Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with high morbidity and mortality worldwide. Although the dysregulation of BARX1 expression has been shown to be associated with malignant cancers, including NSCLC, the underlying mechanism remains elusive. In this study, we identified BARX1 as a common differentially expressed gene in lung squamous cell carcinoma and adenocarcinoma. Importantly, we uncovered a novel mechanism behind the regulation of BARX1, in which ZFP36 interacted with 3'UTR of BARX1 mRNA to mediate its destabilization. Loss of ZFP36 led to the upregulation of BARX1, which further promoted the proliferation, migration and invasion of NSCLC cells. In addition, the knockdown of BARX1 inhibited tumorigenicity in mouse xenograft. We demonstrated that BARX1 promoted the malignant phenotypes by transactivating a set of master oncogenes involved in the cell cycle, DNA synthesis and metastasis. Overall, our study provides insights into the mechanism of BARX1 actions in NSCLC and aids a better understanding of NSCLC pathogenesis.

Reading research literature is a necessary skill that medical students need master as soon as possible and it is also an important way to cultivate their scientific literacy and building of innovation capacity. Guiding junior undergraduates to read research literature in a form of course may help students to master systematic and scientific literature reading methods and lay a solid foundation for their future development. Taking the example of literature reading and academic communication, a college level general education elective course has been offered by the biochemistry teaching team from Peking University School of Basic Medical Sciences. The course is developed for the sophomores and juniors of Peking University Health Science Center and this article described course design, implementation and evaluation which were carried out by final examination and questionnaire survey. The results show that among 137 students who have taken this course, 99.3% (136/137) of the students successfully completed the course and passed the examination. The questionnaire survey of 72 students taking this course during 2020 and 2021 shows that guiding junior undergraduates to read scientific research literature in a form of selective courses significantly improved students' literature reading ability [88.9%(64/72)] and their skill in presentation [66.7%(48/72)], stimulated students' interest in scientific research [51.4%(37/72)], and enabled students to benefit from peer learning [63.9%(46/72)]. This course has initially established a set of early-phase training of research capacity in a form of single course. The learning is guided by teachers and follows the students-centered principle, which is conducive to cultivating students' essential capacity of literature reading and to stimulating their interest in scientific research.

N6-甲基腺嘌呤(N6-methyladenosine),即m6 A修饰,普遍存在于各种真核生物中,是真核细胞RNA中最常见的甲基化修饰,占所有RNA甲基化修饰的80％以上.METTL3作为m6 A甲基转移酶复合体的核心催化亚基,可以修饰多种承担重要功能分子的转录本,并由此参与细胞的分化、增殖和发育等重要生命过程.近年有大量研究发现,METTL3与多种疾病的发生、发展密切相关,如肿瘤、神经系统疾病、心血管疾病等.本文重点介绍了METTL3与这些疾病发生、发展关系的研究进展.

Biochemistry and molecular biology (abbreviated as biochemistry) is a core course for students majoring in life science and medicine. Since 2015, the School of Basic Medical Sciences of Peking University has carried out an interactive teaching reform on biochemistry course in the form of theme reports, which involves students' analyzing and presenting common phenomena and problems in life and clinical performance based on biochemical knowledge following the teacher teaching the core knowledge. This teaching model combines learning and practicing organically and hence encourage communications between teachers and students as well as among students themselves (dual-channel). The results of the questionnaire showed that students approved that the interactive teaching mode based on theme reports could stimulate learning interest of students [90.6%(116/128)], improve students' comprehension of knowledge [93.8%(120/128)], promote their independent learning and reasoning capacity [96.1%(123/128)], strengthen their capacity building to apply the knowledge in practice [93.0%(119/128)], enhance their ability to review literature [96.1%(123/128)], and promote the communication, cooperation and mutual learning among students [89.8%(115/128)], 75.8%(97/128) of the students were willing to apply the interactive teaching model based on theme reports to other courses. This teaching mode makes up for the deficiencies of the traditional teaching, helps to improve the teaching effect of biochemistry course, and promotes the improvement of students' overall quality.

现代医学教育对人才培养提出了更高的要求,"以学生为中心"是组织高效课堂和实现人才培养的有效途径.在教学过程中,学生是学习的主体,教师的任务是帮助学生学习.因而,"以学生为中心"的教学模式能更有效地激发学习主体的积极性、主动性和创造性,使教学更加富有成效.为适应高水平医学人才培养的需要,我们对生物化学教学进行了改革,改变了以教师为中心的传统教学模式,贯彻"以学生为中心"的教学理念,主要采取了如下教学举措:为学生提供展示锻炼的舞台,鼓励学生讲和演;邀请学生参与试题编写和分享学习经验;加强平时考核,注重形成性评价,培养学生良好的学习习惯;尊重学生意愿,积极听取及采纳学生的合理意见和建议;课下与学生谈心交流,进行心理疏导等.经过多年的探索和实践,这些措施在激发学生学习兴趣、培养自主学习意识、提升全面素质等方面取得了良好的效果.

Biochemistry is an important curriculum for all medical students but has long been considered obscure and of very little or indirect relevance to medical or clinical practice, which markedly diminishes the enthusiasm and motivation of medical students in learning. Biochemistry teachers always face a tremendous challenge to deliver an attractive and high-quality lecture class. Inspired by convincing studies that show numerous benefits of undergraduate research, we tried to modify our teaching method in the past 5 years by incorporating classical scientific research stories into our traditional lecture class, such as the discovery of the semi-conservative DNA replication, telomeric DNA and telomerase, the tricarboxylic acid cycle (TCA cycle), and so on. Through this story-based teaching, we not only helped them deeply understand the textbook content, but also introduced the process of real scientific research to the students in an interesting way. Our efforts aim to combine the delivery of knowledge with the inspiration of students' active learning. We found that most students involved in our classes responded positively. As described in the survey, they were strongly attracted by those research stories; rather than feeling bored about the Biochemistry textbook, they experienced curiosity which fostered their active learning. They also learned to appreciate the beauty of science. More importantly, their impression on how the authentic science research was done was instructive for their critical thinking.

Mitochondrial biogenesis and energy metabolism are essential for regulating the inflammatory state of monocytes. This state is partially controlled by peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a coactivator that regulates mitochondrial biogenesis and energy metabolism. Disruption of these processes can also contribute to the initiation of chronic inflammatory diseases, such as pulmonary fibrosis, atherosclerosis, and rheumatoid arthritis. Methyltransferase-like 3 (METTL3)-dependent N6-methyladenosine (m6A) methylation has recently been shown to regulate a variety of inflammatory processes. However, the role of m6A mRNA methylation in affecting mitochondrial metabolism in monocytes under inflammation is unclear, nor is there an established relationship between m6A methylation and PGC-1α. In this study, we identified a novel mechanism by which METTL3 acts during oxidized low-density lipoprotein (oxLDL)-induced monocyte inflammation, where METTL3 and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) cooperatively modify PGC-1α mRNA, mediating its degradation, decreasing PGC-1α protein levels, and thereby enhancing the inflammatory response. METTL3 coordinated with YTHDF2 to suppress the expression of PGC-1α, as well as that of cytochrome c (CYCS) and NADH:ubiquinone oxidoreductase subunit C2 (NDUFC2) and reduced ATP production and oxygen consumption rate (OCR). This subsequently increased the accumulation of cellular and mitochondrial reactive oxygen species (ROS) and the levels of proinflammatory cytokines in inflammatory monocytes. These data may provide new insights into the role of METTL3-dependent m6A modification of PGC-1α mRNA in the monocyte inflammation response. These data also contribute to a more comprehensive understanding of the pathogenesis of monocyte-macrophage inflammation-associated diseases, such as pulmonary fibrosis, atherosclerosis, and rheumatoid arthritis.

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.

生物化学课程(简称生化课程)是医学院校所有专业和综合性大学生命科学相关专业的必修基础课程,也是学生反映学习难度较大的课程之一,物质代谢的学习更是难中之难.在我校生化课程中,核苷酸代谢安排在糖代谢、脂质代谢、生物氧化及氨基酸代谢之后讲授.虽然通过前期代谢相关内容的学习,学生已基本掌握了物质代谢的学习方法和要点,但繁杂抽象的代谢反应和代谢调节使本章的教与学仍然存在很大的挑战.我们在讲授这一章时,主要采用广泛联系的授课策略,并且采用比较、类比、记忆口诀等授课技巧,同时结合授课内容融入思政教育,获得了较为满意的教学效果.本章的教学策略与授课技巧也同样适用于生化课程的其他章节,希望能对同行们的教学工作有所启发和帮助.

目的:探讨医学生应对方式改善学习倦怠进而提高学习成绩的现象,并分析其原因.方法:以“基于问题学习”(Problem-based learning,PBL)为例,以北京大学2016级临床医学专业三年级学生为研究对象,课程前后应用“大学生学习倦怠调查量表”评估学习倦怠情况,课程结束后以“简易应对方式问卷”调查应对倾向,统计PBL课程结束后的考试成绩.PBL学习前后完成学习倦怠量表和应对方式问卷的学生共201人(78.82％),其中男生114人(56.7％),女生87人(43.3％).结果:相关性分析显示应对方式中的积极应对维度与PBL之后学习倦怠(r=-0.400,P＜0.001)及情绪低落(r=-0.366,P＜0.001)、行为不当(r=-0.312,P＜0.001)和成就感低(r=-0.351,P＜0.001)3个因子呈显著负相关,与学习成绩得分(r=0.180,P＜0.01)呈显著正相关;消极应对维度与学习倦怠(r=0.223,P＜0.01)及情绪低落(r=0.224,P＜0.01)、行为不当(r=0.204,P＜0.01)2个因子呈显著正相关,与成就感低和学习成绩无显著相关性.中介效应分析显示,积极应对维度对学习成绩的影响完全是通过学习倦怠发挥的作用,中介效应占比为62.01％.积极应对维度高分组学生,在PBL学习之后,学习倦怠尤其情绪低落因子显著减轻.结论:学生积极应对维度,可以通过减轻学习倦怠发挥提高学习成绩的作用.

高等教育各门课程的第一节课通常是绪论,用以介绍本门课程的学习目的、主要内容,授课安排、考核方式等.其讲授效果直接关系到学生对本门课程的兴趣.在所有医学院校以及设有生命科学相关专业的院校,《生物化学》都是非常重要的必修基础课程.由于生命体的组成物质结构复杂,种类繁多,物质代谢途径相互联系,学生在学习《生物化学》课程时普遍感到深奥难懂.良好的开端,是成功的一半,"课程绪论"在整门课程的授课中发挥着举足轻重的作用.本人在北京大学医学部为基础医学、临床医学、药学、护理学等多个专业主讲《生物化学》20余年.在绪论部分,除了介绍教学安排、课堂要求和考核方式等常规内容,还将动听的生化歌曲、丰富的教学资料、以及医学人文相关内容融入课堂.经实践多年,获得了较为满意的授课效果,希望能对同行们的生物化学教学有所启发和帮助.

BACKGROUND:Although the involvement of individual microRNA and lncRNA in the regulation of p21 expression has largely been evidenced, less is known about the roles of functional interactions between miRNAs and lncRNAs in p21 expression. Our previous work demonstrated that miR-509- 3-5p could block cancer cell growth.METHODS:To gain an insight into the role of miR-509-3-5p in the regulation of p21 expression, we performed in silico prediction and showed that miR-509-3-5p might target the NONHSAT112228.2, a sense-overlapping lncRNA transcribed by a non-code gene overlapping with p21 gene. Mutation and luciferase report analysis suggested that miR-509-3-5p could target NONHSAT112228.2, thereby blocking its expression. Consistently, NONHSAT112228.2 expression was inversely correlated with both miR-509-3-5p and p21 expression in cancer cells. Ectopic expression of miR-509-3-5p and knockdown of NONHSAT112228.2 both promoted proliferation and migration of cancer cells.RESULTS:Interestingly, high-expression of NONHSAT112228.2 accompanied by low-expression of p21 was observed in lung cancer tissues and associated with lower overall survival.CONCLUSION:Taken together, our study found a new regulatory pathway of p21, in which MiR-509-3-5p functionally interacts with NONHSAT112228.2 to release p21 expression. MiR-509-3-5p- NONHSAT112228.2 regulatory axis can inhibit the proliferation and migration of lung cancer cells.

Background Lung squamous cell carcinoma (LUSC) accounts up for approximately 30% of all lung cancers with a high mortality. The study was aimed at finding genes critical in the diagnosis and prognosis of LUSC. Materials and Methods The differentially expressed (DE) genes (DEGs) and DE lncRNAs (DELs) from 501 LUSC and 49 normal lung tissues, and DE miRNAs (DEMs) from 478 LUSC and 45 normal lung tissues were respectively obtained via the TCGA database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and co-expression network analyses were performed. Survival analysis and receiver operating characteristic curve of hub mRNAs were also analyzed. Competitive endogenous RNA networks of lncRNAs, miRNAs and mRNAs were constructed. Results A total of 5747 DEGs, 378 DEMs and 3141 DELs in LUSC were identified in LUSC. The DEGs including AUARK, CDK1, KIF11 and EXO1 were proven to be significant metastatic indicators in LUSC, and 2 DEGs were significantly associated with the survival in LUSC patients. Some genes might have connections with many other gene nodes through a co-expression network. Four lncRNAs, 2 mRNAs and 2 miRNAs were identified as the candidates for the competitive miRNA-mRNA-lncRNA network and might serve as prognostic markers in LUSC. Conclusions We identified the differentially expressed lncRNAs, miRNAs and mRNAs in LUSC, providing further insights into the molecular mechanism of LUSC tumorigenesis and the potential prognostic biomarkers or therapeutic targets for LUSC.

N6-甲基腺嘌呤(N6-methyladenosine,m6 A)是存在于多种RNA中的化学修饰方式,最常见于mRNA.RNA的m6 A含量和效应受到甲基转移酶(Writers)、去甲基酶(Erasers)和甲基化阅读蛋白(Readers)的动态调控.与DNA甲基化修饰和组蛋白修饰相似,它们都参与了多种生物学过程,并与多种疾病的发生发展相关.本文先简要综述m6 A修饰的动态过程及生物学功能,然后重点介绍m6 A修饰与心血管疾病关系的研究进展.

Lipid transport and ATP synthesis are critical for the progression of non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) forms complexes with NAFLD-relevant transcripts. It associates with intron 24 of Apob pre-mRNA, with the 3′UTR of Uqcrb , and with the 5′UTR of Ndufb6 mRNA, thereby regulating the splicing of Apob mRNA and the translation of UQCRB and NDUFB6. Hepatocyte-specific HuR knockout reduces the expression of APOB, UQCRB, and NDUFB6 in mice, reducing liver lipid transport and ATP synthesis, and aggravating high-fat diet (HFD)-induced NAFLD. Adenovirus-mediated re-expression of HuR in hepatocytes rescues the effect of HuR knockout in HFD-induced NAFLD. Our findings highlight a critical role of HuR in regulating lipid transport and ATP synthesis.

BACKGROUND:Problem-based learning (PBL), a pedagogical approach, is widely accepted in medical education. Manipulated by many factors, the internal motivation of learner is the most crucial determinant that affects the nature of the outcome, in which the influences of critical thinking (CT) remained elusive.METHODS:One hundred two third-year undergraduate medical students at Peking University were involved in this study. A Chinese version of the Critical Thinking Disposition Inventory (CTDI-CV) was used to assess the CT disposition, and the performance scores of students in PBL tutorials were compiled. A parametric bivariate correlation analysis was performed between the students' CT scores and their PBL average scores. The PBL scores were compared between the strong and weak CT disposition groups using independent t-test. The analysis of numerical data was conducted using SPSS 16.0.RESULTS:CT disposition of third-year undergraduate medical students at Peking University was at a positive level, with an average score of 297.72. The total CT scores had a positive correlation with the scores of the PBL performance and its five dimensions significantly. In the majority, students with Strong-CT disposition obtained higher scores in PBL tutorials compared with students with Weak-CT disposition. The performance of these two groups was significantly different in the Late-Half but not in the Early-Half PBL tutorials. Furthermore, a significant improvement was observed in the students with strong CT but not weak CT dispositions.CONCLUSION:CT disposition positively correlates to a students' PBL performance. Students with stronger CT dispositions perform better in the PBL process and obtain higher scores. Our work suggested that the open-mindedness of the CT disposition is the primary factor that determines the improvement of the preparation dimensions in the PBL process.

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.

Human lung cancer H1299 (p53-null) cells often display enhanced susceptibility to chemotherapeutics comparing to A549 (p53-wt) cells. However, little is known regarding to the association of DNA damage-response (DDR) pathway heterogeneity with drug sensitivity in these two cells. We investigated the DDR pathway differences between A549 and H1299 cells exposed to 8-chloro-adenosine (8-Cl-Ado), a potential anticancer drug that can induce DNA double-strand breaks (DSBs), and found that the hypersensitivity of H1299 cells to 8-Cl-Ado is associated with its DSB overaccumulation. The major causes of excessive DSBs in H1299 cells are as follows: First, defect of p53-p21 signal and phosphorylation of SMC1 increase S phase cells, where replication of DNA containing single-strand DNA break (SSB) produces more DSBs in H1299 cells. Second, p53 defect and no available induction of DNA repair protein p53R2 impair DNA repair activity in H1299 cells more severely than A549 cells. Third, cleavage of PARP-1 inhibits topoisomerase I and/or topoisomerase I-like activity of PARP-1, aggravates DNA DSBs and DNA repair mechanism impairment in H1299 cells. Together, DDR pathway heterogeneity of cancer cells is linked to cancer susceptibility to DNA damage-based chemotherapeutics, which may provide aid in design of chemotherapy strategy to improve treatment outcomes.

Objective To investigate the learning burnout in problem-based learning and its influential factors. Methods The third-year undergraduate medical students, including 8-year track and 5-year track in Peking University were involved in this study. The scores of student performance, tutor performance and case quality were collected after cases learning. The students' attitude in PBL performance were surveyed with 3 in-house designed questions. The Learning Burnout Scale for college students was used before and after PBL. Correlation was analyzed between the learning burnout and 4 factors of PBL. Multiple linear regression analysis was used to clarify the influential factors with the learning burnout scores as dependent variable. The analysis of numerical data was conducted by using SPSS 16.0. Results The average scores of learning burnout in third-year undergraduate medical students was 52.85, which indicated the learning burnout was at low to moderate level. Significant correlation was found between the scores of learning burnout and the scores of students, tutors, cases quality and the attitude to PBL. Multiple linear regression analysis results showed 2 factors were of significance, that is students' attitude to PBL and the performance in PBL. Conclusions The attitude to PBL and the performance of students in PBL were the key influential factors which exert a significant influence on learning burnout. Students training along with PBL should be improved in medical education. Key words: Problem-based learning; Learning burnout; Influential factors