Workshop on Late Renal Allograft Dysfunction

Despite continued improvement in incidence of acute immune injury and short-term graft survival, late allograft dysfunction remains a significant problem in the renal transplant population. Recent reports suggest that rates of renal function decline are quite varied in the overall recipient population, and that individual rates for many recipients may not change substantially over time. Moreover, analyses also reveal distinct predictive factors for both early and late functional decline. Long-term outcome studies for renal transplantation, however, might be significantly limited by incomplete data sets for assessing clinical endpoints. In view of the heterogeneous factors that may cause progressive allograft injury, more routine biopsy sampling would allow a more complete characterization of induced injuries. Elucidating mechanisms of renal fibrosis in response to injury, in experimental systems and humans, is also an important goal in better understanding chronic allograft damage. Regulation of cell senescence genes and epithelial to mesenchymal transition, studied in other models of renal fibrosis, are likely relevant to studies of renal allograft dysfunction. Recent technical advances in analyzing biological samples may play a pivotal role in identifying and validating surrogate markers of allograft function for future interventional trials in transplantation.     

Mycophenolate Mofetil Is Associated with Altered Expression of Chronic Renal Transplant Histology

Mycophenolate mofetil (MMF) reduces acute rejection in controlled trials of kidney transplantation and is associated with better registry graft survival. Recent experimental studies have demonstrated additional antifibrotic properties of MMF, however, human histological data are lacking. We evaluated sequential prospective protocol kidney biopsies from two historical cohorts treated with cyclosporine (CSA)-based triple therapy including prednisolone and either MMF (n = 25) or azathioprine (AZA, n = 25). Biopsies (n = 360) were taken from euglycemic kidney-pancreas transplant recipients. Histology was independently assessed by the Banff schema and electron microscopic morphometry. MMF reduced acute rejection and OKT3 use (p < 0.05) compared with AZA. MMF therapy was associated with limited chronic interstitial fibrosis, striped fibrosis and periglomerular fibrosis (p < 0.05-0.001), mesangial matrix accumulation (p < 0.01), chronic glomerulopathy scores (p < 0.05) and glomerulosclerosis (p < 0.05). MMF was associated with delayed expression of CSA nephrotoxicity, reduced arteriolar hyalinosis, striped fibrosis and tubular microcalcification (p < 0.05-0.001). The beneficial effects of MMF remained in recipients without acute rejection. Retrospective analysis shows that MMF therapy was associated with substantially reduced fibrosis in the glomerular, microvascular and interstitial compartments, and a delayed expression of CSA nephrotoxicity. These outcomes may be due to a limitation of immune-mediated injury and suggest a direct effect of reduced fibrogenesis.     

干扰素诱导淋巴瘤细胞凋亡实验及临床研究

目的：分析梯度浓度的干扰素(IFN-α)对Burkitt淋巴瘤细胞株Daudi和T细胞淋巴瘤细胞株Jurkut及15例难治性淋巴瘤患者的直接作用。方法：以MTT法测定梯度浓度的IFN-α对两种淋巴瘤细胞株Daudi、Jurkat增殖作用的影响，以DNA末端标记法，流式细胞术，电镜观察测定IFN-α对淋巴瘤细胞的凋亡诱导作用，并采用瘤内注射IFN-α联合化疗治疗15例耐药的难治性淋巴瘤。结果：低浓度亚IFN-α对DaudiJurkat细胞增殖无明显抑制作用，高浓度IFN(10000U／ml)可显著抑制两种细胞增殖，且有时间相关性。高浓度的IFN-α可诱导淋巴瘤细胞凋亡。15例患者CR5例，PR7例，有效率80％，无明显毒副作用。结论：IFN-α可抑制淋巴瘤细胞增殖，诱导凋亡，有显著时间，剂量依赖性。局部应用IFN-α联合化疗是治疗难治性淋巴瘤的有效方法之一。     

PPARY2基因Pro12Ala和C1431T多态性及其单倍型与2型糖尿病和肥胖的相关性研究

目的 研究过氧化物体增殖活化受体γ2(peroxisome proliferator activated receptorγ2,PPARγ2)基因Pro12Ala和C1431T多态性及其单倍型与汉族人2型糖尿病、肥胖的关系.方法 应用聚合酶链反应-限制性片段长度多态性的方法,对207例2型糖尿病患者和101名非糖尿病对照者进行PPARγ2基因Pro12Ala和C1431T多态性研究.结果 (1)在非糖尿病对照人群中Aal 12等位基因频率是0.064,T1431等位基因频率是0.252.单倍型分析显示Pro12Ala和C1431T两个位点连锁不平衡(D'=0.63,r2=0.074),组成了3种常见单倍型Pro-C、Pro-T和Ala-T.(2)Pro12Ala和C1431T多态性分布及其单倍型分布频率在2型糖尿病组与对照组组间差异均无统计学意义(P>0.05).(3)Pro12Ala变异与糖尿病患者的血压、血脂相关,地等位基因降低非肥胖糖尿病患者的舒张压(P<0.05),而对肥胖糖尿病患者的血脂水平无保护作用(P<0.05);C1431T多态性与糖尿病患者的超重和肥胖相关,超重和肥胖的糖尿病者T等位基因频率相对较高(P<0.05).结论 Pro12Ala和C1431T多态性可能在汉族人糖尿病发病中不是起主要作用;C1431T多态性与糖尿病患者的超重和肥胖相关.     

CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted,but Functional in Patients with COVID-19

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高渗和低渗造影剂对大白鼠肾毒性的实验研究

目的 :研究高、低渗造影剂对甘油致肾损害大鼠和正常大鼠的肾毒性 ,观察山莨菪碱预防肾小管损害的作用。方法 :用 2 5 %甘油按 1ml/ 10 0 g制肾损害大鼠模型 ,然后从静脉注射高渗造影剂 (76 %复方泛影葡胺 ,1ml/ 10 0 g)或优维显 (1m l/ 10 0 g) ,2 4h后各组随机处死 10只大鼠 ,肾脏用 10 %福尔马林固定后做病理检查。结果 :在肾功能损害组 ,给高渗造影剂后 ,可使肾小管管型数和肾小管坏死数明显高于低渗造影剂组和甘油对照组 (P<0 .0 1) ,山莨菪碱可明显减轻肾小管损害 (P<0 .0 5 )。正常肾功能组高、低渗造影剂组之间肾小管损害无显著性差异。结论 :肾功能损害时用低渗造影剂对肾毒性较小 ,山莨菪碱对复方泛影葡胺的肾毒性有一定的预防作用。     

高脂饮食诱导的高胆固醇血症对雄性Wistar大鼠肾脏的毒性作用

目的 研究高胆固醇血症对雄性Wistar大鼠肾脏的毒性作用。方法 用5%胆固醇饲料喂养雄性Wistar大鼠,制备高胆固醇动物模型,分别于实验第30、60和90d测定肾功能、24h尿蛋白、肾皮质胆固醇（Ch）及各磷脂含量,并进行病理形态及组织定量分析。结果 在实验周期内实验组（E组）大鼠血浆肌酐水平无显著变化;第90d,E组24h尿微量白蛋白、肾皮质Ch、磷脂酰胆碱（PC）及磷脂酰乙醇胺（PE）显著高于正常对照组（C组）;病理形态及组织定量分析显示肾小球系细胞增垂、炎性细胞浸润、系膜基质增多、毛细血管塌陷、上皮细胞足突融合,肾小球体积增大。IgG直接免疫荧光阴性,肾小球内无电子致密物沉积。相关分析显示肾小球体积、肾皮质Ch含量及24h尿微量白蛋白排泄率等与血浆总胆固醇（TCh）及低密度脂蛋白（LDL）浓度呈显著正相关关系。结论 饮食诱导的高胆固醇血症可导致Wistar大鼠肾毒性损伤。