新诊断2型糖尿病患者血清spexin水平与内脏脂肪面积及代谢指标的相关性分析

目的研究新诊断2型糖尿病（T2DM）患者血清spexin水平与腹部内脏脂肪面积（visceral fat area, VFA）的关系,探寻其与各代谢指标的相关性。方法新诊断T2DM患者分为T2DM内脏型肥胖组（T2DM-ob组）和T2DM非内脏型肥胖组（T2DM-nonob组）,正常血糖且非内脏型肥胖者为正常对照组（NC组）,测量BMI、腰围、臀围、腰臀比（WHR）、收缩压（SBP）和舒张压（DBP）,欧姆龙DUALSCANHDS-2000测量VFA与皮下脂肪面积（subcutaneous fat area, SFA）及内脏脂肪与皮下脂肪比率（visceral fat to subcutaneous fat ratio, VSR）。行口服葡萄糖耐量试验,测定空腹血糖（FPG）、餐后2h血糖（PPG2h）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）及餐后2h胰岛素（PINS2h）,计算HOMA-IR,用ELISA测定血清spexin水平。结果T2DM-ob组BMI、腰围、臀围、总胆固醇（TC）、HOMA-IR、VFA、SFA、VSR均较T2DM-nonob组升高,血清spexin水平较T2DM-nonob组和NC组均明显降低（P<0.05）,VFA与BMI、腰围、WHR、FPG、PPG2h、HbA1c、丙氨酸转氨酶（ALT）、HOMA-IR显著正相关,与高密度脂蛋白胆固醇（HDL-C）呈显著负相关（P<0.05）。spexin水平与VFA、VSR、BMI、WHR、FPG、PPG2h、HbA1c、HOMA-IR呈显著负相关,与HDL-C呈显著正相关,多元回归分析发现HbAlc、VSR为spexin的独立影响因素（P<0.05）。结论新诊断T2DM患者血清spexin水平与VFA密切相关,spexin及VFA与血糖、血脂及胰岛素抵抗显著相关,spexin可能在T2DM患者的内脏脂肪代谢中有重要作用。     

烧伤创面铜绿假单胞菌的分离和耐药谱分析

目的　探讨烧伤创面铜绿假单胞菌耐药谱的变迁及诱导型 β 内酰胺酶的产生。 方法对笔者医院 1996年 6月～ 2 0 0 0年 6月鉴定的 4 5 2株烧伤创面铜绿假单胞菌 ,用VITEK AMS全自动细菌鉴定及药敏系统、E test浓度梯度法做药敏试验 ,以K B法为基础作诱导酶的检测。　结果　 4年中临床常用的头孢菌素及亚胺培南的耐药率均有提高 ;其中以头孢哌酮 /舒巴坦的耐药率最低 ,但 4年中耐药率的变化差异也有显著性意义 (P <0 .0 5 ) ,亚胺培南的耐药率在 2 0 %～ 4 0 %之间。 12 0株野生型铜绿假单胞菌中 ,以亚胺培南为诱导剂 ,检出产生诱导酶者为 72 .5 %。　结论　烧伤创面铜绿假单胞菌耐药谱的分析和诱导酶的检测 ,可以及时监控和调整抗生素的使用 ,对避免铜绿假单胞菌在医院内流行具有重要意义     

伊马替尼治疗慢性移植物抗宿主病2例临床分析

目的探讨伊马替尼治疗异基因造血干细胞移植(allo-HSCT)后慢性移植物抗宿主病(GVHD)伴嗜酸性粒细胞增多的疗效及嗜酸性粒细胞增多与慢性GVHD的关系。方法回顾性分析2例白血病患者allo-HSCT术后慢性GVHD的诊治经过并结合文献复习讨论。结果 2例患者分别于移植后5个月和76d出现口腔溃疡、皮肤瘙痒、皮疹、胆红素水平增高和转氨酶水平增高,伴有嗜酸性粒细胞增多,诊断为局限型慢性GVHD,激素治疗不佳,加用伊马替尼后症状缓解,嗜酸性粒细胞数降至正常,无不良反应。结论伊马替尼治疗慢性移植物抗宿主病安全、有效,嗜酸性粒细胞增多可能与GVHD有一定的关系。     

胃肠道间质瘤中伊马替尼耐药的信号转导机制

目的 评价胃肠道间质瘤（GIST）中不同信号通路的特征,并初步探讨与伊马替尼耐药可能相关的信号通路.方法 选取2003年11月至2008年8月间复旦大学附属肿瘤医院收治的5例GIST患者8份手术新鲜标本,检测其KIT和PDGFRa基因突变情况,并采用Western blot法检测Ras/Raf/MAPK和PI3/AKT两种信号通路中的相关蛋白（KIT、P-KIT、MAPK、P-MAPK、p-AKT、p-MTOR、PCNA、BCL2）的表达.结果 伊马替尼治疗有效的3例患者均存在1次突变,其中2例为KIT基因第11外显子缺失突变,另1例为KIT基因第13外显子点突变;1例伊马替尼原发耐药患者无KIT基因突变,1例继发耐药患者存在KIT基因2次突变;所有标本均未见PDGFRa基因突变.伊马替尼耐药的肿瘤标本磷酸化（p）-KIT和p-AKT表达水平强于伊马替尼敏感的肿瘤标本;KIT、MAPK、p-MAPK及p-MTOR在GIST标本中均有较强的表达,其表达强度在伊马替尼耐药标本与敏感标本间并无明显区别;而PCNA和BCL2则在不同治疗时间及不同部位的标本中表达有所差异.结论 Ras/Raf/MAPK和PI3-K/AKT/MTOR两条信号通路在GIST形成过程中起着非常重要的作用：KIT基因2次突变及PI3-K/AKT/MTOR信号通路可能与伊马替尼继发耐药的形成密切相关.     

The effect of neoadjuvant Imatinib therapy on outcome and survival after rectal gastrointestinal stromal tumour

Aim The study aimed to characterize the pathological and clinical response of rectal gastrointestinal stromal tumours (GISTs) to neoadjuvant Imatinib. Method The medical records of patients with rectal GISTs who were diagnosed and treated in five medical centres in Israel between January 2002 and January 2009 were retrospectively examined. Twelve patients who fulfilled the inclusion criteria of nonmetastatic rectal GIST for which preoperative neoadjuvant treatment with Imatinib was considered were suitable for enrollment. Results Of the 12 patients, nine received neoadjuvant treatment with Imatinib. The three patients who had immediate surgery were excluded. There were five men and four women with a median age of 63 years and a median follow up of 32 months. All tumours were located in the lower two‐thirds of the rectum. One patient had a complete clinical response, six had a partial response and two had stable disease. Seven patients subsequently underwent surgery; six had an R0 resection and one had an R1 resection. Three patients had recurrence. There was no disease‐related mortality. The reduction in both tumour size and mitotic activity during preoperative Imatinib therapy was significant. Conclusion Preoperative Imatinib therapy can shrink large rectal GISTs, improving the chances of successful radical surgery and decreasing the risk of considerable morbidity.     

Colonisation with methicillin‐resistant Staphylococcus aureus prior to renal transplantation is associated with long‐term renal allograft failure

Renal transplant recipients are at an increased risk of developing Methicillin‐resistant Staphylococcus aureus due to their immunosuppressed status. Herein, we investigate the incidence of MRSA infection in patients undergoing renal transplantation and determine the effect of MRSA colonisation on renal allograft function and overall mortality. Between January 1st 2007 and December 31st 2012, 1499 consecutive kidney transplants performed in our transplant unit and a retrospective 1:2 matched case‐control study was performed on this patient cohort. The 1‐, 3‐ and 5‐year overall graft survival rates were 100%, 86% and 78%, respectively, in MRSA positive recipients compared with 100%, 100% and 93%, respectively, in the control group (P < 0.05). The 1‐, 3‐ and 5‐year overall patient survival rates were 100%, 97% and 79%, respectively, in MRSA positive recipients compared with 100%, 100% and 95%, respectively, in the control group (P = 0.1). In a multiple logistic regression analysis, colonisation with MRSA pre‐operatively was an independent predictor for renal allograft failure at 5 years (hazard ratio: 4.6, 95% confidence interval: 1–30.7, P = 0.048). These findings demonstrate that the incidence of long‐term renal allograft failure is significantly greater in this patient cohort compared with a matched control population.     

胃肠道间质瘤伊马替尼术前治疗进展

目的 探讨伊马替尼术前治疗胃肠道间质瘤（gastrointestinal stromal tumor,GIST）的作用。 方法 采用文献复习的方法,对研究伊马替尼术前治疗GIST的文献加以综述。 结果 伊马替尼术前治疗是进展期GIST的有效治疗手段,能显著提高患者的手术切除率,延长总体生存时间。 结论 术前伊马替尼治疗转移性或局部进展期GIST疗效较好,应参考GIST基因分型结果个体化术前给药,值得进一步深入临床研究。     

Current status of countermeasures for infectious diseases and resistant microbes in the field of urology

A worldwide increase in antimicrobial‐resistant microbes due to the improper use of antimicrobial agents, along with a lack of progress in developing new antimicrobials, is becoming a societal problem. Although carbapenem‐resistant Enterobacteriaceae, which are resistant to carbapenem antimicrobials, first appeared in 1993, treatment options remain limited. Mechanisms behind antimicrobial resistance involve changes to microbial outer membranes, drug efflux pump abnormalities, β‐lactamase production and the creation of biofilms around cell bodies. Genetic information related to these forms of antimicrobial resistance exists on chromosomes and plasmids, and when located on the latter can easily be transmitted to other strains, no matter the species, which creates a risk of antimicrobial resistance spreading exceptionally rapidly. To prevent the spread of antimicrobial resistance, the World Health Organization in 2015 published an action plan on antimicrobial resistance, based on which World Health Organization member countries have laid out specific policies and targets. Urinary tract infections are a type of healthcare‐associated infection, and the sexually transmitted disease pathogen, Neisseria gonorrhoeae, has been included in a list of microbes that pose a risk to human health published by the US Centers for Disease Control and Prevention. Urologists face numerous problems when attempting to use antimicrobials properly, which is one method of dealing with antimicrobial resistance. Therefore, this article describes the current state of resistant microbes associated with urinary tract infections and countermeasures for antimicrobial resistance, including new antimicrobials.     

伊马替尼抑制脂多糖诱导的巨噬细胞炎症表型

【目的】探讨伊马替尼（Ima）在体外对脂多糖（LPS）诱导的RAW264.7巨噬细胞炎症表型的影响。【方法】RAW264.7细胞在LPS（0.1μg/mL）或/和Ima（1μmol/L,5μmol/L）处理后,通过Q-PCR方法检测细胞因子IL-1β、IL-10、CCL2、iNOS、TNF-α和Arg1的mRNA表达变化;采用Western Blot检测iNOS蛋白表达变化以及NF-κB和MAPK信号通路活化情况;利用ELISA法检测细胞上清IL-1β、CCL2、IL-10和TNFα的蛋白表达情况。【结果】与对照组相比较,LPS刺激8h后,RAW264.7细胞内的炎症指标IL-1β、CCL2、iNOS和TNF-α的mRNA水平显著升高（P<0.001）以及抗炎指标IL-10的mRNA水平也明显升高（P<0.001）;LPS刺激24h后,细胞上清中IL-1β、IL-10、CCL2和TNF-α的蛋白水平显著上升（P<0.001）,细胞内iNOS蛋白表达以及p65,p38,ERK和AKT的磷酸化水平显著增加。和LPS组相比,Ima提前处理后,IL-1β、CCL2、iNOS和TNF-α的mRNA及蛋白水平显著下降（P<0.01,P<0.001）而IL-10的mRNA及蛋白水平显著升高（P<0.001）,这种抑制作用具有剂量依赖性。Ima的预处理抑制了LPS诱导的p65,p38,ERK和AKT磷酸化。单独用Ima处理RAW264.7细胞后,细胞的功能状态未见明显的改变。【结论】伊马替尼可抑制LPS诱导的巨噬细胞炎症表型,这种作用与抑制NF-κB和MAPK信号通路的过度激活有关。