• 文章类型: Case Reports
    系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,身体对自身抗原失去耐受性,特别是核抗原。T细胞和B细胞的异常反应导致自身抗体的产生和组织中免疫复合物的形成,触发补体激活,炎症,和不可逆的器官损伤。SLE可以影响身体的任何部位,导致不同的临床症状。SLE的一种罕见表现是狼疮肠系膜血管炎(LMV),表现出模糊的症状,异常的实验室发现,和特定的成像特征。LMV,虽然不常见,可以发展为严重的并发症,如肠穿孔,出血,甚至死亡率。这里,我们报告了一例累及多器官系统的LMV(包括皮肤粘膜,肌肉骨骼,浆膜腔,和血液系统),最初出现危及生命的顽固性胃肠道出血,并发严重的肺部感染.通过分享这个案例,我们的目标是增强临床医生对严重SLE病例的管理信心,并提高对疾病监测的认识.
    Systemic lupus erythematosus (SLE) is a complex autoimmune disease where the body loses tolerance to its own antigens, particularly nuclear antigens. Abnormal responses from T and B cells lead to the production of autoantibodies and the formation of immune complexes in tissues, triggering complement activation, inflammation, and irreversible organ damage. SLE can affect any part of the body, resulting in diverse clinical symptoms. One rare manifestation of SLE is lupus mesenteric vasculitis (LMV), which presents with vague symptoms, abnormal laboratory findings, and specific imaging features. LMV, although uncommon, can progress to severe complications such as bowel perforation, haemorrhage, and even mortality. Here, we report a case of LMV with the involvement of multiple organ systems (including mucocutaneous, musculoskeletal, serosal cavities, and haematological systems), presenting initially with life-threatening intractable gastrointestinal bleeding, and complicated by severe pulmonary infection. By sharing this case, we aim to enhance clinicians\' confidence in managing critical SLE cases and raise awareness about disease surveillance.
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  • 文章类型: Journal Article
    目的评价贝利木单抗联合标准方案治疗儿童活动性狼疮性肾炎的疗效和安全性。这个单一中心,回顾性队列研究使用2004年12月至2023年2月期间在肾内科住院的新活动性狼疮性肾炎患儿的临床资料.根据患者是否接受贝利木单抗,将患者分为贝利木单抗组或传统治疗组。比较两组的肾脏缓解率和复发率以及糖皮质激素剂量。纳入47名儿童(平均年龄11岁),包括传统治疗和贝利木单抗组的30和17名儿童,分别。belimumab组儿童系统性红斑狼疮疾病活动指数-2000(SLEDAI-2000)评分(23.59±7.78)高于传统治疗组(19.13±6.10)(P=0.035)。两组出现脓尿的频率差异无统计学意义,肉眼血尿,以及24小时蛋白尿水平和估计的肾小球滤过率。贝利木单抗组补体C3/C4较传统治疗组恢复快(P<0.05)。6个月或12个月时肾脏完全缓解率无组间差异(P=0.442,P=0.759)。组间1年复发率无差异(P=0.303)。此外,治疗后6个月和12个月,贝利木单抗的糖皮质激素剂量低于传统治疗组(17.87±6.96mg/dvs.27.33±8.40mg/d,P=0.000;10.00(5.3)mg/dvs.13.75(10.0)mg/d,P=0.007),分别。
    结论:在肾脏缓解率相等的情况下,贝利木单抗联合标准传统方案可能促进糖皮质激素的减量,不良事件发生率较低。
    背景:•Belimumab被证明是对系统性红斑狼疮(c-SLE)LN具有疗效的辅助治疗。•由于缺乏研究,其在儿童LN中的作用和副作用尚不清楚。
    背景:•这种单中心,回顾性队列研究评估了贝利木单抗联合标准方案治疗儿童增殖性LN的疗效和安全性.•Belimumab与标准传统治疗相结合可能会促进糖皮质激素的逐渐减少,同时表现出不良事件的低发生率。
    The purpose of this study is to evaluate the efficacy and safety of belimumab combined with the standard regimen in treating children with active lupus nephritis. This single-center, retrospective cohort study used clinical data of children with newly active lupus nephritis hospitalized in the Department of Nephrology between December 2004 and February 2023. Patients were divided into a belimumab or traditional treatment group according to whether or not they received belimumab. Renal remission and recurrence rates and glucocorticoid dose were compared between groups. Forty-seven children (median age 11 years) were enrolled, including 30 and 17 children in the traditional treatment and belimumab groups, respectively. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score of children in the belimumab group (23.59 ± 7.78) was higher than that in the traditional treatment group (19.13 ± 6.10) (P = 0.035). The two groups showed no significant difference in the frequency of pyuria, gross hematuria, and the levels of 24-h proteinuria and estimated glomerular filtration rate. The complement C3/C4 in the belimumab group recovered faster than that in the traditional treatment group (P < 0.05). There were no between-group differences in the complete renal remission rate at 6 or 12 months (P = 0.442, P = 0.759). There were no between-group differences in 1-year recurrence rate (P = 0.303). Furthermore, 6 and 12 months after treatment, glucocorticoid doses were lower in the belimumab than the traditional treatment group (17.87 ± 6.96 mg/d vs. 27.33 ± 8.40 mg/d, P = 0.000; 10.00 (5.3) mg/d vs. 13.75 (10.0) mg/d, P = 0.007), respectively.
    CONCLUSIONS: With an equivalent renal remission rate, belimumab combined with the standard traditional regimen might promote the tapering of glucocorticoids, and the incidence of adverse events is low.
    BACKGROUND: • Belimumab is documented as an adjunctive treatment with systemic lupus erythematosus (c-SLE) LN with efficacy. • Due to the paucity of studies, its effects and side effects in children with LN remain unclear.
    BACKGROUND: • This single-center, retrospective cohort study evaluated the efficacy and safety of belimumab combined with the standard regimen in treating children with proliferative LN. • Belimumab combined with the standard traditional treatment might promote the tapering of glucocorticoids, while exhibiting a low occurrence of adverse events.
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  • 文章类型: Journal Article
    目的:评价系统性红斑狼疮(SLE)患者的临床特点,探讨SLE患者病情活动性和肾损害的危险因素。
    方法:对194例患者进行回顾性研究。将患者分为狼疮性肾炎(LN)组(63.40%)和非LN组(36.60%),不同的疾病活动组,根据临床资料不同肾功能组。多因素logistic回归分析显示白蛋白(ALB)、尿酸(UC),总胆固醇(TC),和抗dsDNA抗体是SLE患者LN的影响因素(P<0.05);ALB,UC,补体3(C3)是狼疮疾病活动度的影响因素(P<0.05);UC,C3、血红蛋白(HB)是SLE患者肾功能异常的影响因素。
    结果:ROC曲线结果显示ALB,UA,TC对SLE合并LN有一定的预测价值,ALB的预测价值大于TC(P<0.05);ALB,UA,和C3是SLE患者活动的预测因子;BUN,UA,Hb和Hb均对LN患者肾功能异常有一定的预测价值。SLE患者肾损害发生率高。
    结论:本研究结果表明,SLE患者应定期监测ALB水平,UA,TC,C3和HB,同时注意对SLE患者的高脂血症和高尿酸血症的干预,以更好地控制病情进展。
    OBJECTIVE: To evaluate the clinical features of patients with Systemic Lupus Erythematosus (SLE) and explore the risk factors of disease activity and renal damage.
    METHODS: A retrospective study involving 194 patients were performed. Patients were divided into lupus nephritis (LN) group (63.40%) and non-LN group (36.60%), different disease activity group, and different renal function group according to the clinical data. Multivariate logistic regression analysis showed that albumin (ALB), uric acid (UC), total cholesterol (TC), and anti-dsDNA antibodies were the influencing factors of LN in patients with SLE (P < 0.05); ALB, UC, and complement 3(C3) were the influencing factors of lupus disease activity (P < 0.05); UC, C3, and hemoglobin (HB) were the influencing factors of abnormal renal function in SLE patients.
    RESULTS: The results of the ROC curve showed that ALB, UA, and TC had certain predictive value for combined LN in patients with SLE, and the predictive value of ALB was greater than that of TC (P < 0.05); ALB, UA, and C3 being predictors of the activity of patients with SLE; BUN, UA, and HB all had certain predictive value for the abnormal renal function in patients with LN. SLE patients have the high incidence of renal impairment.
    CONCLUSIONS: The results of this study suggest that patients with SLE should regularly monitor the levels of ALB, UA, TC, C3, and HB, as well as pay attention to the intervention of hyperlipidemia and hyperuricemia in patients with SLE to better control disease progression.
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  • 文章类型: Journal Article
    背景:系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,会影响多个器官系统,在育龄妇女中患病率较高。该疾病的多因素病因涉及遗传,环境,和荷尔蒙成分。最近的研究强调了饮食因素的潜在影响,特别是不饱和脂肪酸,关于SLE的调节,由于它们的抗炎特性。这项荟萃分析旨在评估不饱和脂肪酸消耗与风险之间的关系,programming,和SLE的临床表现,为饮食管理提供循证指导。
    方法:截至2024年1月,我们对主要医学数据库进行了全面搜索,重点是研究不饱和脂肪酸的摄入量以及这种摄入量对SLE的影响。使用PICOS(人口,干预,比较器,结果,研究设计)框架,我们纳入了随机对照试验和病例对照研究,评估结果,如SLE活动,通过SLE疾病活动指数(SLEDAI)或不列颠群岛狼疮评估组(BILAG)指数测量,炎症生物标志物。研究使用基于异质性的固定效应或随机效应模型(I2统计量)进行分析,进行敏感性分析以评估结果的稳健性。
    结果:我们的搜索包括10项研究,涵盖各种各样的设计和人群。荟萃分析显示,富含不饱和脂肪酸的饮食与SLEDAI评分(合并SMD)-0.36,95%CI:-0.61至-0.11,p=0.007显着相关,表明对疾病活动的有益作用。此外,我们发现不饱和脂肪酸的摄入对HDL水平有显著影响,提示对血脂有积极影响。然而,对炎症标志物IL-6或其他脂质成分(LDL和胆固醇)的水平没有观察到显著影响.研究之间的异质性最小(I2≤15%),灵敏度分析证实了这些结果的稳定性和可靠性,强调不饱和脂肪酸在SLE管理中的潜在作用。
    结论:这项荟萃分析表明,饮食摄入不饱和脂肪酸可能在降低SLE活性方面发挥积极作用,并且可能显著影响HDL水平,而对炎症标志物或其他血脂谱没有显著影响。这些发现支持将不饱和脂肪酸纳入SLE患者的饮食管理,尽管需要进一步的研究来完善饮食建议并探索这些关联的潜在机制.
    BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects multiple organ systems, with a higher prevalence among women in their reproductive years. The disease\'s multifactorial etiology involves genetic, environmental, and hormonal components. Recent studies have highlighted the potential impact of dietary factors, particularly unsaturated fatty acids, on the modulation of SLE due to their anti-inflammatory properties. This meta-analysis aims to evaluate the association between unsaturated fatty acid consumption and the risk, progression, and clinical manifestations of SLE, providing evidence-based guidance for dietary management.
    METHODS: We conducted a comprehensive search across major medical databases up to January 2024, focusing on studies that examined the intake of unsaturated fatty acids and the impact of such intake on SLE. Using the PICOS (population, intervention, comparator, outcomes, study design) framework, we included randomized controlled trials and case-control studies, assessing outcomes such as SLE activity, measured by SLE Disease Activity Index (SLEDAI) or the British Isles Lupus Assessment Group (BILAG) index, inflammation biomarkers. Studies were analyzed using either a fixed- or random-effects model based on heterogeneity (I2 statistic), with sensitivity analyses performed to assess the robustness of the findings.
    RESULTS: Our search included 10 studies, encompassing a wide variety of designs and populations. The meta-analysis showed that a diet rich in unsaturated fatty acids is significantly associated with a reduction in SLEDAI scores (pooled SMD) of -0.36, 95% CI: -0.61 to -0.11, p = 0.007, indicating a beneficial effect on disease activity. Additionally, we found that unsaturated fatty acid intake has a significant impact on HDL levels, suggesting a positive effect on lipid profiles. However, no significant effects were observed on levels of the inflammatory marker IL-6 or other lipid components (LDL and cholesterol). With minimal heterogeneity among studies (I2 ≤ 15%), sensitivity analysis confirmed the stability and reliability of these results, highlighting the potential role of unsaturated fatty acids in SLE management.
    CONCLUSIONS: This meta-analysis suggests that dietary intake of unsaturated fatty acids may play a positive role in reducing SLE activity and may significantly affect HDL levels without having significant effects on inflammation markers or other lipid profiles. These findings support the inclusion of unsaturated fatty acids in the dietary management of SLE patients, although further research is required to refine dietary recommendations and explore the mechanisms underlying these associations.
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  • 文章类型: Journal Article
    背景和目的:本研究旨在评估患病率,预测因子,狼疮性肾炎(LN)患者肺动脉高压(PH)的转归。材料与方法:回顾性收集2007年至2017年387例LN患者的基线特征和临床结果。PH定义为静息经胸超声心动图评估的肺动脉收缩压≥40mmHg。主要终点是全因死亡率。次要终点是肾脏事件,定义为基线血清肌酐或终末期肾病的两倍。通过Cox回归模型分析PH与结果之间的关联。结果:15.3%(59/387)的LN患者诊断为PH,与eGFR≥30mL/min/1.73m2的患者相比,肾小球滤过率(eGFR)<30mL/min/1.73m2的患者的PH患病率更高(31.5%vs.12.6%)。较高的平均动脉压,低血红蛋白,和较低的甘油三酯水平与患PH的几率更大相关。调整相关混杂变量后,PH与较高的死亡风险(HR:2.01;95%CI:1.01-4.00;p=0.047)和肾脏事件(HR:2.07;95%CI:1.04-4.12;p=0.039)独立相关。结论:PH是LN患者全因死亡和不良肾脏结局的独立危险因素。
    Background and Objectives: This study aimed to assess the prevalence, predictors, and outcomes of pulmonary hypertension (PH) in patients with lupus nephritis (LN). Materials and Methods: Baseline characteristics and clinical outcomes of 387 patients with LN were retrospectively collected from 2007 to 2017. PH was defined as pulmonary artery systolic pressure ≥40 mmHg assessed by resting transthoracic echocardiography. The primary endpoint was all-cause mortality. The secondary endpoint was renal events, defined as the doubling of baseline serum creatinine or end-stage renal disease. Associations between PH and outcomes were analyzed by Cox regression models. Results: A total of 15.3% (59/387) of patients with LN were diagnosed with PH, and the prevalence of PH was higher for patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 compared to those with an eGFR ≥ 30 mL/min/1.73 m2 (31.5% vs. 12.6%). Higher mean arterial pressure, lower hemoglobin, and lower triglyceride levels were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with a higher risk for death (HR: 2.01; 95% CI: 1.01-4.00; p = 0.047) and renal events (HR: 2.07; 95% CI: 1.04-4.12; p = 0.039). Conclusions: PH is an independent risk factor for all-cause mortality and adverse renal outcomes in patients with LN.
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  • 文章类型: Journal Article
    本研究旨在开发和验证机器学习模型,以预测增殖性狼疮性肾炎(PLN)的发生,当肾活检不可行或不安全时,提供可靠的诊断选择。
    本研究回顾性分析了2011年至2021年在四川大学华西医院接受肾活检的SLE和肾脏受累患者的临床和实验室数据。我们将70%的患者随机分配到一个训练队列,其余30%随机分配到一个测试队列。在训练队列上构建了各种机器学习模型,包括广义线性模型(例如,逻辑回归,最小绝对收缩和选择运算符,岭回归,和弹性网),支持向量机(线性和径向基核函数),和决策树模型(例如,经典决策树,条件推理树,和随机森林)。使用ROC曲线评估诊断性能,校正曲线,和DCA为两个队列。此外,比较了不同的机器学习模型,以识别关键和共享特征,旨在筛选潜在的PLN诊断标志物。
    涉及1312名LN患者,对780例PLN/NPLN病例进行了分析。随机分为训练组(547例)和试验组(233例)。我们在训练组中开发了9种机器学习模型。七个模型在测试队列中表现出出色的辨别能力,随机森林模型的判别能力最高(AUC:0.880,95%置信区间(CI):0.835~0.926)。Logistic回归具有最佳的校准,而随机森林表现出最大的临床净效益。通过比较各种模型的特征,我们证实了传统指标如抗dsDNA抗体的功效,补码水平,血清肌酐,和尿红细胞和白细胞在预测和区分PLN中的作用。此外,我们发现了以前有争议或未充分利用的指标的潜在价值,如血清氯化物,中性粒细胞百分比,血清胱抑素C,血细胞比容,尿液pH值,血常规红细胞,和免疫球蛋白M在预测PLN中的作用。
    这项研究为纳入更广泛的生物标志物以诊断和预测PLN提供了全面的视角。此外,它为无法进行肾活检的SLE患者提供了理想的非侵入性诊断工具。
    UNASSIGNED: This study aims to develop and validate machine learning models to predict proliferative lupus nephritis (PLN) occurrence, offering a reliable diagnostic alternative when renal biopsy is not feasible or safe.
    UNASSIGNED: This study retrospectively analyzed clinical and laboratory data from patients diagnosed with SLE and renal involvement who underwent renal biopsy at West China Hospital of Sichuan University between 2011 and 2021. We randomly assigned 70% of the patients to a training cohort and the remaining 30% to a test cohort. Various machine learning models were constructed on the training cohort, including generalized linear models (e.g., logistic regression, least absolute shrinkage and selection operator, ridge regression, and elastic net), support vector machines (linear and radial basis kernel functions), and decision tree models (e.g., classical decision tree, conditional inference tree, and random forest). Diagnostic performance was evaluated using ROC curves, calibration curves, and DCA for both cohorts. Furthermore, different machine learning models were compared to identify key and shared features, aiming to screen for potential PLN diagnostic markers.
    UNASSIGNED: Involving 1312 LN patients, with 780 PLN/NPLN cases analyzed. They were randomly divided into a training group (547 cases) and a testing group (233 cases). we developed nine machine learning models in the training group. Seven models demonstrated excellent discriminatory abilities in the testing cohort, random forest model showed the highest discriminatory ability (AUC: 0.880, 95% confidence interval(CI): 0.835-0.926). Logistic regression had the best calibration, while random forest exhibited the greatest clinical net benefit. By comparing features across various models, we confirmed the efficacy of traditional indicators like anti-dsDNA antibodies, complement levels, serum creatinine, and urinary red and white blood cells in predicting and distinguishing PLN. Additionally, we uncovered the potential value of previously controversial or underutilized indicators such as serum chloride, neutrophil percentage, serum cystatin C, hematocrit, urinary pH, blood routine red blood cells, and immunoglobulin M in predicting PLN.
    UNASSIGNED: This study provides a comprehensive perspective on incorporating a broader range of biomarkers for diagnosing and predicting PLN. Additionally, it offers an ideal non-invasive diagnostic tool for SLE patients unable to undergo renal biopsy.
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  • 文章类型: Journal Article
    自身免疫性皮肤病(AID)发生在人体免疫系统攻击皮肤或组织时,导致各种类型的皮肤病或损伤。最近的研究表明,Janus激酶(JAKs)通过调节多种细胞因子信号通路在包括AID在内的自身免疫性疾病中发挥关键作用。新型JAK3/JAK1/TBK1抑制剂CS12192,据报道在类风湿性关节炎中发挥改善作用。然而,CS12192对AID的疗效尚未确定。本研究旨在探讨CS12192对银屑病(PSO)的治疗效果。小鼠模型中的系统性红斑狼疮(SLE)和特应性皮炎(AD)。
    白细胞介素-23(IL-23)诱导的PSO模型,MRL/MpJ-Faslpr/J(MRL/lpr)小鼠自发性SLE模型,分别使用恶唑酮(OXA)和二硝基氯苯(DNCB)诱导的小鼠AD模型来评估CS12192的疗效。皮肤损伤,生化参数,耳朵厚度,对耳朵重量和组织病理学进行相应评估.
    在PSO模型中,与载体相比,用CS12192处理的小鼠显示出降低的耳朵厚度和耳朵重量。在SLE模型中,CS12192可以改善皮肤参数,如淋巴结肿大和皮肤病变,但不能改善系统参数,如蛋白尿浓度和评分。血清dsDNA和BUN浓度。在AD模型中,CS12192剂量依赖性地改善耳朵肿胀并降低组织学评分,与巴利替尼发挥同等疗效,一种市售的JAK1/JAK2抑制剂。结论:我们的发现表明,新型JAK3/JAK1/TBK1抑制剂CS12192可能缓解自身免疫性皮肤病。
    UNASSIGNED: Autoimmune dermatosis (AID) occurs when the body\'s immune system attacks skin or tissue, leading to various types of skin disorders or injuries. Recent studies show that Janus kinases (JAKs) play critical roles in autoimmune diseases including AID by regulating multiple cytokine signaling pathways. CS12192, a novel JAK3/JAK1/TBK1 inhibitor, has been reported to exert ameliorative effects in rheumatoid arthritis. However, the efficacy of CS12192 on AID is undetermined. This study aims to investigate the therapeutic efficacy of CS12192 on psoriasis (PSO), systemic lupus erythematosus (SLE) and atopic dermatitis (AD) in mouse models.
    UNASSIGNED: Interleukin-23 (IL-23)-induced PSO model, spontaneous SLE model of MRL/MpJ-Faslpr/J (MRL/lpr) mice, and oxazolone (OXA) and dinitrochlorobenzene (DNCB) induced murine AD models were used for the evaluation of curative effects of CS12192, respectively. The skin lesion, biochemical parameters, ear thickness, ear weight and histopathology were assessed accordingly.
    UNASSIGNED: In PSO model, mice treated with CS12192 show reduced ear thickness and ear weight as compared with vehicle. In SLE model, CS12192 ameliorates cutaneous parameters such as lymphadenectasis and skin lesion but not systematic parameters such as proteinuria concentration and score, serum dsDNA and BUN concentration. In AD models, CS12192 dose-dependently improves ear swelling and reduces histological scores, exerting equivalent efficacy with baricitinib, a marketed JAK1/JAK2 inhibitor. Conclusion: Our findings suggest that the novel JAK3/JAK1/TBK1 inhibitor CS12192 is potentially to alleviate autoimmune dermatosis.
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  • 文章类型: Journal Article
    系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,表现多样。免疫代谢重编程通过调节免疫细胞的表型和功能促进SLE的进展。铁代谢失调与SLE发病机制有关,影响全身和免疫细胞特异性铁稳态。这篇综述探讨了系统和细胞铁的处理和调节。此外,重点介绍了SLE中铁代谢的进展,重点是免疫细胞的不同亚群。通过深入了解铁失调和免疫功能障碍之间的相互作用,潜在的治疗途径可能会揭晓。然而,阐明细胞特异性铁代谢重编程仍然存在挑战,其对SLE发病机制的贡献需要进一步研究,以发现个性化的治疗干预措施和生物标志物.这篇综述提供了对铁代谢的免疫细胞特异性调节机制的深入理解,以及对当前挑战以及可能的临床应用的新见解。
    Systemic lupus erythematosus (SLE) is an intricate autoimmune disease with diverse manifestations. Immunometabolism reprogramming contributes to the progression of SLE by regulating the phenotype and function of immune cells. Dysregulated iron metabolism is implicated in SLE pathogenesis, affecting both systemic and immune cell-specific iron homeostasis. This review explores the systemic and cellular iron handling and regulation. Additionally, the advancements regarding iron metabolism in SLE with a focus on the distinct subsets of immune cells are highlighted. By gaining insight into the interplay between iron dysregulation and immune dysfunction, the potential therapeutic avenues may be unveiled. However, challenges remain in elucidating cell-specific iron metabolic reprogramming and its contribution to SLE pathogenesis needs further research for personalized therapeutic interventions and biomarker discovery. This review provides an in-depth understanding of immune cell-specific regulatory mechanisms of iron metabolism and new insights in current challenges as well as possible clinical applications.
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  • 文章类型: Journal Article
    本研究旨在探讨低疾病活动度(LDAS)在小儿系统性红斑狼疮(pSLE)治疗对目标策略中的临床价值,并寻找从未达到LDAS的危险因素。
    在2012年1月至2019年12月期间,在中国两家三级医院进行诊断和随访的272例SLE儿童参与了这项研究。和临床表现,病理学,和治疗进行了回顾性研究。
    男女比例为1:5.2,诊断年龄为11.1岁(IQR,9.8-13.1年),病程为1.0个月(IQR,0.5-2.0个月),随访36.5个月(IQR,25.7-50.9个月)。随访期间,230名儿童获得了LDAS,42人从未去过。男性(P=0.018),粘膜溃疡(P=0.048),肝功能损害(P=0.026),心腔积液(P=0.034),贫血(P=0.048),尿液红细胞(P=0.017),尿白细胞(P=0.032),肾活检中的内皮细胞增殖(P=0.004)-这些指标在基线时两组之间具有统计学差异。在基线,多因素logistic分析显示,内皮细胞增殖(P=0.02)是从未达到LDAS的独立危险因素.随访期间,通过组间比较,不依从是从未实现LDAS的危险因素.有生物制剂的儿童获得LDAS的比率高于没有生物制剂的儿童(P=0.038)。从未发生LDAS的患者器官损害比例明显高于发生LDAS的患者(P<0.001)。
    肾活检中的内皮细胞增殖和随访期间的不依从性是从未实现LDAS的独立危险因素。在后续行动结束时,缓解组的器官损伤与LDAS组相似,表明LDAS可以作为pSLE治疗的目标。
    UNASSIGNED: This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS.
    UNASSIGNED: A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied.
    UNASSIGNED: The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8-13.1 years), the disease duration was 1.0 month (IQR, 0.5-2.0 months), and follow-up was 36.5 months (IQR, 25.7-50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)-these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001).
    UNASSIGNED: Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.
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  • 文章类型: Journal Article
    狼疮性肾炎(LN)是系统性红斑狼疮(SLE)的严重和常见表现,经常被确定为预后不良。巨噬细胞在其发病机制中起重要作用。不同的巨噬细胞亚型对狼疮受累的肾脏有不同的影响。基于它们的起源,巨噬细胞可分为单核细胞衍生的巨噬细胞(MoMacs)和组织驻留的巨噬细胞(TrMacs)。在肾炎期间,TrMacs发展出一种混合的促炎和抗炎功能表型,因为它们在受细胞因子刺激时不分泌精氨酸酶或一氧化氮(NO)。这些混合表型巨噬细胞的浸润与免疫复合物和暴露于循环炎症介质引起的持续损伤有关,这是无法解决炎症的迹象。另一方面,MoMac在细胞因子刺激下分化成M1或M2细胞。M1巨噬细胞是促炎的,分泌促炎细胞因子,而M2主要表型本质上是抗炎和促进组织修复。相反,响应于细胞因子刺激,MoMac经历分化成M1或M2细胞。M1巨噬细胞被认为是促炎细胞和分泌促炎介质,而M2主要表型主要是抗炎和促进组织修复。此外,基于细胞因子的表达,M2巨噬细胞可进一步分为M2a、M2b,和M2c表型。M2a和M2c具有抗炎作用,参与组织修复,而M2b细胞具有免疫调节和促炎特性。Further,记忆巨噬细胞也在LN的发展中起作用。研究表明,巨噬细胞的极化受多种代谢途径控制,比如糖酵解,磷酸戊糖途径,脂肪酸氧化,鞘脂代谢,三羧酸循环,和精氨酸代谢。这些代谢途径的变化可以受到鱼油等物质的调节,多烯磷脂酰胆碱,牛磺酸,富马酸,二甲双胍,和沙丁胺醇,抑制巨噬细胞的M1极化,促进M2极化,从而减轻LN。
    Lupus nephritis (LN) is a severe and common manifestation of systemic lupus erythematosus (SLE) that is frequently identified with a poor prognosis. Macrophages play an important role in its pathogenesis. Different macrophage subtypes have different effects on lupus-affected kidneys. Based on their origin, macrophages can be divided into monocyte-derived macrophages (MoMacs) and tissue-resident macrophages (TrMacs). During nephritis, TrMacs develop a hybrid pro-inflammatory and anti-inflammatory functional phenotype, as they do not secrete arginase or nitric oxide (NO) when stimulated by cytokines. The infiltration of these mixed-phenotype macrophages is related to the continuous damage caused by immune complexes and exposure to circulating inflammatory mediators, which is an indication of the failure to resolve inflammation. On the other hand, MoMacs differentiate into M1 or M2 cells under cytokine stimulation. M1 macrophages are pro-inflammatory and secrete pro-inflammatory cytokines, while the M2 main phenotype is essentially anti-inflammatory and promotes tissue repair. Conversely, MoMacs undergo differentiation into M1 or M2 cells in response to cytokine stimulation. M1 macrophages are considered pro-inflammatory cells and secrete pro-inflammatory mediators, whereas the M2 main phenotype is primarily anti-inflammatory and promotes tissue repair. Moreover, based on cytokine expression, M2 macrophages can be further divided into M2a, M2b, and M2c phenotypes. M2a and M2c have anti-inflammatory effects and participate in tissue repair, while M2b cells have immunoregulatory and pro-inflammatory properties. Further, memory macrophages also have a role in the advancement of LN. Studies have demonstrated that the polarization of macrophages is controlled by multiple metabolic pathways, such as glycolysis, the pentose phosphate pathway, fatty acid oxidation, sphingolipid metabolism, the tricarboxylic acid cycle, and arginine metabolism. The changes in these metabolic pathways can be regulated by substances such as fish oil, polyenylphosphatidylcholine, taurine, fumaric acid, metformin, and salbutamol, which inhibit M1 polarization of macrophages and promote M2 polarization, thereby alleviating LN.
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