Ankylosing spondylitis

强直性脊柱炎
  • 文章类型: Journal Article
    脊柱疾病,包括椎间盘退变(IDD),强直性脊柱炎,脊髓损伤和其他非感染性脊柱疾病,严重影响患者的生活质量。目前对IDD和其他脊柱疾病的治疗只能缓解症状,不能完全治愈疾病。因此,迫切需要探索这些疾病的原因并开发新的治疗方法。长链非编码RNA(lncRNA),一种非编码RNA,来源丰富多样,有许多功能,在IDD等脊柱疾病的发生发展中起着重要作用。然而,lncRNAs的作用机制尚未完全阐明,在使用lncRNAs作为新的治疗靶标方面仍然存在重大挑战。本文回顾了来源,lncRNAs的分类和功能,并介绍了lncRNAs在脊柱疾病中的作用,例如IDD,和他们的治疗潜力。
    Spinal diseases, including intervertebral disc degeneration (IDD), ankylosing spondylitis, spinal cord injury and other non‑infectious spinal diseases, severely affect the quality of life of patients. Current treatments for IDD and other spinal diseases can only relieve symptoms and do not completely cure the disease. Therefore, there is an urgent need to explore the causes of these diseases and develop new treatment approaches. Long non‑coding RNA (lncRNA), a form of non‑coding RNA, is abundant in diverse sources, has numerous functions, and plays an important role in the occurrence and development of spinal diseases such as IDD. However, the mechanism of action of lncRNAs has not been fully elucidated, and significant challenges remain in the use of lncRNAs as new therapeutic targets. The present article reviews the sources, classification and functions of lncRNAs, and introduces the role of lncRNAs in spinal diseases, such as IDD, and their therapeutic potential.
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  • 文章类型: Journal Article
    水凝胶以其出色的吸收性而著称,与生物系统的相容性令人满意,降解能力,和固有的安全性,所有这些都有助于他们在生物医学领域的高需求。这项研究的重点是使用环境友好的纤维素材料制造水凝胶。通过在NaOH/尿素介质中物理交联制备纤维素水凝胶珠。此外,纳米聚多巴胺作为功能性聚合物被整合到水凝胶基质中,α-mangostin被用作活性药物成分。利用傅里叶变换红外光谱仪对其理化性质进行了综合分析,13C交叉极化/魔角旋转核磁共振,热重分析,和扫描电子显微镜。药物输送特性,包括含水量,溶胀率,和药物释放曲线,进行了评估。使用磺基罗丹明B染色评估针对MC3T3-E1细胞的体外细胞毒性。所有测试水凝胶均表现出对MC3T3-E1细胞生长的抑制活性。这些结果表明这些水凝胶在治疗强直性脊柱炎中作为α-芒果苷的药物递送载体的潜在用途。
    Hydrogels are notable for their outstanding absorbent qualities, satisfactory compatibility with biological systems, ability to degrade, and inherent safety, all of which contribute to their high demand in the field of biomedicine. This study focuses on the fabrication of hydrogels using environmentally friendly cellulosic material. Cellulose hydrogel beads were prepared by physical cross-linking in a NaOH/urea medium. Furthermore, nano polydopamine was integrated into the hydrogel matrix as functional polymers and α-mangostin was employed as an active pharmaceutical ingredient. The physicochemical properties were comprehensively analyzed using Fourier-transform infrared spectrometer, 13C cross-polarization/magic angle spinning nuclear magnetic resonance, thermogravimetric analysis, and scanning electron microscope. The drug delivery properties, including water content, swelling ratio, and drug release profiles, were evaluated. In vitro cytotoxicity against MC3T3-E1 cells was assessed using sulforhodamine B staining. All test hydrogels exhibited inhibitory activity against the growth of MC3T3-E1 cells. These results indicated the potential use of these hydrogels as a drug delivery carrier for α-mangostin in the treatment of ankylosing spondylitis.
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  • 文章类型: Journal Article
    目前的观察性研究提示强直性脊柱炎和心血管健康之间存在潜在的联系。然而,这种因果关系的性质还有待阐明。因此,本研究旨在利用双向双样本孟德尔随机化(MR)方法学评估强直性脊柱炎与心血管相关疾病之间的因果关系.
    在这项研究中,我们使用全基因组关联研究(GWAS)数据进行了孟德尔随机化(MR)分析.采用固定效应逆方差加权(IVW)模型作为主要分析方法,MR-Egger回归和加权中位数法作为补充方法。使用各种统计检验评估水平多效性和异质性,包括MR-PRESSO全球测试,MR-Egger截获,和Cochran的Q测试。
    MR结果显示,强直性脊柱炎患者心力衰竭风险增加(OR:1.0132,95%CI=1.0043-1.0221,p=0.003)。MR分析结果未显示强直性脊柱炎与其他心血管疾病之间的因果关系。比如心房颤动,冠状动脉疾病,缺血性卒中,心肌梗塞,和心脏瓣膜病(均p>0.05)。在反向MR分析中,没有发现强直性脊柱炎与提到的心血管疾病之间存在反向因果关系的证据。灵敏度分析验证了结果的可靠性。
    我们的MR研究表明强直性脊柱炎与心力衰竭风险增加之间存在关系。需要进一步的研究来证实这些发现并阐明所涉及的潜在机制。
    UNASSIGNED: Current observational investigations hint at a potential linkage between ankylosing spondylitis and cardiovascular wellness. However, the nature of this causality remains to be elucidated. Consequently, this study is designed to evaluate the causal interconnection between ankylosing spondylitis and cardiovascular-related conditions utilizing a bidirectional two-sample Mendelian Randomization (MR) methodology.
    UNASSIGNED: In this study, we conducted Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. The fixed-effects inverse variance weighted (IVW) model was used as the primary analysis method, and MR-Egger regression and the weighted median method were employed as supplementary approaches. Horizontal pleiotropy and heterogeneity were evaluated using various statistical tests, including MR-PRESSO global test, MR-Egger intercept, and Cochran\'s Q test.
    UNASSIGNED: The MR result demonstrated an increased risk of heart failure in individuals with ankylosing spondylitis (OR: 1.0132, 95% CI = 1.0043-1.0221, p = 0.003). The MR analysis results did not demonstrate a causal relationship between ankylosing spondylitis and other cardiovascular diseases, such as atrial fibrillation, coronary artery disease, ischemic stroke, myocardial infarction, and valvular heart disease (all p > 0.05). No evidence of reverse causality was found between ankylosing spondylitis and mentioned cardiovascular diseases in reverse MR analyses. Sensitivity analysis verified the reliability of the results.
    UNASSIGNED: Our MR study indicates a relationship between ankylosing spondylitis and an increased risk of heart failure. Further research is needed to confirm these findings and elucidate the underlying mechanisms involved.
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  • 文章类型: Journal Article
    越来越多的证据表明,强直性脊柱炎(AS)患者心血管疾病(CVD)和心血管死亡的风险升高,然而,目前尚不清楚AS是否对CVD风险有因果关系.利用两个样本孟德尔随机化(MR)来检查它们之间可能的因果关系。
    使用公开发布的全基因组关联研究(GWAS)的汇总统计数据进行MR分析。从已发表的GWAS荟萃分析中选择遗传预测的AS作为暴露变量。采用CVD作为结果变量。采用逆变量加权方法获得临时估计。还通过评估单核苷酸多态性的多效性和异质性来检查结果的稳健性。
    根据MR分析,AS的遗传易感性与心力衰竭和缺血性卒中的高风险相关,而在AS和外周动脉粥样硬化之间发现了负遗传易感性。AS与静脉血栓栓塞症之间无统计学关系,心房颤动,冠状动脉粥样硬化,和心脏瓣膜病.敏感性分析显示没有水平多效性或异质性的证据。
    本研究表明,AS对心血管疾病的风险有因果关系,包括心力衰竭,缺血性卒中,和外周动脉粥样硬化。
    UNASSIGNED: Accumulating evidence suggests that patients with ankylosing spondylitis (AS) have an elevated risk for cardiovascular disease (CVD) and cardiovascular death, however, whether AS has causal effects on the risk of CVD is unclear.Two-sample Mendelian randomization (MR) was utilizedto examine the probable causal link between them.
    UNASSIGNED: Summary statistics from publicly released genome-wide association studies (GWAS) was used to perform MR analyses. Genetically predicted AS was selected as the exposure variable from published GWAS meta-analyses. CVD was adopted as the outcome variable. The inverse variant weighted method was employed to obtain the casual estimates. The robustness of the results was also examined by evaluating the pleiotropy and heterogeneity of single-nucleotide polymorphisms.
    UNASSIGNED: According to MR analyses, genetic susceptibility to AS was associated with a high risk of heart failure and ischemic stroke, while negativelygenetic susceptibility was found between AS and peripheral atherosclerosis. No statistical relationship was found between AS and venous thromboembolism, atrial fibrillation, coronary atherosclerosis, and valvular heart disease. Sensitivity analysis showed no evidence of horizontal pleiotropy or heterogeneity.
    UNASSIGNED: The present study suggests that AS exerts causal effects on the risk of CVD, including heart failure, ischemic stroke, and peripheral atherosclerosis.
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  • 文章类型: Journal Article
    背景:强直性脊柱炎(AS)患者经常患有共病睡眠障碍,加重疾病负担,影响他们的生活质量。
    目的:探讨血清炎症因子的临床意义,合并睡眠障碍的AS患者的健康指数和疾病活动评分。
    方法:本研究共纳入106例合并睡眠障碍的AS患者。根据患者的临床结果,将患者分为理想和不良预后组。血清炎症因子水平,包括C反应蛋白,红细胞沉降率,白细胞介素(IL)-6,肿瘤坏死因子-α和IL-1β,被测量。疾病活动评分,如浴AS功能指数,巴斯AS疾病活动指数,BathAS计量学指数和AS疾病活动度评分,被评估。健康指数是通过简短表格36问卷获得的。
    结果:该研究发现血清炎症因子之间存在显着关联,合并睡眠障碍的AS患者的健康指数和疾病活动评分。血清炎症因子与疾病活动度评分呈正相关,提示全身炎症对疾病严重程度和功能损害的影响。相反,疾病活动评分与健康指数参数呈负相关,强调疾病活动对健康相关生活质量各个方面的影响。Logistic回归分析进一步证实了这些因素对患者预后的预测价值,强调它们在风险评估和预测中的潜在效用。
    结论:研究结果表明,疾病活动之间存在复杂的相互作用,合并睡眠障碍的AS患者的全身性炎症和患者报告的健康结局。结果强调需要全面的护理策略,以解决这些患者面临的不同需求和挑战,并强调血清炎症因子的潜在相关性。健康指数和疾病活动评分作为该患者人群的预后指标。
    BACKGROUND: Patients with ankylosing spondylitis (AS) frequently suffer from comorbid sleep disorders, exacerbating the burden of the disease and affecting their quality of life.
    OBJECTIVE: To investigate the clinical significance of serum inflammatory factors, health index and disease activity scores in patients with AS complicated by sleep disorders.
    METHODS: A total of 106 AS patients with comorbid sleep disorders were included in the study. The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes. The serum levels of inflammatory factors, including C-reactive protein, erythrocyte sedimentation rate, interleukin (IL)-6, tumour necrosis factor-α and IL-1β, were measured. Disease activity scores, such as the Bath AS functional index, Bath AS disease activity index, Bath AS metrology index and AS disease activity score, were assessed. The health index was obtained through the Short Form-36 questionnaire.
    RESULTS: The study found significant associations amongst serum inflammatory factors, health index and disease activity scores in AS patients with comorbid sleep disorders. Positive correlations were found between serum inflammatory factors and disease activity scores, indicating the influence of heightened systemic inflammation on disease severity and functional impairment. Conversely, negative correlations were found between disease activity scores and health index parameters, highlighting the effect of disease activity on various aspects of health-related quality of life. Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes, underscoring their potential utility in risk assessment and prognostication.
    CONCLUSIONS: The findings demonstrate the intricate interplay amongst disease activity, systemic inflammation and patient-reported health outcomes in AS patients complicated by sleep disorders. The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors, health index and disease activity scores as prognostic markers in this patient population.
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  • 文章类型: Journal Article
    目的:本研究的目的是调查中国强直性脊柱炎(AS)患者的健康相关生活质量状况,并分析与关节炎国际社会健康指数(ASAS-HI)评估AS的相关因素及其与疾病活动和心理状态的关系。
    方法:对2021年3月至2023年9月在中国10家医院就诊的484例AS患者进行了横断面研究。ASAS-HI评估一般健康和功能状态;抑郁焦虑应激量表(DASS-21)评估心理障碍,如焦虑,抑郁症,和压力;慢性疾病治疗功能评估-疲劳量表(FACIT-F)评估患者的疲劳症状;强直性脊柱炎疾病活动评分-C反应蛋白(ASDAS-CRP),巴斯强直性脊柱炎疾病活动指数(BASDAI),巴斯强直性脊柱炎功能指数(BASFI),和Bath强直性脊柱炎测量指数(BASMI)用于评估患者的疾病活动和功能损害。ASAS-HI与ASDAS之间的相关性,不良的心理状态,并观察到疲劳症状。采用单因素和多因素logistic回归分析探讨ASAS-HI的相关影响因素。
    结果:本研究共纳入484例患者,其中162例健康状况不佳,139中度健康,183,身体健康。在单变量分析中,疾病活动性是影响ASAS-HI的重要因素。疾病活动度极高(ASDAS≥3.5)的人健康状况差的风险增加了12倍(OR=12.53;P<0.001)。其他显著协变量包括年龄≥36岁(OR=1.58;P=0.015),BMI≥24kg/m2(OR=2.93;P=0.013),烟雾(OR=1.96;P=0.002),BASFI(OR=1.49;P<0.001),BASMI(OR=1.22;P<0.001),疲劳(OR=6.28;P<0.001),抑郁等不良心理状况(OR=10.86;P<0.001),焦虑(OR=3.88;P<0.001),和应力(OR=4.65;P<0.001)。bMARDs的使用与不良健康状况的出现呈负相关(OR=0.54;P=0.012)。HLA-B27与性别无显著关系。多因素logistic回归分析显示,疾病活动度(ASDAS≥3.5)较高(OR=5.14;P=0.005),BASMI得分较高(OR=1.10;P=0.009),自我报告抑郁(OR=3.68;P=0.007),和疲劳(OR=2.76;P<0.001)是与不良健康状况相关的因素。
    结论:AS患者的健康状况与年龄有关,BMI,吸烟,疾病活动,不良的心理状态,和疲劳,并受到多种因素的综合影响,如情绪状态,经济水平,疼痛,和功能障碍。因此,临床医生应重视ASAS-HI的早期评估,以改善疾病的预后。要点•强直性脊柱炎(AS)是一种慢性炎症性自身免疫性疾病,病程长,疾病负担重,这极大地影响了患者的生活质量。因此,本研究旨在评估中国人群强直性脊柱炎的健康状况及其影响因素。•这是中国的一项多中心横断面研究,能更好地反映中国人口的整体状况。
    OBJECTIVE: The aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status.
    METHODS: A cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients\' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients\' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI.
    RESULTS: A total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status.
    CONCLUSIONS: The health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients\' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population.
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  • 文章类型: Journal Article
    这项研究评估了游泳运动在注射curdlan的SKG小鼠模型中的治疗潜力,并研究了irisin对炎症的调节作用。注射Curdlan的SKG被随机分配到家庭笼组或游泳组,为期6周。每周测量临床关节炎评分和踝关节厚度的变化。游泳后计划,将小鼠麻醉以收集股外侧肌和血液,随后进行组织学分析,踝关节的显微CT成像,以及促炎细胞因子和irisin水平的测量。此外,用重组irisin蛋白静脉注射注射curdlan的SKG小鼠并观察。最后,ELISA法检测健康对照组和强直性脊柱炎(AS)患者组血清irisin水平。与家庭笼组相比,注射了Curdlan的SKG小鼠的游泳组表现出关节炎和附着性炎的显着改善。特别是,Micro-CT和组织学分析显示,与家庭笼组相比,游泳组的病理性骨特征显着减少。与家庭笼组相比,游泳组的肌肉耐力也得到了增强,由挂线试验确定。有趣的是,游泳组的irisin水平不仅在统计学上增加,而且,还,TNF-α,IL-1β,IL-6水平降低。此外,注射irisin蛋白可略微减轻注射curdlan的SKG小鼠的关节炎和附着点炎。同时,AS患者血清irisin水平下降。总的来说,我们发现游泳运动减弱了AS动物模型的病理性骨特征,可能由与相关的抗炎作用增加的irisin血清水平介导。
    This study assessed the therapeutic potential of swimming exercise in the curdlan-injected SKG mouse model and investigated the modulatory effects of irisin on inflammation. Curdlan-injected SKG were randomly assigned to either a home-cage group or a swimming group for 6 weeks. Changes in clinical arthritis scores and ankle thickness were measured weekly. Post-swimming program, mice were anesthetized for collection of vastus lateralis muscle and blood, which was followed by histological analysis, micro-CT imaging of the ankle joints, and the measurement of pro-inflammatory cytokines and irisin levels. Additionally, curdlan-injected SKG mice were intravenously injected with recombinant irisin protein and observed. Finally, serum levels of irisin in healthy control and ankylosing spondylitis (AS) patient groups were measured by ELISA. The swimming group of curdlan-injected SKG mice exhibited significant improvements in arthritis and enthesitis compared to the home-cage group. In particular, micro-CT and histological analyses revealed a notable reduction in pathological bone features in the swimming group compared to the home-cage group. Muscle endurance was also enhanced in the swimming group compared to the home-cage group, as determined by the wire-hanging test. Intriguingly, irisin levels not only were statistically increased in the swimming group but, also, TNF-α, IL-1β, and IL-6 levels were decreased. Additionally, injection of irisin protein slightly attenuated both arthritis and enthesitis in curdlan-injected SKG mice. Meanwhile, irisin serum levels were declined in AS patients. Overall, we found that swimming exercise attenuated pathological bone features in an AS animal model, potentially mediated by increased irisin serum levels with associated anti-inflammatory effects.
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  • 文章类型: Journal Article
    强直性脊柱炎(AS)是一种具有挑战性的疾病,以慢性炎症和主要影响轴向骨骼的结构损伤为特征,而关节外表现也可能出现。这导致患者生活质量的恶化。在过去的几十年里,肿瘤坏死因子-α(TNF-α)抑制剂彻底改变了AS的管理,提供症状的实质性缓解和改善患者的结果。这篇综述的目的是评估TNF-α抑制剂在活动性AS患者中的疗效。在PubMed数据库中使用以下关键字进行搜索:(\"TNFα抑制剂\"或\"抗TNF-a\"或\"TNF-a抑制剂\"或\"抗TNF-α\"或\"Etanercept\"或\"Golimumab\"或\"英夫利昔单抗\"或\"Certolizumabpegol\"或"阿达利单抗\搜索于2024年2月完成,根据PRISMA指南纳入了35项研究。研究结果表明,有证据支持TNF-α抑制剂在减轻炎症方面的功效,防止结构损坏,并提高AS患者的整体幸福感。总的来说,TNF-α抑制剂已成为抗AS治疗方法的基石,具有非常令人满意的安全性。
    Ankylosing spondylitis (AS) is a challenging disease, characterized by chronic inflammation and structural damage primarily affecting the axial skeleton, while extra-articular manifestations may also appear. This results in the deterioration of patients\' quality of life. Over the past few decades, tumor necrosis factor-α (TNF-α) inhibitors have revolutionized the management of AS, offering substantial relief from symptoms and improving patient outcomes. The aim of this review is to assess the efficacy of TNF-α inhibitors in patients with active AS. A search was performed in the PubMed database using the following keywords: (\"TNF alpha inhibitors\" OR \"anti TNF-a\" OR \"TNF-a inhibitors\" OR \"anti TNF-alpha\" OR \"Etanercept \" OR \"Golimumab\" OR \"Infliximab\" OR \"Certolizumab pegol\" OR \"Adalimumab\") AND \"ankylosing spondylitis\". The search was completed in February 2024, and 35 studies were included in this review following PRISMA guidelines. The findings reveal evidence supporting the efficacy of TNF-α inhibitors in reducing inflammation, preventing structural damage, and enhancing overall well-being in AS patients. Overall, TNF-α inhibitors have emerged as a cornerstone in the therapeutic algorithm against AS with a very satisfactory safety profile.
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  • 文章类型: English Abstract
    探讨组蛋白H3K27me3甲基化及其调控酶JMJD3和EZH2在强直性脊柱炎(AS)Th17细胞分化中的作用,揭示它们在AS发病机制中的潜在参与,分析H3K27me3的甲基化状态及其与Th17相关因子的相互作用,为AS的临床治疗提供新的策略和靶点。
    本研究共纳入84例AS患者(42例活动性AS患者和42例AS稳定期患者),84名健康志愿者作为对照。收集血液样品。分离外周血单核细胞。进行ELISA测定以检查Th17细胞和相关细胞因子IL-21、IL-22和IL-17。RORc的mRNA表达,通过RT-PCR分析JAK2和STAT3,RORc的蛋白质表达,JAK2/STAT3通路蛋白,通过Western印迹测定H3K27me3和相关蛋白酶(EZH2和JMJD3)。采用Pearson相关性分析H3K27me3、EZH2和JMJD3与Th细胞分化关键信号通路分子的相关性。
    RORc的mRNA表达,活动期组JAK2、STAT3明显高于稳定期组(P<0.05)。活性相组H3K27me3和EZH2的相对灰度值低于稳定相组,低于对照组,差异有统计学意义(P<0.05)。JMJD3、RORc、活动相组的JAK2、pJAK2、STAT3、pSTAT3蛋白明显高于稳定期组,均高于对照组(均P<0.05)。活动期组Th17比例及炎症因子表达水平高于其他两组(P<0.05)。H3K27me3与RORc呈负相关,JAK2、STAT3、IL-17、JMJD3与JAK2、STAT3、IL-17呈正相关,EZH2与JAK2、STAT3、IL-17呈负相关(均P<0.05)。
    H3K27me3在AS中的低表达受基因位点JMJD3和EZH2的影响,可以调节Th17细胞的分化,从而在AS的发病和进展中发挥作用。
    UNASSIGNED: To investigate the roles of histone H3K27me3 methylation and its regulatory enzymes JMJD3 and EZH2 in the differentiation of Th17 cells in ankylosing spondylitis (AS), to unveil their potential involvement in the pathogenesis of AS, and to provide new strategies and targets for the clinical treatment of AS by analyzing the methylation state of H3K27me3 and its interactions with Th17-related factors.
    UNASSIGNED: A total of 84 AS patients (42 active AS patiens and 42 patients in the stable phase of AS) were enrolled for the study, while 84 healthy volunteers were enrolled as the controls. Blood samples were collected. Peripheral blood mononuclear cells were isolated. ELISA assay was performed to examine Th17 cells and the relevant cytokines IL-21, IL-22, and IL-17. The mRNA expressions of RORc, JAK2, and STAT3 were analyzed by RT-PCR, the protein expressions of RORc, JAK2/STAT3 pathway protein, H3K27me3 and the relevant protease (EZH2 and JMJD3) were determined by Western blot. Correlation between H3K27me3, EZH2 and JMJD3 and the key signaling pathway molecules of Th cell differentiation was analyzed by Pearson correlation analysis.
    UNASSIGNED: The mRNA expressions of RORc, JAK2, and STAT3 were significantly higher in the active phase group than those in the stable phase group ( P<0.05). The relative grayscale values of H3K27me3 and EZH2 in the active phase group were lower than those of the stable phase group, which were lower than those of the control group, with the differences being statistically significant ( P<0.05). The relative grayscale values of JMJD3, RORc, JAK2, pJAK2, STAT3, and pSTAT3 proteins were significantly higher in the active phase group than those in the stable phase group, which were higher than those in the control group (all P<0.05). The proportion of Th17 and the expression level of inflammatory factors in the active period group were higher than those in the other two groups (P<0.05). H3K27me3 was negatively correlated with RORc, JAK2, STAT3, and IL-17, JMJD3 was positvely correlated with JAK2, STAT3, and IL-17, and EZH2 was negatively correlated with JAK2, STAT3, and IL-17 (all P<0.05).
    UNASSIGNED: The low expression of H3K27me3 in AS is influenced by the gene loci JMJD3 and EZH2, which can regulate the differentiation of Th17 cells and thus play a role in the pathogenesis and progression of AS.
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  • 文章类型: Journal Article
    目的:本研究旨在评估运动疗法对轴性脊柱关节炎(axSpA)患者的有效性。
    方法:从数据库开始到2024年3月,我们搜索了PubMed(通过Medline),科克伦图书馆,Embase,WebofScience,Scopus,和SPORTDiscus适用于所有相关出版物,不受任何语言限制。
    方法:我们纳入了axSpA患者的随机对照试验(RCTs),其中至少有一组患者接受了运动疗法。
    方法:两名独立审稿人使用Cochrane协作偏差风险工具2.0评估文献质量。结果为强直性脊柱炎(AS)疾病活动评分(ASDAS),巴斯AS疾病活动指数(BASDAI),浴AS功能指数(BASFI),BathAS计量学指数(BASMI),6分钟步行距离(6MWT),胸部扩展能力,峰值耗氧量(VO2peak),疼痛,疲劳,C反应蛋白(CRP),和红细胞沉降率(ESR)。
    结果:共20项RCT,包括1670名病人,包括在这项研究中。与对照组相比,运动疗法改善了BASFI(加权平均差[WMD]:-0.49,95%置信区间[CI]:-0.65至-0.32,I2=3.4%,P=0.414),BASMI(大规模毁灭性武器:-0.49,95%CI:-0.87至-0.11,I2=71.9%,P=0.679),BASDAI(大规模杀伤性武器:-0.78,95%CI:-1.08,-0.47,I2=55.9%,P=0.021),ASDAS(大规模毁灭性武器:-0.44,95%CI:-0.64至-0.24,I2=0.0%,P=0.424),VO2peak(WMD:3.16,95%CI:1.37至4.94,I2=0.0%,P=0.873),6MWT(大规模毁灭性武器:27.64,95%CI:12.04至43.24,I2=0.0%,P=0.922),疼痛(标准化平均差[SMD]:-0.47,95%CI:-0.74至-0.21,I2=66.0%,P=0.046)和疲劳(SMD:-0.49,95%CI:-0.71至-0.27,I2=0.0%,P=0.446)。然而,胸部扩张没有发现显著的好处,CRP,和ESR结果。
    结论:运动疗法是改善axSpA疾病控制和症状缓解的有效策略。
    OBJECTIVE: This study aimed to assess the effectiveness of exercise therapy for Axial spondyloarthritis (axSpA) patients.
    METHODS: From the database inception to March 2024, we searched PubMed (via Medline), Cochrane Library, Embase, Web of Science, Scopus, and SPORTDiscus for all relevant publications without any language restriction.
    METHODS: We included randomized controlled trials (RCTs) for axSpA patients in which at least one group received exercise therapy.
    METHODS: Two independent reviewers assessed the quality of the literature using the Cochrane Collaboration Risk of Bias Tool 2.0. The outcomes were ankylosing spondylitis (AS) disease activity score (ASDAS), Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index (BASMI), 6-minute walk distance (6MWT), Chest expansion capacity, Peak oxygen consumption (VO2peak), pain, fatigue, C-reactive protein (CRP), and Eythrocyte sedimentation rate (ESR).
    RESULTS: A total of 20 RCTs, including 1,670 patients, were included in this study. Compared with the control group, exercise therapy improved BASFI (weighted mean difference [WMD]: -0.49, 95% confidence interval [CI]: -0.65 to -0.32, I2= 3.4%, P=0.414), BASMI (WMD: -0.49, 95% CI: -0.87 to -0.11, I2= 71.9%, P=0.679), BASDAI (WMD: -0.78, 95% CI: -1.08, -0.47, I2=55.9%, P=0.021), ASDAS (WMD: -0.44, 95% CI: -0.64 to -0.24, I2 =0.0%, P=0.424), VO2peak (WMD: 3.16, 95% CI: 1.37 to 4.94, I2=0.0%, P=0.873), 6MWT (WMD: 27.64, 95% CI: 12.04 to 43.24, I2= 0.0%, P=0.922), Pain (standardized mean difference [SMD]: -0.47, 95% CI: -0.74 to -0.21, I2= 66.0%, P=0.046) and Fatigue (SMD: -0.49, 95% CI: -0.71 to -0.27, I2= 0.0%, P=0.446). However, no significant benefit was found in Chest expansion, CRP, and ESR outcomes.
    CONCLUSIONS: Exercise therapy is an effective strategy for improving disease control and symptom relief in axSpA.
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