委中穴刺络放血治疗腰椎间盘突出症临床观察

目的观察舒筋止痛水拍打委中穴后刺络放血疗法治疗腰椎间盘突出症的临床疗效。方法将60例腰椎间盘突出症患者随机分成两组,治疗组采用舒筋止痛水拍打委中穴后刺络放血疗法,对照组口服塞来昔布胶囊（西乐葆）。通过NRS评分表及腰椎JOA评分表记录治疗前后临床症状的改善程度。结果治疗组总有效率为100．0％,对照组总有效率为86．7％：治疗组治疗后NRS、JOA评分改善优于对照组,具有统计学意义（P〈0．001）。结论舒筋止痛水拍打委中穴后刺络放血是治疗腰椎间盘突出症的一种有效治疗方法。     

葡聚糖-表柔比星偶合物的制备和性质研究

目的　研究两种方法制备的葡聚糖 表柔比星偶合物的稳定性及体外细胞毒活性。方法　采用高碘酸钠氧化法制备聚醛基葡聚糖 表柔比星偶合物 (PAD EPR) ,将葡聚糖羧甲基化后制备腙健连接的羧甲基葡聚糖 表柔比星偶合物 (CMD EPR)。结果　PAD EPR的载药量为 1∶4,CMD EPR的载药量为 1∶10 ;二者在中性条件下均比较稳定 ,4℃贮存 70d ,药物偶合率都在90 %以上。偶合物的体外细胞毒性比游离药物有所下降 ,游离药物对正常细胞的毒性高于对肿瘤细胞的毒性 ,CMD EPR对肿瘤细胞的毒性高于对正常细胞的毒性 ,PAD EPR对两种细胞的毒性没有差异。结论　CMD EPR优于PAD EPR     

Epidermal growth factor partially restores colonic ion transport responses in mouse models of chronic colitis

BACKGROUND & AIMS: Epidermal growth factor receptor (EGFR) activation, which plays an important role in regulating intestinal ion transport, can alleviate clinical symptoms such as diarrhea in patients with ulcerative colitis and promote mucosal restitution in animal models of colitis. Here, we investigate whether EGFR can regulate colonic ion transport in the setting of colitis. METHODS: Distal colon from control mice and mice with colitis was retained for immunohistochemistry or mounted in Ussing chambers. Ion transport responses across the tissues to the calcium agonist carbachol and the adenosine 3',5'-cyclic monophosphate agonist forskolin were measured with or without epidermal growth factor (EGF) pretreatment. RESULTS: EGF pretreatment of normal colonic mucosa inhibited ion transport responses to carbachol and forskolin but potentiated the reduced ion transport responses seen in dextran sulfate sodium (DSS)-treated and mdr1a knockout mouse colon. Ion substitution studies and the sodium transport inhibitor amiloride showed that sodium movement primarily accounted for the potentiating effect of EGF in DSS-treated tissues, despite decreased sodium channel expression. EGF potentiation of transport responses in DSS-treated colon was completely blocked by the cytoskeletal disruptor cytochalasin D and the phosphatidylinositol 3-kinase inhibitor wortmannin, whereas the novel and conventional protein kinase C isoform inhibitor G?6850 and the extracellular signal-regulated kinase inhibitor PD98059 partially reduced EGF effects. EGFR epithelial distribution and transforming growth factor alpha expression were also altered in DSS-treated tissues. CONCLUSIONS: Chronic inflammation uncovers a potentiating effect of EGFR activation on epithelial electrogenic sodium absorption that would be expected to ameliorate diarrheal symptoms associated with colitis.     

氯吡格雷对早期急性冠状动脉综合征血清sCD40配体的影响

目的观察用氯吡格雷(clopidogrel)治疗早期急性冠状动脉综合征(acute coronary syndrome,ACS)对病人血清可溶性CD40配体(soluble CD40ligand,sCD40L)的影响,了解该药对ACS斑块稳定性和免疫炎症抑制的作用。方法128例初次确诊为ACS病人分为常规治疗组62例和氯吡格雷治疗组66例,用酶联免疫吸附测定ACS病人治疗前后血清sCD40L水平的变化。结果氯吡格雷治疗组66例ACS病人治疗后血清sCD40L水平从(11.8±3.1)μg/L下降至(5.7±3.0)μg/L,与常规治疗组比较,差异有统计学意义(P<0.01)。结论使用氯吡格雷治疗早期ACS,可明显降低病人sCD40L水平。     

风湿性心脏病心房颤动心房肌缝隙连接蛋白40和43 mRNA表达水平的变化

目的测定风湿性心脏瓣膜病(风心病)心房颤动(Af)心房肌缝隙连接蛋白(Connexin)40(Cx40)和Connexin43(Cx43)mRNA表达水平的变化。方法11例风心病患者[Af8例,窦性心律3例;男4例,女7例;平均年龄(50.8±13.7)岁;平均Af时间(5.6±6.5)年]的右心耳心肌1小块,提取所有标本的总RNA,等量转移至尼龙膜上,用PCR合成的特异cDNA探针,标记上放射性同位素(α32PdCTP)后与尼龙膜杂交,然后将杂交膜与X光胶片行放射自显影,在灰度扫描仪下得到每例标本mRNA水平的灰度值,为了进一步矫正转膜时可能的定量不统一,将同1块杂交膜先后与Cx40探针、Cx43探针和内参照βactin杂交,以Cx40/βactin和Cx43/βactin的百分比作为统计变量进行分析。结果在Af与窦性心律标本中,Cx40和Cx43的mRNA表达量未发生明显改变(P>0.05)。结论在风心病Af患者中,未发现缝隙连接蛋白Cx40和Cx43的mRNA表达量明显改变。     

CD40-1C/T单核苷酸多态性与缺血性脑卒中易感性的研究进展

缺血性脑卒中发病受多种遗传和环境因素的影响。动脉粥样硬化是缺血性脑卒中的重要病理、生理基础,目前研究发现CD40/CD40配体（CD40L）系统及血清可溶性CD40配体（sCD40L）参与动脉粥样硬化等炎性反应过程进而影响缺血性脑卒中的发生、发展。而CD40-1C/T单核苷酸多态性可通过调控该系统及血清sCD40L影响缺血性脑卒中的疾病易感性。本文对CD40-1C/T单核苷酸多态性与缺血性脑卒中易感性的研究进展进行综述。     

Expression and function of Fas antigen on activated murine B cells

We have studied the expression and function of Fas antigen on murine B lymphocytes. While Fas was present on only a few B cells in the bone marrow, spleen, lymph node or peripheral blood, its expression could be strongly up-regulated by stimulation with soluble CD40 ligand (CD40L). Treatment with anti-IgM and interleukin-4 (IL-4) alone did not induce significant Fas expression but enhanced CD40L-mediated up-regulation of Fas expression. The T cell-derived signal via CD40 is therefore a potent inducer of Fas expression by B lymphocytes. The sensitivity to Fas-mediated apoptosis was found to depend on the duration of B cell activation. B cells activated for 1 day were resistant to Fas-mediated cell death, whereas B cells activated for 3 days were relatively sensitive. Interestingly, different sensitivity to Fas-mediated death signal was observed in 2-day activated B cells. It was found that B cells stimulated with CD40 L alone were more sensitive to Fas-mediated apoptosis than were cells stimulated with CD40L plus anti-IgM or IL-4, and in particular, the combination of the two. The greater sensitivity exhibited by B cells stimulated with CD40L alone seems to be related to limited activation of these cells in the absence of additional stimulation. Co-stimulation of B cells in the presence of CD40L and anti-Fas antibody resulted initially in activation of B lymphocytes, as reflected by the expression of activation markers and cell growth, but this was followed by growth inhibition and cell death. The data demonstrate that the B cell response can be regulated positively and negatively by signaling through CD40 and Fas antigens, respectively.     

CD40 is functionally expressed on human keratinocytes

The CD40/gp39 pathway is known to be an important feature of B/T cell collaboration leading to T cell-dependent activation, proliferation or differentiation of B cells. Additionally, CD40 is involved in the regulation of B cell survival and apoptosis. Recently, CD40 has been shown to be expressed functionally on non-hematopoietic cells, i.e. endothelial cells. Here, we demonstrate that human keratinocytes (KC) cultured in vitro express CD40 constitutively. The surface expression of CD40 is markedly up-regulated following stimulation with interferon (IFN)-γ, but not with tumor necrosis factor-α or interleukin (IL)-1β. This process is regulated at the CD40 mRNA level as demonstrated by Northern blot analysis. Furthermore, ligation of CD40 via soluble gp39, the CD40 ligand, enhances intercellular adhesion molecule (ICAM)-1 and Bcl-x up-regulation on IFN-γ-stimulated KC, but not lymphocyte function-associated antigen (LFA)-3, B7-2, HLA-DR, or Fas expression. The release of IL-8 is also induced following CD40 ligation on KC. In psoriasis, a T cell-mediated inflammatory skin disease, KC have a markedly enhanced expression of CD40. This expression co-localizes with the expression of ICAM-1, Bcl-x, and an influx of CD3⁺ T cells. These findings suggest a functional role of CD40 on KC in inflammatory skin disorders such as psoriasis and could make a therapeutic intervention by disrupting the CD40/gp39 pathway an approach to consider in these inflammatory skin diseases.     

Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma

Endoglin (CD105) is a proliferation-associated protein abundantly expressed in angiogenic endothelial cells. Recent studies revealed that CD105 is intensively expressed in tumor vasculature, whereas intratumoral microvessel density (MVD) determined with the use of antibodies to CD105 has been found to be an important prognostic indicator for the outcome in a number of malignancies. In the current study, we investigated endoglin expression and evaluated MVD in 108 patients with head and neck squamous cell carcinoma. Endoglin was intensively expressed in intratumoral blood vessels, whilst lymphatics were rarely positive for CD105. High microvessel density was associated with a more aggressive tumor phenotype, including advanced clinical stage (p=0.008) and the presence of lymph node metastasis at the time of diagnosis (p=0.02). When microvessel counts were assessed for their prognostic values (high vs low MVD), there was a statistically significant difference in the overall survival among patients with tumors of the oral cavity and larynx (p<0.001) and in the disease-free survival among patients with tumors of the lower lip (p=0.01). The prognostic impact of microvessel density was not dependent on clinical stage or lymph node status. The results of the current study suggest that CD105 is a promising target for tumor imaging and prognosis.     

Stress‐activated dendritic cells interact with CD4+ T cells to elicit homeostatic memory

Evidence is presented that thermal or oxidizing stress‐activated DC interact with CD4⁺ T cells to induce and maintain a TCR‐independent homeostatic memory circuit. Stress‐activated DC expressed endogenous intra‐cellular and cell surface HSP70. The NF‐κB signalling pathway was activated and led to the expression of membrane‐associated IL‐15 molecules. These interacted with the IL‐15 receptor complex on CD4⁺ T cells, thus activating the Jak3 and STAT5 phosphorylation signalling pathway to induce CD40 ligand expression, T‐cell proliferation and IFN‐γ production. CD40 ligand on CD4⁺ T cells in turn re‐activated CD40 molecules on DC, inducing DC maturation and IL‐15 expression thereby maintaining the feedback circuit. The proliferating CD4⁺ T cells were characterized as CD45RA^? CD62L⁺ central memory cells, which underwent homeostatic proliferation. The circuit is independent of antigen and MHC‐class‐II‐TCR interaction as demonstrated by resistance to TCR inhibition by ZAP70 inhibitor or MHC‐class II antibodies. These findings suggest that stress can activate a DC‐CD4⁺ T‐cell interacting circuit, which may be responsible for maintaining a homeostatic antigen‐independent memory.