The impact of different doses of antithymocyte globulin conditioning on immune reconstitution upon hematopoietic stem cell transplantation

IntroductionAnti-thymocyte globulin (ATG) is used prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for graft-versus-host disease (GVHD) prophylaxis. Two different ATG doses (7.5 or 10 mg/kg) were evaluated in comparison with a group without ATG therapy.MethodsWe retrospectively analyzed 132 patients who were transplanted with HSCT without ATG (non-ATG), or who received 7.5 mg/kg ATG (ATG-7.5) or 10 mg/kg ATG (ATG-10) prior to transplantation. The immune cells (CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, CD19⁺ B cells and CD16⁺CD56⁺ NK cells) were examined in peripheral blood every three months post-HSCT for 12 months.ResultsCompared with non-ATG group, combined ATG-7.5/ATG-10 groups had significantly lower CD3⁺CD4⁺ T cells and higher CD3⁺CD8⁺ T cells at 3, 6, 9, 12 months post-HSCT; thus, displaying a lower CD4/CD8 ratio in the ATG groups compared to non-ATG group. The ratio of CD19⁺ B cells was statistically lower (at 3rd month, p = .014; at 6th month, p = .025) in combined ATG-7.5/ATG-10 groups at 3 and 6 months post-HSCT, but not at 9 and 12 months after HSCT. The ratios of CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, CD19⁺ B cells and CD16⁺CD56⁺ NK cells were similar between the ATG-7.5 and ATG-10 groups at all examined time points. The overall survival (OS), progression-free survival (PFS), relapse and acute GVHD (aGVHD) were comparable among recipients without ATG therapy and with ATG-7.5 or/and ATG-10 therapies. Multivariate analysis revealed that immune cells ratios were not independent factors affecting prognosis.ConclusionThe ATG therapy at higher and lower doses led to a delayed reconstitution of T cells and the inversion of CD4/CD8 ratio for at least one year after HSCT.     

癌组织浸润的FoxP3十调节性T淋巴细胞与CD34表达及肝癌患者的预后相关

目的 探讨FoxP3+调节性T淋巴细胞(Tregs)在肝癌患者癌及癌旁组织中的表达及其对预后的影响.方法 收集55例肝癌患者术后癌及癌旁组织标本,免疫组织化学检测肝癌及相应癌旁组织Tregs数量及癌组织CD34的表达情况.Speaman相关分析法分析Tregs与患者各种临床病理因素的相关性;据中位数将Tregs绝对值分为高低组,Kaplan-Meier分析Tregs高低组的总生存期和无瘤生存期,Log rank检验差异性;Cox回归法分析临床病理因素对预后的影响.结果 肝癌组织中每高倍视野的Tregs数量为10.8 (4.4～ 19.4)个,与相应癌旁组织1.4 (0.6～3.2)个相比,明显升高(P＜0.01).癌组织Tregs与相应癌组织血管内皮细胞标志物CD34的表达呈正相关(r=0.279,P＜0.05);癌及癌旁组织Tregs与其他临床病理因素均无相关性(P＞ 0.05).癌组织高Tregs组患者中位生存时间(18.0个月)明显短于低Tregs组(25.0个月),术后5年累积生存率及无瘤生存率较低(P值均＜0.05).Cox回归分析显示癌组织中Tregs数量是影响肝癌预后的独立因素(累积生存率:风险比=3.310,95％可信区间为1.368 ～ 8.007,P＜0.0l ;无瘤生存率:风险比=2.666,95％可信区间为1.321 ～ 6.394,P＜0.01).结论癌组织中Tregs数量可作为评估手术治疗肝癌患者预后的免疫学指标,Tregs瘤内浸润与肿瘤组织血管生成相关.     

心房颤动治疗的最新进展

本文综述了心房颤动(Af)在治疗方面新的研究进展,主要从Af的转复和维持、控制心室率、预防血栓栓塞等三方面加以介绍。     

Embryonic stem cells-derived exosomes enhance retrodifferentiation of retinal Müller cells by delivering BDNF protein to activate Wnt pathway

ObjectiveThe present study was intended to investigate the role of embryonic stem cell-derived exosomes (ESC-Exos) in Müller cell retrodifferentiation and their specific mechanism.MethodsFollowing co-incubation of the extracted ESC-Exos and Müller cells, their effects on the retrodifferentiation and proliferation of Müller cells were measured by EdU staining, immunofluorescence, and western blot. ESCs transfected with small interfering RNA of BDNF were co-incubated with Müller cells to determine Müller cell proliferation and retrodifferentiation. β-catenin expression in the nucleus and GSK-3β phosphorylation were measured to determine the role of the Wnt pathway in Müller cells. The function of the retina in RCS rats was observed using flash electroretinogram.ResultsCo-incubation of ESCs with Müller cells or overexpression of BDNF contributed to Müller cell retrodifferentiation and proliferation, as evidenced by increased cell proliferation, fluorescence intensities of proliferation markers and retinal stem cell markers, and expression of BDNF and β-catenin, and suppressed GSK-3β phosphorylation. However, co-incubation with ESCs silencing BDNF or treatment with GW4869 inhibited the proliferation and retrodifferentiation of retinal Müller cells. In addition, exosome injection increased BDNF, BrdU, PH3, SOX2, and Pax6 expression, enhanced β-catenin expression in the nucleus, diminished GSK-3β, and improved retinal degeneration in RCS rats.ConclusionESC-Exos accelerated Müller cell retrodifferentiation and proliferation through Wnt pathway activation by delivering BDNF protein to Müller cells.