Clinical Reviews in Allergy & Immunology最新文献

{"title":"Immune Memory in Aging: a Wide Perspective Covering Microbiota, Brain, Metabolism, and Epigenetics.","authors":"Ozlem Bulut,&nbsp;Gizem Kilic,&nbsp;Jorge Domínguez-Andrés","doi":"10.1007/s12016-021-08905-x","DOIUrl":"https://doi.org/10.1007/s12016-021-08905-x","url":null,"abstract":"<p><p>Non-specific innate and antigen-specific adaptive immunological memories are vital evolutionary adaptations that confer long-lasting protection against a wide range of pathogens. Adaptive memory is established by memory T and B lymphocytes following the recognition of an antigen. On the other hand, innate immune memory, also called trained immunity, is imprinted in innate cells such as macrophages and natural killer cells through epigenetic and metabolic reprogramming. However, these mechanisms of memory generation and maintenance are compromised as organisms age. Almost all immune cell types, both mature cells and their progenitors, go through age-related changes concerning numbers and functions. The aging immune system renders the elderly highly susceptible to infections and incapable of mounting a proper immune response upon vaccinations. Besides the increased infectious burden, older individuals also have heightened risks of metabolic and neurodegenerative diseases, which have an immunological component. This review discusses how immune function, particularly the establishment and maintenance of innate and adaptive immunological memory, regulates and is regulated by epigenetics, metabolic processes, gut microbiota, and the central nervous system throughout life, with a focus on old age. We explain in-depth how epigenetics and cellular metabolism impact immune cell function and contribute or resist the aging process. Microbiota is intimately linked with the immune system of the human host, and therefore, plays an important role in immunological memory during both homeostasis and aging. The brain, which is not an immune-isolated organ despite former opinion, interacts with the peripheral immune cells, and the aging of both systems influences the health of each other. With all these in mind, we aimed to present a comprehensive view of the aging immune system and its consequences, especially in terms of immunological memory. The review also details the mechanisms of promising anti-aging interventions and highlights a few, namely, caloric restriction, physical exercise, metformin, and resveratrol, that impact multiple facets of the aging process, including the regulation of innate and adaptive immune memory. We propose that understanding aging as a complex phenomenon, with the immune system at the center role interacting with all the other tissues and systems, would allow for more effective anti-aging strategies.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 3","pages":"499-529"},"PeriodicalIF":9.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39604458","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}

{"title":"A Contemporary Update on the Diagnosis of Systemic Lupus Erythematosus.","authors":"Xin Huang,&nbsp;Qing Zhang,&nbsp;Huilin Zhang,&nbsp;Qianjin Lu","doi":"10.1007/s12016-021-08917-7","DOIUrl":"https://doi.org/10.1007/s12016-021-08917-7","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a complicated autoimmune disease with female susceptibility. It is characterized by over-activation of the immune system and deposit of autoimmune complex in multiple organs. High heterogeneity, unpredictable disease course of SLE as well as the lack of specific and sensitive biomarkers posed diagnostic challenges to clinicians. Despite the complicated clinical presentation and pathogenesis of SLE, research regarding this disease has made many significant breakthroughs over the past decades. Some new learning can potentially be translated into clinical practice. In addition, new classification criteria to increase diagnostic accuracy were defined in 2019 by the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR). Real-world studies have accumulated evidence for the adoption of this new classification criteria. Abundant classification criteria, improved recognition of organ-specific manifestations, and updated knowledge about lupus autoantibodies enable earlier diagnosis and more personalized medicine. Thus, it is important to update our knowledge about the latest clinical practices for lupus diagnosis. This review provides new insight into the diagnosis of SLE by summarizing recent advances in epidemiology, etiology, classification criteria, clinical manifestations, and study of autoantibodies.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 3","pages":"311-329"},"PeriodicalIF":9.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39849017","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":"New Mechanistic Advances in FcεRI-Mast Cell-Mediated Allergic Signaling.","authors":"Yang Li,&nbsp;Patrick S C Leung,&nbsp;M Eric Gershwin,&nbsp;Junmin Song","doi":"10.1007/s12016-022-08955-9","DOIUrl":"https://doi.org/10.1007/s12016-022-08955-9","url":null,"abstract":"<p><p>Mast cells originate from the CD34⁺/CD117⁺ hematopoietic progenitors in the bone marrow, migrate into circulation, and ultimately mature and reside in peripheral tissues. Microbiota/metabolites and certain immune cells (e.g., Treg cells) play a key role in maintaining immune tolerance. Cross-linking of allergen-specific IgE on mast cells activates the high-affinity membrane-bound receptor FcεRI, thereby initiating an intracellular signal cascade, leading to degranulation and release of pro-inflammatory mediators. The intracellular signal transduction is intricately regulated by various kinases, transcription factors, and cytokines. Importantly, multiple signal components in the FcεRI-mast cell-mediated allergic cascade can be targeted for therapeutic purposes. Pharmacological interventions that include therapeutic antibodies against IgE, FcεRI, and cytokines as well as inhibitors/activators of several key intracellular signaling molecues have been used to inhibit allergic reactions. Other factors that are not part of the signal pathway but can enhance an individual's susceptibility to allergen stimulation are referred to as cofactors. Herein, we provide a mechanistic overview of the FcεRI-mast cell-mediated allergic signaling. This will broaden our scope and visions on specific preventive and therapeutic strategies for the clinical management of mast cell-associated hypersensitivity reactions.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 3","pages":"431-446"},"PeriodicalIF":9.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33517269","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}

{"title":"Antimitochondrial Antibodies: from Bench to Bedside.","authors":"Francesca Colapietro,&nbsp;Ana Lleo,&nbsp;Elena Generali","doi":"10.1007/s12016-021-08904-y","DOIUrl":"https://doi.org/10.1007/s12016-021-08904-y","url":null,"abstract":"<p><p>Anti-mitochondrial antibodies (AMA) are directed against the E2 subunits of the 2-oxo acid dehydrogenase complexes (PDC-E2) and are the typical biomarkers of primary biliary cholangitis (PBC), being present in 90-95% of patients, with increasing sensitivity at increasing titers. Albeit being highly specific for PBC diagnosis, AMA can be detected in less than 1% of healthy subjects, and thus the management subjects with no sign or symptom of liver disease is still a challenge and data concerning clinical risk of developing PBC in this subgroup of patients are controversial. Moreover, AMA can also be detected in patients affected by overlap syndrome, as well as hepatic diseases (i.e., NASH and viral hepatitis), while the association with autoimmune diseases, in particular Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus, is well established. Furthermore, new associations are being identified with inflammatory myositis and heart disease. AMA are directed towards the pyruvate dehydrogenase multi enzyme complex (PDC-E2) subunit, which represents an epithelial specific autoantigen for PBC. This review focuses on the main characteristics of AMA, their association with autoimmune diseases and liver diseases.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"166-177"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516050","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}

{"title":"Clinical Significance of Antinucleolar Antibodies: Biomarkers for Autoimmune Diseases, Malignancies, and others.","authors":"Minoru Satoh,&nbsp;Angela Ceribelli,&nbsp;Tomoko Hasegawa,&nbsp;Shin Tanaka","doi":"10.1007/s12016-022-08931-3","DOIUrl":"https://doi.org/10.1007/s12016-022-08931-3","url":null,"abstract":"<p><p>Nucleolar staining is one of the standard patterns in immunofluorescence antinuclear antibodies (ANA), seen in 5-9% of ANA in various conditions. Antinucleolar antibodies (ANoA) are classified into 3 patterns in the International Consensus on ANA Patterns (ICAP) classification; AC-8 homogeneous pattern, AC-9 clumpy pattern, and AC-10 punctate pattern. Specificities known to show AC-8 include anti-Th/To, -PM-Scl, -nucleophosmin/B23, -nucleolin/C23, -No55, and others. AC-9 is seen by anti-fibrillarin/U3RNP and AC-10 by anti-RNA polymerase I and hUBF/NOR-90. ANoA has been classically known to be associated with scleroderma (SSc) and the characterization of nucleolar antigens identified several autoantigens recognized by SSc autoantibodies. The clinical association of anti-Th/To, PM-Scl, fibrillarin/U3RNP, and RNA polymerase I with SSc or SSc-overlap syndrome is well established, and commercial assays are developed. Anti-hUBF/NOR90, nucleophosmin/B23, and nucleolin/C23 are known for decades and reported in systemic autoimmune rheumatic diseases (SARDs), malignancies, graft versus host disease (GVHD), and others; however, their clinical significance remains to be established.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"210-239"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516857","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":"Autoantibody Markers of Increased Risk of Malignancy in Patients with Dermatomyositis.","authors":"Milena Marzęcka, Anna Niemczyk, Lidia Rudnicka","doi":"10.1007/s12016-022-08922-4","DOIUrl":"10.1007/s12016-022-08922-4","url":null,"abstract":"<p><p>Dermatomyositis is a chronic inflammatory disease involving the skin and muscles. It most commonly occurs in adults with preponderance in females, but pediatric occurrence is also possible. The risk of malignancy in adult patients with dermatomyositis was reported to be 4.66-fold higher compared to that in the general population. A significantly increased risk of malignancy was reported within the first 12 months following the diagnosis of dermatomyositis (standardized incidence ratio equaled 17). One of the characteristic laboratory findings associated with dermatomyositis is the presence of circulating autoantibodies which are classified into two subgroups: myositis-specific and myositis-associated autoantibodies. It was shown that specific types of antibodies might be associated with an increased risk of malignancy. Current literature data indicate that the strongest correlation with malignant diseases was reported in anti-TIF1-γ-positive patients who were at a 9.37-fold higher risk of cancer. A 3.68-fold increase in the risk of cancer was also reported among patients with anti-NXP2 antibodies. Malignant diseases were reported in 14-57% of patients with anti-SAE antibodies. The presence of other autoantibodies may also be associated with an increased risk of malignancy. These data indicate that patients with circulating anti-TIF1-γ, anti-NXP2, and anti-SAE should be very closely monitored for dermatomyositis-associated malignant comorbidities. The aim of this review is to summarize the current data regarding the link between malignancy and the presence of specific antibodies in patients with dermatomyositis.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"289-296"},"PeriodicalIF":8.4,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10521155","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}

{"title":"Does Adjusted Global Antiphospholipid Syndrome Score (aGAPSS) Predict the Obstetric Outcome in Antiphospholipid Antibody Carriers? A Single-Center Study.","authors":"Sara Del Barrio-Longarela,&nbsp;Víctor M Martínez-Taboada,&nbsp;Pedro Blanco-Olavarri,&nbsp;Ana Merino,&nbsp;Leyre Riancho-Zarrabeitia,&nbsp;Alejandra Comins-Boo,&nbsp;Marcos López-Hoyos,&nbsp;José L Hernández","doi":"10.1007/s12016-021-08915-9","DOIUrl":"https://doi.org/10.1007/s12016-021-08915-9","url":null,"abstract":"<p><p>The adjusted Global Antiphospholipid Syndrome (APS) Score (aGAPSS) is a tool proposed to quantify the risk for antiphospholipid antibody (aPL)-related clinical manifestations. However, aGAPSS has been validated mainly for thrombotic events and studies on APS-related obstetric manifestations are scarce. Furthermore, the majority of them included patients with positive aPL and different autoimmune diseases. Here, we assess the utility of aGAPSS to predict the response to treatment in aPL carriers without other autoimmune disorders. One-hundred and thirty-seven women with aPL ever pregnant were included. Sixty-five meet the APS classification criteria, 61 had APS-related obstetric manifestations, and 11 were asymptomatic carriers. The patients' aGAPSS risk was grouped as low (< 6, N = 73), medium (6-11, N = 40), and high risk (≥ 12, N = 24). Since vascular risk factors included in the aGAPSS were infrequent in this population (< 10%), the aGAPSS score was mainly determined by the aPL profile. Overall, the live birth rate was 75%, and 37.2% of the patients had at least one adverse pregnancy outcome (APO). When considering patients according to the aGAPSS (high, medium, and low risk), no significant differences were found for pregnancy loss (29.2%, 25%, and 21.9%) or APO (33.3%, 47.5%, and 32.9%). In the present study, including aPL carriers without other autoimmune diseases, aGAPSS is not a valuable tool to identify patients at risk for obstetric complications despite treatment. In these patients with gestational desire, in addition to the aPL profile, other pregnancy-specific factors, such as age or previous obstetric history, should be considered.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"297-310"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10506806","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}

{"title":"Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus (NPSLE): Can They Be Used as Biomarkers for the Differential Diagnosis of This Disease?","authors":"Elias Manca","doi":"10.1007/s12016-021-08865-2","DOIUrl":"10.1007/s12016-021-08865-2","url":null,"abstract":"<p><p>Systemic lupus erythematosus is a complex immunological disease where both environmental factors and genetic predisposition lead to the dysregulation of important immune mechanisms. Eventually, the combination of these factors leads to the production of self-reactive antibodies that can target any organ or tissue of the human body. Autoantibodies can form immune complexes responsible for both the organ damage and the most severe complications. Involvement of the central nervous system defines a subcategory of the disease, generally known with the denomination of neuropsychiatric systemic lupus erythematosus. Neuropsychiatric symptoms can range from relatively mild manifestations, such as headache, to more severe complications, such as psychosis. The evaluation of the presence of the autoantibodies in the serum of these patients is the most helpful diagnostic tool for the assessment of the disease. The scientific progresses achieved in the last decades helped researchers and physicians to discover some of autoepitopes targeted by the autoantibodies, although the majority of them have not been identified yet. Additionally, the central nervous system is full of epitopes that cannot be found elsewhere in the human body, for this reason, autoantibodies that selectively target these epitopes might be used for the differential diagnosis between patients with and without the neuropsychiatric symptoms. In this review, the most relevant data is reported with regard to mechanisms implicated in the production of autoantibodies and the most important autoantibodies found among patients with systemic lupus erythematosus with and without the neuropsychiatric manifestations.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"194-209"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12016-021-08865-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10513831","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}

{"title":"The Role of Autoantibody Testing in Modern Personalized Medicine.","authors":"Cristiane Kayser,&nbsp;Lívia Almeida Dutra,&nbsp;Edgard Torres Dos Reis-Neto,&nbsp;Charlles Heldan de Moura Castro,&nbsp;Marvin J Fritzler,&nbsp;Luis Eduardo C Andrade","doi":"10.1007/s12016-021-08918-6","DOIUrl":"https://doi.org/10.1007/s12016-021-08918-6","url":null,"abstract":"<p><p>Personalized medicine (PM) aims individualized approach to prevention, diagnosis, and treatment. Precision Medicine applies the paradigm of PM by defining groups of individuals with akin characteristics. Often the two terms have been used interchangeably. The quest for PM has been advancing for centuries as traditional nosology classification defines groups of clinical conditions with relatively similar prognoses and treatment options. However, any individual is characterized by a unique set of multiple characteristics and therefore the achievement of PM implies the determination of myriad demographic, epidemiological, clinical, laboratory, and imaging parameters. The accelerated identification of numerous biological variables associated with diverse health conditions contributes to the fulfillment of one of the pre-requisites for PM. The advent of multiplex analytical platforms contributes to the determination of thousands of biological parameters using minute amounts of serum or other biological matrixes. Finally, big data analysis and machine learning contribute to the processing and integration of the multiplexed data at the individual level, allowing for the personalized definition of susceptibility, diagnosis, prognosis, prevention, and treatment. Autoantibodies are traditional biomarkers for autoimmune diseases and can contribute to PM in many aspects, including identification of individuals at risk, early diagnosis, disease sub-phenotyping, definition of prognosis, and treatment, as well as monitoring disease activity. Herein we address how autoantibodies can promote PM in autoimmune diseases using the examples of systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, Sjögren syndrome, systemic sclerosis, idiopathic inflammatory myopathies, autoimmune hepatitis, primary biliary cholangitis, and autoimmune neurologic diseases.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"251-288"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516856","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":"The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies.","authors":"Yaqi Wang,&nbsp;Shengxiang Xiao,&nbsp;Yumin Xia,&nbsp;Huixia Wang","doi":"10.1007/s12016-021-08898-7","DOIUrl":"https://doi.org/10.1007/s12016-021-08898-7","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple organ damage, especially the kidney, skin, and central nervous system. Anti-dsDNA antibodies play a pivotal role in SLE, and researchers have developed therapeutic strategies targeting these antibodies. Approaches to reduce anti-dsDNA antibodies via B cell targeted biologics against B cell surface antigens, B cell survival factors, or Bruton's tyrosine kinase have effectively eliminated B cells. However, their non-specific depletion hampers normal immune system functioning and limits the therapeutic benefits. Thus, scientists have attempted anti-dsDNA antibodies or lupus-specific strategies, such as the immature dendritic cell vaccine and immunoadsorption. Recently, synthetic mimic peptides (hCDR1, pCONs, DWEYS, FISLE-412, and ALW) that directly block anti-dsDNA autoantibodies have attracted attention, which could ameliorate lupus, decrease the serological autoantibody titer, reduce the deposition of renal autoantibodies, and improve pathological performance. These potent small peptide molecules are well tolerated, non-toxic, and non-immunogenic, which have demonstrated a benign safety profile and are expected to be hopeful candidates for SLE management. In this review, we clarify the role of anti-dsDNA antibodies in SLE, mainly focus on the current strategies targeting anti-dsDNA antibodies, and discuss their potential clinical value.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"152-165"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10570238","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}