Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.     

T cell antigenicity and immunogenicity of allogeneic exosomes

Extracellular vesicles, including exosomes, are regularly released by allogeneic cells after transplantation. Recipient antigen-presenting cells (APCs) capture these vesicles and subsequently display donor MHC molecules on their surface. Recent evidence suggests that activation of alloreactive T cells by the so-called cross-dressed APCs plays an important role in initiating the alloresponse associated with allograft rejection. On the other hand, whether allogeneic exosomes can bind to T cells on their own and activate them remains unclear. In this study, we showed that allogeneic exosomes can bind to T cells but do not stimulate them in vitro unless they are cultured with APCs. On the other hand, allogeneic exosomes activate T cells in vivo and sensitize mice to alloantigens but only when delivered in an inflammatory environment.     

Targeting NF-κB c-Rel in regulatory T cells to treat corneal transplantation rejection

The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-κB c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-κB c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-κB c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-κB c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment.     

磁处理水对抗癌药物的解毒作用

我们的实验发现，磁处理水对环磷酰胺等五种抗癌药物的毒性具有不同程度的缓解作用，能增加小鼠的存活率，能降低药物引起的白细胞减少。对目前癌化疗中使用率最高的环磷酰胺，其作用最明显。     

Design and application research of nucleotide sequence analysis system software

INTRODUCTION　　From integrallevel and celllevel,the research of organism and diseasediagnosishave already entered molecular level.Molecular biology is the science to researchstructure and function of organism macromolecule.Based on differentgene code se-…     

生态药理与生物药理—论中药药性理论的本质

目的：探讨中药药性理论的本质,方法：通过对医学人体理论,医学模式和药理理论内在关系的分析来剖析中药药性理论的本质,提出对中药药性理论本质的认识。结果：认为中药药性理论是传统中药药理理论,是适应中医学“生态－生物人体理论”的产物,中药药性理论是“生态药理”与“生物药理”相结合的产物即“生态－生物理”这是其本质所在,结论：传统中药药理即中药药性理论是“生态－生物药理”理论。     

膜表面型与可溶型HLA-B27 分子在人C1R细胞内的细胞生物学研究

目的 :了解两型HLA B2 7分子在人细胞系内的合成、组装及转运过程。方法 :克隆到真核表达载体RSV 5neo的膜表面型与可溶型B2 7(sB2 7)cDNA以电转法转入人B淋巴母细胞突变细胞系C1R ,并使其稳定表达。以免疫沉淀、脉冲追踪及内切糖苷酶H消化实验观察两型B2 7分子在C1R细胞系内的细胞生物学特点。结果 :sB2 7分子与膜表面型B2 7分子一样 ,约需 30min完成细胞内的修饰过程 ,均与Calnexin及BiP这两种分子伴侣相关等 ,但与膜表面型B2 7分子相比 ,仅部分sB2 7分子被转运到细胞表面 ,相当一部分sB2 7分子 4h后仍滞留在内质网腔内。结论 :sB2 7分子在人C1R细胞内的合成、组装与转运过程与膜表面型B2 7分子相似 ,滞留在内质网腔的sB2 7分子的酶解片段有可能通过Ⅱ类分子而递呈给CD4 T细胞 ,这一现象将为研究HLA Ⅱ类分子与脊柱关节病的相关提供新线索 ,并为今后探讨B2 7及环境因素与脊柱关节病的相关、寻找早期诊断与早期治疗措施提供理论依据     

温州地区鼠类肝毛细线虫流行学和生物学研究

目的：了解温州地区鼠体肝毛细线虫的感染情况,为肝毛细线虫病防治提供科学依据,并探讨肝毛线虫幼虫经皮肤和经腹腔注射感染小白鼠的可行性。方法：从温州境内部分地区收集鼠体以检查肝毛细线虫虫卵,分离虫卵并培养成幼虫作感染小白鼠试验。结果：温州地区鼠及臭 毛细线虫总感染率是１８．３％,不同鼠种和硒居范围不同的鼠体感染率不同,鼠体感染率和感染度随鼠体年龄增大而增高（强）。肝毛细线虫幼虫经皮肤和经腹腔注射感染小     

条件致病菌与非淋菌性尿道炎的关系初探

目的：为了解非淋菌性尿道炎和条件致病菌感染的关系。方法：采用常规细菌培养,Ｋ－Ｂ药敏试验法,支原体培养及衣原体直接免疫荧光染色法检测患者尿道分泌物或前泌物或前列腺液标本。结果：２３８例非淋菌性尿道炎病人标本中,细菌培养阳性２１１例（８８．６％）,支原体培养阳性３７例（１５．６％）,其中与细菌共同阳性３０例,衣原体阳性２４例（１０．８％）,其中与细菌共同阳性１４例,与念珠菌共同阳性１例,念珠菌阳性７