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关键词： allergy   cytokine   human   IgE   inflammation   lectin   tumor immunity  

摘要： Galectin-3 (Gal-3) is implicated in innate immune cell activation in a host of diseases/conditions. We identified a unique response whereby human basophils secrete interleukin (IL)-4/IL-13 when cocultured with A549 cells-lung adenocarcinoma. While displaying parameters consistent with standard IgE-dependent activation, these Gal-3-dependent responses occurred in the absence of specific IgE/allergens and required cell-to-cell contact. We now hypothesize that this mode of activation also impacts A549 function. Our findings show that cytokines are induced in basophil/A549 cocultures that are not detected when either cell is cultured alone, in particular IL-6. As previously shown for IL-4/IL-13, IL-6 production also required cell-to-cell contact and was dependent on A549- Gal-3, as clones deficient of this lectin induced less cytokine. Using culture-derived basophils (CDBAs), we demonstrate that the IL-6 response and production of another tumorigenic factor, vascular endothelial growth factor A (VEGF-A), are induced in CDBA/A549 cocultures but only after passively sensitizing CDBAs with IgE, in a manner similar to IL-4/IL-13. However, IgE-dependent activation of basophils/CDBAs cultured alone failed to induce IL-6/VEGF. Importantly, IL-3-primed basophils, even those fixed with paraformaldehyde, readily induced IL-6/VEGF-A in cocultures, thus verifying that these cytokines are derived from A549. Overall, these results suggest a complex mechanism whereby Gal-3/IgE interactions between IL-3-primed basophils and A549 have the potential to modulate cytokine production by both cells. With Gal-3 implicated not only in many diseases ranging from asthma to cancer, but also in normal physiological conditions, such as wound healing, these findings are predicted to provide insight into the molecular mechanisms by which this lectin (and IgE) functions in these processes.

关键词： 多发性骨髓瘤   慢性淋巴细胞白血病   合并症   不同类型轻链  

摘要： 多发性骨髓瘤（multiple myeloma， MM）是一种克隆性浆细胞异常增殖并伴有单克隆免疫球蛋白异常增多的肿瘤，也是常见的血液系统恶性肿瘤之一，发病率约占血液系统疾病的10%，其主要临床特征包括高钙血症、肾功能损伤、贫血和骨痛[1]。

关键词： intestinal Beh & ccedil   et's disease   upadacitinib   case report   mucosal healing   anti-TNF-refractory  

摘要： Background The limited therapeutic options and inconsistent treatment efficacy of Intestinal Beh & ccedil;et's disease complicate its management, with the absence of standardized guidelines further exacerbating the challenges faced by *** Presentation In this case report, we present a patient with refractory intestinal Beh & ccedil;et's disease who experienced treatment failure with prior biologic agents. This case sheds light on managing this complex scenario with Janus kinase (JAK) inhibitors, the patient achieved mucosal healing after switching to *** This case underscores the potential of Upadacitinib as an effective alternative for managing difficult cases of intestinal Beh & ccedil;et's disease.

关键词： TCR signaling   Tfh cell   cytokine plasticity   IL-21   T cell differentiation  

摘要： The development of T follicular helper (Tfh) cells is an ongoing process resulting in the formation of various Tfh subsets. Despite advancements, the precise impact of T cell receptor (TCR) stimulation on this process remains incompletely understood. This study explores how TCR-CD3 signaling strength influences naive CD4+ T cell differentiation into Tfh-like cells and the concurrent expression of interleukin-21 (IL-21), interleukin-4 (IL-4), and interferon-gamma (IFN-gamma). Strong TCR-CD3 stimulation induces proliferation and increased IL-21 expression in Tfh-like cells, which exhibit a characteristic phenotype expressing CXCR5 and PD1. The coexpression of IL-4 and IFN-gamma in IL-21-producing Tfh-like cells is controlled by the strength TCR-CD3 stimulation;low stimulation favors IL-4, while strong stimulation enhances IFN-gamma secretion. Exogenous addition of the effector cytokines IL-21 and IL-4 further modulate cytokine coexpression. These findings highlight the intricate regulatory mechanisms governing cytokine production and plasticity in Tfh-like cells, providing insights into B cell response modulation. In vivo, antigen availability may regulate Tfh cell plasticity, impacting subsequent B cell differentiation, emphasizing the need for further exploration through animal models or antigen-specific Tfh cell analyses in human lymph node biopsies

关键词： mRNA   Oral cancer   Precancer   Saliva   Salivary biomarkers  

摘要： The research examined the salivary concentrations of various biomarkers, such as OAZ1, SAT, S100P, IL-1β, and IL-8 aiming to detect early-stage oral squamous cell carcinoma (OSCC). These biomarkers show potential as indicators for detecting both pre-cancerous and cancerous states within the oral cavity. Analyzing these specific molecules in saliva could help clinicians enhance diagnostic accuracy and refine early detection methods for OSCC. The research encompassed a cohort of nine OSCC patients, ten with oral submucous fibrosis (OSF), eleven individuals with oral lichen planus (OLP), and ten healthy controls. The study focused on assessing the expression levels of key biomarkers-IL-1β, IL-8, SAT, S100P, and OAZ1 mRNA-in extracellular RNA extracted from saliva samples. This evaluation was conducted using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) with sequence-specific primers. Additionally, receiver operating characteristic curve (ROC) curve analysis was employed to gauge the efficacy of these biomarkers in detecting OSCC. Based on the results we observe, when these five biomarkers are used together, they give a 90% predictive probability for patients with OLP, an 80% predictive probability for OSF, and an impressive 100% predictive probability for patients with OSCC (AUC = 1.000, p = 0.000). This study demonstrates the efficacy of salivary transcriptome diagnostics in detecting OSCC. This novel clinical technique has the potential to be a powerful, efficient, and reliable tool for early detection of cancer. Salivary transcriptomes can be further analyzed to evaluate their effectiveness in other important illness contexts and for regular health monitoring. © 2024. The Author(s).

关键词： 脓毒症   淋巴细胞计数   白细胞介素-6   D-二聚体   严重程度  

摘要： 目的 探讨LYM、IL-6及D-D对脓毒症患者病情严重程度的评估。方法 回顾性分析2023年1月至2023年11月新疆维吾尔自治区人民医院急救中心（EICU）收治符合诊断脓毒症3.0的患者。收集患者临床基本资料，入EICU24h内的实验室常规炎性指标、免疫指标和凝血指标及相关病情评分。根据是否出现脓毒性休克情况分组，比较上述指标在不同组别间的差异；采用多因素 logistic回归模型分析发生脓毒性休克的危险因素，绘制受试者工作特征（ROC）曲线并计算各曲线下面积（AUC）；采用Spearman等级相关法分析脓毒症患者LYM、IL-6及D-D与发生脓毒性休克的相关性。结果 最终纳入脓毒症患者107例，脓毒症54例，脓毒性休克53例。脓毒性休克组IL-6、D-D 水平较脓毒症组明显升高，LYM水平较脓毒症组明显下降，两组间比较差异均有统计学意义（均 P＜0.01）。根据Spearman等级相关分析，脓毒症患者IL-6、D-D 水平与病情严重程度呈显著正相关，LYM水平与病情严重程度呈显著负相关。多因素logistic回归分析显示，IL-6、D-D是发生脓毒性休克的危险因素，LYM是发生脓毒性休克的保护因素（均P＜0.05）。ROC 曲线分析结果，LYM、IL-6和D-D单独或联合应用对评估脓毒性休克发生均有一定的预测价值，三项指标联合检测的 ROC 曲线下面积大于单独检测，敏感度为98.1%，特异度为68.5%，阳性预测值为75.4％，阴性预测值为97.4％。结论 LYM、IL-6、D-D三项指标联合应用更有效提高对脓毒症患者病情严重程度的评估。

关键词： 麻黄连翘赤小豆汤   IgA肾病   补体激活   炎症反应   C3  

摘要： 探究麻黄连翘赤小豆汤（Mahuang Lianqiao Chixiaodou Decoction， MHLQ）及其主要效应成分治疗IgA肾病（immunoglobin A nephropathy， IgAN）的可能作用机制。采用牛血清白蛋白（bovine serum albumin， BSA）灌胃、皮下注射四氯化碳(carbon tetrachloride， CCl4)、尾静脉注射脂多糖（lipopolysaccharide， LPS）等综合措施建立IgAN大鼠模型。成模后，将IgAN大鼠随机分为模型组，MHLQ低、中、高剂量组，PHI组，PSE组及LP组，并以Wistar大鼠为对照。MHLQ低、中、高剂量组分别给予MHLQ颗粒剂1.773、3.545、7.090 g·kg-1灌胃，PHI组给予连翘苷（phillyrin， PHI）0.020 g·kg-1灌胃，PSE组给予盐酸伪麻黄碱（pseudoephedrine， PSE）0.020 g·kg-1灌胃，LP组给予氯沙坦钾（losartan potassium， LP）9.003 mg·kg-1灌胃，对照组和模型组每日灌胃等体积生理盐水，各组均连续干预4周。给药结束后收集各组大鼠尿液、血清、肝组织和肾组织。检测24h尿蛋白定量（24 hUTP）和肾功能；病理染色观察肾组织病理改变；免疫荧光（immunofluorescence， IF）检测肾脏IgA和补体C3/C3b/C3c表达；电镜观察肾组织超微结构；酶联免疫吸附测试（enzyme linked immunosorbent assay， ELISA）检测血清和肾组织补体C3、可溶性端补体复合物（sC5b-9）蛋白表达；蛋白免疫印迹法（Western blot）检测肝、肾补体C3/C3b/C3c、C5/C5a、C5b-9及B因子（complement factor B， CFB）蛋白表达；免疫组化（immunohistochemistry， IHC）进一步检测肾组织补体C3/C3b/C3c蛋白表达。结果显示，与对照组比较，模型组大鼠尿素氮（blood urea nitrogen， BUN）、血肌酐（serum creatinine， SCr）含量升高，肾小球代偿性扩张，球内系膜细胞增殖，系膜基质扩张，肾小球可见IgA免疫复合物或电子致密物沉积；血清补体C3含量增加；肾组织CFB，补体C3/C3b/C3c， C5/C5a， C5b-9蛋白表达升高；肝组织中补体C3/C3b/C3c和C5b-9蛋白表达升高。而经过MHLQ及其效应成分干预后，上述指标皆逆转。综上所述，MHLQ及其效应成分干预IgAN大鼠疗效肯定，能够改善肾功能，减轻肾脏免疫复合物沉积和病理损伤，其机制可能与抑制IgAN大鼠替代途径（alternative pathway， AP）补体激活有关。

关键词： Arthritis   Methotrexate   Osteoporosis   Inflammation   Glucocorticoids  

摘要： Objectives Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by the synovitis and bone erosion. The combination therapy of glucocorticoids (GCs) and methotrexate (MTX) is recommended in early RA management, although the precise underlying mechanism of action remains unclear. This study is aimed to clarify the mechanism of MTX in combined with GC in treating *** GC-induced osteoporosis (GIOP) mouse model was used to investigate the bone-protective role of MTX. Lipopolysaccharide-induced arthritis mouse model was used to evaluate the anti-inflammatory effects of GCs and MTX. Functional role of MTX on osteoclastogenesis was assessed by trap staining and micro-computer tomography. Western blot, RT-qPCR and coimmunoprecipitation were used to explore the underlying *** We demonstrate that GCs, but not MTX, rapidly inhibited synovitis in arthritis model. MTX treatment was observed to inhibit osteoclastogenesis induced by GC in vitro and mitigate bone loss attributed by GIOP. GCs were found to augment the interaction between the membrane GC receptor (mGR) and signal transducer and activator of transcription 1 (STAT1), leading to the suppression of IFN-gamma R/STAT1 signalling pathways. Interestingly, MTX was found to inhibit osteoclastogenesis induced by GCs through the enhancement of the A2AR and IFN-gamma R interaction, thereby activating the IFN-gamma R/STAT1 signalling cascade. Consequently, this process results in a reduction in the mGR and STAT1 *** Our study provides compelling evidence that MTX can make GCs effectively to suppress synovitis and reduce bone loss induced by GCs. This sheds light on the potential mechanistic insights underlying the efficacy of GCs in conjunction with MTX for treating RA.