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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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Impact of lifestyle interventions on pathogenesis of nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2024年第20期30卷 2633-2637页

作者： Wafaa Mohamed Ezzat Department of Internal medicine Medical Research and Clinical Studies InstituteNational Research CenterGiza 12311Egypt

This editorial builds on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et *** carried out a critical examination of nonalcoholic fatty liver disease(NAFLD)pathogenesis and how lifestyle interventions could facilitate disease resolution,particularly highlighting that non-alcoholic steatohepatitis(NASH)is a severe form of *** discussion details that weight loss is a pivotal factor in disease outcomes:A 3%-5%reduction is enough for resolution in 50%of non-obese individuals,while a 7%-10%reduction achieves similar benefits in obese individuals,as demonstrated by magnetic resonance ***,the editorial underscores that such lifestyle changes are instrumental not only in resolving NAFLD but also in reversing hepatic steatosis and *** insights,derived from the research,emphasize the critical role of personalized lifestyle modifications in halting the progression of NAFLD to NASH and even reversing fibrosis,thus offering a template for effective patient management.

关键词： Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Diet Physical activity Life style

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Multi-omics integration reveals potential stage-specific druggable targets in T-cell acute lymphoblastic leukemia

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Genes & Diseases 2024年第5期11卷 374-389页

作者： Zijun Yan Jie Xia Ziyang Cao Hongyang Zhang Jinxia Wang Tienan Feng Yi Shu Lin Zou clinical Research Unit Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China institute of Pediatric Infection Immunityand Critical Care MedicineShanghai Jiao Tong University School of MedicineShanghai 200062China Center for clinical Molecular Laboratory medicine of Children’s Hospital of Chongqing Medical University Chongqing 400014China clinical Research institute Shanghai Jiao Tong University School of MedicineShanghai 200025China Bioinformatics and BioMedical Bigdata Mining Laboratory School of Big HealthGuizhou Medical UniversityGuiyangGuizhou 554300China

T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell *** development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this *** this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this *** multi-omics integration helped identify 29 potential pathological genes for *** genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling *** these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in *** TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive ***6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation ***,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in ***,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.

关键词： Multi-omics Stage-specific druggable targets Targeted therapeutic strategies T-cell acute lymphoblastic leukemia Drug repositioning

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Neutrophils are shaped by the tumor microenvironment:novel possibilities for targeting neutrophils in cancer

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1788-1790页

作者： Carlos Silvestre-Roig Lydia Kalafati Triantafyllos Chavakis institute of Experimental Pathology(ExPat) Center for Molecular Biology of Inflammation(ZMBE)University of MünsterMünsterGermany institute for clinical Chemistry and Laboratory medicine University Hospital and Faculty of MedicineTechnische Universität DresdenDresdenGermany

In a recent paper published in Science,Ng et *** seminal insights into the process through which neutrophils are reprogrammed by the tumor environment,leading to a convergent transition from different neutrophil states towards a unique end-stage differentiated pro-tumor phenotype.1 These findings have major translational implications as they provide potential neutrophil-related targets for tumor immunotherapy.

关键词： al. neutrophils tumor

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Characteristics and quality of clinical practice guidelines for diabetic kidney disease: a systematic review

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Journal of Traditional Chinese medicine 2024年第3期44卷 609-619页

作者： WANG Yuhuang ZHANG Le ZHANG Zhengshan YAO Zhi LI Xiyao SUN Luying LIAO Xing Department of Nephropathy and Endocrine Dongzhimen HospitalBeijing University of Chinese Medicine Centre for Evidence-Based Chinese medicine Institute of Basic Research in Clinical MedicineChina Academy of Chinese Medical Sciences Department of Endocrine One Zone Fangshan HospitalBeijing University of Chinese Medicine

OBJECTIVE: To assess the quality of clinical practice guidelines(CPGs) in the context of diabetic kidney disease(DKD) and determine whether any factors affect the quality. METHODS: We searched eight databases along with five international and national organizations to develop or archive guidelines from their inception to July 2023, with an additional search of ***. And the authoritative organizations related to nephrology. CPGs and consensus statements created using direct differential diagnosis or therapy for DKD were included without language restrictions. Their quality was evaluated by four reviewers using the Appraisal of Guidelines for Research and Evaluation Ⅱ(AGREE Ⅱ) instrument. Along with the item and domain scores, the guideline was also allocated an overall quality score, which ranged from 1(lowest possible quality) to 7(highest possible quality). Moreover, an overall recommendation for use was also assigned(“recommended”, “recommended with modifications” or “not recommended”). RESULTS: A total of 16 CPGs were included, of which 14 were from Asia and the remaining two from Europe. These two CPGs were updated in the third version. Six CPGs were recommended for use because their primary domains scored in the medium or high category. Furthermore, five CPGs were recommended with modifications as the stakeholder involvement, applicability, and editorial independence domains were evaluated as low categories. In all domains, the lowest average score was for rigour of development(33%), followed by application(36%), and stakeholder involvement(51%). The highest average score was for scope and purpose(79%), followed by clarity of presentation(75%). None of the CPGs considered the patient's viewpoint, and six of 16 CPGs did not use any grading system to translate the evidence into recommendations. Additionally, only three of 16 CPGs shared search strategy, and eight of 16 CPGs did not declare a funding source. CONCLUSIONS: According to the AGREE II evaluation

关键词： appraisal of guidelines for research and evaluation II diabetic nephropathies practice guideline quality assessment systematic review

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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei institute of clinical Pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China Department of clinical Pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex ***-derived macrophages(MDMs)infiltration are associated with RA *** have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor ***,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been ***,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)*** inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)*** experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting *** further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγ***,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 ***,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and ***,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular *** GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

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Dietary cooking oils and cardiometabolic measurements in an elderly Chinese population

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Journal of Geriatric Cardiology 2024年第6期21卷 642-650页

作者： Xin-Yu WANG Chao-Ying MIAO Xiao-Fei YE Wen-Yuan-Yue WANG Jia-Bo ZHU Yi ZHOU Yan LI Ji-Guang WANG School of Public Health Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Cardiovascular medicine Centre for Epidemiological Studies and Clinical TrialsThe Shanghai Institute of HypertensionRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

OBJECTIVE To investigate three features of dietary cooking oil intake,namely,the consumption,cooking style,and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese *** The elderly(≥65 years)participants for this study were recruited from two community health centers in the urban area of Shanghai.A questionnaire was administered to collect information on dietary oil consumption(low,medium and high)and cooking styles(fry or stir-fry ***)and the composition of fatty acids(poly-unsaturated ***-unsaturated).The cardiometabolic measurements included anthropometry,blood pressure,fasting plasma glucose and serum *** The 1186 study participants had a mean age of 70.9±5.4 *** mean dietary oil consumption was 35.0 g/d,being low(<25 g/d),medium(25-49 g/d)and high(≥50 g/d)in 485,467 and 234 participants,*** proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4%and 27.4%,*** before and after adjustment for sex,age,current smoking and alcohol intake,dietary oil consumption was significantly(P≤0.02)and positively associated with the prevalence of treated hypertension and fasting plasma glucose *** similar adjustments as above and additional adjustment for dietary oil consumption,the fry or stir-fry cooking style was significantly(P≤0.048)and positively associated with body mass index,but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol,and the dietary intake of oils rich in mono-unsaturated fat acids was significantly(P≤0.02)and positively associated with diastolic blood pressure,serum triglycerides,total cholesterol and low-density lipoprotein cholesterol,and the prevalence of hypertriglyceridemia and *** This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to sev

关键词： cooking elderly unsaturated

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Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China:Findings from real-world data

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Chinese Medical Journal 2024年第10期137卷 1179-1189页

作者： Ruoxi He Xiaoxia Ren Ke Huang Jieping Lei Hongtao Niu Wei Li Fen Dong Baicun Li Ye Wang Ting Yang Chen Wang School of Population medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Respiratory medicine National Key Clinical SpecialtyBranch of National Clinical Research Center for Respiratory DiseaseXiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Pulmonary and Critical Care medicine Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China institute of Respiratory medicine Chinese Academy of Medical SciencesBeijing 100029China National Center for Respiratory medicine Beijing 100029China National clinical Research Center for Respiratory Diseases Beijing 100029China Department of clinical Research and Data Management Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China

Background:Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease(COPD).However,limited information is available on vaccination coverage among patients with acute exacerbations of COPD(AECOPD)in *** study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with ***:Baseline data from a national,multicenter,hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were *** outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 *** ensure national representativeness,rates were weighted according to the distribution of hospital levels and types enrolled in this *** Poisson regression based on mixed-effects models were used to determine the associated *** independent variables included the region and hospital features where the participants were located,sociodemographic characteristics(age,sex,rural/urban residence,education,etc.),and clinical indicators(COPD disease history,lung function parameters,comorbidities,etc.).The treatment profiles of the vaccinated and unvaccinated participants were ***:Of 6949 eligible participants,the weighted rates of influenza/pneumococcal,influenza,and pneumococcal vaccination were 2.72%(95%confidence interval[CI]:2.34%-3.10%),2.09%(95%CI:1.76%-2.43%),and 1.25%(95%CI:0.99%-1.51%),*** multivariable models,age≥60 years(60-69 years,odds ratio[OR]:1.90,95%CI:1.11-3.25;≥80 years,OR:2.00,95%CI:1.06-3.78),geographical regions(Northern China relative to Eastern China,OR:5.09,95%CI:1.96-13.21),urban residence(OR:1.69,95%CI:1.07-2.66),a higher education level(junior high school,OR:1.77,95%CI:1.21-2.58;senior high school or above,OR:2.61,95%CI:1.69-4.03),former smoking(OR:1.79,95%CI:1.15-2.79),and regular inhaled medication treatment(OR:3.28,95%CI:2.29-4.70)were

关键词： Chronic obstructive pulmonary disease Influenza Pneumococcal Vaccine AECOPD

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Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis

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Asian Journal of Andrology 2024年第2期26卷 144-154页

作者： Rossella Cannarella Carmelo Gusmano Claudia Leanza Vincenzo Garofalo Andrea Crafa Federica Barbagallo Rosita A Condorelli Sandro La Vignera Aldo E Calogero Department of clinical and Experimental medicine University of CataniaCatania 95123Italy Glickman Urological&Kidney institute Cleveland Clinic FoundationClevelandOH44195USA

To evaluate the relationship between testosterone replacement therapy(TRT)and arterial and/or venous thrombosis in patients with pre-treatment total testosterone(TT)<12 nmol I^(-1),we performed a meta-analysis following the Population Intervention Comparison Outcome ***:men with TT<12 nmol I^(-1) or clear mention of hypogonadism in the inclusion criteria of patients;intervention:TRT;comparison:placebo or no therapy;outcomes:arterial thrombotic events(stroke,myocardial infarction[MI],upper limbs,and lower limbs),VTE(deep vein thrombosis[DVT],portal vein thrombosis,splenic thrombosis,and pulmonary embolism),and mortality.A total of 2423 abstracts were assessed for ***-four studies,including 14 randomized controlled trials(RCTs),were finally included,with a total of 4027 and 310288 hypotestosteronemic male patients,from RCTs and from observational studies,*** on RCT-derived data,TRT did not influence the risk of arterial thrombosis(odds ratio[OR]=1.27,95%confidence interval[CI]:0.47-3.43,P=0.64),stroke(OR=1.34,95%CI:0.09-18.97,P=0.83),MI(OR=0.51,95%CI:0.11-2.31,P=0.39),VTE(OR=1.42,95%CI:0.22-9.03,P=0.71),pulmonary embolism(OR=1.38,95%CI:0.27-7.04,P=0.70),and mortality(OR=0.70,95%CI:0.20-2.38,P=0.56).Meanwhile,when only observational studies are considered,a significant reduction in the risk of developing arterial thrombotic events,Ml,venous thromboembolism,and mortality was *** risk for DVT remains uncertain,due to the paucity of RCT-based *** in men with TT<12 nmol I^(-1) is safe from the risk of adverse cardiovascular *** studies specifically assessing the risk of DVT in men on TRT are needed.

关键词： hypogonadism testosterone testosterone replacement therapy thromboembolism thrombosis TRT

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Investigating the Mechanism of Qu Du Qiang Fei 1 Hao Fang Formula against Coronavirus Disease 2019 Based on Network Pharmacology Method

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World Journal of Traditional Chinese medicine 2024年第1期10卷 93-103页

作者： Yuan-Hua Wang He-Yang Zhou Jin-Yun Ma Gui-Qing Ding Hua Yu Yong-Sheng Jin Xiao-Dong Cheng institute of clinical Immunology Yue-Yang Hospital of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghaiChina School of Pharmacy Naval Medical UniversityShanghaiChina

Objective:Qu Du Qiang Fei 1 Hao Fang(QDQF1)is a novel Chinese herbal medicine formula used to treat coronavirus disease 2019(COVID-19).However,the pharmacological mechanisms of action of QDQF1 remain *** objective of this study was to identify the effective ingredients and biological targets of QDQF1 for COVID-19 *** and Methods:The effective ingredients and mechanisms of action of QDQF1 were analyzed by using network pharmacology methods,which included an analysis of the effective ingredients and corresponding targets,COVID-19-related target acquisition,compound-target network analyses,protein-protein interaction network analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses,and molecular docking ***:In total,288 effective QDQF1 ingredients were *** identified 51 core targets from the 148 targets through an overlap between putative QDQF1 targets and COVID-19-related *** key components,including formononetin,kaempferol,luteolin,naringenin,quercetin,and wogonin were identified through component-target network *** functional enrichment analysis of the core targets revealed 1296 items,while KEGG pathway enrichment analysis identified 148 signaling *** central targets(CCL2,CXCL8,IL1B,IL6,MAPK1,MAPK3,MAPK8,STAT3,and TNF)related to the COVID-19 pathway were identified in the KEGG pathway enrichment ***,molecular docking analysis suggested that the docking scores of the six key components to the nine central targets were better than those to ***:QDQF1 may regulate multiple immune-and inflammation-related targets to inhibit the progression of severe acute respiratory syndrome coronavirus 2,and thus,may be suitable for the treatment of COVID-19.

关键词： Coronavirus disease 2019 molecular docking molecular mechanism network pharmacology Qu Du Qiang Fei 1 Hao Fang formula

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