左卡尼汀联合蔗糖铁对血液透析患者肾性贫血及氧化应激的影响

目的:探讨左卡尼汀联合蔗糖铁对血透患者肾性贫血及氧化应激的影响。方法:抽选我院2010年3月-2013年5月行维持血透治疗的肾性贫血患者79例,采用数字表法分为对照组(39例)和观察组(40例),对照组采用促红细胞生成素(EPO)、单用蔗糖铁及常规对症治疗,观察组在对照组基础上联用左卡尼汀治疗。比较两组患者治疗前、治疗6个月后血红蛋白(Hb)、血细胞比容(Hct)、血浆铁蛋白(SF)、转铁蛋白饱和度(TSAT)、晚期蛋白质氧化产物(AOPP)及血丙二醛(MDA)水平,并对两组治疗开始时、治疗3、6个月时EPO使用剂量进行比较。结果:治疗6个月后,观察组患者Hb、Hct、SF、TSAT明显高于对照组(P0.05),AOPP、MDA明显低于对照组(P0.05);对照组从治疗开始到治疗6个月时一直维持较高的EPO使用剂量,而观察组EPO用量依次递减,至治疗6个月时EPO用量显著低于对照组(P0.05)。结论:左卡尼汀能联合蔗糖铁治疗肾性贫血的疗效显著,能有效缓解氧化应激反应,降低EPO用量,值得临床推广。     

Mechanism of indoleamine 2, 3-dioxygenase inhibiting cardiac allograft rejection in mice

Indoleamine 2, 3-dioxygenase (IDO)-mediated regulation of tryptophan metabolism plays an important role in immune tolerance in transplantation, but it has not been elucidated which mechanism specifically induces the occurrence of immune tolerance. Our study revealed that IDO exerts immunosuppressive effects through two pathways in mouse heart transplantation, ‘tryptophan depletion’ and ‘tryptophan metabolite accumulation’. The synergism between IDO⁺DC and TC (tryptophan catabolic products) has stronger inhibitory effects on T lymphocyte proliferation and mouse heart transplant rejection than the two intervention factors alone, and significantly prolong the survival time of donor-derived transplanted skin. This work demonstrates that the combination of IDO⁺DC and TC can induce immune tolerance to a greater extent, and reduce the rejection of transplanted organs.     

Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis

WW domain binding protein 1‐like (WBP1L), also known as outcome predictor of acute leukaemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which correlates with ETV6‐RUNX1 (t(12;21)(p13;q22)) translocation and favourable prognosis in childhood leukaemia. It has a broad expression pattern in haematopoietic and in non‐haematopoietic cells. However, its physiological function has been unknown. Here, we show that WBP1L negatively regulates signalling through a critical chemokine receptor CXCR4 in multiple leucocyte subsets and cell lines. We also show that WBP1L interacts with NEDD4‐family ubiquitin ligases and regulates CXCR4 ubiquitination and expression. Moreover, analysis of Wbp1l‐deficient mice revealed alterations in B cell development and enhanced efficiency of bone marrow cell transplantation. Collectively, our data show that WBP1L is a novel regulator of CXCR4 signalling and haematopoiesis.     

Defibrotide inhibits donor leucocyte‐endothelial interactions and protects against acute graft‐versus‐host disease

Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is an effective therapy for the treatment of high‐risk haematological malignant disorders and other life‐threatening haematological and genetic diseases. Acute graft‐versus‐host disease (aGvHD) remains the most frequent cause of non‐relapse mortality following allo‐HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi‐target drug successfully employed for prophylaxis and treatment of veno‐occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo‐HCT. Using a fully MHC‐mismatched murine model of allo‐HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD‐associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo‐HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte‐endothelial interactions by down‐regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo‐HCT, paving the way for new therapeutic approaches.     

超微血流成像术用于肾移植患者术后评估的临床价值分析

目的:探讨超微血流成像术用于肾移植患者术后评估的临床价值。方法:选取我院2019年2月-2019年8月收治的60例肾移植患者的临床资料,根据术后恢复情况分为A、B、C三组,A组(27例,术后肾功能恢复良好)、B组(20例,术后发生过敏肾功能异常病变但治疗后肾功恢复正常)、C组(13例,术后血肌酐水平持续增高肾功能异常者),三组均采用超微血管流成像术检测血管指数,比较不同组患者的血管指数并分析其与血肌酐水平的关系。结果:三组患者的肾移植长径、前后径、左右径、皮质厚度、叶间动脉阻力指数比较无显著差异(P0.05)。C组患者的肾皮质血管指数(23.34±6.03%)明显低于A组(33.23±3.45%)、B组(31.23±4.23%)(P0.05)。肾功能异常患者肾皮质的血管指数较低,且随着血肌酐水平的升高而下降,两者呈显著负相关(r=-0.23,P0.05)。结论:超声微血流成像术用于肾移植患者术后评估可较好地反映肾皮质血供及术后肾功能的变化。     

西格列汀通过增加肾组织中SOCS 1和Podocalyxin的表达改善糖尿病肾病大鼠肾功能

目的:探讨西格列汀对糖尿病肾病大鼠肾功能及肾组织中细胞因子信号传导负调控因子1(Suppressors of cytockine signaling,SOCS 1)和足细胞特异蛋白抗体(Podocalyxin)表达的影响。方法:将大鼠随机分为4组:对照组,模型组,西格列汀组和贝那普利组。模型组、西格列汀组和贝那普利组采用腹腔注射链脲佐菌素建立模型,对照组给予腹腔注射等量生理盐水。造模成功后,西格列汀组(n=8)和贝那普利组(n=8)分别灌胃给予7 mg/kg/d的西格列汀和贝那普利。模型组(n=8)和对照组(n=10)均给予等体积的蒸馏水灌胃,连续8周。检测并对比各组大鼠代谢相关指标,肾组织纤维化程度指标,肾组织中炎症因子水平以及Podocalyxin、SOCS 1和结蛋白(Desmin)表达。结果:干预8周后,与对照组对比,模型组空腹血糖、糖化血红蛋白、甘油三酯、总胆固醇、24 h尿蛋白排泄率、肌酐、体重、肾组织转化生长因子-β1(Transforming growth factor,TGF-β1)、白介素(Interleukin,IL)-6、IL-1β、SOCS 1和Desmin水平均显著增加,Ⅳ型胶原蛋白(Collagen-Ⅳ,C-Ⅳ)、纤维连接蛋白(Fibronectin,FN)、层黏连蛋白(Laminin,LN)和Podocalyxin水平显著降低(P0.05);与模型组对比,西格列汀组和厄贝沙坦组空腹血糖、糖化血红蛋白、甘油三酯、总胆固醇、24 h尿蛋白排泄率、肌酐、体重、肾组织TGF-β1、IL-6、IL-1β和Desmin水平均显著降低,Podocalyxin和SOCS 1蛋白表达增加(P0.05)。但厄贝沙坦组与西格列汀组以上各指标对比差异无统计学意义(P0.05)。结论:西格列汀可能通过增加Podocalyxin和SOCS 1蛋白表达,降低肾组织中炎症因子和Desmin蛋白表达,进而改善糖尿病肾病大鼠肾纤维化和肾功能。     

特发性膜性肾病患者外周血中性粒细胞-淋巴细胞比值的临床与病理价值分析

摘要 目的：探讨外周血中性粒细胞与淋巴细胞比值（NLR）在特发性膜性肾病（IMN）中的临床及病理价值。方法：收集2017年1月至2019年12月确诊为IMN患者221例作为IMN组,将2019年7月至2019年9月体检且尿常规和肾功能指标正常的87例健康体检者作为正常对照组,计算每个研究对象的NLR值,比较两组间NLR值的差异。记录IMN患者的血生化指标及患者的肾脏病理分期及纤维化程度,并且根据MDRD公式计算肾小球滤过率(eGFR),分析NLR与IMN患者的血生化指标及病理特征的相关性。ROC曲线分析外周血NLR评估IMN患者肾间质纤维化的敏感性和特异性。结果：IMN组外周血NLR值高于对照组,差异有统计学意义（P<0.05）。外周血NLR值与IMN患者年龄和肾间质纤维化有关联（P均<0.05）,但与IMN患者性别及肾脏病理分期无关联（P均>0.05）。IMN外周血NLR值与IMN患者hs-CRP、SCr、BUN呈正相关（P<0.05）,与eGFR呈负相关（P<0.05）,与ESR、UA、TP、Alb、24小时蛋白尿定量均无相关性（P均>0.05）。不同程度肾间质纤维化的IMN患者外周血NLR值不同,差异有统计学意义（P<0.05）,且肾间质纤维化程度在1、2、3级时,纤维化程度越重,NLR值越大;3个级别间两两比较,差异均有统计学意义（P均<0.05）。外周血NLR值预测IMN患者肾间质纤维化的ROC曲线下面积为0.715[95%CI(0.626,0.803)],其截断值为1.858时,灵敏度为68.6%,特异度为66.7%。结论：外周血NLR可作为IMN肾脏功能水平的一个有效评价指标,且与IMN患者肾间质纤维化有关,可作为判断肾间质纤维化的参考指标。     

狼疮性肾炎患者血清sTM、KIM-1、sCD134水平的表达及临床意义

摘要 目的：研究狼疮性肾炎（LN）患者血清可溶性血栓调节蛋白（sTM）、肾损伤分子-1（KIM-1）及可溶性CD134（sCD134）水平的表达及临床意义。方法：选择2016年12月至2018年12月我院收治的LN患者100例,根据系统性红斑狼疮疾病活动度指数(SLEDAI)将患者分为活动期组(SLEDAI≥10分)56例,非活动期组(SLEDAI<10分)44例。另取同期于我院接受体检的健康志愿者50例记为对照组。比较各组受试者的各项肾功能指标、血清sTM、KIM-1及sCD134水平,分析血清sTM、KIM-1及sCD134水平与肾功能指标的相关性。应用受试者工作特征（ROC）曲线分析血清sTM、KIM-1及sCD134水平在LN诊断中的能效。结果：活动期组血尿素氮（BUN）、血肌酐（Scr）以及红细胞沉降率（ESR）水平均高于非活动期组、对照组,且非活动期组BUN、Scr以及ESR水平均高于对照组（P＜0.05）。活动期组血清sTM、KIM-1及sCD134水平均高于非活动期组、对照组,且非活动期组血清sTM、KIM-1及sCD134水平均高于对照组（P＜0.05）。经Pearson相关性分析显示,LN患者血清sTM、KIM-1、sCD134水平与患者BUN、Scr、ESR水平呈正相关（P＜0.05）。ROC曲线分析显示,sTM最佳临界值为24.46 ng/mL,曲线下面积为0.823;KIM-1最佳临界值为8.27μg/L,曲线下面积为0.823;sCD134最佳临界值为15.25 ng/mL,曲线下面积为0.823。结论：LN患者血清sTM、KIM-1及sCD134水平与患者疾病活动程度密切相关,对LN具有很好的诊断效能,临床可能通过联合检测血清sTM、KIM-1及sCD134水平,为LN的诊断以及疾病活动程度提供评估参考。