{"title":"Twenty shades of the mosaic of autoimmunity","authors":"","doi":"10.1016/j.autrev.2024.103575","DOIUrl":"10.1016/j.autrev.2024.103575","url":null,"abstract":"<div><p>Accelerated, inflammatory atherosclerosis and cardiovascular disease have been associated with several autoimmune diseases including RA, AS, SLE, APS and SSc. Non-invasive, ultrasound- based techniques are suitable for the assessment of preclinical vascular pathophysiology. Multiple vascular and other biomarkers including vitamin D, ferritin, prolactin, suPAR, BNP fragments, oxLDL/β2GPI complexes, anti-Hsp60 and others have been associated with cardiometabolic comorbidities. The control of the underlying inflammatory disease is crucial for minimising cardiovascular risk in autoimmune diseases.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 9","pages":"Article 103575"},"PeriodicalIF":9.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224000661/pdfft?md5=c479f6284d3315b57243118cf3badb2c&pid=1-s2.0-S1568997224000661-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Piero Ruscitti , Yannick Allanore , Chiara Baldini , Giuseppe Barilaro , Elena Bartoloni Bocci , Pietro Bearzi , Elisa Bellis , Onorina Berardicurti , Alice Biaggi , Michele Bombardieri , Luca Cantarini , Francesco Paolo Cantatore , Roberto Caporali , Francesco Caso , Ricard Cervera , Francesco Ciccia , Paola Cipriani , Loukas Chatzis , Serena Colafrancesco , Fabrizio Conti , Roberto Giacomelli
{"title":"Tailoring the treatment of inflammatory rheumatic diseases by a better stratification and characterization of the clinical patient heterogeneity. Findings from a systematic literature review and experts' consensus","authors":"Piero Ruscitti , Yannick Allanore , Chiara Baldini , Giuseppe Barilaro , Elena Bartoloni Bocci , Pietro Bearzi , Elisa Bellis , Onorina Berardicurti , Alice Biaggi , Michele Bombardieri , Luca Cantarini , Francesco Paolo Cantatore , Roberto Caporali , Francesco Caso , Ricard Cervera , Francesco Ciccia , Paola Cipriani , Loukas Chatzis , Serena Colafrancesco , Fabrizio Conti , Roberto Giacomelli","doi":"10.1016/j.autrev.2024.103581","DOIUrl":"10.1016/j.autrev.2024.103581","url":null,"abstract":"<div><p>Inflammatory rheumatic diseases are different pathologic conditions associated with a deregulated immune response, codified along a spectrum of disorders, with autoinflammatory and autoimmune diseases as two-end phenotypes of this continuum. Despite pathogenic differences, inflammatory rheumatic diseases are commonly managed with a limited number of immunosuppressive drugs, sometimes with partial evidence or transferring physicians' knowledge in different patients. In addition, several randomized clinical trials, enrolling these patients, did not meet the primary pre-established outcomes and these findings could be linked to the underlying molecular diversities along the spectrum of inflammatory rheumatic disorders. In fact, the resulting patient heterogeneity may be driven by differences in underlying molecular pathology also resulting in variable responses to immunosuppressive drugs. Thus, the identification of different clinical subsets may possibly overcome the major obstacles that limit the development more effective therapeutic strategies for these patients with inflammatory rheumatic diseases. This clinical heterogeneity could require a diverse therapeutic management to improve patient outcomes and increase the frequency of clinical remission. Therefore, the importance of better patient stratification and characterization is increasingly pointed out according to the precision medicine principles, also suggesting a new approach for disease treatment. In fact, based on a better proposed patient profiling, clinicians could more appropriately balance the therapeutic management. On these bases, we synthetized and discussed the available literature about the patient profiling in regard to therapy in the context of inflammatory rheumatic diseases, mainly focusing on randomized clinical trials. We provided an overview of the importance of a better stratification and characterization of the clinical heterogeneity of patients with inflammatory rheumatic diseases identifying this point as crucial in improving the management of these patients.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 7","pages":"Article 103581"},"PeriodicalIF":9.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut-tropic T cells and extra-intestinal autoimmune diseases","authors":"","doi":"10.1016/j.autrev.2024.103544","DOIUrl":"10.1016/j.autrev.2024.103544","url":null,"abstract":"<div><p>Gut-tropic T cells primarily originate from gut-associated lymphoid tissue (GALT), and gut-tropic integrins mediate the trafficking of the T cells to the gastrointestinal tract, where their interplay with local hormones dictates the residence of the immune cells in both normal and compromised gastrointestinal tissues. Targeting gut-tropic integrins is an effective therapy for inflammatory bowel disease (IBD). Gut-tropic T cells are further capable of entering the peripheral circulatory system and relocating to multiple organs. There is mounting evidence indicating a correlation between gut-tropic T cells and extra-intestinal autoimmune disorders. This review aims to systematically discuss the origin, migration, and residence of gut-tropic T cells and their association with extra-intestinal autoimmune-related diseases. These discoveries are expected to offer new understandings into the development of a range of autoimmune disorders, as well as innovative approaches for preventing and treating the diseases.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 7","pages":"Article 103544"},"PeriodicalIF":9.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140788796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The pipeline of immunomodulatory therapies in polymyalgia rheumatica and giant cell arteritis: A systematic review of clinical trials","authors":"Lou Kawka , Baptiste Chevet , Laurent Arnaud , Guillaume Becker , Guillermo Carvajal Alegria , Renaud Felten","doi":"10.1016/j.autrev.2024.103590","DOIUrl":"10.1016/j.autrev.2024.103590","url":null,"abstract":"<div><h3>Introduction</h3><p>The objective of this systematic review was to provide an overview of current developments and potentially available therapeutic options for polymyalgia rheumatic (PMR) and giant cell arteritis (GCA), in the coming years.</p></div><div><h3>Methods</h3><p>We conducted a systematic review of 17 national and international clinical trial databases for all disease-modifying anti-rheumatic drugs (DMARDs) for PMR and GCA that are already marketed, in clinical development or withdrawn. The search was performed on January 2024, with the keywords “polymyalgia rheumatica” and “giant cell arteritis”. For each molecule, we only considered the study at the most advanced stage of clinical development.</p></div><div><h3>Results</h3><p>For PMR, a total of 15 DMARDs were identified: 2 conventional synthetic DMARDs (csDMARDs), 11 biologic DMARDs (bDMARDs) and 2 targeted synthetic DMARDs (tsDMARDs). For GCA, 18 DMARDs were identified: 2 csDMARDs, 14 bDMARDs and 2 tsDMARDs. Currently, there are only 2 approved corticosteroid-sparing therapies in these diseases, which both target the IL-6 signaling pathway, namely tocilizumab in GCA and sarilumab in PMR. Most of the molecules in current development are repurposed from from other conditions and clinical research in PMR/GCA seems to be mostly driven by the potential to repurpose existing treatments rather than by translational research.</p></div><div><h3>Conclusion</h3><p>This systematic review identified 23 DMARDs evaluated for PMR and GCA: 3 csDMARDs, 17 bDMARDs and 3 tsDMARDs. Several promising treatments are likely to be marketed in the coming years.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 7","pages":"Article 103590"},"PeriodicalIF":9.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224000818/pdfft?md5=a504745a0a378dca766e507eb98d0ea2&pid=1-s2.0-S1568997224000818-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Víctor M. Martínez-Taboada , Ana Micieces Gómez , Ana Merino , Marcos López-Hoyos , Sara del Barrio-Longarela , Alejandra Comins-Boo , Rafael Galvez , José L. Hernández
{"title":"Are the new 2023 ACR/EULAR classification criteria suitable for advancing the knowledge of obstetric antiphospholipid syndrome?","authors":"Víctor M. Martínez-Taboada , Ana Micieces Gómez , Ana Merino , Marcos López-Hoyos , Sara del Barrio-Longarela , Alejandra Comins-Boo , Rafael Galvez , José L. Hernández","doi":"10.1016/j.autrev.2024.103592","DOIUrl":"10.1016/j.autrev.2024.103592","url":null,"abstract":"","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 7","pages":"Article 103592"},"PeriodicalIF":9.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elvis Hysa , Andrea Casabella , Emanuele Gotelli , Rosanna Campitiello , Carlotta Schenone , Carlo Genova , Enrica Teresa Tanda , Alberto Sulli , Vanessa Smith , Marco Amedeo Cimmino , Sabrina Paolino , Maurizio Cutolo
{"title":"Polymyalgia rheumatica and giant cell arteritis induced by immune checkpoint inhibitors: A systematic literature review highlighting differences from the idiopathic forms","authors":"Elvis Hysa , Andrea Casabella , Emanuele Gotelli , Rosanna Campitiello , Carlotta Schenone , Carlo Genova , Enrica Teresa Tanda , Alberto Sulli , Vanessa Smith , Marco Amedeo Cimmino , Sabrina Paolino , Maurizio Cutolo","doi":"10.1016/j.autrev.2024.103589","DOIUrl":"10.1016/j.autrev.2024.103589","url":null,"abstract":"<div><h3>Introduction</h3><p>An altered immune tolerance disturbed by immune checkpoint inhibitors (ICIs) may contribute to new-onset polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). This systematic literature review (SLR) examines the characteristics of PMR and GCA-like syndromes following anticancer treatment with ICIs, summarizing their demographic, clinical and treatment-related features to provide insights whether they differ from the idiopathic forms.</p></div><div><h3>Methods</h3><p>The SLR was conducted in Medline and EMBASE databases from inception to July 2024, and in the EULAR/ACR abstract database (2021−2023). ICI-induced PMR and GCA syndromes were compared to the primary forms of the diseases using data from studies that included both groups as comparators. For manuscripts lacking direct comparisons, we summarized the main findings and discussed the differences using systematic reviews or large observational studies on the primary forms.</p></div><div><h3>Results</h3><p>From 1237 screened abstracts, 46 met the inclusion criteria, involving 358 patients (314 with ICI-PMR and 44 with ICI-GCA). ICI-PMR had an estimated pooled prevalence of 0.1% [95% CI: 0.07%, 0.14%] among ICI recipients and 15.9% [95% CI: 12.6%, 19.9%] among patients experiencing rheumatic immune-related adverse events.</p><p>Patients with ICI-PMR had a male-to-female ratio of 1.7:1 and a mean age of 71 ± 4 years. Most cases were associated with PD1/PDL1 blockers (87%). Clinical features included inflammatory pain in the girdles (100%), though pelvic girdle involvement was under-reported in some cases (3/28 studies). Peripheral arthritis was present in 35% of patients. Laboratory tests showed normal or slightly elevated inflammatory markers in 26% of cases. Glucocorticoids (GCs) led to symptom improvement in 84% of cases although 20% required immunosuppressive treatment and 14% experienced relapses.</p><p>ICI-GCA had a prevalence of 0.06% among ICI recipients, with equal gender distribution and a mean age of 71 ± 5 years. Most patients received anti-PD1/PDL1 blockers (57%). Clinical manifestations included cephalic symptoms (75%), permanent visual loss (23%) and symptoms related to large-vessel involvement (54%). High-dose GCs were effective, with 96% achieving remission, though 17% experienced relapses.</p></div><div><h3>Conclusions</h3><p>ICI-induced PMR and GCA may have distinct clinical profiles compared to idiopathic forms, with potentially milder symptoms and better treatment responses. Further studies are needed to confirm these findings and better understand the long-term outcomes and pathophysiology of these conditions.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 7","pages":"Article 103589"},"PeriodicalIF":9.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Serena Longhi , Lina Zhang , Giorgina Mieli-Vergani , Diego Vergani
{"title":"B and T cells: (Still) the dominant orchestrators in autoimmune hepatitis","authors":"Maria Serena Longhi , Lina Zhang , Giorgina Mieli-Vergani , Diego Vergani","doi":"10.1016/j.autrev.2024.103591","DOIUrl":"10.1016/j.autrev.2024.103591","url":null,"abstract":"<div><p>Autoimmune hepatitis (AIH) is a severe hepatopathy characterized by hypergammaglobulinemia, presence of serum autoantibodies and histological appearance of interface hepatitis. Liver damage in AIH is initiated by the presentation of a liver autoantigen to uncommitted Th0 lymphocytes, followed by a cascade of effector immune responses culminating with the production of inflammatory cytokines, activation of cytotoxic cells and subsequent hepatocyte injury. B cells actively participate in AIH liver damage by presenting autoantigens to uncommitted T lymphocytes. B cells also undergo maturation into plasma cells that are responsible for production of immunoglobulin G and autoantibodies, which mediate antibody dependent cell cytotoxicity. Perpetuation of effector immunity with consequent progression of liver damage is permitted by impairment in regulatory T cells (Tregs), a lymphocyte subset central to the maintenance of immune homeostasis. Treg impairment in AIH is multifactorial, deriving from numerical decrease, reduced suppressive function, poor response to IL-2 and less stable phenotype. In this review, we discuss the role of B and T lymphocytes in the pathogenesis of AIH. Immunotherapeutic strategies that could limit inflammation and halt disease progression while reconstituting tolerance to liver autoantigens are also reviewed and discussed.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 7","pages":"Article 103591"},"PeriodicalIF":9.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuyi Shen, Ming Hu, Yi Peng, Yi Zheng, Rong Zhang
{"title":"Research Progress in pathogenesis of connective tissue disease-associated interstitial lung disease from the perspective of pulmonary cells","authors":"Shuyi Shen, Ming Hu, Yi Peng, Yi Zheng, Rong Zhang","doi":"10.1016/j.autrev.2024.103600","DOIUrl":"10.1016/j.autrev.2024.103600","url":null,"abstract":"<div><p>The lungs are a principal factor in the increased morbidity and mortality observed in patients with Connective Tissue Disease (CTD), frequently presenting as CTD-associated Interstitial Lung Disease (ILD). Currently, there is a lack of comprehensive descriptions of the pulmonary cells implicated in the development of CTD-ILD. This review leverages the Human Lung Cell Atlas (HLCA) and spatial multi-omics atlases to discuss the advancements in research on the pathogenesis of CTD-ILD from a pulmonary cell perspective. This facilitates a more precise localization of disease sites and a more systematic consideration of disease progression, supporting further mechanistic studies and targeted therapies.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 7","pages":"Article 103600"},"PeriodicalIF":9.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jean C. Pfau , Brett McLaurin , Brenda J. Buck , Frederick W. Miller
{"title":"Amphibole asbestos as an environmental trigger for systemic autoimmune diseases","authors":"Jean C. Pfau , Brett McLaurin , Brenda J. Buck , Frederick W. Miller","doi":"10.1016/j.autrev.2024.103603","DOIUrl":"10.1016/j.autrev.2024.103603","url":null,"abstract":"<div><p>A growing body of evidence supports an association between systemic autoimmune disease and exposure to amphibole asbestos, a form of asbestos typically with straight, stiff, needle-like fibers that are easily inhaled. While the bulk of this evidence comes from the population exposed occupationally and environmentally to Libby Amphibole (LA) due to the mining of contaminated vermiculite in Montana, studies from Italy and Australia are broadening the evidence to other sites of amphibole exposures. What these investigations have done, that most historical studies have not, is to evaluate amphibole asbestos separately from chrysotile, the most common commercial asbestos in the United States. Here we review the current and historical evidence summarizing amphibole asbestos exposure as a risk factor for autoimmune disease. In both mice and humans, amphibole asbestos, but not chrysotile, drives production of both antinuclear autoantibodies (ANA) associated with lupus-like pathologies and pathogenic autoantibodies against mesothelial cells that appear to contribute to a severe and progressive pleural fibrosis. A growing public health concern has emerged with revelations that a) unregulated asbestos minerals can be just as pathogenic as commercial (regulated) asbestos, and b) bedrock and soil occurrences of asbestos are far more widespread than previously thought. While occupational exposures may be decreasing, environmental exposures are on the rise for many reasons, including those due to the creation of windborne asbestos-containing dusts from urban development and climate change, making this topic an urgent challenge for public and heath provider education, health screening and environmental regulations.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 7","pages":"Article 103603"},"PeriodicalIF":9.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Early skeletal muscle manifestations in polyarteritis nodosa and ANCA-associated vasculitis","authors":"Yasuhiro Shimojima, Shun Nomura, Satoru Ushiyama, Takanori Ichikawa, Ryota Takamatsu, Dai Kishida, Yoshiki Sekijima","doi":"10.1016/j.autrev.2024.103602","DOIUrl":"10.1016/j.autrev.2024.103602","url":null,"abstract":"<div><p>Skeletal muscle involvement is common in patients with small- and medium-sized vasculitis, particularly polyarteritis nodosa (PAN) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Despite being not included in the standard classification criteria for PAN and AAV, skeletal muscle involvement is an important clinical indicator, particularly when vasculitic myopathy is the only pathological evidence in the absence of other organ involvement. Herein, we comprehensively reviewed and compared the clinical features of 71 and 135 patients with PAN and AAV, respectively, with skeletal muscle involvement at the time of disease onset. Most patients with PAN and AAV exhibited skeletal muscle involvement, often characterized by myalgia and occasional muscular weakness, predominantly in the lower extremities. Myalgia and weakness were observed more frequently in the distal lower extremities in patients with PAN than in those with AAV. In contrast, skeletal muscle involvement tended to exhibit a more dispersed distribution across all four extremities in those with AAV. Muscle magnetic resonance imaging T2-weighted and short-tau inversion recovery sequences can effectively identify hyperintense areas attributed to hypervascularity of affected muscle tissues and serve as a sensitive and useful modality for visually determining the suitable biopsy site. >90% of patients with PAN and AAV demonstrated perivascular inflammation in their affected muscle tissues, whereas fibrinoid necrosis of the vessel walls was reported in two-thirds of patients. Serum creatine kinase (CK) levels were within the normal range in approximately 80% of patients presenting with skeletal muscle involvement in PAN and AAV. Furthermore, muscle fiber damage was milder in patients with skeletal muscle involvement in PAN and AAV than those with idiopathic inflammatory myositis. Meanwhile, serum CK levels were elevated in 65–85% of patients with PAN and AAV who had myofiber necrosis and degeneration in the affected muscles. Most patients with PAN and AAV showed improvement in skeletal muscle involvement following glucocorticoids (GCs) administration; however, relapse was observed in some patients during the tapering of GCs. In summary, skeletal muscle involvement is a potential indicator for establishing PAN and AAV diagnoses during the early phases of the disease.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":"23 7","pages":"Article 103602"},"PeriodicalIF":9.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}