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O08 Problem-based learning in the school of basic medical sciences, Peking University

中国药理通讯 2006年第2期23卷 7-8页

作者： Jiang Gu Xuejun Li You Wen Chunyan Chou Hong Zhu School of Basic Medical Sciences Beijing University Beijing China

In order to enhance the self learning ability of medical students and to stimulate their interests in basic medical science subjects, the School of Basic Medical Sciences, Peking University experienced with problem-based learning (PBL) in its teaching of the third year medical students. Ten teaching topics were selected and they were taught over a three-semester period. They consisted of arteriosclerosis, diabetes, cancer, AIDS, SARS, hepatitis. Each topic was taught for 2 weeks by a group of teaching faculty members across different disciplines including clinicians led by a professor in the most relevant field. We condensed the previous teaching schedule of traditional content and used 20 weeks to conduct the above PBL. The ten topics were taught in a similar manner but considerable freedom was given to faculty members in determining the content and the manner in which the teaching activity was organized and executed. For most of the topics, the teaching plan consisted of an introductory lecture of the general concept of the topic, presentation of a case or cases of patients related to the subject, student research of the literature and group discussion of the subjects. The students then made presentations on the topic in small student groups. After initial presentation, professors and physicians who are very familiar with the subject gave in-depth lectures on the topics and conduct question and answer sessions. A representative from each group was then presented in a larger group. The best presenters selected by the students and the teachers then made presentations in front of the whole class of about 100 -200 students. Questions and debates were encouraged after each presentation. All activities were guided by at least one professor. Finally, the students were asked to write brief theses about their opinions on the subjects. The performances of the students were graded according to their activities and performance in class and during discussions. Motivation and creativity in presentation, discussion and thesis

关键词：学习方法医学研究北京大学药理学

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Protecting People from Tobacco Smoke in China: Current Status and Challenges

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China CDC weekly 2022年第21期4卷 460-464页

作者： Xia Wan Institute of basic medical sciences Chinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeBeijingChina

Over the past two years,many people have encountered difficulties because of the advent of coronavirus disease 2019(COVID-19).The COVID-19 pandemic has unleashed many concerns,such as social isolation and loneliness,drastic changes to lifestyles,uncertainty for the future,and financial pressure.Some people reported smoking more than usual to reduce stress or loneliness(1),which made more people vulnerable to be exposed to second-hand tobacco smoke(SHS).As we know there is no safe level of exposure to SHS,and even brief exposure can cause harm(2).Under this circumstance,it is quite meaningful to reiterate the topic of protecting people from the harms of SHS.

关键词： smoke meaningful exposure

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The Association between Exposure to Second-Hand Smoke and Disease in the Chinese Population: A Systematic Review and Meta-Analysis

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Biomedical and Environmental sciences 2023年第1期36卷 24-37页

作者： WANG Yu Tong HU Kui Ru ZHAO Jian AI Fei Ling SHI Yu Lin WANG Xue Wei YANG Wen Yi WANG Jing Xin AILiMei WAN Xia Department of Epidemiology and Biostatistics Institute of Basic Medical SciencesChinese Academy of Medical Sciences/School of Basic MedicinePeking Union Medical CollegeBeijing 100005China

Objective To analyze the association between exposure to second-hand smoke(SHS) and 23 diseases,categorized into four classifications, among the Chinese population.Methods We searched the literature up to June 30, 2021, and eligible studies were identified according to the PECOS format: Participants and Competitors(Chinese population), Exposure(SHS),Outcomes(Disease or Death), and Study design(Case-control or Cohort).Results In total, 53 studies were selected. The odds ratio(OR) for all types of cancer was 1.79(1.56–2.05), and for individual cancers was 1.92(1.42–2.59) for lung cancer, 1.57(1.40–1.76) for breast cancer, 1.52(1.12–2.05) for bladder cancer, and 1.37(1.08–1.73) for liver cancer. The OR for circulatory system diseases was 1.92(1.29–2.85), with a value of 2.29(1.26–4.159) for stroke. The OR of respiratory system diseases was 1.76(1.13–2.74), with a value of 1.82(1.07–3.11) for childhood asthma. The original ORs were also shown for other diseases. Subgroup analyses were performed for lung and breast cancer. The ORs varied according to time period and were significant during exposure in the household;For lung cancer, the OR was significant in women.Conclusion The effect of SHS exposure in China was similar to that in Western countries, but its definition and characterization require further clarification. Studies on the association between SHS exposure and certain diseases with high incidence rates are insufficient.

关键词： Second-hand smoke Chinese population Cancer Diseases of the respiratory system Diseases of the circulatory system Systematic review Meta-analysis

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Evaluating the Quality of Case-control Studies involving the Association between Tobacco Exposure and Diseases in a Chinese Population based on the Newcastle-Ottawa Scale and Post-hoc Power

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Biomedical and Environmental sciences 2022年第9期35卷 861-866页

作者： SHI Yu Lin ZHAO Jian AI Fei Ling WANG Yu Tong HU Kui Ru WANG Xue Wei YANG Wen Yi WANG Jing Xin AI Li Mei WAN Xia Department of Epidemiology and Biostatistics Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China

According to the 2017 Global Burden of Disease Study,smoking is among the four leading risk factors contributing to deaths and disability-adjusted life years(DALYs)in China.In the past 20 years,there has been a substa... 详细信息

关键词： China. Population life

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Updates on CRISPR-based gene editing in HIV-1/AIDS therapy

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Virologica Sinica 2022年第1期37卷 1-10页

作者： Zhihao Zhang Wei Hou Shuliang Chen Institute of medical Virology School of Basic Medical SciencesWuhan UniversityWuhan430071China

Although tremendous efforts have been made to prevent and treat HIV-1 infection,HIV-1/AIDS remains a major threat to global human health.The combination antiretroviral therapy(cART),although able to suppress HIV-1 replication,cannot eliminate the proviral DNA integrated into the human genome and thus requires lifelong treatment that may lead to various side effects.In recent years,clustered regularly interspaced short palindromic repeat(CRISPR)-associated nuclease 9(Cas9)related gene-editing systems have been developed and designed as effective ways to treat HIV-1 infection.However,new gene-targeting tools derived from or functioning like CRISPR/Cas9,including base editor,prime editing,SHERLOCK,DETECTR,PAC-MAN,ABACAS,pfAGO,have been developed and optimized for pathogens detection and diseases correction.Here,we summarize recent studies on HIV-1/AIDS gene therapy and provide more gene-editing targets based on studies relating to the molecular mechanism of HIV-1 infection.We also identify the strategies and potential applications of these new gene-editing technologies for HIV-1/AIDS treatment in the future.Moreover,we discuss the caveats and problems that should be addressed before the clinical use of these versatile CRISPR-based gene targeting tools.Finally,we offer alternative solutions to improve the practice of gene targeting in HIV-1/AIDS gene therapy.

关键词： HIV-1/AIDS CRISPR/Cas9 Gene editing Gene therapy

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Targeting macrophagic 17β-HSD7 by fenretinide for the treatment of nonalcoholic fatty liver disease

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Acta Pharmaceutica Sinica B 2023年第1期13卷 142-156页

作者： Xiaoyu Dong Yiting Feng Dongqin Xu Mengya Zhang Xiao Wen Wenhao Zhao Qintong Hu Qinyong Zhang Hui Fu Jie Ping Department of Pharmacology School of Basic Medical SciencesWuhan UniversityWuhan 430071China Department of Anatomy School of Basic Medical SciencesWuhan UniversityWuhan 430071China

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis.However,which molecule regulates macrophage polarization in NAFLD remains unclear.Herein,we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7(17β-HSD7)expression in hepatic macrophages concomitantly with elevated M1 polarization.Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet(HFD)for 6 weeks revealed that lipid metabolism pathways were notably changed.Furthermore,17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis,insulin resistance and liver injury.Mechanistically,17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content,thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines.In addition,to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD,fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity.Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production,and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages.In conclusion,our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.

关键词： Nonalcoholic fatty liver disease 17β-HSD7 Macrophage Cholesterol Insulin resistance Fenretinide

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Targeting macrophages in cancer immunotherapy

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1212-1232页

作者： Zhaojun Duan Yunping Luo Department of Immunology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijingChina Collaborative Innovation Center for Biotherapy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijingChina

Immunotherapy is regarded as the most promising treatment for cancers.Various cancer immunotherapies,including adoptive cellular immunotherapy,tumor vaccines,antibodies,immune checkpoint inhibitors,and small-molecule inhibitors,have achieved certain successes.In this review,we summarize the role of macrophages in current immunotherapies and the advantages of targeting macrophages.To better understand and make better use of this type of cell,their development and differentiation characteristics,categories,typical markers,and functions were collated at the beginning of the review.Therapeutic strategies based on or combined with macrophages have the potential to improve the treatment efficacy of cancer therapies.

关键词： immunotherapy cancer treatment

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A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第4期23卷 286-299页

作者： Xing DU Jingjing ZHANG Ling LIU Bo XU Hang HAN Wenjie DAI Xiuying PEI Xufeng FU Shaozhang HOU Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China Department of Clinical Pathology School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China

Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women.Lycium barbarum polysaccharide(LBP)is an extract from the fruits of the traditional Chinese herb,L.barbarum.LBP is a promising anticancer drug,due to its high activity and low toxicity.Although it has anticancer properties,its mechanisms of action have not been fully established.Ferroptosis,which is a novel anticancer strategy,is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species(ROS)accumulation.In this study,human breast cancer cells(Michigan Cancer Foundation-7(MCF-7)and MD Anderson-Metastatic Breast-231(MDA-MB-231))were treated with LBP.LBP inhibited their viability and proliferation in association with high levels of ferroptosis.Therefore,we aimed to ascertain whether LBP reduced cell viability through ferroptosis.We found that the structure and function of mitochondria,lipid peroxidation,and expression of solute carrier family 7 member 11(SLC7 A11,also known as x CT,the light-chain subunit of cystine/glutamate antiporter system X_(c)^(-))and glutathione peroxidase 4(GPX4)were altered by LBP.Moreover,the ferroptosis inhibitor,Ferrostatin-1(Fer-1),rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione(GSH)production,accumulation of intracellular free divalent iron ions and malondialdehyde(MDA),and down-regulation of the expression of x CT and GPX4.Erastin(x CT inhibitor)and RSL3(GPX4 inhibitor)inhibited the expression of x CT and GPX4,respectively,which was lower after the co-treatment of LBP with Erastin and RSL3.These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the x CT/GPX4 pathway.Therefore,LBP exhibits novel anticancer properties by triggering ferroptosis,and may be a potential therapeutic option for breast cancer.

关键词： Lycium barbarum polysaccharide Ferroptosis Breast cancer cells xCT Glutathione peroxidase 4(GPX4)

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The lymphatic drainage systems in the brain:a novel target for ischemic stroke?

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Neural Regeneration Research 2023年第3期18卷 485-491页

作者： Ying-Jie Wang Yan-Rong Sun Yan-Hong Pei Hao-Wen Ma Ya-Kun Mu Li-Hua Qin Jun-Hao Yan Department of Anatomy and Histology School of Basic Medical SciencesPeking UniversityBeijingChina

Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological diseases have been widely explored.The glymphatic system is a fluid drainage and waste clearance pathway that utilizes perivascular space and aquaporin-4 protein located in the astrocyte endfeet to provide a space for exchange of cerebrospinal fluid and interstitial fluid.The intramural periarterial drainage pathway drives the flow of interstitial fluid through the capillary basement membrane and the arterial tunica media.Meningeal lymphatic vessels within the dura mater are involved in the removal of cerebral macromolecules and immune responses.After ischemic stroke,impairment of these systems could lead to cerebral edema,accumulation of toxic factors,and activation of neuroinflammation,while restoration of their normal functions can improve neurological outcomes.In this review,we summarize the basic concepts of these drainage systems,including drainage routes,physiological functions,regulatory mechanisms,and detection technologies.We also focus on the roles of lymphatic drainage systems in brain injury after ischemic stroke,as well as recent advances in therapeutic strategies targeting these drainage systems.These findings provide information for potential novel strategies for treatment of stroke.

关键词： aquaporin-4 brain edema glymphatic system intramural periarterial drainage ischemic stroke lymphatic drainage meningeal lymphatic vessels neuroinflammation neurotoxicity

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N-methyl-D-aspartate receptor subunit 1 regulates neurogenesis in the hippocampal dentate gyrus of schizophrenia-like mice

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Neural Regeneration Research 2019年第12期14卷 2112-2117页

作者： Juan Ding Chun Zhang Yi-Wei Zhang Quan-Rui Ma Yin-Ming Liu Tao Sun Juan Liu Ningxia Key Laboratory of Cerebrocranial Diseases Institute of Basic Medical Sciences School of Basic Medical Sciences Ningxia Medical University

N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the N-methyl-D-aspartate receptor subunit 1 (NR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In N-methyl-D-aspartate-treated mice, N-methyl-D-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of NR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of NR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. N-methyl-D-aspartate could reverse the above changes. These results indicated that NR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting NR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the Ningxia medical University, China (approval No. 2014-014) on March 6, 2014.

关键词： nerve regeneration schizophrenia MK-801 N-methyl-D-aspartate neurogenesis N-methyl-D-aspartate receptor N-methyl-Daspartate receptor subunit 1 BrdU Ki67 hippocampal dentate gyrus hippocampal neurogenesis neural regeneration

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