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Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi Zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang Ding Hong Liu mingQing Zhu Xiao Ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang yang Xu Depei Wu national clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina institute of Blood and Marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Department of Hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes Hematology Hospital SuzhouChina Department of Hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

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Experts’Consensus on the Management of Respiratory Disease Syndemic

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China CDC weekly 2024年第8期6卷 131-138页

作者： Weizhong yang Zhongjie Li Ting yang Yanming Li Zhengde Xie Luzhao Feng Zhibin Peng Jue Liu School of Population medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina State Key Laboratory of Respiratory Health and Multimorbidity BeijingChina Key Laboratory of Pathogen Infection Prevention and Control Peking Union Medical CollegeMinistry of EducationBeijingChina national Center for Respiratory Diseases State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijingChina Department of Pulmonary and Critical Care medicine National Center of GerontologyBeijing HospitalInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of Pediatric Respiratory Infection Diseases Key Laboratory of Major Diseases in ChildrenMinistry of EducationNational Clinical Research Center for Respiratory DiseasesResearch Unit of Critical Infection in ChildrenChinese Academy of Medical Sciences2019RU016National Key Discipline of Pediatrics(Capital Medical University)Beijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina Chinese Center for Disease Control and Prevention BeijingChina Department of Epidemiology and Biostatistics School of PublicHealthKey Laboratory of Epidemiology of Major DiseasesMinistry of EducationPeking University Health Science Center-Weifang Joint Research Center for Maternal and Child HealthPeking UniversityBeijingChina

The global burden of respiratory diseases is a significant and increasing threat to individuals *** 2017,there were 544.9 million cases of chronic respiratory diseases,a 39.8%increase since 1990(1).These diseases were the third leading cause of global mortality in 2017,accounting for 7.0%of all deaths,an 18.0%increase compared to 1990.

关键词： diseases respiratory mortality

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Enhanced homing of mesenchymal stem cells for in situ niche remodeling and bone regeneration

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Nano Research 2024年第8期17卷 7449-7460页

作者： Yin Yuan Lijun Chen Jing yang Sining Zhou yangxin Fang Qi Zhang Ning Zhang Yifei Li Li Yuan Fan Jia Shuo Ni Charlie Xiang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Biology The David H.Koch Institute for Integrative Cancer Research at MITMassachusetts Institute of TechnologyCambridgeMA 02139USA Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China Innovative Precision medicine(IPM)Group Hangzhou 311215China MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China Key Laboratory of Cardiovascular Intervention and Regenerative medicine of Zhejiang Province Department of CardiologySir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Department of Cancer Immunology and Virology Dana-Farber Cancer InstituteBostonMA 02215USADepartment of ImmunologyHarvard Medical SchoolBoston MA 02115USA Department of Orthopedic Surgery and Shanghai institute of Microsurgery on Extremities Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200233China

Mesenchymal stem cells(MSCs)transplantation is a promising strategy for osteoporosis ***,limited sources and poor tissue-homing efficiency limit their clinical *** this study,we isolated a kind of MSCs from women’s menstrual blood(MenSCs)noninvasively and established a novel MSCs bone marrow-targeted delivery system by utilizing waterin-oil-in-water droplet *** were encapsulated withinβ-cyclodextrin-functionalized alginate microcapsules loaded with zoledronates,which has a high affinity for *** this delivery system,MenSCs could be preferentially delivered to the bone marrow tissues via intravenous infusion,and restored bone mass by remodeling the bone marrow niche in situ in ovariectomized mouse ***,scRNA-seq analysis demonstrated that those MenSCs homed to the bone marrow recruited CD4^(+)FOXP3^(+)natural regulatory T(nT_(reg))cells by secreting *** recruited nTreg promoted CD8^(+)T cells to secret Wnt family member 10B(WNT10B),activating the Wnt signaling in osteoblasts and thus promoting bone formation in situ in the bone *** study reveals a promising application of MenSCs in postmenopausal osteoporosis treatment and highlights the clinical value of MenSCs by encouraging women to reserve autologous MenSCs before menopause to prevent and alleviate postmenopausal osteoporosis.

关键词： mesenchymal stem cells microfluidics bone marrow homing stem cell niche postmenopausal osteoporosis

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CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence

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Science China(Life Sciences) 2024年第3期67卷 460-474页

作者： Daoyuan Huang Qian Zhao Kuan yang Jinghui Lei Ying Jing Hongyu Li Chen Zhang Shuai Ma Shuhui Sun Yusheng Cai Guibin Wang Jing Qu Weiqi Zhang Si Wang Guang-Hui Liu Advanced Innovation Centerfor Human Brain Protection National Clinical Research Centerfor Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational medicineCenter International Centerfor Aging and CancerBejing Municipal GeriatricMedical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China university of Chinese Academy of Sciences Beijing 100049China Beijing institute for Stem Cell and Regenerative medicine Beijing100101China CAS Key Laboratory of Genomic and Precision medicine Bejing Institute of Genomics and China National Center for BioinformationChinese Academy of SciencesBeijing 100101China institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Sino-Danish Cllege University of Chinese Academy of SciencesBeijing101408China national Laboratory of Biomacromolecules CAS Center for Excelence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing100101China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China

Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining ***,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and *** this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome *** all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to *** investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2 deletion markedly accelerates hMSC ***,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn downregulates one of the canonical aging marker-P21^(waf1/cip1),and thereby delays *** work provides important insights into how CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.

关键词： Cullins stem cell senescence aging proteostasis ubiquitination APPBP2 TSPYL2

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Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

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Journal of Pharmaceutical Analysis 2024年第3期14卷 348-370页

作者： Binbin Zhao Dongfeng Wei Qinghua Long Qingjie Chen Fushun Wang Linlin Chen Zefei Li Tong Li Tao Ma Wei Liu Linshuang Wang Caishui yang Xiaxia Zhang Ping Wang Zhanjun Zhang State Key Laboratory of Cognitive Neuroscience and Learning&IDG/McGovern institute for Brain Research Beijing Normal UniversityBeijing100875China institute of Gerontology Hubei University of Chinese MedicineWuhan430065China institute of Basic Research in clinical medicine China Academy of Chinese Medical SciencesBeijing100700China Medical School Hubei Minzu UniversityEnshiHubei445000China HuBei university of Science and Technology XianningHubei437100China institute of Brain and Psychological Science Sichuan Normal UniversityChengdu610066China Key Laboratory of Traditional Chinese medicine Resource and Compound Prescription Ministry of EducationHubei University of Chinese MedicineWuhan430065China Dongfang Hospital Beijing University of Chinese MedicineBeijing100078China Beijing Key Laboratory of Traditional Chinese medicine Basic Research on Prevention and Treatment for Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing100700China School of Systems Science Beijing Normal UniversityBeijing100875China BABRI Centre Beijing Normal UniversityBeijing100875China

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial ***,the specific associations between these pathological changes remain *** this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro *** investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular *** results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD ***,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic *** cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular *** intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and ***,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial *** conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

关键词： Alzheimer's disease Synaptic currents Mitophagy Mitochondrial fusion and fission Dengzhan Shengmai capsules

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Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation

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Chinese Medical Journal 2024年第2期137卷 172-180页

作者： Jing Lin Deyong Long Chenxi Jiang Caihua Sang Ribo Tang Songnan Li Wei Wang Xueyuan Guo Man Ning Zhaoqing Sun Na yang Yongchen Hao Jun Liu Jing Liu Xin Du Louise Morgan Gregg C.Fonarow Sidney C.Smith Jr Gregory Y.H.Lip Dong Zhao Jianzeng Dong Changsheng Ma On behalf of CCC-AF investigators Department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing 100029China national clinical Research Center for Cardiovascular Diseases Beijing 100029 China Department of Epidemiology Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLung and Blood Vessel DiseasesBeijing 100029China International Quality Improvement Department American Heart AssociationDallasTX 07076USA Division of Cardiology Geffen School of Medicine at University of CaliforniaLos Angeles CA 90024USA Division of Cardiology University of North CarolinaChapel HillNC 27599USA Department of Cardiology Liverpool Centre for Cardiovascular ScienceUniversity of Liverpool and Liverpool Heart&Chest HospitalLiverpool L143PEUK Department of clinical medicine Aalborg UniversityAalborg 9000Denmark 不详

Background:Oral anti-coagulants(OAC)are the intervention for the prevention of stroke,which consistently improve clinical outcomes and survival among patients with atrial fibrillation(AF).The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in ***:Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation(CCC-AF)registry,guideline-recommended OAC use in eligible patients was ***:A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019,of whom 38,203 were at a high risk of stroke,9717 were at a moderate risk,and 4610 were at a low *** admission,only 20.0%(6075/30,420)of patients with a diagnosed AF and a high risk of stroke were taking *** use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population(adjusted odds ratio:0.54,95%confidence interval:0.43-0.68;P70%of AF patients were at a high risk of *** poor performance on guideline-recommended OAC use was found in this study,over time the CCC-AF project has made progress in stroke prevention in the Chinese AF ***

关键词： Atrial fibrillation Oral anti-coagulants OAC Stroke prevention Contraindication

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Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Protein & Cell 2024年第1期15卷 36-51页

作者： Jinghui Lei Xiaoyu Jiang Daoyuan Huang Ying Jing Shanshan yang Lingling Geng Yupeng Yan Fangshuo Zheng Fang Cheng Weiqi Zhang Juan Carlos Izpisua Belmonte Guang-Hui Liu Si Wang Jing Qu Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational medicine Center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China university of Chinese Academy of Sciences Beijing 100049China institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing institute for Stem Cell and Regenerative medicine Beijing 100101China national Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China national Center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological ***,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely ***,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response *** comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular *** found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic ***,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

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Impact of corticosteroids on initiation and half-year durability of humoral response in COVID-19 survivors

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Chinese Medical Journal Pulmonary and Critical Care medicine 2024年第1期2卷 48-55页

作者： Yeming Wang Li Guo Guohui Fan yang Han Qiao Zhang Lili Ren Hui Zhang Geng Wang Xueyang Zhang Tingxuan Huang Weiyang Wang Lan Chen Lixue Huang Xiaoying Gu Xinming Wang Jingchuan Zhong Ying Wang Hui Li Jiapei Yu Zhibo Liu Chaolin Huang Bin Cao Jianwei Wang national Center for Respiratory medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesChina-Japan Friendship HospitalBeijing 100029China national Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical SciencesBeijing 100029China School of Population medicine and Public Health Chinese Academy of Medical Sciences&Peking Union Medical CollegeState Key Laboratory of Respiratory Health and MultimorbidityKey Laboratory of Pathogen Infection Prevention and Control(Peking Union Medical College)Ministry of EducationBeijing 100730China national Center for Respiratory medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Clinical research and Data managementCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Jin Yin-tan Hospital WuhanHubei 430023China Department of Pulmonary and Critical Care medicine West China HospitalSichuan UniversityChengduSichuan 610041China Department of Rheumatology and clinical Immunology Chinese Academy of Medical Sciences&Peking Union Medical CollegeNational Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID)Ministry of Science&TechnologyState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College Hospital(PUMCH)Key Laboratory of Rheumatology and Clinical ImmunologyMinistry of EducationBeijing 100730China Department of Pulmonary and Critical Care medicine Center of Respiratory MedicineChina-Japan Friendship HospsitalInstitute of Respiratory MedicineChinese

Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains *** study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection ***:We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020,which involved adults hospitalized with severe COVID-19(LOTUS,ChiCTR2000029308).Anti-body samples were collected from 192 patients during hospitalization,and kinetic antibodies were monitored at all available time points after ***,plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up *** main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid ***:From illness onset to day 30,the median antibody titre areas under the receiver operating characteristic curve(AUCs)of nucleoprotein(N),spike protein(S),and receptor-binding domain(RBD)immunoglobulin G(IgG)were significantly lower in the corticosteroids *** AUCs of N-,S-,and RBD-IgM as well as neutralizing antibodies(NAbs)were numerically lower in the corticosteroids group compared with the non-corticosteroid ***,peak titres of N,S,RBD-IgM and-IgG and NAbs were not influenced by *** 6-month follow-up,we observed a delayed decline for most binding antibodies,except N-IgM(𝛽−0.05,95%CI[−0.10,0.00])in the corticosteroids group,though not reaching statistical *** significant difference was observed for ***,for the half-year seropositive rate,corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-,S-,and RBD-IgG or ***,corticosteroids group showed a trend towards d

关键词： COVID-19 Corticosteroid Immunity Antibody Humoral response

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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 *** TCM and WM has a long history in China,and has made important achievements in the process of clinical diagnosis and ***,the methodological defects in currently published clinical practice guidelines(CPGs)limit its *** organic integration of TCM and WM is a deeper integration of TCM and *** realize the progression of"integration"to"organic integration",a targeted and standardized guideline development methodology is ***,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)

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Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

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Protein & Cell 2024年第2期15卷 121-134页

作者： Hui Sun Tingting Deng Yali Zhang Yanling Lin Yanan Jiang Yichao Jiang yang Huang Shuo Song Lingyan Cui Tingting Li Hualong Xiong Miaolin Lan Liqin Liu Yu Li Qianjiao Fang Kunyu Yu Wenling Jiang Lizhi Zhou Yuqiong Que Tianying Zhang Quan Yuan Tong Cheng Zheng Zhang Hai Yu Jun Zhang Wenxin Luo Shaowei Li Qingbing Zheng Ying Gu Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China national institute of Diagnostics and Vaccine Development in Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China State Key Laboratory of Vaccines for Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China Xiang An Biomedicine Laboratory Xiamen 361102China institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalSchool of MedicineSouthem University of Science and TechnologyShenzhen 518112China The Second Affliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or *** rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus ***,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron ***-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric *** antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant ***,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

关键词： SARS-CoV-2 broad neutralizing antibody rearrangement synergistic neutralization

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