抗人甲状腺球蛋白单克隆抗体的制备及其对抗原决定簇特异性的研究

用杂交瘤技术建立三株分泌抗甲状腺球蛋白(TG)单克隆抗体的杂交瘤细胞株。所获三种单克隆抗体经兔抗小鼠IgG亚类、IgM及IgA血清鉴定表明,两种为IgG_1,一种为IgA;三种含单克隆抗体小鼠腹水的滴度(ELISA法)均为51200以上;以竞争性固相抗体结合试验测定它们对抗原决定簇的特异性差异,结果发现三种单克隆抗体的抗原结合部位是不同的,但对抗原的结合有一定的相互竞争抑制现象。     

塞来昔布对大鼠化学性乳腺癌的抑制作用及机制

目的 观察环氧化酶-2(cyclooxygenase-2,COX-2)选择性抑制剂塞来昔布对化学致癌剂7,12-二甲基苯蒽(7,12-dimethybenz[a]anthracene,DMBA)化学诱发的大鼠乳腺癌的抑制作用并探讨其机制.方法 将DMBA油剂灌胃复制大鼠乳腺癌模型,大鼠分为对照组(24只)和实验组(25只),观察塞来昔布对大鼠乳腺癌的抑制作用,并采用基因芯片技术了解治疗后2组肿瘤的基因表达谱差异.结果 实验组塞来昔布处理后乳腺肿瘤的数目、直径、体积分别为(2.56±1.26)个、(1.162±0.355)cm、(1.967±1.725)cm.;明显小于实验前的(3.40±1.22)个、(1.948±0.481)cm、(8.794±6.389)cm3;明显小于对照组(3.88±1.73)个、(2.231±0.736)cm、(10.268±5.447)cm3,差异有显著性意义(均P＜0.01).对照组COX一2蛋白表达为62.5%(15/24),实验组COX-2蛋白表达为36.0%(9/25),差异有显著性意义(P＜O.05).基因表达谱显示两组之间表达丰度差异2倍及以上的基因共有243条,其中表达上调2倍或以上的基因片段124条,表达下调2倍或以上的基因片段119条,发现功能不明的新基因6条,其中表达上调的4条.结论 塞来昔布能抑制DMBA诱发的大鼠乳腺癌进展,其机制和多种基因改变有关.     

A phenytoin-sensitive cationic current participates in generating the afterdepolarization and burst afterdischarge in rat neocortical pyramidal cells

We report here on the ionic mechanisms underlying the depolarizing afterpotential (DAP) in neocortical pyramidal cells, with special interest in those underlying the burst afterdischarge. Injections of short depolarizing current pulses under whole-cell current clamp with a CsCl-based internal medium generated, in most pyramidal cells, a single action potential with a plateau phase (plateau-AP), followed by a slowly decaying DAP both in the absence and presence of TTX. Under voltage-clamp, the same cells displayed a slow tail current (tail-I) at the offset of depolarization. When intracellular free Ca²⁺ was chelated with 10 mm BAPTA or when extracellular Ca²⁺ was replaced with equimolar Ba²⁺, neither the slow DAP nor the slow tail-I was observed. Extracellular application of Co²⁺ or Cd²⁺ reduced Ca²⁺ currents and the slow tail-I. Cation substitution experiments revealed that the channel generating the slow tail-I was permeable to K⁺ and Cs⁺ more than to Na⁺ (P_K≈P_Cs > P_Na > P_NMDG≈P_TEA). The cationic slow tail-I was not reduced by applying antagonists of the metabotropic glutamate receptor (MCPG, 1 mm ) and the muscarinic receptor (atropine, 1–10 μm ). Thus, the slow DAP was produced by activation of the cationic channel whose gating is solely dependent on [Ca²⁺]_i. An increase in [K⁺]_o from 3 to 6 or 9 mm enhanced the slow DAP, and resulted in a generation of burst afterdischarges. An anticonvulsant, phenytoin (PT; 1–10 μm ) suppressed the slow DAP while enhancing the plateau-AP in the presence of TTX, most likely by blocking the cationic channel.     

INVOLVEMENT OF PHOSPHOPROTEIN PHOSPHATASE 1 IN COLLAGEN-PLATELET INTERACTION

The binding of type I collagen to its receptor initiates platelet aggregation, but the relationship of the receptor to other signal transduction components is not yet established. Correlation of platelet aggregation and anti-type I collagen receptor antibody immunoprecipitation of type I collagen treated [³²PO4]-labeled platelets showed that there are two phosphoproteins (M_r 53 kDa and 21 kDa) that coprecipitated with the 65 kDa platelet type I collagen receptor. In the present investigation, we have identified one of the phosphoproteins. A soluble component the 100,000×g supernatant fraction of 53 kDa protein is recognized by polyclonal anti-PP1 antibody. The activity of the precipitated phosphatase is inhibited by okadaic acid and inhibitor 1, suggesting that it is protein phosphatase 1 (PP 1). Phosphorylation decreases PP 1 activity as was found with [³²PO4]-phosphorylase b as the substrate. The immunocoprecipitation of the type-1 collagen receptor and PP 1 inot the result of cross reactivity of the anti-type I collagen receptor antibody with the PP I protein. These results indicate that the platelet type I collagen receptor, PP 1, and unidentified 21 kDa protein are in close association with the platelet type I collagen receptor upon the binding of type I collagen by the receptor. Copyright © 1996 Elsevier Science Ltd     

A prospective randomized study on the use of nadroparin calcium in the prophylaxis of thromboembolism in Korean patients undergoing elective total hip replacement

Summary. Because of the belief that post-operative deep vein thrombosis (DVT) is rare in Asian patients, thromboprophylaxis is not usually prescribed for surgical patients. This study reports an open multi-centre controlled study of the use of a low molecular weight heparin, nadroparin calcium (Fraxoparine Sanofi France), as opposed to no prophylaxis in 100 patients undergoing uncemented total hip replacement. The patients had bilateral venography performed preoperatively and 10 days after operation. Eight patients (16%) developed DVT in the control group of 50 patients and 1 (2%) in the treatment group, also of 50 patients. Pulmonary embolus occurred in 1 patient in the treatment group and in 3 in the control group. Intraoperative and postoperative blood loss did not differ significantly between the two groups. Our study suggests that the incidence of DVT in Asian patients, though somewhat less than in their Western counterparts, is still considerable. It confirms the safety and efficacy of nadroparin calcium in preventing post-operative DVT in patients undergoing elective total hip replacement.

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Résumé. A cause de l’idée selon laquelle la thrombose veineuse profonde post-opéraloire est rare parmi les patients asiatiques, la tromboprophylaxie pour les patients opérés est inhabituelle. Nous avons accompli une étude, comparant la prophylaxie au moyen d’héparine de bas poids moléculaire en utilisant du calcium nadroparine (Fraxiparine Sanofi France) et la non-prophylaxie sur 100 patients subissant un remplacement total de la hanche. Les patients ont subi une vénographie bilatérale avant l’opération et 10 jours après. Huit patients (16%) ont développé une thrombose veineuse dans le groupe de contr?le, contre 1 (2%) dans le groupe traité (p = 0.015, 95% CI 0.02 – 0.67). Trois embolies pulmonaires sont survenues dans le groupe de contr?le et 1 dans le groupe traité (p = 0.27 95% CI 0.04 – 2.44) aucune n’étant fatale. La perte de sang intra-opératoire et post-opératoire n’a pas varié de manière significative entre les deux groupes. Notre étude démontre que l’incidence de la thrombose veineuse profonde post-opératoire chez les patients asiatiques est notable bien qu’elle soit moindre que dans les pays occidentaux et confirme la s?reté et l’efficacité du calcium nadroparine pour la prévenir aprés un remplacement total de la hanche.

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Accepted: 19 March 1997     

Synthesis of two nitro analogs of tranylcypromine: Relations of aromatic substitution of nitro groups to MAO-Inhibitory activity

Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treatingt-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate andt-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate withp-toluenesulfonic acid in CH₃CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at bothin vitro andex vivo levels. It was found fromin vitro measurements that(E)-p-NTCP at 6.0×10^?5M elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast,(E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with IC₅₀ values, 2.5×10^?7M and 1.4×10^?6M, respectively. It was also noted from(E)-m-NTCP thatm-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According toex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by(E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas,(E)-p-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between(E)-m-NTCP and(E)-p-NTCP were sought in relation to differing electron withdrawing effects ofm-andp-substituents which will influence electron density of the side chain amino functions and the partitions.     

翻转课堂结合PBL在诊断听力学教学中的应用研究

目的 将翻转课堂与以问题为基础的学习（problem-based learning,PBL）相结合,应用于诊断听力学课程教学中,并评估其教学效果。方法 选取重庆医科大学2019级和2020级听力与言语康复专业本科学生共72人作为研究对象,以诊断听力学课程中的3个章节进行教学改革。其中2019级34人作为对照组,采用传统教学（lecture-based learning,LBL）;2020级38人作为试验组,采用翻转课堂+PBL进行教学。比较两种教学模式下学生的随堂测试成绩、课堂参与度评分、教学效果满意度及教学总体满意度,以评价教学效果。运用SPSS 23.0软件采用t检验、卡方检验、曼-惠特尼秩和检验进行统计分析。结果 试验组随堂测试成绩（25.95±1.21）分高于对照组成绩（23.21±1.55）分,两组比较差异有统计学意义（P<0.001）。在课堂参与度评分方面,试验组课堂讨论参与度、合作与协作能力,以及提问能力评分均高于对照组,两组比较差异有统计学意义（P<0.001,<0.001,<0.001）。在教学满意度方面,试验组学生在学习兴趣、理论知识掌握情况、团队协作能力、自主学习能力和自我展示能力等维度的满意度均高于对照组,两组比较差异有统计学意义（P=0.005,0.009,0.001,0.016,0.005）。此外,试验组对教学的总体满意度也高于对照组,两组比较差异有统计学意义（P=0.006）。结论 在诊断听力学课程教学中,采用翻转课堂结合PBL教学获得了良好的教学效果,值得推广。     

广州地区高校医学生自主学习差异性研究

目的 了解广州地区医学生自主学习情况,分析影响广州地区医学生自主学习的要素,探讨提高医学生自主学习能力的策略。方法 采用自编的《医学生自主学习问卷》对广州市6所高等院校的2 480名医学生进行分层抽样调查。采用SPSS 22.0统计软件对资料进行统计学分析。结果 医学生专业与自主学习频率（χ²=21.33,P<0.001）、性别与自主学习有效性（χ²=4.86,P=0.027）、学年制与自主学习必要性认知（χ²=4.65,P=0.031）、家庭指导与自主学习方法选择能力适宜性的差异有统计学意义（χ²=32.43,P<0.001）。结论 学校、个人和家庭共同影响医学生的自主学习,三方应该相互协作,提高医学生自主学习能力,培育具备终身学习能力的高素质医学人才。     

443例胃癌根治术后发生肺部并发症的危险因素

目的 探讨胃癌根治术术后肺部并发症(PPCs)的相关危险因素,为PPCs的个体化防治提供相应的对策。 方法 回顾性分析2019年1月至2021年3月兰州大学第二医院普通外科443例胃癌患者的临床资料,统计患者的临床病理特征,采用二分类Logistic回归分析胃癌根治术PPCs的危险因素。 结果 443例胃癌根治术PPCs的发生率为18.1%(80/443),其中肺部感染的发生率为12.4%(55/443),胸腔积液的发生率为11.7%(52/443),发生PPCs较未发生PPCs住院时间延长。Logistic回归分析显示,年龄≥60岁(OR=0.424、95%CI: 0.241~0.746)、糖尿病史(OR=0.318、95%CI: 0.146~0.693)、每分钟最大通气量(MVV)(%)<85%(OR=0.509、95%CI: 0.297~0.874)、术中失血量≥200 mL(OR=0.496、95%CI: 0.276~0.797)和术后吻合口并发症(OR=4.038、95%CI: 1.250~13.049)是胃癌根治术发生PPCs的独立危险因素。 结论 对于年龄≥60岁、糖尿病史、MVV(%)<85%、术中失血量≥200 mL、术后吻合口并发症的胃癌患者,应注意预防PPCs的发生。     

糖尿病肾病中足细胞损伤机制的研究进展

摘要：糖尿病肾病是终末期肾病的主要病因。肾小球滤过屏障损伤导致的高蛋白尿是糖尿病肾病的主要特征,而足细胞功能及其结构的完整性对于肾小球滤过屏障至关重要。造成足细胞损伤的因素复杂且相互串扰,该文从糖脂代谢异常、氧化应激、慢性炎症、自噬、表观遗传学变化等角度阐释糖尿病肾病中足细胞的损伤机制,以期为糖尿病肾病的发生发展机制探讨、治疗及预后预测奠定理论基础。