胃肠道间质瘤的预后

随着对胃肠道间质瘤（gastrointestinal stromal tumor，GIST）分子生物学的认识和激酶抑制剂类靶向治疗药物的诞生，GIST的预后也发生了明显改善，疾病缓解率和手术切除率显著提高，生存期延长。不同的临床病理因素和治疗方法对GIST病人生存期具有根本影响。     

JAK2激酶抑制剂AG490对结肠癌HT-29细胞侵袭性的影响

目的观察JAK2激酶抑制剂AG490对结肠癌HT-29细胞侵袭以及对基质金属蛋白酶-2（MMP-2）表达的影响，探讨STAT3信号转导通路在结肠癌侵袭转移调控中的作用。方法应用JAK2激酶抑制剂AG490处理结肠癌HT-29细胞，Matrigel肿瘤体外侵袭模型检测肿瘤细胞侵袭；Western blot检测STAT3蛋白表达；逆转录-聚合酶链反应（RT—PCR）检测MMP2mRNA表达。结果AG490可抑制JAK2／STAT3信号转导通路活化及结肠癌HT-29细胞侵袭，在此过程中AG490在mRNA水平抑制MMP-2表达。结论STAT3信号转导通路参与结肠癌细胞侵袭调控，阻断STAT3通路活化可抑制结肠癌细胞侵袭，这一作用可能是通过抑制MMP-2表达实现的。     

GENERAL SURGERY——Breast The effect of HO-1 activated via P38α pathway in the genesis and chemotherapy resistance of breast carcinoma

Objective To investigate the role of p38a pathway and HO-1 in the genesis and chemotherapy resistance of breast cancer. Methods The proliferation and apoptosis of human breast cancer cells were examined by MTT assay. The expression of p38a and HO-1 mRNA were examined by RT-PCR. Results The p38a mRNA level in 78 % of samples was significantly greater than that in the normal tissue and the p38a mRNA level in patients with lymph node metastasis was higher than that without lymph node metastasis （P 〈 0.01 ）. The HO-1 activated with 5 μmol/L pirarubicin increased more in MCF-7/adr cells than in MCF-7 cells, and was completely blocked by p38a inhibitor in MCF-7/ADR but only partially in the MCF-7 cell line.     

转录信号传导子和激活子3信号传导通路调控选择性环氧化酶2抑制剂抗结肠癌的机制

目的探究转录信号传导子和激活子3(Stat3)信号传导通路与选择性环氧化酶2(COX-2)抑制剂抗结肠癌细胞株HT-29机制的关系,明确COX-2抑制剂抗结肠癌细胞内信号传导机制。方法将选择性COX-2抑制剂NS-398,作用于结肠癌细胞系HT-29,运用MTT法检测细胞增殖状态;流式细胞仪观察NS-398对细胞凋亡的影响,进一步用RT-PCR检测药物作用前后HT-29中COX-2mRNA的表达;ELISA法测定体系前列腺素E2(PGE2)水平;Westernblot检测药物作用前后Stat3通路相关蛋白JAK2、Stat3的磷酸化活性和cyclinD1、Bcl-2的表达。结果结肠癌细胞系HT-29中COX-2mRNA呈高表达,NS-398呈时间、剂量依赖性方式抑制HT-29细胞增殖,促进其凋亡。NS-398使HT-29细胞COX-2mRNA和PGE2表达水平显著下降。同时p-JAK2、p-Stat3、cyclinD1、Bcl-2表达水平随作用时间延长而下降。结论癌基因Stat3信号传导通路调控了NS-398抗结肠癌的细胞内信号传导机制,最终通过其下游靶基因cyclinD1、Bcl-2影响结肠癌细胞系HT-29的增殖与凋亡。     

Kindlin-2在胃癌组织中的表达及其与肿瘤侵袭转移的关系

目的探讨胃癌组织中Kindlin-2的表达及其与肿瘤侵袭转移和预后的关系。方法连续收集50例胃癌患者手术切除的胃癌及相应癌旁组织标本,应用蛋白印迹进法及定时定量聚合酶链反应检测Kindlin-2在蛋白水平及RNA水平的表达,并分析其与胃癌患者临床病理指标及预后的相关性。结果Kindlin-2在胃癌组织中的表达水平明显高于癌旁组织[（0．421±0．334）比（0．137±0．016）],差异有统计学意义（P=0．012）。胃癌组织Kindlin-2／[3-actinmRNA的表达水平明显高于癌旁组织[（1．05±0．20）比（0．77±0．14）],差异有统计学意义（P=0．034）。Kindlin-2蛋白表达水平与患者年龄、性别和肿瘤分化程度无明显关系。肿瘤侵犯深度为T3-4患者（12例）的Kindlin-2表达明显高于T1-2（38例）患者。N3、N3期患者（分别为14、13例）的Kindlin-2表达水平明显高于N,期患者（23例）,差异有统计学意义（P=0．013）。TNM综合分期为Ⅲ-Ⅳ期的患者Kindlin-2表达水平明显高于I～Ⅱ期的患者（12例）,差异有统计学意义（P=0．016）。Kindlin-2高表达胃癌患者（27例）平均生存时间明显短于低表达患者（23例）[（23-4-4）个月比（65-4-10）个月],差异有统计学意义（P=0．017）。Kindlin-2高表达胃癌患者无病生存时间亦短于低表达患者[（12±4）个月比（55±10）个月],差异有统计学意义（P=0．019）。结论Kindlin-2可能在胃癌发生发展中起重要作用,并且可能成为靶向治疗及评估胃癌患者预后的指标。     

Clinical and microbiological features of community acquired and nosocomial bloodstream infections in the surgical department of a tertiary care hospital in Beijing

Background Bloodstream infections （BSls） remain a major cause of morbidity and mortality in patients undergoing surgery. This study aimed at elucidating the clinical characteristics of community-acquired BSIs （CABs） and nosocomial BSIs （nBSIs） in patients admitted to the surgical wards of a teaching hospital in Beijing, China. Methods This cross-sectional study compared 191 episodes of BSIs in 4074 patients admitted to the surgical wards between January 2008 and December 2011. Cases of BSIs were classified as CABs or nBSIs, and the characteristics, relevant treatments, and outcomes of CABs and nBSIs were compared. Results Of the 191 BSIs, 52 （27.2%） and 139 （72.8%）were CABs and nBSIs, respectively. Escherichia coli, coagulasenegative staphylococci, and Klebsiella spp, were the most frequently isolated microorganisms. There were significant differences between CABs and nBSIs with respect to the use of hormonal drugs, ventilation, acute physiology and chronic health evaluation （APACHE） Ⅱand American Society of Anesthesiologists scores, and prevalence of cancer （P 〈0.05）. Empirical antibacterial therapy did not decrease the crude mortality, but multivariate analysis showed that high APACHE Ⅱwas independently associated with a risk of mortality （odds ratio =0.97, 95% confidence interval： 0.93-1.02 for APACHE Ⅱ）. Conclusions We found significant differences in the clinical characteristics of surgical patients with CABs and nBSIs. The outcome of patients seems to be related to hiah APACHE Ⅱ scores.     

胃肠间质瘤基础研究进展

胃肠间质瘤（gastrointestinal stromal tumors,GIST）是胃肠道最常见的间叶性肿瘤．占所有胃肠道恶性肿瘤的1％～3％．小肠恶性肿瘤的20％和全部软组织肉瘤的5％．GIST平均年发病率大约为1／10万^[1]。近年来．GIST的生物学研究取得了重大进展,本文就GIST生物学特点、生物学治疗及生物学预后因素作一综述。     

格拉斯哥预后评分可用作结肠癌预后的指标

目的 研究术前格拉斯哥预后评分(Glasgow prognostic score,GPS)对于可切除的结肠癌患者预后的判断价值.方法 作为以炎症为基础的GPS评分系统仅包括C反应蛋白(C-reactive protein,CRP)和白蛋白水平.根据术前的检验结果 计算GPS.对282例患者的临床资料进行分析;对CRP升高(＞10mg/L)和低蛋白血症(＜35g/L)两项均阳性者记作2分,1项异常的记作1分,无异常的记作0分.按GPS值的不同分为3组.采用多因素分析和生存曲线分析计算预后价值.结果 Log-rank分析显示,高GPS评分的病例死亡率高(P＜0.01).Kaplan-Meier分析提示,3组间生存时间差异明显:GPS 2组(平均40.9个月;95%CI:31.5～50.3个月),GPS 1组(平均49.6个月;95% CI:43.2～56.1个月),GPS 0组(平均62.7个月;95% CI:58.8～66.7个月).3组间无进展生存时间也存在明显差异:GPS 2组(平均26.4个月;95% CI:18.5～34.3个月),GPS 1组(平均34.7个月;95% CI:28.2～41.3个月),GPS 0组(平均53.4个月;95% CI:48.8～58.1个月).多因素分析显示,术后TNM分期(OR,0.210;95% CI,0.102～0.432;P＜0.01)术前的癌胚抗原(carcinoma embryonic antigen,CEA)(OR,0.356;95% CI,0.179～0.707;P=0.003),CA19-9(OR,0.260;95% CI,0.120～0.564;P＜0.01),CRP(OR,4.503;95% CI,1.590～12.751;P=0.005),GPS(OR,0.340;95% CI,0.181～0.920;P＜0.01)均与术后死亡相关.结论 术前的GPS评分可以作为结肠癌患者术后预测的新指标.

Abstract：

Objective To investigate the significance of preoperative Glasgow prognostic score (GPS) for postoperative prognosis in patients of resectable colon cancer. Recent studies have revealed that the GPS, an inflammation-based prognostic score that includes only C-reactive protein (CRP) and albumin, is a useful tool for predicting postoperative outcome in cancer patients. However, few studies have investigated the GPS in the field of colon surgery. Methods The GPS was calculated on the basis of admission data as follows; patients with an elevated level of both CRP ( ＞ 10 mg/L) and hypoalbuminemia (Alb ＜ 35 g/L) were allocated a score of 2, and patients showing 1 or none of these blood chemistry abnormalities were allocated a score of 1 or 0, respectively. Prognostic significance was analyzed by multivariate analyses. Overall survival and disease-free survival was estimated using the Kaplan-Meier method. Results A total of 282 patients were evaluated. Kaplan-Meier analysis and log-rank test revealed that a higher GPS predicted a higher risk of postoperative mortality and reccurence ( P ＜ 0.001 ). multivariate analyses revealed that postoperative TNM was the most sensitive predictor of postoperative mortality (OR, 0.210; 95% CI, 0.102-0.432; P＜0.01) and CEA(OR,0. 356;95% CI,0. 179 -0. 707; P = 0.003),CA19-9(OR,0. 260;95% CI,0. 120 -0. 564;P ＜ 0.01),CRP( OK,4. 503;95% CI, 1. 590 -12. 751 ;P =0.005) , GPS( OR, 0. 340 ;95% CI,0.181 -0.920;P＜0.01)were associated with postoperative mortality. Conclusions Preoperative GPS is considered to be a useful predictor of postoperative mortality in patients with colon cancer.     

NF-κB信号传导通路在大鼠急性结肠炎应激反应中的作用

目的探讨NF-κB通路在大鼠急性结肠炎应激反应中的作用.方法建立大鼠急性结肠炎应激模型,固定化蛋白印迹法（Western blot）检测脊髓内I-κB蛋白水平,逆转录-聚合酶链式反应法（RT-PCR）检测脊髓内COX-2 mRNA水平,免疫组化法检测L5-S1和C2-4脊髓内COX-2蛋白水平.结果结肠内灌注6%醋酸可产生明显局部炎症反应;急性结肠炎0.5 h后L5-S1脊髓内I-κB蛋白表达明显上调（P＜0.05）;急性结肠炎3 h后L5-S1脊髓内COX-2 mRNA表达开始增加,24 h后达到高峰;免疫组化结果显示结肠炎24 h后胞浆内COX-2蛋白表达增加.结论大鼠急性结肠炎时,NF-κB通路可能通过调控COX-2的表达而介导炎症反应,I-κB有可能成为急性结肠炎治疗的靶点.     

Stat3显性负性基因调控人结肠癌细胞增殖与凋亡的分子机制

目的 探讨转染Stat3（转录信号传导子和激活子3）显性负性基因Stat3β质粒阻断人结肠癌细胞系SW480细胞的Stat3信号传导通路对人结肠癌细胞增殖和凋亡的影响及可能的机制.方法 应用阳离子脂质体向人结肠癌细胞系SW480细胞中转染携带Stat3β基因的质粒,四唑盐法检测细胞增殖能力,流式细胞术检测细胞周期和细胞凋亡,反转录聚合酶链反应检测Stat3靶基因cyclinD1、bcl-xL mRNA表达情况.数据统计分析采用独立样本t检验.结果 转染Stat3β质粒36 h后,SW480细胞的增殖受到显著抑制（t=5.216,P=0.006）;G0/G1期的细胞比例由40.37%上升至67.25%,S期细胞由44.68%下降至31.23%;发生早期凋亡的细胞比例由5.34%上升至24.42%;同时cyclin D1、bcl-xLmRNA表达水平较对照组显著下降（t=5.228,P=0.010;t=3.517,P=0.025）.结论 转染携带Stat3β基因的质粒可以通过下调Stat3靶基因的表达抑制人结肠癌细胞的增殖,促进凋亡,为以Stat3为靶点的结肠癌基因治疗提供了实验基础.