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关键词： 多发性骨髓瘤   胸腺法新   淋巴细胞亚群   免疫调节  

摘要： 目的通过检测多发性骨髓瘤(MM)患者外周血中T/B/NK淋巴细胞计数了解胸腺法新对免疫系统的影响。方法选择2021年6月至2023年6月娄底市中心医院血液内科收治的40例一线使用硼替佐米化疗的MM患者,根据是否同步使用胸腺法新1.6 mg皮下注射2次/周,分为试验组(n=15)和对照组(n=25),收集化疗前及化疗后2周T/B/NK淋巴细胞亚群的数值,比较两组内及组间各细胞表达水平的差异。结果对照组治疗前后的T/B/NK淋巴细胞的变化差异无统计学意义(P>0.05);试验组治疗前后比较,使用胸腺法新可增加CD3^(+)T淋巴细胞绝对计数,主要表现在CD3^(+)CD8^(+)T淋巴细胞百分比及绝对计数,差异有统计学意义(P<0.05)。治疗前试验组CD3^(+)、CD3^(+)CD4^(+)、CD3^(+)CD8^(+)T淋巴细胞绝对计数均明显低于对照组,差异有统计学意义(P<0.05),CD19^(+)B淋巴细胞百分比和绝对计数低于对照组,差异有统计学意义(P<0.05);治疗后试验组CD19^(+)B淋巴细胞和CD3-CD16^(+)/56^(+)NK细胞绝对计数低于对照组,差异有统计学意义(P<0.05)。结论MM患者治疗期间联合使用胸腺法新可提高T淋巴细胞计数,对改善机体细胞免疫、增强抗感染能力具有临床应用价值。

关键词： 腰椎间盘突出症   中医证型   缺氧诱导因子1α   NOD样受体热蛋白结构域相关蛋白3   白细胞介素1β   预后   相关性   生物学指标  

摘要： 【目的】探讨腰椎间盘突出症(LDH)患者的中医证型分布及其与血清缺氧诱导因子1α(HIF-1α)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、白细胞介素1β(IL-1β)水平的关系。【方法】收集2022年10月~2024年6月武汉市汉口医院门诊及住院部收治的160例LDH患者(LDH组)病例资料及同期在该院体检的20例健康志愿者(健康对照组)资料,比较2组受试者血清HIF-1α、NLRP3、IL-1β水平,分析血清HIF-1α、NLRP3、IL-1β水平与LDH患者疼痛视觉模拟量表(VAS)、日本骨科协会腰痛评价量表(JOA)、Oswestry功能障碍指数(ODI)评分的相关性;统计LDH患者的中医证型分布情况,探讨LDH患者中医证型与血清HIF-1α、NLRP3、IL-1β水平的关系;分析血清HIF-1α、NLRP3、IL-1β水平与LDH预后的相关性。【结果】(1)与健康对照组比较,LDH组患者的血清HIF-1α、NLRP3、IL-1β水平均显著升高,差异均有统计学意义(P<0.01)。(2)经Spearman相关分析,VAS、ODI评分与血清HIF-1α、NLRP3、IL-1β水平呈正相关,JOA评分与血清HIF-1α、NLRP3、IL-1β水平呈负相关,差异均有统计学意义(P<0.01)。(3)160例LDH患者的中医证型分布由高到低依次为:血瘀证65例(40.63%)>肾虚证45例(28.13%)>寒湿证30例(18.75%)>湿热证20例(12.50%)。(4)不同中医证型LDH患者血清HIF-1α、NLRP3、IL-1β水平比较,差异均有统计学意义(P<0.01)。其中,寒湿证患者血清HIF-1α、NLRP3、IL-1β水平高于肾虚证(P<0.05),湿热证患者血清HIF-1α、NLRP3、IL-1β水平高于寒湿证(P<0.05),血瘀证患者血清HIF-1α、NLRP3、IL-1β水平高于湿热证(P<0.05)。(5)多因素Logistic回归分析结果显示:血清HIF-1α、NLRP3、IL-1β为LDH患者预后的危险因素,且均呈负相关(P<0.05或P<0.01)。【结论】LDH患者的证型分布以血瘀证为主,其次为肾虚证;不同中医证型的血清HIF-1α、NLRP3、IL-1β水平存在显著差异,血清HIF-1α、NLRP3、IL-1β水平有可能成为LDH中医辨证的潜在生物学指标,是LDH预后的危险因素。

关键词： Osteoarthritis   Benzophenone-3   IL-6   STAT3   Exposure  

摘要： Currently, limited research exists on the relationship between osteoarthritis (OA) and Benzophenone-3 (BP-3). This study aims to explore the potential molecular pathways involved, using both in vivo and in vitro biological experiments. In vivo experiments revealed that exposure to BP-3 leads to cartilage damage in the knee joints of rats, suggesting that BP-3 may be a significant risk factor in the development and progression of osteoarthritis. Proteomic sequencing of knee cartilage tissue revealed alterations in multiple inflammatory pathways in the BP-3 group. In vitro cellular experiments further demonstrated the toxic effects of BP-3 on chondrocytes, including inflammatory changes and increased transcriptional levels of IL-6. Cellular transcriptomics sequencing revealed significant changes in multiple intracellular inflammatory pathways, particularly the JAK-STAT pathway. Additional experiments demonstrated that BP-3 enhances STAT3 phosphorylation, promoting the degradation of extracellular matrix (ECM) proteins. Silence of STAT3 alleviated the impaired effects of BP-3 on chondrocytes. Overall, our data suggest that BP-3 exposure may be a significant risk factor for OA development. This study provides substantial evidence and a comprehensive understanding of the impact of BP-3 on OA development.

关键词： PMHC   TCR   Neoantigen-specific T cells   SpyCatcher/SpyTag  

摘要： Peptide-major histocompatibility complex (pMHC) multimers, most commonly used in streptavidin-based tetrameric form, are exceptional for detecting, isolating, and analyzing antigen-specific T cells. However, classical pMHC tetramer staining methods may not detect fully functional T-cells with lower-affinity T-cell receptors (TCRs), which are common in antitumor and autoimmune responses. This limitation has driven the innovation of new methods to improve pMHC binding through multivalent scaffolds, thereby increasing the avidity of weak TCR-pMHC interactions. In this study, we present a novel method for creating multimeric pMHC complexes using the SpyCatcher/SpyTag system. Our approach simplifies the multimer production process by eliminating biotinylation steps, instead employing SpyTag technology for efficient assembly. The method allows for the production of MHC molecules with SpyTags, which can be coupled to various SpyCatcher variants, enabling diverse oligomeric configurations. Our research demonstrates that these novel multimeric pMHC complexes significantly enhance the binding avidity for low-affinity antigen-specific TCRs compared to classical tetramers. This advancement presents a versatile platform for T cell response studies across diverse immunological contexts, offering advantages in specificity, stability, and scalability for both basic research and clinical applications.

关键词： 感染   副感染脑病   呼吸道病毒   细胞因子   免疫治疗  

摘要： 副感染脑病是继发于系统性感染性疾病,特别是呼吸道病毒感染的一组急性脑病综合征。副感染性脑病不是由病毒直接侵袭中枢神经系统引起的,也不属于特异性的适应性免疫介导的自身免疫性脑炎,而是与细胞因子导致的炎性综合征和个体遗传因素等相关。副感染脑病的表型多样,或可初步归纳为11种表型。重症类型的病死率与致残率较高,及时确诊与积极的免疫治疗有助于改善疾病的预后。

关键词： IL-6诱导肽   图神经网络   结构特征   图注意力机制   图卷积神经网络  

摘要： 白细胞介素6(简称IL-6)是一种高多效性的糖蛋白因子,可以调节先天性免疫、适应性免疫以及代谢的各个方面,包括糖酵解、脂肪酸氧化和氧化磷酸化等。许多研究已证明,病毒感染患者体内的IL-6表达和释放量显著增加,并且与疾病的严重程度呈正相关,因此,识别IL-6诱导肽并探究其作用机制,对于开发免疫治疗以及疾病严重程度生物标志物具有重要的意义。目前对于IL-6诱导肽的识别大多采用传统的机器学习方法,特征选择与提取较为复杂,且需要依赖领域专家知识。鉴于此,该文提出一种基于图神经网络的IL-6诱导肽预测方法SFGNN-IL6。该方法根据所预测的IL-6诱导肽的结构特征,通过阈值筛选距离信息构建邻接矩阵,结合氨基酸的编码方式(One-hot编码、位置编码和BLOSUM62编码)提取氨基酸节点特征并进行图表示;然后,采用图注意力机制层和图卷积神经网络层,由双通道分别提取多视角特征,既关注节点权重的更新,也考虑节点信息的更新;最后,将两类特征进行融合,用于IL-6诱导肽的分类。实验结果验证了该方法的有效性。

关键词： 冠状动脉CT血管造影   白细胞介素-12p70   蛋白C   蛋白S   冠心病   冠状动脉狭窄程度  

摘要： 目的探究冠状动脉CT血管造影(CCTA)联合血清白细胞介素(IL)-12p70、蛋白C(PC)、蛋白S(PS)诊断冠心病冠状动脉狭窄程度的价值。方法前瞻性选取2022年4月至2024年4月江苏大学附属武进医院(常州市武进人民医院)收治的冠心病患者186例作为研究组,均行CCTA检查,根据Gensimi积分将患者分为轻度组、中度组和重度组,另选取186例同期体检健康者作为对照组;采用酶联免疫吸附试验(ELISA)检测IL-12p70水平,采用全自动血凝仪检测PC、PS水平;采用多因素Logistic回归分析冠心病冠状动脉重度狭窄的影响因素;绘制受试者工作特征(ROC)曲线分析CCTA参数联合血清IL-12p70、PC、PS对冠心病冠状动脉重度狭窄的诊断价值。结果研究组血清IL-12p70水平显著高于对照组(P<0.05),PC、PS水平显著低于对照组(P<0.05)。轻度组、中度组及重度组最小管腔直径(MLD)、最小管脖面积(MLA)、血清PC、PS水平依次降低(P<0.05),面积狭窄百分比(%AS)、直径狭窄百分比(%DS)、血清IL-12p70水平依次升高(P<0.05)。根据多因素Logistic回归分析得知,IL-12p70为影响冠心病冠状动脉重度狭窄的危险因素(P<0.05),PC、PS为保护因素(P<0.05)。根据ROC曲线得知,MLD、MLA、%AS、%DS、血清IL-12p70、PC、PS诊断冠心病冠状动脉重度狭窄的曲线下面积(AUC)为0.810、0.767、0.782、0.779、0.776、0.809、0.805,联合诊断冠心病冠状动脉重度狭窄的AUC为0.982,联合诊断优于各自单独诊断(Z_(联合***)=2.489、Z_(联合***)=2.502、Z_(联合vs.%AS)=2.531、Z_(联合vs.%DS)=2.602、Z_(联合***-12p70)=2.643、Z_(联合***)=2.537、Z_(联合***)=2.546,均P<0.05)。结论冠心病患者中血清IL-12p70显著升高,PC、PS显著降低,CCTA联合血清IL-12p70、PC、PS可有效提高诊断冠心病冠状动脉狭窄程度的价值。

关键词： endometrial tuberculosis   pulmonary tuberculosis   pathological characteristics   HLA-G   tuberculous granuloma   IL-1ra  

摘要： Endometrial tuberculosis (ETB) is a reproductive system infection caused by Mycobacterium tuberculosis, primarily invading the endometrium through hematogenous dissemination. This study included 10 patients diagnosed with ETB and 10 patients with pulmonary tuberculosis (PTB) to analyze their clinical, pathological, and immunological characteristics. Anatomically, PTB presented the highest prevalence among tuberculosis cases. Compared to PTB imaging, CT scans of ETB showed less distinctive diagnostic features. Pathologically, abscess formation was more frequently observed in ETB patients than in PTB patients, suggesting a more intense local inflammatory response in ETB. However, there were no statistically significant differences in granulomatous lesions, caseous necrosis, coagulative necrosis, inflammatory necrosis, exudation, acute inflammation, or fibrous tissue hyperplasia between the two groups. Immunohistochemical analysis revealed higher infiltration of macrophages (CD68) in ETB lesions compared to PTB, whereas the counts of T cells (CD3+, CD4+, CD8+) and B cells (CD20) showed no significant differences. Notably, the expression levels of HLA-G and IP-10 were significantly elevated in the lesion areas of ETB compared to PTB. Similarly, the expression of HLA-G, IP-10, IL-1Ra, and IL-10 was significantly higher in the ETB group than in the PTB group. Furthermore, HLA-G and IL-1Ra expression levels were markedly elevated in ETB lesion areas compared to surrounding normal endometrial tissue. HLA-G plays a pivotal role in immune tolerance by modulating local immune responses, while IP-10 is involved in chronic inflammatory signaling. IL-1Ra and IL-10 are key regulators of endometrial immune homeostasis, counterbalancing inflammatory responses that could otherwise disrupt reproductive function. These immunoregulatory factors are crucial in maintaining immune tolerance within the endometrium and may influence immune responses associated with endometrial tuberculosis.

关键词： 加味清肺苇金汤   支气管扩张,急性加重期   痰热郁肺证   炎性因子   肺功能   血气指标  

摘要： 目的探讨加味清肺苇金汤在痰热郁肺型支气管扩张急性加重期患者治疗中的应用价值,观察其对炎性指标、血气指标的影响。方法92例痰热郁肺型支气管扩张急性加重期患者随机分组。对照组46例用西医常规治疗,观察组46例联合加味清肺苇金汤口服治疗,治疗2 w后比较临床疗效。结果治疗后观察组血清中血氧分压(PaO_(2))、基质金属蛋白酶(MMP)-9、血清白细胞(WBC)、降钙素原(PCT)、白细胞介素(IL)-6水平低于对照组,MMP抑制剂(TIMP)-1、FEV1/FVC、FEV1、血氧饱和度(SaO_(2))、二氧化碳分压(PaCO_(2))高于对照组,差异具统计学意义(P<0.05);观察组总有效率显著高于对照组(P<0.05)。结论对于痰热郁肺型支气管扩张急性加重期患者而言联合加味清肺苇金汤治疗有重要意义,有助于减少炎症指标水平,改善肺功能,恢复血气指标,提高临床疗效。