Recent Advances in Structure-Based Virtual Screening of G-Protein Coupled Receptors

In addition to the rhodopsin crystal structure, high-resolution crystal structures of ligand-mediated G-protein-coupled receptors (GPCRs) have recently become available, and these have become attractive templates for developing homology models of several GPCRs of therapeutic interest. These crystal structures and the homology models derived from them have provided significant insights into ligand–receptor interactions. Moreover, several studies have demonstrated that the structural models are indeed suitable for virtual screening of compound databases to identify new ligands for various GPCRs. Recent examples of such virtual screening against GPCRs are discussed in this review.     

Characterization of bortezomib-adapted I-45 mesothelioma cells

Background  

Bortezomib, a proteasome-specific inhibitor, has emerged as a promising cancer therapeutic agent. However, development of resistance to bortezomib may pose a challenge to effective anticancer therapy. Therefore, characterization of cellular mechanisms involved in bortezomib resistance and development of effective strategies to overcome this resistance represent important steps in the advancement of bortezomib-mediated cancer therapy.     

试析陆懋修从阳明论治温病之特色

陆懋修（1818-1886），又名免研，字九芝，号江左下工，又号林屋山人，江苏元和（今江苏吴县）人，为清代后期著名的医学家。陆氏出身于官宦之家，儒医兼通，陆氏秉承家学，对先人的医学成就颇为敬重。他曾三十余年坚持潜心研究《内经》、《伤寒》等医学经典著作，终于贯通医理而成为一代名医。陆氏一生博览群书之余，著述不断，     

Feasibility of treating hyperfibrinogenemia with intermittently administered batroxobin in patients with ischemic stroke/transient ischemic attack for secondary prevention.

This study evaluated the safety and efficacy of batroxobin in treating hyperfibrinogenemia for secondary stroke prevention. Patients with ischemic stroke or transient ischemic attack (TIA) were measured for plasma fibrinogen levels. Selected participants had concomitant hyperfibrinogenemia (plasma fibrinogen > or = 3.0 g/l). Patients enrolled between 1 July 2003 and 31 December 2004 were treated with batroxobin; patients enrolled between 1 January 2002 and 30 June 2003 were treated without batroxobin. Batroxobin was administered intermittently via intravenous injection at 3-monthly intervals. Patients in both groups were followed for 1 year. Any cerebrovascular events and suspected adverse events were recorded. In total, 112 ischemic stroke/TIA patients with concomitant hyperfibrinogenemia were enrolled, 52 being treated with batroxobin and 60 without batroxobin. Six patients (11.5%) with batroxobin and 16 patients (26.7%) without batroxobin had recurrent cerebral ischemic events during follow-up. Stroke/TIA recurrence in patients without batroxobin was higher than that in patients with batroxobin (P < 0.05). Two patients with batroxobin and two patients without batroxobin developed hemorrhagic stroke during follow-up. There were five deaths (9.6%) in the batroxobin group, and seven deaths (11.7%) in the nonbatroxobin group during follow-up (P > 0.05). Intermittent intravenous injection of batroxobin can efficiently reduce the risk for stroke/TIA recurrence in patients with concomitant hyperfibrinogenemia.     

大脑中动脉支架内血栓形成1例报告

支架内血栓形成是支架置入术后的一种常见并发症。术后血管内皮损伤、胶原组织暴露和作为异物的支架均为引发血栓形成的可能机制。不能及时识别处理则成为再狭窄的重要原因。我们报告1例发生在大脑中动脉（middle cerebral artery，MCA）支架内的血栓形成，探讨其识别处理过程和可能的机制。     

臂丛加强化麻醉后并发颈部抽动9例分析

目的探讨臂丛加强化麻醉后颈部抽动的原因及防治。方法对近年来在麻醉方法、用药相同,术后颈部抽动患者的观察治疗过程进行分析。结果臂丛麻醉并发颈部抽动给予充分镇静后可完全治愈。结论麻醉后并发颈部抽动为药物副作用及颈局部刺激的综合作用。     

还原型谷胱甘肽在预防糖尿病大鼠勃起功能障碍中的研究

目的探讨还原型谷胱甘肽(GSH)在预防糖尿病大鼠勃起功能障碍中的作用。方法通过腹腔注射链脲佐菌素65mg/kg建立糖尿病大鼠模型,然后随机分成DM组和DM+GSH组,DM+GSH组每天肌肉注射GSH200mg/kg。10周后观察大鼠勃起功能,并获取海绵体组织检测其谷胱甘肽、一氧化氮合酶(NOS)与丙二醛(MDA)水平,用TUNEL法检测细胞凋亡。结果成功建立糖尿病大鼠模型。与未注射GSH的DM组相比,DM+GSH组和正常对照组(C组)勃起功能更好,勃起率分别是20%,62.5%和100%。GSH水平DM+GSH组和C组明显比DM组高,其3组含量每克蛋白分别是(75.83±15.62)、(61.47±8.65)和(35.03±12.29)mg(P<0.05);NOS水平在DM+GSH组每毫克蛋白为(133.9±31.9)U,与正常对照组每毫克蛋白为(142.2±31.2)U相当,但较DM组每毫克蛋白为(58.4±18.9)U高(P<0.05);MDA含量在DM组每毫克蛋白为(3.71±0.62)nmol,明显高于正常对照组和DM+GSH组(P<0.05),这两组每毫克蛋白为(2.08±0.34)nmol和(2.44±0.28)nmol;细胞凋亡率在DM组、DM+GSH组和C组的分别是(22.6±3.6)%、(10.8±1.7)%和(7.2±2.1)%(P<0.05)。结论还原型谷胱甘肽对糖尿病大鼠阴茎组织有较好的抗氧化作用,能减少细胞凋亡,对延缓糖尿病性ED的发生有一定的作用。     

三氧化二砷对CO2气腹下小鼠肿瘤腹壁戳口种植影响的实验研究

目的 研究腹腔内注射三氧化二砷(arsenic trioxide,As2O3)对小鼠CO2气腹下肝癌H22转移的影响. 方法 昆明鼠40只(清洁级),中腹部穿刺置入1 mm套管针,自套管针注入1×106肿瘤细胞后,建立CO2气腹,压力8 mm Hg,时间30 min.术后随机分4组,每组10只,分别腹腔内注入生理盐水,1 ml;As2O3(2 mg/kg),1 ml;As2O3(4 mg/kg),1 ml;As2O3(4mg/kg)+肝素(10 U/ml),共1 ml.气腹后第3、7天测量肿瘤黏附因子(CD44)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的变化;比较各组生存状态、腹围、体重变化及转移瘤直径.结果 气腹后第3、7天,与对照组相比,各As2O3组CD44、VEGF表达均明显降低(P＜0.05).2个高剂量组的气腹后第3天VEGF、第7天CD44比低剂量组降低明显(P＜0.05).4组戳口种植率分别为9/10、8/10、7/10、6/10,差异无显著性(x2=2.667,P=0.446). 结论 As2O3对CO2气腹腹腔镜肿瘤生长转移有抑制作用.