ATG4A及ATG16L1基因多态性与肺结核易感性的关系

目的：探讨自噬相关基因４Ａ（autophagy related 4A,ATG4A）及自噬相关基因１６Ｌ１（autophagy related １６ like 1,ATG16L1）的多态性位点与中国西南地区人群肺结核易感性的关系。方法：采用聚合酶链反应-限制性片段长度多态性技术检测218例肺结核患者及248例健康对照者ATG4A基因rs807185位点及ATG16L1基因rs2241880位点的基因型,用logistic回归分析上述２个位点与肺结核病易感的相关性。结果：2组人群中rs807185位点的A等位基因、AT基因型及显性模型AA+AT vs. TT的频率分布存在统计学差异（P＜0.05）,且在女性中差异更突出。而rs2241880位点的各指标频率分布差异均不明显（P >0.05）。结论：ATG4A基因rs807185位点多态性与中国西南地区人群肺结核易感性呈负相关,而ATG16L1基因rs2241880位点多态性则与该地区人群肺结核易感性无明显相关。     

胸苷酸合成酶基因多态性与儿童急性淋巴细胞白血病风险的Meta分析

目的 综合评价胸苷酸合成酶（TS）基因del6多态性与儿童急性淋巴细胞白血病（ALL）易感性的关系。方法 系统检索Pubmed、Science Direct、Google Scholar、中国知网（CNKI）和万方数据库,获取有关TS基因del6多态性与儿童ALL发生风险的文献资料,评估纳入研究的方法学质量并提取相关数据。以比值比（OR）和95%可信区间（CI）作为效应指标评估关联强度,纳入研究之间的异质性检验和合并OR值计算采用Revman 5.3软件,发表性偏倚应用漏斗图评估。结果 共纳入6个病例-对照研究,包括ALL患儿2104例,对照2320例。Meta分析结果显示,在整体人群比较中4种遗传模型均未发现TS基因del6多态性与儿童ALL易感性有显著性关联（杂合子模型：OR=0.99,95% CI：0.85~1.15,P=0.87;纯合子模型：OR=1.11,95% CI：0.90~1.38,P=0.33;隐性模型：OR=0.97,95% CI：0.76~1.25,P=0.84;显性模型：OR=1.01,95% CI：0.88~1.17,P=0.86）;根据种族进行分层分析也未发现显著性关联。漏斗图未检测到显著性发表性偏倚,敏感度分析表明合并结果是稳健可靠的。结论 目前的Meta分析表明TS基因del6多态性与儿童ALL易感性无关联。     

血清学生物标志物对急性呼吸窘迫综合征进展及预后的预测研究

目的 探讨血清学生物标志物对急性呼吸窘迫综合征(ARDS)早期诊断预警及预后判断的预测效果.方法 采用多中心、前瞻队列研究的方法,从2014年1月开始纳入各中心收治的ARDS与ARDS高危病例.采集患者的人口学资料,检测患者在入组24 h内的血清学指标(sRAGE、CC16、Ang-2、sICAM-1、PAI-1、SuPAR、HMGB1).采用Logistic回归分析对影响高危ARDS患者发展成为ARDS危险因素和影响ARDS预后的危险因素.用ROC曲线比较单个危险因素或联合多个危险因素对ARDS发生的预警及ARDS死亡预后的预测效果,计算其预测的灵敏度、特异度及约登指数.结果 共纳入ARDS患者59例,ARDS高危患者41例.ARDS发生的独立危险因素有HMGB1、sICAM-1、Ang-2、CC16、PAI-1.其中HMGB1预测效果最好(AUC=0.908),其次根据AUC大小顺序为CC16(AUC=0.861),Ang-2(AUC=0.858),PAI-1(AUC=0.801),sICAM-1(AUC=0.773).单指标分析中,敏感度最高的单指标为HMGB1与sICAM-1,皆为79.7％,特异度最高的指标为HMGB1、CC16与Ang-2,皆为87.8％.在联合预测中,HMGB1与Ang-2联合预测,特异度最高,为95.1％,其AUC也为最高(0.92).HMGB1、Ang-2与PAI-1指标联合预测,敏感度最高,为89.9％.多指标联合预测,可以在一定程度上提高对ARDS诊断预测的灵敏度和特异度.对ARDS预后分析,sRAGE与Ang-2是其死亡的独立危险因素.sRAGE(AUC=0.791)比Ang-2(AUC=0.67)对ARDS患者死亡预测效果好.两指标联合可以提高ARDS死亡预测的特异性.结论 在ARDS高危患者中,HMGB1、sICAM-1、Ang-2、CC16、PAI-1是其发展成为ARDS的独立危险因素.HMGB1与Ang-2联合预测有较好的特异性,HMGB1、Ang-2与PAI-1联合预测有较好的敏感性.对于ARDS患者,sRAGE与Ang-2的增高预示着ARDS患者预后不良,两者联合预测可以提高预测的特异性.     

MicroRNA-93及Tspan1在结肠癌中的表达及其临床病理意义*

目的 探讨microRNA-93（miR-93）及Tspan1在结肠癌组织及细胞中的表达及其临床病理意义,预测两者的靶向调控关系。方法 选取手术切除结肠癌组织及对应癌旁组织74例,人结肠癌细胞株（SW480、SW620、HCT116、CaCo-2、LoVo、HT29）及正常人结肠上皮细胞株（FHC）,分别采用qRT-PCR及Western blotting检测miR-93、Tspan1 mRNA及Tspan1蛋白表达,观察两者在不同临床病理特征患者的表达差异,Pearson法分析miR-93与Tspan1 mRNA的相关性,采用TargetScan及GeneCard软件预测两者的靶向调控关系。结果 与癌旁组织比较,miR-93在结肠癌组织中表达降低（P?<0.05）,Tspan1 mRNA及蛋白在结肠癌组织中表达升高（P?<0.05）;与正常人结肠上皮细胞比较,miR-93在结肠癌细胞株中表达降低（P?<0.05）,Tspan1 mRNA及蛋白在结肠癌细胞株中表达升高（P?<0.05）;miR-93在远处转移、淋巴结转移阳性、血管浸润阳性及高TNM分期患者中低表达（P?<0.05）,Tspan1 mRNA在远处转移、淋巴结转移阳性、血管浸润阳性及高TNM分期患者中高表达（P?<0.05）。Pearson法相关性分析显示,miR-93与Tspan1 mRNA表达呈负相关[r?=-0.735（95% CI：-0.855,-0.535）,P?=0.000]。生物信息学预测,miR-93及Tspan1在3''-UTR区可能具有靶向调控关系。结论 miR-93在结肠癌中低表达,Tspan1在结肠癌中高表达,miR-93及Tspan1具有靶向调控关系,两者可能成为结肠癌的肿瘤标志物或预测因子。     

腹腔镜精索静脉高位结扎术治疗精索静脉曲张

目的:探讨腹腔镜精索静脉高位结扎术治疗精索静脉曲张的临床价值。方法:回顾分析腹腔镜精索静脉高位结扎术治疗精索静脉曲张19例患者的临床资料,并评价手术方法的优缺点。结果:19例患者手术均获成功,手术时间20~80m in,基本无出血,术毕拔除导尿管,术后1~4d出院,平均住院2.5d。结论:腹腔镜精索静脉高位结扎术可避免开腹手术的较大损伤和对输精管的误伤,而且双侧可同时手术治疗;尽管费用稍高,仍不失为一种较好的治疗手段。     

Vertebral body stenting. A method for repositioning and augmenting vertebral compression fractures

Purpose of the study was to demonstrate the effectiveness of expanding a fractured vertebral body by transpedicular dilatation and stenting. 7 human cadaveric vertebral bodies from L2 to L5 underwent axia compression until a vertebral burst fracture was provoked. Then, by bilateral transpedicular approach, balloon-catheters were introduced, which were armed with stents, usually used for angioplasty. The catheters were inflated with radiolucent fluid and the stents expanded under radiologic control. After expansion, the balloon was deflated and removed, the stents resting inside the vertebral body, holding their inflated shape. Then, the resulting hole was filled with an injectable biodegradable calcium-phosphate. CT-scans were performed after destruction and after expansion. Morphology before and after expansion was judged, using 3-D reconstructions. Vertebral body strength was measured before destruction and after treatment with an Instron testing machine. RESULTS: Vertebral body shape could be restored. Also impressed central parts of the bony endplate could be elevated by using a convergent approach through the pedicles. There was no collapse of the vertebral body after removing the catheter-balloons The vertebral body strength could be restored up to a physiologic level. This procedure gives new perspectives in the treatment either of osteoporotic compression or traumatic vertebral fracture. By using CT-guided technique, it could be performed by a minimally invasive approach percutaneously.     

促纤维化小圆细胞肿瘤的临床分析

目的 提高对促纤维化小圆细胞肿瘤的认识和诊断水平。方法 回顾性总结本病2例患者的临床、病理资料,结合文献分析该肿瘤的发病情况、组织来源、病理特征、免疫组织化学、诊治及预后。结果 该肿瘤临床表现复杂多样,病理检查肿瘤细胞呈小圆形、核深染、胞浆少且无特殊排列的巢状,其间有大量增生的纤维结缔组织。免疫组织化学检测上皮、神经、肌、间质的相关蛋白细胞角蛋白、上皮膜抗原、结蛋白、神经原特异性烯醇化酶、波形蛋白表达阳性。2例均于术后9个月内相继死亡。结论 该肿瘤临床表现多样,常规检查不能正确诊断,必须进行免疫组化检测确诊。大多预后险恶。     

ox-LDL特异性人血管平滑肌细胞cDNA消减文库的构建

目的:构建ox-LDL特异性人血管平滑肌细胞cDNA消减文库。方法:35％ug/ml ox-LDL刺激培养的人血管平滑肌细胞,利用消减杂交技术,构建cDNA消减文库,并运用蓝白斑筛选和影印杂交进一步确定文库克隆的特异性。结果:成功构建ox-LDL特异性血管平滑肌细胞cDNA消减文库,约2000个白色克隆。影印杂交后共获82个差异表达克隆。结论:消减文库的构建为进一步克隆ox-LDL特异性基因cDNA片段和全长奠定了基础。     

Recombinant adenovirus mediated prostate-specific enzyme pro-drug gene therapy regulated by prostate-specific membrane antigen (PSMA) enhancer/promoter

Gene directed enzyme pro-drug therapy (GDEPT) is one of the adjuvant therapeutic regimens for advanced prostate adenocarcinoma, and this research intended to explore how to apply targeting therapy of prostate adenocarcinoma under the mediation of a promoter/enhancer of prostate-specific membrane antigen (PSMA(EP)) as a specific regulatory element. Recombinant adenoviruses (Ad-PSMA(E-P)-enhanced green fluorescent protein [EGFP], Ad-CMV-EGFP, Ad-PSMA(E-P)-CD, and Ad-CMV-CD) were constructed and could express cytosine deaminase (CD) or the EGFP reporter gene driven by a PSMA(EP) or cytomegalovirus (CMV) promoter. LNCaP, CL-1, MCF-7, and A549 were infected with CD-produced recombinant adenoviruses and treated with pro-drug 5-fluorocytosine (5-FC) in vivo and vitro; then, the growth inhibition of the cells and the cell cycle variation were assessed by an [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and flow cytometry. Growth suppression of the xenograft tumor was also adopted to evaluate the efficiency of the suicide system. Morphologic changes after treatment in vivo were assessed with hematoxylin and eosin staining. In the 4 examined cancer cell lines, PSMA-positive prostate cancer cells LNCap and CL-1 were exclusively sensitive to the Ad-PSMA(E-P)-CD/5-FC system. The S phase of cell cycle arrest was thought to be involved in the cytotoxicity of 5-fluorouracil (5-FU) converted from 5-FC by CD. CL-1 implanted Athymic BALB/c mice showed growth inhibition of tumors when they were treated with the Ad-PSMA(E-P)-CD/5-FC system without systemic conversion toxicity. The PSMA-based, CD-produced adenovirus, deserving further investigation in the future, might be a good candidate for targeting gene therapy of prostate adenocarcinoma.