Birefringent crystals deposition and inflammasome expression in human atheroma plaques by levels of uricemia

ObjectiveTo verify the monosodium urate (MSU) crystal deposition in artery walls following a structure assessment and to assess NLRP3 inflammasome expression in human atheroma plaques by levels of uricemia.MethodsPatients with peripheral arterial disease who were candidates for amputation were recruited and classified as normouricemic or hyperuricemic. During surgery, an artery segment from the amputated limb was sampled, divided and fixed separately by cryo-embedding, 100% ethanol or Glyo-fixx. Samples were assessed by compensated polarized-light microscopy to identify MSU crystals on the artery walls. Afterwards, macrophages, neutrophils and NLRP3 inflammasome components at the plaque were categorized by immunostaining and compared between normouricemics and hyperuricemics.ResultsThirty artery samples from 27 patients were studied; 10 (37.0%) participants were hyperuricemic. Birefringent needle-shaped crystals were found in three samples (10.0%), all processed by frozen sectioning. Other methods showed no crystals. No accompanying inflammatory process was noted, and the presence of crystals was equally distributed across ranges of uricemia, making it unlikely they were MSU crystals. Regarding immunostaining, 28 artery samples were available for analysis, with similar infiltration of macrophages and neutrophils. NLRP3 and gasdermin-D expression were significantly greater in hyperuricemics compared to normouricemics (P = 0.044 and P = 0.017, respectively). ASC content was numerically larger in hyperuricemics as well, while caspase-1 and IL-1beta expression were similar between groups.ConclusionsThe presence of MSU crystals on artery walls was not confirmed. Hyperuricemia was associated with greater NLRP3 and gasdermin-D expression on human atheroma plaques in patients with peripheral artery disease.     

Trained immunity and inflammation in rheumatic diseases

BackgroundRheumatic diseases include a variety of autoimmune and autoinflammatory conditions that are characterised by musculoskeletal involvement and systemic disease. Both innate and adaptive immunity can contribute to the complex inflammatory processes that take part in the pathogenesis of these debilitating disorders.FindingsOver the past decade, studies have led to a paradigm-shift around the concept of immune memory, generating the knowledge that cells of the innate immune system can develop a de facto memory mediated by epigenetic reprograming and metabolic changes (trained immunity).Here we provide an overview of current data that describe features of trained immunity in rheumatic diseases. We link evidence on inflammatory mediators and cytokine production, immunometabolism and epigenetic regulation of immunological programs, and outline the fact that trained immunity could play mechanistic roles in rheumatic diseases such as gout, rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis.ConclusionThis review describes recent findings in several important rheumatic disorders and emphasizes changes in the functional program of innate immune cells that are reminiscent of a trained immune phenotype. Further assessment of trained immunity in rheumatic disease can provide targetable mechanisms that could potentially alter the disease symptomatology and evolution.     

JAK/STAT信号通路在风湿免疫性疾病中作用的研究进展

Janus激酶/信号转导和转录激活子（JAK/STAT）信号通路是一种普遍表达的细胞内信号转导通路,参与细胞增殖、分化、凋亡和免疫调节等生物学过程。目前的研究证实该信号通路的持续激活与许多风湿免疫性疾病的发病及相关临床表现的发生密切相关。本文阐述了JAK/STAT信号通路的作用机制及其在类风湿关节炎、系统性红斑狼疮、痛风等风湿免疫性疾病发生、发展中的作用,提示JAK/STAT信号通路可作为风湿免疫性疾病的治疗靶点,为临床治疗提供新的思路与方向。     

调整空气距离与骨距离参数减少足部双能量CT痛风石成像指甲伪影

目的 探讨通过调整空气距离与骨距离参数减少足部双能量CT(DECT)痛风石成像指甲伪影的可行性。方法 收集20例痛风患者进行足部DECT扫描,分别采用标准空气距离与骨距离参数、调整后空气距离与骨距离参数对图像进行重建,应用自动体积计算软件测量痛风石体积及指甲伪影体积,并进行统计学分析。结果 20例患者均存在痛风石及指甲伪影。采用标准参数检测到66个痛风石,63个指甲伪影。调整参数后共检测到66个痛风石,31个指甲伪影。调整参数后痛风石体积[0.07(0.03~0.12)cm³]与标准参数下[0.07(0.03~0.16)cm³]的差异无统计学意义(Z=-0.2,P=0.84),指甲伪影体积[(0.02±0.02)cm³]较标准参数下[(0.07±0.06)cm³]明显减小(t=4.56,P<0.01)。结论 通过调整空气距离与骨距离参数可以明显减少DECT痛风石成像中的指甲伪影,且不影响痛风石的观察。     

How is Gout Managed in Primary Care? A Review of Current Practice and Proposed Guidelines

Twelve practices with a total list of 74 111 patients were audited; 429 patients were identified with a diagnosis of gout. A wide variation in various clinical and laboratory assessments was detected. Similar variations were also noted regarding dietary advice and medical treatment. Monitoring of patients was infrequent. As a result of this audit, guidelines are proposed to improve the diagnosis and management of gout in the community. Received: 22 March 1999 / Accepted: 15 June 1999     

老年2型糖尿病患者高尿酸血症的相关因素分析

目的探讨老年2型糖尿病患者高尿酸血症的临床特征。方法将256例2型糖尿病住院患者分为老年糖尿病组(老年组)168例和非老年糖尿病组(非老年组)88例并选择37例无糖尿病老年人作为对照(对照组)。分别记录年龄、性别、体重指数、糖尿病病程,检测血清尿酸及肌酐,尿尿酸及肌酐、尿pH,计算24h尿尿酸排泄总量、尿酸清除率、肌酐清除率、尿酸清除分数等,3组间进行比较。结果老年组血清尿酸水平显著高于非老年组和对照组(均为P<0.01);而肌酐清除率〔(52.8±28.5)ml/min〕低于非老年组〔(89.9±34.3)ml/min〕(P<0.01)和对照组〔(57.9±37.6)ml/min〕(P<0.05),尿pH值下降,24h尿量增加。非老年组尿酸清除率〔(7.63±4.80)ml/min〕显著高于老年组〔(4.47±3.60)ml/min〕和对照组〔(3.75±3.20)ml/min〕(P<0.01);24h尿酸排泄量显著高于老年组和对照组(均为P<0.01)。结论老年组血清尿酸水平与年龄、血清肌酐、尿酸清除率、24h尿尿酸排泄量相关,尿酸生成增多、尿酸清除能力减退及尿量减少、尿pH值减低等多种因素共同导致老年2型糖尿病患者高尿酸血症。     

PPAR酌激动剂吡格列酮对尿酸钠晶体诱导炎症的防治作用

目的通过尿酸钠(MSU)晶体诱导的炎症动物模型,探讨炎性细胞中过氧化物酶体增殖物激活受体酌(PPAR酌)表达的规律及其激动剂吡格列酮防治痛风的可行性及机制。方法选用Wistar大鼠和昆明小鼠作为实验对象,相应部位注射MSU晶体制作大鼠急性腹膜炎和小鼠皮下气腔炎症模型。在大鼠腹膜炎实验中,以半定量反转录聚合酶链反应(RT-PCR)动态检测PPAR酌在炎症发生发展过程中腹腔巨噬细胞的表达规律,检测炎症诱导后4、8、24、48h不同组别大鼠腹腔浸润的炎性细胞数变化,以评价吡格列酮的抗炎作用;在皮下气腔炎症实验中,观察不同剂量吡格列酮对小鼠皮下气腔炎症不同时间点浸润的炎性细胞数的影响。结果PPAR酌在正常大鼠腹腔巨噬细胞的表达明显高于外周血单个核细胞和中性粒细胞,在MSU诱导的急性腹膜炎大鼠的腹腔巨噬细胞中表达迅速降低,并与炎性细胞数呈显著负相关,随炎症缓解而趋恢复。MSU诱发的腹膜炎自发缓解早于皮下气腔炎症。在大鼠腹膜炎模型,20mg·kg-1·d-1的吡格列酮在4h和8h即可显著抑制炎性细胞浸润,抑制率分别为70.6%和64.5%;在小鼠皮下气腔炎症模型,20mg·kg-1·d-1和10mg·kg-·1d-1的吡格列酮在48h方可显著减少炎性细胞浸润,抑制率分别为49.3%和42.4%,而4mg·kg-·1d-1吡格列酮无明显作用。结论PPAR酌参与了MSU诱导的痛风相关炎症过程。吡格列酮可减轻MSU诱导的动物体内炎症反应,该作用在MSU诱导的大鼠腹膜炎早期即可出现,而在小鼠皮下气腔模型诱导后48h才表现出来。吡格列酮的上述抗炎作用可能主要通过巨噬细胞实现。     

上海市杨浦区痛风的流行病学调查

目的　调查上海市杨浦区原发性痛风的流行情况。方法　按照统一制定的表格 ,对上海市杨浦区 65 84名自然人群 (≥ 16岁 )进行问卷调查 ,对回答阳性者进行体检、X线检查和血尿酸检验。结果　共发现原发性痛风患者 2 2例 (男性 2 0例、女性 2例 ) ,患病粗率为 0 .3 3 % (男性0 .63 %、女性 0 .0 6% ) ,标化患病率为 0 .2 2 % (男性 0 .44 %、女性 0 .0 3 % )。男女性标化患病率之比约为 15∶1。结论　痛风在上海地区的患病率为 0 .2 2 % ,且主要发生于男性     

Interleukin-1β gene polymorphisms in Taiwanese patients with gout

The purpose of this study was to examine whether interleukin-1 beta (IL-1) promoter and exon 5 gene polymorphisms are markers of susceptibility or clinical manifestations in Taiwanese patients with gout. The study included 196 patients in addition to 103 unrelated healthy control subjects living in central Taiwan. From genomic DNA, polymorphisms of the gene for IL-1 promoter and IL-1 exon 5 were typed. Allelic frequencies were compared between the two groups, and the relationship between allelic frequencies and clinical manifestations of gout was evaluated. No significant differences were observed in the allelic frequencies of the IL-1 promoter between patients with gout and healthy control subjects. Additionally, we did not detect any association of the IL-1 promoter genotype with the clinical and laboratory profiles of gout patients. However, there was a significant difference between the two groups in terms of hypertriglyceridemia (P=0.0004, ²=12.52, OR 7.14, 95%CI 0.012–0.22). There was also a significant difference in the genotype of IL-1 exon 5 polymorphism between patients with and without hypertriglyceridemia. Results of the present study suggest that polymorphisms of the IL-1 promoter and IL-1 exon 5 are not related to gout patients in central Taiwan.     

高尿酸血症与恶性肿瘤的关系与治疗概述

高尿酸血症是代谢异常性疾病,其可继发痛风、急性肾损伤、加重冠心病和高血压、诱发或加重糖尿病等,尤其是近代研究指出其可能加速肿瘤进展、增加癌症患者的死亡风险.另外,本无高水平尿酸的癌症患者,又可因为多种原因导致高尿酸水平升高,故对恶性肿瘤患者的高血尿酸的及时控制、治疗十分重要.