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An update on the genetics and pathogenesis of hereditary angioedema

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Genes & Diseases 2020年第1期7卷 75-83页

作者： Aaqib Zaffar Banday Anit Kaur Ankur Kumar Jindal Amit Rawat Surjit Singh allergy immunology Unit Department of PediatricsAdvanced Pediatrics CentrePostgraduate Institute of Medical Education and ResearchChandigarhIndia

Hereditary angioedema(HAE)is an uncommon genetic disorder characterized by recurrent episodes of edema involving subcutaneous tissue and *** pathogenesis of HAE reflects an intricate coordinated regulation of components of complement,kinin and hemostatic *** date,mutations in 4 different genes have been identified to cause HAE which includes serine protease inhibitor G1(SERPING1),factor XII(F12),plasminogen(PLG)and angiopoietin 1(ANGPT 1).These mutations lead to increased bradykinin 2 receptor mediated signalling via increased production of bradykinin except mutations in ANGPT1 gene that disturbs the cytoskeletal assembly of vascular endothelial *** this review we aim to summarize the recent advances in the pathogenesis and genetics of *** also provide an overview of possible future prospects in the identification of new genetic defects in HAE.

关键词： Angiopoietin 1 C1 inhibitor Factor XII Genetics Hereditary angioedema Plasminogen

Effects and Mechanisms of Actions of Chinese Herbal Medicines for Asthma

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Chinese Journal of Integrative Medicine 2011年第7期17卷 483-491页

作者：洪敏俐宋英李秀敏 Center for Chinese Medicine for allergy and Asthma Jaffe Food Allergy InstitutePediatric DepartmentDivision of Allergy and ImmunologyThe Mount Sinai School of Medicine Respiratory department Zhangzhou Traditional Chinese Medicine HospitalAffiliated Hospital of Fujian University of Traditional Chinese Medicine

Asthma is a chronic inflammatory disorder of airways that affects approximately 300 million adults and children *** therapy currently uses bronchodilators and *** side effects from chronic use of these drugs are *** medicine（CM）has a long history of human use in China and other Asian countries and well received by the *** as one component of Western integrative medicine（WIM）,it is required that CM use is supported by scientific *** the other hand,there are also suggestions that Western standardized medicine should consider personalized *** recent years there have been an increasing studies to narrow the gap between CM,the personalized medicine and Western medicine,evidence based *** communication reviews several CM studies published in the English language in details by reviewing the effects and mechanisms of actions on asthma from clinic and experimental studies. Chinese herbal medicines exhibit broad actions on multiple asthma pathologic *** mechanisms may involve antiinflammatory and immunomodulatory effects,inhibiting airway remodeling and normalization of hypothalamus,pituitary and adrenal（HPA）-axis ***,the mechanisms of actions of Chinese herbal medicines for asthma are not fully *** controlled clinical studies are warranted and some anti-asthma CM may be proved to be effective when used as monotherapy or complementary asthma therapies.

关键词： asthma complementary and alternative medicine Chinese medicine Chinese herbal medicine mechanism of action

An updated review on activated PI3 kinase delta syndrome(APDS)

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Genes & Diseases 2020年第1期7卷 67-74页

作者： Ankita Singh Vibhu Joshi Ankur Kumar Jindal Babu Mathew Amit Rawat allergy immunology Unit Department of PediatricsAdvanced Pediatrics CentrePostgraduate Institute of Medical Education and ResearchChandigarhIndia

Activated Phosphoinositide 3-kinase d syndrome(APDS)is a newly recognised primary immunodeficiency *** has currently been a hot topic of clinical research and new data are emerging regarding its pathogenesis,clinical manifestations and *** with APDS syndrome have significant autoimmune manifestations and *** is important to differentiate APDS from the usual polygenic CVID in view of the availability of targeted therapy like mTOR inhibitors such as Rapamycin and selective PI3Kd *** provide a comprehensive review on this interesting disorder focusing light on its etiology,genetic research and emerging therapy.

关键词： Activated phosphoinositide 3-kinase d syndrome(APDS) Gain of function Immunodeficiency Lymphadenopathy Lymphoproliferation p110d-activating mutation causing senescent T cells

Recent advances in elucidating the genetics of common variable immunodeficiency

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Genes & Diseases 2020年第1期7卷 26-37页

作者： Vaishali Aggarwal Aaqib Zaffar Banday Ankur Kumar Jindal Jhumki Das Amit Rawat allergy and immunology Unit Department of PediatricsAdvanced Pediatrics CentrePostgraduate Institute of Medical Education and ResearchChandigarhIndia

Common variable immunodeficiency disorders(CVID),a heterogeneous group of inborn errors of immunity,is the most common symptomatic primary immunodeficiency *** with CVID have highly variable clinical *** the advent of whole genome sequencing and genome wide association studies(GWAS),there has been a remarkable improvement in understanding the genetics of *** has also helped in understanding the pathogenesis of CVID and has drastically improved the management of these patients.A multiomics approach integrating the DNA sequencing along with RNA sequencing,proteomics,epigenetic and metabolomics profile is the need of the hour to unravel specific CVID associated disease pathways and novel therapeutic *** this review,we elaborate various techniques that have helped in understanding the genetics of CVID.

关键词： Common variable immunodeficiency(CVID) Epigenome Genetics Next generation sequencing(NGS) Transcriptome

Recent advances in chronic granulomatous disease

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Genes & Diseases 2020年第1期7卷 84-92页

作者： Gummadi Anjani Pandiarajan Vignesh Vibhu Joshi Jitendra Kumar Shandilya Dharmagat Bhattarai Jyoti Sharma Amit Rawat allergy immunology Unit Department of PediatricsAdvanced Pediatrics CentrePostgraduate Institute of Medical Education and ResearchChandigarhIndia

Chronic granulomatous disease(CGD)is an inherited defect of phagocyte function due to defective NADPH *** with CGD are not able to effectively clear the infections because of the defect in the phagocyte production of oxygen free radicals and are prone to recurrent bacterial and fungal *** complications are also noted in CGD such as colitis,non-infective granulomas causing gastrointestinal or urinary tract obstruction,hemophagocytic lymphohistiocytosis,and *** on toll-like receptor pathways and neutrophil extracellular traps in CGD have shed light on the role of NADPH oxidase in the innate immunity and pathogenesis of infections in *** reports also indicate a reduction of memory B cells and defective production of functional antibodies in *** the exact mechanisms for non-infective inflammatory complications in CGD are not yet clear,studies on efferocytosis and defective autophagy with inflammasome activation have made a substantial contribution to our understanding of the pathogenesis of inflammation in *** also discuss the clinical and molecular features of p40phox defects and a newer genetic defect,*** phenotypes of X-linked carriers of CYBB are also discussed.

关键词： Chronic granulomatous disease Colitis EROS Genetics Infections Inflammation p40phox

TLR-mediated metabolic reprogramming in the tumor microenvironment: potential novel strategies for cancer immunotherapy

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Cellular & Molecular immunology 2018年第5期15卷 1-10页

作者： Lan Huang Huaxi Xu Guangyong Peng Division of Infectious Diseases Allergy and ImmunologyDepartment of Internal MedicineSaint Louis University School of MedicineSaint LouisMO 63104USA department of Microbiology and immunology Jiangsu University School of MedicineZhenjiang 212013China Correspondence:G PengMDPhDDivision of Infectious DiseasesAllergy and ImmunologyDepartment of Internal MedicineSaint Louis University School of MedicineSaint LouisMO 63104USA.

Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival,proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment.A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer ***-like receptors(TLRs)have recently been recognized as critical factors involved in tumor pathogenesis,regulating both tumor cells and tumor-infiltrating innate and adaptive immune ***,little is known about the molecular crosstalk between TLR signaling and tumor or/and immune cell metabolism,although there is abundant expression of TLRs in these *** this review,we explore the functional role of TLR signaling in reprogramming cell metabolism in the tumor *** particular,we discuss how malignant tumors regulate metabolism to support their growth and survival,summarize more recently identified metabolic profiles of different immune cell subsets and TLR-mediated regulation of cellular metabolism in both tumor and immune cells,and further explore potential strategies targeting cell metabolism for TLR-based cancer *** improved understanding of these issues should open new avenues for the development of novel strategies via TLR-mediated metabolic reprogramming of the tumor microenvironment for cancer immunotherapy.

关键词： checkpoint blockade immunotherapy metabolic reprogramming tumor microenvironment warburg effect

Cardiovascular events in hyperuricemia population and a cardiovascular benefit-risk assessment of urate-lowering therapies:a systematic review and meta-analysis

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Chinese Medical Journal 2020年第8期133卷 982-993页

作者： Li Zhao Ling Cao Tian-Yi Zhao Xue Yang Xiao-Xia Zhu He-Jian Zou Wei-Guo Wan Yu Xue department of Rheumatology Huashan HospitalFudan UniversityShanghai 200040China Institute of Rheumatology Immunology and AllergyFudan UniversityShanghai 200040China

Background:Hyperuricemia and gout have become public health concerns;many important guidelines have recommended xanthine oxidase inhibitors(XOIs)as the first-line urate-lowering therapies(ULTs)to treat chronic gout with ***,whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains *** aim of this study was to assess the incident risk of cardiovascular(CV)events(CVE)in hyperuricemia population,assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups,and specify the safety of different ***:We searched PubMed,Embase,the Cochrane Library,Wanfang,Chongqing VIP(CQVIP,***),and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials(RCTs)in English and *** medications included XOIs,and *** were divided into sub-groups analysis based on blinding status and patients’history of CV *** ratios(RRs)were calculated and were reported with corresponding 95%confidence intervals(CIs)by fixed-effects or random-effects ***:Seven prospective cohort studies and 17 RCT studies were *** risks of both major adverse cardiovascular events(MACE)(RR=1.72,95%CI 1.28-2.33)and CVE(RR=1.35,95%CI 1.12-1.62)were higher in the hyperuricemia population than non-hyperuricemia *** seven RCT studies where XOIs were compared with no-treatment or placebo,the results of five low CV risk studies showed that XOIs lowered the risks of both MACE(RR=0.35,95%CI 0.20-0.62)and CVE(RR=0.61,95%CI 0.44-0.85);whereas two high CV risk studies showed that XOIs lowered the risk of CVE(RR=0.69,95%CI 0.54-0.88)rather than MACE(RR=0.62,95%CI 0.29-1.35).In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared,no statistical difference was found in the risk of MACE or ***:The hyperuricemia population doe

关键词： Hyperuricemia Gout Cardiovascular event Febuxostat Allopurinol

Salmonella Typhi:from a Human Pathogen to a Vaccine Vector

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Cellular & Molecular immunology 2008年第2期5卷 91-97页

作者： Victor Tunje Jeza department of immunology The State Key Laboratory of VirologyHubei Province Key Laboratory of Allergy and Immune-related DiseasesWuhan UniversitySchool of Medicine

Salmonella （S.） typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector. Cellular ＆ Molecular immunology.

关键词： Salmonella typhi vaccine vector typhoid Vi polysaccharide Ty21a

Rheumatology and functional genome analysis in East Asia

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Rheumatology & Autoimmunity 2022年第1期2卷 1-4页

作者： Keishi Fujio department of allergy and Rheumatology Graduate School of MedicineThe University of TokyoTokyoJapan

Rheumatic diseases differ in severity and outcome across ethnic *** genetic predisposition is an important factor influencing the development of rheumatic diseases,genomic data to date have been accumulated mainly in ***,East Asia has become an influential center for genetic studies worldwide,and there is also a growing need for a functional genome database for East *** quantitative trait locus data for immune cell subsets can be extremely useful in interpreting the function of disease-associated genetic *** development of a functional genome database for East Asians is expected to make a significant contribution to the understanding and stratification of the pathogenesis of rheumatic diseases in this population in the future.

关键词： ethnicity expression quantitative trait locus functional genome analysis rheumatic diseases