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关键词： IL-6   病毒感染   细胞因子风暴   信号通路  

摘要： 白介素6（Interleukin-6， IL-6）作为机体先天免疫抵抗病毒感染所分泌的一种细胞因子，因其在细胞因子风暴中产生的影响而受到广泛关注。过去研究表明高水平的IL-6可以有效抑制病毒感染，但越来越多的研究表明，在体内复杂的免疫应答中，IL-6分泌过多不仅会适得其反，还会对机体造成严重损害。本文综述了在乙型肝炎病毒 、甲型流感病毒 、呼吸道合胞病毒、新型冠状病毒、轮状病毒、脑心肌炎病毒感染过程中IL-6作用的最新研究进展，以期为阻断病毒感染和研制新型抗病毒药物提供新思路和新途径。

关键词： 涤痰汤   慢阻肺合并肺部感染   促炎因子   肺胀  

摘要： 目的 研究以涤痰汤为基础，随证加减化裁方治疗慢性阻塞性肺病（chronic obstructive pulmonary disease，COPD）合并肺部感染的临床疗效及对血清白介素-6（interleukin-6，IL-6）、干扰素γ（interferon gamma，IFN-γ）及肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平的影响。方法 纳入2022年1月至2023年6月本院收治的124例慢阻肺合并肺部感染患者，采用随机数字表法分为研究组（n=62）和对照组（n=62）。对照组采用西医常规治疗，研究组在常规治疗的基础上联合涤痰汤化裁方治疗。对比两组治疗后的临床疗效、中医证候积分、血气指标血氧分压(partial pressure of oxygen， PaO2)、血氧饱和度(oxygen saturation of blood， SaO2)、动脉血二氧化碳分压(partial pressure of arterial blood carbon dioxide， PaCO2)水平、肺功能第一秒用力呼气量(forced expiratory volume in the first second， FEV1)、最大自主通气量（maximalvoluntaryventilation， MVV）、用力肺活量（forced vital capacity， FVC）、第一秒用力呼气量与用力肺活量的比值(FEV1/FVC)水平、促炎因子IL-6、IFN-γ及TNF-α水平。结果 两组患者治疗前各项肺功能检测指标、血气指标、中医证候积分、血清IL-6、IFN-γ及TNF-α差异均无统计学意义（P>0.05）。治疗后，研究组患者的总有效率为96.77%高于对照组的87.10%（P<0.05）；研究组患者治疗后的中医证候积分值小于对照组（P<0.05）；两组患者治疗后的血气指标如PaO2、SaO2均升高、PaCO2均降低，且研究组改善更明显（P<0.05）；两组患者治疗后的肺功能指标如FEV1、MVV、FVC、FEV1/FVC均升高，且研究组改善更明显（P<0.05）；两组患者治疗后血清IL-6、IFN-γ及TNF-α水平均降低，且研究组改善更明显，差异具有统计学意义（P<0.05）。结论 涤痰汤化裁方治疗慢阻肺合并肺部感染有较高的疗效，其能改善患者肺功能、缓解临床症状及降低血清IL-6、IFN-γ及TNF-α水平。

关键词： Breast cancer   TNF-alpha   Single-nucleotide polymorphism   Carcinogenesis   Risk factor   Predictive index  

摘要： Background Compared with all other cancer types, Breast cancer (BC) among women has now exceeded them all as the primary reason for cancer worldwide. The BC represents 11.7% of all cancer cases and accounts for a predestined 2.3 million new cases. It is the fourth primary reason for cancer-associated deaths in women. With a staggering 200-400% increase in the relative incidence of BC in Egypt, there is an urgent need for new diagnostic or predictive markers. Purpose The current investigation aims to explore the connection of the functional TNF-alpha-308G > A (rs1800629) single-nucleotide polymorphism (SNP) with different breast cancer predictive indices. Methods The ARMS-PCR method was used for genotyping TNF-alpha(-308)G > A SNP. Three groups were recruited for the study: 79 patients with benign breast inflammation (BBI);163 with breast cancer (BC) and 144 controls (C). Results The TNF-alpha(-308)G > A SNP was distributed among different groups in a unique pattern;in the control group 63.9% of cases were in the GG, 34% were in the GA, and 2.1% were in the AA. The BC group had 14% GG, 79% GA, and 7% AA, while the BBI group had 24% GG, 76% GA, and 0% AA. The AA genotype and A allele represented a strong significant correlation with risk factors in the BC group (ORAA: 14.67 [95% CI = 3.78-56.91] and ORA: 0.27 [95% CI = 0.19-0.39], respectively;P < 0.0001) in contrast to the control group. However, in the BBI group, a strong significant correlation was noted with the GA genotype (ORGA: 5.93 [95% CI = 3.18-11.04] P < 0.0001). In the BC group, the AA genotype shows a significant increase in Nottingham Prognostic Index (NPI) in positive ER and PR in contrast to the relevant negative ones (P = 0.02 and 0.002, respectively). However, the GA genotype significantly increased NPI in positive Her2 and metastatic patients (P = 0.03 and 0.01, respectively). Conclusion This research is the first to correlate TNF-alpha(-308)G > A (rs1800629) SNP in Egyptian BC patients. The A allel

关键词： 早产儿   坏死性小肠结肠炎   牛奶蛋白过敏   干扰素γ   白细胞介素4  

摘要： 目的 通过测定患儿血清中β-乳球蛋白、酪蛋白特异性相关的细胞因子IFN-γ、IL-4水平，结合免疫球蛋白IgE和IgG4水平探究早产儿坏死性结肠炎（NEC）与不同机制牛奶蛋白过敏（CMPA）的相关性。方法 纳入81例NEC早产儿并根据皮肤点刺试验和牛奶回避/激发试验结果，按是否牛奶蛋白过敏分为NEC组37例和NEC+CMPA组44例，比较两组患儿血清IFN-γ、IL-4水平差异，并采用Logistic回归分析两种血清因子与NEC早产儿发生CMPA的相关性。在NEC+CMPA组基础上根据IgE检查结果按发病机制将44例患儿分为NEC+IgE组18例和NEC非IgE组26例，比较两组患儿与NEC组血清IFN-γ、IL-4水平、IgE和IgG4水平差异，并探究早产儿NEC与不同机制CMPA的相关性。结果 与NEC组相比，NEC+CMPA组患儿血清IFN-γ、IL-4水平均升高（P＜0.001）。Logistic回归分析显示，血清IL-4水平（OR=2.475），血清IFN-γ水平（OR=2.489）为NEC患儿发生CMPA的危险因素。Spearman相关性分析结果显示，IL-4（r=0.385）水平、IFN-γ（r=0.324）水平与NEC患儿发生CMPA呈正相关关系。与NEC组相比，NEC+IgE组的IFN-γ水平有所降低但差异无统计学意义（P＞0.05），而IL-4水平升高，差异有统计学意义（P＜0.001）；NEC+非IgE组的IFN-γ水平升高（P＜0.001），而IL-4水平差异无统计学意义（P＞0.05）。结论 NEC的发生与IgE介导和非IgE介导的牛奶蛋白过敏引起的免疫反应均有关联。血清IL-4水平、IFN-γ水平与NEC患儿发生CMPA呈正相关。

关键词： 淋巴瘤   化疗   化毒祛邪汤   疗效   细胞免疫功能  

摘要： 目的 探讨化毒祛邪汤联合CHOP化疗方案治疗淋巴瘤的疗效及对细胞免疫功能的影响。方法 选择本院选取2020年1月到2023年12月所接诊的102例淋巴瘤患者作为研究对象，根据随机数表法将患者分为对照组（n=51）、观察组（n=51）。对照组采用CHOP化疗方案治疗，观察组在对照组基础上联合化毒祛邪汤治疗，4周为1个治疗周期，两组患者均接受4个周期的治疗。治疗4个周期后，比较两组的临床疗效，并比较治疗前、治疗4个周期后的细胞免疫功能(CD4+、CD8+、CD4+/CD8+)、肿瘤标志物[血管内皮生长因子（VEGF）、胸腺嘧啶脱氧核甘激酶（TK-1）]变化，并记录治疗期间不良反应的发生情况。结果 观察组治疗后的总有效率明显高于对照组，有统计学意义（P＜0.05）；观察组治疗后的细胞免疫功能指标 CD3+、CD4+及CD4+/CD8水平均明显高于对照组，有统计学意义（P＜0.05）；观察组治疗后的肿瘤标志物血清VEGF、TK-1水平均明显低于对照组，有统计学意义（P＜0.05）；两组在治疗期间的不良反应总发生率比较，无统计学意义（P＞0.05）。结论 化毒祛邪汤联合CHOP化疗方案治疗淋巴瘤的疗效显著，能提高细胞免疫功能，降低肿瘤标志物血清VEGF、TK-1水平表达，值得在临床中推广应用。

摘要： Class 1 major histocompatibility complexes (MHC-I), encoded by the highly polymorphic HLA-A, HLA-B, and HLA-C genes in humans, are expressed on all nucleated cells. Both self and foreign proteins are processed to peptides of 8 to 10 amino acids, loaded into MCH-1 within the endoplasmic reticulum and then presented on the cell surface. Foreign peptides presented in this fashion activate CD8+ T cells and their immunogenicity correlates with their affinity for the MHC-1 binding groove. Thus, predicting antigen binding affinity for MHC-I is a valuable tool for identifying potentially immunogenic antigens. While quite a few predictors for MHC-I binding exist, there are no currently available tools that can predict antigen/MHC-I binding affinity for antigens with explicitly labeled post-translational modifications or unusual/non-canonical amino acids (NCAAs). However, such modifications are increasingly recognized as critical mediators of peptide immunogenicity. In this work, we propose a machine learning application that quantifies the binding affinity of epitopes containing NCAAs to MHC-I and compares its performance with other commonly used regressors. Our model demonstrates robust performance, with 5-fold cross-validation yielding an R value of 0.477 and a root-mean-square error (RMSE) of 0.735, indicating strong predictive capability for peptides with NCAAs. This work provides a valuable tool for the computational design and optimization of peptides incorporating NCAAs, potentially accelerating the development of novel peptide-based therapeutics with enhanced properties and efficacy.

关键词： Innate immunity and inflammation   Solid tumors   Tumor immunology  

摘要： Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of <30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of beta-glucan and IFN gamma (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. beta-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacy in vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.

关键词： ANCA   IL-7Rα   T lymphocytes   glomerulonephritis   immunology   vasculitis  

摘要： BACKGROUND AND HYPOTHESIS:Increased T cell IL-7Rα signaling is associated with a poorer prognosis in ANCA-associated vasculitis. These studies examined the functional role of IL-7Rα (CD127) in experimental glomerulonephritis mediated by anti-MPO T cell autoimmunity. We hypothesized that T cells would express IL-7Rα in the kidney and that blocking the function of IL-7Rα, without cellular depletion, would be protective. METHODS:Mice were immunised with mouse MPO, then low-dose sheep anti-mouse basement membrane (BM) globulin was administered to trigger glomerulonephritis. Flow cytometry and RNA-sequencing characterised intrarenal CD127+ expressing CD4+ and CD8+ T cells in mice with anti-MPO glomerulonephritis. To assess the functional role of IL-7Rα, mice with established anti-MPO autoimmunity were treated with anti-IL-7Rα antibodies. RESULTS:Control ovalbumin-immunized mice given anti-BM globulin developed minimal injury, while MPO-immunised mice given anti-BM globulin developed albuminuria with glomerular and tubulointerstitial injury. Numbers of intrarenal IL-7Rα+ (CD127+) CD4+ and CD8+ T cells were increased in mice with anti-MPO glomerulonephritis. There were 3 738 and 2 726 genes differentially expressed between intrarenal CD127¯PD-1+ and CD127+PD-1¯ CD8+ and CD4+ T cells, respectively, with substantially overlapping differentially expressed genes between CD8+ and CD4+ T cells. Both CD127¯PD-1+ CD8+ and CD4+ T cells were enriched for previously described T cell exhaustion signatures associated with prognosis in autoimmune disease. As effector memory T cells drive inflammation, we blocked the IL-7Rα after inducing anti-MPO autoimmunity. Anti-IL-7Rα antibodies limited histological injury, and reduced albuminuria numbers of glomerular and interstitial leukocytes, with reduced intrarenal chemokine and pro-inflammatory cytokine expression. CONCLUSIONS:Intrarenal effector memory and exhausted CD4+ and CD8+ T cells are present in experimental anti-MPO glomerulonephriti

关键词： 原核表达   体液免疫   筛选   ELISA   GST  

摘要： 猪肺炎支原体Mhp336、Mhp460和Mhp677蛋白是体液免疫显性蛋白，本研究的目的是筛选这3个蛋白的体液免疫显性区段。将编码3个蛋白的基因划分为不同的片段。设计不同片段的引物，以重组质粒pGEX-6P-1-mhp336、pGEX-6P-1-mhp460和pGEX-6P-1-mhp677为模板，采用不同引物组合扩增相应片段。扩增产物连接pGEX-6P-1或pGEX-4T-3载体质粒后，转化至大肠杆菌BL21（DE3）感受态构建重组菌。重组菌经IPTG诱导和超声破菌、离心后，上清液与谷胱甘肽琼脂糖珠结合，SDS-PAGE电泳检测目的蛋白表达情况。表达目的蛋白的重组菌破菌、离心后的上清液包被谷胱甘肽板。以HRP标记的兔抗猪IgG为酶标二抗，ELISA试验筛选Mhp336、Mhp460和Mhp677蛋白的体液免疫显性区段。最终成功构建了19个能以可溶形式表达目的蛋白的重组菌，其中11个重组蛋白为体液免疫显性。3个不同蛋白的最佳体液免疫显性区段为全长Mhp336蛋白、Mhp460-F5（311-464位氨基酸）和Mhp677-F4（1-418位氨基酸）。本研究为猪肺炎支原体基因工程亚单位疫苗的研发提供了候选抗原靶标。