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Identification of Immune-Related Genes as Potential Biomarkers in Early Septic Shock. 鉴定作为早期脓毒性休克潜在生物标志物的免疫相关基因
IF 2.5 4区 医学 Q3 ALLERGY Pub Date : 2024-09-30 DOI: 10.1159/000540949
Beibei Liu, Yonghua Fan, Xianjing Zhang, Huaqing Li, Fei Gao, Wenli Shang, Juntao Hu, Zhanhong Tang

Introduction: Septic shock, a severe manifestation of infection-induced systemic immune response, poses a critical threat resulting in life-threatening multi-organ failure. Early diagnosis and intervention are imperative due to the potential for irreversible organ damage. However, specific and sensitive detection tools for the diagnosis of septic shock are still lacking.

Methods: Gene expression files of early septic shock were obtained from the Gene Expression Omnibus (GEO) database. CIBERSORT analysis was used to evaluate immune cell infiltration. Genes related to immunity and disease progression were identified using weighted gene co-expression network analysis (WGCNA), followed by enrichment analysis. CytoHubba was then employed to identify hub genes, and their relationships with immune cells were explored through correlation analysis. Blood samples from healthy controls and patients with early septic shock were collected to validate the expression of hub genes, and an external dataset was used to validate their diagnostic efficacy.

Results: Twelve immune cells showed significant infiltration differences in early septic shock compared to control, such as neutrophils, M0 macrophages, and natural killer cells. The identified immune and disease-related genes were mainly enriched in immune, cell signaling, and metabolism pathways. In addition, six hub genes were identified (PECAM1, F11R, ITGAL, ICAM3, HK3, and MCEMP1), all significantly associated with M0 macrophages and exhibiting an area under curve of over 0.7. These genes exhibited abnormal expression in patients with early septic shock. External datasets and real-time qPCR validation supported the robustness of these findings.

Conclusion: Six immune-related hub genes may be potential biomarkers for early septic shock.

导言:脓毒性休克是由感染引起的全身免疫反应的一种严重表现,会导致多器官功能衰竭,危及生命。由于可能造成不可逆的器官损伤,早期诊断和干预势在必行。然而,目前仍缺乏诊断脓毒性休克的特异性和敏感性检测工具:方法:从基因表达总库(GEO)数据库中获取早期脓毒性休克的基因表达文件。CIBERSORT分析用于评估免疫细胞浸润。利用加权基因共表达网络分析(WGCNA)确定与免疫和疾病进展相关的基因,然后进行富集分析。然后使用 CytoHubba 来确定枢纽基因,并通过相关性分析探讨它们与免疫细胞的关系。收集健康对照组和早期脓毒性休克患者的血液样本来验证中心基因的表达,并使用外部数据集来验证其诊断效果:结果:与对照组相比,12种免疫细胞在早期脓毒性休克中出现了明显的浸润差异,如中性粒细胞、M0巨噬细胞和自然杀伤细胞。鉴定出的免疫和疾病相关基因主要富集在免疫、细胞信号传导和新陈代谢通路中。此外,还发现了六个枢纽基因(PECAM1、F11R、ITGAL、ICAM3、HK3 和 MCEMP1),它们都与 M0 巨噬细胞显著相关,曲线下面积超过 0.7。这些基因在早期脓毒性休克患者中表现出异常表达。外部数据集和实时 qPCR 验证证实了这些发现的可靠性:结论:六个免疫相关枢纽基因可能是早期脓毒性休克的潜在生物标记物。
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引用次数: 0
Baicalin Attenuates Type 2 Immune Responses in a Mouse Allergic Asthma Model through Inhibiting the Production of Thymic Stromal Lymphopoietin. 黄芩苷通过抑制胸腺基质淋巴细胞生成素的产生减轻小鼠过敏性哮喘模型中的2型免疫反应
IF 2.5 4区 医学 Q3 ALLERGY Pub Date : 2024-09-19 DOI: 10.1159/000541100
Zhisen Zeng, Yaoxin Ruan, Haoran Ying, Jie Wang, Huangbin Wang, Shuzhen Chen

Introduction: Baicalin is a flavonoid chemical extracted and purified from the traditional Chinese medicine named Scutellaria baicalensis Georgi, which possesses broad pharmacological properties. Our work aimed to explore the protective role of baicalin in allergic asthma and its potential mechanisms on regulating type 2 immune response.

Methods: Mice were injected intraperitoneally with ovalbumin (OVA) twice, further challenged with OVA aerosol for continuous 5 days. For baicalin group, mice were pre-administrated with baicalin. After the final challenge, the immune cells in bronchoalveolar lavage fluid (BALF) and blood were examined. The cytokines were evaluated by ELISA. Histological inspections were examined by hematoxylin and eosin staining and Periodic Acid-Schiff staining. Thymic stromal lymphopoietin (TSLP) expression in lungs were detected using immunohistochemistry and Western blotting.

Results: The eosinophils infiltrating in BALF were reduced remarkably in baicalin-treated asthmatic mice. Baicalin decreased OVA-induced inflammatory cytokines and total serum immunoglobulin E secretion significantly. Moreover, baicalin alleviated the asthmatic pathological changes and substantially suppressed TSLP expression in the lung tissues.

Conclusion: Our study indicates that baicalin attenuates OVA-induced allergic asthma in mice effectively by suppressing type 2 immune responses, which might provide a novel insight into the anti-asthmatic activity of baicalin.

简介黄芩苷是从中药黄芩中提取纯化的一种黄酮类化学物质,具有广泛的药理作用。我们的研究旨在探讨黄芩苷对过敏性哮喘的保护作用及其调节2型免疫反应的潜在机制:方法:给小鼠腹腔注射卵清蛋白(OVA)两次,然后用 OVA 气雾剂连续挑战 5 天。黄芩苷组的小鼠预先服用黄芩苷。最后一次挑战后,检测支气管肺泡灌洗液(BALF)和血液中的免疫细胞。细胞因子通过 ELISA 进行评估。组织学检查采用苏木精、伊红染色法和周期性酸-希夫染色法。采用免疫组织化学和 Western 印迹法检测肺部胸腺基质淋巴细胞生成素(TSLP)的表达:结果:嗜酸性粒细胞在黄芩苷治疗的哮喘小鼠中明显减少。黄芩苷能显著降低 OVA 诱导的炎性细胞因子和血清免疫球蛋白 E 的总分泌量。此外,黄芩苷还能缓解哮喘的病理变化,并大幅抑制肺组织中 TSLP 的表达:我们的研究表明,黄芩苷能通过抑制2型免疫反应有效减轻OVA诱导的小鼠过敏性哮喘,这可能为黄芩苷的抗哮喘活性提供了新的见解。
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引用次数: 0
Fritillaria cirrhosa D. Don Alleviates Inflammatory Progression and Suppresses M1 Polarization of Macrophages in Chronic Obstructive Pulmonary Disease. Fritillaria cirrhosa D. Don 可缓解慢性阻塞性肺病的炎症进展并抑制巨噬细胞的 M1 极化。
IF 2.5 4区 医学 Q3 ALLERGY Pub Date : 2024-09-16 DOI: 10.1159/000539755
Lei Li, Jihui Sun, Qian Li, Kexin Sun, Jianhua Jiang

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive and largely irreversible disease. Current therapeutic approaches for COPD are limited in terms of slowing disease progression and suppressing pulmonary inflammation. Therefore, this study aimed to identify a method for alleviating inflammation in COPD.

Methods: A COPD-like mouse model was established and treated with or without Fritillaria cirrhosa D. Don (hereinafter referred to as Fritillaria). The expression levels of inflammatory cytokines in mouse serum were detected by using enzyme-linked immunosorbent assay (ELISA). Additionally, lung tissue was analyzed by hematoxylin-eosin staining and immunohistochemistry analysis, respectively. MLE-12 cells were exposed to cigarette smoke extract (CSE) and treated with or without Fritillaria. The MTT assay was conducted to assess cell viability. The activation of NF-κB p65 was determined by Western blotting (WB). Finally, flow cytometry was applied to analyze the M1 macrophage percentage.

Results: The results displayed that Fritillaria downregulated the levels of IL-1β, IL-6, IL-8, and TNF-α in the COPD-like mouse serum and MLE-12 cells. Fritillaria alleviated the inflammatory response in lung tissue of COPD-like mice. The cell viability of MLE-12 cells considerably decreased when exposed to CSE, which could be restored by adding Fritillaria. The Fritillaria reduced the activation of the pro-inflammatory factor NF-κB p65 and inhibited M1 polarization of macrophages, thereby mitigating the inflammatory response.

Conclusion: In conclusion, Fritillaria exhibits beneficial effects in suppressing pulmonary infection-related inflammation in both the COPD-like mouse model and in vitro cell experiments.

导言慢性阻塞性肺疾病(COPD)是一种进展性疾病,且在很大程度上不可逆转。目前治疗慢性阻塞性肺病的方法在减缓疾病进展和抑制肺部炎症方面存在局限性。因此,本研究旨在找出缓解慢性阻塞性肺病炎症的方法:方法:建立慢性阻塞性肺病小鼠模型,并用或不用 Fritillaria cirrhosa D. Don(以下简称 Fritillaria)进行治疗。采用酶联免疫吸附试验(ELISA)检测小鼠血清中炎症细胞因子的表达水平。此外,还分别通过苏木精-伊红染色法和免疫组化分析法对肺组织进行了分析。将 MLE-12 细胞暴露于香烟烟雾提取物(CSE)中,并用或不用飞燕草处理。MTT 试验用于评估细胞活力。通过 Western 印迹(WB)检测 NF-κB p65 的活化情况。最后,应用流式细胞术分析 M1 巨噬细胞的百分比:结果:结果表明,青蒿能降低 COPD 样小鼠血清和 MLE-12 细胞中 IL-1β、IL-6、IL-8 和 TNF-α 的水平。青蒿能减轻慢性阻塞性肺病样小鼠肺组织的炎症反应。当 MLE-12 细胞暴露于 CSE 时,其细胞存活率大大降低,而在添加磷脂后,细胞存活率得以恢复。此外,青钱柳还能减少促炎因子 NF-κB p65 的活化,抑制巨噬细胞的 M1 极化,从而减轻炎症反应:总之,在类似慢性阻塞性肺病的小鼠模型和体外细胞实验中,青蒿都表现出了抑制肺部感染相关炎症的有益作用。
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引用次数: 0
Sex-Specific and Long-Term Trends of Asthma, Allergic Rhinitis, and Atopic Dermatitis in South Korea, 2007-2022: A Nationwide Representative Study. 2007-2022 年韩国哮喘、过敏性鼻炎和特应性皮炎的性别特异性和长期趋势:一项具有全国代表性的研究。
IF 2.5 4区 医学 Q3 ALLERGY Pub Date : 2024-09-16 DOI: 10.1159/000540928
Yesol Yim, Hyesu Jo, Seoyoung Park, Yejun Son, Jaeyu Park, Hyeon Jin Kim, Sooji Lee, Hayeon Lee, Damiano Pizzol, Lee Smith, Saiah Kim, Jiseung Kang, Selin Woo, Dong Keon Yon

Introduction: Although sex differences in allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and asthma are considered important, a limited number of studies during the COVID-19 pandemic investigated this aspect. Therefore, this study aimed to analyze sex-specific and long-term trends and risk factors for allergic diseases before and during the pandemic.

Methods: This study utilized data from the Korea National Health and Nutrition Examination Survey, 2007-2022, including 92,135 participants aged 19 years and older. This study used weighted multivariate regression analysis to examine the estimates of related factors and assessed weighted odds ratios or β-coefficients for these factors across multiple categories.

Results: During the study period (2007-2022), the prevalence of AR was more common in females than in males. Particularly in 2022, the prevalence among females was 19.3% (95% confidence interval, 17.3-21.3), while among males, it was 15.6% (13.8-17.4). The prevalence of AD and asthma showed a slight disparity between males and females. Before and during the pandemic, the prevalence of AD and AR showed a continuous increase (AD: from 2.8% [2.5-3.2] in 2007-2009 to 4.7% [3.9-5.4] in 2022; AR: from 11.7% [11.1-12.4] in 2007-2009 to 17.4% [16.0-18.9] in 2022), while asthma maintained a relatively stable trend. Moreover, this study identified several sex-specific factors that seem to be associated with a higher prevalence of allergic diseases in females, such as high household income, smoking, and being overweight or obese.

Conclusions: Throughout all the periods examined, females consistently exhibited a higher prevalence of AR compared to males. Moreover, the risk factors for males and females varied depending on the disease, with females generally facing a greater number of risk factors. Consequently, this study highlights the necessity for sex-specific health interventions and further research to comprehend the complex influence of socioeconomic factors and lifestyle choices on the prevalence and risk of AD, AR, and asthma.

导言:虽然特应性皮炎(AD)、过敏性鼻炎(AR)和哮喘等过敏性疾病的性别差异被认为很重要,但在 COVID-19 大流行期间,对这方面进行调查的研究数量有限。因此,本研究旨在分析大流行之前和期间过敏性疾病的性别特异性和长期趋势及风险因素:本研究利用了 2007-2022 年韩国国民健康与营养调查的数据,其中包括 92 135 名 19 岁及以上的参与者。本研究采用加权多元回归分析法来检验相关因素的估计值,并评估了这些因素在多个类别中的加权几率比或β系数:在研究期间(2007-2022 年),女性的 AR 患病率高于男性。特别是在 2022 年,女性的患病率为 19.3%(95% 置信区间,17.3-21.3),而男性的患病率为 15.6%(13.8-17.4)。注意力缺失症和哮喘的发病率在男性和女性之间略有差异。在大流行之前和期间,AD 和 AR 的患病率呈持续上升趋势(AD:从 2007-2009 年的 2.8% [2.5-3.2] 升至 2022 年的 4.7% [3.9-5.4];AR:从 2007-2009 年的 11.7% [11.1-12.4] 升至 2022 年的 17.4% [16.0-18.9]),而哮喘则保持了相对稳定的趋势。此外,本研究还发现了一些与性别相关的因素,如家庭收入高、吸烟、超重或肥胖等,这些因素似乎与女性过敏性疾病的发病率较高有关:在所有研究期间,女性的 AR 患病率始终高于男性。此外,男性和女性的风险因素因疾病而异,女性通常面临更多的风险因素。因此,这项研究强调,有必要针对不同性别采取不同的健康干预措施,并开展进一步研究,以了解社会经济因素和生活方式选择对注意力缺失症、注意力缺失综合症和哮喘的发病率和风险的复杂影响。
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引用次数: 0
Yao Syndrome: An Overview of Genotypic Associations, Clinical Manifestations, Diagnosis, and Treatment. 姚氏综合征:基因型关联、临床表现、诊断和治疗概述。
IF 2.5 4区 医学 Q3 ALLERGY Pub Date : 2024-09-13 DOI: 10.1159/000540188
Ayesha Khalid, Alan Kaell

Background: Yao syndrome (YAOS) is a rare systemic autoinflammatory disorder (AID) of the innate immune system. It was recently categorized as genetically transitional disease (GTD) and is associated with NOD2 variants located at multiple NOD2 gene loci. Unlike most other periodic fever syndromes, the estimated disease prevalence is 1-10/100,000 with a predominance for females and white adult population. In this review, we aimed to provide a detailed analysis of different aspects of this syndrome to help better understand the underlying pathogenesis and incorporate the current evidence-based medicine published to diagnose and manage these patients.

Summary: We conducted literature search on YAOS from 2011 to 2024 using PubMed, Embase, and Scopus databases. Thirty-two studies were included in our narrative review. A descriptive analysis was performed of both Yao and non-Yao authored records to embrace the syndrome reported from all investigators and assess differences and similarities. The most reported gene variant is the homozygous IVS8+158 followed by compound heterozygous IVS8+158 and R702W. Mean age of disease onset is between 36 and 42 years. The mean age of disease diagnosis is between 40 and 45 years with a variable disease duration. Fever is the most commonly reported symptom followed by musculoskeletal, gastrointestinal symptoms and dermatitis. On laboratory workup, patients have elevated levels of erythrocyte sedimentation rate, C-reactive protein, and serum ferritin with negative autoantibody workup. Arthritic symptoms in YAOS patients have a positive response to sulfasalazine and glucocorticoids, while nonsteroidal anti-inflammatory drugs and colchicine produce minimal response. Anti-IL1 and anti-IL6 agents (canakinumab, anakinra, and tocilizumab) are effective treatment modalities.

Key messages: The evolving concept and acceptance of GTD will hopefully further our understanding about this SAID and similar disorders. We suggest developing a registry of patients with YAOS to keep track of expanding data on this subject. It is important to understand various aspects of YAOS including genetic and environmental factors, differential diagnosis, clinical manifestations, laboratory findings, and treatment options available to diagnose and manage these patients appropriately and timely.

背景:姚氏综合征(YAOS)是一种罕见的先天性免疫系统自身炎症性疾病(AID)。它最近被归类为遗传过渡性疾病(GTD),与位于多个 NOD2 基因位点的 NOD2 变异有关。与其他大多数周期性发热综合征不同,该病的估计发病率为 1-10/100,000,女性和成年白人占多数。在这篇综述中,我们旨在对该综合征的不同方面进行详细分析,以帮助更好地理解其潜在的发病机制,并结合当前发布的循证医学证据来诊断和管理这些患者。摘要:我们使用 PubMed、Embase 和 Scopus 数据库对 2011 年至 2024 年期间有关 YAOS 的文献进行了检索。我们的叙述性综述共纳入 32 项研究。我们对姚氏和非姚氏作者的记录进行了描述性分析,以囊括所有研究者报告的综合征并评估其异同。报告最多的基因变异是同型杂合子 IVS8+158,其次是复合杂合子 IVS8+158 和 R702W。平均发病年龄在 36 至 42 岁之间。确诊的平均年龄为 40 至 45 岁,病程长短不一。发热是最常见的症状,其次是肌肉骨骼、胃肠道症状和皮炎。在实验室检查中,患者的红细胞沉降率、C 反应蛋白和血清铁蛋白水平升高,但自身抗体检查结果为阴性。YAOS患者的关节炎症状对柳氮磺胺吡啶和糖皮质激素有积极反应,而对非甾体抗炎药和秋水仙碱的反应很小。抗IL1和抗IL6药物(canakinumab、anakinra和tocilizumab)是有效的治疗方式:关键信息:GTD 的概念和接受程度不断发展,有望进一步加深我们对这种 SAID 和类似疾病的了解。我们建议建立一个 YAOS 患者登记册,以跟踪有关该主题的不断扩大的数据。重要的是要了解 YAOS 的各个方面,包括遗传和环境因素、鉴别诊断、临床表现、实验室检查结果和治疗方案,以便及时对这些患者进行适当的诊断和管理。
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引用次数: 0
Possible Association of CD3+CD4-CD8- Phenotype of T-Cell Lymphoma with Peripheral Blood Eosinophilia. T 细胞淋巴瘤的 CD3+CD4-CD8- 表型与外周血嗜酸性粒细胞增多症的可能联系
IF 2.5 4区 医学 Q3 ALLERGY Pub Date : 2024-09-13 DOI: 10.1159/000541097
Rie Tabata, Chiharu Tabata

Introduction: Because the prognosis of patients with peripheral T-cell lymphoma is poor compared to that of patients with B-cell lymphoma, we want to avoid further organ damage by eosinophilia. Moreover, in patients with some types of lymphoma, blood eosinophilia is implicated in a worse prognosis. To study the risk factors of eosinophilia, the association between lymphoma type, immunophenotypic features, and peripheral blood eosinophil counts were examined in the patients with mature T-cell lymphoma.

Methods: We retrospectively examined 28 patients with mature T-cell lymphoma who were admitted to our hospital and whose immunophenotypic features were confirmed using flow cytometric, immunohistochemical analysis, or both between December 2012 and November 2023.

Results: We report a possible association between peripheral eosinophilia and peripheral T-cell lymphoma - not otherwise specified and CD3+CD4-D8- (double-negative) phenotypes. Mild eosinophilia was observed in various types, but moderate and severe eosinophilia were observed in patients with peripheral T-cell lymphoma - not otherwise specified. Double-negative phenotype was rarely observed; however, all patients with double-negative phenotype exhibited peripheral blood eosinophilia. In addition, four of the five cases of the double-negative type were peripheral T-cell lymphoma - not otherwise specified.

Conclusion: Here, we retrospectively examined patients with peripheral T-cell lymphoma whose immunophenotypic features were confirmed and report a possible association between peripheral eosinophilia and peripheral T-cell lymphoma - not otherwise specified and CD3+CD4-CD8- (double-negative) phenotypes. In addition, clinicians should be aware of the possible risk that patients with lymphocytic hypereosinophilic syndrome of the double-negative phenotype may develop peripheral T-cell lymphoma.

导言与 B 细胞淋巴瘤患者相比,外周 T 细胞淋巴瘤患者的预后较差,因此我们希望避免嗜酸性粒细胞增多对器官造成进一步损害。此外,在某些类型的淋巴瘤患者中,血液嗜酸性粒细胞增多与预后不良有关。为了研究嗜酸性粒细胞增多的危险因素,我们对成熟T细胞淋巴瘤患者的淋巴瘤类型、免疫表型特征和外周血嗜酸性粒细胞计数之间的关系进行了研究:我们对 2012 年 12 月至 2023 年 11 月期间本院收治的 28 例成熟 T 细胞淋巴瘤患者进行了回顾性研究,这些患者的免疫分型特征通过流式细胞术、免疫组化分析或两者同时使用得到证实:我们报告了外周嗜酸性粒细胞增多与外周T细胞淋巴瘤--未另作说明和CD3+CD4-D8-(双阴性)表型之间可能存在的关联。轻度嗜酸性粒细胞增多见于各种类型的淋巴瘤,但中度和重度嗜酸性粒细胞增多见于外周T细胞淋巴瘤--非特异性淋巴瘤患者。很少观察到双阴性表型,但所有双阴性表型患者都有外周血嗜酸性粒细胞增多。此外,5 例双阴型病例中有 4 例为外周 T 细胞淋巴瘤(未另作说明):在此,我们对免疫表型特征得到证实的外周T细胞淋巴瘤患者进行了回顾性研究,并报告了外周血嗜酸性粒细胞增多与外周T细胞淋巴瘤--非特异性和CD3+CD4-CD8-(双阴性)表型之间可能存在的关联。此外,临床医生应注意双阴性表型的淋巴细胞高嗜酸性粒细胞综合征患者可能会罹患外周T细胞淋巴瘤。
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引用次数: 0
The Function of RhoA/ROCK Pathway and MYOCD in Airway Remodeling in Asthma. RhoA/ROCK 通路和 MYOCD 在哮喘气道重塑中的功能
IF 2.8 4区 医学 Q3 ALLERGY Pub Date : 2024-09-11 DOI: 10.1159/000540963
Yunfei Cui,Chendi Yu,Qinghua Lu,Xiao Huang,Weinan Lin,Ting Huang,Lichao Cao,Qin Yang
INTRODUCTIONAsthma is a common chronic respiratory disease characterized by chronic airway inflammation and abnormal airway remodeling. The RhoA/ROCK pathway and myocardin-related transcription factor A (MRTF-A) demonstrate significant associations with the proliferation of airway smooth muscle cells (ASCMs), which tightly correlates with the process of airway remodeling. MYOCD, which is homologous to MRTF-A but specifically expressed in smooth muscle cells, potentially regulates RhoA/ROCK activated cell proliferation and subsequent airway remodeling.METHODSThe RhoA/ROCK overexpression and silencing cell lines were constructed in vitro, as well as MYOCD overexpression/silencing. The cytoskeleton alterations induced by RhoA/ROCK pathway were identified by the measuring of globular actin and filamentous actin.RESULTSThe comparison between controls for overexpression/silencing and ROCK overexpression/silencing revealed that MYOCD presented consistent change trends with cytoskeleton and RhoA/ROCK pathway. The ROCK1 facilitates the proliferation and migration of ASCMs. The MYOCD enhanced the proliferation and migration of HASMCs.CONCLUSIONOur study indicates that Rho/ROCK/MYOCD is a key pathway involved in the migration and proliferation of airway smooth muscle cells. Inhibition of Rho/ROCK may be an effective approach to breaking the vicious cycle of asthmatic ASCMs proliferation, providing a novel strategy in treating asthma airway remodeling.
简介:哮喘是一种常见的慢性呼吸系统疾病,以慢性气道炎症和气道异常重塑为特征。RhoA/ROCK 通路和肌钙蛋白相关转录因子 A(MRTF-A)与气道平滑肌细胞(ASCMs)的增殖密切相关,而气道平滑肌细胞的增殖与气道重塑过程密切相关。MYOCD与MRTF-A同源,但在平滑肌细胞中特异性表达,可能调节RhoA/ROCK激活的细胞增殖和随后的气道重塑。结果对照组过表达/沉默细胞系与ROCK过表达/沉默细胞系比较发现,MYOCD与细胞骨架和RhoA/ROCK通路呈现一致的变化趋势。ROCK1 可促进 ASCMs 的增殖和迁移。结论我们的研究表明,Rho/ROCK/MYOCD 是参与气道平滑肌细胞迁移和增殖的关键通路。我们的研究表明,Rho/ROCK/MYOCD 是参与气道平滑肌细胞迁移和增殖的关键通路。抑制 Rho/ROCK 可能是打破哮喘 ASCMs 增殖恶性循环的有效方法,为治疗哮喘气道重塑提供了一种新策略。
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引用次数: 0
Elevated Serum IL-17A in Kawasaki Disease Patients Predicts Responsiveness to Intravenous Immunoglobulin Therapy. 川崎病患者血清 IL-17A 升高可预测对静脉注射免疫球蛋白疗法的反应。
IF 2.8 4区 医学 Q3 ALLERGY Pub Date : 2024-09-10 DOI: 10.1159/000540697
Yan Lu,Fang-Qi Hu
INTRODUCTIONThis study aimed to investigate the correlation between serum interleukin (IL)-17A levels and responsiveness to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD) patients.METHODSA retrospective analysis on data from 192 KD patients admitted to the Anqing Municipal Hospital between January 2021 and January 2024 was conducted. Patients were categorized into IVIG-nonresponsive and IVIG-sensitive groups as per the treatment outcomes. Outcome measures included serum IL-17A levels, left coronary artery (LCA) Z scores, and relevant laboratory parameters. Logistic regression analysis was performed to identify predictive factors for IVIG responsiveness, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC).RESULTSA total of 40 IVIG-nonresponsive cases and 152 IVIG-sensitive cases were included. Prior to intervention, IVIG-nonresponsive patients had significantly higher serum IL-17A levels compared to IVIG-sensitive patients, with a statistically significant difference. After intervention, serum IL-17A levels significantly decreased in IVIG-sensitive patients while remaining elevated in IVIG-nonresponsive patients. IVIG-nonresponsive patients exhibited significantly higher levels of C-reactive protein (CRP), white blood cell count (WBC), NE, and ALT compared to IVIG-sensitive patients, whereas no significant differences in LCA Z scores between the two groups existed. Multivariable logistic regression analysis identified pre-IL-17A, CRP, WBC, and ALT as independent predictors of IVIG-nonresponsiveness in KD. When pre-IL-17A was ≥39.96 pg/mL, the specificity and sensitivity for predicting IVIG-nonresponsive KD were 63.9% and 71.9%, respectively, with an AUC of 0.637. The combined diagnosis of IL-17A, CRP, WBC, and ALT yielded an AUC of 0.780.CONCLUSIONSerum IL-17A levels were remarkably elevated in IVIG-nonresponsive KD patients both before and after intervention. A serum IL-17A level (≥39.96 pg/mL) demonstrated good predictive profile for IVIG-nonresponsive KD, and combining IL-17A with CRP, WBC, and ALT improved diagnostic performance.
方法对安庆市立医院2021年1月至2024年1月期间收治的192例川崎病(KD)患者的血清白细胞介素(IL)-17A水平与静脉注射免疫球蛋白(IVIG)治疗反应性之间的相关性进行回顾性分析。根据治疗结果将患者分为 IVIG 无应答组和 IVIG 敏感组。结果指标包括血清IL-17A水平、左冠状动脉(LCA)Z评分和相关实验室指标。结果共纳入 40 例 IVIG 无应答病例和 152 例 IVIG 敏感病例。干预前,IVIG 无反应患者的血清 IL-17A 水平明显高于 IVIG 敏感患者,差异有统计学意义。干预后,IVIG 敏感患者的血清 IL-17A 水平明显降低,而 IVIG 无反应患者的血清 IL-17A 水平仍然升高。与 IVIG 敏感患者相比,IVIG 无反应患者的 C 反应蛋白 (CRP)、白细胞计数 (WBC)、NE 和 ALT 水平明显更高,而两组患者的 LCA Z 评分无明显差异。多变量逻辑回归分析发现,IL-17A 前值、CRP、WBC 和 ALT 是 KD 患者对 IVIG 无反应的独立预测因素。当IL-17A前值≥39.96 pg/mL时,预测IVIG无反应性KD的特异性和敏感性分别为63.9%和71.9%,AUC为0.637。综合诊断 IL-17A、CRP、WBC 和 ALT 的 AUC 为 0.780。血清IL-17A水平(≥39.96 pg/mL)对IVIG无反应性KD有良好的预测作用,将IL-17A与CRP、WBC和ALT结合可提高诊断效果。
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引用次数: 0
Negative Predictive Value of Single-Day Drug Provocation Test for Immediate and Non-Immediate Beta-Lactam Hypersensitivity Reactions in Children. 单日药物刺激试验对儿童即刻和非即刻β-内酰胺超敏反应的负预测值
IF 2.5 4区 医学 Q3 ALLERGY Pub Date : 2024-09-05 DOI: 10.1159/000540796
Cankat Genis, Fatma Nur Kuzucu, Zeynep Sengül Emeksiz, Emine Dibek Mısırlıoglu

Introduction: Beta-lactam antibiotics (BLAs) commonly cause hypersensitivity reactions in children. These reactions are categorized into immediate reactions, which include urticaria, angioedema, bronchospasm, and anaphylaxis, and non-immediate reactions, such as maculopapular rashes and delayed-onset urticaria/angioedema. Rashes in children, often caused by infections, may be misdiagnosed as BLA allergy. However, over 90% tolerate the medication following an allergic evaluation.

Methods: We aimed to evaluate patients with negative single-day drug provocation test (sdDPT) results for subsequent reactions and to determine the negative predictive value (NPV) of sdDPT for immediate (less than 1 h) and non-immediate (more than 1 h) suspected BLA allergy. In addition, non-immediate reactions were assessed by classifying them as occurring within 1-6 h or after 6 h. Patients who underwent sdDPT for suspected BLA allergy and tested negative between 2019 and 2023 were included in the study. They were questioned via telephone interviews about their reuse of the tested drug.

Results: 404 patients who underwent sdDPT for suspected BLA allergy were evaluated. The NPV of BLA sdDPT was determined to be 97.3%. When patients were categorized based on the time interval between the last dose and the reaction, the NPV was 97% for those experiencing a reaction within the first hour of drug use and 96.7% for reactions occurring after more than 1 h. Non-immediate reactions were further evaluated, revealing an NPV of 98.7% for reactions occurring between 1 and 6 h, and 92.5% for reactions occurring after 6 h.

Conclusion: Our findings demonstrate that sdDPT has a high NPV for both immediate and non-immediate reactions. However, the NPV of sdDPT was lower for reactions occurring more than 6 h after the last dose.

简介:β-内酰胺类抗生素(BLAs)通常会引起儿童超敏反应。这些反应可分为即时反应(包括荨麻疹、血管性水肿、支气管痉挛和过敏性休克)和非即时反应(如斑丘疹和迟发性荨麻疹/血管性水肿)。儿童皮疹通常由感染引起,可能会被误诊为 BLA 过敏。然而,90% 以上的患者在接受过敏评估后可以耐受药物:我们的目的是对单日药物激发试验(sdDPT)结果为阴性的患者进行后续反应评估,并确定单日药物激发试验对即刻(少于 1 小时)和非即刻(超过 1 小时)疑似 BLA 过敏的阴性预测值(NPV)。此外,还对非即刻反应进行了评估,将其分为 1-6 小时内发生的反应和 6 小时后发生的反应。该研究纳入了 2019 年至 2023 年期间因疑似 BLA 过敏而接受 sdDPT 并检测结果呈阴性的患者。研究人员通过电话访谈询问了他们再次使用受测药物的情况:对 404 名因疑似 BLA 过敏而接受 sdDPT 的患者进行了评估。经测定,BLA sdDPT 的 NPV 为 97.3%。如果根据最后一次用药与反应之间的时间间隔对患者进行分类,用药后 1 小时内发生反应的患者的 NPV 为 97%,超过 1 小时后发生反应的患者的 NPV 为 96.7%。对非即刻反应进行进一步评估后发现,1 至 6 小时内发生反应的患者的 NPV 为 98.7%,6 小时后发生反应的患者的 NPV 为 92.5%:我们的研究结果表明,sdDPT 对即刻反应和非即刻反应都有很高的 NPV。然而,对于最后一次用药后 6 小时以上发生的反应,sdDPT 的 NPV 值较低。
{"title":"Negative Predictive Value of Single-Day Drug Provocation Test for Immediate and Non-Immediate Beta-Lactam Hypersensitivity Reactions in Children.","authors":"Cankat Genis, Fatma Nur Kuzucu, Zeynep Sengül Emeksiz, Emine Dibek Mısırlıoglu","doi":"10.1159/000540796","DOIUrl":"https://doi.org/10.1159/000540796","url":null,"abstract":"<p><strong>Introduction: </strong>Beta-lactam antibiotics (BLAs) commonly cause hypersensitivity reactions in children. These reactions are categorized into immediate reactions, which include urticaria, angioedema, bronchospasm, and anaphylaxis, and non-immediate reactions, such as maculopapular rashes and delayed-onset urticaria/angioedema. Rashes in children, often caused by infections, may be misdiagnosed as BLA allergy. However, over 90% tolerate the medication following an allergic evaluation.</p><p><strong>Methods: </strong>We aimed to evaluate patients with negative single-day drug provocation test (sdDPT) results for subsequent reactions and to determine the negative predictive value (NPV) of sdDPT for immediate (less than 1 h) and non-immediate (more than 1 h) suspected BLA allergy. In addition, non-immediate reactions were assessed by classifying them as occurring within 1-6 h or after 6 h. Patients who underwent sdDPT for suspected BLA allergy and tested negative between 2019 and 2023 were included in the study. They were questioned via telephone interviews about their reuse of the tested drug.</p><p><strong>Results: </strong>404 patients who underwent sdDPT for suspected BLA allergy were evaluated. The NPV of BLA sdDPT was determined to be 97.3%. When patients were categorized based on the time interval between the last dose and the reaction, the NPV was 97% for those experiencing a reaction within the first hour of drug use and 96.7% for reactions occurring after more than 1 h. Non-immediate reactions were further evaluated, revealing an NPV of 98.7% for reactions occurring between 1 and 6 h, and 92.5% for reactions occurring after 6 h.</p><p><strong>Conclusion: </strong>Our findings demonstrate that sdDPT has a high NPV for both immediate and non-immediate reactions. However, the NPV of sdDPT was lower for reactions occurring more than 6 h after the last dose.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1-9"},"PeriodicalIF":2.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immediate Hypersensitivity Reactions to Biologic Drugs in Children with Inflammatory Bowel Diseases. 炎症性肠病患儿对生物制剂药物的即刻超敏反应。
IF 2.5 4区 医学 Q3 ALLERGY Pub Date : 2024-09-04 DOI: 10.1159/000540795
Sinem Polat Terece, Hacer Ilbilge Ertoy Karagol, Demet Teker Duztas, Gizem Koken, Hakan Ozturk, Dilek Yapar, Odul Egritas Gurkan, Sinan Sari, Buket Dalgic, Arzu Bakirtas

Introduction: The increased use of biologic drugs (BDs) may lead to an increase in immediate hypersensitivity reactions (I-HSRs) in pediatric patients with inflammatory bowel disease (IBD). Our aim was to assess I-HSRs to BDs in pediatric IBD, examining frequency, clinical features, management, and associated risk factors.

Methods: All children diagnosed with IBD at our institution between January 1, 2006, and August 1, 2023, and who developed I-HSRs related to any BD were included in the study.

Results: In a study of 197 pediatric IBD patients, 61 used BD. Among these, 52.4% were male, with a median diagnosis age of 145 months (13-215). Out of a total of 1,679 administrations, 6 patients developed I-HSRs (5 with infliximab, 1 with adalimumab), resulting in a frequency of 9.8% per patient and 0.36% per administration. Of these, 66.7% were cases of Type 1 HSRs (skin test positivity n = 1), while the rest were infusion-related reactions (anti-drug antibody positivity n = 4), all of which were mild to moderate in severity. In the age and gender-adjusted logistic regression model, the presence of any comorbid allergic disease was significantly associated with the occurrence of I-HSR (aOR = 8.35; 95% CI = 1.24-56.38; p = 0.029).

Conclusion: The frequency of I-HSRs to BDs in children with IBD is not rare but not severe in the long term. The presence of any comorbid allergic disease is a risk factor for the development of I-HSRs to BDs.

导言:生物制剂药物(BDs)使用的增加可能会导致炎症性肠病(IBD)儿科患者的即刻超敏反应(I-HSRs)增加。我们的目的是评估小儿 IBD 患者对 BDs 的即刻超敏反应,研究其发生频率、临床特征、处理方法和相关风险因素:研究纳入了我院 2006 年 1 月 1 日至 2023 年 8 月 1 日期间诊断为 IBD 的所有患儿,这些患儿均出现了与任何 BD 相关的 I-HSRs :在 197 名小儿 IBD 患者中,61 人使用了 BD。其中 52.4% 为男性,诊断年龄中位数为 145 个月(13-215)。在总共1,679次用药中,有6名患者出现了I-HSR(5例使用英夫利昔单抗,1例使用阿达木单抗),每位患者的发生率为9.8%,每次用药的发生率为0.36%。其中,66.7%为1型HSR(皮试阳性n = 1),其余为输注相关反应(抗药物抗体阳性n = 4),所有反应的严重程度均为轻度至中度。在年龄和性别调整后的逻辑回归模型中,合并过敏性疾病与 I-HSR 的发生显著相关(aOR = 8.35; 95% CI = 1.24-56.38; p = 0.029):结论:IBD患儿对BD的I-HSR发生率并不罕见,但长期来看并不严重。结论:IBD患儿对BD发生I-HSRs的频率并不罕见,但长期来看并不严重,任何合并过敏性疾病的存在都是导致对BD发生I-HSRs的风险因素。
{"title":"Immediate Hypersensitivity Reactions to Biologic Drugs in Children with Inflammatory Bowel Diseases.","authors":"Sinem Polat Terece, Hacer Ilbilge Ertoy Karagol, Demet Teker Duztas, Gizem Koken, Hakan Ozturk, Dilek Yapar, Odul Egritas Gurkan, Sinan Sari, Buket Dalgic, Arzu Bakirtas","doi":"10.1159/000540795","DOIUrl":"https://doi.org/10.1159/000540795","url":null,"abstract":"<p><strong>Introduction: </strong>The increased use of biologic drugs (BDs) may lead to an increase in immediate hypersensitivity reactions (I-HSRs) in pediatric patients with inflammatory bowel disease (IBD). Our aim was to assess I-HSRs to BDs in pediatric IBD, examining frequency, clinical features, management, and associated risk factors.</p><p><strong>Methods: </strong>All children diagnosed with IBD at our institution between January 1, 2006, and August 1, 2023, and who developed I-HSRs related to any BD were included in the study.</p><p><strong>Results: </strong>In a study of 197 pediatric IBD patients, 61 used BD. Among these, 52.4% were male, with a median diagnosis age of 145 months (13-215). Out of a total of 1,679 administrations, 6 patients developed I-HSRs (5 with infliximab, 1 with adalimumab), resulting in a frequency of 9.8% per patient and 0.36% per administration. Of these, 66.7% were cases of Type 1 HSRs (skin test positivity n = 1), while the rest were infusion-related reactions (anti-drug antibody positivity n = 4), all of which were mild to moderate in severity. In the age and gender-adjusted logistic regression model, the presence of any comorbid allergic disease was significantly associated with the occurrence of I-HSR (aOR = 8.35; 95% CI = 1.24-56.38; p = 0.029).</p><p><strong>Conclusion: </strong>The frequency of I-HSRs to BDs in children with IBD is not rare but not severe in the long term. The presence of any comorbid allergic disease is a risk factor for the development of I-HSRs to BDs.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1-8"},"PeriodicalIF":2.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
International Archives of Allergy and Immunology
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