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Successful clearance of persistent SARS-CoV-2 asymptomatic infection following a single dose of Ad5-nCoV vaccine

Signal Transduction and Targeted Therapy 2023年第4期8卷 1942-1952页

作者： Shaofu Qiu Zhao Chen Airu Zhu Qiuhui Zeng Hongbo Liu Xiaoqing Liu Feng Ye Yingkang Jin Jie Wu Chaojie Yang Qi Wang Fangli Chen Lan Chen Sai Tian Xinying Du Qingtao Hu Jinling Cheng Canjie Chen Fang Li Jing Sun Yanqun Wang Jingxian Zhao Jincun Zhao Hongbin Song The Chinese PLA Center for disease Control and Prevention 100071 BeijingChina State Key Laboratory of Respiratory disease National Clinical Research Centre for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical University510182 GuangzhouGuangdongChina pediatric Pulmonary Department Guangzhou Women and Children’s Medical CenterGuangzhou Medical University510623 GuangzhouGuangdongChina Guangdong Provincial Center for disease Control and Prevention 510399 GuangzhouGuangdongChina Guangzhou Laboratory Bio-island510320 GuangzhouGuangdongChina Institute of Infectious disease Guangzhou Eighth People’s Hospital of Guangzhou Medical University510060 GuangzhouGuangdongChina Shanghai Institute for Advanced Immunochemical Studies School of Life Science and TechnologyShanghaiTech University201210 ShanghaiChina National Clinical Research Center for Infectious disease Shenzhen Third People’s HospitalThe Second Affiliated HospitalSchool of MedicineSouthern University of Science and Technology518112 ShenzhenGuangdongChina

Persistent asymptomatic(PA)SARS-CoV-2 infections have been *** immune responses in these patients are unclear,and the development of effective treatments for these patients is ***,we report a cohort of 23 PA cases carrying viral RNA for up to 191 *** cases displayed low levels of inflammatory and interferon response,weak antibody response,diminished circulating follicular helper T cells(cTfh),and inadequate specific CD4+and CD8+T-cell responses during infection,which is distinct from symptomatic infections and resembling impaired immune *** of a single dose of Ad5-nCoV vaccine to 10 of these PA cases elicited rapid and robust antibody responses as well as coordinated B-cell and cTfh responses,resulting in successful viral ***-induced antibodies were able to neutralize various variants of concern and persisted for over 6 months,indicating long-term ***,our study provides an insight into the immune status of PA infections and highlights vaccination as a potential treatment for prolonged SARS-CoV-2 infections.

关键词： infection impaired asymptomatic

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Evaluating active leprosy case identifcation methods in six districts of Nepal

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Infectious diseases of Poverty 2023年第6期12卷 105-106页

作者： Ram Kumar Mahato Uttam Ghimire Madhav Lamsal Bijay Bajracharya Mukesh Poudel Prashnna Napit Krishna Lama Gokarna Dahal David T.S.Hayman Ajit Kumar Karna Basu Dev Pandey Chuman Lal Das Krishna Prasad Paudel Epidemiology and disease Control Division Department of Health Services Ministry of Health and Population Kathmandu Nepal Epidemiology and disease Control Division-Malaria Program Management Unit- SCI-GF Kathmandu Nepal Leprosy Control & Disability Management Section EPidemiology and Disease Control Division DoHS Kathmandu Nepal Lalgadh Leprosy Hospital & Service Center Nepal Leprosy Trust Lalgadh Nepal Molecular Epidemiology and Public Health Laboratory Infectious Disease Research Centre Hopkirk Research Institute Massey University Palmerston North New Zealand Center for Health and disease Studies-Nepal Kathmandu Nepal DEJIMA Infectious disease Research Alliance Nagasaki University Nagasaki Japan

Background Nepal has achieved and sustained the elimination of leprosy as a public health problem since 2009,but 17 districts and 3 provinces with 41%(10,907,128)of Nepal’s population have yet to eliminate the *** cases and grade-2 disabilities(G2D)indicate recent transmission and late diagnosis,respectively,which necessitate active and early case *** operational research was performed to identify approaches best suited for early case detection,determine community-based leprosy epidemiology,and identify hidden leprosy cases early and respond with prompt *** Active case detection was undertaken in two Nepali provinces with the greatest burden of leprosy,Madhesh Province(40%national cases)and Lumbini Province(18%)and at-risk prison populations in Madhesh,Lumbini and Bagmati *** detection was performed by(1)house-to-house visits among vulnerable populations(n=26,469);(2)contact examination and tracing(n=7608);in Madhesh and Lumbini Provinces and,(3)screening prison populations(n=4428)in Madhesh,Lumbini and Bagmati Provinces of *** case direct medical and nonmedical costs for each approach were *** New case detection rates were highest for contact tracing(250),followed by house-to-house visits(102)and prison screening(45)per 100,000 population ***,the cost per case identifed was cheapest for house-to-house visits[Nepalese rupee(NPR)76,500/case],followed by contact tracing(NPR 90,286/case)and prison screening(NPR 298,300/case).House-to-house and contact tracing case paucibacillary/multibacillary(PB:MB)ratios were 59:41 and 68:32;female/male ratios 63:37 and 57:43;pediatric cases 11%in both approaches;and grade-2 disabilities(G2D)11%and 5%,*** leprosy was not signifcantly diferent among household and neighbor contacts[odds ratios(OR)=1.4,95%confdence interval(CI):0.24-5.85]and for contacts of MB versus PB cases(OR=0.7,95%CI 0.26-2.0).Attack rates were not signifcantly d

关键词： Leprosy Early case detection Community-based epidemiology Hidden case New case detection rate Attack rate Cost per case identifed Nepal

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Antibodies in celiac disease:implications beyond diagnostics

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Cellular & Molecular Immunology 2011年第2期8卷 103-109页

作者： Sergio Caja Markku Maki Katri Kaukinen Katri Lindfors pediatric Research centre University of Tampere and Tampere University HospitalTampereFinland Medical School University of Tampere and Department of Gastroenterology and Alimentary Tract SurgeryTampere University HospitalTampereFinland

Celiac disease is a multisystemic dietary,gluten-induced autoimmune disorder characterized by the presence of transglutaminase(TG)2 serum *** autoantibodies targeting members of the TG family(TG2,TG3 and TG6)are found deposited in small-bowel mucosa and in extraintestinal tissues affected by the *** autoantibodies against other self-antigens also emerge in untreated celiac disease *** villous atrophy and crypt hyperplasia in small-bowel biopsy samples are still the gold standards in diagnostics,celiac disease-specific antibodies are widely used as diagnostic ***-induced small-bowel mucosal T-cell response is the cornerstone in the pathogenesis of the disorder,but humoral immunity may also play a central *** review article is focused on the autoantibodies that occur in the context of celiac *** article summarizes the diagnostic utility of different celiac-related antibodies and discusses their roles in the pathogenesis of the disease.

关键词： antibody celiacdisease diagnostics pathogenesis

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Adipocytokine profile in children with Kawasaki disease at a mean follow-up period of 5.5 years: A study from North India

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World Journal of Clinical pediatrics 2022年第4期11卷 360-368页

作者： Dibya Lochan Praharaj Amit Rawat Anju Gupta Kanika Arora Rakesh Kumar Pilania Sagar Bhattad Surjit Singh pediatric Allergy and Immunology Unit Advanced Pediatrics CentrePost Graduate Institute of Medical Education and ResearchChandigarh 160012India

BACKGROUND Kawasaki disease(KD)is an acute self-limited vasculitis with a predilection for coronary *** with KD may have altered lipid metabolism and abnormal lipid profiles that may last for prolonged ***,there is a paucity of literature on the role of adipocytokines in *** To estimate the levels of adipocytokines(adiponectin,leptin and resistin)during the convalescent phase of *** Twenty children,who had KD at least three years earlier,were enrolled in this *** addition,20 healthy controls were also *** and laboratory profiles of patients were obtained from hospital *** adiponectin,leptin and resistin levels were estimated by enzyme-linked immunosorbent *** Mean age of the patients in the study group was 10.15±3 years and the male:female ratio was 1.5:*** serum resistin levels in patients with KD(27.77 ng/mL;[IQR:18.66,48.90])were decreased compared to controls(21.20 ng/mL;[IQR:14.80,27.00])(P=0.04).Median serum leptin levels in cases and controls were 1.83 ng/mL;(IQR:1.13,3.80),and 1.10 ng/mL;(IQR:0.41,2.88),respectively(P=0.09).Median serum adiponectin levels were similar in both cases(12.20μg/mL;[IQR:9.76,17.97])and controls(13.95μg/mL;[IQR:11.17,22.58]);(P=0.18).There was no significant difference in all 3 adipocytokines between children with(4/20)and without coronary artery abnormalities(16/20).CONCLUSION Serum resistin levels were significantly elevated in patients with KD during the convalescent phase compared to *** leptin levels appeared to be higher in patients with KD,although the difference was not statistically *** levels were similar in both cases and *** resistin and leptin levels may partially explain lipid perturbations observed during the convalescent phase of KD.

关键词： Adipocytokines Adiponectin Resistin Leptin Lipid metabolism Kawasaki disease Convalescent phase

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Brain-derived neurotrophic factor and its related enzymes and receptors play important roles after hypoxic-ischemic brain damage

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Neural Regeneration Research 2021年第8期16卷 1453-1459页

作者： Liu-Lin Xiong Jie Chen Ruo-Lan Du Jia Liu Yan-Jun Chen Mohammed Al Hawwas Xin-Fu Zhou Ting-Hua Wang Si-Jin Yang Xue Bai National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center Department of Cardiovascular DiseaseAffiliated Traditional Chinese Medicine HospitalSouthwest Medical UniversityLuzhouSichuan ProvinceChina Cinical and Health Sciences University of South AustraliaAdelaideAustralia Animal Zoology Department Institute of NeuroscienceKunming Medical UniversityKunmingYunnan ProvinceChina Institute of neurological disease Translational Neuroscience CenterWest China HospitalSichuan UniversityChengduSichuan ProvinceChina

Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The m RNA expression levels of BDNF and its processing enzymes and receptors(Furin, matrix metallopeptidase 9, tissuetype plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury;however, the expression levels of these m RNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia(approval No. U12-18) on July 30, 2018.

关键词： brain injury brain-derived neurotrophic factor enzyme hypoxia-ischemia receptors recovery repair

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Eight novel mutations in the ABCD1 gene and clinical characteristics of 25 Chinese patients with X-linked adrenoleukodystrophy

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World Journal of pediatrics 2015年第4期11卷 366-373页

作者： Shan-Shan Chu Jun Ye Hui-Wen Zhang Lian-Shu Han Wen-Juan Qiu Xiao-Lan Gao Xue-Fan Gu Department of pediatric Endocrinology and Genetic Metabolism Shanghai Institute for Pediatric ResearchXinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Background:X-linked adrenoleukodystrophy(X-ALD)is a fatal neurodegenerative disease caused by mutations in the adenosine triphosphate-binding cassette D1(ABCD1)*** study aimed to retrospectively investigate the clinical characteristics of 25 patients with X-ALD including members of large pedigrees,to analyze ABCD1 gene mutations,the effect of gene novel variants on ALD protein(ALDP)structure and function,and to expand gene mutation spectrum of Chinese ***:Twenty-five male patients diagnosed with X-ALD were enrolled in this *** clinical characteristics of the patients were retrospectively summarized by reviewing medical records or telephone ***1 gene mutations were *** pathogenicity of novel missense variants was analyzed using cobalt constraint-based multiple protein alignment tool,polymorphism phenotyping,sorting intolerant from tolerant,Align-Grantham variation and Grantham deviation,and Swiss-Program Database Viewer 4.04 software,***:Childhood cerebral form ALD(CCALD)is the most common phenotype(64%)in the 25 patients with *** progressive deterioration of neurological and cognitive functions is the main clinical *** demyelination of the brain white matter and elevated plasma very long chain fatty acids(VLCFAs)were found in all *** phenotypes were also presented within family members of the ***-two different mutations including 8 novel mutations in the ABCD1 gene were identifi ed in the 25 *** the mutations,63.6%were missense mutations and 34.8%located in exon *** amino acid residues of three novel missense mutations in eight species were highly conserved,and were predicted to be"probably"damaging to ALDP *** other five novel mutations were splice,nonsense,deletion or duplication ***:CCALD is the most common phenotype(64%)in our patients with *** novel mutations in the ABCD1 gene identifi ed are disease-causing muta

关键词： ABCD1 protein adrenoleukodystrophy adrenoleukodystrophy protein missense variant mutation

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A Protocol for Developing Chinese Clinical Practice Guidelines of Hypertension

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Cardiology Discovery 2024年第3期4卷 187-191页

作者： Ying Lou Wenjun Ma Zijun Wang Nan Yang Yajia Sun Yunlan Liu Ruobing Lei Junxian Zhao Xufei Luo Lu Wang Yaolong Chen Yaling Han Yingxian Sun Yuming Li Jun Cai Hypertension Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical SciencesBeijing 100037China Evidence-Based Medicine centre School of Basic Medical SciencesLanzhou UniversityLanzhouGansu 730000China School of Public Health Lanzhou UniversityLanzhouGansu 730000China Department of pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Cardiology General Hospital of Northern Theater CommandShenyangLiaoning 110000China Department of Cardiology First Hospital of China Medical UniversityShenyangLiaoning 110000China Department of Cardiology TEDA International Cardiovascular HospitalTianjin 300450China.

To improve the standard screening, diagnosis, and treatment of hypertension in patients in China;realize the standardization of clinical practice of hypertension;and improve the prevention and control level of hypertension in China, it is both important and necessary to develop a clinical practice guideline for hypertension according to a recognized methodology. Jointly sponsored by the National Center for Cardiovascular diseases, Chinese Medical Doctor Association, Hypertension Committee of the Chinese Medical Doctor Association, Chinese Society of Cardiology, and Hypertension Committee of Cross-Straits Medicine Exchange Association, the “Chinese Clinical Practice Guidelines of Hypertension” was proposed. Research Unit of Evidence-Based Evaluation and Guidelines, Chinese Academy of Medical Sciences, Guideline and Standards Research centre of Chinese Medical Association Publishing House, Lanzhou University Institute of Health Data Science, and Lanzhou University GRADE Center will provide methodological support for the guidelines.

关键词： Hypertension Clinical practice guidelines Protocol

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Drugging SUMOylation for neuroprotection and oncotherapy

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Neural Regeneration Research 2018年第3期13卷 415-416页

作者： Joshua D. Bernstock Daniel G. Ye Yang-ja Lee Florian Gessler Gregory K. Friedman Wei Zheng John M. Hallenbeck Stroke Branch National Institute of Neurological Disorders and Stroke National institutes of Health (NINDS/NIH) Bethesda MD USA Department of Clinical Neurosciences - Division of Stem Cell Neurobiology Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre University of Cambridge UK Department of pediatrics Division of Pediatric Hematology and Oncology University of Alabama at Birmingham Birmingham AL USA National Center for Advancing Translational Sciences National Institutes of Health (NCATS/NIH) Bethesda MD USA

Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due to numerous factors, including subject heterogeneity and improper therapeutic windows （Tymianski, 2017）. Moreover, it is becoming clearer that the complex and evolving pathobiology of stroke requires multimodal therapeutic approaches capable of modulating the numerous axes that contribute to ischemia/reperfusion damage, rather than targeting a single axis （Bernstock et al., 2018a）. With the success of recent endovascular thrombectomy （EVT） trials, it has been suggested that clinical trials of EVT with adjunct neuroprotection can overcome past difficulties and maximize the effect size by using imaging to reduce patient heterogeneity （i. e., selecting those with large vessel occlusions, small ischemic cores, and good collateral circulation）, restoring perfusion using better EVT devices, and enrolling patients in the correct therapeutic window （i.e., when they still have salvageable brain tissue）（Tymianski, 2017）. Considering the opportunity that this represents for new, better clinical trials of neuroprotective agents, the search is on for high-potential compounds that may be investigated in these future studies.

关键词： Drugging SUMOylation for neuroprotection and oncotherapy OGD

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Medium-Term Results of Balloon Valvuloplasty of Native Pulmonary Valve Stenosis with and without Supravalvular Obstruction in Childhood

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Congenital Heart disease 2022年第2期17卷 161-172页

作者： Olivia Lenoir Daniel Quandt Oliver Kretschmar Walter Knirsch pediatric Cardiology Pediatric Heart CenterChildren’s Research CenterUniversity Children’s Hospital ZurichZurichSwitzerland University of Zurich ZurichSwitzerland

Objectives:Factors influencing results of balloon valvuloplasty(BVP)of pulmonary valve stenosis(PS)in children are ***:BVP has become the standard of care for PS,medium-term results are not uniform and depend on various ***:We analysed the medium-term results of BVP of PS in children in an observational,single centre *** for additional procedure was defined as outcome after initial ***:We included 143 children(83 female)at a median(IQR)age of 2.6(0.26–9.24)months and body weight of 5(3.4–8)kg at BVP with a follow–up of 5.04(1.6–10.2)*** used balloon size of 10(9–14)mm and maximal balloon pressure of 4(3.5–10)atm,resulting in balloon–to–pulmonary annulus ratio of 1.28(1.2–1.4).Systolic pressure gradient of PS was reduced with BVP(43.5 mmHg vs.14.0 mmHg,p<0.001)and confirmed by echocardiography(68.0 mmHg vs.25.0 mmHg,p<0.001)day 1 post *** BVP with associated supravalvular PS resulted in a relevant reduction of systolic pressure gradient in 23 of 31 patients(74.2%).Early additional procedure was necessary in 14 patients(9.8%)after 0.2(0.1–0.7)years due to residual PS(n=13)and infective endocarditis(n=1).Factors for additional procedures were associated supravalvular PS with a higher residual pressure gradient,but not genetic *** further follow–up of 5.04(1.6–10.2)years no further additional procedures were ***:Pulmonary BVP of native pulmonary valve stenosis leads to excellent medium-term results,even in 3 of 4 infants with associated supravalvular obstruction sufficient pressure relief can be obtained.

关键词： pediatric catheter congenital pulmonary balloon valvuloplasty

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New perspectives on cytoskeletal dysregulation and mitochondrial mislocalization in amyotrophic lateral sclerosis

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Translational Neurodegeneration 2021年第4期10卷 595-610页

作者： Frances Theunissen Phillip K.West Samuel Brennan Bojan Petrovic Kosar Hooshmand P.Anthony Akkari Matt Keon Boris Guennewig Perron Institute for neurological and Translational Science NedlandsWAAustralia centre for Molecular Medicine and Innovative Therapeutics Murdoch UniversityMurdochWAAustralia GenieUs Genomics Pty Ltd SydneyNSWAustralia Brain and Mind centre and Central Clinical School Faculty of Medicine and Healththe University of SydneyamperdownNSWAustralia Division of Neurology Duke University Medical CentreDuke UniversityDurhamNCUSA

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by selective,early degeneration of motor neurons in the brain and spinal *** neurons have long axonal projections,which rely on the integrity of neuronal cytoskeleton and mitochondria to regulate energy requirements for maintaining axonal stability,anterograde and retrograde transport,and signaling between *** formation of protein aggregates which contain cytoskeletal proteins,and mitochondrial dysfunction both have devastating effects on the function of neurons and are shared pathological features across several neurodegenerative conditions,including ALS,Alzheimer's disease,Parkinson's disease,Huntington's disease and Charcot-Marie-Tooth ***,it is becoming increasingly clear that cytoskeletal integrity and mitochondrial function are intricately ***,dysregulations of the cytoskeletal network and mitochondrial homeostasis and localization,may be common pathways in the initial steps of *** we review and discuss known contributors,including variants in genetic loci and aberrant protein activities,which modify cytoskeletal integrity,axonal transport and mitochondrial localization in ALS and have overlapping features with other neurodegenerative ***,we explore some emerging pathways that may contribute to this disruption in ALS.

关键词： Cytoskeleton Neurofilament Mitochondria Amyotrophic lateral sclerosis Neurodegeneration Axonal transport Gut microbiome

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