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A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

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Genes & Diseases 2024年第4期11卷 400-410页

作者： Han Chan Fenfen Ni Bo Zhao Huimin Jiang Juanjuan Ding Li Wang Xiaowen Wang Jingjing Cui Shipin Feng Xiaojie Gao Xueying Yang Huan Chi Hao Lee Xuelan Chen Xiaoqin Li Jia Jiao Daoqi Wu Gaofu Zhang Mo Wang Yupeng Cun Xiongzhong Ruan Haiping Yang Qiu Li Department of Nephrology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China Department of Nephrology Shenzhen Children's HospitalShenzhenGuangdong 518034China Department of Nephrology Kunming Children's HospitalKunming Medical UniversityKunmingYunnan 650228China Department of Nephrology Wuhan Children's HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanHubei 430015China Department of Nephrology Chengdu Women and Children Central HospitalChengduSichuan 610073China Pediatric Research institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Department of Nephrology John Moorhead Research LaboratoryUniversity College London Medical SchoolRoyal Free CampusUniversity College LondonLondon NW32PFUnited Kingdom

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the *** conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy ***,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for *** significant SNPs were observed between SSNSWR and SDNS/***,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through ***,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/*** study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

关键词： Frequentrelapse Genome-wide association study Human leukocyte antigen region Steroid-sensitive nephrotic syndrome

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Bifidobacterium longum subsp. infantis CCFM1269 promotes intestinal barrier and release of IFN-β through TLR4-TRIF dependent way in growing mice

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Food Science and Human Wellness 2024年

作者： Mengfan Ding Bo Yang Bowen Li Haiqin Chen Renqiang Yu R.Paul Ross Catherine Stanton Shilong Jiang Jianxin Zhao Wei Chen State Key Laboratory of Food Science and Resources Jiangnan University Teagasc Food Research centre Nutrition and Metabolism Research Division Innovation Center Heilongjiang Feihe Dairy Co. Ltd. Department of Neonatology Wuxi Maternity and child health Care Hospital Affiliated Women's Hospital of Jiangnan University National Engineering Research Center for Functional Food Jiangnan University School of Food Science and Technology Jiangnan University PKUHSC-China Feihe Joint Research institute of Nutrition and healthy Lifespan development international Joint Research Center for Probiotics & Gut health Jiangnan University APC Microbiome Ireland University College Cork

Bifidobacterium longum subsp. infantis is a commensal bacterium that predominates in the infant gut， playing a critical role in both preventing foreign infections and facilitating immune development. This study aimed to explore the effects of B. longum subsp. infantis supplementation on interferon-beta (IFN-β) secretion and intestinal barrier improvement in growing mice. Female and male mice were orally administered either saline or B. longum subsp. infantis CCFM1269 or I5TI (1 × 109CFU/mice per day， n = 8) from 1-week-age until 3-， 4-， and 5-week-age. RNA sequencing analysis revealed that CCFM1269 exhibited potential antiviral capacity through increasing 2’-5’ oligoadenylate synthetase (OAS). Additionally， CCFM1269 supplementation significantly increased colonic IFN-β levels which combined with OAS in 3-week-old female and male mice by activating the TLR4-TRIF-dependent signaling pathway. However， this effect was not observed in 4- and 5-week-old mice. Furthermore， both CCFM1269 were found to modulate the gut microbiota composition and enhance the intestinal barrier function in 3-， 4-， and 5-week-old mice. In summary， the results of this study suggested that B. longum subsp. infantis CCFM1269 promoting intestinal barrier and releasing IFN-β in growing mice was in a strain-specific and time-dependent manner.

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The immune response to SARS-CoV-2 in people with HIV

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Cellular & Molecular Immunology 2024年第2期21卷 184-196页

作者： Maxine A.Höft Wendy A.Burgers Catherine Riou institute of Infectious Disease and Molecular Medicine University of Cape TownCape TownSouth Africa Division of Medical Virology Department of PathologyUniversity of Cape TownCape TownSouth Africa Wellcome centre for Infectious Diseases Research in Africa University of Cape TownCape TownSouth Africa

This review examines the intersection of the HIV and SARS-CoV-2 *** with HIV(PWH)are a heterogeneous group that differ in their degree of immune suppression,immune reconstitution,and viral *** COVID-19 in those with wellcontrolled HIV infection poses no greater risk than that for HIV-uninfected individuals,people with advanced HIV disease are more vulnerable to poor COVID-19 ***-19 vaccines are effective and well tolerated in the majority of PWH,though reduced vaccine efficacy,breakthrough infections and faster waning of vaccine effectiveness have been demonstrated in *** is likely a result of suboptimal humoral and cellular immune responses after *** with advanced HIV may also experience prolonged infection that may give rise to new epidemiologically significant variants,but initiation or resumption of antiretroviral therapy(ART)can effectively clear persistent ***-19 vaccine guidelines reflect these increased risks and recommend prioritization for vaccination and additional booster doses for PWH who are moderately to severely *** recommend continued research and monitoring of PWH with SARS-CoV-2 infection,especially in areas with a high HIV burden.

关键词： SARS-CoV-2 HIV Immune dysfunction Vaccine efficacy Prolonged infection Immunogenicity

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Downregulated nuclear lncRNA NRON inhibits SHP2/Wnt/β-catenin signaling and cardiomyocyte differentiation during the development of Tetralogy of Fallot

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Genes & Diseases 2023年第3期10卷 750-752页

作者： Hui Zhang Lei Lu Chao Li Hongdou Li Jie Tian Hongyan Wang Zhang Zhongjing School of Chinese Medicine Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for ImmunoregulationNanyang Institute of TechnologyNanyangHenan 473004China Department of Cardiology Heart CentreMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Pediatrics China International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Shanghai Key Laboratory of Metabolic Remodeling and health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200011China Obstetrics and Gynecology Hospital NHC Key Laboratory of Reproduction RegulationShanghai Institute of Planned Parenthood ResearchState Key Laboratory of Genetic Engineering at School of Life SciencesChildren's HospitalFudan UniversityShanghai 200438China

Tetralogy of Fallot(TOF)is the most common cyanotic congenital heart disease and the incidence of late cardiac death in long-term survivors continues to increase.1 So,there is an urgent need to explore the etiology and pathogenesis of *** precise cause of TOF is currently unclear,and exploration of the pathogenesis has focused increasingly in recent years on the roles of noncoding gene products,especially long noncoding RNAs(lncRNAs).

关键词： pathogenesis cardiac congenital

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Dengue:epidemiology,prevention and pressing need for vaccine development

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Asian Pacific Journal of Tropical Medicine 2010年第12期3卷 997-1000页

作者： Kuldeep Kumar Pankaj Kumar Singh Juhi Tomar Swati Baijal ucl centre for international health and development institute of child health 30 Guilford StreetLondon WC1N 1EHUK Department of Medical Physics and Neurosurgery Royal Hallamshire hospitalSheffieldUK Medical Education centre Northern General HospitalSheffieldUK Cambridge School SriniwaspuriNew DelhiIndia 110065

Dengue fever is a mosquito born viral infection,and the complicated form of dengue is dengue hemorrhagic fever(DHF).In the recent decades incidence and distribution of dengue has increased *** viruses belong to family flaviviridae with four serotypes and are transmitted mainly by mosquito Aedes *** almost two-fifth of world’s population (2.5 million) is at risk of dengue and no specific antiviral drug or vaccine is available against *** population growth in Africa and South East Asia has increased number of susceptible hosts in urban and semi urban *** 40%of world population resides in the high risk area for dengue *** to latest estimates by WHO,yearly 50 to 100 million infections occur globally,this includes around 500 000 DHF and 22 000 deaths,mostly among *** symptomatic treatment in the form of analgesic,antipyretics and body fluid management is provided to the *** strategies mainly focus on two approaches, firsdy on activities to control vector and secondly on activities to protect human from mosquito bite but there is always concerns regarding their sustainably and *** development of an effective dengue vaccine is feasible and production of an effective and affordable vaccine could be a viable option to save humans from this dreadful disease. Conceptually vaccine production is possible,but it has to be tetravalent,providing immunity against all *** candidate vaccines are in advance stage of their development:however international cooperation is needed to make these vaccines available on cheaper rates to the poor and vulnerable *** of this review is to discuss various aspects related to dengue,its epidemiology,available preventive methods,need for vaccine and challenges in its development.

关键词： Dengue Epidemiology Prevention Vaccine

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Dedifferentiated human umbilical cord mesenchymal stem cell reprogramming of endogenous hSDF-1a expression participates in neural restoration in hypoxic-ischemic brain damagerats

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Genes & Diseases 2021年第3期8卷 331-343页

作者： Zhou Xiaoqin Liu Jia Dai Mengjie Gu Jialu Bi Yang Wang Yuting Hu Huajian Liu Bo Zhang Xiaojun Li Zhongyue Chen Jie Li Tingyu Zhan Xue Department of Gastroenterology Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and Disorders(Chongqing)401122PR China international Science and Technology Cooperation Base of child development and Critical Disorders Children’sHospital of Chongqing Medical UniversityChongqing401122PR China Department of Pediatric Research institute Chongqing Key Laboratory of Child Health and NutritionChildren’s Hospital of Chongqing Medical UniversityChongqing401122PR China Department of Neonatology Chongqing Health Center for Womenand Children400021PR China child health centre of Northwest Women and children’s Hospital USA

The transplantation of human umbilical cord mesenchymal stem cells(hUC-MSCs)can promote hypoxic-ischemic brain damage(HIBD)nerve repair,but finding suitable seed cells to optimize transplantation and improve treatment efficiency is an urgent problem to be *** this study,we induced hUC-MSCs into dedifferentiated hUC-MSCs(De-hUC-MSCs),and the morphology,stem cell surface markers,proliferation and tri-directional differentiation ability of the De-hUC-MSCs and hUC-MSCs were detected.A whole-gene chip was utilized for genome cluster,gene ontology and KEGG pathway analyses of differentially expressed ***-hUC-MSCs were transplanted into HIBD rats,and behavioral experiments and immunofluorescence assays were used to assess the therapeutic effect.A lentivirus vector for human stromal cell-derived factor-1(hSDF-1a)was constructed,and the role of hSDF-1a in the neuroprotective effect and mechanism of De-hUC-MSCs was ***-hUC-MSCs displayed similar cell morphology,stem cell surface marker expression,cell proliferation and even three-dimensional differentiation ability as hUC-MSCs but exhibited greater treatment potential in *** reprogramming mechanism of hSDF-1a participated in the dedifferentiation *** successfully constructing a stable hSDF-1a cell line,we found that De-hUC-MSCs might participate in nerve repair through the hSDF-1a/CXCR4/PI3K/Akt ***-hUC-MSCs reprogramming of endogenous hSDF-1a expression may mediate the hSDF-1a/CXCR4/PI3K/Akt pathway involved in nerve repair in HIBD rats.

关键词： Dediffer entiation Human umbilicalcord mesenchymal stem cells Hypoxic-ischemic brain damage Neurorestoration Reprogramming Stromal cell-derived factor-1

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Glutamate and GABAA receptor crosstalk mediates homeostatic regulation of neuronal excitation in the mammalian brain

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4156-4173页

作者： Ya Wen Zhifang Dong Jun Liu Peter Axerio-Cilies Yehong Du Junjie Li Long Chen Lu Zhang Lidong Liu Jie Lu Ning Zhou Dong Chuan Wu Yu Tian Wang DM centre for Brain health and Department of Medicine Vancouver Coastal Health Research InstituteUniversity of British ColumbiaVancouverBCV6T 2B5Canada Pediatric Research institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing400014P.R.China iHuman Institue ShanghaiTech UniversityShanghaiP.R.China

Maintaining a proper balance between the glutamate receptor-mediated neuronal excitation and the A type of GABA receptor(GABAAR)mediated inhibition is essential for brain functioning;and its imbalance contributes to the pathogenesis of many brain disorders including neurodegenerative diseases and mental *** we identify a novel glutamate-GABAAR interaction mediated by a direct glutamate binding of the *** HEK293 cells overexpressing recombinant GABAARs,glutamate and its analog ligands,while producing no current on their own,potentiate GABA-evoked *** potentiation is mediated by a direct binding at a novel glutamate binding pocket located at theα+/β−subunit interface of the ***,the potentiation does not require the presence of aγsubunit,and in fact,the presence ofγsubunit significantly reduces the potency of the glutamate *** addition,the glutamate-mediated allosteric potentiation occurs on native GABAARs in rat neurons maintained in culture,as evidenced by the potentiation of GABAAR-mediated inhibitory postsynaptic currents and tonic *** importantly,we found that genetic impairment of this glutamate potentiation in knock-in mice resulted in phenotypes of increased neuronal excitability,including decreased thresholds to noxious stimuli and increased seizure *** results demonstrate a novel cross-talk between excitatory transmitter glutamate and inhibitory *** a rapid and short feedback loop between the two principal excitatory and inhibitory neurotransmission systems may play a critical homeostatic role in fine-tuning the excitation-inhibition balance(E/I balance),thereby maintaining neuronal excitability in the mammalian brain under both physiological and pathological conditions.

关键词： excitation thereby maintained

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development of a molecular feature-based survival prediction model of ovarian cancer using the deep neural network

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Genes & Diseases 2023年第4期10卷 1190-1193页

作者： Tingyuan Lang Muyao Yang Yunqiu Xia Jingshu Liu Yunzhe Li Lingling Yang Chenxi Cui Yunran Hu Yang Luo Dongling Zou Lei Zhou Zhou Fu Qi Zhou Department of Gynecologic Oncology Chongqing University Cancer Hospital&Chongqing Cancer Institute&Chongqing Cancer HospitalChongqing 400030China Reproductive Medicine Center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400042China Bioengineering College of Chongqing University Chongqing 400044China Department of Dermatology Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina international Science and Technology Cooperation Base of child development and Critical Disorders Chongqing Engineering Research Center of Stem Cell TherapyChildren’s Hospital of Chongqing Medical UniversityChongqingChina Department of Gynaecology and Obstetrics Reproductive Medicine CenterThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400030China School of Medicine Chongqing UniversityChongqing 400044China Department of Pharmacy Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China School of Basic Medicine and Clinical Pharmacy China Pharmaceutical UniversityNanjing 210009Jiangsu ProvinceChina Center of Smart Laboratory and Molecular Medicine School of MedicineChongqing UniversityChongqing 400044China centre for Eye and Vision Research School of OptometryThe Hong Kong Polytechnic UniversityHong Kong SARChina centre for Eye and Vision Research Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHong Kong SARChina centre for Eye and Vision Research Research Centre for SHARP Vision(RCSV)The Hong Kong Polytechnic UniversityHong Kong SARChina Department of Respiratory Children’s Hospital of Chongqing Medical University&National Clinical Research Center for Child Health and Disorders&Ministry of Education Key Laboratory of Child Development and DisordersChongqing 400044China

Ovarian cancer(OC)is one of the most lethal gynecologic cancer worldwide,and survival prediction is meaningful for personalized treatment.^(1)The survival outcome of cancer patients mainly depended on the malignancy of the primary tumor which is tightly linked with the expression profile of the molecular features.^(2)Therefore,in this study,we developed a molecular feature-based survival prediction model of OC using a deep neural network(DNN).

关键词： cancer prediction neural

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A decline in snow cover area of Passu and Ghulkin valleys between 1995 and 2022

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Journal of Mountain Science 2023年第12期20卷 3542-3551页

作者： Imran HUSSAIN Mumtaz ALI Sher MUHAMMAD Wajid HASSAN Salar ALI Zakir HUSSAIN Syed Hammad ALI Shaukat ALI Muhammad Younis KHAN Department of Environmental Sciences University of BaltistanSkardu 16100Pakistan Micromaps IT and GIS Consultancy LLC 26135UAE international Centers for Integrated Mountain development(ICIMOD) G.P.O.Box 3226KathmanduNepal institute of Mountain Hazards and Environment Chinese Academy of SciencesChengdu 610041China University of Chinese Academy of Sciences Beijing 100049China Glacier Monitoring Research centre(GMRC) Water and Power Development Authority(WAPDA)Lahore 54000Pakistan SickKids centre for Global child health The Hospital for Sick ChildrenTorontoOntario M5G 2L3Canada Global Change Impact Studies Center(GCISC) Islamabad 44000Pakistan Departments of Earth Sciences College of ScienceSultan Qaboos UniversityMuscat 123Oman National Centers of Excellence in Geology(NCEG) University of PeshawarPeshawar 25130Pakistan

The global cryosphere is experiencing accelerated melting due to climate ***,the Karakoram anomaly is under discussion with a debate about the possibility that the anomaly may have recently *** study aims to evaluate the up-to-date changes in snow cover in the western Karakoram *** observed the snow cover changes in Passu and Ghulkin valleys in the Hunza River basin(HRB)of the Karakoram through multitemporal Landsat satellite data between 1995 and *** found a significant reduction in snow cover in these valleys,with an average reduction rate of 0.42 km~2/yr,resulting in a total reduction of~11.46 km~2 between 1995 and *** reduction in snow cover is consistent with the mass loss of glaciers in the Karakoram region in recent *** decline in snow cover in these valleys is also consistent with the meteorological *** temperature in summer(June)has significantly increased whereas the precipitation in the accumulation season(March)has *** rapid changes suggest that it is crucially important to monitor the snow cover on a regular basis to support downstream management of snowmelt *** addition,there is a need of planning for mitigation and adaptation strategies for snow-related hazards.

关键词： Cryosphere Snow covers area Climate change Karakoram

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Update on global epidemiology of viral hepatitis and preventive strategies

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World Journal of Clinical Cases 2018年第13期6卷 589-599页

作者： Meryem Jefferies Bisma Rauff Harunor Rashid Thao Lam Shafquat Rafiq Drug health Western Sydney Local Health District Westmead institute for Medical Research Westmead Hospital Sydney Medical School University of Sydney National centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases the Children’s Hospital at Westmead and the Discipline of Child and Adolescent Health Sydney Medical School Croydon University Hospital NHS Trust

Viral hepatitis is one of the major public health concerns around the world but until recently it has drawn little attention or funding from global health *** year 1.4 million people die from viral hepatitisrelated cirrhosis and liver ***,the majority of the infected population are unaware of their *** population have significant obstacles to overcome such as lack of awareness,vulnerability,increased migration,disease stigma,discrimination,as well as poor health resources,conflict in policy development and program *** implementing infection control measures over the last few decades eradication or significant disease reduction remains *** study aims to present the current global prevalence status and examines potential elimination *** information for this research were obtained through a systematic review,published scientific literatures,the official websites of various government organisations,international public health organisations and internationally recognised regulatory bodies over a period of 40 years between 1978 and2018.

关键词： Cirrhosis Global epidemiology Outreach clinic Liver cancer Vaccination Viral hepatitis

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