阻断Notch信号通路治疗多发性骨髓瘤的研究进展

Notch在多个物种中均有表达,其家族成员的结构具有高度保守性,Notch信号通路更是在众多病理生理过程中发挥关键作用。Notch家族成员Notchl不仅全程参与正常MM细胞的发育。同时也与多发性骨髓瘤的发生密切相关。Notch信号通路激活后可通过对NF—κB、C—myc的相互作用,调节细胞的增殖,促进骨髓瘤细胞的生长,从而抑制骨髓瘤细胞的凋亡,它与骨髓瘤的发生和耐药有关。通过对Notch及其通路的研究,使得对MM的发病机制有了更深入的了解,从而为MM的诊治提供了新靶点。一些阻断Notch信号的药物如砷剂及γ-分泌酶抑制剂等应用使MM的治疗得到了极大的突破。本文就该领域的研究现状进展进行综述。     

强直性脊柱炎外周血破骨细胞前体细胞活性的研究

Objective To investigate the number of osteoclast (OC) precursor in the peripheral blood of patients with ankylosing spondylitis (AS) and its relationship with serum receptor activator of nuclear factor KB-ligand (RANKL) and Osteoprotegerin (OPG) concentration as well as the disease activity. Methods The peripheral blood mononuclear cells from 8 cases of AS patients and 5 healthy controls were cultured in the medium containing macrophage colony-stimulating factor (M-CSF) (25 ng/ml) and RANKL (40 ng/ml). After being cultured for 14 days, cytochemistry was applied to detect tartrate-resistant acid phosphatase (TRAP) expression and the cells with TRAP expression and ≥3 nuclei were counted and defined as OC. Bone resorption assay was used to demonstrate OC function. ELISA was used to measure serum RANKL and OPG concentration in 23 cases of AS and 17 healthy controls. The relationship was analyzed in AS patients between the number of OC precursors and serum RANKL and OPG concentration as well as the disease activity. The indicators of disease activity were Bath ankylosing spondylitis disease activity index (BASDAI), Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). T test, t' test and Spearman correlation were selec-ted. Results ① Significantly higher OC production was observed in the peripheral blood of AS patients than that of healthy control group. The OC number per ten fields was 10.9±3.4 and 6.2±1.3 respectively (P<0.05); ② There was significant difference between AS patients and healthy controls in serum concentration of OPG and RANKL and the ratio of RANKL/OPG. OPG was significantly higher in AS patients [(157±49) pg/ml] than in healthy controls [(105±20) pg/ml] (P<0.05). RANKL was significantly higher in AS patients [(5.4± 3.8) pg/ml] than in healthy controls [(1.6±0.8) pg/ml] (P<0.05). The ratio of RANKL/OPG was significantly higher in AS patients (0.037±0.026) than in healthy controls (0.016±0.008) (P<0.01 );③Significantly positive correlation was observed between the OC number and the serum concentration of RANKL (r=0.692, P=0.009), the ratio of RANKL/OPG (r=0.813, P=0.001);④ In AS patients, serum concentration of OPG was found to have significantly negative correlation with BASDAI (r=-0.444, P=0.044). Serum RANKL concentration was found to have significantly positive correlation with BASDAI (r=0.543, P=0.011). The ratio of RANKL/OPG was found to have significantly positive correlation with BASDAI (r=0.672, P=0.001). Conclusion ① More OC precursors exist in the peripheral blood of AS patients. These cells may differentiate into osteoclasts, which might play a role in joints destructions in AS;② The mechanism of high OC production is likely to be due to high RANKL concentration which is caused by inflammatory reaction.     

类风湿性关节炎贫血患者血清TNFα,IFNγ和Epo的变化及意义

目的 探讨肿瘤坏死因子α（ＴＮＦα）、干扰素γ（ＩＦＮγ）和促红细胞生成素（Ｅｐｏ）在类风湿性关节炎（ＲＡ）伴慢性疾病性贫血（ＡＣＤ煌发生机制中的作用。方法 采用ＥＬＩＳＡ法检测ＲＡ患者血清中ＴＮＦα、ＩＦＮγ、及ＲＡ伴ＡＣＤ患者的Ｅｐｏ变化,并测定ＲＡ患者的铁代谢指标。结果 与对照组比较,ＲＮＡ组及ＲＡ伴ＡＣＤ组血清中,ＴＮＦα,ＩＦＮγ均显著增高,ＴＮＦα、ＩＦＮγ与知清铁、血红蛋白浓度呈负相     

自体干细胞移植治疗慢性髓系白血病

慢性髓系白血病（ＣＭＬ）是一种造血克隆性疾病，其特征是白血病的干／祖细胞有Ｐｈ染色体标志，含ｂｃｒ／ａｂｌ融合基因。常规治疗，如马利兰或羟基脲可使多数ＣＭＬ患者得到血液学缓解，在经历约３～５年的慢性期后，患者最终进入加速期和急变期而死亡。近年来在治疗ＣＭＬ方面已取得新的进展，一致的看法是，同种骨髓移植是治愈ＣＭＬ的唯一方法，如施行于慢性期，约３０％～７０％的患者可获得长期无病生存，这些患者可能已被治愈。然而由于患者年龄限制或得不到ＨＬＡ匹配的供者，实际能从此受益的患者很少（可能不到２０％）。干扰…     

TNFα、Epo与RA贫血相关性的研究

贫血是类风湿性关节炎(RA)常见的关节外表现,而最常见的贫血类型是慢性疾病性贫血(ACD),其发病机制未完全明确。本文检测RA患者血中肿瘤坏死因子(TNF)α和促β_2细胞生成素(Epo)的变化,探讨它们在RA伴ACD发病中所起的作用。1 材料与方法1.1 病例组 RA患者77例,男21例,女56例,年龄16～75岁(14.3±14.0);病程1月至40年。所有患者均符合美国风湿病协会(ARA)1987年修订的诊断标准。按血红蛋白(Hb)男≤     

自体树突状细胞活化的骨髓细胞对慢性粒细胞白血病细胞毒性作用研究

目的 考察自体树突状细胞（DC）活化的骨髓细胞对慢性粒细胞白血病（CGL）细胞的毒性作用。方法 用免疫磁珠从2例缓解的CGL患者骨髓单个核细胞（BMMNC）分离DC,另取BMMNC分成3份,分别加入长期培养基,建立Dexter培养体系。第1份为对照,第2份加重组人白细胞介素2（rhIL-2),第3份于培养第4天加入收获的DC,培养10d后收集非贴壁细胞。以上述3份非贴壁细胞为效应细胞,对照非贴壁细胞为靶细胞,采用双色流式细胞技术进行细胞毒性实验,同时用流式细胞技术检测BMMNC的P210表达。结果 DC活化的效应细胞比rhIL-2活化的效应细胞对靶细胞有更大的杀伤作用,靶细胞中的死细胞比例例1分别为63．12％和42．59％,例2分别为61．60％和21．46％。另外,DC活化的效应细胞与靶细胞混合孵育后,效应细胞本身的死细胞比例明显增加,rhIL-2活化的效应细胞无此现象。BMMNC经培养后非贴壁细胞中P210阳性细胞比例明显减少,以含DC者最为显著,含rhIL-2者次之。结论 自体DC活化的骨髓细胞能对CGL细胞产生明显的细胞毒性作用,DC的作用胜过rhIL-2。这些经DC活化的骨髓回输后可能在体内发挥移植物抗白血病（GVL）效应。     

糖尿病患者血细胞体积增大在微血管病变中的作用

目的探讨糖尿病患者血细胞体积增大的原因及在微血管病变中的作用。方法52例糖尿病患者部分血细胞参数和红细胞膜Na+-K+-ATPase、Ca2+-ATPase活性分别采用全自动血细胞分析仪和改良的Hanahan法、Luthra法测定,并设对照组比较。结果糖尿病患者红细胞膜Na+-K+ATPase、Ca2+-ATPase活性降低,以合并微血管病变组最为明显;微血管病变组平均红细胞体积(MCV)、平均血小板体积(MPV)增大,平均红细胞血红蛋白浓度(MCHC)降低;而无微血管病变组则正常。MCV、MCHC和MPV的变化与红细胞膜两种ATPase活性降低有关。结论与ATPase活性改变有关的血细胞体积增大可能是糖尿病微血管病变发生的重要因素。     

H3K27甲基化与EZH2在B细胞非霍奇金淋巴瘤中表观遗传调控的研究进展

异常的组蛋白修饰与DNA甲基化是表观遗传学研究的重要领域,两者相互作用可导致特定基因的转录激活或抑制。H3K27的甲基化水平及其甲基转移酶EZH2可能与B细胞非霍奇金淋巴瘤（B-cell NHL）的特殊分型及不良预后密切相关。本文着重介绍H3K27me3与EZH2在B细胞非霍奇金淋巴瘤中的发生和发展过程的作用及相应机制。     

ABC－ELISA法定量检测IgM、IgG、IgA型类风湿因子的临床意义

目的探讨ＩｇＭ型、ＩｇＧ型及ＩｇＡ型类风湿因子（ＲＦ）定量检测方法的意义。方法应用生物素—亲和素结合ＥＬＩＳＡ法（ＡＢＣ—ＥＬＩＳＡ）测定类风湿关节炎５７例，其他疾病６６例，并以１００例健康人作对照。结果类风湿关节炎患者各型ＲＦ的阳性率及滴度均明显高于其他病患者（Ｐ＜０．００５），其中ＩｇＡＲＦ与ＩｇＭＲＦ相关性较大（Ｐ＜０．０１）。结论定量方法检测各型类风湿因子，有助于类风湿关节炎的早期诊断和鉴别。     

36例成人Still病血清铁蛋白水平变化及临床意义观察

目的探讨血清铁蛋白(SF)检测在成人Still病(AOSD)的诊断价值以及与病情活动性的关系。方法检测36例AOSD患者血清铁蛋白(SF)、C反应蛋白(CRP)、血沉(ESR)值,与同期31例非AOSD患者进行比较。结果AOSD组SF水平显著高于非AOSD组(P<0.01),两组ESR、CRP水平差异无统计学意义(P>0.05)。AOSD组中,SF>正常值5倍的例数所占比例明显高于非AOSD组(P<0.01)。SF>正常值5倍和SF>正常值10倍诊断AOSD的临床概率的敏感性分别为75%、44.4%;特异性分别为80.7%、96.8%;阳性预测值分别为79.4%、94.1%;阴性预测值分别为75.8%、60%。AOSD组患者经糖皮质激素治疗病情好转者,其SF、ESR、CRP水平较治疗前明显下降(P<0.01)。结论SF可作为AOSD的辅助诊断指标及病情活动度指标,且对指导糖皮质激素治疗剂量具有重要意义。