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Elevated DLL3 in stomach cancer by tumor-associated macrophages enhances cancer-cell proliferation and cytokine secretion of macrophages

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Gastroenterology Report 2022年第1期10卷 322-334页

作者： Jian-Bin Ye Jun-Jie Wen Dan-Lin Wu Bing-Xin Hu Mei-Qun Luo Yan-Qing Lin Yun-Shan Ning Yan Li School of Laboratory medicine and Biotechnology Southern Medical UniversityGuangzhouGuangdongP.R.China Service Union Medicine Southern Medical UniversityZhuhaiGuangdongP.R.China

Background The notch signal pathway is important in the development of both tumor-associated macrophages(TAMs)and stomach cancer,but how Notch signaling affects TAMs in stomach cancer is barely understood.Methods The expressions of Notch1,Notch2,Notch3,Notch4,hes family bHLH transcription factor 1(Hes1),and delta-like canonical Notch ligand 3(DLL3)were detected by Western blot and the expressions of interleukin(IL)-10,IL-12,and IL1-b were detected using enzyme-linked immunosorbent assay after the co-culture of macrophages and stomach-cancer cells.The proliferation and migration of cancer cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scratch assay,respectively,and the cell cycle was detected using Annexin V/propidium iodide assay.The protein interactions with DLL3 were detected using co-immunoprecipitation and mass spectrometry.Results The co-culture of macrophages and stomach-cancer cells MKN45 and BGC823 could enhance cell proliferation accompanied by the activation of Notch1/Notch2 signaling and upregulation of DLL3.Notch signaling gamma-secretase inhibitor(DAPT)blocked this process.The overexpression of DLL3 in stomach-cancer cells could promote the proliferation of cancer cells,enhance the activation of Notch1/Notch2 signaling,induce the expression of IL-33,lead to the degradation of galectin-3–binding protein(LG3BP)and heat shock cognate 71 kDa protein(HSPA8),and result in elevated IL-1b,IL-12,and IL-10 secretion by macrophages.Higher expression of DLL3 or IL-33 could lead to a lower survival rate based on University of California,Santa Cruz Xena Functional Genomics Explorer and The Cancer Genome Atlas data set.Conclusions This is evidence that DLL3 regulates macrophages in stomach cancer,suggesting that DLL3 may be a novel and potential target for stomach-cancer therapy.

关键词： stomach cancer DLL3 macrophages Notch signaling,proliferation cytokines

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Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning Li Jun Gao Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of International Medical service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

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Myocarditis as an extraintestinal manifestation of ulcerative colitis:A case report and review of the literature

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World Journal of Clinical Cases 2022年第27期10卷 9750-9759页

作者： You-Yang Wang Wen Shi Jian Wang Yue Li Zhuang Tian Yang Jiao Department of General Internal medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Gastroenterology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Radiology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Cardiology and International Medical service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

BACKGROUND Although extraintestinal manifestations of inflammatory bowel disease(IBD) are well documented,myocarditis has only rarely been reported as an extraintestinal manifestation,and it can be fatal.The various clinical presentations and causes of myocarditis in IBD patients complicate making a correct and timely diagnosis.CASE SUMMARY Here we report a 15-year-old boy who presented with myocarditis as the initial presentation of a relapse of ulcerative colitis.In reviewing the literature for cases of myocarditis complicating IBD,we found 21 other cases,allowing us to expand our understanding of the clinical presentation,diagnosis,management,and outcomes of this rare condition.The most frequent diagnostic clues for myocarditis in IBD patients are dyspnea,chest pain,tachycardia,raised cardiac biomarkers,and abnormalities on trans-thoracic echocardiography.Additionally,we discuss the etiology of myocarditis in IBD patients,which include an extraintestinal manifestation,the adverse effects of mesalamine and infliximab,selenium deficiency,and infection,to help provide a framework for diagnosis and management.CONCLUSION Myocarditis as an extraintestinal manifestation of IBD can be life-threatening.Trans-thoracic echocardiogram and cardiac magnetic resonance may assist its diagnosis.

关键词： Inflammatory bowel disease Myocarditis Ulcerative colitis Crohn’s disease Extraintestinal manifestation Case report

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Establishment and evaluation of animal models of sepsis-associated encephalopathy

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World Journal of Emergency medicine 2023年第5期14卷 349-353页

作者： Mubing Qin Yanxia Gao Shigong Guo Xin Lu Qian Zhao Zengzheng Ge Huadong Zhu Yi Li Emergency Department State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China Emergency Department the First Affi liated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Rehabilitation medicine Southmead HospitalSouthmead RoadBristol BS105NBUK Health service Department of the Guard Bureau of the Joint Staff Department Beijing 100017China

BACKGROUND:Sepsis-associated encephalopathy(SAE) is a critical disease caused by sepsis.In addition to high mortality,SAE can also adversely aff ect life quality and lead to significant socioeconomic costs.This review aims to explore the development of evaluation animal models of SAE,giving insight into the direction of future research in terms of its pathophysiology and therapy.METHODS:We performed a literature search from January 1,2000,to December 31,2022,in MEDLINE,PubMed,EMBASE,and Web of Science using related keywords.Two independent researchers screened all the accessible articles based on the inclusion and exclusion criteria and collected the relevant data of the studies.RESULTS:The animal models for sepsis are commonly induced through cecal ligation and puncture(CLP) or lipopolysaccharide(LPS) injection.SAE can be evaluated using nervous reflex scores and sepsis evaluation during the acute phase,or through Morris water maze(MWM),openfield test,fear condition(FC) test,inhibitory avoidance,and other tests during the late phase.CONCLUSION:CLP and LPS injection are the most common methods for establishing SAE animal models.Nervous reflexs cores,MWM,FC test,and inhibitory avoidance are widely used in SAE model analysis.Future research should focus on establishing a standardized system for SAE development and analysis.

关键词： Sepsis Sepsis-associated encephalopathy Animal model Systematic review

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CHDbase:A Comprehensive Knowledgebase for Congenital Heart Disease-related Genes and Clinical Manifestations

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Genomics, Proteomics & Bioinformatics 2023年第1期21卷 216-227页

作者： Wei-Zhen Zhou Wenke Li Huayan Shen Ruby W.Wang Wen Chen Yujing Zhang Qingyi Zeng Hao Wang Meng Yuan Ziyi Zeng Jinhui Cui Chuan-Yun Li Fred Y.Ye Zhou Zhou State Key Laboratory of Cardiovascular Disease Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular DiseasesCenter of Laboratory MedicineFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China International Joint Informatics Laboratory&Jiangsu Key Laboratory of Data Engineering and Knowledge service School of Information ManagementNanjing UniversityNanjing 210023China Institute of Molecular medicine Peking UniversityBeijing 100871China

Congenital heart disease(CHD)is one of the most common causes of major birth defects,with a prevalence of 1%.Although an increasing number of studies have reported the etiology of CHD,the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice.We therefore developed CHDbase,an evidence-based knowledgebase of CHD-related genes and clinical manifestations manually curated from 1114 publications,linking 1124 susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes.Metadata such as the information of each publication and the selected population and samples,the strategy of studies,and the major findings of studies were integrated with each item of the research record.We also integrated functional annotations through parsing50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity.We further prioritized the significance of these CHD-related genes with a gene interaction network approach and extracted a core CHD sub-network with 163 genes.The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin.Overall,CHDbase provides a comprehensive and freely available resource to study CHD susceptibilities,supporting a wide range of users in the scientific and medical communities.CHDbase is accessible at http://***.

关键词： Congenital heart disease Congenital heart defect Database Genetics Classification

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Obstetric anesthesia in China:associated challenges and long-term goals

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Chinese Medical Journal 2020年第5期133卷 505-508页

作者： Jing Wu Shang-Long Yao Department of Anesthesiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Institute of Anesthesia and Critical Care medicine Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

China has recently experienced extraordinary development in medical care and has achieved both Millennium Development Goals 4 and 5.According to the 2012 China Medical and Health service White Paper,the pregnancyrelated mortality rate(pregnancy-related deaths per 100,000 live births;PRMR)in China dropped from 51.3 in 2002 to 26.1 in 2011.A subnational analysis of 2852 Chinese counties between 1996 and 2015 has demonstrated that PRMR has declined from 108.7 in 1996 to 21.8 in 2015,with an annualized rate of decline of 8.5%per year.[1]According to the 2018 National Medical service and Quality Safety Report,the PRMR in 2018 was 18.3 per 100,000 live births.In contrast,the PRMR in United States was 17.2 per 100,000 live births between 2011 and 2015.[2]

关键词： Millennium birth goals

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Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy

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Journal of Geriatric Cardiology 2019年第4期16卷 354-361页

作者： Pei-Pei LU Xu MENG Ying ZHANG Yan-Qi LI Shu WANG Li-Sheng LIU Wen WANG Yu-Ling LI Yu-Qing ZHANG Ai-Hua HU Xian-Liang ZHOU Li-Hong MA Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina Clinical Trial and Research Center Beijing Hypertension League InstituteChinese Hypertension LeagueBeijingChina Xinjiekou Community Health service Center BeijingChina Department of Traditional Chinese medicine Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.

关键词： Aging Ambulatory blood pressure monitoring Antihypertensive drugs Beta-blockers Diuretics

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Epidemiological data on acupuncture and physical and rehabilitation medicine in the European union

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Journal of Traditional Chinese medicine 2015年第4期35卷 478-482页

作者： María Victoria González-López-Arza Patrick Sautreuil Enrique Varela-Donoso Juan Rodríguez-Mansilla Elisa Garrido-Ardila Department of Medical-Surgical Therapy Medicine FacultyExtremadura University Neuro-orthopedic Rehabilitation service Rothschild Hospital Department of Physical medicine and Rehabilitation Medicine FacultyComplutense University

OBJETIVE: To know the prevalence of acupuncturists within physical and rehabilitation medicine specialists in Europe and their characteristics,as well as to analyze the pathologies treated and therapeutic techniques used.METHODS: This is a cross-sectional descriptive study based on a structured and closed questionnaire. The study was carried out from October 2011 to May 2014.RESULTS: A total of 115 specialists from 19 countries completed the questionnaire. The mean characteristics of the physical and rehabilitation medicine(PRM) specialists who are also acupuncturists in Europe were: women(62.6 %); mean age of47.91 years old; 4.20 years of physical and rehabilitation medicine school and 2.00 years of acupuncture training; 15.03 years of mean time of clinical practice as physical and rehabilitation medicine specialists and 10.42 years of experience as acupuncturists; 35.65 % had a doctorate(Ph D) degree,obtained at a mean age of 33.55 years old; working in a public hospital(80%); treating mainly neurological conditions(48.1%) and using mainly techniques such as kinesiotherapy(11.81%),orthosis(10.40%) and electrotherapy(9.92%). Acupuncture was applied by 32.2% of the participants mainly in musculoskeletal conditions(27.38%). A mean number of more than 20 patients a day were treated by47.04% of the specialists,being 41.8% of the patients(adults and children). Significant differences were found between the variables,acupuncture and gender(Pearson's correlation Index = 0.007).However,no differences were observed in relation to acupuncture and age,doctorate degree,years of clinical practice and workplace(all with P values >0.05).CONCLUSION: In the European area,physical and rehabilitation medicine specialists who are also acupuncturists are mainly female,middle-aged,with15 years of professional experience,Ph D holders,working in public hospitals,treating mainly neurological conditions with kinesiotherapy and acupuncture,and treating over 20 patients a day(adults and children) during a 7 h shift. Further epidemiological

关键词：针灸治疗康复医学欧洲联盟流行病学神经系统疾病博士学位平均年龄平均特性

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Impact of regional differences in stroke symptom awareness and low-income status on seeking emergency medical service in China

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Chinese Medical Journal 2021年第15期134卷 1812-1818页

作者： Jing Yuan Guang-Liang Shan Sheng-De Li Chun-Peng Gao Li-Ying Cui Bin Peng Department of Neurology Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China Department of Epidemiology and Statistics Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijingChina Disease Control and Prevention Office Dalian Municipal Central HospitalDalianLiaoning 116021China

Background:Unawareness of stroke symptoms and low income are two barriers that affect the seeking of emergency medical service(EMS).This study aimed to assess the effect of unawareness and low income on seeking EMS and to investigate the regional distribution of the unawareness and low-income status and their associations with failing to call EMS in China.Methods:A total of 187,723 samples from the China National Stroke Screening Survey was interviewed cross-sectionally.Four status of awareness and annual income were identified:unaware and low-income,unaware-only,low-income-only,and aware and regular income.The outcomes were whether they intended to call EMS or not.The regional distribution of each status and their associations with not calling EMS were presented.Results:The status of unaware and low-income,unaware-only,and low-income-only accounted for 6.3%(11,806/187,673),11.9%(22,241/187,673),and 21.5%(40,289/187,673)of the total sample,respectively.Not calling EMS was significantly associated with the status of unaware and low-income(odds ratio[OR]:3.21,95%confidence interval[Cl]:3.07-3.35),unaware-only(OR:2.38,95%Cl:2.31-2.46),and low-income-only(OR:1.67,95%Cl:1.63-1.71),compared with the aware and regular income status.The Midwest regions had higher percentages of people in the unaware and low-income status;the East,South,and Central had higher percentages of unaware-only status;the North and Northeast regions had a higher percentage of low-income-only status,compared with other regions.Conclusion:The existence of the regional difference in unawareness and low income justifies the specific stroke education strategies for the targeted regions and population.

关键词： Stroke Cerebrovascular disease Awareness Income Emergency medical service Developing countries

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Resuscitation fluids as drugs:targeting the endothelial glycocalyx

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Chinese Medical Journal 2022年第2期135卷 137-144页

作者： Guangjian Wang Hongmin Zhang Dawei Liu Xiaoting Wang Chinese Critical Ultrasound Study Group Department of Critical Care medicine Peking Union Medical College HospitalPeking Union Medical College&Chinese Academy of Medical SciencesBeijing 100730China

Fluid resuscitation is an essential intervention in critically ill patients,and its ultimate goal is to restore tissue perfusion.Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions,hypoperfusion,shock,and so forth,leading to disturbed microcirculatory perfusion and organ dysfunction.Therefore,maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy.Like drugs,however,different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx.The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx.Many animal studies have shown that normal saline might be associated with glycocalyx degradation,but clinical studies have not confirmed this finding.Hydroxyethyl starch(HES),rather than other synthetic colloids,may restore the glycocalyx.However,the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies.Some studies have suggested that albumin may restore the glycocalyx,whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation.Notably,most studies did not correct the effects of the infusion rate or fluid volume;therefore,the results of using balanced crystalloids remain unclear.Moreover,mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity,and this still requires confirmation by high-quality clinical studies.

关键词： Fluid resuscitation Resuscitation fluid Fluid therapy Endothelial glycocalyx Glycocalyx

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