血管细胞黏附分子-1及P-选择素在喉咽癌中的表达及与微血管密度的相关性研究

目的：检测喉咽癌组织中血管细胞黏附分子-1（vascular cell adhesion molecule-1，VCAM-1）及P-选择素的表达及其与微血管密度（mierovessel density，MVD）间的关系，探讨VCAM-1及P选择素在喉咽癌血管生成中的意义。方法：用免疫组织化学方法检测40例喉咽癌组织和10例正常口咽部黏膜组织中VCAM-1、P选择素及CD34表达并计数MVD。结果：VCAM-1及P-选择素在喉咽癌组织中的表达率显著高于正常口咽部黏膜组织（P〈0．01）；喉咽癌组织的MVD值显著高于正常口咽部黏膜组织（P〈O．01），MVD值与有无淋巴结转移密切相关（P〈0．01）；VCAM-1及P-选择素表达阳性组MVD值显著高于表达阴性组（P〈0．01），且VCAM-1及P-选择素表达均与MVD呈正相关（P〈0．05）；在喉咽癌淋巴结转移组中，VCAM-1及P选择素的表达呈正相关关系。结论：VCAM-1及P-选择素在喉咽癌组织中的高表达在肿瘤的浸润和转移中起重要作用，并与肿瘤血管生成有关．     

Genetic ablation of steroid receptor coactivator‐3 promotes PPAR‐β‐mediated alternative activation of microglia in experimental autoimmune encephalomyelitis

Steroid receptor coactivator‐3 (SRC‐3) has been demonstrated to regulate lipid metabolism by inhibiting adipocyte differentiation. In this study, the potential role of SRC‐3 in experimental autoimmune encephalomyelitis (EAE), which characterized by inflammatory demyelination in central nervous system (CNS), was examined by analyzing disease progression in SRC‐3‐deficient (SRC‐3^−/−) mice. We found that SRC‐3 deficiency significantly attenuated the disease severity of EAE along with decreased inflammatory infiltration and demyelination. However, these effects are not caused by inhibition of peripheral T cell response, but by upregulated expression of peroxisome proliferator‐activated receptor (PPAR)‐β in CNS, which induced an alternative activation state of microglia in SRC‐3^−/− mice. These alternatively activated microglia inhibited CNS inflammation through inhibition of proinflammatory cytokines and chemokines, such as TNF‐α, IFN‐γ, CCL2, CCL3, CCL5, and CXCL10, as well as upregulation of anti‐inflammatory cytokine IL‐10 and opsonins, such as C1qa and C1qb. Moreover, microglia alternative activation promoted myelin regeneration through increased accumulation of oligodendrocyte precursors in white matter and elevated expression of myelin genes in the spinal cords of SRC‐3^−/− mice. Our results build up a link between lipid metabolic regulation and immune functions, and the modulation of the expression of SRC‐3 or PPAR‐β may hopefully has therapeutic modality in MS and possibly other neurodegenerative diseases. © 2010 Wiley‐Liss, Inc.     

足三里注射地塞米松治疗慢性重度乙型肝炎黄疸28例

目的:观察小剂量地塞米松足三里穴位注射治疗慢性重度乙型肝炎黄疸的临床疗效。方法:将60例慢性重度乙型肝炎黄疸患者随机分为两组,对照组给予常规对症支持治疗及普通退黄治疗,治疗组在此基础上给予小剂量地塞米松足三里穴位注射。治疗4周后分析疗效。结果:治疗组乏力、纳差及皮肤、巩膜黄染恢复正常时间均优于对照组(P<0.05),治疗后TBIL及ALT下降时间少于对照组,下降水平高于对照组(P<0.05)。结论:地塞米松足三里穴位注射治疗慢性重度乙型肝炎黄疸有较好疗效。     

胸腺瘤治疗的现状和进展(附127例临床报告)

目的 总结胸腺瘤的诊断与治疗经验.方法 复习近年文献,结合我科127例胸腺瘤的临床资料,对其手术途径,单纯胸腺瘤和、扩大胸腺瘤切除术=胸腺瘤综合治疗现状和回顾性分析.结果 胸部X线,CT等影像学检查是本病诊断的主要手段.重症肌无力是常见伴随症状,发生率为43.3%(55/127).扩大胸腺瘤切除治疗效果优于单纯胸腺瘤切除.Ⅱ期以上病变进行放疗或化疗及综合治疗可提高疗效.结论 胸腺瘤不宜行单纯切除,无论病理分期如何均应行扩大切除,有利降低复发率.术中发现胸腺肿瘤有明显外侵或累及器官,术后应辅以综合治疗(化疗或放化疗),以提高疗效.     

A short course of tofacitinib sustains the immunoregulatory effect of CTLA4-Ig in the presence of inflammatory cytokines and promotes long-term survival of murine cardiac allografts

Costimulation blockade-based regimens are a promising strategy for management of transplant recipients. However, maintenance immunosuppression via CTLA4-Ig monotherapy is characterized by high frequency of rejection episodes. Recent evidence suggests that inflammatory cytokines contribute to alloreactive T cell activation in a CD28-independent manner, a reasonable contributor to the limited efficacy of CTLA4-Ig. In this study, we investigated the possible synergism of a combined short-term inhibition of cytokine signaling and CD28 engagement on the modulation of rejection. Our results demonstrate that the JAK/STAT inhibitor tofacitinib restored the immunomodulatory effect of CTLA4-Ig on mouse alloreactive T cells in the presence of inflammatory cytokines. Tofacitinib exposure conferred dendritic cells with a tolerogenic phenotype reducing their cytokine secretion and costimulatory molecules expression. JAK inhibition also directly affected T cell activation. In vivo, the combination of CTLA4-Ig and tofacitinib induced long-term survival of heart allografts and, importantly, it was equally effective when using grafts subjected to prolonged ischemia. Transplant survival correlated with a reduction in effector T cells and intragraft accumulation of regulatory T cells. Collectively, our studies demonstrate a powerful synergism between CTLA4-Ig and tofacitinib and suggest their combined use is a promising strategy for improved management of transplanted patients.     

复杂病例行机器人辅助腹腔镜前列腺癌根治术的初步经验

目的：探讨机器人辅助腹腔镜前列腺癌根治术(robot-assisted laparoscopic prostatectomy,RALP)治疗复杂前 列腺癌病例的初步经验。方法：回顾性分析中南大学湘雅三医院2015年10月至11月行RA LP的4例复杂前列腺癌患者的 临床和病理资料。4例患者,年龄58~70岁,均接受过经尿道等离子镜下前列腺癌剜除术和内分泌治疗。结果：4例患 者手术均获成功,基线前列腺特异抗原(prostate specifi c antigen,PSA)6.04~70.15 ng/mL,临床分期T2b~T3b,手术时间 180~360 min,术中出血量50~250 mL,均未输血,手术切缘均为阴性。结论：虽然经尿道前列腺手术史和内分泌治疗 史会增加手术难度,RA LP仍可用于此类复杂前列腺癌病例的治疗。     

Deoxycytidyl-deoxyguanosine oligonucleotide classes A, B, and C induce distinct cytokine gene expression patterns in rhesus monkey peripheral blood mononuclear cells and distinct alpha interferon responses in TLR9-expressing rhesus monkey plasmacytoid dendritic cells

To determine if deoxycytidyl-deoxyguanosine oligonucleotides (CpG ODN) can be used effectively as nonspecific inducers of innate immune defenses for preventative or therapeutic interventions in infectious disease models for nonhuman primates, the present study evaluated the response of rhesus monkey peripheral blood mononuclear cells to three different synthetic CpG ODN classes by defining the cytokine gene expression patterns and by characterizing IFN-alpha/beta responses. Depending on the type and dose of CpG ODN used for stimulation, distinct gene expression patterns were induced. CpG ODN class A (CpG-A ODN) and CpG-C ODN, but not CpG-B ODN, were potent inducers of alpha interferon (IFN-alpha), and this response was due to IFN-alpha production by TLR9-positive plasmacytoid dendritic cells. Importantly, there was a dose-dependent increase in IFN-alpha responses to CpG-A ODN but a dose-dependent decrease in IFN-alpha responses by CpG-B ODN. The most sustained IFN-alpha response was induced by CpG-A ODN and was associated with a stronger induction of interferon regulatory factor 7 and the induction of several interferon-stimulated genes. In contrast, and independent of the dose, CpG-B ODN were the weakest inducers of IFN-alpha but the most potent inducers of proinflammatory cytokines. CpG-C ODN induced cytokine gene expression patterns that were intermediate between those of CpG-A and CpG-B ODN. Thus, the different types of CpG ODN induce different post-TLR9 signaling pathways that result in distinct cytokine gene expression patterns. Based on these findings, A and C class CpG ODN, but not B class CpG ODN, may be particularly suited for use as therapeutic or prophylactic antiviral interventions.     

Cytoplasmic DNA sensing by KU complex in aged CD4+ T cell potentiates T cell activation and aging-related autoimmune inflammation

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同型半胱氨酸等生化指标与糖尿病足关系的研究

目的探讨同型半胱氨酸（Hcy）等生化指标与糖尿病足的关系。方法对比分析137例2型糖尿病合并糖尿病足病患者（糖尿病足组）及137例未合并糖尿病足的2型糖尿病患者（非糖尿病足组）的年龄、性别、病程、Hcy、Hb、糖化血红蛋白（HbA1c）、肌酐（Cr）、LDL-C、血白蛋白（ALB）等,采用logistic回归分析糖尿病足的危险因素。结果两组患者性别、年龄、病程、LDL-C比较差异均无统计学意义（均P＞0.05）,而Hcy、HbA1c、Hb、Cr、ALB差异均有统计学意义（均P＜0.05）。logistic回归分析显示Hcy（OR＝1.156,P＝0.000）及HbA1c（OR＝1.641,P＝0.003）是糖尿病足的独立危险因素,Hb（OR＝0.976,P＝0.001）是糖尿病足的保护性因素。性别（＝1.162,P＝0.569）、年龄（OR＝0.989,P＝0.521）、病程（OR＝1.045,P＝0.251）、LDL-C（OR＝0.953,P＝0.770）、Cr（OR＝1.009,P＝0.555）、ALB（OR＝0.943,P＝0.112）等指标未见与糖尿病足明显相关。结论Hcy及HbA1c是糖尿病足的危险因素,Hb是糖尿病足的保护性因素。     

吡柔比星对大鼠心肌细胞的损伤作用及其模型建立

目的：探讨吡柔比星（THP）对大鼠心肌细胞的损伤作用,阐明THP诱导心肌细胞损伤模型的建立方法。方法：常规体外培养大鼠心肌细胞H9C2,将细胞分为空白对照组和不同浓度（1×10^-6 mol·L^-1、1×10^-5 mol·L^-1、1×10^-4 mol·L^-1、1×10^-3 mol·L^-1和1 μmol·L^-1、3 μmol·L^-1、5 μmol·L^-1、7 μmol·L^-1、9 μmol·L^-1和10 μmol·L^-1 THP组,采用不同浓度THP处理细胞,并在6、12、24、36和48 h时间点采用CCK-8法检测各组细胞存活率,DCFH-DA活性氧（ROS）探针法检测细胞中ROS水平,硫代巴比妥酸比色法检测各组细胞中丙二醛（MDA）水平,黄嘌呤氧化法检测各组细胞中超氧化物歧化酶（SOD）活性,二硝基苯肼显色法检测各组细胞中乳酸脱氢酶（LDH）活性,TUNEL染色法检测各组细胞凋亡率,qRT-PCR法检测各组细胞中B淋巴细胞瘤-2相关X蛋白（Bax）、B淋巴细胞瘤2（Bcl-2）、半胱氨酸蛋白酶3（Caspase-3）和半胱氨酸蛋白酶9（Caspase-9）mRNA表达水平,Western blotting法检测各组细胞中Bax、Bcl-2、活化型Caspase-3（Cleaved Caspase-3）和活化型Caspase-9（Cleaved Caspase-9）蛋白表达水平。结果：与空白对照组比较,1、5和9μmol·L^-1 THP组H9C2细胞存活率降低（P<0.05或P<0.01）,细胞中ROS和MDA水平及LDH活性升高（P<0.05或P<0.01）,SOD活性降低（P<0.05）,细胞凋亡率升高（P<0.05）,细胞中Bax、Caspase-3和Caspase-9 mRNA表达水平升高（P<0.05或P<0.01）,Bcl-2 mRNA表达水平降低（P<0.05）,Bax、Cleaved Caspase-3和Cleaved Caspase-9蛋白表达水平升高（P<0.05或P<0.01）,Bcl-2蛋白表达水平降低（P<0.01）。结论：THP对大鼠心肌细胞具有损伤作用,其中5 μmol·L^-1是THP诱导H9C2细胞损伤模型的最佳造模浓度。