As a basic compulsory course for medical students, biochemistry and molecular biology (abbreviated as biochemistry) has a direct and far-reaching influence on the construction of knowledge structure and the students' capacity building. Considering the weakness of traditional teaching of biochemistry in meeting the needs of discipline and comprehensive capacity training of students, it is an urgent demand to construct an innovative biochemistry characteristic course that meets the professional needs and conforms to the development of the times. The School of Basic Medical Sciences of Peking University has carried out in-depth teaching reform on biochemistry course and first set up a biochemistry online course that was specifically tailored for students majoring in pharmacy in 2020. Following formulating the teaching objectives according to the professional needs, the teaching content was designed accurately and the student-oriented blended teaching mode was used to stimulate students' interest in learning, to improve their understanding and application of abstract knowledge, and to build their capacity of problem-solving and self-regulated learning. Meanwhile, the ideological education was penetrated into the curriculum.

目的:探究研究生助教与教师在生化实验课中的教学效果差异.方法:选取2016级基础、临床等专业的467名学生期末考试实验成绩作为数据来源,并在本科生和研究生助教中进行相关问卷调查.结果:研究生助教和教师授课班级学生的实验课期末成绩之间没有统计学差异(P>0.05).学生对研究生助教授课和教师授课的满意度基本一致(P>0.05).结论:研究生助教在生化实验课中的教学效果较好,学生满意度高.

Curriculum evaluation is an important component in teaching activities. Adopting scientific, reasonable and efficient curriculum evaluation method can not only elevate students' interest in learning, but also promote teachers to optimize the teaching method and improve the teaching quality. Since 2011, the School of Basic Medical Sciences in Peking University has adopted a combination of formative evaluation and summative evaluation in biochemistry course in a number of majors including basic medicine, clinical medicine, oral medicine, preventive medicine, pharmacy and nursing. It includes many forms, such as questionnaire and survey, in-class test, drawing mind maps, students writing test questions, subject reports and stage-assessment. The trial implementation for 8 years has obtained relatively satisfactory teaching efficiency. At the same time, it has also been welcomed and accepted by the vast majority of students, and teachers' teaching enthusiasm and teaching quality have also been significantly enhanced.

TAp73 is a member of the P53 family,which can regulate the formation,invasion and metastasis of tumor.However,the role of TAp73 in regulating tumor angiogenesis is controversial.In this study,we transfected TAp73 into lung adenocarcinoma cell lines H1299 (P53-null) and A549 (wt P53) with different P53 gene status to observe the effect of TAp73 on angiogenesis and to explore the relationship with P53 gene.For this purpose,we first verified the transfection efficiency using RT-PCR and Western blotting.Wound healing assay showed that TAp73 promoted cell migration in A549 cell line and inhibited cell migration in H1299 cell line after TAp73 was overexpressed.Similarly,in vitro HUVEC tube formation assay showed that TAp73 promoted the ability of tube formation in A549 cell line and inhibited the ability of tube formation in H1299 cell line after TAp73 was overexpressed.At the same time,the expression level of VASH1 also increased in A549 cells or decreased in H1299 cells,respectively.Our results suggest that the effect of TAp73 on angiogenesis in lung adenocarcinoma cells depends on the status of P53 gene.TAp73 promotes angiogenesis in the presence of wild-type P53 gene,and TAp73 inhibits angiogenesis in the absence of P53 gene,which is perhaps significant for TAp73 as a potential therapeutic target in tumors.

目前我国医学夜大学教育普遍沿用全日制高校的教学模式,严重脱离夜大学生的特点和教育需求.本研究在分析我国医学夜大学教育现状的基础上,借鉴国外成人继续教育经验,按照“必须、够用、适度”原则,对夜大学医学生物化学课程的教学方式进行了改革尝试.初步研究显示,改革后的教学方式可明显提高夜大学生的生物化学课程成绩;问卷调查结果显示,大多数夜大学生对我们的改革措施给予肯定.我们希望这些改革思路和举措能为我国医学夜大学教育改革提供一些参考经验.

肿瘤有多种机制产生化疗药物耐药性.自噬是一种在正常细胞和病理细胞中普遍存在的生理机制,调控自噬的分子和信号传导通路错综复杂.自噬与凋亡有着独特的交叉联系,使得自噬在肿瘤化疗耐药性中发挥着促进或抑制耐药的双重作用.自噬在肿瘤耐药中的这种截然相反的作用与化疗给药浓度、细胞类型、自噬强度等因素有关,但具体机制尚未完全明确.然而,将自噬途径作为治疗肿瘤、降低化疗药物耐药性的靶点有着广阔的应用前景.

北京大学基础医学院各专业的生物化学课程考核大多采用结业式考试,即在课程全部结束后进行一次性考试.这种考核方式既不利于教师根据考核结果及时调整教学内容和教学方法,也不利于发挥考试对学生平时学习的激励和引导作用.为此,北京大学基础医学院自2011年起,在长学制基础医学和临床医学专业试行生物化学课程分阶段考核.初步研究显示,这种基于形成性评价的考核方式对课程的教学效果起到明显的改善作用.

目的 探讨肾上腺髓质素(adrenomedullin,AM)对转化生长因子β1(transforming growth factor-β1,TGF-β1)促肺成纤维细胞增殖及c-myc基因表达的影响.方法 体外原代培养人胚肺成纤维细胞(human fetal lung fibroblasts,HFLFs),分为对照组、AM组、TGF-β1组和AM+ TGF-β1组,采用MTT法观察各组光吸度(optical density,OD)值;各组提取细胞总RNA,采用反转录PCR观察c-myc基因mRNA表达情况.结果 AM+ TGF-β1组HFLFs细胞培养24、48、72 h时OD值(0.615±0.054、0.483±0.017、0.675±0.014)明显低于TGF-β1组(0.830±0.012、0.753±0.089、0.929±0.039) (P＜0.05),TGF-β1组HFLFs细胞培养72 h时OD值(o.929±0.039)明显高于对照组(0.605±0.274)(P＜0.05),AM组HFLFs细胞培养24、48 h时OD值(o.559±0.019、0.412±0.096)明显低于对照组(0.785±0.081、0.646±0.038) (P＜0.05);AM组c-myc mRNA相对表达量(0.450±0.025)明显低于对照组(P＜0.01);TGF-β1组c-myc mRNA相对表达量(1.160±0.100)高于对照组(P＜0.05);AM+ TGF-β1组c-myc mRNA相对表达量(0.340±0.030)低于TGF-β1组(P＜0.01).结论 AM能抑制肺成纤维细胞增殖和c-myc基因表达,AM可能具有抗纤维化作用.

近年的研究发现,在心肌细胞分化过程中,转录因子可以与表观修饰蛋白质结合进行更为精细的转录调控.作为转录因子的胰岛素基因增强子结合蛋白1 (islet1,ISL1),在心血管发育过程中发挥至关重要的作用.然而,ISL1是否能够与表观修饰蛋白质相互作用,从而发挥更为精细的调控作用,目前尚未明确.本室研究发现,ISL1在小鼠胚胎干细胞向心肌细胞分化过程中,能够与组蛋白去甲基化酶PHD指蛋白8(PHF8)相互作用从而促进分化.实时RT-PCR和Western印迹的方法检测显示,ES细胞向心肌细胞分化过程中ISL1和PHF8具有相似的表达谱.通过免疫共沉淀的方法检测分化过程中ISL1与PHF8的结合,通过染色质免疫沉淀的方法对二者在ISL1下游靶基因增强子区的结合水平进行检测,利用实时RT-PCR检测二者的相互结合对心肌细胞分化的影响.结果显示,ISL1能够与PHF8相互作用,共同结合在ISL1下游靶基因Mef2c和Myocd的增强子区,协同促进ES细胞向心肌细胞的分化.本研究证实,在心肌细胞分化过程中,ISL1存在与表观修饰蛋白质PHF8的相互作用,从而进一步促进心肌细胞的分化.

缺血再灌注产生的氧自由基会导致心肌细胞凋亡.近年研究发现,α-硫辛酸( α-lipoic acid,LA)具有抗氧化作用,但LA是否能够对抗心肌细胞凋亡,保护心脏功能的作用尚未明确.本研究利用H2O2诱导的心肌细胞H9c2氧化应激模型,分别用CCK-8方法检测细胞存活率、Hoechst33342染色观察细胞核的形态变化、流式细胞术检测细胞凋亡率、real-time PCR法检测Bcl-2/Bax基因表达变化,评价LA是否具有对抗氧化损伤引起的心肌细胞凋亡能力.结果显示,LA能提高H2O2损伤的H9c2细胞存活率,降低心肌细胞凋亡,而且LA通过上调Bcl-2的表达而发挥抑制细胞凋亡的作用.研究结果证实,LA对氧化应激损伤的心肌细胞具有较好的保护作用.该研究为LA在临床上用于治疗氧化应激引起的心肌细胞凋亡提供了实验依据.

The expression of α 1,3 Gal in inbred strain Wuzhishan miniature porcine was determined by flow cytometry and confocal analysis.The porcine peripheral blood mononuclear cells(PBMCs) were isolated from heparinised whole blood of 5-month old porcine by density gradient centrifugation and then incubated with FITC-isolectin.The specificity of FITC-isolectin binding to α 1,3 Gal was tested in porcine kidney epithelial PK15 and human HEK293 cells.No detectable fluorescence was observed in HEK293 cells with 100 ng/μl FITC-isolectin treatment,while the fluorescence was detected in PK15 cells with only 1.560 ng/μl FITC-isolectin treatment.The optimal concentration of FITC-isolectin was determined as 25 ng/μl(labeling rate85%) for PK15 cells.The samples were analyzed on a Calibur FACScan and BX51 Laser scanning confocal microscope.The α 1,3 Gal levels were found to display a 1.25～2.09 folds variation in the samples examined,indicating the variation of α 1,3 Gal expression between individual porcine appeared to be limited.These findings may further validate the inbred Wuzhishan miniature porcines as the candidate organ donors for xenotransplantation.

Objective: To investigate the effect of agmatine on alcohol-drinking behavior in alcohol-preferring FH/Wjd rats.Methods: FH/Wjd rats were individually housed in standard plastic cages,and offered with two bottles,one filled with alcohol(5% in tap water,v/v) and the other with tap water.Alcohol,water and food consumption were monitored once daily during the period of pre-and post-treatment with saline or agmatine.Results: Compared with pre-treatment(saline control),subcutaneous agmatine(80 and 160mg·kg-1) significantly reduced the daily alcohol consumption by 25.9% and 34.7%,respectively.Moreover,intragastric agmatine(500mg·kg-1) notably reduced alcohol consumption by 41.2%.In addition,a declining tendency of alcohol preference was observed in rats after subcutaneous and intragastric administration of agmatine.A slight increase was observed in water consumption during the period of treatment with agmatine.Intragastric administration of agmatine did not affect food consumption.Conclusion: Agmatine inhibits alcohol consumption in alcohol-preferring FH/Wjd rats,suggesting a potential to treat alcoholism.

胰-十二指肠同源盒1(Pdx1)基因作为胰岛素基因转录激活的关键性调控因子,已成为糖尿病基因/细胞治疗策略中最具希望的候选基因.利用Pdx1对非β细胞(包括肝细胞、小肠细胞、骨髓间充质细胞和胚胎干细胞)进行直接或间接的基因修饰和修饰细胞移植,并与其他辅助手段相协同,可有效启动胰岛素基因表达,从而改善糖尿病的高血糖症状.这一基因/细胞治疗策略为糖尿病的治疗提供了新的线索.

胰岛素基因的转录是一个十分复杂的网络式调控过程,主要通过该基因上游调控序列的启动子、增强子与转录因子复合物的相互作用来实现;多种证据表明胰岛因子1可能参与其中,对其具体机制的研究将是该领域的研究方向之一.