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Prognostic Factors Related to In-hospital Death in Children with Biliary Atresia:Analysis of a Nationwide Inpatient Database

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Journal of Clinical and Translational Hepatology 2023年第2期11卷 416-424页

作者： Yu Shi Yi-Zhou Jiang Guang-Peng Zhou Ying Shi Lan-Xia Gan Yuan-Yuan Kong Hai-Bo Wang Zhi-Jun Zhu Li-Ying Sun Liver Transplantation Center Beijing Friendship HospitalCapital Medical UniversityBeijingChina National Clinical Research Center for Digestive Diseases Beijing Friendship HospitalCapital Medical UniversityBeijingChina Department of Critical Liver Diseases Liver Research CenterBeijing Friendship HospitalCapital Medical UniversityBeijingChina Clinical Center for Pediatric Liver Transplantation Capital Medical UniversityBeijingChina National Clinical Research Center for Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical SciencesShenzhenGuangdong ProvinceChina China Standard medical Information Research Center ShenzhenGuangdongChina Clinical Trial Unit Precision Medicine InstituteFirst Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina

Background and Aims:Patients with biliary atresia(BA)are prone to hepatic decompensation,which might eventually lead to *** study aimed to identify the possible risk factors affecting in-hospital death in BA patients in ***:We collected data from the Hospital Quality Monitoring System,a national inpatient *** patients aged up to 2 years old with a diagnosis of BA were *** subjects were divided to three groups,including Kasai portoenterostomy(KP),liver transplantation(LT),and no *** regression with Firth’s method was performed to identify potential influencing variables associated with in-hospital ***:During the year 2013 to 2017,there were 14,038 pediatric admissions with a diagnosis of *** proportion of in-hospital death in pediatric BA admissions was 1.08%.Compared with patients under six months,there was a higher risk of in-hospital death for children aged six months to 1 year and 1–2 years *** signs,including cirrhosis,variceal bleeding,and hepatic encephalopathy,were significantly associated with the risk of in-hospital *** no surgery group,compared to those in Beijing and Shanghai,BA patients admitted in other districts had a lower risk of in-hospital death(OR=0.39,95%CI:0.21,0.70).However,in the LT group,patients admitted in other districts had a higher risk of in-hospital death(OR=9.13,95%CI:3.99,20.87).Conclusions:In-hospital survival remains unsatisfactory for pediatric BA patients with severe ***,more resources and training for BA treatment,especially LT,are essential for districts with poor medical care in the future.

关键词： Biliary atresia In-hospital death Liver transplantation Kasai portoenterostomy

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Decreases in Both the Seroprevalence of Serum Antibodies and Seroprotection against Japanese Encephalitis Virus among Vaccinated Children

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Virologica Sinica 2019年第3期34卷 243-252页

作者： Ran Wang Lyu Xie Na Gao Dongying Fan Hui Chen Peigang Wang Hongning Zhou Jing An Department of Microbiology School of Basic Medical Sciences. Chinese Capital Medical UniversityBeijing 100069China Yunnan Provincial Key Laboratory of Vector-borne Disease Control and Research Yunnan Institute of Parasitic DiseasesPu'er 665000China Center of Epilepsy Beijing Institute for Brain DisordersBeijing 100069China

The incidence of Japanese encephalitis(JE)has significantly decreased in China due to JE *** this study,we investigated the post-JE vaccination seroprevalence and protection provided by vaccinated sera against Japanese encephalitis virus(JEV)to elucidate the persistence and waning of antibodies to JEV among JE-SA14-14-2-vaccinated children.A total of 300 serum samples were collected from vaccinated children aged 3-10 years in Zhaotong,Yunnan,*** seroprevalence of anti-JEV antibodies was determined by enzyme-linked immune sorbent assay and plaque reduction neutralization *** highest seropositivity of 82%was observed in vaccinated children during the first 0.5-1.5 years after booster ***,the seropositivity began to decline and remained lower than the original level observed in the 0.5-1.5-year *** association was found between the waning of seroprevalence and elapsed time of the post-booster ***,the neutralizing antibody(nAb)titres gradually decreased over time,and the levels showed a positive correlation with the protective efficacy in *** finding suggests that nAbs play an important role in the antiviral process and that the nAb titre is an adequately credible parameter for evaluating the protective efficacy induced by the JE *** results provide data that clarify the persistence and waning of antibodies to JEV,which may help elucidate the pathogenesis of JE.

关键词： Japanese encephalitis virus(JEV) SA14-14-2 Seroprevalence Neutralizing antibodies Waning of antibody

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Genetic variation of TGF-BR2 as a protective genotype for the development of colorectal cancer in men

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World Journal of Gastrointestinal Oncology 2021年第11期13卷 1766-1780页

作者： Noyko Stanilov Antonia Grigorova Tsvetelina Velikova Spaska Angelova Stanilova Oncoplastic Unit University College London HospitalLondon NW12BUUnited Kingdom Department of Molecular Biology Immunology and Medical GeneticsMedical FacultyTrakia UniversityStara Zagora 6000Bulgaria Department of Clinical Immunology University Hospital LozenetzSofia 1407Bulgaria medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria

BACKGROUND The role of transforming growth factor beta(TGF-β)signaling,including both the cytokine and their receptors,in the etiology of colorectal cancer(CRC)has been of particular interest *** To investigate the association between promoter polymorphism in TGF-β receptor 2 TGF-BR2G^([-875])A with a CRC risk in a cohort of Bulgarian patients using a casecontrol gene association study approach,as well as the protein levels of TGF-β1 in the peripheral *** A cohort of 184 CRC patients and 307 sex and age-matched healthy subjects were recruited in the study.A genotyping of the TGF-BR2G^([-875])A(rs3087465)polymorphism was performed by primer-introduced restriction analysespolymerase chain reaction *** The frequency of TGF-BR2G^([-875])A genotype was decreased in male patients with CRC than in healthy men(31.3%vs 44.8%;P=0.058).Among males,the TGF-BR2G[-509]G genotype was related to a significantly increased risk of CRC development(OR=1.820,95%CI:0.985-3.362,P=0.055)than the GA+AA ***,TGF-BR2^([-875])*A-allele itself was rarer in men with CRC than healthy men(19.1%vs 26.9%,P=0.086)and was associated with a protective effect(OR=0.644;95%CI:0.389-1.066;P=0.086).Regarding the genotypes,we found that TGF-β1 serum levels were higher in GG genotype in healthy persons above 50 years than the CRC patients[36.3 ng/mL interquartile range(IQR)19.9-56.5 vs 22.4 ng/mL IQR 14.8-29.7,P=0.014].We found significant differences between higher levels of TGF-β1 serum levels in healthy controls above 50 years(GG genotype)and CRC patients(GG genotype)at the early stage(36.3 ng/mL IQR 19.9-56.5 vs 22.8 ng/mL IQR 14.6-28.6,P=0.037)and advanced CRC(36.3 ng/mL IQR 19.9-56.5 vs 21.6 ng/mL IQR 15.9-33.9,P=0.039).CONCLUSION In summary,our results demonstrated that TGF-BR2 AG and AA genotypes were associated with a reduced risk of CRC,as well as circulating levels of TGF-βcould prevent CRC development in a gender-specific ***,male carriers of TGF

关键词： Colorectal carcinoma Cytokine TGF-BR2 gene TGF-ΒR2G^([-875])A Single nucleotide polymorphism

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Atherosclerosis,its risk factors,and cognitive impairment in older adults

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Journal of Geriatric Cardiology 2020年第7期17卷 434-440页

作者： Yun-Li XING Michael A Chen Ying SUN Moni B Neradilek Xi-Ting WU Dai ZHANG Wei HUANG Yining CUI Qi-Qi YANG Hong-Wei LI Xue-Qiao ZHAO Department of Geriatrics and Gerontology Beijing Friendship HospitalCapital Medical UniversityBeijingChina Division of Cardiology University of WashingtonSeattleWAUSA The Mountain-Whisper-Light Statistics SeattleWAUSA Cardiovascular Center Beijing Friendship HospitalCapital Medical UniversityBeijingChina

Objective To examine the association of atherosclerotic cardiovascular disease(ASCVD)and its risk factors with cognitive impairment in older *** Six hundred and fourteen subjects,aged≥65 years,from one center(2016–2018)underwent clinical,laboratory assessments and the Montreal Cognitive Assessment(Mo CA).Using regression analysis,the relationship between ASCVD and its risk factors was evaluated in subjects with and without cognitive impairment(MoCA score<26).Results Older age(b=-1.3 per 5 years,95%CI:-1.7 to-0.9,P<0.001),history of stroke(b=-1.6,95%CI:-3.0 to-0.3,P=0.01),and myocardial infarction(MI;b=-2.2,95%CI:-3.6 to-0.8,P=0.003)were independently associated with lower MoCA scores,whereas more education(b=1.5 per 3 years,95%CI:1.1 to 1.9,P<0.001),higher body mass index(BMI;b=0.5 per 3 kg/m^2,95%CI:0.0 to 1.0,P=0.04),higher estimated glomerular filtration rate(eGFR;b=0.8 per 15 U,95%CI:0.1 to 1.4,P=0.03),left ventricular ejection fraction(LVEF;b=0.4 per 5%,95%CI:0 to 0.8,P=0.04)and statin use(b=1.3,95%CI:0.3 to 2.3,P=0.01)were associated with a higher MoCA *** impairment was independently associated with older age(OR=1.51 per 5 yrs,95%CI:1.28 to 1.79,P<0.001),less education(OR=0.55 per 3 years,95%CI:0.45 to 0.68,P<0.001),lower BMI(OR=0.78 per 3 kg/m^2,95%CI:0.62 to 0.98,P=0.03)and higher levels of high sensitivity c-reactive protein(hsCRP;OR=1.08 per 1 mg/L,95%CI:1.02 to 1.15,P=0.01).Conclusions Beyond age,cognitive impairment was associated with prior MI/stroke,higher hsCRP,statin use,less education,lower eGFR,BMI and LVEF.

关键词： Atherosclerosis Cognitive impairment Correlation Older adults Risk factors

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METTL7A-mediated m6A modification of corin reverses bisphosphonates-impaired osteogenic differentiation of orofacial BMSCs

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International Journal of Oral Science 2024年第3期16卷 528-538页

作者： Yizhou Jin Xiao Han Yuejun Wang Zhipeng Fan Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina Research Unit of Tooth Development and Regeneration Chinese Academy of Medical SciencesBeijingChina

Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic ***,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic *** knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion ***,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ***,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin ***98059(a selective ERK inhibitor)blocks the corin-mediated promotion *** regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion ***,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation *** conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK *** hope this brings new insights into future clinical treatments for BRONJ.

关键词： impaired cor mediated

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Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure

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International Journal of Oral Science 2023年第1期15卷 50-62页

作者： Wanhao Yan Xiao Lin Yiqian Ying Jun Li Zhipeng Fan Laboratory of Molecular Signaling and Stem Cells Therapy Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionCapital Medical University School of StomatologyBeijingChina Department of Dental Implant Center Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina Department of Oral Implantology Tianjin Stomatological HospitalSchool of MedicineNankai UniversityTianjinChina Research Unit of Tooth Development and Regeneration Chinese Academy of Medical SciencesBeijingChina

The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus(T2DM)is higher than that in nondiabetic *** due,in part,to the impaired function of bone marrow mesenchymal stem cells(BMSCs)from the jawbone marrow of T2DM patients(DM-BMSCs),limiting implant *** N6-methyladenine(m6A)is important for BMSC function and diabetes ***,it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance *** on the“m6A site methylation stoichiometry”of m6A single nucleotide arrays,we identified 834 differential m6Amethylated genes in DM-BMSCs compared with normal-BMSCs(N-BMSCs),including 43 and 790 m6A hypermethylated and hypomethylated genes,respectively,and 1 gene containing hyper-and hypomethylated m6A *** m6A hypermethylated sites were primarily distributed in the coding sequence,while hypomethylated sites were mainly in the 3’-untranslated *** largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21,*** F-PCR and real-time RTPCR results for the validation of erythrocyte membrane protein band 4.1 like 3,activity-dependent neuroprotector homeobox(ADNP),growth differentiation factor 11(GDF11),and regulator of G protein signalling 2 agree with m6A single nucleotide array results;ADNP and GDF11 m RNA expression decreased in ***,gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic *** study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.

关键词： patients impaired implantation

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Improved Fertility Following Enucleation of Intramural Myomas in Infertile Women

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Chinese medical Journal 2017年第14期130卷 1648-1653页

作者： Yu-Cui Tian Jian-Hong Wu Hong-Mei Wang Yin-Mei Dai Department of Perinatal Medicine Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100026 China Department of Gynecology Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100026 China Department of Minimal Invasive Gynecology Center Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100026 China

Background：The relationship between intramural myomas and fertility remains *** main debate rests on whether cavity-distorting intramural lnyomas （CDMs） adversely affect fertility more than *** aimed to compare the effects ofenucleating non-CDMs and CDMs on fertility improvement in females with unexplained ***：We prospectively recruited 83 women undergoing myomectomy for unexplained infertility with intramural myomas between June 2008 and November 2012 and classified them into non-CDMs group （n =45） and CDMs group （n =38）.We then compared postoperative infertility rates,spontaneous pregnancy rates,pregnancy outcomes,live birth rates,and obstetric *** continuous variables,we calculated the mean ± standard deviation,median and interquartile range,and analyzed the data using Student＇s t-test and the Mann-Whitney *** categorical variables,the Pearson＇s Chi-square test,the continuity correction test,and Fisher＇s exact test were ***：Patients＇ demographics and myoma characteristics were comparable between the two *** overall spontaneous pregnancy rate increased from 0% to 68.42% following *** postoperative infertility rate was significantly higher in the non-CDMs group than that in the CDMs group （50.00% vs.23.53%,t =5.579,P =0.018）,whereas the postoperative spontaneous pregnancy rate was significantly lower in the non-CDMs group than that in the CDMs group （47.62% vs.70.59%,t 4.067,P =0.044）.Compared with the enucleation ofnon-CDM,the enucleation of CDM patients was a protective factor for the fertility restoration （risk ratio [RR] =3.717,95% confidence interval [CI]：1.284-10.753,P =0.015）,although postoperative fertility restoration declined with age （RR =1.141,95% CI：1.005-1.295,P =0.041）.Conclusions：Intramural myomas are associated with impaired *** experiencing unexplained infertility,and possessing intramural myomas,have a better chance of conception following myomectomy,and t

关键词： Infertility Myoma Pregnancy Outcome Uterine Myomectomy

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Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma

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Cancer Biology & Medicine 2020年第3期17卷 726-739页

作者： Liang Wang Steven Mo Xin Li Yingzhi He Jing Yang Department of Hematology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine Beihang University and Capital Medical UniversityBeijing Tongren HospitalBeijing 100730China Nanning Life-Ontology Biotechnology Co. Ltd.Nanning 530000China Department of Hematology Zhujiang Hospital of Southern Medical UniversityGuangzhou 510280China

Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence *** heterogenous cell populations contribute to relapse remains to be ***:We performed single cell RNA sequencing(scRNA-seq)on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant *** identified 10 subpopulations comprising 4 malignant B cell subtypes,3 T cell subtypes,2 dendritic cell subtypes and 1 natural killer(NK)cell ***,we identified cell markers,including a series of genes associated with immune escape and drug *** addition,we explored the roles of these genes in the mechanism of immune escape and drug resistance,and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL ***:The major immune escape mechanisms of MCL included anti-perforin activity,decreased immunogenicity and direct inhibition of apoptosis and cell killing,as mediated by type I and II B *** drug resistance mechanisms of different cell clusters included drug metabolism,DNA damage repair,apoptosis and survival *** III B cells closely communicate with other *** key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic ***:This study investigated potential immune escape and drug resistance mechanisms in *** results may guide individualized treatment and promote the development of therapeutic drugs.

关键词： Cell heterogeneity immune escape mantle cell lymphoma multidrug resistance scRNA-seq

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Alterations of the Ca2＋ signaling pathway in pancreatic beta-cells isolated from db/db mice

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Protein & Cell 2014年第10期5卷 783-794页

作者： Kuo Liang Wen Du Jingze Lu Fei Li Lu Yang Yanhong Xue Bertil Hille Liangyi Chen Department of General Surgery XuanWu Hospital Capital Medical University Beijing 100053 China National Key Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Science Beijing 100101 China The State Key Laboratory of Biomembrane and Membrane Biotechnology Beijing Key Laboratory of CardiometabolicMolecular Medicine Institute of MolecuLar Medicine Peking University Beijing 100871 China Department of Physiology and Biophysics University of Washington School of Medicine Seattle WA 98195 USA

Upon glucose elevation, pancreatic beta-cells secrete insulin in a Ca2＋-dependent manner. In diabetic animal models, different aspects of the calcium signaling path- way in beta-cells are altered, but there is no consensus regarding their relative contributions to the development of beta-cell dysfunction. In this study, we compared the increase in cytosolic Ca2＊（[Ca2＊]~） via Ca2＋ influx, Ca2＊ mobilization from endoplasmic reticulum （ER） calcium stores, and the removal of Ca2＋ via multiple mechanisms in beta-cells from both diabetic db/db mice and non- diabetic C57BL/6J mice. We refined our previous quan- titative model to describe the slow [Ca2＋]i recovery after depolarization in beta-cells from db/db mice. According to the model, the activity levels of the two subtypes of the sarco-endoplasmic reticulum Ca2＋-ATPase （SERCA） pump, SERCA2 and SERCA3, were severely down-reg- ulated in diabetic cells to 65% and 0% of the levels in normal cells. This down-regulation may lead to a reduc- tion in the Ca2＋ concentration in the ER, a compensatory up-regulation of the plasma membrane Na＋/Ca2＋ exchanger （NCX） and a reduction in depolarizationevoked Ca2＋ influx. As a result, the patterns of glucosestimulated calcium oscillations were significantly different in db/db diabetic beta-cells compared with normal cells. Overall, quantifying the changes in the calcium signaling pathway in db/db diabetic beta-cells will aid in the development of a disease model that could provide insight into the adaptive transformations of beta-cell function during diabetes development.

关键词： diabetic beta-cells calcium signalingalterations SERCA pump db/db mice

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Dissemination of brain inflammation in traumatic brain injury

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Cellular & Molecular Immunology 2019年第6期16卷 523-530页

作者： Kaibin Shi Jianning Zhang Jing-fei Dong Fu-Dong Shi Departments of Neurology and Neurosurgery Tianjin Neurological InstituteTianjin Medical University General HospitalTianjin 300052China Center for Neuroinflammation Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China Department of Neurology Barrow Neurological InstituteSt.Joseph’s Hospital and Medical CenterPhoenixAZ 85013USA BloodWorks Northwest Research Institute Division of HematologyDepartment of MedicineSchool of MedicineUniversity of WashingtonSeattleWA 98195USA

Traumatic brain injury(TBI)is recognized as a global health problem due to its increasing occurrence,challenging treatment,and persistent impacts on brain *** cell death in patients with TBI swiftly causes inflammation in the injured brain areas,which is recognized as focal brain *** brain inflammation causes secondary brain injury by exacerbating brain edema and neuronal death,while also exerting divergent beneficial effects,such as sealing the damaged limitans and removing cellular *** evidence from patients with TBI and studies on animal models suggest that brain inflammation after TBI is not only restricted to the focal lesion but also disseminates to remote areas of the *** dissemination of inflammation has been detected within days after the primary injury and persists *** state of inflammation may be related to remote complications of TBI in patients,such as hyperthermia and hypopituitarism,and may lead to progressive neurodegeneration,such as chronic traumatic *** studies should focus on understanding the mechanisms that govern the initiation and propagation of brain inflammation after TBI and its impacts on post-trauma brain pathology.

关键词： disseminated brain inflammation traumatic brain injury microglia post-injury neurodegeneration

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