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Neglected Mendelian causes of stroke in adult Chinese patients who had an ischaemic stroke or transient ischaemic attack

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Stroke & Vascular Neurology 2024年第3期9卷 194-201,I0001-I0103页

作者： Wei Li Hao Li Chaoxia Lu Jialu Zhao Huichun Xu Zhe Xu Braxton Mitchell Yong Jiang Hong-Qiu Gu Qin Xu Anxin Wang Xia Meng Jinxi Lin Jing Jing Zixiao Li Wanlin Zhu Zhigang Liang Mengxing Wang Yongjun Wang China National Clinical Research Center for Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina division of Endocrinology Diabetes and NutritionDepartment of MedicineUniversity of Maryland School of MedicineBaltimoreMarylandUSA department of Neurology Qindao University Medical College Affiliated Yantai Yuhuangding HospitalYantaiShandongChina Clinical Center for Precision medicine.in Stroke Capital Medical UniversityBeijingChina

Background and purpose Multiple factors play important roles in the occurrence and prognosis of ***,the roles of monogenic variants in all-cause ischaemic stroke have not been systematically *** aim to identify underdiagnosed monogenic stroke in an adult ischaemic stroke/transient ischaemic attack(TIA)cohort(the Third China National Stroke Registry,CNSR-III).Methods Targeted next-generation sequencing for 181 genes associated with stroke was conducted on DNA samples from 10428 patients recruited through *** genetic and clinical data from electronic health records(EHRs)were reviewed for completion of the diagnostic *** assessed the percentages of individuals with pathogenic or likely pathogenic(P/LP)variants,and the diagnostic yield of pathogenic variants in known monogenic disease genes with associated *** In total,1953 individuals harboured at least one P/LP variant out of 10428 ***,792(7.6%)individuals(comprising 759 individuals harbouring one P/LP variant in one gene,29 individuals harbouring two or more P/LP variants in different genes and 4 individuals with two P/LP variants in ABCC6)were predicted to be at risk for one or more monogenic diseases based on the inheritance ***,230 of 792 individuals manifested a clinical phenotype in the EHR data to support the diagnosis of stroke with a monogenic *** most diagnosed Mendelian cause of stroke in the cohort was cerebral autosomal dominant arteriopathy with subcortical infarcts and *** were no relationships between age or family history and the incidence of first symptomatic monogenic stroke in *** The rate of monogenic cause of stroke was 2.2%after reviewing the clinical *** reasons that Mendelian causes of stroke may be missed in adult patients who had an ischaemic stroke/TIA include a late onset of stroke symptoms,combination with common vascular risks and the absence of a promine

关键词： patients transient likely

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Ferritin and mortality in hemodialysis patients with COVID-19:A systematic review and meta-analysis

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Asian Pacific Journal of Tropical medicine 2024年第1期17卷 4-11页

作者： Ni Wayan Anantika Riani I Gde Raka Widiana Yenny Kandarini Nephrology division Department of Internal MedicineUdayana University/Udayana University HospitalBaliIndonesia Nephrology division Department of Internal MedicineUdayana University/Prof.Dr.I.G.N.G.Ngoerah General HospitalBaliIndonesia

Objective:To investigate the difference in serum ferritin levels between deceased and surviving regular hemodialysis patients with ***:We conducted a systematic search across four databases following the PRISMA statement *** reporting ferritin levels and mortality of regular hemodialysis patients with COVID-19 were *** the random-effects model,we performed a meta-analysis to determine the mean difference in serum ferritin levels between the studied groups,along with their corresponding 95%confidence *** meta-analysis was carried out using Review Manager 5.4 and Stata ***:A total of 1013 patients from seven studies were included in this *** meta-analysis showed higher mean serum ferritin in the deceased compared to surviving regular hemodialysis patients with COVID-19,with a mean difference of 449.43 ng/mL[95%CI(244.07,654.80),P<0.0001;I2=58%,P=0.003].Conclusions:Our study found a higher mean of serum ferritin levels in the deceased compared to surviving regular hemodialysis patients with COVID-19.

关键词： Ferritin Mortality Hemodialysis COVID-19 Inflammation

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New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

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Oncology Research 2024年第6期32卷 1021-1030页

作者： HYUNHO KIM UIJU CHO SOOK HEE HONG HYUNG SOON PARK IN-HO KIM HO JUNG AN BYOUNG YONG SHIM JIN HYOUNG KANG division of Medical Oncology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea department of Pathology St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea division of Medical Oncology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulKorea

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)*** cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival ***,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing ***:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with *** APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot *** blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B *** viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with ***:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with *** with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B *** treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B *** to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B ***:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR *** result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

关键词： Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC) Ataxia telangiectasia and Rad3-related(ATR) Bladder cancer DNA damage response DNA replication stress

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Risk factors for esophagogastric variceal-related poor outcomes in primary biliary cholangitis:A prospective cohort study

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iLIVER 2024年第1期3卷 30-37页

作者： Lin Han Huan Xie Xue-Mei Ma Xiao-Long Lu Jun Zhao Qing-Sheng Liang Zheng-Sheng Zou Jing-Feng Bi Bo Jin Ying Sun Senior department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China Senior department of infectious diseases medicine The Fifth Medical Center of PLA General HospitalBeijing 100039China Graduate School Medical School of Chinese PLABeijing 100039China

Background and aims:Esophagogastric varices(EGV)are common complications of primary biliary cholangitis(PBC).We examined the risk factors for variceal bleeding-related liver transplantation(LT)or ***:This prospective observational cohort study involved PBC in our hospital from 1 January 2005 to 1 January *** clinical endpoints were variceal bleeding-related LT and *** analysis was performed using the Kaplan-Meier estimate,cox regression analysis was performed to investigate risk ***:PBC with EGV had significantly shorter survival than those without(p?0.002).Endoscopic prophylaxis significantly improved poor outcomes in PBC with EGV(p1.2ULN at baseline,total bilirubin of>1.2ULN,aspartate aminotransferase(AST)of>2.3ULN after 1 year of ursodeoxycholic acid(UDCA)treatment,non-biochemical responders according to the Paris criteria,and no history of endoscopic *** PBC without EGV,risk factors included AST of>2.3ULN,INR of>1.2ULN at baseline,CHE of***:This study provides evidence that AST,INR and CHE are major risk factors for variceal bleedingrelated poor outcomes in *** PBC with EGV,a good biochemical response to UDCA and endoscopic prophylaxis may improve *** findings can aid for guiding initial PBC risk stratification and screening endoscopy in patients without EGV.

关键词： Primary biliary cholangitis Esophagogastric varices Ursodeoxycholic acid Liver transplant-free survival Endoscopic therapy Risk factors

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Natural medicine.can substitute antibiotics in animal husbandry:protective effects and mechanisms of rosewood essential oil against Salmonella infection

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Chinese Journal of Natural medicine. 2024年第9期22卷 785-796页

作者： WANG Lanqiao FANG Juan WANG Heng ZHANG Baoyu WANG Nan YAO Xinyu LI He QIU Jiazhang DENG Xuming LENG Bingfeng WANG Jianfeng TAN Wenxi ZHANG Qiaoling State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationInstitute of Zoonosisand College of Veterinary MedicineJilin UniversityChangchun 130062China Shenzhen Beichen Biotech Co. Ltd.Shenzhen 518057China department of Obstetrics and Gynecology The Second Hospital of Jilin UniversityChangchun 130041China

Aniba rosaeodora essential oil(RO) has been traditionally used in natural medicine.as a substitute for antibiotics due to its notable antidepressant and antibacterial properties. Salmonella, a prevalent pathogen in foodborne illnesses, presents a major challenge to current antibiotic treatments. However, the antibacterial efficacy and mechanisms of action of RO against Salmonella spp. remain underexplored. This study aims to elucidate the chemical composition of RO, evaluate its antibacterial activity and mechanisms against Salmonella in vitro, and further delineate its anti-inflammatory mechanisms in vivo during Salmonella infection. Gas chromatography-mass spectrometry(GC-MS) was utilized to characterize the chemical constituents of RO. The antibacterial activity of RO was assessed using minimal inhibitory concentration(MIC) and time-kill assays. Various biochemical assays were employed to uncover the potential bactericidal mechanisms. Additionally, mouse and chick models of Salmonella infection were established to investigate the prophylactic effects of RO treatment. RO exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacteria, with an MIC of 4 mg·mL^(-1) for Salmonella spp. RO treatment resulted in bacterial damage through the disruption of lipid and purine metabolism. Moreover, RO reduced injury and microbial colonization in infected mice and chicks. RO treatment also modulated the host inflammatory response by inhibiting proinflammatory pathways. In conclusion, our findings demonstrate that RO is effective against Salmonella infection, highlighting its potential as an alternative to antibiotics for antibacterial therapy.

关键词： Rosewood essential oil Salmonella Aniba rosaeodora Antibacterial effect Anti-inflammation Anti-infection

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Understanding acute kidney injury (AKI) in liver cirrhosis from the acute-on-chronic liver failure (ACLF) perspective

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 715-717页

作者： Jeong-Ju Yoo Sang Gyune Kim division of Gastroenterology and Hepatology Department of Internal MedicineSoonchunhyang University School of Medicine Bucheon HospitalBucheonKorea

In the field of hepatology,managing complications in patients with liver diseases is of paramount *** these,acute kidney injury(AKI)in patients with acute-on-chronic liver failure(ACLF)stands out due to its prevalence and significant impact on patient outcomes(1,2).AKI in ACLF differs substantially from AKI in simple liver cirrhosis in its clinical significance(3).AKI developed in ACLF is a manifestation of a multi-organ failure syndrome and is closely associated with a high mortality rate and severe complications.

关键词： Acute kidney injury(AKI) acute-on-chronic liver failure(ACLF) biomarker

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Lecanemab Unveiled:Exploring Alzheimer’s Treatment Advancements,Assessing Strengths,Limitations,and Its Therapeutic Landscape Position

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Biomedical and Environmental Sciences 2024年第4期37卷 428-431页

作者： VICTOR Abiola Adepoju OKECHUKWU Innocent Onyezue SAFAYET Jamil OLALEKAN John Okesanya DON Eliseo Lucero-Prisno Ⅲ department of HIV and infectious diseases Jhpiegoan affiliate of John Hopkins UniversityAbujaNigeria department of Prevention and Community Directorate APIN Public Health InitiativesAbujaNigeria department of Public Health Daffodil International UniversityDhaka-1216Bangladesh department of Public Health and Maritime Transport University of ThessalyVolosGreece department of Global Health and Development London School of Hygiene and Tropical MedicineLondonUnited Kingdom

In the ever-evolving landscape of Alzheimer’s treatment,lecanemab(Leqembi)has emerged as a promising *** conventional therapies that merely alleviate symptoms,lecanemab is a humanized monoclonal antibody with a distinct *** targets protofibrils,insoluble fibrils,amyloid oligomers,and soluble amyloid-beta protofibrils,which are known to be especially damaging to neurons,with high accuracy.

关键词： Alzheimer amyloid Therapeutic

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Impact of Atrial Septal Defect Closure on Mortality in Older Patients

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Congenital Heart Disease 2024年第1期19卷 93-105页

作者： Sipawath Khamplod Yodying Kaolawanich Khemajira Karaketklang Nithima Ratanasit division of Cardiology Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand Her Majesty Cardiac Center Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand department of medicine Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand

Background:Atrial septal defect(ASD)is a common form of adult congenital heart disease that can lead to long-term adverse outcomes if left *** closure of ASD has been associated with excellent outcomes and lower complication ***,there is limited evidence regarding the prognosis of ASD closure in older *** study aims to evaluate the mortality rates in older ASD patients with and without ***:A retrospective cohort study was conducted on patients aged 40 years or older with ASD between 2001 and *** were followed up to assess all-cause *** and multivariable analyses were performed to identify the predictors of mortality.A p-value of<0.05 was considered statistically signiﬁ***:The cohort consisted of 450 patients(mean age 56.6±10.4 years,77.3%female),with 66%aged between 40 and 60 years,and 34%over 60 *** the cohort,299 underwent ASD closure(201 with transcatheter and 98 with surgical closure).During the median follow-up duration of 7.9 years,51 patients *** unadjusted cumulative 10-year rate of mortality was 3%in patients with ASD closure,and 28%in patients without ASD closure(log-rank p<0.001).Multivariable analysis revealed that age(hazard ratio[HR]1.04,95%conﬁdence interval[CI]1.006–1.06,p=0.01),NYHA class(HR 2.75,95%CI 1.63–4.62,p<0.001),blood urea nitrogen(BUN)(HR 1.07,95%CI 1.03–1.12,p<0.001),right ventricular systolic pressure(RVSP)(HR 1.07,95%CI 1.003–1.04,p=0.01),and lack of ASD closure(HR 15.12,95%CI 5.63–40.59,p<0.001)were independently associated with ***:ASD closure demonstrated favorable outcomes in older ***,NYHA class,BUN,RVSP,and lack of ASD closure were identiﬁed as independent factors linked to mortality in this population.

关键词： Atrial septal defect congenital heart disease defect closure long-term survival mortality

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RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang Guan-Min Jiang Hao Wang department of Laboratory medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of Clinical medicine Shandong UniversityJinanChina Core Unit of National Clinical Research Center for Laboratory medicine HefeiChina Neurosurgical department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina department of Clinical Laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of *** studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of *** a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular *** be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological *** this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied *** regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial *** we highlight the regulation of RNA modifications on immunometabolism,further influencing immune *** all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted ***,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

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Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis

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Science China Life Sciences 2024年

作者： Xizi Luo Nan Zhang Yuntao Liu Beibei Du Xuan Wang Tianxu Zhao Bingqiang Liu Shishun Zhao Jiazhang Qiu Guoqing Wang State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of Education College of Basic Medicine Jilin University State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of Education College of Veterinary Medicine Jilin University College of Mathematics Jilin University Bioinformatic Lab School of Mathematics Shandong University department of Cardiology China-Japan Union Hospital Jilin University

The coronavirus disease 2019(COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) developed into a global health emergency. Systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors,patients who died during the hypercoagulable period of characteristic coagulation abnormality(CAC), and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

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