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Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression

Research 2024年第3期2023卷 35-50页

作者： June Li Danielle Karakas Feng Xue Yingyu Chen Guangheng Zhu Yeni H.Yucel Sonya A.MacParland Haibo Zhang John W.Semple John Freedman Qizhen Shi Heyu Ni Department of Laboratory Medicine and Pathobiology University of TorontoTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada Keenan Research Centre for Biomedical Science of St.Michael's Hospital TorontoONCanada Canadian Blood Services Centre for Innovation TorontoONCanada Departments of Pediatrics Medical College of WisconsinMilwaukeeWIUSA Blood Research Institute Versiti WisconsinMilwaukeeWIUSA Departments of Ophthalmology and Vision Sciences Medicine University of TorontoTorontoONCanada Faculty of Engineering and Architectural Science Ryerson UniversityTorontoONCanada Multi-Organ Transplant Program Toronto General Hospital Research InstituteTorontoONCanada Department of Immunology University of TorontoTorontoONCanada Critical Care Medicine Department ofAnesthesiology and PainUniversity of TorontoTorontoONCanada Department of Physiology University of TorontoTorontoONCanada Department of Pharmacology University of TorontoTorontoONCanada. Division of Hematology and Transfusion Medicine Lund UniversityLundSweden clinical Immunology and Transfusion Medicine Ofice of Medical ServicesRegion SkaneLundSweden Department of Medicine University of TorontoTorontoONCanada Children's Research Institute Children's WisconsinWauwatosaWIUSA Midwest Athletes Against Childhood Cancer Fund Research Center MilwaukeeWIUSA.

Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. However, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. Here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell–Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4+ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

关键词： Platelet transfusion homeostasis

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Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang Sara Chaothai Tsz Chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

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肺PET图像的定量分析:挑战和机遇

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中华核医学与分子影像杂志 2019年第11期39卷 698-704页

作者：陈聪霞(译) 李文婵(译) 郭悦(译) 姚稚明(审校者) Delphine L.Chen Joseph Cheriyan Edwin R.Chilvers Gourab Choudhury Christopher Coello Martin Connell Marie Fisk Ashley M.Groves Roger N.Gunn Beverley F.Holman Brian F.Hutton Sarah Lee William MacNee Divya Mohan David Parr Deepak Subramanian Ruth Tai-Singer Kris Thielemans Edwin J.R.van Beek Laurence Vass Jeremy W.Wellen Ian Wilkinson Frederick J.Wilson 北京医院核医学科、国家老年医学中心 100730 Mallinckrodt Institute of Radiology Washington University School of MedicineSt.LouisMissouri Department of Medicine University of CambridgeCambridgeUnited Kingdom Cambridge University Hospitals NHS Foundation Trust CambridgeUnited Kingdom Queen's Medical Research Institute University of EdinburghEdinburghUnited Kingdom Imanova Ltd. London y United Kingdom Institute of Nuclear Medicine University College LondonLondonUnited Kingdom Department of Medicine Imperial College LondonLondonUnited Kingdom Medical Image Analysis Consultant LondonUnited Kingdom Clinical Discovery Respiratory Therapy Area UnitGlaxoSmithKline R&DKing of PrussiaPennsylvania University Hospitals Coventry and Warwickshire CoventryUnited Kingdom Derby Teaching Hospitals NHS Foundation Trust DerbyUnited Kingdom Worldwide Research and Development PfizerInc.CambridgeMassachusetts Experimental Medicine Imaging GlaxoSmithKlineStevenageUnited Kingdom

数百万人受呼吸系统疾病的影响,导致巨大的全球性健康困扰。由于目前对导致呼吸系统疾病发展和进展的潜在机制认识不足,治疗选择仍然有限。为克服此局限和理解相关分子变化,将无创影像技术如PET和SPECT用于探索生物标志物,其中18F-脱氧... 详细信息

数百万人受呼吸系统疾病的影响,导致巨大的全球性健康困扰。由于目前对导致呼吸系统疾病发展和进展的潜在机制认识不足,治疗选择仍然有限。为克服此局限和理解相关分子变化,将无创影像技术如PET和SPECT用于探索生物标志物,其中18F-脱氧葡萄糖(FDG)PET显像的研究最多。由于肺内组织、气体、血液和水的构成比变异,定量分析肺的分子影像数据仍具挑战性。这些成分的比例随着肺部疾病的不同而不同,因此有不同的定量分析方法来显示这种变化,但迄今为止还没有开发出对数据标准化的方法。该文回顾了肺部疾病中18F-FDG PET定量分析方法的数据,聚焦于解释肺内成分变化的方法,解读衍生参数。分析的疾病包括急性呼吸窘迫综合征、慢性阻塞性肺疾病、肺间质性疾病如特发性肺纤维化。基于对既往文献、进行中的研究以及作者间讨论的回顾,作者提出了建议性的注意事项,以协助解读从这些方法及未来研究设计中衍生的参数。

关键词：肺肺部炎症分子成像正电子发射计算机断层显像

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Journal of the American Heart Association|肝硬化退伍军人心肺血流动力学与病死率的关系:一项回顾性队列研究

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临床肝胆病杂志 2024年第6期40卷 1254-1254页

作者：杜佳霖温晓玉吉林大学第一医院肝胆胰内科

门脉性肺动脉高压(PoPH)与患者病死率增加相关,可能会限制肝脏疾病的治疗选择。目前缺乏与PoPH心肺血流动力学相关的临床风险连续性的数据。2024年4月,美国辛辛那提大学医学系Jose等探讨了肝硬化退伍军人心肺血流动力学与死亡率的关系。

关键词：肺血流动力学回顾性队列研究医学系门脉性肺动脉高压临床风险辛辛那提大学肝硬化病死率

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Notch1和Bmi-1蛋白在肺癌组织中的表达及意义

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中国组织工程研究 2016年第5期20卷 683-687页

作者：蔡华荣江跃全重庆市肿瘤研究所胸外科重庆市400030

背景:有研究发现,Notch通路与Bmi-1基因均有调节干细胞自我更新的能力,二者功能障碍可能与肿瘤的发生有很大的关系。目的:探讨Notch1和Bmi-1蛋白在肺癌组织中的表达水平及其临床意义。方法:获取87例肺癌患者术后肺癌组织(肺癌组)、40例... 详细信息

背景:有研究发现,Notch通路与Bmi-1基因均有调节干细胞自我更新的能力,二者功能障碍可能与肿瘤的发生有很大的关系。目的:探讨Notch1和Bmi-1蛋白在肺癌组织中的表达水平及其临床意义。方法:获取87例肺癌患者术后肺癌组织(肺癌组)、40例心胸外科开胸手术和肺部纤维支气管镜检查所取经病理证实的正常肺组织(正常组)作为研究对象。采用免疫组织化学SP法检测两组标本中的Notch1和Bmi-1蛋白表达情况,并分析Notch1、Bmi-1蛋白表达与肺癌患者临床病理特征的关系。结果与结论:肺癌组Notch1、Bmi-1蛋白表达阳性率分别为61%、47%,均显著高于正常组标本(P0.05);低分化肺癌、发生淋巴结转移、TNM分期Ⅲ-Ⅳ级患者的Notch1、Bmi-1蛋白阳性表达率显著高于高中分化肺癌、无淋巴结转移、TNM分期Ⅰ、Ⅱ级患者(P<0.05)。结果表明Notch1基因和Bmi-1基因可能与肺癌的发生、发展有一定的关系。

关键词：肿瘤干细胞肺肿瘤受体,Notch 组织工程实验动物心肺损伤及修复动物模型 Notch1基因 Bmi-1基因肺癌组织

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Improved outcome with standardized plan for clinical management of acute decompensated chronic heart failure

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Journal of Geriatric Cardiology 2019年第1期16卷 12-18页

作者： Marie-Louise Edvinsson Albin Stenberg Karin Astrom-Olsson Department of Emergency and Internal Medicine University'Hospital of LundSweden Institute of Clinical Sciences L und UniversityL undSweden Department of Cardiology University>Hospital of MalmoSweden

Background Our overall goal is to improve clinical care for inpatients with chronic heart failure(CHF).A retrospective assessment of CHF patients admitted to our hospital over the past decade(2005 vs.2014)indicated a need for better strategies to evaluate clinical treatment,implement best practices and achieve optimal patient *** that purpose,we developed a standardized plan to improve in-hospital treatment of acute decompensated CHF ***&Results Retrospective chart reviews were conducted to compare three cohorts of CHF patients admitted to the University Hospital of Lund at different time points over a 12-year period:2005(365 patients),2014(172 patients)and 2017-2018(57 patients).Little improvement was seen between 2005 and 2014 with respect to one-year mortality(35%vs.34%)and adequate treatment with recommended medications,e.g.,use of renin-angiotensin system blockers(45%vs.51%).A standardized treatment plan was devised to improve outcomes.A third cohort,treated under the plan(2017-2018),was compared with the 2014 ***-year mortality(18%vs.34%)and 30-day readmission(5%vs.30%)were dramatically decreased,and adherence to medication guidelines was *** elements of the plan included well-defined treatment procedures,enhanced communication and teamwork,education,adequate time for treatment(5 days)and post-discharge follow-up as *** peptide(NT-proBNP)levels were useful for assessing patient status,prognosis and response to *** Developmeof a standard plan for clinical management of acute decompensated CHF patients resulted in significant improvements in patient outcome,as reflected in decreased rates of 30-day readmission and one-year mortality.

关键词： Chronic heart failure Medication NT-proBNP Prognosis

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Talin and kindlin： the one-two punch in integrin activation

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Frontiers of Medicine 2014年第1期8卷 6-16页

作者： Feng Ye Adam K. Snider Mark H. Ginsberg Department of Medicine University of California San Diego La Jolla CA 92093 USA

Proper cell-cell and cell-matrix contacts mediated by integrin adhesion receptors are important for development, immune response, hemostasis and wound healing. Integrins pass trans-membrane signals bidirectionally through their regulated affinities for extracellular ligands and intracellular signaling molecules. Such bidirectional signaling by integrins is enabled by the conformational changes that are often linked among extracellular, transmembrane and cytoplasmic domains. Here, we review how talin-integrin and kindlin-integrin interactions, in cooperation with talin-lipid and kindlin-lipid interactions, regulate integrin affinities and how the progress in these areas helps us understand integrin-related diseases.

关键词： signal transduction transmembrane domain nanodisc integrin talin kindling cell adhesion

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Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes

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Cancer Innovation 2024年第3期3卷 81-94页

作者： Sahil Seth Runzhe Chen Yang Liu Junya Fujimoto Lingzhi Hong Alexandre Reuben Susan Varghese Carmen Behrens Tina McDowell Luisa Solis Soto Cara Haymaker Annikka Weissferdt Neda Kalhor Jia Wu Xiuning Le Natalie I Vokes Chao Cheng John V.Heymach Don L.Gibbons P.Andrew Futreal Ignacio IWistuba Humam Kadara Jianhua Zhang Cesar Moran Jianjun Zhang Department of Genomic Medicine The University of Texas MD Anderson Cancer CenterHoustonTexasUSA TRACTION The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Graduate School of Biomedical Sciences The University of Texas MD Anderson and the University of Texas Health Science CenterHoustonTexasUSA Department of Thoracic/Head and Neck Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Epidemiology The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Pathology The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Imaging Physics The University of Texas MD Anderson Cancer CenterHoustonTexasUSA Department of Medicine Baylor College of MedicineHoustonTexasUSA

Background:Pulmonary sarcomatoid carcinoma(PSC)is a rare and aggressive subtype of non-small cell lung cancer(NSCLC),characterized by the presence of epithelial and sarcoma-like *** molecular and immune landscape of PSC has not been well ***:Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel,whole-exome,and RNA *** describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical ***:In total,27 canonical cancer gene mutations were identified,with TP53 the most frequently mutated gene,followed by ***,most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors,suggesting branching evolution in most PSC *** identified two distinct molecular subtypes of PSC,driven primarily by immune infiltration and *** Immune High(IM-H)subtype was associated with superior survival,highlighting the impact of immune infiltration on the biological and clinical features of localized ***:We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with ***-H tumors were associated with favorable recurrence-free survival and overall survival,highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

关键词： genomic immune pulmonary sarcomatoid carcinoma survival

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Effect of "Yang-warming and kidney essence-replenishing" herbal paste on cold-related asthma exacerbation

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Journal of Traditional Chinese Medicine 2013年第4期33卷 468-472页

作者： Binqing Tang Kehua Shi Xiaoqi Li Hongchang Wang Hong Fang Bidan Xiong Yingen Wu Emergency Department Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Department of Respiratory Medicine Shanghai Hospital of Traditional Chinese Medicine Department of Internal Medicine Tianshan Hospital of Traditional Chinese Medicine Department of Internal Medicine Fenglin Community Health Service Center Preventive Treatment of Disease Center Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Department of Respiratory Medicine Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

OBJECTIVE: To observe the effect of "Yang-warming and kidney essence-replenishing" herbal paste on cold-related asthma exacerbation. METHODS: One hundred and fifty one patients with moderate to severe persistent asthma were randomly divided into a treatment group (n=74) and a control group (n=69). Both groups were given basic treatment according to the Global Initiative for Asthma scheme. The treatment group was also treated with herbal paste in the winter. The frequency of asthma exacerbation, cold and cold-re-lated asthma exacerbation, scores of the asthma control test (ACT), and kidney-deficiency syndrome during the one-year follow-up in each group were recorded. RESULTS: Compared with the control group, the onset frequencies of catching cold, asthma exacerbation, cold-related asthma exacerbation, and kidney-deficiency syndrome score were significantly reduced. There was no significant difference in scores of ACT between the two groups. CONCLUSION: "Yang-warming and kidney essence-replenishing" herbal paste could reduce cold-related asthma exacerbation.

关键词： Yang-warming and kidney essence-replenishing Herbal paste Asthma Cold-related asthma exacerbation

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Human mitochondrial DNA diseases and Drosophila models

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Journal of Genetics and Genomics 2019年第4期46卷 201-212页

作者： Zhe Chen Fan Zhang Hong Xu National Heart Lung and Blood InstituteNational Institute of Health

Mutations that disrupt the mitochondrial genome cause a number of human diseases whose phenotypic presentation varies widely among tissues and individuals. This variability owes in part to the unconventional genetics of mitochondrial DNA(mtDNA), which includes polyploidy, maternal inheritance and dependence on nuclear-encoded factors. The recent development of genetic tools for manipulating mitochondrial genome in Drosophila melanogaster renders this powerful model organism an attractive alternative to mammalian systems for understanding mtDNA-related diseases. In this review, we summarize mtDNA genetics and human mtDNA-related diseases. We highlight existing Drosophila models of mtDNA mutations and discuss their potential use in advancing our knowledge of mitochondrial biology and in modeling human mitochondrial disorders. We also discuss the potential and present challenges of gene therapy for the future treatment of mtDNA diseases.

关键词： Mitochondrial DNA mtDNA disease mtDNA genetics Drosophila model

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