical need for effective therapies. Recently, tanshinone IIA has been identified as a promising therapeutic agent for myocardial infarction. However, efficient delivery remains a major issue that limits clinical translation. To address this problem, an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid) gel(PLGA-PEG-PLGA) system encapsulating tanshinone IIA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinone IIA) has been designed and synthesized in this study. The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature. Microspheres initially immobilized by the gel exhibit excellent reactive oxygen speciestriggered release properties in a high-reactive oxygen species environment after myocardial infarction onset. As a result, encapsulated tanshinone IIA is effectively released into the infarcted myocardium, where it exerts local antipyroptotic and anti-inflammatory effects. Importantly, the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinone ***, this novel, precision-guided intra-tissue therapeutic system allows for customized local release of tanshinone IIA, presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.

关键词： myocardial infarction ROS-sensitive polymer tanshinone IIA thermoreversible hydrogel ventricular remodeling

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Biological Evaluation of Lysionotin:a Novel Inhibitor of 5-Lipoxygenase for Anti-glioma

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chinese Journal of Integrative medicine 2024年第9期30卷 826-834页

作者： SHAO Xin-xin CHEN Cong LIU Jie LI Qing-jun HE Shan QI Xiang-hua FU Xian-jun WANG Zhen-guo The First Clinical College of medicine Shandong University of Traditional Chinese MedicineJinan250355China Institute for Literature and Culture of chinese medicine Shandong University of Traditional Chinese MedicineJinan250355China Key Laboratory of Classical Theory of Traditional chinese medicine Ministry of EducationShandong University of Traditional Chinese MedicineJinan250355China College of Pharmacy Shandong University of Traditional Chinese MedicineJinan250355China Experimental Center Shandong University of Traditional Chinese MedicineJinan250355China Neurology Department Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan250014China Marine Traditional chinese medicine Research Center Qingdao Academy of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineQingdao266114Shandong ProvinceChina

Objective:To explore the potential mechanism of lysionotin in treating ***:First,target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of *** binding between 5-lipoxygenase(5-LO)and lysionotin was detected by surface plasmon resonance(SPR)and molecular docking,and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis,***,the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry(LC-MS/MS).The protein expression,intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot,flow cytometry and fluorescence labeling,***:Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO,a key enzyme involved in the arachidonic acid metabolism pathway,to inhibit the proliferation of *** docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds,forming bonds with His600,Gln557,Asn554,and *** analysis further confirmed the interaction between 5-LO and ***,enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50%inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58µmol/L,respectively,and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid(P<0.05),and moreover,the LC-MS/MS results indicated that lysionotin can enter glioma cells well(P<0.01)and inhibit their *** blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO(P<0.05)and downstream leukotriene B4 receptor(P<0.01).In addition,the results showed that lysionotin affected intracellular calcium ion concentration by inh

关键词： 5-lipoxygenase inhibitor lysionotin 5-lipoxygenase leukotriene B4 calcium ion cytoskeleton

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Shuxuening Injection Inhibits Apoptosis and Reduces Myocardial Ischemia-Reperfusion Injury in Rats through PI3K/AKT Pathway

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chinese Journal of Integrative medicine 2024年第5期30卷 421-432页

作者： YUE Tong-tong CAO Ying-jie CAO Ya-xuan LI Wei-xia WANG Xiao-yan SI Chun-ying XIA Han ZHU Ming-jun TANG Jin-fa WANG He The First Clinical Medical College of Henan University of chinese medicine Zhengzhou 450046China Department of Pharmacy the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China Department of Cardiovascular Diseases the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China

Objective: To investigate the main components and potential mechanism of Shuxuening Injection(SXNI) in the treatment of myocardial ischemia-reperfusion injury(MIRI) through network pharmacology and in vivo research. Methods: The Traditional chinese medicine Systems Pharmacology(TCMSP) and Pharm Mapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man(OMIM) and Gene Cards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose(3.68 mg/kg), medium-dose(7.35 mg/kg), and high-dose(14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group(14.7 mg/kg), SXNI+LY294002 group,and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride(TTC) double staining, hematoxylin-eosin(HE) staining, terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay, enzyme-linked immunosorbent assay(ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Results: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) pathway was

关键词： myocardial ischemia reperfusion injury PI3K/AKT signaling pathway Shuxuening Injection apoptosis Ginkgo biloba leaves

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Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention

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chinese Journal of Integrative medicine 2024年第9期30卷 842-851页

作者： GAO Kai-xin YANG Yi-hong LIANG Qi MEI Li-yan LIANG You-bang WANG Mao-jie CHEN Xiu-min HUANG Qing-chun WEN Ze-huai HUANG Run-yue Section of Rheumatology and Immunology Research The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510120China The Second Clinical Medical College Guangzhou University of Chinese MedicineGuangzhou510405China State Key Laboratory of Dampness Syndrome of chinese medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510120China Guangdong-Hong Kong-Macao Joint Lab on chinese medicine and Immune Disease Research Guangzhou University of Chinese MedicineGuangzhou510405China Guangdong Provincial Key Laboratory of Clinical Research on Traditional chinese medicine Syndrome Guangzhou510120China Guangdong Provincial Key Laboratory of chinese medicine for Prevention and Treatment of Refractory Chronic Diseases Guangzhou510120China The Key Unit of Methodology of Clinical Research The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510120China

Rheumatoid arthritis(RA)is a worldwide public health *** to delay or prevent the onset of RA have attracted much attention in recent years,and researchers are now exploring various prevention *** present,there is still no unified consensus for RA prevention,but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely *** to the limited number of clinical trials on pharmacologic interventions,further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to *** this review,we introduce the RA disease process and risk factors,and present research on the use of both Western and chinese medicine from clinical perspectives regarding RA ***,we describe several complete and ongoing clinical studies on the use of chinese herbal formulae for the prevention of RA.

关键词： rheumatoid arthritis prevention chinese medicine review

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Computed tomography-based radiomics diagnostic approach for differential diagnosis between early-and late-stage pancreatic ductal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1256-1267页

作者： Shuai Ren Li-Chao Qian Ying-Ying Cao Marcus J Daniels Li-Na Song Ying Tian Zhong-Qiu Wang Department of Radiology Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of Geratology Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing 210022Jiangsu ProvinceChina Department of Radiology NYU Langone HealthNew YorkNY 10016United States

BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late *** is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest *** A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography(CT)within 30 d prior to surgery were included in the *** staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging *** features were extracted from the region of interest(ROI)for each patient using Analysis Kit *** most important and predictive radiomics features were selected using Mann-Whitney U test,univar-iate logistic regression analysis,and minimum redundancy maximum relevance(MRMR)*** forest(RF)method was used to construct the radiomics model,and 10-times leave group out cross-validation(LGOCV)method was used to validate the robustness and reproducibility of the *** A total of 792 radiomics features(396 from late arterial phase and 396 from portal venous phase)were extracted from the ROI for each patient using Analysis Kit *** most important and predictive features were selected using Mann-Whitney U test,univariate logistic regression analysis,and MRMR *** method was used to construct the radiomics model with the nine most predictive radiomics features,which showed a high discriminative ability with 97.7%accuracy,97.6%sensitivity,97.8%specificity,98.4%positive predictive value,and 96.8%negative predictive *** radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built *** The radiomics model based on CT could serve as a promising non-invasive method in differential diag

关键词： Pancreatic ductal adenocarcinoma Radiomics Computed tomography American Joint Committee on Cancer staging

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Chemical Constituents and Pharmacological Properties of Frankincense:Implications for Anticancer Therapy

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chinese Journal of Integrative medicine 2024年第8期30卷 759-767页

作者： WU Yong-rong XIONG Wei DONG Ying-jing CHEN Xin ZHONG Yuan-yuan HE Xin-ling WANG Yu-jia LIN Qun-fang TIAN Xue-fei ZHOU Qing College of Traditional chinese medicine Hunan University of Chinese MedicineChangsha410208China Department of Andrology the First Hospital of Hunan University of Chinese MedicineChangsha41007China College of medicine Hunan University of Chinese MedicineChangsha410208China College of Traditional chinese and Western medicine Hunan University of Chinese MedicineChangsha410208China Hunan Provincial Key Laboratory of Traditional chinese medicine Prescription and Transformation Changsha410208China Hunan Sexual and Reproductive Health Clinical Medical Research Center of Traditional chinese medicine Changsha410021China

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug ***,a widely recognized natural antitumor medicine,has undergone a systematic review encompassing its species,chemical constituents,and diverse pharmacological activities and *** different species of frankincense include Boswellia serrata,Somali frankincense,Boswellia frereana,and Boswellia *** frankincense extracts and compounds exhibit antitumor,anti-inflammatory,and hepatoprotective properties and antioxidation,memory enhancement,and immunological regulation *** also have comprehensive effects on regulating *** and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against *** review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents,thus laying the foundations for developing effective tumor-combating targets.

关键词： frankincense species chemical constituents anticancer therapy chinesemedicine

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Fu-Zheng-Yi-Liu Formula inhibits the stem cells and metastasis of prostate cancer via tumor-associated macrophages/C-C motif chemokine ligand 5 pathway in tumor microenvironment

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chinese Journal of Natural medicines 2024年第6期22卷 501-514页

作者： CHEN Chiwei HUANG Renlun WANG Neng ZHENG Yifeng ZHOU Jianfu YANG Bowen WANG Xuan ZHANG Juping PAN Bo CHEN Zhiqiang WANG Shengqi WANG Zhiyu XIANG Songtao The Research Center of Integrative Cancer medicine Discipline of Integrated Chinese and Western Medicinethe Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510000China The First Clinical College of Guangzhou University of chinese medicine Guangzhou 510000China Guangdong Provincial Key Laboratory of Clinical Research on Traditional chinese medicine Syndrome Guangdong Provincial Academy of Chinese Medical SciencesGuangdong Provincial Hospital of Chinese MedicineGuangzhou 510000China Guangdong-Hong Kong-Macao Joint Lab on chinese medicine and Immune Disease Research Guangzhou University of Chinese MedicineGuangzhou 510000China The Research Center for Integrative medicine School of Basic Medical SciencesGuangzhou University of Chinese MedicineGuangzhou 510000China State Key Laboratory of Dampness Syndrome of chinese medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000China

Prostate cancer(PCa)is the second most common malignancy among men *** Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of *** study investigates whether the FZYL Formula can inhibit PCa by tar-geting the TAMs/CCL5 *** conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their *** showed that the FZYL Formula significantly reduced the proliferation,colony formation,subpopulations of PCSCs,and sphere-formation efficacy of PCa cells,even in the presence of TAM ***,the Formula markedly decreased the migration,invasion,and epithelial-mesenchymal transition(EMT)of PCa cells induced by *** FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion,with minimal cytotoxicity *** studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula,as the addition of exogen-ous CCL5 partially reversed the formula’s inhibitory effects on PCSCs self-renewal in the co-culture ***,the Formula also significantly inhibited the growth of PCa xenografts,bone metastasis,and PCSCs activity in vivo by targeting the TAMs/CCL5 ***,this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.

关键词： Traditional chinese medicine Tumor-associated macrophages Prostate cancer stem cells CCL5 Tumor microenvironment

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Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway

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Food Science and Human Wellness 2024年第1期13卷 414-420页

作者： Zitian Gao Gaorui Wang Yujie Chen Wuke Yuan Jun Cai Aiping Feng Jie Fang Qi Xu Xiaojun Wu School of Public Health Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Key Laboratory of Compound chinese medicines The Ministry of Education(MOE)Key Laboratory for Standardization of Chinese MedicineInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Longhua hospital affiliated to Shanghai University of Traditional chinese medicine Shanghai University of Traditional Chinese MedicineShanghai 201203China

Parkinson’s disease(PD)is a common neurodegenerative disorder with no *** membranaceus is used in chinese culture as a food supplement to boost *** present study aimed to explore the neuroprotective effects of total flavonoids extracted from ***(TFA)and their protective *** offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of *** also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen *** addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.

关键词： Parkinson’s disease Total fl avonoids of Astragalus membranaceus Ferroptosis SLC7A11

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Mechanism underlying the effects of exercise against type 2 diabetes:A review on research progress

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World Journal of Diabetes 2024年第8期15卷 1704-1711页

作者： Chen-Jian Peng Shuo Chen Su-Ying Yan Jian-Ning Zhao Zhi-Wen Luo Yuan Qian Guo-Liang Zhao Department of Sports medicine Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing 210022Jiangsu ProvinceChina Department of Sports medicine Huashan HospitalFudan UniversityShanghai 200040China Department of Outpatient Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese MedicineNanjing 210006Jiangsu ProvinceChina

Exercise has emerged as one of the important and effective non-drug therapies used for management of type 2 diabetes(T2D)in certain *** present report summarizes the latest findings from the research on the beneficial effect of exercise on *** objectives were to provide references for the theoretical study and the clinical practice of exercise-based management of T2D,in addition to identify the limitations of the existing literature,thereby provide direction for future research in this field.

关键词： Type 2 diabetes Diabetes Exercise Mechanism Inflammation

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