{"title":"A Novel Subset of Regulatory T Cells Induced by B Cells Alleviate the Severity of Immunological Diseases.","authors":"Kuan-Hua Chu, Bor-Luen Chiang","doi":"10.1007/s12016-024-09009-y","DOIUrl":"https://doi.org/10.1007/s12016-024-09009-y","url":null,"abstract":"<p><p>Regulatory T (Treg) cells are crucial for maintaining immune tolerance by suppressing response to self-antigens and harmless antigens to prevent autoimmune diseases and uncontrolled immune responses. Therefore, using Treg cells is considered a therapeutic strategy treating inflammatory diseases. Based on their origin, Treg cells are classified into thymus-derived, peripherally induced, and in vitro induced Treg cells. Our group discovered a novel Treg cell subset, namely, Treg-of-B (Treg/B) cells, generated by culturing CD4<sup>+</sup>CD25<sup>-</sup> T cells with B cells, including Peyer's patch B cells, splenic B cells and peritoneal B1a cells, for 3 days. Treg/B cells express CD44, OX40 (CD134), cytotoxic T-lymphocyte-associated antigen-4 (CD152), glucocorticoid-induced tumor necrosis factor receptor family-related protein (CD357), interleukin-10 receptor, lymphocyte activation gene-3 (CD223), inducible co-stimulator (CD278), programmed-death 1 (CD279), tumor necrosis factor receptor II, and high levels of IL-10, but not forkhead box protein P3, similar to type 1 Treg (Tr1) cells. However, unlike Tr1 cells, Treg/B cells do not express CD103, CD226, and latency-associated peptide. Treg/B cells have been applied for the treatment of some murine models of inflammatory diseases, including allergic asthma, inflammatory bowel disease, collagen-induced arthritis, gout, psoriasis and primary biliary cholangitis. This review summarizes the current knowledge of Treg/B cells.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MDA5 Is a Major Determinant of Developing Symptoms in Critically Ill COVID-19 Patients.","authors":"Amit K Maiti","doi":"10.1007/s12016-024-09008-z","DOIUrl":"https://doi.org/10.1007/s12016-024-09008-z","url":null,"abstract":"<p><p>Apart from the skin and mucosal immune barrier, the first line of defense of the human immune system includes MDA5 (ifih1 gene) which acts as a cellular sensor protein for certain viruses including SARS-CoV-2. Upon binding with viral RNA, MDA5 activates cell-intrinsic innate immunity, humoral responses, and MAVS (mitochondrial antiviral signaling). MAVS signaling induces type I and III interferon (IFN) expressions that further induce ISGs (interferon stimulatory genes) expressions to initiate human cell-mediated immune responses and attenuate viral replication. SARS-CoV-2 counteracts by producing NSP1, NSP2, NSP3, NSP5, NSP7, NSP12, ORF3A, ORF9, N, and M protein and directs anti-MDA5 antibody production presumably to antagonize IFN signaling. Furthermore, COVID-19 resembles several diseases that carry anti-MDA5 antibodies and the current COVID-19 vaccines induced anti-MDA5 phenotypes in healthy individuals. GWAS (genome-wide association studies) identified several polymorphisms (SNPs) in the ifih1-ifn pathway genes including rs1990760 in ifih1 that are strongly associated with COVID-19, and the associated risk allele is correlated with reduced IFN production. The genetic association of SNPs in ifih1 and ifih1-ifn pathway genes reinforces the molecular findings of the critical roles of MDA5 in sensing SARS-CoV-2 and subsequently the IFN responses to inhibit viral replication and host immune evasion. Thus, MDA5 or its pathway genes could be targeted for therapeutic development of COVID-19.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aurore Collet, Diane Pelletier de Chambure, Emmanuelle Moitrot, Gaëlle Breyne, Floriane Mirgot, Stéphanie Rogeau, Mathieu Tronchon, Amélie Nicolas, Sébastien Sanges, Sarah Stabler, Emmanuel Ledoult, Louis Terriou, David Launay, Eric Hachulla, Myriam Labalette, Sylvain Dubucquoi, Guillaume Lefèvre
{"title":"Non-allergic Hypersensitivity Reactions to Immunoglobulin Preparations in Antibody Deficiencies: What Role for Anti-IgA IgG and Complement Activation?","authors":"Aurore Collet, Diane Pelletier de Chambure, Emmanuelle Moitrot, Gaëlle Breyne, Floriane Mirgot, Stéphanie Rogeau, Mathieu Tronchon, Amélie Nicolas, Sébastien Sanges, Sarah Stabler, Emmanuel Ledoult, Louis Terriou, David Launay, Eric Hachulla, Myriam Labalette, Sylvain Dubucquoi, Guillaume Lefèvre","doi":"10.1007/s12016-024-09007-0","DOIUrl":"https://doi.org/10.1007/s12016-024-09007-0","url":null,"abstract":"<p><p>The presence of IgG anti-IgA in the serum of primary immunodeficiency (PID) patients has long been considered responsible for hypersensitivity (HS) to immunoglobulin preparations (IgPs), but this link is increasingly being questioned. The aim of this work was to describe the prevalence of IgG anti-IgA and its association with HS, and to explore a new pathophysiological hypothesis involving the complement system. We measured IgG anti-IgA, using a standardised commercial technique, in controls and PID patients, and compared our results to a systematic literature review. We measured complement activation in PID patients before and after IgP infusion, and in vitro after incubation of IgP with serum from controls and PID patients. IgG anti-IgA was detected in 6% (n = 2/32) of PID patients, 30% (n = 3/10) of selective IgA deficiency patients and 2% (n = 1/46) of healthy controls. In the literature and our study, 38 PID patients had IgG anti-IgA and HS to IgPs and 9 had IgG anti-IgA but good tolerance to IgPs. In our patients, we observed a constant complement activation after IgP infusion compared to baseline. In vitro, IgP induced significant complement activation with all sera from tested individuals. IgA immunisation is not rare in PID, higher in selective IgA deficiency, but may also occur in healthy controls. Our results question the clinical relevance and pathophysiological implication of IgG anti-IgA in the context of HS with IgPs. Complement activation-related pseudoallergy could explain the clinical characteristics and natural history of HS symptoms.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy of Capsaicin for Non-allergic Rhinitis: An Updated Systematic Review and Meta-analysis.","authors":"Jiatong Wang, Leilani Zhang, Kangyang Zheng","doi":"10.1007/s12016-024-09005-2","DOIUrl":"https://doi.org/10.1007/s12016-024-09005-2","url":null,"abstract":"<p><p>Non-allergic rhinitis (NAR) is a prevalent condition with limited effective treatments. Capsaicin, an agonist of the transient receptor potential vanilloid subfamily 1 (TRPV1) receptor, has emerged as a potential therapeutic option for NAR by targeting heightened nasal reactivity. This systematic review and meta-analysis, conducted in accordance with PRISMA guidelines and registered on PROSPERO, evaluated the efficacy of capsaicin for NAR treatment. Nine studies with placebo-controlled group were included, with primary outcomes assessed as total nasal symptom scores (TNSS), visual analog scale (VAS) scores, and the proportion of therapeutic responders. Meta-analysis revealed significant improvements in TNSS and VAS scores, along with a higher proportion of therapeutic responders in patients receiving capsaicin treatment compared to placebo. While some studies demonstrated reductions in substance P levels and TRPV1 expression after capsaicin treatment, further investigation is warranted. This meta-analysis provides preliminary evidence suggesting that capsaicin treatment holds promise for alleviating symptoms in patients with NAR. However, the limited number of studies and methodological heterogeneity necessitate larger and more rigorously designed clinical trials with standardized methodologies and advanced diagnostic techniques to establish their definitive roles in clinical practice.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chih-Chao Chiang, Wei-Jen Cheng, Joseph Renz Marion Santiago Dela Cruz, Thiyagarajan Raviraj, Nan-Lin Wu, Michal Korinek, Tsong-Long Hwang
{"title":"Neutrophils in Atopic Dermatitis","authors":"Chih-Chao Chiang, Wei-Jen Cheng, Joseph Renz Marion Santiago Dela Cruz, Thiyagarajan Raviraj, Nan-Lin Wu, Michal Korinek, Tsong-Long Hwang","doi":"10.1007/s12016-024-09004-3","DOIUrl":"https://doi.org/10.1007/s12016-024-09004-3","url":null,"abstract":"<p>Neutrophils have a critical role in inflammation. Recent studies have identified their distinctive presence in certain types of atopic dermatitis (AD), yet their exact function remains unclear. This review aims to compile studies elucidating the role of neutrophils in AD pathophysiology. Proteins released by neutrophils, including myeloperoxidase, elastase, and lipocalin, contribute to pruritus progression in AD. Neutrophilic oxidative stress and the formation of neutrophil extracellular traps may further worsen AD. Elevated neutrophil elastase and high-mobility group box 1 protein expression in AD patients' skin exacerbates epidermal barrier defects. Neutrophil-mast cell interactions in allergic inflammation steer the immunological response toward Th2 imbalance and activate the Th17 pathway, particularly in response to allergens or infections linked to AD. Notably, drugs alleviating pruritic symptoms in AD inhibit neutrophilic inflammation. In conclusion, these findings underscore that neutrophils may be therapeutic targets for AD symptoms, emphasizing their inclusion in AD treatment strategies.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anahita Kate, Swapna S. Shanbhag, Jyothirmai Gattu, Sayan Basu
{"title":"Allergen Testing: A Review of the Indications, Procedures, and Limitations in Ocular Allergy","authors":"Anahita Kate, Swapna S. Shanbhag, Jyothirmai Gattu, Sayan Basu","doi":"10.1007/s12016-024-09002-5","DOIUrl":"https://doi.org/10.1007/s12016-024-09002-5","url":null,"abstract":"<p>Allergen-based diagnostics are essential in the management algorithm of allergic diseases. Unlike systemic allergy, where the indications and interpretation of these diagnostic modalities are well established, their utility in ocular allergy is not well-defined. With the rising prevalence of ocular allergies and the need for personalized treatment strategies, there is a growing demand for precision allergen diagnostics. This review describes the commonly used tests with their indications, procedures, and limitations. A review of the literature was carried out on articles on allergen diagnostics in ocular allergy, and after excluding articles that were not relevant, 82 papers were included in the current review. IgE-mediated pathways contribute significantly to seasonal and perennial ocular allergy and partly to vernal keratoconjunctivitis. Most diagnostic techniques aim to detect IgE sensitization. In vivo tests include skin prick (SPT), intradermal, and patch tests. SPT is considered the gold standard and directly evaluates the presence of allergen-specific IgE in the skin. In vitro tests measure total and specific IgE from either tears or sera. Tear IgE measurement is relatively specific for allergic conjunctivitis and can provide insight into the potential allergens responsible for local sensitization. The conjunctival provocation test can help establish true allergy, especially in patients with polysensitization. This review also provides an overview of evidence in literature segregated based on the test employed. This includes 17 studies on only SPT; 42 studies on IgE measured in serum, tears, or both; and 20 studies which have evaluated both SPT and IgE. The pattern of allergen sensitization can guide recommendations for avoidance measures and immunotherapy. Thus, this could create a corticosteroid-sparing therapy avenue in these patients, reducing disease severity and resulting visual morbidity.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.","authors":"Tiantian Deng, Zihan Wang, Qishun Geng, Zhaoran Wang, Yi Jiao, Wenya Diao, Jiahe Xu, Tingting Deng, Jing Luo, Qingwen Tao, Cheng Xiao","doi":"10.1007/s12016-024-09003-4","DOIUrl":"10.1007/s12016-024-09003-4","url":null,"abstract":"<p><p>The role of abnormal epigenetic modifications, particularly DNA methylation, in the pathogenesis of autoimmune rheumatic diseases (ARDs) has garnered increasing attention. Lymphocyte dysfunction is a significant contributor to the pathogenesis of ARDs. Methylation is crucial for maintaining normal immune system function, and aberrant methylation can hinder lymphocyte differentiation, resulting in functional abnormalities that disrupt immune tolerance, leading to the excessive expression of inflammatory cytokines, thereby exacerbating the onset and progression of ARDs. Recent studies suggest that methylation-related factors have the potential to serve as biomarkers for monitoring the activity of ARDs. This review summarizes the current state of research on the impact of DNA and RNA methylation on the development, differentiation, and function of T and B cells and examines the progress of these epigenetic modifications in studies of six specific ARDs: systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, juvenile idiopathic arthritis, and ankylosing spondylitis. Additionally, we propose that exploring the interplay between RNA methylation and DNA methylation may represent a novel direction for understanding the pathogenesis of ARDs and developing novel treatment strategies.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuening Tang, Yudi Zhang, Hao Zhang, Nan Zhang, Ziyu Dai, Quan Cheng, Yongzhen Li
{"title":"Single-Cell Sequencing: High-Resolution Analysis of Cellular Heterogeneity in Autoimmune Diseases.","authors":"Xuening Tang, Yudi Zhang, Hao Zhang, Nan Zhang, Ziyu Dai, Quan Cheng, Yongzhen Li","doi":"10.1007/s12016-024-09001-6","DOIUrl":"10.1007/s12016-024-09001-6","url":null,"abstract":"<p><p>Autoimmune diseases (AIDs) are complex in etiology and diverse in classification but clinically show similar symptoms such as joint pain and skin problems. As a result, the diagnosis is challenging, and usually, only broad treatments can be available. Consequently, the clinical responses in patients with different types of AIDs are unsatisfactory. Therefore, it is necessary to conduct more research to figure out the pathogenesis and therapeutic targets of AIDs. This requires research technologies with strong extraction and prediction capabilities. Single-cell sequencing technology analyses the genomic, epigenomic, or transcriptomic information at the single-cell level. It can define different cell types and states in greater detail, further revealing the molecular mechanisms that drive disease progression. These advantages enable cell biology research to achieve an unprecedented resolution and scale, bringing a whole new vision to life science research. In recent years, single-cell technology especially single-cell RNA sequencing (scRNA-seq) has been widely used in various disease research. In this paper, we present the innovations and applications of single-cell sequencing in the medical field and focus on the application contributing to the differential diagnosis and precise treatment of AIDs. Despite some limitations, single-cell sequencing has a wide range of applications in AIDs. We finally present a prospect for the development of single-cell sequencing. These ideas may provide some inspiration for subsequent research.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brian Hom, Natalie K Boyd, Benjamin N Vogel, Nicole Nishimori, Mellad M Khoshnood, Saba Jafarpour, Deepti Nagesh, Jonathan D Santoro
{"title":"Down Syndrome and Autoimmune Disease.","authors":"Brian Hom, Natalie K Boyd, Benjamin N Vogel, Nicole Nishimori, Mellad M Khoshnood, Saba Jafarpour, Deepti Nagesh, Jonathan D Santoro","doi":"10.1007/s12016-024-08996-2","DOIUrl":"10.1007/s12016-024-08996-2","url":null,"abstract":"<p><p>Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple organ systems. The high prevalence of autoimmune disease, in conjunction with other inflammatory and infectious diseases, in this population suggests an intrinsic immune dysregulation associated with triplication of chromosome 21. Emerging data on the role of chromosome 21 in interferon activation, cytokine production, and activation of B-cell mediated autoimmunity are emerging hypotheses that may explain the elevated prevalence of autoimmune thyroid disease, celiac disease, type I diabetes, autoimmune skin disease, and a variety of autoimmune neurologic conditions. As the life expectancy for individuals with Down syndrome increases, knowledge of the epidemiology, clinical features, management and underlying causes of these conditions will become increasingly important. Disorders such as Hashimoto's thyroiditis are prevalent in between 13 and 34% of individuals with Down syndrome but only 3% of the neurotypical population, a pattern similarly recognized in individuals with Celiac Disease (5.8% v 0.5-2%), alopecia areata (27.7% v. 2%), and vitiligo (4.4% v. 0.05-1.55%), respectively. Given the chronicity of autoimmune conditions, early identification and management can significantly impact the quality of life of individuals with Down syndrome. This comprehensive review will highlight common clinical autoimmune conditions observed in individuals with Down syndrome and explore our current understanding of the mechanisms of disease in this population.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian Xie, Qinhui Li, Hong Fang, Rong Zhang, Huan Tang, Lin Chen
{"title":"Gut-Derived Short-Chain Fatty Acids and Macrophage Modulation: Exploring Therapeutic Potentials in Pulmonary Fungal Infections.","authors":"Qian Xie, Qinhui Li, Hong Fang, Rong Zhang, Huan Tang, Lin Chen","doi":"10.1007/s12016-024-08999-z","DOIUrl":"10.1007/s12016-024-08999-z","url":null,"abstract":"<p><p>Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, modulate immune cell functions, particularly macrophages. This review explores the potential therapeutic applications of SCFAs in pulmonary fungal infections, a critical concern due to their high mortality rates and antifungal resistance. SCFAs enhance macrophage functions by promoting phagosome-lysosome fusion, increasing reactive oxygen species production, and balancing cytokine responses. Pulmonary fungal infections, caused by pathogens like Aspergillus fumigatus, are prevalent in immunocompromised patients, including those with diabetes, chronic obstructive pulmonary disease, and those on high-dose corticosteroids. SCFAs have shown promise in improving macrophage function in these contexts. However, the application of SCFAs must be balanced against potential side effects, including gut microbiota disruption and metabolic disorders. Further research is needed to optimize SCFA therapy for managing pulmonary fungal infections.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}