摘要：DPP-Ⅳ(二肽基肽酶-Ⅳ)抑制剂是目前研究最广泛深入的一类抗糖尿病药物。梳理DPP-Ⅳ的蛋白结构和功能,分析各类型上市或临床DPP-Ⅳ抑制剂的设计思想及关键基团作用模式,为通过基于结构的药物设计获得新型选择性DPP-Ⅳ抑制剂提供参考。

摘要：To minimize the deviation of the predicted creep curves obtained under constant load conditions by the original θ projection model, a new modified version that can be expressed by ε = θ_1(1-e^(-θ2t)) +θ3 (e^(θ_4e^θ5^εt)-1), was derived and experimentally validated in our last study. In the present study, the predictive capability of the modified θ projection model was investigated by comparing the simulated and experimentally determined creep curves of K465 and DZ125 superalloys over a range of temperatures and stresses. Furthermore, the linear relationship between creep temperature and initial stress was extended to the 5-parameter model. The results indicated that the modified model could be used as a creep life prediction method, as it described the creep curve shape and resulted in predictions that fall within a specified error interval. Meanwhile, this modified model provides a more accurate way of describing creep curves under constant load conditions. The limitations and future direction of the modified model were also discussed. In addition, this modified θ projection model shows great potential for the evaluation and assessment of the service safety of structural materials used in components governed by creep deformation.

摘要：Bromodomains(BRDs)是一类能够特异性识别乙酰化赖氨酸并形成驱动活性转录的蛋白质复合物的保守蛋白结构域,而组蛋白赖氨酸的N端乙酰化或去乙酰化修饰可改变染色质的结构,调控基因的转录激活和转录抑制。BRDs小分子抑制剂能够和乙酰化赖氨酸竞争性地与BRDs的疏水口袋结合,在表观遗传调控中发挥重要作用,在治疗肿瘤、炎症、自身免疫疾病和心血管疾病等方面也显示出巨大的研究潜力。综述BRDs抑制剂及其在疾病治疗中的作用研究进展,为高效、选择性BRDs小分子抑制剂的设计与开发提供参考。

摘要：目的 基于“易感-应激-应对”模型,分析童年期虐待经历、近期生活事件和应对方式对医学生抑郁症状的影响机制。方法 采用纵向研究设计,于2019年11—12月整群抽取合肥市和安庆市各1所医学专科学校的4211名大一新生开展基线调查,于2020年11—12月开展随访调查,最终有3662名医学生同时完成基线和随访调查。采用儿童期虐待问卷、青少年负性生活事件量表、应对方式问卷和抑郁自评量表分别评价童年期虐待经历、近期生活事件、应对方式以及医学生抑郁症状。应用PROCESS软件模型1(双重交互作用分析)和模型3(三重交互作用分析)探讨童年期虐待经历、近期生活事件、不同应对方式对医学生随访抑郁症状的独立和交互作用。结果 3662名医专学生中男生976名,女生2686名,年龄(19.2±1.0)岁。童年期虐待经历、近期生活事件和自责、幻想、退避、合理化的应对方式与基线和随访抑郁症状均存在正向关联(P<0.05),而解决问题、求助的应对方式与基线和随访抑郁症均状存在负向关联(P<0.05)。模型1中童年期虐待经历(β=0.097,95%CI 0.065~0.129)和近期生活事件(β=0.102,95%CI 0.073~0.132)均对抑郁症状有正向的预测作用,二者的交互项(β=0.030,95%CI 0.025~0.004)也与抑郁症状有正向关联。模型3中童年期虐待经历、近期生活事件和求助(β=-0.034,95%CI-0.061~-0.007)或幻想(β=-0.039,95%CI-0.065~-0.013)的应对方式三者对抑郁症状存在负向交互作用。结论 童年期虐待经历和近期生活事件是医专学生抑郁症状的易感性因素,同时二者可以相互促进作用于抑郁症状,而求助和幻想的应对方式能够弱化二者的促进作用。

摘要：Estimating long-term creep deformation and life of materials is an effective way to ensure the service safety and to reduce the cost of long-term integrity evaluation of high temperature structural *** the 1980 s, the θ projection model has been widely used for predicting creep lives due to its ability to capture the characteristic transitions observed in creep curves obtained under constant true stress conditions. However, the creep rupture behavior under constant load or engineering stress conditions cannot be simulated accurately using this model because of the different stress states. In this paper, creep curves obtained under constant load conditions were analyzed using a modified θ projection model by considering the increase in true stress with creep deformation during the creep tests. This model is expressed as ε = θ_1(1-e^(-θ_2t)) + θ3 e^(θ_4e^θ5^εt)-1, and was validated using the creep curves of K465 and DZ125 superalloys tested at a range of temperatures and engineering stresses. Moreover, it was shown that the predictive capability of the modified θ projection model was significantly improved over the original one, as it reduces the prediction uncertainty from a range of 10% to 20% to below 5%. Meanwhile,it was shown that the model can be reasonably used for predicting constant stress creep conditions, when appropriate parameters are used. The prediction performance of the modified model will be discussed in another paper. The results of this study show great potential for the evaluation and assessment of the service safety of structural materials used in applications where designs are limited by creep deformation.

摘要：本研究选择地理位置居中、经济社会发展处于全国中等水平的安徽省合肥市为研究对象,运用文献资料、问卷调查、专家访谈、数理统计等研究方法,结合合肥市庐阳区开展“安徽省体卫融合慢病干预试点工作”的有利条件,依托慢病干预试点工作有效整合社区的卫生医疗团队、科学健身指导团队,针对高血压、糖尿病、高血脂等人群开展了为期一年的体卫融合慢病干预试点应用,取得了显著健康成效,初步验证了本文设计的智慧体育服务体系的合理性和可行性,为全民健身与全民健康深度融合提供了典型经验。

摘要：随着粤港澳大湾区、中国特色社会主义先行示范区等国家战略的推进,深圳迎来了新的发展机遇,然而当前会计职业教育与大湾区经济发展需求不匹配,高职会计人才培养亟需转型。推动深圳会计职业教育高质量发展,使之成为深圳产业结构升级的重要动力,是职业教育必须担负的使命。以OBE理念为指导,采用文本挖掘方法分析高职会计专业人才的社会需求,按照社会需求、培养目标和培养规格、课程体系、课程考核逆向路径设计课程体系,以期为高职院校培养符合社会需求的会计人才提供借鉴。

摘要：RAS是人类癌症中最常发生突变的致癌基因,而KRAS则是RAS家族中最常发生突变的亚型,其中多数为12位密码子的突变。突变之后的KRAS使细胞的生长、增殖不受控制,进而导致癌症的发生与发展。尽管经过了30多年的努力,但直接靶向KRAS活性位点的药物开发均以失败告终。由于KRAS与GTP的亲和力极强,同时细胞中GTP浓度较高,以至于使KRAS成为"不可成药"靶点。近期,针对突变的KRAS G12C特异性共价抑制剂在临床试验中取得了突破性进展,为KRAS抑制剂的可成药性提供了临床证据。综述KRAS的结构功能及其小分子抑制剂的设计和临床研究概况,着重介绍具有代表意义的KRAS G12C抑制剂和其作为抗肿瘤药物的最新研发进展,为以KRAS为靶点的药物开发提供研究思路。

摘要：本论文以中国药科大学国际留学生班药学、临床药学、国际经济与贸易三个专业的"计算机应用基础"以及"计算机程序设计"课程的全英文教学为基础,对具有药学背景的留学生计算机基础课程全英文教学的教学特点、教学方式、改革途径等层面进行剖析,并提出了相应的整改策略.

摘要：溴结构域蛋白4(BRD4)在组蛋白乙酰化修饰过程中发挥着重要的作用,与多种包括恶性肿瘤在内的疾病发生发展密切相关。目前,已有多个BRD4抑制剂进入临床研究阶段。因泛BRD4小分子抑制剂因其选择性差而导致的不良反应等问题,最终多数临床研究被终止。BRD4高选择性抑制剂靶向肿瘤等疾病已成为BRD4抑制剂开发的新趋势。对BRD4蛋白的结构和生物学功能进行研究,并对目前已经报道的选择性BRD4 BD1和BRD4 BD2抑制剂以及BRD4选择性抑制剂产生选择性的结构基础和独特的适应证进行综述,旨在加深对BRD4蛋白功能了解的同时,为后续BRD4高选择性抑制剂的设计和拓展研究奠定基础。