双靶点抗肿瘤疫苗研制项目提升大学生综合能力

以大学生创新训练项目为契机,依托国家级生物制药实验教学示范中心平台,围绕"双靶点抗肿瘤疫苗研制"项目指导大学生进行相关理论知识的学习、科研思路的设计,并完成实验操作、数据整理、专利申请和论文写作等训练。初步选择鼠源粒细胞巨噬细胞集落刺激因子(mGM-CSF)和促胃泌素释放肽(GRP)为双靶点,完成了基因工程菌的构建、目标蛋白的制备、细胞培养、动物肿瘤模型的建立、肿瘤疫苗药效初步分析与探索。通过指导学生申请专利、发表文章、参加药苑论坛、挑战杯等各类比赛完成对学生的训练,提升其自主设计实验、自主完成实验、自主管理实验等综合能力。     

Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α⁺ isoform but not the α⁻ isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.     

PD-L1促进大鼠断尾再植成活及可能机制

目的研究程序性死亡受体-1(PD-L1)对断尾再植成活的影响,探讨可能的机制。方法建立大鼠断尾再植模型,随机选取40只断尾再植模型成功大鼠,分为两组:PD-L1组(术后立即环手术切口浸润注射重组大鼠PD-L1蛋白生理盐水溶液)和生理盐水组(术后立即环手术切口浸润注射生理盐水0.1ml),另取10只正常大鼠作为对照。ELISA检测手术前后各个时间点的血清样本中PD-L1水平,应用重组大鼠PD-L1蛋白干预断尾再植大鼠的断尾成活,评价术后断尾发生血管危象请况,Western blot法检测断尾再植大鼠尾组织中血管内皮生长因子(VEGF)、CD34蛋白表达水平。结果术后PD-L1水平显著增高(0.05),至术后48 h时达最高值,之后开始降低,至术后7d接近术前水平。经重组大鼠PD-L1蛋白干预的大鼠断尾血液循环较好,血管危象发生几率显著低于生理盐水预处理组。与正常大鼠相比,PD-L1蛋白干预组、生理盐水干预组断尾再植鼠尾组织中VEGF、CD34蛋白表达水平均显著增高(0.05),与生理盐水干预组相比,PD-L1蛋白干预组术后48h鼠尾组织中VEGF、CD34蛋白表达均显著增高(0.05),术后12d鼠尾组织中仅见VEGF蛋白表达显著增高(0.05)。结论 PD-L1促进断尾再植成活可能与上调VEGF及CD34表达相关。     

Influence of Fine Grains on the Bending Fatigue Behavior of Two Implant Titanium Alloys

By means of the ultrasonic surface impact (amplitude of 30 μm, strike number of 48,000 times/mm²), nanograins have been achieved in the surfaces of both Ti6Al4V(TC4) and Ti3Zr2Sn3Mo25Nb(TLM) titanium alloys, mainly because of the dislocation motion. Many mechanical properties are improved, such as hardness, residual stress, and roughness. The rotating–bending fatigue limits of TC4 and TLM subjected to ultrasonic impact are improved by 13.1% and 23.7%, separately. Because of the bending fatigue behavior, which is sensitive to the surface condition, cracks usually initiate from the surface defects under high stress amplitude. By means of an ultrasonic impact tip with the size of 8 mm, most of the inner cracks present at the zone with a depth range of 100~250 μm in the high life region. The inner crack core to TC4 usually appears as a deformed long and narrow α-phase, while the cracks in TLM specimens prefer to initiate at the triple grain boundary junctions. This zone crosses the grain refined layer and the deformed coarse grain layer. With the gradient change of elastic parameters, the model shows an increase of normal stress at this zone. Combined with the loss of plasticity and toughness, it is easy to understand these fatigue behaviors.     

从中医“阳气亏虚，痰瘀内阻”理论探讨中医药防治心肌缺血再灌注损伤的机制＊

目的 从文献探讨中医“阳气亏虚，痰瘀内阻”理论防治急性心肌梗死（Acute myocardial infarction，AMI）后心肌缺血再灌注损伤（Myocardial ischemia reperfusion injury，MIRI）的机制，为其科研及防治提供依据。方法 检索中国知网数据库、万方数据库、NCBI数据库从建库到2020年6月14日有关MIRI的文献，总结MIRI的发病机制及中医证治的新观点，分析可信度较高的相关实验数据，对运用中医“阳气亏虚，痰瘀内阻”理论防治MIRI进行探讨。结果 文献表明温阳化气、活血化瘀、祛痰化浊的中医方药可通过抑制细胞内Ca²⁺超载，稳定线细胞膜，减少氧自由基的生成，改善细胞能量代谢等多条途径参与缺血心肌的保护作用。结论 MIRI的发病机制文献表明，涉及多种病因，中医药可通过多靶点、多路径参与对MIRI的防治，且可能对MIRI的临床辨证论治提供理论依据。     

运动康复治疗在心血管疾病中的机制研究

近年来,心血管疾病的发病率呈逐年升高趋势,其中冠心病、心力衰竭等具有病程长、致死率高的特点,严重影响患者的生存质量。运动康复治疗可有效改善患者生存质量,降低住院率及病死率。运动康复治疗对心血管疾病的作用较为复杂,可对冠心病、心力衰竭等患者带来不同程度的获益。目前,心脏运动康复治疗相关机制的研究较多,本文从心脏血管适应和心肌细胞适应2个方面总结了心脏康复治疗的最新相关机制研究进展,其内容涉及血管内皮功能、侧支形成、血小板抑制、心肌代谢、心肌兴奋耦联收缩、心肌电重构等,以期为心血管疾病的康复治疗方案提供依据。     

新冠疫情背景下组织学与胚胎学网络教学的实施及教学反思*

2020年1月,突发的新冠肺炎疫情给我国经济社会发展带来巨大的挑战,能否将信息技术和网络教学完美融合,确保网络教学的质量,是摆在每一位教育工作者面前的问题[1].按照国家关于新型冠状病毒肺炎疫情防控工作部署要求,遵循"停课不停教、停课不停学"的原则,在2020年春季学期面向本校中医学、针灸推拿学、临床医学等专业开设组织学与胚胎学课程的网络教学.组织学与胚胎学是医学院校中非常重要的专业基础课,与现代医学及生命科学相互交叉与渗透,该学科研究的是正常人体的微观结构及功能,具有教学内容多、知识点繁杂、专业术语多、教学学时偏少、学生学习难度较高等特点[2].