目的:经土大黄干预,探讨P物质(SP)及其神经激肽-1受体(NK-1R)在银屑病皮肤组织中的表达及意义.方法:收集对照组,银屑病模型组,甲氨蝶呤片组(1.3 mg/kg),阿瑞匹坦胶囊组(5 mg/kg),土大黄组(1、2、4 g/kg)小鼠皮肤、血液标本,经苏木精-伊红(HE)染色,观察银屑病小鼠皮肤组织病理学变化;采用实时荧光定量聚合酶链反应(RT-qPCR)技术,检测银屑病小鼠皮肤SP、NK-1R mRNA表达;采用酶联免疫吸附测定、蛋白免疫印迹技术,检测银屑病小鼠血液SP、皮肤、NK-1R蛋白表达;随后分析SP、NK-1R表达水平与银屑病的关系.结果:与银屑病模型组比较,所有药物干预组均能改善银屑病小鼠皮肤组织病理学变化;同时,小鼠皮肤SP、NK-1RmRNA表达,血清SP、皮肤NK-1R蛋白表达均降低(P＜0.05,P＜0.01).与阳性对照药甲氨蝶呤片组、阿瑞匹坦胶囊组比较,1 g/kg大黄组小鼠皮肤组织NK-1R蛋白表达升高(P＜0.05).与土大黄组(1 g/kg)比较,土大黄组(2、4 g/kg)小鼠皮肤组织NK-1R蛋白表达均降低,其中土大黄组(2 g/kg)(P＞0.05)、土大黄组(4 g/kg)(P＜0.05).结论:土大黄可能通过降低焦虑相关神经递质SP及其NK-1R受体基因、蛋白表达,从而改善小鼠银屑病样皮损,其作用不亚于阳性对照药甲氨蝶呤片、阿瑞匹坦胶囊.

近日,医学学科顶尖期刊Acta Pharmaceutica Sinica B(影响因子IF=14.7)在线发表了本刊青年编委、我校药学院胡庆华/周梦泽团队的最新研究成果"Macrophage P2Y6R activation aggravates psoriatic inflammation through IL-27-mediated Th1 responses".药学院博士尹力为本论文的第一作者,药学院胡庆华教授、周梦泽助理研究员和苏州大学李环球副教授为共同通信作者,中国药科大学为第一通信单位.

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease related to psoriasis involving bone and cartilage. It is a heterogeneous disorder with a variety of clinical manifestations, which can include peripheral arthritis, axial spondylitis, enthesitis, skin and nail disease, dactylitis, uveitis, osteitis, inflammatory bowel disease. The distinctive feature of PsA is enthesitis. The characteristic bone erosion at the bone-pannus junction in PsA is mediated by osteoclasts, which are multinucleated giant cells derived from hematopoietic stem cells. Although the pathological mechanism of osteoclasts in PsA is mainly related to the destruction of the diseased joint, the exact pathogenesis of PsA is complex and the factors involved in initiation and termination of osteoclast need to be further explored. Much attention has been paid to the importance of osteoclast in psoriasis arthritis for decades. Based on the role of osteoclasts in PsA, our review discusses the formation and characteristics of multinucleated osteoclasts in PsA, summarizes current developments in osteoclast-related pathways in PsA including classical receptor activator of nuclear factor-κB-receptor activator of nuclear factor-κB ligand-osteoprotegerin pathway and immunomodulatory factors, as well as their advances and corresponding treatment. At present, the molecular and signal pathway that interacts with osteoclasts in the pathogenesis of PSA has not been fully elucidated, therefore more detailed studies are expected in the near future.

Antimicrobial peptides (AMPs) are small molecules produced by a myriad of cells and play important roles not only in protecting against infections and sustaining skin barrier homeostasis but also in contributing to immune dysregulation under pathological conditions. Recently, increasing evidence has indicated that AMPs, including cathelicidin (LL-37), human β-defensins, S100 proteins, lipocalin 2, and RNase 7, are highly expressed in psoriatic skin lesions. These peptides broadly regulate immunity by interacting with various immune cells and linking innate and adaptive immune responses during the progression of psoriasis. In this review, we summarize the recent findings regarding AMPs in the pathogenesis of psoriasis with a main focus on their immunomodulatory abilities.

Objective::Psoriasis is a chronic inflammatory systemic disease that severely impacts patients’ quality of life (QoL) and psychological health. While biologics have been shown to be effective in treating psoriatic lesions, thus improving QoL, real-life data regarding such effects remain scant. We administered a repeated cross-sectional survey to assess the effects of 8 weeks of biologics treatment on the QoL and mental health status of patients with moderate-to-severe plaque psoriasis.Methods::From March to May 2022, patients with moderate-to-severe plaque psoriasis were enrolled and treated with biologics in the outpatient clinic at the Dermatology Hospital of Southern Medical University. Assessments were performed before treatment and after 4 and 8 weeks of treatment with biologics. Psoriasis severity, QoL, and mental health status were evaluated using the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), 36-Item Short-form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS). A multivariate generalized estimating equations (GEE) analysis was used to account for repeated measures and to determine the effects of treatment duration and type of biological agent on relevant indicators.Results::Among the 78 enrolled patients, the ranges of pretreatment scores were 4.6 to 46.8 for the PASI, 1 to 30 for the DLQI, 31.5 to 100.0 for the physical component score (PCS) of the SF-36, 16.6 to 100.0 for the mental component score (MCS) of the SF-36, 0 to 15 for the HADS-A, and 0 to 17 for the HADS-D. After 8 weeks of biologics treatment, 98.7% (77/78) of patients had obtained PASI 75. All assessed scores changed over time (GEE, P < 0.001). Moreover, there were group-by-time interaction effects for the DLQI score (GEE, P = 0.023) and PCS (GEE, P = 0.029). The HADS-A and HADS-D scores were both decreased at week 8 compared with pretreatment values. Correlation analyses revealed that higher DLQI scores were associated with lower levels of QoL and higher levels of anxiety or depression. Conclusion::Biologics are not only effective in the treatment of skin lesions but also exert beneficial effects upon the QoL and mental health of patients with psoriasis as determined in the short-term assessments conducted in this study.

Background::The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts.Methods::Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts.Results::In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0–18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59–3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01–1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01–1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs’ (csDMARDs) use. Conclusions::Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.

目的:研究PsA患者中代谢综合征（MS）的患病率及MS各组分与PsA临床特征的关联。方法:纳入自2017年1月至2019年9月就诊于我科的PsA患者，收集其人口学及临床资料、实验室检查、MS相关指标（身高、体质量、腰围、血压、空腹血糖、血脂谱）及有无高血压、糖尿病、动脉粥样硬化、冠状动脉粥样硬化性心脏病（冠心病）、脑血管病等合并疾病，分析PsA患者中合并MS及其各种亚型表现的患病率和临床特点。结果:共纳入162例符合银屑病关节炎分类标准（CASPAR）的PsA患者，其中36例（22.2%）合并高血压，28例（17.2%）合并糖尿病，24例（14.8%）合并动脉粥样硬化，11例（6.7%）合并冠状动脉粥样硬化性心脏病，7例（4.3%）合并脑血管疾病。按照国际糖尿病联盟（IDF）诊断标准，58例（35.8%）PsA患者合并MS。与不合并MS的PsA患者相比，合并MS或高血压、空腹血糖升高的PsA患者年龄更大[分别为（54±10）岁和（44±13）岁，（56±11）岁和（45±12）岁，（54±11）岁和（44±13）岁， t=5.058， P<0.01； t=4.450， P<0.01； t=5.150， P<0.01]、疾病活动度更高[PsA疾病活动度评分（DAPSA）分别为16.75（11.25，26.7）和8.8（4.8，16.4），16.3（9.6，27.8）和10.0（5.1，18.0），14.4（9，25.7）和9.5（5,17.7）， t=4.539， P<0.01； t=3.046， P<0.01； t=3.063， P<0.01]。线性回归分析显示MS组分数量与DAPSA评分呈正相关（ r=0.273， P<0.01），而多元线性回归现实各代谢综合征各组分中除高血压（标准化系数=0.334， P<0.01）及空腹血糖升高（标准化系数=0.247， P=0.023）外，其余组分与DAPSA评分相关性差异无统计学意义（ P>0.05）；合并高血压的PsA患者ESR更快[16.5（9.5，34.25）mm/1 h与10（5，24.5）mm/1 h， Z=2.127， P=0.012]；合并脂代谢异常的PsA患者CRP更高[5.6（2.1，17.8）mg/L与3.7（1.5，6.5）mg/L， Z=2.543， P<0.01]，炎性腰背痛比例更高（41.3%和22.4%， χ2=5.901， P=0.016），DAPSA评分更高[14.1（8.4，24.3）和9.9（5.0，19.4）， Z=2.152， P=0.031]。 结论:PsA患者合并MS并不少见；合并MS的PsA患者年龄更大、疾病活动度更高，临床上需要更多关注。

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

目的:在单细胞水平上探究与银屑病致病相关的潜在生物标志物和细胞间的异质性水平。方法:对银屑病皮肤活检组织的单细胞测序数据进行质控、降维聚类及细胞亚群注释，以及对细胞类群进行差异基因(differentially expressed genes，DEGs)、细胞通讯及拟时序分析，并构建TFs-miRNA-hub基因调控网络。结果:基于多算法共鉴定出6个共同交集的hub基因，分别为 SPRR2A、 SPRR2D、 IL7R、 IL1RN、 IER3、 LCN2。KEGG显示其主要涉及NF-κB信号通路、TNF信号通路、MAPK信号通路等。在内皮细胞、成纤维细胞以及免疫细胞如朗格汉斯细胞、CD8 + T细胞、M1巨噬细胞、静息T细胞里 SPRRs基因表达量均显著上调，IL7R则主要在多种免疫细胞中过表达。成纤维细胞、树突状细胞、Treg细胞和CD8 + T细胞在银屑病皮损的含量显著增多( P＝0.023、 P＝0.007、 P＝0.046、 P＝0.028)。皮损组内细胞间的相互作用数量、强度和通路富集程度的活跃性均高于对照组，Treg细胞、CD8 + T细胞以及静息T细胞仅在银屑病组内与其他细胞有交互作用。拟时序分析显示免疫细胞主要分布在轨迹早期，单核细胞全程参与并在轨迹后期表达增加。除 IL7R的表达量随着拟时序变化而减少外，其余hub基因的表达量均一直增加。预测转录因子 NFKB1同时参与hub基因 SPRR2A、 IL1RN、 IL7R和 IER3的调控。 结论:SPRRs基因和 IL7R的过度表达以及多种免疫细胞如Treg细胞、CD8 + T细胞、静息T细胞以及单核细胞的交互作用可能通过MAPK和NF-κB途径参与银屑病的关键致病过程。本研究结果可为进一步研究银屑病的致病机制奠定理论依据。