4+4临床医学人才培养美国模式与交医模式的比较及思考

上海交通大学医学院借鉴北美医学院校的培养模式，从2002年起在国内率先开展临床医学专业"4+4"培养项目，招收优秀非医学应届本科毕业生攻读4年医学课程。经过20年的实践，交大医学院已积累了一系列具有中国特色且行之有效的办学经验，同时也面临问题和困惑。本研究对比分析交大医学院和美国一流医学院校哈佛医学院、斯坦福大学医学院的"4+4"人才培养模式，并从培养目标、招生方式与规模、课程设置、学位授予标准等方面展开深入探讨。研究表明，未来交大医学院还需通过凸显特色人才培养目标，完善招生标准与流程，优化课程体系，平衡临床和科研能力培养等举措加大教育教学改革力度，助力推进"4+4"临床医学人才培养模式从优秀迈向卓越。     

The third-generation retinoid adapalene triggered DNA damage to induce S-phase arrest in HaCat cells

Epidermal proliferative diseases consisted of a series of common skin diseases, most of which were recurrent chronic skin diseases, and had greatly negative influence on the life quality of patient. Retinoids exhibited vital roles in the treatment of many skin diseases. Our recent study demonstrated that adapalene significantly inhibited the growth of HaCat cells, and the inhibitory activity was stronger than other retinoids, such as all-trans-retinoic acid, acitretin, isotretinoin, tazarotene, and bexarotene. Further study showed that adapalene suppressed the colony formation of HaCat cells, and it dramatically triggered S-phase arrest and apoptosis, rather than G1 phase arrest which was reported in other retinoids in several studies. Additionally, adapalene treatment greatly upregulated the protein expression of DNA damage marker γ-H2AX, which was in accord with the results of the elongation of tail moment by comet electrophoresis analysis. Moreover, DNA damage was triggered and DNA repair was suppressed synchronously with adapalene treatment, which accounted for the mechanism of S-phase arrest induced by adapalene. In summary, our recent work demonstrated that adapalene showed strong anti-proliferation activity in HaCat cells and could be an alternative agent for the epidermal proliferative disease.     

三七HPLC指纹图谱及5种成分测定

目的 建立三七HPLC指纹图谱,并测定5种成分的含有量.方法 三七70%甲醇提取物的分析采用Waters XBridge C18色谱柱(4.6 mm×250 mm,5μm);流动相乙腈-水,梯度洗脱;体积流量1.5 mL/min;柱温25℃;检测波长203 nm.结果 15批样品指纹图谱中有5个共有峰,相似度均大于0.99.三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1和人参皂苷Rd分别在0.000 76~0.567 64(r=0.9999)、0.002 69~2.017 43 (r=0.9998)、0.000 38~0.283 82 (r=1.000 0)、0.002 83~2.12483 (r=0.999 8)、0.000 78~0.582 98 mg/mL (r=0.999 8)范围内线性关系良好,平均加样回收率分别为101.78%、97.22%、102.14%、98.96%、101.73%,RSD分别为1.58%、1.31%、2.17%、1.55%、1.80%.结论 该方法简便、快速、准确,可用于三七的质量控制.     

电针干预佐剂性关节炎大鼠踝关节滑膜细胞凋亡的MMP-3、MMP-9分子调节机制

目的观察电针干预对佐剂性关节炎大鼠踝关节滑膜细胞凋亡和相关蛋白基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-9(MMP-9)表达的影响。方法32只雄性SD大鼠被随机分为生理盐水组、模型组、电针干预组和假电针干预组,每组8只。生理盐水组大鼠在双侧足垫部注射模拟造模,其余大鼠用弗氏完全佐剂在双侧足垫部注射造模。电针干预组大鼠予以电针干预。假电针干预组予以假电针刺激处理。HE染色观察模型大鼠踝关节炎症进展情况,Tunnel法检测模型大鼠踝关节滑膜细胞凋亡情况,RT-PCR检测踝关节滑膜的MMP-3、MMP-9的mRNA表达,Western blot检测踝关节滑膜的MMP-3、MMP-9的蛋白表达。结果HE染色显示,电针干预组大鼠的关节炎症显著轻于模型组。Tunnel法检测,电针干预可以促进关节炎大鼠的滑膜细胞凋亡。RT-PCR和Western blot检测结果显示,电针干预可以显著降低关节炎大鼠踝关节滑膜组织中的MMP-3、MMP-9 mRNA和蛋白表达水平(P<0.05)。结论电针干预可以显著减轻佐剂性关节炎大鼠的关节炎症和增殖的滑膜细胞数量,其分子机制可能和电针降低局部的MMP-3、MMP-9蛋白的表达有关。     

A Network Pharmacology Study of Reduning Injection for the Treatment of Coronavirus Disease-19

Objective: The 2019 novel coronavirus (2019?nCoV) outbreak has escalated into a global pandemic. According to Chinese guidance for coronavirus disease?19 (COVID?19): Prevention, control, diagnosis, and management, Reduning injection can effectively treat, the disease caused by the virus. To identify the active ingredients of Reduning injection and COVID?19 disease?related pathways, we conducted a network pharmacology study. Methods: The Traditional Chinese Medicine Systems Pharmacology database was used to screen the chemical constituents and potential targets of Reduning injection. The gene names were converted to the corresponding protein names using UniProt. GeneCards and OMIM databases were used to select targets related to 2019?nCoV. Using Cytoscape 3.7.2 software platform and STRING database, we constructed drug?common target and target protein protein?protein interaction network diagrams. Rx64 3.6.2 software and Bioconductor biological information software package were used for? Gene Ontology (GO) functional enrichment and KEGG pathway analyses. Results: In Reduning injection, a total of 33 effective chemical components were obtained that were involved in 151 signaling pathways, of which 44 targets were considered therapeutically relevant. Conclusion: Reduning injection can be potentially applied for the treatment of COVID-19 based on the results of our network pharmacology study.     

基于网络药理学与分子对接探讨木瓜治疗膝骨关节炎的分子机制

目的:基于网络药理学探索木瓜治疗膝骨性关节炎的分子作用机制。方法:基于口服生物利用度(OB)及药物相似性(DL),通过中药系统药理学数据库(TCMSP)筛选木瓜的主要活性成分。运用GeneCards、OMIM数据库建立膝骨性关节炎靶标数据库。通过Cytoscape 3.7.1软件构建"活性成分-作用靶标-疾病"可视化交互网络;运用STRING数据库构建蛋白互作网络,分析相关蛋白互作关系;对核心靶点进行京都基因与基因百科全书(KEGG)通路及基因本体(GO)生物过程富集分析。通过Discovery Studio软件对药物活性成分与疾病靶点进行分子对接验证。结果:筛选得到木瓜活性成分3个,涉及44个作用靶点。网络分析结果表明,靶点主要涉及调节细胞代谢、凋亡等生物学过程,通过调节细胞凋亡、肿瘤坏死因子(TNF)、p53、核转录因子-κB(NF-κB)、糖基化终末产物(AGE)及其受体(RAGE)等信号通路来发挥治疗膝骨关节炎的作用。分子对接结果表明,木瓜活性成分与膝骨性关节炎的血管内皮生长因子A(VEGFA)、白细胞介素-6(IL-6)、雌激素受体1(ESR1)等靶点对接吻合度较好。结论:木瓜治疗膝骨性关节炎具有多系统、多成分、多靶点的特点;其可能的作用机制包括控制炎症,调控关节软骨代谢、生长和修复,促进细胞增殖、分化,抑制细胞凋亡和抵抗氧化应激等以达到控制疾病发生发展的目的;木瓜中槲皮素、白桦脂酸、表儿茶酸等活性成分可能是其治疗膝骨性关节炎的物质基础。