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关键词： 哮喘   气道上皮细胞   细胞因子  

摘要： 哮喘是一种常见的慢性气道炎症性疾病,其主要特点是气道的非特异性炎症、气道结构重塑及气道高反应性。多年来关于哮喘的发病机制主要集中于过敏反应导致的免疫失衡,而近年来针对气道上皮损伤在哮喘发生发展中的作用及机制受到重视,认为它可能是哮喘发病与控制的关键因素。气道上皮是人体呼吸系统抵御外界环境有害刺激的第一道屏障,也是气道最为重要的结构细胞。当哮喘患者吸入外界有害物质及过敏原时,气道上皮细胞首先受到侵犯并出现损伤,合成和释放多种炎性介质和细胞因子激活免疫细胞,诱导哮喘发生发展。本文旨在对目前有关哮喘气道上皮损伤的发生机制以及哮喘患者气道上皮的病理变化及其关键细胞因子进行综述,以发现潜在的生物标记物与治疗靶点,为哮喘的早期预测和精准防治提供依据。

关键词： 脓毒症   中性粒细胞胞外诱捕网   C反应蛋白   T淋巴细胞   评估价值  

摘要： 目的探讨血清中性粒细胞胞外诱捕网(NETs)、C反应蛋白(CRP)、外周血CD4^(+)与脓毒症患儿病情严重程度及预后的评估价值。方法回顾性选取我院收治的124例脓毒症患儿作为研究对象,根据疾病严重程度分为脓毒症组(n=49)、严重脓毒症组(n=30)、脓毒症休克组(n=45),比较三组一般资料及NETs、CRP、CD4^(+)水平,Spearman分析其与脓毒症患儿疾病严重程度的相关性。根据治疗28 d后生存情况分为生存组(n=74)和死亡组(n=50),比较两组一般资料及NETs、CRP、CD4^(+)水平,COX回归分析影响脓毒症患儿预后相关因素;ROC分析NETs、CRP、CD4^(+)联合检测对脓毒症患儿预后的预测价值;并绘制生存曲线分析不同血清NETs、CRP、外周血CD4^(+)水平脓毒症患儿预后情况。结果严重脓毒组血清NETs、CRP水平高于脓毒症组而低于脓毒症休克组,外周血CD4^(+)水平低于脓毒症组、高于脓毒症休克组(P<0.05);血清NETs、CRP水平与脓毒症疾病严重程度呈正相关,CD4^(+)水平呈负相关(r=0.280、0.468、-0.407,P<0.05);死亡组血清NETs、CRP水平比生存组更高,外周血CD4^(+)水平比生存组更低(P<0.05);血清NETs、CRP均是影响脓毒症患儿病情预后的相关因素(P<0.05);三者联合预测脓毒症病情预后的曲线下面积(AUC)值高于单项检测(P<0.05);血清NETs≤49.319%、CRP≤62.500 mg/L、外周血CD4^(+)≥24.481%者生存时间比血清NETs>49.319%、CRP>62.500 mg/L、外周血CD4^(+)<24.481%者更长(Z=25.795、29.135、15.883,P<0.05)。结论血清NETs、CRP、CD4^(+)与脓毒症患儿疾病严重程度有关,三者联合检测对脓毒症患儿病情及预后评估价值较高。

关键词： FAT10   UBD   proteasome   MHC-I   antigen processing   antigen presentation   cytotoxic T cells  

摘要： Introduction The presentation of pathogen-derived antigens on major histocompatibility complex (MHC) class I is crucial for the antiviral immune response. Degradation of intracellular pathogen-derived proteins by the 26S proteasome generates peptides that can be loaded on MHC-I molecules and presented to cytotoxic T cells. The cytokine-inducible ubiquitin-like modifier (ULM) HLA-F adjacent transcript 10 (FAT10) is encoded in the MHC locus and targets its substrates for proteasomal degradation. Therefore, it acts as an alternative signal for protein degradation, indicating a role in generating the peptide pool for MHC-I presentation. In this study, we aimed to elucidate the role of FAT10 in MHC class I *** Using different human and mouse cell lines deficient for FAT10, the effect of FAT10 on MHC-I surface expression and recovery was studied. For the evaluation of antigen presentation of viral and endogenous epitopes, T cell hybridoma assays and flow cytometry analysis were *** In our study, using model antigens and FAT10-deficient cells, we found that the absence of FAT10 does not affect the abundance of MHC-I molecules or the generation of endogenous and virus-derived MHC-I epitopes. Furthermore, we demonstrated that the cytotoxic T cell response to different viruses remains unchanged in FAT10-deficient mice compared to wild-type *** In summary, our findings indicate that the lack of FAT10 does not impact antigen presentation or the cytotoxic T-cell response across a number of different MHC-I-restricted peptides. Hence, we conclude that the contribution of FAT10 to MHC-I antigen presentation has previously been overestimated.

关键词： Rh血型   抗原   检验   精准输血   输血安全  

摘要： 目的 对Rh血型D、C、E抗原的分布和其临床应用情况进行分析。方法 收集近5年(2020年3月—2025年3月)因上消化道出血、失血性休克等原因需多次输血治疗的55例病例资料,均完成RhD的血型检测,研究组为符合Rh相容性输血优先Ⅰ级和Ⅱ级,对照组为符合优先Ⅲ级和交叉配血随机盲配,分别是25例、30例。采用抗人球蛋白试验进行抗体筛查,比较两组血红蛋白、红细胞比容差异。结果 55例病例的血液标本Rh血型D、C、E抗原检测:D抗原阳性占比98.18%、C抗原阳性占比94.55%、E抗原阳性占比49.09%;输血前,两组的血红蛋白水平、红细胞比容无显著差异(P>0.05);输血后,研究组的血红蛋白、红细胞比容高于对照组(P<0.05)。对照组血红蛋白尿、腰背疼痛发生率要显著高于研究组(P<0.05)。结论 根据对输血者Rh血型D、C、E抗原的检测为其提供相同血型抗原血液,能保证输血治疗有效性及安全性。

关键词： 再生障碍性贫血   异体淋巴细胞   X射线   外周血   生存率   骨髓   免疫  

摘要： 目的探讨不同剂量X射线联合异体淋巴细胞输注对建立再生障碍性贫血小鼠模型的影响。方法取BALB/c小鼠40只,随机分为对照组(n=12)、3 Gy组(n=9)、4 Gy组(n=9)、5 Gy组(n=10)。3 Gy、4 Gy、5 Gy组指经过相应剂量的X射线辐照并在辐照后4 h内尾静脉输注0.2 mL DBA/2小鼠胸腺、脾脏细胞混合悬液,浓度为1×107个/mL。对照组不经过X射线辐照,并输注等体积生理盐水。BALB/c小鼠经眼眶静脉丛采血,用小鼠血常规分析仪检测外周血红细胞(RBC)、白细胞(WBC)、血小板(PLT)。每日观察小鼠一般情况,统计各组生存率。实验终点,取小鼠胫骨做苏木精-伊红染色(HE),同时取股骨做骨髓涂片进行形态学检测;流式细胞术检测5 Gy组T细胞亚群,酶联免疫吸附测定(ELISA)检测细胞因子。结果3 Gy组,全血细胞减少,但血小板恢复较快,造模第17天恢复正常水平。观察期内小鼠无死亡。实验终点,骨髓形态学表明骨髓增生活跃,粒细胞系、红细胞系比值正常,各阶段细胞形态未见明显异常。HE结果表明对照组骨髓组织致密,组织中充满血细胞。4 Gy组,全血细胞减少且一直维持到观察终点。观察期内生存率为90%。实验终点,骨髓形态学表明骨髓增生降低。HE结果表明骨髓组织较少脂肪浸润。5 Gy组,全血细胞减少,但红细胞在24 d恢复正常水平。观察期内生存率为50%。实验终点,骨髓形态学表明骨髓小粒空虚,造血细胞减少,多呈非造血细胞。HE结果表明5 Gy组骨髓组织严重脂肪浸润,几乎无幼稚细胞和造血前体细胞。流式检测结果显示CD4+T(%)细胞比例降低、CD8+T(%)细胞比例增加。ELISA结果显示负造血调控因子干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)的分泌升高。结论不同剂量的射线联合异体淋巴细胞输注均可导致小鼠外周血RBC、WBC、PLT降低。结合骨髓形态学、骨髓HE染色和免疫学相关指标,5 Gy X射线联合2×106个异体淋巴细胞输注可用于建立再生障碍性贫血小鼠模型。

关键词： IL-1 alpha   iNOS   macrophages   obesity   Th17 cells   tuberculosis  

摘要： IL-1 alpha, IL-1 beta, IFN-gamma, IL-17 and the expression of inducible nitric oxide synthase (iNOS) enzyme by macrophages, which generate nitric oxide, are protective against tuberculosis, a disease caused by Mycobacterium tuberculosis. The severity of tuberculosis can be dependent on bacterial load and/or lung immunopathology. Tuberculosis is aggravated by existing comorbidities such as obesity. Obesity induces metabolic dysfunction, meta inflammation and dysbiosis, which increase the prevalence of respiratory diseases and worsen immunopathology. The deficiency of IL-1 alpha (IL-1 alpha-/-) induces deleterious lung monocytic inflammation and functional activation of the adaptive immune response mediated by T cells during M. tuberculosis infection in non-obese mice. Although iNOS and IFN-gamma have been described as protective in experimental tuberculosis, using a model of obesity induced by high-fat diet, we show here an increase in iNOS-expressing interstitial macrophages positively correlated with M. tuberculosis numbers in the lungs of IL-1 alpha-/- animals, followed by increased frequency of IFN-gamma and decreased frequency of IL-17-producing T cells, showing that IFN-gamma and iNOS contribute to immunopathology and pulmonary damage. The protective effect of IL-1 alpha, characterised by reduction of lung immunopathology, is dependent on IL-17-producing CD4+ cells that negatively regulate iNOS expression on macrophages. Our data provide important implications for tuberculosis with existing obesity that aggravates lung immunopathology associated with an exacerbation of IFN-gamma-producing and iNOS-expressing cells.

摘要： Background Rheumatoid arthritis is an inflammatory disease frequently treated with TNF inhibitors. Little is known about predictors of response to TNF inhibitors. Because clinical response in rheumatoid arthritis is measured by composite scores containing subjective patient-orientated domains (eg, pain and global disease perception), we hypothesised that patients with high disease representation in the CNS might respond better to TNF inhibitors than patients with less CNS disease representation. Methods We did a phase 3, multicentre, double-blind, placebo-controlled, parallel-group randomised trial in patients with active rheumatoid arthritis at six rheumatology centres across Germany, Portugal, and Serbia. All patients had a functional MRI (fMRI) brain scan at baseline to measure CNS pain activation. Patients (aged >= 18 years) with active rheumatoid arthritis who have active disease despite the use of at least one conventional synthetic disease-modifying antirheumatic drug were stratified according to fMRI (high volume or low volume) and were randomly assigned 2:1 using a randomisation list generated by a study statistician to treatment with the TNF inhibitor certolizumab pegol (400 mg subcutaneously on weeks 0, 2, and 4, and 200 mg once every 2 weeks for maximum 24 weeks) or placebo. Patients and clinicians were masked to allocation. The primary outcome was the proportion of patients reaching low disease activity (Disease Activity Score in 28 joints <= 32) at week 12, analysed in the intention-to-treat population. There was no lived experience involvement in study design. The study was registered with EudraCT (2013-000337-13) and *** (NCT01864265). Findings Between Sept 3, 2013, and Jan 10, 2020, 148 patients with rheumatoid arthritis were screened and 139 (99 [71%] women and 40 [29%] men) were randomly assigned to the high-volume certolizumab pegol group (n=49), the low-volume certolizumab pegol group (n=43), or the placebo group (n=47

关键词： Endothelial cells   Monocytes   Anthocyanins   Phenolic metabolites   Inflammation  

摘要： PurposeIn this study we investigated how anthocyanins and their metabolites exert protection on the vasculature by reducing the inflammation-induced monocyte adhesion to endothelial cells, a fundamental stage in endothelial dysfunction (ED) and *** umbilical vein endothelial cells (HUVECs) were pre-treated with varying concentrations (1,5 and 10 mu M) of cyanidin-3-glucoside or phenolic metabolites, protocatechuic acid (PCA) and vanillic acid (VA), for 24 h, followed by TNF-alpha stimulation for 24 h, with or without the presence of THP-1 monocytes for 1 *** the co-culture model, the adhesion of fluorescent monocytes attached to HUVECs was quantified, as well as pro-inflammatory cytokine IL-6 and MCP-1 in cell supernatant. Expression levels of transcription factors Nrf2 and NF-kappa B-p65, as well as vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule (ICAM-1) and heme oxygenase 1 (HO-1) were measured in HUVECs. All treatments prevented the adhesion of monocytes to endothelial cells, which was associated with reductions in IL-6 and MCP-1. Additionally, phenolic metabolites suppressed adhesion molecules, potentially by their ability to upregulate Nrf2 expression and suppress NF-kappa B p65 phosphorylation. Furthermore, VA caused an upregulation of HO-1 *** findings suggest that pre-exposed physiologically relevant concentrations of phenolic metabolites may hinder ED and inflammation by reducing the adhesion of monocytes to endothelial cells and the inflammatory response via the modulation of NF-kappa B and Nrf2 pathway.

摘要： Background. The presence of antibodies to donor-specific HLAs is a well-known risk factor associated with heart transplantation (HTx) outcomes. Recently, non-HLA antibodies were reported to be associated with HTx outcomes. Methods. We evaluated the association between the presence of non-HLA antibodies with early (<= 1 y) and long-term graft failure in 192 patients undergoing HTx in 4 large transplant centers in Korea. Results. Antibodies to vimentin (AVA) and type II collagen (ACA) were associated with a lower rate of 1-y graft survival (78.6% versus 92.6%, log-rank P = 0.006 for AVA+;72.2% versus 91.1%, log-rank P = 0.015 for ACA+). AVA+ stratified 1-y graft survival in patients with donor-specific antibodies (DSAs+;45.5% versus 94.1%, log-rank P = 0.002). AVA+ also improved the prediction models based on conventional risk factors derived from Cox regression analysis (integrated discrimination improvement, 9%;P < 0.001;net reclassification index, 24%;P = 0.047). Compared with AVA-/ACA- patients, AVA+/ACA+ patients had poor graft survival both in the early and late periods (all log-rank P < 0.001). Conclusions. In conclusion, the presence of non-HLA antibodies to vimentin and type II collagen was associated with poor graft outcomes in patients undergoing HTx. These findings highlight the need to consider non-HLA antibodies in assessing transplant recipients and tailoring immune modulation strategies.