Synthesis and biological activities of 2-amino-thiazole-5-carboxylic acid phenylamide derivatives

In an attempt to develop potent and selective anti‐tumor drugs, a series of novel 2‐amino‐thiazole‐5‐carboxylic acid phenylamide derivatives were designed based on the structure of dasatinib. All compounds were synthesized by a systematic combinatorial chemical approach. Biological evaluation revealed that N‐(2‐chloro‐6‐methylphenyl)‐2‐(2‐(4‐methylpiperazin‐1‐yl)acetamido)thiazole‐5‐carboxamide ( 6d ) exhibited high antiproliferative potency on human K563 leukemia cells comparable to dasatinib. Against mammary and colon carcinoma cells 6d was either inactive (MDA‐MB 231) or distinctly less active (MCF‐7 and HT‐29: IC₅₀ = 20.2 and 21.6 µM, respectively). Dasatinib showed at each cell line IC₅₀ < 1 µM. The results of this structure activity relationship study clearly documented that the pyrimidin‐4‐ylamino core of dasatinib is responsible for the anti‐tumor activity against non‐leukemia cell lines.     

腹腔镜手术治疗妊娠期急腹症28例

目的探讨妊娠期急腹症的腹腔镜手术适用证和手术技巧。方法对应用腹腔镜手术治疗的28例妊娠期急腹症患者的诊疗过程及随访结果进行回顾性分析。结果28例中9例妊娠9～12周,19例妊娠13～20周。均行腹腔镜探查并手术治疗：卵巢囊肿蒂扭转13例,其中5例行囊肿剥除,8例行附件切除;子宫肌瘤蒂扭转2例;急性阑尾炎11例;急性胆囊炎2例。所有病例均获得随访,随访时间为18～30周;先兆流产2例,早产2例。结论妊娠期急腹症采用腹腔镜手术治疗安全可靠,基本不影响妊娠过程和妊娠结局。     

嗜铬细胞瘤的术前准备

目的 提高嗜铬细胞瘤围术期治疗水平,降低病死率.方法 2003年11月-2008年11月收治92例嗜铬细胞瘤患者,应用嗜铬细胞瘤围术期管理方案,即在术前应用选择性al受体阻滞剂甲磺酸多沙唑嗪控释片(商品名可多华),最大剂量为12 mg/d,最小剂量为4 mg/d,同时在术中补充血容量.使术前准备时间明显缩短,中位时间为11 d,且术中血压稳定.结果 所有患者的血压稳定,收缩压≤140 mmHg(1 mmHg=0.133 kPa)及舒张压≤90 mmHg,无阵发性血压升高、心悸和多汗等现象,心率为80～90次/min,外周循环改善,肿瘤直径为2.5～13.0 cm,中位直径为4.5 cm,肿瘤大小与功能和用药时间长短无明显关系.85%的患者在麻醉诱导和术中挤压肿瘤时血压仍发生波动,但易控制,术后血压平稳.结论 嗜铬细胞瘤术前充分的准备是保证麻醉、术中及术后血压平稳控制、减少心血管并发症及降低病死率的关键.     

肾上腺功能隐匿性嗜铬细胞瘤的诊治体会(附12例报告)

目的 探讨如何提高肾上腺功能隐匿性嗜铬细胞瘤的诊断意识和手术安全性.方法 肾上腺功能隐匿性嗜铬细胞瘤患者12例,术前均行内分泌检查、常规B超及CT检查.除两例肿瘤直径≤5 cm的患者术前未服用a受体阻滞剂(甲磺酸多沙唑嗪控释片)外,其他均以4 mg/d的剂量口服1～3周.严格按嗜铬细胞瘤进行麻醉准备,术中尽量减少肿瘤挤压,尽早控制中央静脉,主要操作及时告知麻醉师,术后严密监测,及时纠正低血压.结果 12例肿瘤均完整切除,病理检查证实为嗜铬细胞瘤.术中均发生血压波动,最高升至170/100 mmHg(1 mmHg=0.133 kPa),发生在触及或挤压肿瘤时.术后仅1例术前未服用a受体阻滞剂的患者出现低血压,予去甲肾上腺素静脉微量泵推注,术后24 h内血压纠正撤退.结论 提高功能隐匿性嗜铬细胞瘤的诊断意识以及严格的围术期准备是保障其手术安全性的关键.     

大鼠面神经切断和切断修复后面神经核内鞘脂激活蛋白原的变化

BACKGROUND： Studies have demonstrated that damaged facial nerves synthesize prosaposin to promote repair of facial neurons. OBJECTIVE： To observe time-course changes of prosaposin expression in the facial nerve nucleus of Sprague Dawley rats following facial nerve transection and repair. DESIGN, TIME AND SETTING： A randomized control neuropathological animal experiment was performed in Chongqing Medical University between March 2007 and September 2008. MATERIALS： A total of 48 adult, male, Sprague Dawley rats were selected and randomly divided into transection and transection ＋ end-to-end anastomosis groups （n =24）. Rabbit anti-rat prosaposin antibody, instant SABC immunohistochemical kit, and antibody dilution solution were purchased from Wuhan Uscn Science Co., Ltd., China. METHODS： In the transection group, the nerve trunk of the distal retroauricular branch of the left facial nerves was ligated in Sprague Dawley rats, and a 5-mm nerve trunk at the distal end of the ligation site was removed. In the transection ＋ end-to-end anastomosis group, epineurial anastomosis was performed immediately following transection of the left facial nerves. The right facial nerves in the two groups served as the normal control group. MAIN OUTCOME MEASURES： The number of prosaposin-positive neurons, as welt as intensity of immunostaining in facial nerve nucleus, following transection and end-to-end anastomosis were determined by immunohistochemistry at 1, 3, 7, 14, 21, and 35 days after injury. RESULTS： Transection group： transection of facial nerves resulted in increased number of prosaposin-positive neurons and immunoreactivity intensity in the facial nucleus on day 1. These values significantly increased by day 3. Expression was greater than in the control side. The peak of the reduction was reached at 7 days post-surgery. Transection ＋ end-to-end anastomosis group： the number of prosaposin-positive neurons and immunoreactivity intensity was reduced in the facial nerve nucleus following immediate end-to-end anastomosis on day 7 post-surgery. These values began to gradually increase by day 14 post-anastomosis. By day 35 post-anastomosis, the number of prosaposin-positive neurons in the operated side recovered to normal levels. The number of prosaposin-positive neurons, as well as immunoreactivity intensity, was significantly greater in the facial nerve nucleus, compared with the transection group on days 14, 21, and 35 post-surgery （P 〈 0.05）. The rhythmic whisking of vibrissa recovered, and recovery time was consistent with increased numbers of prosaposin-positive neurons. CONCLUSION： Within 7 days after injury, prosaposin expression in the facial nerve nucleus exhibited an initial increase, followed by a decrease, and was not affected by facial nerve repair. Following facial nerve damage, neural anastomosis was shown to increase prosaposin expression in the facial nerve nucleus after 14 days. Recovery of prosaposin occurred simultaneously with reinnervation.     

肺部结节性病灶X线数字成像的实验与临床研究

目的：探讨X线数字成像及后处理对肺部结节性病灶的诊断价值。材料和方法：使用SiemensPolystar·FluorospotHX线数字成像和处理系统分别对12个用Philips肺部Phantom叠加肥皂制作之不同大小及形态之结节模型以及30例不同病理之肺部结节性病灶，进行摄片及图像后处理，分别作0％～100％边缘增强。结果：经对12个不同肺部结节模型及30例肺部结节性病灶的原始图像与后处理图像比较研究后发现，所有图像都明显地提高了质量，并以15％～60％的边缘增强为好；所有结节模型及结节性病灶之内部及表面结构比原始图像显示更好。结论：胸部平片是诊断肺部结节性病灶的首选方法，用数字成像及边缘增强等后处理后能显示直径更小的病灶（≥0．2cm），能更好地显示病灶的内部及表面结构，对病灶的检出及良恶性病变的鉴别诊断有很大帮助。     

法轮功之类伪科学所致精神障碍

目的：分析法轮功之类伪科学所致精神障碍。方法；选择因“练功”等而发生精神障碍患者共２０６例进行临床分析。结果；发现患者在“练功”后表现精神病性发作，精神症状内容与“练功”密切相关。结论：法轮功之类缺乏中医学理论基础，实为伪科学，训练方法与炒信巫术的性质相似，可使易感人群有精神病性发作。     

Video-assisted thoracoscopic surgery segmentectomy by non-intubated or intubated anesthesia: a comparative analysis of short-term outcome

Background

The aim of this study was to reveal the short-term outcomes of video-assisted thoracoscopic surgery (VATS) segmentectomy without tracheal intubation compared with intubated general anesthesia with one-lung ventilation (OLV).

Methods

We performed a retrospective review of our institutional database of consecutive 140 patients undergoing VATS anatomical segmentectomy from July 2011 to June 2015. Among them, 48 patients were treated without tracheal intubation using a combination of thoracic epidural anesthesia (TEA), intrathoracic vagal blockade, and sedation (non-intubated group). The other 92 patients were treated with intubated general anesthesia (intubated group). Safety and feasibility was evaluated by comparing the perioperative profiles and short-term outcomes of these two groups.

Results

Two groups had comparable surgical durations, intraoperative blood loss, postoperative chest tube drainage volume, and numbers of dissected lymph nodes (P>0.05). Patients who underwent non-intubated segmentectomy had higher peak end-tidal carbon dioxide (EtCO₂) during operation (44.81 vs. 33.15 mmHg, P<0.001), less white blood cell changes before and after surgery (△WBC) (6.08×10⁹ vs. 7.75×10⁹, P=0.004), earlier resumption of oral intake (6.76 vs. 17.58 hours, P<0.001), shorter duration of postoperative chest tube drainage (2.25 vs. 3.16 days, P=0.047), less cost of anesthesia (¥5,757.19 vs. ¥7,401.85, P<0.001), and a trend toward shorter postoperative hospital stay (6.04 vs. 7.83 days, P=0.057). One patient (2.1%) in the non-intubated group required conversion to intubated OLV since a significant mediastinal movement. In the intubated group, there was one patient (1.1%) required conversion to thoracotomy due to uncontrolled bleeding. The incidence difference of postoperative complications between groups was not significant (P=0.248). There was no in-hospital death in either group.

Conclusions

Compared with intubated general anesthesia, non-intubated thoracoscopic segmentectomy is a safe, technically feasible and economical alternative with comparable short-term outcomes. Patients underwent non-intubated thoracoscopic segmentectomy could gain a prompt recovery.     

人前列腺LRIG1蛋白三维结构同源模建及其小分子激动剂的虚拟筛选

目的 LRIG1(tandem leucine-rich repeat sand immunoglobulin-like domains 1,LRIG1)是新近发现的抑癌基因,在前列腺癌中表达下降,通过对人前列腺LRIG1蛋白的三维结构进行同源模建,虚拟筛选出LRIG1的功能蛋白,试图为前列腺癌新靶点治疗提供新思路.方法 以LRIG1的同源蛋白LRRC4 C蛋白的晶体结构(PDB号3 ZYJ)为模型,通过MODELLER软件搭建LRIG1蛋白的三维空间结构;采用柔性对接的虚拟筛选技术,以荷兰SPECS公司的202490个化合物进行对接和打分,挑选出排名靠前的10个小分子化合物;通过AMBER软件分别进行20 ns的分子动力学模拟,并分析这10个小分子的结合模式、 动力学轨迹的RMSD、RMSF、 结合口袋的氢键以及它们的结合能量.结果 10个小分子化合物都具有一致的结合模式,而且都具有激活LRIG1活性的潜在能力.结论 发现与人LRIG1具有潜在特异结合能力的激动剂,可以为前列腺癌治疗新靶点的确立及开发具有药理活性的先导化合物提供理论依据.     

Comparative tests on methods for automatic mapping of land cover dynamics from multi-year images

Most land use/land cover (LULC) mapping methods require us to collect ground reference data at the time when the remotely sensed data are acquired. However, the high cost of the data collection limits the production of annual LULC maps in a short time span. In this study, in order to reduce the mapping cost and improve the timeliness of the map products, several simple and effective methods were tested and compared with same-year mapping (SY), including cross-year mapping (CY), multiple-indices automatic classification (MI), and spectral transfer (ST) and index transfer (IT). For the study years of 2001–2016, SY yields accuracies higher than 93%, the mean CY accuracy is about 83%, and the MI accuracy reaches 88%. Both the overall accuracies (above 90%) and the detailed accuracy indicators of the ST and IT are higher than those of CY and MI, and very close to the SY accuracy. It can, therefore, be stated that the methods are able to map urban LULC variations automatically, withsatisfactory performance.