白藜芦醇下调肌球蛋白轻链激酶过表达抑制大鼠肝肿瘤增生

目的研究白藜芦醇(Res)通过影响肌球蛋白轻链激酶(MLCK)在肝脏中表达水平抑制原发性肝癌的增生。方法采用口服饮水中含0.9 mmol.L-1二乙基亚硝胺10周诱发原发性肝肿瘤;20周后,治疗组大鼠每天给予肌肉注射Res 50 mg.kg-16周;26周后,处死大鼠,计数肝表面癌结节数,称量和计算体重、肝重,肝/体重比,测定血清中甲胎蛋白的变化,观察大鼠肝脏的病理改变;用免疫组化和Westernblot法检测Res对MLCK的表达影响,用细胞凋亡试剂盒检测Res诱导肿瘤细胞的凋亡。结果 Res治疗组大鼠和模型组大鼠相比,体重增加,肝肿瘤结节数和肝/体重比和血清甲胎蛋白值减少或降低(P<0.05)。模型组大鼠肝组织MLCK的表达水平明显增加,而Res治疗可逆转MLCK的过表达水平,并诱导肿瘤细胞凋亡。结论 Res通过下调肝组织MLCK的表达水平诱导凋亡,抑制大鼠肝肿瘤细胞的增生。     

薄层扫描法测定复方鱼腥草滴丸中连翘苷含量

目的：用薄层扫描法测定复方鱼腥草滴丸中连翘苷的含量。方法：以氯仿∶甲醇∶冰乙酸（75∶12∶0.5）为展开剂,采用硅胶G薄层板,以5%香草醛硫酸液为显色剂,采用双波长反射锯齿扫描测定其含量,最大吸收波长λS520nm,参比波长λR700nm。结果：线性范围1～10μg, r=0.9985,平均回收率为98.65%,RSD=1.86%。结论：本方法灵敏、简便、准确,结果稳定,可作为复方鱼腥草滴丸的质量控制方法。     

胸腺五肽脂质体的处方及制备工艺研究

目的研究胸腺五肽脂质体的处方筛选及制备工艺。方法采用逆向蒸发法制备胸腺五肽脂质体,超速离心法测其包封率,以包封率和粒径为指标,采用正交试验设计法优化处方,并对其表面特征、包封率、粒径等情况进行考察。结果最佳处方制备的胸腺五肽脂质体平均粒径为108.2 nm,药物的平均包封率为62.10%,Zeta电位为-48 mV,脂质体外观圆整均匀,分散性好。结论所制胸腺五肽脂质体工艺简单、重现性好,粒径小,包封率较高,为其进一步研究奠定了基础。     

免疫抑制因子B7-H4与肿瘤关系的研究进展

B7同源体4（B7 homolog 4,B7-H4）是B7家族的新成员,在介导肿瘤免疫应答过程中发挥着重要作用,它可以通过抑制T细胞的增殖、细胞因子（如白介素-2）的产生和细胞周期（G0/G1期）的进程来负性调控T细胞的免疫应答。研究发现B7-H4在多种肿瘤细胞中呈现高表达,在正常组织中低表达或不表达,它可以使肿瘤细胞逃脱机体的免疫防御机制,促进上皮细胞的恶性转化和避免上皮细胞发生凋亡。所以在恶性肿瘤中B7-H4的表达具有重要的临床诊断意义,并可能提供一个用于癌症治疗的新靶点。     

转运体在药物排泄中的作用及在新药研发中的意义

本文介绍了药物转运体在药物排泄过程中的作用,探讨了其在新药研发和临床应用中的可能性。通过对药物转运体功能的了解和利用,可以开发出对某些器官有靶向性的药物,或避免药物分布到某些器官中,从而提高药物的疗效,降低其毒副作用;也可以通过对转运体介导的药物相互作用及肝肠循环的研究,指导临床更加安全有效的用药。在药物研发的初始阶段,就开始重视其药动学特性,这一观念近年来已被很多人所接受。对药物转运体的深入认识和利用,建立高通量的药物转运体筛选体系,对于加速新药研发的进程将具有极其重要的意义。     

淫羊藿总黄酮对大鼠肝微粒体CYP1A2、CYP3A4和CYP2E1活性的影响

评估淫羊藿总黄酮对大鼠肝细胞色素P450及其主要亚型活性的潜在影响。淫羊藿总黄酮以300mg／kg／d的剂量对SD大鼠进行连续灌胃处理15天，测定肝微粒体中cYP450含量与CYP1A2、CYP3A4和CYP2E1亚型活性，观察淫羊藿总黄酮的效应。CYP1A2的活性用荧光比色法进行测定，CYP3A4和CYP2E1的活性用紫外可见分光光度法测定。淫羊藿总黄酮处理后的大鼠肝脏CYP450含量及CYP1A2、CYP3A4和CYP2E1亚型活性均明显增高，其中CYP1A2和CYP2E1活性升高显著（P〈0．01）。淫羊藿总黄酮对大鼠肝脏CYP450及主要亚型CYP1A2、CYP3A4和CYP2E1活性均有诱导效应。     

我国药品上市后重点监测相关问题的探讨

摘 要为加强我国药品上市后监管力度,保障药品安全,国家食品药品监督管理总局于2011年正式提出了开展重点监测的要求,并于2013年进一步制定了《生产企业药品重点监测工作指南》（征求意见稿）。该指南对我国药品重点监测这一新制度的含义、内容、责任主体、程序、标准等进行了初步规定,以指导药品生产企业规范开展重点监测工作,保障重点监测制度的顺利实施。重点监测制度目前尚处于起步阶段,各界理解存在差异,通过对指南内容进行解读,对重点监测实施中可能存在的相关问题进行探讨,有助于更好地达到重点监测工作的目的和预期效果。     

替扎尼定治疗脑卒中后肩关节疼痛患者的不良反应

目的观察替扎尼定治疗脑卒中后肩关节疼痛患者过程中的不良反应。方法将脑卒中后肩关节疼痛患者172例随机分为试验组91例和对照组81例。2组患者均予以常规治疗,试验组同时给予替扎尼定口服,比较2组患者在治疗前后的肝肾功能、血压变化,并询问不良反应。结果治疗过程中,2组患者均出现胃肠道反应、嗜睡、口干、乏力、头晕、肝功能异常、体位性低血压等不良反应。其中试验组的嗜睡、头晕发生率显著高于对照组,而胃肠道反应发生率显著低于对照组,差异均有统计学意义（P〈0.05）。结论替扎尼定作为一种新型抗痉挛药,在有效缓解脑卒中后肩关节疼痛的同时,具有不良反应少的特点,值得临床推广。     

改良Ⅱ期法耳廓再造术

目的 探讨改良Ⅱ期法耳廓再造的方法并总结6年来的临床应用经验。方法 对146例（155耳）小耳畸形患者行耳廓再造术,手术分Ⅱ期进行。Ⅰ期：采用“U”形切口,切除残耳,在耳后分离合适的腔隙,置入肋软骨耳支架,耳垂向后转位衔接于再造的耳廓下方。6个月后行Ⅱ期手术：掀起耳廓,耳后置入软骨块,颞浅筋膜瓣转移覆盖后行中厚皮片移植术。结果 146例患者中141例（150耳）Ⅰ期术后恢复顺利,伤口愈合良好;5例（5耳）Ⅰ期术后4～6d出现皮瓣尖端坏死,范围约1.0 cm×1.5 cm,经换药后痊愈,未出现软骨外露、感染等;139例（147耳）Ⅱ期术后耳后移植皮片成活良好,7例（8耳）Ⅱ期术后出现耳后移植皮片部分成活不良,换药1周后愈合。146例患者随访94例（97耳）,失访52例（58耳）,随访时间为术后6个月至2年,随访病例均无感染、软骨吸收等并发症,再造耳廓结构清晰,耳颅角稳定。结论 改良Ⅱ期法耳廓再造手术操作相对简单,易于掌握,是耳廓再造的较为理想的方法之一。     

Topology Optimization and Multiobjective Optimization for Drive Axle Housing of a Rear Axle Drive Truck

As one of the important load-bearing components of a truck, the drive axle housing must meet the requirements of stiffness and strength. The traditional design method uses redundancy design to meet the performance requirements. The joint design between the three-dimensional mathematical model and finite element model is adopted, and the optimal design of the drive axle housing is realized based on topology optimization and multiobjective optimization. Firstly, the static analysis of the drive axle housing of a rear axle drive truck was carried out with four typical working conditions. It was concluded that the four working conditions all operate under the yield limit of the material, and it was found that the maximum equivalent stress of the four working conditions occurs at the step of the half-shaft casing. Among the four working conditions, the most critical one is the maximum vertical force working condition. Then, based on the maximum vertical force working condition, the fatigue life analysis is conducted, and the minimum fatigue life appears at the transition position of the half-shaft sleeve and the arc transition position of the main reducer chamber. The remaining parts can meet the design requirements. The overall safety factor of the drive axle housing is mainly between 1 and 5 when operating under this working condition. Then, through modal analysis, the first to sixth natural frequency and vibration modes of the drive axle housing are extracted. Based on the modal analysis, the dynamic characteristics of the drive axle housing are further studied by harmonic response analysis and random vibration analysis. Finally, two kinds of lightweight optimization schemes for the drive axle housing are given. Topology optimization reduces the mass of the drive axle housing by 17.4%, but the overall performance slightly decreases. Then, the five dimensional parameters of the drive axle housing are selected as design variables. The mass, maximum deformation, equivalent stress, service life, and the first-, second- and third-order natural frequencies are defined as objective functions. Through the optimal space-filling design method, the experimental designs are performed and the sample points are obtained. Based on the results of experiment design, the multiobjective genetic algorithm and response surface method are combined to optimize the objective functions. The analysis results show that the mass is reduced by 4.35%, the equivalent stress is reduced by 21.05%, the minimum life is increased by 72.28%, and the first-, second-, and third-order natural frequency are also increased to varying degrees. Two different optimization strategies are provided for the design of the drive axle housing.