高原地区部队医院谋求新发展应处理好七个关系

从高原部队医院实际出发,阐述了适应新形势谋求新发展应处理好的七个关系:即继承与创新的关系;坚持“姓军为兵的服务方向与对外有偿服务的关系;基础建设与人才建设的关系;日常医疗保障与科研的关系;发挥自身特色与学习借鉴的关系;硬件建设与软件建设的关系;科技研究与成果转化的关系。     

医院质量管理发展现状及展望

卫生改革逐步深化、中国入世给医院带来前所未有的机遇与挑战。论述了当前医院质量管理的研究热点:医疗质量实时控制、持续质量改进、ISO9000质最体系认证、循证医学、临床途径等。介绍了医院质量管理发展趋势:以超严质量要求为目标,数字化管理为基础,持续质量改进和质量管理创新为手段,科学管理和“文化管理”的有机结合为根本。     

The clinical utility of inhibiting CD28-mediated costimulation

Summary:  This volume covers many topics in the field of T-cell costimulation. The need for such a volume is testament to the growth of the field. From its beginning as a concept in the 1980s, we have now progressed to the point where many molecules now have functionally defined roles in T-cell costimulation. In addition, the field has progressed 'from bench to bedside'. Abatacept [cytotoxic T-lymphocyte antigen-4 (CTLA-4)-immunoglobulin (Ig) (CTLA-4-Ig)], an inhibitor of CD28-mediated T-cell costimulation, was approved for the treatment of moderate-to-severe rheumatoid arthritis in 2006 by the Food and Drug Administration and in 2007 by the European Medicines Agency. This chapter first presents a personal historical perspective on the early basic studies on the elucidation of the CD28/B7 T-cell costimulatory pathway and the discovery of CTLA-4-Ig. We next present an overview of studies of CTLA-4-Ig in preclinical animal studies. The material discussed in these first two sections is selective rather than exhaustive; their purpose is to provide context for the final section, a summary of human clinical studies performed with abatacept.     

Conveying glycan information into T-cell homeostatic programs: a challenging role for galectin-1 in inflammatory and tumor microenvironments

Summary:  The immune system has evolved sophisticated mechanisms composed of several checkpoints and fail-safe processes that enable it to orchestrate innate and adaptive immunity, while at the same time limiting aberrant or unfaithful T-cell function. These multiple regulatory pathways take place during the entire life-span of T cells including T-cell development, homing, activation, and differentiation. Galectin-1, an endogenous glycan-binding protein widely expressed at sites of inflammation and tumor growth, controls a diversity of immune cell processes, acting either extracellularly through specific binding to cell surface glycan structures or intracellularly through modulation of pathways that remain largely unexplored. In this review, we highlight the discoveries that have led to our current understanding of the role of galectin-1 in distinct immune cell process, particularly those associated with T-cell homeostasis. Also, we emphasize findings emerging from the study of experimental models of autoimmunity, chronic inflammation, fetomaternal tolerance, and tumor growth, which have provided fundamental insights into the critical role of galectin-1 and its specific saccharide ligands in immunoregulation. Challenges for the future will embrace the rational manipulation of galectin-1-glycan interactions both towards attenuating immune responses in autoimmune diseases, graft rejection, and recurrent fetal loss, while at the same overcoming immune tolerance in chronic infections and cancer.     

Galectin-3 regulates T-cell functions

Summary:  Galectin-3 is absent in resting CD4⁺ and CD8⁺ T cells but is inducible by various stimuli. These include viral transactivating factors, T-cell receptor (TCR) ligation, and calcium ionophores. In addition, galectin-3 is constitutively expressed in human regulatory T cells and CD4⁺ memory T cells. Galectin-3 exerts extracellular functions because of its lectin activity and recognition of cell surface and extracellular matrix glycans. These include cell activation, adhesion, induction of apoptosis, and formation of lattices with cell surface glycoprotein receptors. Formation of lattices can result in restriction of receptor mobility and cause attenuation of receptor functions. Consistent with the presence of galectin-3 in intracellular locations, several functions have been described for this protein inside T cells. These include inhibition of apoptosis, promotion of cell growth, and regulation of TCR signal transduction. Studies of cell surface glycosylation have led to convergence of glycobiology and galectin biology and provided new clues on how galectin-3 may participate in the regulation of cell surface receptor activities. The rapid expansion of the field of galectin research has positioned galectin-3 as a key regulator in T-cell functions.     

Contributions of Wiskott–Aldrich syndrome family cytoskeletal regulatory adapters to immune regulation

Summary:  Cytoskeletal structure and dynamic rearrangement are integrally involved in coupling external stimuli to the orchestrated network of molecular interactions and cellular responses required for T-cell effector function. Members of the Wiskott––Aldrich syndrome protein (WASp) family are now widely recognized as cytoskeletal scaffolding adapters that coordinate the transmission of stimulatory signals to downstream induction of actin remodeling and cytoskeletal-dependent T-cell responses. In this review, we discuss the structural and functional properties of the WASp family members, with an emphasis on the roles of these proteins in the molecular pathways underpinning T-cell activation. The contributions of WASp family proteins and the cytoskeletal reorganization they evoke to expression of specific T-cell effector functions and the implications of such activity to normal immune responses and to the immunologic deficits manifested by Wiskott–Aldrich syndrome patients are also described.     

Adapters in the organization of mast cell signaling

Summary:  Mast cells are pivotal in innate immunity and play an important role in amplifying adaptive immunity. Nonetheless, they have long been known to be central to the initiation of allergic disorders. This results from the dysregulation of the immune response whereby normally innocuous substances are recognized as non-self, resulting in the production of IgE antibodies to these 'allergens'. Preformed and newly synthesized inflammatory (allergic) mediators are released from the mast cell following allergen-mediated aggregation of allergen-specific IgE bound to the high-affinity receptors for IgE (FcεRI). Thus, the process by which the mast cell is able to interpret the engagement of FcεRI into the molecular events necessary for release of their allergic mediators is of considerable therapeutic interest. Unraveling these molecular events has led to the discovery of a functional class of proteins that are essential in organizing activated signaling molecules and in coordinating and compartmentalizing their activity. These so-called 'adapters' bind multiple signaling proteins and localize them to specific cellular compartments, such as the plasma membrane. This organization is essential for normal mast cell responses. Here, we summarize the role of adapter proteins in mast cells focusing on the most recent advances toward understanding how these molecules work upon FcεRI engagement.     

The role of costimulation in antibody deficiencies: ICOS and common variable immunodeficiency

Summary:  The identification of mutations in the inducible costimulator ( ICOS ) gene in nine patients with common variable immunodeficiency (CVID) was a major breakthrough. CVID is a complex, highly heterogeneous primary immunodeficiency disease, and the discovery of these mutations revealed a molecular basis. ICOS belongs to the CD28 family of costimulatory molecules and is expressed exclusively on activated T cells. It has at least three critical functions: germinal center formation, isotype class switching, and the development of memory B cells. The discovery of human ICOS deficiency showed that a monogenic disorder could account for the full spectrum of manifestations seen in childhood and adulthood-onset CVID, including autoimmune, inflammatory, and malignant disease complications, as well as recurrent infections. Moreover, this discovery showed that a disorder which had previously been perceived as a B-cell disease might in fact have its genetic origin in human T cells. In this article, we review the role of ICOS in the mammalian immune system and human disease, as well as the discovery and characteristics of patients with ICOS deficiency. Finally, we also discuss how these 'human knockouts' have contributed to our understanding of ICOS functions and have suggested potential avenues for using therapeutic ICOS manipulation to treat other diseases.     

解放思想开拓创新继续推进卫生改革与发展

指出卫生工作要以“三个代表”重要思想为指导,紧扣改革与发展的总目标;要按照“三个代表”的要求,加快卫生体制的改革与创新,要明确政府卫生职责,转变职能,实现“政事分开”,建立符合社会主义市场经济规律和人民健康需求的卫生服务体系,建立权责明晰、富有生机的医疗机构管理体制;要全面引入竞争机制,加快医疗机构运行机制的改革与创新,继续推进病人选医院和选医生,调动医疗机构内在的动力和广大医务人员的积极性,发展多样化、多种形式办医模式,形成公平、有序的竞争局面。