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Treat-to-Target in Pediatric Rheumatic Diseases. 治疗小儿风湿病。
IF 5 2区 医学 Q1 Medicine Pub Date : 2023-11-01 Epub Date: 2023-08-16 DOI: 10.1007/s11926-023-01112-x
Silvia Rosina, Ana Isabel Rebollo-Giménez, Alessandro Consolaro, Angelo Ravelli

Purpose of review: To summarize the current evidence on the adoption of the treat-to-target (T2T) strategy in pediatric rheumatic diseases (PRD).

Recent findings: The recent advances in the management of PRD have markedly increased the ability to achieve disease remission. Complete disease quiescence is regarded as the ideal therapeutic goal because its attainment leads to lesser long-term damage and physical disability, and to optimization of quality of life. Studies in adult rheumatic diseases have shown that patient outcomes are improved if complete suppression of the inflammatory process is aimed for by frequent adjustments of therapy according to quantitative indices. This approach, which underlies the T2T concept, has been applied in strategic trials in rheumatoid arthritis (RA). Furthermore, recommendations for the T2T have been issued for RA and other adult rheumatic diseases. There is currently a growing interest for the introduction of T2T in PRD, and recommendations for treating juvenile idiopathic arthritis (JIA) to target were promulgated. A similar initiative has been undertaken for childhood-onset systemic lupus erythematosus. Preliminary therapeutic studies have explored the T2T design in JIA. The T2T strategy is a modern therapeutic approach that holds the promise of improving the outcomes in patients with PRD.

综述目的:总结目前在儿童风湿性疾病(PRD)中采用靶向治疗(T2T)策略的证据。最新发现:PRD管理的最新进展显著提高了实现疾病缓解的能力。完全疾病静止被认为是理想的治疗目标,因为它的实现可以减少长期损伤和身体残疾,并优化生活质量。对成人风湿性疾病的研究表明,如果通过根据定量指标频繁调整治疗来完全抑制炎症过程,患者的预后会得到改善。这种方法是T2T概念的基础,已应用于类风湿性关节炎(RA)的战略试验。此外,还针对RA和其他成人风湿性疾病发布了T2T的建议。目前,人们对在PRD中引入T2T越来越感兴趣,并颁布了针对青少年特发性关节炎(JIA)的治疗建议。针对儿童期系统性红斑狼疮也采取了类似的措施。初步的治疗研究已经探索了JIA的T2T设计。T2T策略是一种现代治疗方法,有望改善PRD患者的预后。
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引用次数: 0
Machine Learning Approaches to the Prediction of Osteoarthritis Phenotypes and Outcomes. 预测骨关节炎表型和结果的机器学习方法。
IF 5 2区 医学 Q1 Medicine Pub Date : 2023-11-01 Epub Date: 2023-08-10 DOI: 10.1007/s11926-023-01114-9
Liubov Arbeeva, Mary C Minnig, Katherine A Yates, Amanda E Nelson

Purpose of review: Osteoarthritis (OA) is a complex heterogeneous disease with no effective treatments. Artificial intelligence (AI) and its subfield machine learning (ML) can be applied to data from different sources to (1) assist clinicians and patients in decision making, based on machine-learned evidence, and (2) improve our understanding of pathophysiology and mechanisms underlying OA, providing new insights into disease management and prevention. The purpose of this review is to improve the ability of clinicians and OA researchers to understand the strengths and limitations of AI/ML methods in applications to OA research.

Recent findings: AI/ML can assist clinicians by prediction of OA incidence and progression and by providing tailored personalized treatment. These methods allow using multidimensional multi-source data to understand the nature of OA, to identify different OA phenotypes, and for biomarker discovery. We described the recent implementations of AI/ML in OA research and highlighted potential future directions and associated challenges.

综述目的:骨关节炎(OA)是一种复杂的异质性疾病,尚无有效的治疗方法。人工智能(AI)及其子领域机器学习(ML)可以应用于来自不同来源的数据,以(1)基于机器学习证据帮助临床医生和患者做出决策,以及(2)提高我们对OA的病理生理学和机制的理解,为疾病管理和预防提供新的见解。这篇综述的目的是提高临床医生和OA研究人员了解AI/ML方法在OA研究中应用的优势和局限性的能力。最近的发现:AI/ML可以通过预测OA的发病率和进展以及提供量身定制的个性化治疗来帮助临床医生。这些方法允许使用多维多源数据来了解OA的性质,识别不同的OA表型,并用于生物标志物的发现。我们描述了AI/ML在OA研究中的最新实现,并强调了潜在的未来方向和相关挑战。
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引用次数: 0
Systemic Lupus Erythematosus and COVID-19. 系统性红斑狼疮与新冠肺炎。
IF 5 2区 医学 Q1 Medicine Pub Date : 2023-10-01 Epub Date: 2023-07-21 DOI: 10.1007/s11926-023-01110-z
Maria Pappa, Alexandros Panagiotopoulos, Konstantinos Thomas, Antonis Fanouriakis

Purpose of review: To describe the current state of knowledge regarding COVID-19 in patients with systemic lupus erythematosus (SLE). We focus on (i) SARS-CoV-2 vaccination uptake, immunogenicity and safety, and (ii) outcomes of COVID-19 in patients with SLE and pertinent risk factors for adverse sequelae.

Recent findings: Notwithstanding the potential concern of patients about possible post-vaccination side-effects, the safety of anti-SARS-CoV-2 vaccines in patients with SLE has been undisputedly confirmed in numerous studies. Humoral immunogenicity is generally attained in SLE, although affected by the use of background immunosuppressive drugs, especially rituximab. The latter has also clearly been implicated with adverse COVID-19 outcomes in SLE, including need for hospitalization, mechanical ventilation and death. Although the wide adoption of vaccination has significantly improved COVID-19 outcomes, patients with SLE continue to pose challenges during the pandemic, mainly owing to administered immunosuppressive medications.

综述目的:描述系统性红斑狼疮(SLE)患者对新冠肺炎的认识现状。我们重点关注(i)SARS-CoV-2疫苗接种率、免疫原性和安全性,以及(ii)SLE患者的新冠肺炎结果和不良后遗症的相关风险因素。最近的发现:尽管患者可能担心疫苗接种后可能出现的副作用,但抗严重急性呼吸系统综合征冠状病毒2型疫苗在SLE患者中的安全性已在大量研究中得到证实。SLE通常会获得体液免疫原性,尽管会受到背景免疫抑制药物的影响,尤其是利妥昔单抗。后者也明显与SLE的新冠肺炎不良后果有关,包括需要住院、机械通气和死亡。尽管疫苗接种的广泛采用显著改善了新冠肺炎的结果,但SLE患者在大流行期间仍然面临挑战,主要是由于服用了免疫抑制药物。
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引用次数: 0
Flares in Lupus Nephritis: Risk Factors and Strategies for Their Prevention. 狼疮性肾炎中的片状物:危险因素及其预防策略。
IF 5 2区 医学 Q1 Medicine Pub Date : 2023-10-01 Epub Date: 2023-07-15 DOI: 10.1007/s11926-023-01109-6
Aggelos Banos, George Bertsias

Purpose of review: Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies.

Recent findings: Recently performed clinical trials and observational cohort studies underscore the high frequency of relapses of kidney disease, following initial response, in patients with proliferative and/or membranous lupus nephritis. Analysis of hard disease outcomes such as progression to chronic kidney disease or end-stage kidney disease, coupled with histological findings from repeat kidney biopsy studies, have drawn attention to the importance of renal function preservation that should be pursued as early as lupus nephritis is diagnosed. In this respect, non-randomized and randomized evidence have suggested a number of factors associated with reduced risk of renal flares such as attaining a very low level of proteinuria (< 700-800 mg/24 h by 12 months), using mycophenolate over azathioprine, adding belimumab to standard therapy, maintaining immunosuppressive/biological treatment for at least 3 to 5 years, and using hydroxychloroquine. Other factors that warrant further clarification include serological activity and the use of repeat kidney biopsy to guide the intensity and duration of treatment in selected cases. The results from ongoing innovative studies integrating kidney histological and clinical outcomes, together with an expanding spectrum of therapies in lupus nephritis, are expected to facilitate individual medical care and long-term disease and patient prognosis.

综述的目的:讨论狼疮性肾炎患者肾闪变的预后意义、相关危险因素和可能的预防策略。最近的发现:最近进行的临床试验和观察性队列研究强调,在增殖性和/或膜性狼疮肾炎患者中,肾脏疾病在最初反应后复发的频率很高。对硬疾病结果的分析,如进展为慢性肾脏疾病或终末期肾脏疾病,再加上重复肾活检研究的组织学结果,引起了人们对肾功能保护重要性的关注,在诊断为狼疮性肾炎时就应该尽早进行。在这方面,非随机和随机的证据表明,许多因素与肾功能发作风险降低有关,例如蛋白尿水平非常低(
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引用次数: 2
Emerging Concepts in Precision Medicine in Axial Spondyloarthritis. 轴性脊柱炎精准医学的新概念。
IF 5 2区 医学 Q1 Medicine Pub Date : 2023-10-01 Epub Date: 2023-07-28 DOI: 10.1007/s11926-023-01113-w
Hugues Allard-Chamard, Quan Li, Proton Rahman

Purpose of review: Axial spondyloarthritis (AxSpA) is among the rheumatology's most heritable complex diseases, yet precision medicine at clinics still needs to be explored. We reviewed the emerging concepts and recent developments in polygenic risk scores, Mendelian randomization, pharmacogenomics, single-cell sequencing, and spatial transcriptomics.

Recent findings: Polygenic risk score has resulted in encouraging results with potential diagnostic utility as it appears to outperform current diagnostic tools. Its performance and generalizability vary with ethnicity. Mendelian randomization has elucidated multiple causal associations, particularly between inflammatory bowel disease and AxSpA. Single-cell transcriptomics (particularly scRNA-seq and scATAC-seq) has identified numerous cell types, including synovial and blood immunological cells, to understand the contribution of both innate and adaptative immunity in AxSpA. Current molecular tools provide an exciting opportunity to advance precision medicine for AxSpA patients. However, extensive research and implementation strategies are still required before they can have an impact in the clinic.

综述目的:轴性脊椎关节炎(AxSpA)是风湿病中最具遗传性的复杂疾病之一,但临床上的精准医学仍有待探索。我们综述了多基因风险评分、孟德尔随机化、药物基因组学、单细胞测序和空间转录组学的新概念和最新进展。最近的发现:多基因风险评分产生了令人鼓舞的结果,具有潜在的诊断实用性,因为它似乎优于当前的诊断工具。它的表现和可推广性因种族而异。孟德尔随机化已经阐明了多种因果关系,特别是炎症性肠病和AxSpA之间的关系。单细胞转录组学(特别是scRNA-seq和scATAC-seq)已经鉴定了许多细胞类型,包括滑膜和血液免疫细胞,以了解先天免疫和适应性免疫在AxSpA中的作用。目前的分子工具为AxSpA患者提供了一个推进精确医学的令人兴奋的机会。然而,在对临床产生影响之前,仍然需要广泛的研究和实施策略。
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引用次数: 1
Neuroimmune Mechanisms Underlying Post-acute Sequelae of SARS-CoV-2 (PASC) Pain, Predictions from a Ligand-Receptor Interactome. SARS-CoV-2急性后遗症(PASC)疼痛的神经免疫机制,配体-受体相互作用组的预测。
IF 5.7 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2023-09-01 Epub Date: 2023-06-10 DOI: 10.1007/s11926-023-01107-8
Joseph B Lesnak, Khadijah Mazhar, Theodore J Price

Purpose of review: Individuals with post-acute sequelae of SARS-CoV-2 (PASC) complain of persistent musculoskeletal pain. Determining how COVID-19 infection produces persistent pain would be valuable for the development of therapeutics aimed at alleviating these symptoms.

Recent findings: To generate hypotheses regarding neuroimmune interactions in PASC, we used a ligand-receptor interactome to make predictions about how ligands from PBMCs in individuals with COVID-19 communicate with dorsal root ganglia (DRG) neurons to induce persistent pain. In a structured literature review of -omics COVID-19 studies, we identified ligands capable of binding to receptors on DRG neurons, which stimulate signaling pathways including immune cell activation and chemotaxis, the complement system, and type I interferon signaling. The most consistent finding across immune cell types was an upregulation of genes encoding the alarmins S100A8/9 and MHC-I. This ligand-receptor interactome, from our hypothesis-generating literature review, can be used to guide future research surrounding mechanisms of PASC-induced pain.

审查目的:SARS-CoV-2(PASC)急性后遗症患者主诉肌肉骨骼持续疼痛。确定 COVID-19 感染是如何产生持续性疼痛的,这对开发旨在缓解这些症状的疗法很有价值:为了提出有关 PASC 神经免疫相互作用的假设,我们使用配体-受体相互作用组来预测 COVID-19 感染者的 PBMCs 中的配体如何与背根神经节 (DRG) 神经元沟通以诱发持续性疼痛。在对 -组学 COVID-19 研究的结构化文献综述中,我们确定了能够与 DRG 神经元上的受体结合的配体,这些配体可刺激信号通路,包括免疫细胞活化和趋化、补体系统和 I 型干扰素信号传导。在各种免疫细胞类型中,最一致的发现是编码警戒素 S100A8/9 和 MHC-I 的基因上调。从我们的假设生成文献综述中得出的配体-受体相互作用组,可用于指导未来围绕 PASC 诱发疼痛机制的研究。
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引用次数: 0
Intravenous Immunoglobulin in Idiopathic Inflammatory Myopathies: a Practical Guide for Clinical Use. 静脉注射免疫球蛋白治疗特发性炎性肌病:临床使用实用指南。
IF 5 2区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1007/s11926-023-01105-w
Prateek C Gandiga, Daniela Ghetie, Elizabeth Anderson, Rohit Aggrawal

Purpose of review: Idiopathic inflammatory myopathies (IIM) are a complex family of autoimmune systemic disorders which often affect muscle and/or skin. IIM cause significant morbidity and mortality, but optimal treatment is uncertain. This review provides a practical guide for using intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) in the management of IIM, including dermatomyositis (DM), polymyositis (PM), immune-mediated necrotizing myositis (IMNM), and spontaneous inclusion body myositis (IBM), based on relevant recent literature and experience. We summarize pertinent considerations when using IVIG in special circumstances, including myositis-related dysphagia, interstitial lung disease (ILD), calcinosis cutis, and pregnant patients. This review also discusses IVIG safety, available formulations, and costs.

Recent findings: While IVIG has been used de facto for severe IIM for over 30 years, prior clinical trials of IVIG were notably limited. Recently, however, IVIG has proven safe and effective against IIM in several high-impact publications, including a large prospective, randomized placebo-controlled phase III study in DM. IVIG is useful against both muscular and extra-muscular manifestations in many types of IIM. It can be used as a first-line, steroid-sparring agent or as add-on to other treatments, tailored to specific clinical IIM scenarios. It is generally well-tolerated and has good safety profile, but accessibility and cost still limit its use.

综述目的:特发性炎症性肌病(IIM)是一种复杂的自身免疫系统疾病家族,通常影响肌肉和/或皮肤。IIM引起显著的发病率和死亡率,但最佳治疗尚不确定。本文综述了静脉注射免疫球蛋白(IVIG)和皮下免疫球蛋白(SCIG)在IIM治疗中的应用,包括皮肌炎(DM)、多发性肌炎(PM)、免疫介导坏死性肌炎(IMNM)和自发性包涵体肌炎(IBM),基于近期相关文献和经验。我们总结了在特殊情况下使用IVIG的相关考虑,包括肌炎相关的吞咽困难,间质性肺疾病(ILD),皮肤钙质沉着症和孕妇。本综述还讨论了IVIG的安全性、可用的配方和成本。最近的研究发现:虽然IVIG实际上已经用于治疗严重IIM超过30年,但IVIG之前的临床试验明显有限。然而,最近在一些高影响力的出版物中,IVIG已被证明对IIM是安全有效的,包括一项大型前瞻性、随机安慰剂对照的糖尿病III期研究。IVIG对许多类型IIM的肌肉和肌肉外表现都是有用的。它可以作为一线的类固醇辅助剂,也可以作为其他治疗的补充,根据特定的临床IIM情况量身定制。它通常耐受性好,安全性好,但可及性和成本仍然限制其使用。
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引用次数: 0
An Update on the Diagnosis and Management of Calcium Crystal Disease. 钙晶体病的诊断和治疗进展。
IF 5 2区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1007/s11926-023-01106-9
Rachael Flood, John Stack, Geraldine McCarthy

Purpose of review: This article aims to review the challenges to diagnosis and management of calcium crystal deposition diseases and evaluate the literature published over the past 3 years.

Recent findings: The awaited development of classification criteria is an essential step in the progression of calcium crystal deposition disease clinical research. There have been recent improvements in the accuracy of imaging for the diagnosis of crystal deposition diseases with published definitions of characteristic features. Factors associated with acute flares of disease have been identified and an association with increased cardiovascular risk has been demonstrated. Targeted treatment options for calcium crystal diseases remain elusive. However, there have been advances in understanding the molecular mechanisms of disease revealing potential targets for future drug development. Calcium-crystal deposition diseases are increasing in incidence and prevalence as populations age and continue to associate with a high burden of disability. Despite this, calcium crystal deposition disease remains under-studied with a paucity of evidence-based treatment guidelines.

综述目的:本文旨在回顾钙晶体沉积病的诊断和治疗面临的挑战,并对近3年来发表的文献进行评价。最新发现:分级标准的制定是钙晶体沉积病临床研究进展的重要一步。最近在晶体沉积疾病的影像学诊断准确度方面有了一些改进,这些疾病具有已发表的特征定义。已经确定了与疾病急性发作相关的因素,并证明了与心血管风险增加的关联。钙晶体疾病的靶向治疗方案仍然难以捉摸。然而,在了解疾病的分子机制方面取得了进展,揭示了未来药物开发的潜在靶点。随着人口老龄化,钙晶体沉积病的发病率和流行率不断增加,并继续与残疾的高负担相关。尽管如此,钙晶体沉积病的研究仍然不足,缺乏循证治疗指南。
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引用次数: 0
Syndesmophyte Growth in Ankylosing Spondylitis: from Laboratory to Bedside. 强直性脊柱炎伴生菌生长:从实验室到床边。
IF 5 2区 医学 Q1 Medicine Pub Date : 2023-07-01 DOI: 10.1007/s11926-023-01104-x
Michael M Ward, Sovira Tan

Purpose of review: This study aims to review recent studies on risk factors for syndesmophyte growth in ankylosing spondylitis (AS) and on treatment effects.

Recent findings: New genetic studies, including a genome-wide association study, provided only limited evidence of specific genetic associations with radiographic severity. Measures of inflammation, including vertebral osteitis and C-reactive protein level, were strongly associated with radiographic progression, while studies of adipokines had mixed results. Mesenchymal stem cells from HLA-B27 positive AS patients were found to promote vertebral ossification via a pathway of B27 misfolding, retinoic acid receptor-β activation, and increased bone alkaline phosphatase. Low vertebral trabecular bone density is associated with syndesmophyte growth, with reciprocal effects when bridged. Several observational studies suggested radiographic severity was reduced by treatment with tumor necrosis factor inhibitors, particularly when longer than 2 years. Syndesmophyte development in AS is the result of a complex, incompletely understood, interplay of inflammatory and mechanical factors.

综述目的:本研究旨在综述强直性脊柱炎(AS)伴发真菌生长的危险因素及治疗效果的最新研究。最新发现:新的遗传学研究,包括一项全基因组关联研究,仅提供了有限的证据,证明特定的遗传与放射学严重程度有关。炎症的测量,包括椎体骨炎和c反应蛋白水平,与放射学进展密切相关,而脂肪因子的研究结果则好坏参半。来自HLA-B27阳性AS患者的间充质干细胞通过B27错误折叠、视黄酸受体-β激活和骨碱性磷酸酶增加的途径促进椎体骨化。低椎骨小梁骨密度与副骨生长有关,桥接时相互作用。几项观察性研究表明,使用肿瘤坏死因子抑制剂治疗可降低放射学的严重程度,特别是治疗时间超过2年。AS伴生菌的发育是炎症和机械因素复杂而不完全了解的相互作用的结果。
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引用次数: 0
Has the COVID 19 Pandemic Impacted the Management of Chronic Musculoskeletal Pain? COVID - 19大流行是否影响了慢性肌肉骨骼疼痛的治疗?
IF 5 2区 医学 Q1 Medicine Pub Date : 2023-07-01 DOI: 10.1007/s11926-023-01103-y
Mahdokht Parsirad, Samon Oomen-Lochtefeld, Brigette Suerig, Chenchen Wang

Purpose of review: The COVID-19 pandemic has affected the management of chronic musculoskeletal pain; however, the extent of its impact has not been established. We conducted a comprehensive review of the pandemic's impact on clinical outcomes and healthcare accessibility for osteoarthritis (OA), rheumatoid arthritis (RA), fibromyalgia (FM), lower back pain (LBP), and other musculoskeletal disorders and chronic pain syndromes to better inform clinical decision-making.

Recent findings: We examined 30 studies (n = 18,810) from 36 countries investigating the impact of the COVID-19 pandemic on chronic musculoskeletal pain outcomes. The available evidence suggests that the pandemic significantly impacted pain levels, mental health, quality of life and healthcare accessibility in patients with chronic musculoskeletal pain. Of 30 studies, 25 (83%) reported symptom worsening, and 20 (67%) reported reduced healthcare accessibility. Patients were unable to access necessary care services during the pandemic, including orthopedic surgeries, medications, and complementary therapies, leading to worsened pain, psychological health, and quality of life. Across conditions, vulnerable patients reported high pain catastrophizing, psychological stress, and low physical activity related to social isolation. Notably, positive coping strategies, regular physical activity, and social support were associated with positive health outcomes. Most patients with chronic musculoskeletal pain had greatly affected pain severity, physical function, and quality of life during the COVID-19 pandemic. Moreover, the pandemic significantly impacted treatment accessibility, preventing necessary therapies. These findings support further prioritization of chronic musculoskeletal pain patient care.

综述目的:COVID-19大流行影响慢性肌肉骨骼疼痛的治疗;但是,其影响的程度尚未确定。我们对大流行对骨关节炎(OA)、类风湿性关节炎(RA)、纤维肌痛(FM)、腰痛(LBP)以及其他肌肉骨骼疾病和慢性疼痛综合征的临床结果和医疗可及性的影响进行了全面回顾,以更好地为临床决策提供信息。最近的发现:我们检查了来自36个国家的30项研究(n = 18810),这些研究调查了COVID-19大流行对慢性肌肉骨骼疼痛结果的影响。现有证据表明,大流行显著影响了慢性肌肉骨骼疼痛患者的疼痛水平、心理健康、生活质量和医疗保健可及性。在30项研究中,25项(83%)报告了症状恶化,20项(67%)报告了医疗保健可及性降低。在大流行期间,患者无法获得必要的护理服务,包括整形手术、药物治疗和补充疗法,导致疼痛、心理健康和生活质量恶化。在各种情况下,易受伤害的患者报告了与社会孤立相关的高疼痛灾难化、心理压力和低体力活动。值得注意的是,积极的应对策略、定期的体育活动和社会支持与积极的健康结果有关。在COVID-19大流行期间,大多数慢性肌肉骨骼疼痛患者的疼痛严重程度、身体功能和生活质量受到严重影响。此外,大流行病严重影响了治疗的可及性,妨碍了必要的治疗。这些发现支持进一步优先考虑慢性肌肉骨骼疼痛患者的护理。
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引用次数: 0
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Current Rheumatology Reports
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