EGFR抑制剂耐药机制研究的新进展

表皮生长因子受体(EGFR)通路在肿瘤发生、发展过程中起到非常重要的作用,它已成为肿瘤分子治疗领域最主要的研究和开发靶点之一。目前有单克隆抗体与小分子受体酪氨酸激酶抑制剂两类EGFR抑制剂在临床治疗中取得成功。然而,该类药物在临床前研究及临床治疗中已经出现耐药现象。由于EGFR调节多种细胞功能,该耐药现象可能与多个传导通路紊乱有关,包括配体自分泌/旁分泌的产生、受体突变、下游信号蛋白的组成性活化以及旁路信号途径的激活。本文就EGFR抑制剂耐药机制的最新研究进展进行综述。     

脑源性神经营养因子样化合物筛选系统的建立及应用

目的建立简便有效的筛选系统,筛选脑源性神经营养因子(BDNF)样小分子化合物,用于探讨中枢神经系统神经损伤保护。方法依次利用多巴胺能SH-SY5y细胞、稳定转染BDNF受体基因trkB的NIH3T3/trkB细胞和正常生长的NIH3T3细胞组成BDNF样化合物筛选系统,以BDNF为阳性对照,通过试验样品对去血清致细胞凋亡的抵抗作用,确定其是否具有BDNF样活性。结果利用所建筛选系统筛选化合物400个,获得能够促进SH-SY5y细胞存活的化合物11个,同时能够相对特异抵抗去血清致NIH3T3/trkB细胞凋亡的BDNF样小分子2个。进一步实验表明该2个化合物对6-OHDA致SH-SY5y细胞损伤具有一定的保护作用。结论该工作为大规模筛选和深入研究BDNF样化合物的神经保护功能提供了模型和先导化合物基础。     

参芪扶正注射液联合NP方案治疗晚期非小细胞肺癌的疗效观察

目的观察参芪扶正注射液联合NP方案在晚期非小细胞肺癌(NSCLC)中的疗效。方法所有病例均经病理和(或)细胞学确诊为晚期NSCLC。其中:治疗组42例行长春瑞滨(NVB)加顺铂(DDP)方案化疗,同时加用参芪扶正注射液;对照组26例单用NP化疗。参芪扶正注射液250ml, d1-10;NVB25mg/m2,d1,d8;DDP:30mg/m2d2-4,均静脉滴注。结果治疗组和对照组的总RR分别为28．6％和19．2％(P=0．003),总临床受益率(CBR)分别为71．4％和61．5％(P=0．0032),中位进展时间分别为6．2个月和4．9个月(P=0．06),治疗组与对照组化疗后的生活质量(QOL)评分比较有明显提高(P=0．008),毒副反应亦较轻(P=0．006)。结论参芪扶正注射液能明显改善晚期NSCLC的RR、CBR、QOL,并且能增效减毒,具有良好的应用价值。     

肾内小动脉重构的研究现状

血管重构（VR）是引起高血压、糖尿病等血管疾病和循环功能紊乱的病理基础,其能促进靶器官损害和功能衰竭,提升疾病危险分层,故逆转VR已成为临床治疗靶向之一。肾脏是包括高血压、糖尿病等多种疾病的重要靶器官,肾内小动脉决定了肾脏血流灌注的绝大部分阻力,其重构直接影响肾脏血流供应,引发神经内分泌过度激活及其恶性循环,促进肾脏及其他靶器官损害及功能衰竭,影响预后。本文对VR尤其肾内小动脉VR研究现状及其重要意义作一综述。     

Evaluation of Dry Eye after Minimal in Situ Conjunctival Incision for Segmental Scleral Buckling Surgery

Objective: To compare dry eye signs and symptoms after minimal in situ conjunctival incision for segmental scleral buckling surgery. Methods: In this prospective clinical study, consecutive patients, enrolled in the Department of Ophthalmology, the First Affiliated Hospital of Xi'an Jiaotong University, from May 2015 to April 2017, who had minimal in situ conjunctival incision or standard segmental scleral buckling surgery were assessed. Dry eye markers including the ocular surface disease index (OSDI) and subjective symptom questionnaire, tear-film assessment using Keratograph 5M corneal topography, Schirmer Ⅰ testing, and fluorescein staining were sequentially evaluated preoperatively and at 1 day, 1 week, and 1 month postoperatively. A Chi-square test, Student's t-test or Mann-Whitney U test was used to compare differences between the two groups. Results: Seventy-eight patients (78 eyes) with similar baseline characteristics were recruited. Most patients developed dry eye postoperatively. Subjective symptoms and fluorescein staining scores elevated from baseline, tear break-up time and Schirmer Ⅰ testing values decreased postoperatively, which peaked at 1 day and did not return to baseline within 1 month. There were no significant differences between the 2 groups (all P>0.05) at 1 day and 1 week except for the higher tear meniscus height (Z=1.04, P=0.041), noninvasive first tear break-up time and average break-up time (t=2.51, P<0.001), and Schirmer Ⅰ test values (Z=2.34, P=0.043), in the minimal in situ conjunctival incision group at 1 month postoperatively. OSDI scores and subjective symptoms were lower in the minimal in situ conjunctival incision group at 1 week and 1 month postoperatively (OSDI: t1 week=2.54, P=0.012; Z1 month=-1.03, P=0.020; subjective symptoms: t1 week=3.04, P=0.011; t1 month=3.94, P<0.001). Sub group analysis using flouesecein staining showed obvious worsening 1 day, 1 week and 1 month postoperatively in patients with preoperative dry eye (Z=-2.42, P<0.001; Z=-1.54, P=0.034; Z=-1.83, P=0.041). Conclusions: Segmental scleral buckling surgery can induce or aggravate dry eyes. Compared with standard procedures, minimal in situ conjunctival incision segmental scleral buckling surgery can improve and shorten the ocular surface discomfort in the early postoperative period, especially in patients with dry eyes before surgery.     

Novel Aminomethylindole Derivatives as Inhibitors of pp60c‐Src Tyrosine Kinase: Synthesis and Biological Activity

The pp60^c‐Src is one of the ubiquitously expressed Src family kinases and has important functions in malignant cells, including regulation of cell division, growth factor signaling, and movement. Therefore, investigating new small molecule inhibitors of pp60^c‐Src is important to discover and develop novel therapeutics for cancer and metastasis. Moreover, some of the small molecule inhibitors that do not qualify for therapeutic use may become very useful tool to explore the role of Src kinase in normal cells as well as in a variety of disease models. Our continuous efforts to find novel inhibitors of pp60^c‐Src aimed for therapeutic and research use, we synthesized newly designed aminomethylindole derivatives as novel small molecule inhibitors and investigated their inhibitory effect on pp60^c‐Src tyrosine kinase. Here, we report one potential inhibitor of the pp60^c‐Src from five active molecules of all nine compounds, which were synthesized and screened for the biological activity of the molecules against pp60^c‐Src target.     

葡萄膜炎并发性白内障瞳孔粘连的手术治疗

目的:探讨葡萄膜炎并发白内障虹膜后粘连小瞳孔状态下手术技巧、时机及疗效。方法:对45例56眼葡萄膜炎并发性白内障小瞳孔患者,在葡萄膜炎控制稳定,炎症消退3个月后,借助粘弹剂分离虹膜后粘连或施行瞳孔环型扩张,再行白内障超声乳化或囊外摘出及人工晶体植入。结果:术后48眼(85%)视力较术前提高,其中≥0.5者19眼,0.3～0.5者13眼,0.1～0.3者16眼。瞳孔圆形或椭圆形。术后眼压均控制在正常范围。结论:葡萄膜炎并发性白内障虹膜后粘连,可使瞳孔扩大成圆形或椭圆型,有利于实施白内障超声乳化或囊外摘除,且瞳孔括约肌不受损伤,避免术后眩光,可获得良好视力,术中、术后并发症减少。     

4种化疗方案治疗Ⅲb～Ⅳ期非小细胞肺癌的最小成本分析

目的:评价术后复发转移和局部晚期的非小细胞肺癌4种化疗方案的成本-效果。方法:74例术后复发转移和局部晚期的非小细胞肺癌化疗患者分为PC、GP、NP、TC组,治疗2个周期评价疗效和进行成本-效果分析。结果:4组成本分别为15679.72、10688.00、7665.98、13627.38元,有效率分别为40.00%、40.91%、38.46%、42.11%(P>0.05)。不良反应为不同程度的骨髓抑制、血小板变化、恶心呕吐、脱发等,经对症治疗均痊愈。结论:NP组成本较低,但此方案的不良反应较重;如患者经济条件好,重视生活质量,可选用GP方案。     

原发性小肠恶性肿瘤误诊原因分析

目的探讨原发性小肠恶性肿瘤的临床特点及误诊原因。方法回顾性分析1998年以来我院外科诊治的26例原发性小肠恶性肿瘤患者的临床特点及诊断、治疗。结果肿瘤位于十二指肠3例（11．5％），空肠9例（34．6％），回肠14例（53．9％）；病类型腺癌3例，印戎细胞癌2例，平滑肌肉瘤18例，恶性淋巴瘤3例。常见症状为：腹痛、腹部肿块、不明原因肠梗阻和消化道出血。术前误诊或不能明确诊断18例（69．2％）。26例均手术治疗，术后死亡3例。结论原发性小肠恶性肿瘤少见，缺乏特异性症状和体征，误诊率高，对诊断不明确的患者应综合各项检查，必要时尽早行剖腹探查术。治疗应以手术切除为主。     

可溶性上皮型钙黏附蛋白在大肠癌患者血清中检测的临床意义

目的检测大肠癌患者血清可溶性上皮型钙黏附蛋白（sE—cad）与癌胚抗原（CEA）含量的变化及临床意义。方法采用酶联免疫吸附法分别检测125例大肠癌患者（大肠癌组）、33例炎症性肠病患者（炎症性肠病组）及30例健康志愿者（正常组）血清sE—cad与CEA的含量，并分别检测大肠癌患者术后各亚组血清sE—cad与CEA的含量；同时观察sE—cad含量与大肠癌病理特征的关系。结果与正常组比较，大肠癌组、术后1周亚组及肿瘤复发亚组血清sE—cad与CEA含量显著升高（P〈0．01），术后1周亚组、术后1个月亚组、术后6个月亚组、术后1年亚组血清sE—cad与CEA含量较大肠癌组显著降低（P〈0．01），而肿瘤复发亚组与大肠癌组比较差异无统计学意义（P〉0．05），炎症性肠病组与正常组比较差异无统计学意义（P〉0．05）。大肠癌组血清sE—cad含量与分化程度、临床Duke分期均呈显著正相关。结论血清sE—cad含量变化与大肠癌的发生、发展密切相关，可作为一种新的大肠癌标志物，对判断预后与复发有一定价值。