G-CSF-Mobilized Blood and Bone Marrow Grafts as the Source of Stem Cells for HLA-Identical Sibling Transplantation in Patients with Thalassemia Major

As an inherited anemia, thalassemia major (TM) is currently only curable with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here we report an allo-HSCT protocol for patients with TM who received a combination of granulocyte colony-stimulating factor-primed bone marrow and peripheral blood stem cells (G-BM & PBSCs) from a matched sibling donor (MSD). The conditioning regimen consisted of i.v. busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin. Chimerism analysis was performed for all patients. Immunosuppressive treatment was terminated if rejection was suspected, and donor lymphocyte infusion was administered once no response was observed. A total of 184 patients with TM were enrolled in the study between July 2007 and July 2018. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 13.1%, and that of moderate or severe chronic GVHD was 5.7%. The cumulative incidence of graft rejection was .6%. In the total cohort, the 3-year overall survival, thalassemia-free survival, and GVHD-free, relapse-free survival were 97.8%, 97.3%, and 89.5%, respectively. Collectively, our results indicate that G-BM & PBSCs from an MSD is be a good stem cell source for patients with TM undergoing allo-HSCT.     

社区常见恶性肿瘤筛查研究

目的探寻一种简便的恶性肿瘤初筛自查方法。方法将人体肿瘤分为三类:体表肿瘤约占15％;空腔脏器肿瘤占65％;深层实体脏器肿瘤20％。通过科普宣传教育,让群众学会自查体表部位肿瘤,每年用自查盒助查各空腔脏器有无微量出血,隐血阳性时,去医院进一步精查。北京部分大学选40～70岁居民1万人,分成试验组、对照组各5千人。结果试验四年后:试验组共查出79例癌,年平均癌检出率482.5人/10万,癌死亡率为12.2/10万;对照组癌死亡率206.2人/10万,两组有显著性差异。在癌症高发区,同时作扩大普查试验:广东四会市肿瘤所,在门诊普查1669人,检出25例癌,鼻咽癌占24例。1999～2000年,江苏省食管胃癌高发区,普查近8万人,检出480例癌。加上“九五”以前的普查统计,用秦氏自查盒已筛查431075人,检出1272例癌,癌前病变1万多例。结论试验证明该方案设计合理,在当前是一种最简便的恶性肿瘤初筛自查方法。     

饲喂乳源免疫调节肽对大鼠生长和免疫的影响

目的探讨乳源免疫调节肽(PGPIPN)对大鼠生长和免疫的影响。方法取42只40日龄的SD大鼠(♀♂各半)随机分为两个实验组和一个对照组(每组14只且♀♂相等,分开饲养)。预饲1周后,实验组Ⅰ和Ⅱ分别被灌喂2.5×10-3g/L和2.5×10-2g/L免疫调节肽,对照组灌喂生理盐水,记录大鼠日采食量和体重。饲养1个月后检测对照组和实验组大鼠淋巴细胞转化、红细胞免疫、巨噬细胞吞噬、日采食量和体重等差别。结果乳源免疫调节肽对大鼠腹腔巨噬细胞吞噬和红细胞免疫有显著促进功能(P<0.05);而对淋巴细胞转化作用有增长的趋势,但未达到显著水平(P>0.05)。与对照组相比,实验组Ⅱ的大鼠日采食量显著地增加(P<0.05),♀♂大鼠分别提高了10.95%和8.03%;增重率有提高的趋势,♀♂大鼠增重率分别提高了5.13%和7.10%,但均未达显著水平(P>0.05)。实验组Ⅰ的大鼠,其日采食量和增重与对照组相比均变化不大。结论乳源免疫调节肽能促进机体的免疫功能,提高其免疫力;增加日采食量。     

不同剂量甘露醇对脑卒中肾功能的影响

大样本观察分析不同剂量甘露醇对脑卒中肾功能的影响,探讨甘露醇治疗脑卒中病人的最佳剂量。 1.资料与方法:参照1995年全国第四届脑血管会议通过脑血管疾病分类诊断要点选择脑卒中患者3431例,男2235例,女1196例。年龄26～81岁,平均48.2±2.3岁。其中急性脑梗死(ACI)2208例     

Chloride channel 3 (CIC-3) predicts the tumor size in hepatocarcinoma

Chloride channel 3 (CIC-3) has been suggested to be implicated in the carcinogenesis though; it still remains ill understood in hepatocarcinoma, especially in terms of clinicopathological meaning of its expression. Given this, herein, to understand the clinicopathological significance of CIC-3 expression in hepatocarcinoma, Immunohistochemistry was performed to examine the level of CIC-3, followed by statistical analysis of the correlation between expression versus clinicopathological variables, including gender, age, TNM classifications, tumor size, lymph node metastasis and overall prognosis. It was shown that positive staining of CIC-3 can be present in both hepatocarcinoma and its paired normal controls; and that CIC-3 was significantly over-expressed in hepatcarcioma on the whole relative to paired normal controls. Moreover, up-regulation of CIC-3 markedly correlated with tumor size and overall prognosis, suggesting that CIC-3 expression could predict both tumor size and overall prognosis in hepatocarcinoma.     

T follicular regulatory cells suppress Tfh-mediated B cell help and synergistically increase IL-10-producing B cells in breast carcinoma

T follicular regulatory (Tfr) cell is a recently discovered subset of T regulatory (Treg) cells. The main function of Tfr cells is thought to suppress germinal cancer reaction and inhibit B cell proliferation and Ig production. However, recent studies demonstrate that Tfr cells may be required for high-affinity Ig formation during acute virus infections. The role of Tfr cells in breast cancer is not thoroughly investigated. In this study, total circulating CD4 T cells were sorted into CD25⁺CXCR5⁻ Treg-like, CD25⁺CXCR5⁺ Tfr-like, and CD25⁻CXCR5⁺ Tfh-like subsets. Data showed that the Tfr-like subset presented intermediate levels of both Foxp3 and Bcl-6, while the Treg-like subset was high in Foxp3 and low in Bcl-6, and the Tfh-like was high in Bcl-6 and low in Foxp3. Of note, the frequencies of Tfr-like and Treg-like cells were significantly elevated in breast cancer (BC) patients than in non-cancer (NC) controls. Tfr-like cells in BC patients also expressed significantly higher levels of Foxp3 than those in NC controls. Neither Treg-like nor Tfr-like cells could support Ig production from naive B cells, while Tfh-like cells potently supported Ig production from naive B cells. Tfr-like cells increased the availability of IL-10, both by directly producing IL-10 and by increasing IL-10 production from B cells. Interestingly, Tfr-like cells increased IL-10 production from B cells synergistically with Tfh cells, but at the same time, significantly reduced Ig production in the Tfh-B cell coculture. These Tfr-mediated effects on Tfh cells were not found in canonical Treg cells. Overall, this study demonstrates several distinctive features in circulating Tfr cells and suggests that Tfr cells may promote the formation of IL-10-producing B cells in BC.

     

Enhanced Anti-Leukemic Effects through Induction of Immunomodulating Microenvironment by Blocking CXCR4 and PD-L1 in an AML Mouse Model

Previously, we found that dual therapy by the CXCR4 inhibitor Plerixafor and cytosine arabinoside (Ara-C) effectively eradicated leukemia cells and concurrently activated immune cells in acute myeloid leukemia (AML). To reveal the significance of programmed death-ligand1 (PD-L1) in AML and as a strategic approach, we investigated the anti-leukemic effect of a triple combinational therapy by utilizing Plerixafor and anti-PD-L1 in combination with chemotherapy in an AML mouse model. We examined leukemic myeloid blast cells in multiple organs after the successive treatment with Ara-C, Plerixafor, and anti-PD-L1. The results showed that noticeable benefits of triple combinational therapy for eradication of myeloid blast cells in vivo with prolonged survival rates. The frequencies of regulatory T cells (Tregs), monocytic-myeloid-derived suppressor cells (M-MDSCs), and granulocytic-myeloid-derived suppressor cells (G-MDSCs), in the peripheral blood of leukemic mice were consistently decreased, even when mice were sacrificed alive at D + 26 after completion of the triple combinational therapy, compared to the other subgroups. These findings imply that the modulation by the triple combinational therapy may lead to more efficient leukemic myeloid blast cell ablation through the suppression of Tregs or M-MDSCs and G-MDSCs in AML. Although Plerixafor and PD-L1 antagonist do not have a direct anti-leukemic role, our results provide some clues and guidelines to develop clinically therapeutic strategies for chemotherapy-resistant patients by the modulation of leukemic microenvironments.