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Bioengineered skin organoids:from development to applications

Military Medical Research 2024年第3期11卷 449-466页

作者： Zi-Xuan Hong Shun-Tian Zhu Hao Li Jing-Zhi Luo Yu Yang Yang An Xi Wang Kai Wang Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China Department of Hepatopancreatobiliary Surgery the Third Affiliated Hospital of Soochow UniversityChangzhou 213000JiangsuChina Department of Plastic Surgery Peking University Third HospitalBeijing 100191China clinical Stem Cell Research Center Peking University Third HospitalBeijing 100191China State Key Laboratory of Cardiovascular Disease Fuwai HospitalBeijing 100037China Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease Capital Medical UniversityBeijing 100050China

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

关键词： Skin organoid Organoid generation Skin appendage Tissue engineering Disease modelling Regenerative medicine

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The impacts of gradually terminating nonpharmaceutical interventions for SARS-CoV-2:A mathematical modelling analysis

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Fundamental Research 2024年第2期4卷 401-411页

作者： Bin Wu Yuetian Yu Xing Lin Feng Medical Decision and Economic Group Department of PharmacyRen Ji HospitalSouth CampusSchool of MedicineShanghai Jiaotong UniversityShanghai 200000China Department of Critical Care medicine Ren Ji HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 200001China Department of Health Policy and Management School of Public HealthPeking UniversityBeijing 100191China

With the expansion of vaccination programs,the policy of terminating nonpharmaceutical interventions for preventing the SARS-CoV-2 pandemic should become more flexible.The current study investigated the clinical and economic outcomes of intervention policies combining nonpharmaceutical interventions and vaccination programs for dealing with the SARS-CoV-2 pandemic.An agent-based transmission model was adopted that describes how a SARS-CoV-2 virus spreads in the populations of China.The model inputs were derived from the literature and expert opinion.The following intervention policies were simulated:no intervention,strict nonpharmaceutical interventions,and nonpharmaceutical interventions for workplace,community,school and home gradually terminated by combining vaccination programs for specified age groups(vaccination age in years:20-60,20-70,20-80,≥20,≥10 and whole population).Cumulative infections and deaths in one calendar year,costs and quality-adjusted life years(QALYs)were measured.When the vaccination program was taken up in at least the≥20 years age group in all populations,nonpharmaceutical interventions for workplace and community settings could be gradually terminated because the cumulative number of infections wasschool and home settings could not meet the target even when the vaccination program had been taken up in all populations.When cumulative deaths were used as the endpoint,nonpharmaceutical interventions in workplace,community and school settings could be gradually terminated.Vaccine efficacy and coverage have substantial impacts.Terminating nonpharmaceutical interventions in workplace settings could produce the lowest cost when vaccination programs are taken up at least in the≥10 years age group;this method dominates most intervention strategies due to its lower costs and higher QALYs.According to our findings,nonpharmaceutical interventions might be gradually terminated in Chinese settings.

关键词： SARS-CoV-2 Nonpharmaceutical interventions Vaccination program Cumulative infections and deaths Economic outcomes

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Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

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Military Medical Research 2024年第2期11卷 287-307页

作者： Pan Luo Fu-Qiang Gao Wei Sun Jun-You Li Cheng Wang Qing-Yu Zhang Zhi-Zhuo Li Peng Xu Department of Joint Surgery Honghui HospitalXi'an Jiaotong UniversityXi'an 710054China Department of Orthopedics China-Japan Friendship HospitalBeijing 100029China Department of Orthopaedic Surgery of the Perelman school of medicine University of PennsylvaniaPhiladelphiaPA 19104USA school of Mechanical Engineering Sungkyunkwan UniversitySuwon 16419South Korea Department of Orthopaedic Surgery Peking University Third HospitalPeking UniversityBeijing 100191China Department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

关键词： Rheumatoid arthritis Fluorescent probe Imaging Diagnosis Biomarker

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Amplifying protection against acute lung injury: Targeting both inflammasome and cGAS-STING pathway by Lonicerae Japonicae Flos-Forsythiae Fructus drug pair

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Chinese Herbal medicines 2024年第3期16卷 422-434页

作者： Junjie Li Ming Dong Qing Yao Xu Dong Yuanyuan Chen Jincai Wen Yingjie Xu Zhixin Wu Xiaomei Zhao Ye Xiu Xiaoyan Zhan Zhaofang Bai Xiaohe Xiao Chengde Medical university Department of Hepatology The Fifth Medical Center of PLA General Hospital China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General Hospital National Key Laboratory of Kidney Diseases The Fifth Medical Center of PLA General Hospital school of Stomatology Heilongjiang Key Lab of Oral Biomedicine Materials and Clinical Application & Experimental Center for Stomatology EngineeringJiamusi University Southern Medical university

Objective:Acute lung injury(ALI) is characterized by inflammation and currently lacks an efficacious pharmacological intervention.The medicine combination of Lonicerae Japonicae Flos(LJF) and Forsythiae Fructus(FF) demonstrates combined properties in its anti-infective,anti-inflammatory,and therapeutic effects,particularly in alleviating respiratory symptoms.In previous studies,Chinese medicine has shown promising efficacy in lipopolysaccharides(LPS)-induced ALI.However,there have been no reports of LJF and FF pairing for lung injury.The aim of this study is to compare the efficacy of herb pair Lonicerae Japonicae Flos-Forsythiae Fructus(LF) with LJF or FF alone in the treatment of ALI,and to explore whether LJF and FF have a combined effect in the treatment of lung injury,along with the underlying mechanism involved.Methods:A total of 36 mice were divided into six groups(control,model,LJF,FF,LF,dexamethasone)based on the treatments they received after undergoing sham-operation/LPS tracheal instillation.H&E staining and pulmonary edema indexes were used to evaluate lung injury severity.Alveolar exudate cells(AECs) were counted based on cell count in bronchoalveolar lavage fluid(BALF),and neutrophil percentage in BALF was measured using flow cytometry.Myeloperoxidase(MPO) activity in BALF was measured using enzyme-linked immunosorbent assay(ELISA),while the production of IL-1β,TNF-α,and IL-6 in the lung and secretion level of them in BALF were detected by quantitative polymerase chain reaction(qPCR)and ELISA.The effect of LJF,FF,and LF on the expression of Caspase-1 and IL-1β proteins in bone marrow derived macrophages(BMDMs) supernatant was assessed using Western blot method under various inflammasome activation conditions.In addition,the concentration of IL-1β and changes in lactatedehydrogenase(LDH) release levels in BMDMs supernatant after LJF,FF,and LF administration,respectively,were measured using ELISA.Furthermore,the effects of LJF,FF and LF on STING and IRF3 phosphorylation in BMDMs were detected by West

关键词： acute lung injury BMDMs inflammasomes Lonicerae Japonicae Flos - Forsythia Fructus drug pair STING

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Mesenchymal stem cell-derived extracellular vesicles in skin wound healing:roles,opportunities and challenges

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Military Medical Research 2024年第3期11卷 400-429页

作者： Jia-Yi Ding Min-Jiang Chen Ling-Feng Wu Gao-Feng Shu Shi-Ji Fang Zhao-Yu Li Xu-Ran Chu Xiao-Kun Li Zhou-Guang Wang Jian-Song Ji Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research Institute of Imaging Diagnosis and Minimally Invasive Intervention Researchthe Fifth Affiliated Hospital of Wenzhou Medical UniversityZhejiangLishui 323000China Oujiang Laboratory(Zhejiang Lab for Regenerative medicine Vision and Brain Health)School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhou 325035ZhejiangChina clinical College of the Affiliated Central Hospital School of MedicineLishui UniversityLishui 323000ZhejiangChina Department of Overseas Education College Jimei UniversityXiamen 361021FujianChina Department of medicine II Internal MedicineCardio-Pulmonary Institute(CPI)Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Justus-Liebig University Giessen35392 GiessenGermany Pulmonary and Critical Care Department of Medicine VInternal MedicineInfectious Diseases and Infection ControlUniversities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Justus-Liebig University Giessen35392 GiessenGermany

Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or contusions.As such injuries are common to all human groups,they may at times represent a serious socioeconomic burden.Currently,increasing numbers of studies have focused on the role of mesenchymal stem cell(MSC)-derived extracellular vesicles(EVs)in skin wound repair.As a cell-free therapy,MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy.Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures,including the regeneration of vessels,nerves,and hair follicles.In addition,MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization,wound angiogenesis,cell proliferation,and cell migration,and by inhibiting excessive extracellular matrix production.Additionally,these structures can serve as a scaffold for components used in wound repair,and they can be developed into bioengineered EVs to support trauma repair.Through the formulation of standardized culture,isolation,purification,and drug delivery strategies,exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair.In conclusion,MSCderived EV-based therapies have important application prospects in wound repair.Here we provide a comprehensive overview of their current status,application potential,and associated drawbacks.

关键词： Mesenchymal stem cell(MSC) Extracellular vesicles(EVs) Wound repair Engineered nanoparticles

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Plant-based dietary patterns and risk of esophageal cancer:A prospective cohort study spanning 17 years

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Chinese Journal of Cancer Research 2024年第1期36卷 36-45页

作者： Xiaorui Zhang Feifan He Jiayue Li Ru Chen Xinqing Li Li Li Fen Liu Shaoming Wang Wenqiang Wei Department of Epidemiology and Health Statistics School of Public HealthBeijing Municipal Key Laboratory of Clinical EpidemiologyCapital Medical UniversityBeijing 100069China National Central Cancer Registry office National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

关键词： Esophageal cancer diet dietary pattern epidemiology nutrition prospective cohort study

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Insights from TARGET-seq:Inflammation drives TP53-mediated clonal evolution

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The Innovation 2024年第2期5卷 7-8页

作者： Yeqian Zhao Wenxuan Huo Yue Liang Xiaodong Mo Shanshan Pei Yanmin Zhao Bone Marrow Transplantation Center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou 311121China Institute of Hematology Zhejiang UniversityHangzhou 311121China peking university People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing 100044China

Approximately 10%–20%myeloproliferative neoplasms(MPNs)can progress into blast-phase MPNs,also termed secondary acute myeloid leukemias(sAMLs),presenting dismal prognoses.sAML exhibits a distinctive clinical and pathological profile compared to de novo AML,marked by a higher incidence of erythroid leukemias and reduced responsive to conventional chemotherapies,resulting in a median survival of approximately 6 months.TP53 alterations are prevalent adverse events in leukemic transformation(LT),occurring in around one-third of sAML subjects.

关键词： TP53 neoplasms alterations

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Oxidative stress-initiated one-carbon metabolism drives the generation of interleukin-10-producing B cells to resolve pneumonia

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Cellular & Molecular Immunology 2024年第1期21卷 19-32页

作者： Ying Fu Baichao Yu Qi Wang Zhou Lu Hushan Zhang Dan Zhang Feifei Luo Ronghua Liu Luman Wang Yiwei Chu Department of Immunology School of Basic Medical SciencesShanghai Key Laboratory of Medical Epigenetics and MetabolismInstitutes of Biomedical SciencesFudan UniversityShanghaiChina Zhongshan Hospital Institute of clinical Science Zhongshan HospitalShanghaiChina Zhaotong Health Vocational College ZhaotongYunnanChina Department of Digestive Diseases Huashan HospitalFudan UniversityShanghaiChina Shanghai fifth People’s Hospital Fudan UniversityShanghaiChina

The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains unknown.Using a Pseudomonas aeruginosa-induced pneumonia model,we reported that IL-10-producing B cells(IL-10+B cells)play a key role in spontaneously resolving infection-mediated inflammation.Accumulated cytosolic reactive oxygen species(ROS)during inflammation were shown to drive IL-10+B-cell generation by remodeling one-carbon metabolism.Depletion of the enzyme serine hydroxymethyltransferase 1(Shmt1)led to inadequate one-carbon metabolism and decreased IL-10+B-cell production.Furthermore,increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine(SAM),altering histone H3 lysine 4 methylation(H3K4me)at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B cells.Therefore,the one-carbon metabolism-associated compound ethacrynic acid(EA)was screened and found to potentially treat infectious pneumonia by boosting IL-10+B-cell generation.Overall,these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.

关键词： IL-10-producing B cell Reactive oxygen species One-carbon metabolism H3K4me Pneumonia

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Pathological diagnosis and immunohistochemical analysis of giant retrosternal goiter in the elderly: A case report

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World Journal of clinical Cases 2024年第3期12卷 643-649页

作者： Yong-Chang Meng Liu-Sheng Wu Ning Li Hong-Wei Li Jing Zhao Jun Yan Xiao-Qiang Li Peng Li Jiang-Qi Wei Department of Cardiothoracic Surgery Xinxiang First People's HospitalXinxiang 453000Henan ProvinceChina school of clinical medicine Tsinghua UniversityBeijing 100084China Graduate school Qinghai UniversityXining 810016Qinghai ProvinceChina Department of Pathology Xinxiang First People's HospitalXinxiang 453000Henan ProvinceChina Department of Thoracic Surgery Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina

BACKGROUND Elderly giant retrosternal thyroid goiter is a rare yet significant medical condition,often presenting clinical symptoms that can be confused with other diseases,posing diagnostic and therapeutic challenges.This study aims to delve into the characteristics and potential mechanisms of this ailment through pathological diagnosis and immunohistochemical analysis,providing clinicians with more precise diagnostic and treatment strategies.A 77-year-old male,was admitted to hospital with the chief complaint of finding a goiter in the semilunar month during physical examination,accompanied by dyspnea.Locally protruding into the superior mediastinum,the adjacent structure was compressed,the trachea was compressed to the right,and the local lumen was slightly narrowed.The patient was diagnosed with giant retrosternal goiter.Considering dyspnea caused by trachea compression,our department planned to perform giant retrosternal thyroidectomy.Immunohistochemical results:Tg(+),TTF-1(+),Calcitonin(CT)(I),Ki-67(+,about 20%),CD34(-).Retrosternal goiter means that more than 50%of the volume of the thyroid gland is below the upper margin of the sternum.As retrosternal goiter disease is a relatively rare disease,once the disease is diagnosed,it should be timely surgical treatment,and the treatment is more difficult,the need for professional medical team for comprehensive treatment.CONCLUSION The imaging manifestations of giant retrosternal goiter are atypical,histomorphology and immunohistochemistry can assist in its diagnosis.This article reviews the relevant literature of giant retrosternal goiter immunohisto-chemistry and shows that giant retrosternal goiter is positive for Tg,TTF-1,and Ki-67.

关键词： Giant retrosternal goiter Pathology Immunohistochemistry Case report

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang school of Life Sciences Shanghai UniversityShanghaiChina school of medicine Shanghai UniversityShanghaiChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New Drug Development and clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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