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关键词： 变应性鼻炎   特异性免疫治疗   奥马珠单抗   Meta分析  

摘要： 目的探讨奥马珠单抗联合特异性免疫治疗与单纯特异性免疫治疗的疗效差异,为临床治疗变应性鼻炎提供一定依据。方法采用知网、Pubmed、SinoMed、Embase和Cochrane检索文献,文献检索起止时间从建库至2023年6月,按纳入标准筛选文献并对纳入文献进行严格质量评价后提取资料,应用R 4.3.1软件进行Meta分析。结果共纳入5篇随机对照研究,共计445例患者。奥马珠单抗联合特异性免疫治疗223例,单纯特异性免疫治疗222例,Meta分析结果显示与单纯特异性免疫治疗相比,奥马珠单抗联合特异性免疫治疗严重程度评分与使用救援药物评分均降低(P<0.001),两组不良反应评分差异无统计学意义(P=0.52)。结论当前证据表明特异性免疫治疗联合奥马珠单抗较单纯特异性免疫治疗能更好控制变应性鼻炎患者临床症状,减少缓解药物的使用,但未来仍需更多大样本、多中心、双盲随机对照试验研究来进一步证实。

关键词： 冠心病   经皮冠状动脉介入治疗   急性肾损伤   白细胞介素-18  

摘要： 目的:探讨冠心病病人尿白细胞介素(IL)-18水平对经皮冠状动脉介入治疗(PCI)术后急性肾损伤(AKI)风险的预测价值。方法:选取2021年9月—2023年9月我院收治的冠心病病人109例作为研究对象,均予以PCI。记录PCI术后AKI发生情况,并根据是否发生AKI分为AKI组和非AKI组,对比两组术后即刻及术后2、6、12、24 h血清肌酐、尿IL-18水平。绘制受试者工作特征(ROC)曲线评估尿IL-18水平对PCI术后AKI风险的预测价值。结果:PCI术后48 h,23例病人血肌酐水平较基线值升高≥0.3 mg/dL(26.5μmol/L),将其纳入AKI组,其余86例纳入非AKI组。AKI组糖尿病占比、造影剂剂量较非AKI组高(P<0.05);两组术后即刻、术后2、6 h血清肌酐水平比较差异无统计学意义(P>0.05),AKI组术后12、24、48 h血清肌酐水平高于术后即刻且高于非AKI组(P<0.05);两组术后即刻尿IL-18水平比较差异无统计学意义(P>0.05),AKI组术后2、6、12、24 h尿IL-18水平高于术后即刻且高于非AKI组(P<0.05)。以术后2 h血清肌酐、尿IL-18水平绘制ROC曲线,结果显示,术后2 h尿IL-18水平预测冠心病PCI术后AKI的ROC曲线下面积(AUC)为0.837[95%CI(0.754,0.901)],高于术后2 h血清肌酐的AUC 0.523[95%CI(0.425,0.619)]。结论:冠心病病人尿IL-18水平可预测PCI术后AKI风险,术后早期监测尿IL-18水平有助于早期识别AKI。

关键词： cytokines   drug reactions   interleukins   lichen planus   psoriasis   H&E   hematoxylin-eosin   LP   lichen planus   CD4   cluster of differentiation 4-positive   STAT   signal transducer and activator of transcription   IL   interleukin   Th17   T helper 17  

摘要： Biopsy of the labia stained with H&E showing compact orthokeratosis overyling an epidermis with irregular sawtooth-like acanthosis and hypergranulosis, robust interface activity with dyskeratosis and civatte bodies, and a band-like lymphocytic inf...

关键词： cytokine-mediated immunotherapy   interleukin-18   molecular dynamics simulation   structure-guided design  

摘要： Cytokine-mediated immunotherapy has rapidly emerged as an effective alternative approach for cancer treatment by modulating the anti-tumor response. Interleukin-18 (IL-18) is considered as a promising cancer therapeutic agent due to the ability of cytokines to inhibit cancer by enhancing natural killer (NK) cell and cytotoxic T cell responses. Since the activity of IL-18 is required for the specific binding to IL-18 receptors, the modification of binding residue at the protein interface is an attractive strategy for IL-18 activity enhancement. The aim of this study was to design and predict mutations increasing the activity of IL-18 through computational structure-based energy calculation and molecular dynamic simulations. Four candidate mutations, E6M, E6M+N111S+R131G, E6M+K129M+R131G, and E6M+N111S+K129M+R131G, could affect/facilitate the receptor binding and stability compared to the wild-type via electrostatic interaction. MD simulations demonstrated that the predicted mutation on IL-18 had no influence on the overall conformation stability, but increased flexibility in the β8–β9 hairpin loop. Furthermore, the dynamic behavior suggested that these candidates could be an alternative for the improvement of IL-18 biological activity, though the full simulation of the IL-18 complex remains necessary. In summary, this study offered a computer-aided design strategy which was of beneficial use in the design and development of IL-18 to increase its cytokine potency and efficiency. © 2025 by the authors.

关键词： IgA肾病   免疫系统   补体途径   补体因子  

摘要： IgA肾病是经肾活检确诊的最常见的原发性肾小球疾病,也是肾衰竭的重要原因。尽管“四重打击”假说尝试解释其发病机制,但人们对IgA沉积引发的肾脏炎症和损伤仍不完全清楚。研究显示补体系统在IgA肾病中起关键作用。替代途径和凝集素途径的激活标志物与疾病活动度相关,可用于识别可能进展为显著肾功能损害的患者。因此,抑制补体系统可能成为减轻肾小球损伤和改善预后的有效方法。本文对补体相关因子在IgA肾病预测和诊断中的应用价值进行探讨。

关键词： IL-2Rα   IL-2Rβ   IL-2Rγ subunits   interleukin-2   renal cell carcinoma  

摘要： Renal cell carcinoma (RCC) is the most common form of kidney cancer in adults. Immunotherapy, such as the application of interleukin-2 (IL-2), is a crucial treatment. It is known that IL-2 is involved in the upregulation of the anti-tumor immune response;however, a direct action of IL-2 on RCC cells has not yet been demonstrated. In this project, we aimed to investigate the expression and the functionality of the IL-2Rα, IL-2Rβ, and IL-2Rγ subunits on the four human RCC cell lines A-498, ACHN, Caki-1, and Caki-2. The expression of the three subunit genes was investigated via PCR, agarose gel of PCR products, Western blot, and flow cytometry. IL-2R functionality was assessed in RCC cells cultured with or without rhIL-2 using MTT and BrdU assays to investigate cell viability and proliferation;LDH assays, Live-or-Dye staining, and Annexin V/PI staining to study cell death;and Western blot to detect apoptotic markers, cleaved PARP, and cleaved caspases 3 and 9. Expression of IL-2Rα, IL-2Rβ, and IL-2Rγ subunits in the four cell lines was observed at the protein level with Western blot. Flow cytometry confirmed the cell-surface expression of IL-2Rα, IL-2Rβ, and IL-2Rγ subunits. In addition, we observed that rhIL-2 influenced cell survival/proliferation and cell death, depending on the cell line. We conclude that IL-2R is functional in RCC cells and that rhIL-2 could be used as a therapeutic option to act directly on RCC cells. However, further studies are required to elucidate the signaling pathways triggered by the IL-2-receptor binding on RCC cells. © 2025 by the authors.

关键词： 甲型H1N1流感病毒   安和怡养茶   网络药理学   分子对接   分子动力学模拟   细胞因子  

摘要： 目的 研究安和怡养茶抗甲型H1NI流感的主要活性成分及其作用机理。方法 应用网络药理学、分子对接以及分子动力学模拟技术探讨安和怡养茶抗甲型H1NI流感的潜在作用机制。以及体内实验研究探讨安和怡养茶对甲型H1NI流感病毒感染小鼠的肺指数、脾指数、肺部病理变化以及对TNF-α、IFN-γ、IL-6、IL-4等细胞因子的影响。结果 安和怡养茶抗甲型H1NI流感的核心靶点有EGFR和AKT1,其核心通路包括:HIF-1信号通路、甲型H1N1流感信号通路等;安和怡养茶能下调TNF-α、IFN-γ、IL-6,上调IL-4,下调黏附分子CD54、CD106和IFN-γ。结论 安和怡养茶能通过多靶点多通路交互作用以达到抗炎反应或免疫调节等间接效果从而对机体产生保护作用;通过下调促炎因子的分泌并上调抗炎因子的分泌来控制炎症反应,下调黏附分子CD54、CD106和IFN-γ,以增强机体免疫能力,发挥其治疗甲型H1N1流感病毒感染的作用。

关键词： 骨髓增生异常综合征   DNA甲基转移酶3A   非典型钙黏蛋白   白细胞介素-7受体   异基因造血干细胞移植  

摘要： 目的研究DNA甲基转移酶3A(DNMT3A)、非典型钙黏蛋白1(FAT1)和白细胞介素-7受体(IL-7R)基因突变对核型正常骨髓增生异常综合征(MDS)患者接受异基因造血干细胞移植(allo-HSCT)治疗预后的影响。方法采用单中心回顾性队列方法,分析2021年1月~2023年12月邯郸市第一医院血液科收诊的核型正常且接受allo-HSCT治疗的380例MDS患者临床资料。二代测序法(NGS)分析患者基因突变概况,根据基因测序结果将具有DNMT3A,FAT1和IL-7R中任一基因突变的患者纳为突变组(n=61),其余未发现上述突变的患者纳入野生组(n=319);分析两组患者临床特征;Kaplan-Meier法分析患者累积生存情况,Log Rank检验比较组间差异。根据随访结局,将患者分为死亡组(n=130)与生存组(n=250),COX回归分析影响接受allo-HSCT治疗后MDS患者生存的影响因素。结果NGS显示380例核型正常MDS患者中,突变组占16.05%(61/380)。与野生组相比,突变组患者年龄、平均血小板体积(MPV),IL-6水平显著升高,差异具有统计学意义(t=7.320,23.774,17.838,均P<0.05)。突变组与野生组患者总生存率(59.02%vs67.08%)对比,差异无统计学意义(Logrankχ^(2)=1.610,P>0.05)。年龄、性别、IL-6,MPV,DFI基因突变及骨髓原始细胞比例与allo-HSCT治疗后MDS患者总生存时间相关(t/χ^(2)=5.286~42.498,均P<0.05)。COX回归分析表明,骨髓原始细胞比例≥50%是影响经allo-HSCT治疗后MDS患者总生存时间(OS)的独立危险因素(HR=1.734,95%CI:1.046~2.829,P=0.026)。结论DNMT3A,FAT1和IL-7R基因突变对接受allo-HSCT治疗核型正常的MDS患者OS无显著影响,骨髓原始细胞比例≥50%是其独立危险因素。

关键词： 白细胞介素6   基因多态性   射血分数降低型心力衰竭   预后  

摘要： 目的探讨白细胞介素6(IL-6)-634位点基因多态性对冠心病合并射血分数降低型心力衰竭(HFrEF)1年预后的预测价值。方法选取2022年1月至2023年12月于福建中医药大学附属人民医院心血管科住院的冠心病合并HFrEF患者188例,采用TaqMan探针法对IL-6-634位点进行基因多态性检测,比较不同基因型(GG、GC、CC)患者的人口学特征、临床资料等基线资料,并进行12个月的随访观察,采用Kaplan-Meier生存曲线法比较三组患者1年生存率差别,Cox回归分析影响患者1年主要不良心血管事件(MACE)的危险因素。结果最终182例患者完成研究并纳入分析(6例患者在研究开始前自愿退出)。GG基因型、GC基因型、CC基因型患者的1年的因心衰加重再住院率分别为30.8%、16.4%、9.9%(P<0.05),1年全因死亡率分别为19.2%、7.3%、5.0%;Kaplan-Meier生存曲线分析显示GG基因型、GC基因型、CC基因型1年生存率依次升高,组间生存曲线差异存在统计学意义(P<0.05)。Cox回归分析显示,以CC基因型为参照,GG和GC基因型均为冠心病合并HFrEF患者1年不良预后的危险因素,携带GG基因型和GC基因型的冠心病合并HFrEF患者1年MACE的风险分别是CC基因型患者的3.23倍(95%CI:1.74~6.25)和1.94倍(95%CI:1.03~3.51)。结论IL-6-634位点基因多态性与冠心病合并HFrEF患者1年预后有关联性,GG和GC基因型是预测冠心病合并HFrEF患者1年不良预后的独立危险因素。

关键词： ADRB2/JNK/c-Jun signaling pathway   cardiac fibroblasts   Cinnamomum migao H.W. Li   hecogenin   IL-6   laurolitsine  

摘要： This study aims to elucidate the active components and underlying molecular mechanisms by which the ethanol-water extract of Cinnamomum migao H.W. Li (MG-EWE) inhibits cardiac fibroblast (CF) transdifferentiation and IL-6 production, providing insights into its anti-myocardial fibrosis effects. The chemical composition of MG-EWE was characterized using UPLC-Q-TOF-MS. Network pharmacology analysis identified active constituents and their mechanisms in inhibiting IL-6 production in CFs. An isoproterenol (ISO)-induced rat CF model was established to evaluate the effects of MG-EWE and its main monomers, Laurolitsine and Hecogenin, on cell proliferation, migration, collagen metabolism, IL-6 production, and key proteins in the ADRB2/JNK signaling pathway. A total of 173 compounds were identified in MG-EWE, with 14 core constituents regulating IL-6 synthesis via 16 key targets, including ADRB2 and MAPK9. Gene Ontology enrichment indicated that MG-EWE affects phosphorylation and the JNK signaling cascade. Molecular docking showed strong binding affinities between Laurolitsine, Hecogenin, and their targets ADRB2 and JNK. Experimentally, MG-EWE, Laurolitsine, and Hecogenin significantly inhibited ISO-induced CF proliferation, migration, and hydroxyproline synthesis, as well as the expression of p-ADRB2, p-JNK, p-c-Jun, and IL-6. MG-EWE inhibits CF transdifferentiation and IL-6 production via the ADRB2/JNK/c-Jun signaling axis, mediated by its constituents Laurolitsine and Hecogenin, highlighting its potential for drug development targeting myocardial fibrosis. © 2025 by the authors.