Psoriasis is a chronic inflammatory disease whose etiology is directly related to the dysregulation of cutaneous immune homeostasis. However, how to finely modulate the skin immune microenvironment to restore homeostasis remains an important challenge. Inspired by the natural attribute of tumor exosomes in the immune escape, the tumor-derived exosomes as an active targeting nanoplatform for the effective treatment of inflammatory skin disorder were first reported. As keratinocytes and immune cells express high PD-1 during the onset of psoriasiform skin inflammation, the PD-L1-positive exosomes derived from melanoma cells carrying pristimerin with extremely anti-inflammatory potential were yielded to treat psoriasis. The PD-L1+ exosomes carrying pristimerin were characterized, and the cellular uptake was performed to evaluate the PD-1 target capability. The anti-inflammatory action of PD-L1+ exosomes carrying pristimerin was observed in both in vitro and in vivo models of psoriasis. Our exosomes substantially increased pristimerin uptake with CD4+ T cells and keratinocytes, significantly inhibited the proliferation of Th17 cells, and promoted Treg differentiation in a psoriasis-like model. Obviously, PD-L1+ exosomes carrying pristimerin significantly and safely reversed imiquimod (IMQ)-induced psoriasis in mice, indicated by reducing epidermal thickness, decreasing plaque formation, and suppressed excessive inflammatory response, due to its dual targeting of both CD4+ T cells and keratinocytes gathering around the lesion. The inflammatory cell infiltration and pro-inflammatory cytokine production in psoriasis were suppressed by our engineered exosomes. Besides, PD-L1+ exosomes carrying pristimerin treatment alleviated ferroptosis-related changes in psoriatic skin, thereby dampening excessive inflammation and, in turn, decreasing the abnormal proliferation of keratinocytes in psoriatic lesions. This study demonstrates that our engineered exosomes can not only act as a treat-to-target strategy for psoriasis treatment but also provide insight in clinical application of inflammatory disorders.

目的:研究N-乙酰半胱氨酸(N-Acetyl-L-cysteine,NAC)对PM2.5诱导的HaCaT细胞损伤的影响.方法:HaCaT细胞分为NAC干预组、不同浓度PM2.5组(25、50、100、200、400μg/mL)及空白对照组.DCFH-DA荧光探针法检测HaCaT细胞内活性氧(ROS)的水平,RT-PCR和ELISA法分别检测IL-1β、IL-33、TSLP mRNA表达及蛋白水平.CCK-8法和Western blot法分别检测细胞存活率和NF-κB信号通路相关蛋白表达水平.结果:不同浓度PM2.5组HaCaT细胞ROS水平均显著高于对照组(P<0.05);200μg/mL和400μg/mL PM2.5处理组细胞中IL-1β、TSLP、IL-33 mRNA表达水平显著高于对照组(P<0.05).与PM2.5组比较,NAC干预组HaCaT细胞存活率增高,ROS水平降低,NF-κB p-p65蛋白表达降低,IL-1β、TSLP、IL-33分泌水平降低,差异有统计学意义(P<0.05).结论:NAC对PM2.5诱导的HaCaT细胞损伤具有保护作用,其机制可能与其降低细胞内氧化应激水平有关.

N-乙酰半胱氨酸(N-acetylcysteine,NAC),因结构中含有巯基(-SH),常用作黏液溶解药物.研究显示NAC还具有抗氧化、抗炎症和改善血管舒张的功能.近年来,其独特作用机制受到广泛的关注,在皮肤病的治疗应用中展现良好潜力.本文就NAC的药物代谢、药理机制、治疗应用及不良反应等进行系统综述,以期为皮肤病的治疗提供更优选择.

近年来我国空气中PM2.5污染严重,皮肤是人体抵御环境污染物的重要屏障,容易受到PM2.5的损害.角质形成细胞是皮肤表皮层的主要组成细胞,在皮肤天然免疫反应中发挥着关键作用.PM2.5作用于角质形成细胞,可引发多种生物学效应.本文综述了PM2.5对皮肤角质形成细胞增殖活性、细胞凋亡、细胞自噬、芳香烃受体激活、氧化应激、炎性反应及皮肤屏障相关成分表达改变等方面的影响,为进一步从机制上阐述PM2.5对人体皮肤的损害提供参考.

The roles of PM2.5-induced mitochondria! damage and oxidative stress on mast cell degranulation were examined in vitro. Mast cells were treated with suspensions of PM2.5 in Dulbecco's modified Eagle's medium at concentrations from 25 to 200 mg/L in the absence or presence of 10 mmol/L N-acetyl-L-cysteine. Biological effects and mitochondrial function were assessed by determining cell viability, beta-hexosaminidase release, interleukin-4 secretion, reactive oxygen species generation, adenosine triphosphate production, potential alteration of mitochondrial membrane, and activities of mitochondrial electron transport chain complexes I and HI. Exposure of mast cells to PM2.5 induced reduction of adenosine triphosphate production, collapse of mitochondrial membrane potential, and inhibition of the activity of complex III. Co-treatment of mast cells exposed to PM2.5 with N-acetyl-L-cysteine attenuated cytotoxicity and the production of reactive oxygen species, and decreased the release of beta-hexosaminidase and interleukin-4. Evidently, PM2.5-induced oxidative stress plays an essential role in mitochondrial toxicity and mast cell activation.

目的:明确N-乙酰半胱氨酸(NAC)对颗粒物PM2.5诱导肥大细胞P815活化作用的影响.方法:用100μg/mL PM2.5刺激肥大细胞建立脱颗粒模型,设空白组,模型组,不同浓度NAC组(浓度分为100,50,25μmol/L);不同浓度NAC处理肥大细胞6 h后,再以PM2.5刺激6 h,CCK-8法测定细胞增殖活性,酶标仪测定活性氧(ROS)水平及β-氨基己糖苷酶(β-Hex)水平、ELISA检测IL-4水平,Western blot检测蛋白酶激活受体2(PAR2)蛋白表达水平.结果:与空白组比较,模型组ROS、β-Hex、IL-4含量及PAR2蛋白表达显著增高(均P<0.05);与模型组比较,NAC组肥大细胞ROS、β-Hex、IL-4含量及PAR2蛋白表达水平降低(均P<0.05),其中50μmol/L NAC组降低最明显.结论:NAC可降低肥大细胞氧化应激,抑制PAR2蛋白表达,减少炎症介质释放.

线粒体是细胞能量代谢的核心场所,线粒体内膜两侧产生电化学梯度形成线粒体膜电位(△ψm).细胞在外界刺激作用下,△ψm降低或丧失,线粒体能量代谢和氧化应激状态改变,并通过正反馈逐级放大.一系列研究发现,线粒体Ca2+运可改变△ψm,从而调控肥大细胞脱颗粒,并影响哮喘、过敏性接触性皮炎、荨麻疹的发生.线粒体是一种独立细胞器,作为营养物质氧化并释放能量的场所,其主要功能是合成三磷酸腺苷(ATP)并提供能量,被称为细胞的动力室[1].此外,线粒体还参与Ca2+言号传导和细胞凋亡等许多关键生化过程,是氧自由基的主要来源,线粒体受损后可产生活性氧(ROS),诱导△ψm快速去极化,进一步加重呼吸链损伤,最终导致ATP产能障碍[2].因此,线粒体功能可通过评估△ψm这一关键参数实现.近年研究表明,哮喘[3]、过敏性皮炎[4]、荨麻疹四等过敏性疾病的病理生理学机制与氧化应激下线粒体功能障碍密切相关.现就△ψm的作用意义、检测方法及其在过敏性疾病和其他疾病中的作用研究进行综述.

患者女,50岁,双手反复疼痛3年,加重伴双侧下颌包块1年.患者头皮以及腰骶部散在红色斑块,其上可见银白色鳞屑、薄膜以及点状出血现象;双手远端指间关节畸形;颌下以及耳后可触及肿大淋巴结;右侧腮腺淋巴结病理活检示:纤维组织增生伴较多浆细胞及淋巴细胞浸润;免疫组织化学示:IgG4/IgG＞ 40％,IgG4＞ 40个/HPF.诊断:IgG4相关性腮腺炎.

目的 观察细颗粒物(PM2.5)对肥大细胞P815线粒体膜电位(△Ψm)的影响.方法 用PM2.5体外刺激肥大细胞,设对照组,PM2.5高、中、低剂量组(100,50,25 μg/ml),处理12h后,采用Cell Counting Kit-8法检测细胞增殖活性,流式细胞术分析△Ψm水平.结果 与对照组比较,各剂量PM2.5组的细胞存活率、正常△Ψm细胞的比例均明显降低(P＜0.05);各PM2.5组中,PM2.5剂量越大,细胞存活率、正常△Ψm细胞的比例越低,组间差异显著(P＜0.05).结论 PM2.5能够降低肥大细胞线粒体膜电位水平,影响线粒体功能.

目的 探讨大气颗粒物(PM2.5)对皮肤角质形成细胞的生物学效应.方法 角质形成细胞株(HaCaT细胞)暴露于不同浓度PM2.5混悬液(0～400μg/ml)24 h,采用CCK-8法检测不同浓度及不同暴露时间(1～24 h)的细胞存活率;Annexin V法检测细胞凋亡率;实时荧光定量聚合酶链反应(RT-PCR)、酶联免疫吸附试验(ELISA)分别检测不同浓度处理组细胞内细胞因子CCL20 mRNA的表达水平及CCL20分泌浓度;免疫印迹试验(Western blot)检测细胞中核转录因子(NF)-κB信号通路相关蛋白的表达水平.结果 与对照组(0μg/ml)相比,当PM2.5浓度≥50μg/ml或刺激时间≥3 h时,各组细胞存活率均显著降低(P<0.05);随着PM2.5刺激浓度增高(PM2.5浓度≥50μg/ml),各组细胞凋亡率均显著增高(P<0.01),细胞中炎性因子CCL20的mRNA表达水平显著上调(P<0.05);随着PM2.5刺激浓度增高(PM2.5浓度≥25μg/ml),CCL20分泌水平显著上调(P<0.05);Western blot检测显示细胞中NF-κB信号通路关键蛋白p65的磷酸化水平表达上调.结论 PM2.5可降低角质形成细胞存活率,促进细胞凋亡,且可能通过激活NF-κB信号通路诱导角质形成细胞内细胞因子CCL20的表达上调,进而介导多种慢性皮肤炎症反应.

目的:定量分析并系统评价常规剂量玉屏风散联合抗组胺药用于慢性荨麻疹疗效的影响.方法:计算机联网检索从建库至2019年10月中国知网、中国生物医学文献数据库、维普数据库、万方数据库、PubMed及EMBase等数据库发表的玉屏风散联合抗组胺药治疗慢性荨麻疹的随机对照试验文献(联合组干预措施为常规剂量玉屏风散与抗组胺药联合应用;对照组干预措施为单纯使用常规剂量抗组胺药;抗组胺药包括咪唑斯汀、依巴斯汀、西替利嗪、左西替利嗪、氯雷他定、枸地氯雷他定、非索非那定、奥洛他定、阿伐斯汀、氮卓斯汀、苯磺贝他斯汀及地氯雷他定等).采用RevMan 5.3和Stata 14.2软件进行荟萃分析(Meta分析).结果:共纳入28篇文献,涉及1422例患者.Meta分析结果显示,联合组患者的总有效率明显高于对照组(OR=3.85,95％CI=2.91～5.11,P<0.00001),复发率明显低于对照组(OR=0.36,95％CI=0.27～0.49,P<0.00001),差异均有统计学意义;两组患者不良反应发生率比较,差异无统计学意义(OR=0.79,95％CI=0.52～1.20,P=0.27).结论:相较于单纯使用抗组胺药,玉屏风散联合抗组胺药治疗慢性荨麻疹的疗效更优,复发率更低,且安全性大致相当.

目的:定量评估环境微细颗粒物PM10、PM2.5与过敏性皮肤病的关系.方法:检索国内外文献数据库,系统收集相关文献并提取效应量.使用RevMan 5.3和Stata 14.2软件对文献进行Meta分析,根据异质性结果进行亚组分析和敏感性分析,并检验发表偏倚及校正合并效应量.结果:共纳入25篇文献;PM10、PM2.5每增高10μg/m3,对过敏性皮肤病影响的合并效应量分别为1.0049(95％CI:1.0016～1.0081)与1.0066(95％CI:1.0033～1.0100);亚组分析显示PM10和PM2.5对特应性皮炎影响的合并效应量分别为1.0108(95％CI:0.9999～1.0219)、1.0320(95％CI:1.0056～1.0590),对湿疹影响的合并效应量分别为1.0040(95％CI:1.0006～1.0075)、1.0066(95％CI:1.0029～1.0103);PM2.5对荨麻疹影响的合并效应量为0.9994(95％CI:0.9852～1.0139).结论:环境微细颗粒物与过敏性皮肤病发生相关,PM10和PM2.5浓度升高会增加特应性皮炎和湿疹的发生风险.

荨麻疹是一种在普通人群中常见且直接导致生活质量降低的疾病,但其流行病学特征并不是特别清楚.最新研究发现荨麻疹在不同地区、种族以及年龄段的流行病学、疾病特征以及疾病管理均具有差异.本文就慢性自发性荨麻疹、物理性荨麻疹以及胆碱能性荨麻疹的最新流行病学研究进展作一综述,了解其危险因素以及疾病特征,并分析性别、年龄、种族等因素对其流行病学的影响,进而为疾病管理、临床治疗提供更精准的方案.

Objective The second messenger inositol triphosphate (IP3) is involved in signal transduction in multiple cell types. We evaluated the effects of high-dose levocetirizine on chronic spontaneous urticaria (CSU) and examined the significance of serum IP3 level in the pathogenesis of CSU. Methods Fifteen patients with refractory CSU were given oral levocetirizine at a dose of 15 mg once daily for 7 days, and treatment efficacy was determined using the Urticaria Activity Score and by evaluating wheal-and-erythema reactions and itching. The serum concentration of IP3 at specific time points was determined by enzyme-linked immunosorbent assay. Results The mean serum concentration of IP3 was 43.54 ± 41.97 pg/mL prior to treatment, 18.40 ± 17.53 pg/mL after treatment, and 1.31 ± 0.92 pg/mL in a healthy control group. The mean concentration of IP3 was significantly higher before treatment than after treatment, and the level of IP3 in the patient group before and after treatment was significantly higher than that in the control group. Conclusion High-dose levocetirizine was shown to be effective in the treatment of CSU. The level of serum IP3 was positively correlated with CSU activity, indicating that IP3 may play an important role in the pathogenesis of this condition.

大气细颗粒物(PM2.5)污染形势日趋严峻,可对全身多个系统造成损害,对人类健康构成严重威胁.为探讨PM2.5对皮肤健康的影响,本文就PM2.5对过敏性皮肤病、皮肤老化、色斑形成等方面的影响作一综述,从机制上阐述PM2.5对皮肤的危害,以期为皮肤病的防治提供新思路.

The etiology of chronic urticaria (CU) remains elusive. Histamine-releasing factor (HRF) is reported to have a proinflammatory role in asthma and immediate hypersensitivity of the skin. The aim of this study was to examine the role of HRF in the pathogenesis of CU. Forty patients with CU were enrolled and their serum HRF concentrations were determined by ELISA. The results demonstrated that the concentrations of HRF and HRF-reactive IgE in the CU group were significantly higher than those in the control group, and there was a significant linear correlation between HRF and HRF-reactive IgE concentrations (r = 0.859, p < 0.001) in CU patients. Additionally, the HRF-reactive IgE concentration was significantly correlated with the disease activity (r = 0.693, p < 0.0001). HRF and HRF-reactive IgE alone failed to activate LAD2 cells. After being primed by the patient sera with the highest IgE concentrations and stimulated by HRF, β-hexosaminidase can be released from LAD2 cells. Our findings suggest that the synergistic actions of HRF and HRF-reactive IgE may play important roles in the pathogenesis of CU.

With the rapid development of industrialization and city construction, air pollution has become an increasingly serious problem. All kinds of air pollutants such as smoke and suspended particulate matter (PM), nitrogen dioxide, sulfur dioxide, carbon monoxide, ozone, volatile organiccompounds continue to threaten human health; especially the PM2.5 which can easily deposite in the bronchioles and alveoli, enter the human blood circulation, and causes a series of pathological and physiological changes, finally leading to the occurrence of the disease. In recent years, most of the research is focus on the impact of PM2.5 on respiratory and cardiovascular system, meanwhile the research on the relationship between PM2.5 and allergic diseases is also increasing gradually. This article reviews the relationship between PM2.5 and allergic diseases, on the basis of the summarization of the new understanding of allergic disease mechanisms.

Particulate matter (PM2.5) is an important element of atmospheric pollutant in city. Because of having the features such as small particle size, large area, strong activity, easy to carry toxic and harmful substances such as heavy metals, microorganisms, and the long stay in the atmosphere and long-conveyed distance, PM2.5 has a great impact on human health. At present, there are a lot of studies on the pathogenic mechanism of PM2.5, such as the change of immune function, the induction of oxidative stress and damage, gene mutation and DNA damage, but the pathogenic mechanism is not yet fully understood. In this paper, we review the pathogenic mechanisms of PM2.5.

Objective To investigate the biological effect of atmospheric fine particulate matter (PM2.5) on mast cells in vitro.Methods PM2.5 was collected in the nonindustrial zone of Chongqing city using an intelligent medium-volume total suspended particulate air sampler and prepared into mixed suspensions of different concentrations (0,12.5,25.0,50.0,100.0,200.0,400.0 and 800.0 μg/mL).Human mast cell line LAD2 exposed to these suspensions were examined for cellular production of β-hexosaminidase using microplate method and for the release levels of histamine,interleukin 4 (IL-4) and reactive oxygen species (ROS) using ELISA.Results Exposure of the mast cells to 25 μg/mL PM2.5 resulted in significant increases in the levels of β-hexosaminidase [(23.78 ± 3.98) ％ vs (14.05 ± 1.12) ％,P＜0.01],histamine (12.32 ±0.18 vs 9.72 ±0.23 μg/mL,P＜0.01) and IL-4 (267.63 ±7.97 vs 154.25 ±7.71 pg/mL,P ＜0.01) in the supernatant as compared with the cells without PM2.5 exposure.Within the concentration range from 12.5 to 100.0 g/mL,an increasing concentration of PM2.5 suspension caused progressive increase in ROS levels in the cells,and the cells exposed to 25 g/mL of the suspension showed a significantly higher ROS level than the cells without PM2.5 exposure (7.99 ±0.29 vs 5.88 ±0.49 ng/mL,P ＜0.01).Conclusion PM2.5 exposure may induce ROS production via oxidative stress to promote the production of cytokines and inflammatory factors in LAD2 cells in vitro.

Objective:To analyze the causative drugs in 239 inpatients with drug eruptions. Methods:Da-ta of inpatients suffered from drug eruptions from May 2007 to April 2017 in our department were analyzed ret-rospectively. Results:Out of 239 patients, the allergenic drugs in 105 patients were identified, including 88 patients with severe drug eruption and 17 patients with non-severe drug eruption. The allergenic drugs in the patients with non-severe drug eruptions mainly included antibiotics in 32 patients (36.4%), antipyretic anal-gesics in 17 (19.3%) and traditional Chinese medicine in 16 (18.2%). The allergenic drugs in the patients with severe drug eruptions mainly included antibiotics in 5 patients ( 29. 4%) , antipyretic analgesics in 3 (17.6%) carbamazepine in 3 (17.6%) and antigout drugs in 3 (17.6%). Conclusion: The most allergenic drugs are antibiotics in this study.