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Chinese medical Journal 2024年第8期137卷 883-886页

作者： Xiaoshuang Wang Jing Wang Tao Cheng institute of Basic medical Sciences Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

The institute of Basic medical Sciences(IBMS)is a global leader in biomedical research and advanced medical *** year(2023)marks the 65^(th)anniversary of its foundation at the Chinese Academy of medical Sciences(CAMS)and School of Basic Medicine(SBM)of the Peking Union medical College(PUMC).In the beginning,the IBMS and SBM incorporated the premedical departments of the PUMC,which was established by the Rockefeller Foundation in *** then,these departments have been committed to undertakingrstrate medical science research in China.

关键词： Basic IBMS foundation

Construction of Simple Modules over the Quantum Affine Space

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Algebra Colloquium 2024年第1期31卷 1-10页

作者： Snehashis Mukherjee Sanu Bera School of Mathematical Sciences Ramakrishna mission Vivekananda Educational and Research institute Belur Math HowrahWest Bengal 711202India

The coordinate ring O_(q)(K^(n))of quantum affine space is the K-algebra presented by generators x_(1),...,x_(n) and relations x_(i)x_(j)=q_(ij)a_(j)a_(i) for all i,*** construct simple O_(q)(K^(n))-modules in a more general setting where the parameters qij lie in a torsion subgroup of K^(*)and show that analogous results hold as in the uniparameter case.

关键词： simple module quantum affine space quantum torus polynomial identity algebra

The value of toxicological analysis in acute poisoning patients with uncertain exposure histories:a retrospective and descriptive study from an institute of poisoning

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World Journal of Emergency Medicine 2024年第2期15卷 98-104页

作者： Qifang Shi Gen Ba Zhenyu Xia Zhengsheng Mao Hao Sun Jinsong Zhang institute of Poisoning Nanjing Medical UniversityNanjing 211100China Department of Emergency Medicine the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Forensic Medicine Nanjing Medical UniversityNanjing 211166China The Key Laboratory of Modern Toxicology of Ministry of Education Nanjing Medical UniversityNanjing 211166China

BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison *** aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis ***:This was a retrospective and descriptive study from an institute of *** registration information and test reports spanning the period from April 1,2020 to March 31,2022,were *** with uncertain exposure histories and who underwent toxicological analysis were *** manifestations and categories of toxics were ***:Among the 195 patients with positive toxicological analysis results,the main causes of uncertain exposure history was disturbance of consciousness(62.6%),unawareness(23.6%)and unwillingness or lack of cooperation(13.8%).The predominant clinical manifestations were disturbed consciousness(62.6%),followed by vomiting and nausea(14.4%)and liver function abnormalities(8.7%).A comparison of clinical manifestations between patients with positive and negative(n=99)toxicological analyses results revealed significantly different proportions of disturbances in consciousness(63%vs.21%),dizziness(1.5%vs.5.1%),multi-organ failure(1.5%vs.7.1%),and local pain(0 vs 4%).The main categories of substances involved were psychiatric medications(23.1%),sedatives(20.5%),insecticides(13.8%),and herbicides(12.8%).CONCLUSION:The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific,and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.

关键词： Acute poisoning Toxic exposure Toxicological analysis Clinical manifestation

Movement Trend Alterations in the Periaqueductal Gray(PAG)-Employed Ratbot Navigation Are Correlated with Stimulation Parameters

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Journal of Bionic Engineering 2024年第2期21卷 866-876页

作者： Sina Khajei Abed Khorasani Mohammad Reza Afarinesh Vahid Sheibani Neuroscience Research Center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran Cognitive Neuroscience Research Center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran

In previous studies,Periaqueductal Gray(PAG)stimulation was used to stop ratbots from *** to the homology between the PAG and the intercollicular nucleus,which has been used for forward movement in birds,we investigated the possibility of PAG application to induce forward locomotion for the first *** a corridor maze,the traveled distances via PAG electrical stimulation were examined in nine Wistar male rats during three sessions.A custom-designed stimulator was developed to apply the *** results showed reductions in responses to stimulation over ***,the traveled distances had negative slopes during the consecutive trials(in 8 out of the 9 rats),and the slope mean was significantly different from *** was a strong correlation between the stimulation parameters(electric Charge per Phase(CPP)and the Number of Pulses(NP))and the observed *** negative Movement Slopes(MS)were highly correlated with the CPP and the NP,as the Pearson's linear correlation coefficients were−0.87 and−0.79,*** MS-CPP coefficients of determination(R-squared)were also between 0.76 and *** addition,the MS-NP coefficients of determination were between 0.63 and ***,it is concluded that the electrical stimulation parameters influence the behavioral outcomes ***,the PAG area may be considered a suitable candidate for forward locomotion control in the future if the area is harnessed effectively to prevent undesirable chaotic behaviors.

关键词： Periaqueductal Gray(PAG) Navigation Ratbot Animal-robot Forward locomotion Movement slope

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon Kim Deok Ryong Kim Department of Biochemistry and Convergence medical Sciences and institute of medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea Department of Anatomy and Convergence medical Sciences and institute of medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

Neg-Entropy Mechanism as a Target for Natural Medicines

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Engineering 2024年第7期38卷 11-12页

作者： Tian-Le Gao Hui-Hui Guo Jian-Dong Jiang institute of Materia Medica Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Current strategies for drug discovery research mainly focus on molecular targets,in which structure biology plays a central role,such as the detailed mechanism of a drug-target *** principle of this approach is the presumed molecular mechanism or genetic background of the disease being *** this approach has brought progress in understanding the mode of action for some drugs,most prevalent illnesses-especially chronic diseases-are multifactorial and present with a group of symptoms,as is often the case in cardiovascular diseases,metabolic disorders,cancers,and so *** newly emerging term“multi-morbidity”(i.e.,multiple co-occurring diseases)describes a grand challenge for this strategy,and successful drug intervention for multimorbidity should be multifaceted[1].So,our research team has shifted its attention to a new direction that views the disease as a whole instead of a single-molecule abnormality,and focusing on drugs with multiple targets.

关键词： drugs diseases cardiovascular

Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

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Neural Regeneration Research 2024年第9期19卷 2010-2018页

作者： Yan Wang Dai Li Lan Zhang Zhenyu Yin Zhaoli Han Xintong Ge Meimei Li Jing Zhao Shishuang Zhang Yan Zuo Xiangyang Xiong Han Gao Qiang Liu Fanglian Chen Ping Lei Department of Geriatrics Tianjin Medical University General HospitalTianjinChina Tianjin Geriatrics institute Tianjin Medical University General HospitalTianjinChina Tianjin Neurological institute Tianjin Medical University General HospitalTianjinChina

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain ***,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains *** this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of *** found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum ***,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured ***,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly *** findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum ***,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

关键词： apoptosis C/EBP homologous protein endoplasmic reticulum stress exosome inositol-requiring enzyme 1α microglia miR-124-3p neuron repetitive mild traumatic brain injury X-box binding protein 1

Resurgence of measles virus infection in an eliminated country, Sri Lanka

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Asian Pacific Journal of Tropical Medicine 2024年第5期17卷 208-213页

作者： Merennage Anusha Yasanthi Fernando Gankandage Prabhath Chathuranga Kaanthaka Gunaradha Abeygunasekara Dedunu Dias Weligamage Janaki Indira Abeynayake Department of medical Microbiology and Immunology Faculty of MedicineUniversity of ColomboSri Lanka Department of Virology Medical Research InstituteColombo 08Sri Lanka Department of medical Administration Medical Research InstituteColombo 08Sri Lanka

Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the ***:This retrospective study analyzed all samples tested for measles from 1st of May to 30th of November,2023 at National Measles Rubella Laboratory,Sri *** to the World Health Organization(WHO)algorithm,serum and oropharyngeal/nasopharyngeal swabs were tested with WHO recommended kits for anti-measles IgM and measles virus specific RNA,*** RNA positive samples were sequenced at reference laboratory,*** of sequencing data and construction of phylogenetic tree were carried out at National Measles Rubella *** was analyzed using descriptive ***:Of the total 1132 serum samples and 497 oropharyngeal/nasopharyngeal swabs from 1326 patients,657(49.5%)patients were confirmed as measles by anti-measles IgM,measles virus specific RNA or ***(55.6%,n=365)and the age group from>20 to≤30 years(33.0%,n=217)predominated positive *** provinces reported measles positive *** samples sequenced(100%,n=42)were genotype D8 with 95.2%(n=40)bearing *** ***:We described resurgence of measles in an eliminated country,confirming the genotype to be D8,one of the two genotypes currently circulating ***,the study strongly convinced the importance of a strengthened virological surveillance system in an eliminated country,despite its eliminated status.

关键词： Measles elimination Resurgence of measles Sri Lanka Genotype D8 National Measles Rubella Laboratory

Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1230-1243页

作者： Jun Zhou Jiaqi Liu Bingjing Wang Nan Li Juan Liu Yanmei Han Xuetao Cao institute of Immunology Zhejiang University School of MedicineHangzhou 310058China National Key Laboratory of Immunity and Inflammation Institute of ImmunologyNaval Medical UniversityShanghai 200433China Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100005China institute of Immunology College of Life SciencesNankai UniversityTianjin 300071China

Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against *** cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains *** can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune *** we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell ***-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against Listeria monocytogenes(L.m.)***,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon *** in ***,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of *** in *** transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory ***,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against *** study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

关键词： impaired immunity spleen