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Mutations and intron polymorphisms in voltage-gated sodium channel genes of different geographic populations of Culex pipiens pallens/ Culex pipiens quinquefasciatus in China

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贫困所致传染病(英文) 2024年第2期13卷 1-11页

作者： Li Wenyu Ma Delong Mu Qunzheng Zhou Xinxin Hua Dongdong Zhao Chunchun Liu Qiyong Wang Jun Meng Fengxia state Key Laboratory of Infectious disease Prevention and Control Department of Vector Biology and Control National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention WHO Collaborating Centre for Vector Surveillance and Management Beijing People’s Republic of China Ningxia center for disease Prevention and Control YinChuan NingXia People’s Republic of China Jinan shizhong center for disease Control and Prevention Jinan Shandong China Vanke school of Public Health Tsinghua University Beijing People’s Republic of China Weifang No. People’s Hospital Weifang Shandong People’s Republic of China Beijing Daxing center for disease Control and Prevention Beijing People’s Republic of China Jinan second Maternal and Child Health Hospital Jinan Shandong China

Background Culex pipiens pallens andCulex pipiens quinquefasciatus are the dominant species ofCulex mosquitoes in China and important disease vectors. Long-term use of insecticides can cause mutations in the voltage-gated sodium channel (vgsc) gene of mosquitoes, but little is known about the current status and evolutionary origins ofvgsc gene in different geographic populations. Therefore, this study aimed to determine the current status ofvgsc genes inCx. p. pallens andCx. p. quinquefasciatus in China and to investigate the evolutionary inheritance of neighboring downstream introns of thevgsc gene to determine the impact of insecticides on long-term evolution.Methods sampling was conducted from July to september 2021 in representative habitats of 22 provincial-level administrative divisions in China. Genomic DNA was extracted from 1308 mosquitoes, the IIs6 fragment of thevgsc gene on the nerve cell membrane was amplified using polymerase chain reaction, and the sequence was used to evaluate allele frequency and knockdown resistance (kdr) frequency. MEGA 11 was used to construct neighborjoining (NJ) tree. PopART was used to build a TCs network.Results There were 6 alleles and 6 genotypes at the L1014 locus, which included the wild-type alleles TTA/L and CTA/L and the mutant alleles TTT/F, TTC/F, TCT/s and TCA/s. The geographic populations with akdr frequency less than 20.00% were mainly concentrated in the regions north of 38° N, and the geographic populations with akdr frequency greater than 80.00% were concentrated in the regions south of 30° N.kdr frequency increased with decreasing latitude. And within the same latitude, the frequency ofkdr in large cities is relatively high. Mutations were correlated with the number of introns. The mutant allele TCA/s has only one intron, the mutant allele TTT/F has three introns, and the wild-type allele TTA/L has 17 introns.Conclusions Cx. p. pallens andCx. p. quinquefasciatus have developed resistance to insecticides in most regions of China. The neighboring downstream i

关键词： Culex pipiens pallens Culex pipiens quinquefasciatus vgsc gene Mutation Frequency Intron Haplotype China

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Epidemiological Characteristics of Human Parainfluenza Viruses Infections-China,2019-2023

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China CDC weekly 2024年第12期6卷 235-241,I0003,I0004页

作者： Yixuan Gao Yingwei Ma Daxing Feng Feng Zhang Biao Wang Xiaoqing Liu Bing Zhu Hui Xie Linqing Zhao Xiaoru Long Ying Chen Bing Wang Jie Jiang Zhen Zhu Yan Zhang Aili Cui Baicheng Xia Naiying Mao National Key Laboratory of Intelligent Tracking and Forecasting for Infectious diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Precision Medicine research center Children’s Hospital of ChangchunChangchun CityJilin ProvinceChina Henan Provincial center for disease Control and Prevention Zhengzhou CityHenan ProvinceChina Laboratory of Viral diseases Qingdao Municipal Centre for Disease Control and PreventionQingdao CityShandong ProvinceChina Virus Laboratory Gansu Provincial Center for Disease Control and PreventionLanzhou CityGansu ProvinceChina Jiangxi Provincial center for disease Control and Prevention Nanchang CityGansu ProvinceChina Virus Laboratory Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina Institute for Immunization and Prevention Beijing Center for Disease Prevention and ControlAcademy for Preventive MedicineInstitute of Tuberculosis Control Research and PreventionBeijingChina Laboratory of Virology Beijing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBeijingChina Department of Infection Children’s Hospital of Chongqing Medical UniversityChongqingChina Inner Mongolia Autonomous Region Comprehensive center for disease Control and Prevention Hohhot CityInner Mongolia Autonomous RegionChina shenyang Prefecture center for disease Control and Prevention Shenyang CityLiaoning ProvinceChina

Introduction:A retrospective study based on sentinel surveillance was conducted in 10 provinciallevel administrative divisions(PLADs)in China to enhance the understanding of the epidemiological characteristics of human parainfluenza viruses(HPIVs).Methods:From January 2019 to June 2023,respiratory specimens were collected from individuals with acute respiratory infections(ARIs)and screened for four HPIVs serotypes and other common respiratory viruses using multiplex real-time polymerase chain reaction(PCR).This study analyzed the association of HPIVs infections with seasonal patterns,geographical distribution,demographic profiles,clinical features,and co-infection status.Results:During the study period,a total of 12,866 ARIs were included.The overall detection rate of HPIVs was 6.15%,varying from 5.04%in 2022 to 9.70%in 2020.The median age of HPIVs-infected patients was 3 years.HPIV2 was more prevalent among individuals aged 5–17 years(42.57%),while HPIV4 was more common in those over 65 years(12.24%).HPIV3(54.16%)and HPIV1(27.18%)were the predominant serotypes,and their prevalence exhibited significant seasonal fluctuations postcoronavirus disease 2019(COVID-19)pandemic.The peak of HPIV3 shifted three months later in 2020 compared to 2019 and returned to a summer peak thereafter.Two peaks of HPIV1 were observed in 2021 following the peak of HPIV3.Additionally,coinfections were frequent in HPIVs cases(overall rate:22.12%),with human rhinovirus being the most common co-infecting virus.Conclusions:The prevalence of HPIVs in China was predominantly due to HPIV3 and HPIV1,and their seasonal patterns were altered by pandemic restrictions.Hence,continuous surveillance of HPIVs is essential.

关键词： prevalence seasonal Human

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Circadian rhythm disruption and retinal dysfunction:a bidirectional link in alzheimer’s disease?

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Neural Regeneration research 2024年第9期19卷 1967-1972页

作者： Laura Carrero DesireéAntequera Cristina Municio Eva Carro Group of Neurodegenerative diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpainNetwork Center for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurobiology of alzheimer’s disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpainNetwork Centre for Biomedical Research in Neurodegenerative Diseases(CIBERNED)ISCIIIMadridSpain

Dysfunction in circadian rhythms is a common occurrence in patients with alzheimer’s disease.A predominant function of the retina is circadian synchronization,carrying information to the brain through the retinohypothalamic tract,which projects to the suprachiasmatic nucleus.Notably,alzheimer’s disease hallmarks,including amyloid-β,are present in the retinas of alzheimer’s disease patients,followed/associated by structural and functional disturbances.However,the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in alzheimer’s disease is not fully understood,although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.

关键词： alzheimer’s disease amyloid circadian rhythm neurodegeneration retina

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Current assessment and management of measurable residual disease in patients with acute lymphoblastic leukemia in the setting of CAR-T-cell therapy

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Chinese Medical Journal 2024年第2期137卷 140-151页

作者： Minghao Lin Xiaosu Zhao Yingjun Chang Xiangyu Zhao Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy.Common MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGs),and each method has advantages and limitations.It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse.Thus,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice.This review assesses the common and novel MRD assessment methods.In addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HsCT),as well as other therapeutic strategies to improve treatment effect.Furthermore,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

关键词： Measurable/minimal residual disease Acute lymphoblastic leukemia Chimeric antigen receptor-modified T-cell therapy Allogeneic hematopoietic stem cell transplantation Relapse

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Toward tuberculosis elimination by understanding epidemiologic characteristics and risk factors in Hainan Province, China

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Infectious diseases of Poverty 2024年第1期13卷 107-108页

作者： Changqiang Zhou Tao Li Jian Du Dapeng Yin Xiujun Li shixue Li Department of Biostatistics School of Public Health Cheeloo College of Medicine Shandong University Jinan People’s Republic of China National center for Tuberculosis Control and Prevention Chinese Center for Disease Control and Prevention Beijing People’s Republic of China Clinical center On TB Control Beijing Chest Hospital Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing People’s Republic of China Hainan center for disease Control and Prevention Haikou People’s Republic of China research center for Tuberculosis Control Shandong University Jinan People’s Republic of China

Background The disease burden of tuberculosis(TB)was heavy in Hainan Province,China,and the information on transmission patterns was limited with few studies.This atudy aims to further explore the epidemiological charac-teristics and influencing factors of TB in Hainan Province,and thereby contribute valuable scientific evidences for TB elimination in Hainan Province.Methods The TB notification data in Hainan Province from 2013 to 2022 were collected from the Chinese National disease Control Information system Tuberculosis surveillance system,along with socio-economic data.The spatial-temporal and population distributions were analyzed,and spatial autocorrelation analysis was conducted to explore TB notification rate clustering.In addition,the epidemiological characteristics of the cases among in-country migrants were described,and the delay pattern in seeking medical care was investigated.Finally,a geographically and tem-porally weighted regression(GTWR)model was adopted to analyze the relationship between TB notification rate and socio-economic indicators.The tailored control suggestions in different regions for TB elimination was provided by understanding epidemiological characteristics and risk factors obtained by GTWR.Results From 2013 to 2022,64,042 cases of TB were notified in Hainan Province.The estimated annual percent-age change of TB notification rate in Hainan Province from 2013 to 2020 was-6.88%[95%confidence interval(CI):-5.30%,-3.69%],with higher rates in central and southern regions.The majority of patients were males(76.33%)and farmers(67.80%).Cases among in-country migrants primarily originated from sichuan(369 cases),Heilongjiang(267 cases),Hunan(236 cases),Guangdong(174 cases),and Guangxi(139 cases),accounting for 53%.The majority(98.83%)of TB cases were notified through passive case finding approaches,with delay in seeking care.The GTWR analysis showed that gross domestic product per capita,the number of medical institutions and health personnel per 10,oo0 people were main factors affecting t

关键词： Tuberculosis Elimination Hainan Province China Epidemiological characteristics Geographically Temporally weighted regression

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soluble alpha-synuclein post-translational modifications:unexpected regulators of pathological alpha-synuclein amplification

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Neural Regeneration research 2024年第5期19卷 959-960页

作者： simran Kapila Yuhan sun Chao Peng shujing Zhang Department of Neurology David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Molecular Biology Institute Brain Research InstituteMary S.Easton Center for Alzheimer’s ResearchUniversity of CaliforniaLos AngelesCAUSA

The build-up of misfoldedα-synuclein(α-syn)in the central nervous system is the pathological hallmark of a number of neurodegenerative diseases that are known asα-synucleinopathies.These include Parkinson’s disease(PD),Parkinson’s disease with dementia(PDD),dementia with Lewy body(LB),multiple system atrophy(MsA),and a subset of alzheimer’s disease.Growing evidence underscores that the intercellular transmission and amplification of pathologicalα-syn are critical processes underlying the progression ofα-synucleinopathies(Peng et al.,2020),and as such,the study of these processes could lead to the identification of promising therapeutics to mitigate disease progression.Most previous studies have focused solely on pathological seeds in relation to disease progression.

关键词： pathological diseases

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The role of inflammasomes in human diseases and their potential as therapeutic targets

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signal Transduction and Targeted Therapy 2024年第2期9卷 479-508页

作者： Jing Yao Keenan sterling Zhe Wang Yun Zhang Weihong song The National Clinical research center for Geriatric disease Xuanwu HospitalCapital Medical UniversityBeijing 100053China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingP.R.China Zhejiang Clinical research center for Mental Disorders Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and The Affiliated Kangning HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325000China

Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune response.Each inflammasome complex has three major components:an upstream sensor molecule that is connected to a downstream effector protein such as caspase-1 through the adapter protein AsC.Inflammasome formation typically occurs in response to infectious agents or cellular damage.The active inflammasome then triggers caspase-1 activation,followed by the secretion of pro-inflammatory cytokines and pyroptotic cell death.Aberrant inflammasome activation and activity contribute to the development of diabetes,cancer,and several cardiovascular and neurodegenerative disorders.As a result,recent research has increasingly focused on investigating the mechanisms that regulate inflammasome assembly and activation,as well as the potential of targeting inflammasomes to treat various diseases.Multiple clinical trials are currently underway to evaluate the therapeutic potential of several distinct inflammasome-targeting therapies.Therefore,understanding how different inflammasomes contribute to disease pathology may have significant implications for developing novel therapeutic strategies.In this article,we provide a summary of the biological and pathological roles of inflammasomes in health and disease.We also highlight key evidence that suggests targeting inflammasomes could be a novel strategy for developing new disease-modifying therapies that may be effective in several conditions.

关键词： inflam therapeutic potential

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Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma solé-Guardia Amanda J.Kiliaan Department of Medical Imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

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Identification of TNFRsF1A as a novel regulator of carfilzomib resistance in multiple myeloma

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Oncology research 2024年第2期32卷 325-337页

作者： JIE ZHAO XUANTAO YANG HAIXI ZHANG XUEZHONG GU Department of Hematology The First People’s Hospital of Yunnan ProvinceYunnan Province Clinical Research Center for Hematologic DiseaseYunnan Province Clinical Center for Hematologic DiseaseKunming650032China Department of Pathology The First People’s Hospital of Yunnan ProvinceKunming650032China

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GsE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRsF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRsF1A overexpression and TNFRsF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRsF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRsF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRsF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRsF1A in MM cells.

关键词： Multiple myeloma Carfilzomib Drug resistance Major histocompatibility complex TNFRsF1A

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Commentary:Mammokine directs beige adipocytes to reserve energy for milk production in breast

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Acta Pharmaceutica sinica B 2024年第3期14卷 1472-1476页

作者： Lina Tang Jianping Ye Metabolic disease research center Zhengzhou University Affiliated Zhengzhou Central HospitalZhengzhou 450007China research center for Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Beige/brown adipocytes play a crucial role in regulating the body’s overall energy balance.The thermogenic function is under the influence of various tissues,including the brain,muscles,and liver.However,the breast t... 详细信息

关键词： Beige Breast Epitheliail cells scRNA-seq Thermogenesis

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