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关键词： 慢性阻塞性肺疾病   可溶性生长刺激表达基因2蛋白   白细胞介素-6   N末端脑钠肽前体  

摘要： 目的:分析慢性阻塞性肺疾病(COPD)患者血清中可溶性生长刺激表达基因2蛋白(ST2)、白细胞介素-6(IL-6)、N末端脑钠肽前体(NT-proBNP)水平与疾病严重程度的关系。方法:选取2022年1月—2023年12月泰兴市第二人民医院收治的103例COPD患者为研究对象,将40例急性加重期COPD(AECOPD)患者纳入AECOPD组,63例稳定期患者纳入稳定期组。根据肺功能将AECOPD组患者分为轻度组(13例)、中度组(19例)和重度组(8例)。检测患者血清ST2、IL-6、NT-proBNP水平,分析ST2、IL-6、NT-proBNP水平与病情严重程度的相关性。结果:AECOPD组ST2、IL-6、NT-proBNP水平高于稳定期组(P<0.001);中度组ST2、IL-6、NT-proBNP水平高于轻度组,重度组ST2、IL-6、NT-proBNP水平高于轻度组、中度组(P<0.05)。Pearson相关性分析显示,COPD患者ST2、IL-6、NT-proBNP水平与第1秒用力呼气容积、第1秒用力呼气容积/用力肺活量呈负相关(P<0.001)。结论:血清ST2、IL-6、NT-proBNP水平有助于评估COPD患者病情严重程度,可为COPD的临床诊断和治疗提供参考依据。

关键词： 晚期原发性肝癌   茯苓四逆汤   卡瑞利珠单抗   阿帕替尼   近期疗效   淋巴细胞亚群   肿瘤标志物  

摘要： 目的 探究茯苓四逆汤联合卡瑞利珠单抗及阿帕替尼对晚期原发性肝癌患者近期疗效及淋巴细胞亚群水平的影响。方法 选择晚期原发性肝癌患者84例,按随机数字表法分两组,各42例。对照组予以卡瑞利珠单抗及阿帕替尼治疗,观察组联合茯苓四逆汤治疗,均于治疗3个月后评估。比较两组近期疗效、淋巴细胞亚群水平、肿瘤标志物水平、不良反应。结果 观察组客观缓解率(ORR)(35.71%)、疾病控制率(DCR)(85.71%)均较对照组(16.67%)、(59.52%)高(P<0.05);对比两组治疗前淋巴细胞亚群水平、肿瘤标志物水平(P>0.05);观察组治疗后CD3+(78.23±5.28)%、CD4+(36.71±5.20)%、CD4+/CD8+(1.30±0.21)均较对照组高,CD8+(28.14±2.13)%较对照组低,组织多肽抗原(TPA)(302.07±16.19)U/L、甲胎蛋白(AFP)(24.15±3.12)ng/mL、癌胚抗原(CEA)(13.21±1.75)ng/mL、糖类抗原199(CA199)(213.08±14.29)U/mL均较对照组低(P<0.05);两组不良反应对比(P>0.05)。结论 茯苓四逆汤联合卡瑞利珠单抗及阿帕替尼治疗晚期原发性肝癌患者近期疗效显著,可调节肿瘤标志物水平,改善免疫功能,且安全性高。

关键词： 化学发光免疫分析   细胞因子   精密度   正确度   线性区间   参考区间   方法学比对  

摘要： 目的:评估KunLun i6800全自动化学发光免疫分析仪定量检测细胞因子的性能。方法:依据相关实验室质量管理标准的规定,运用KunLun i6800全自动化学发光免疫分析仪及其配套试剂,针对白细胞介素-1β(IL-1β)、白细胞介素-2受体(IL-2R)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)展开定量分析,对检测系统结果在精密度、正确度、线性区间、检出限、可报告范围以及参考区间等性能维度进行评价。特别针对白细胞介素-6(IL-6)的定量检测数据结果,与参比系统进行方法学比对。结果:在对上述六种细胞因子(IL-1β、IL-2R、IL-6、IL-8、IL-10、TNF-α)进行定量检测时,KunLun i6800全自动化学发光免疫分析仪在精密度、正确度、线性区间、检出限、可报告范围、参考区间这些性能方面的表现,均与厂家声明以及相应标准的要求契合。该系统针对IL-6的检测结果数据与参比系统相比,二者相关系数高达R 2=0.9954,远超R 2≥0.95的标准,展现出了高度的一致性。结论:KunLun i6800全自动化学发光免疫分析仪在对上述细胞因子进行定量分析时,其检测性能与厂家声明相符,能够充分满足临床检测的要求。

关键词： 结肠癌   双侧结肠癌移植瘤   溶瘤病毒   特异性免疫  

摘要： 为了验证oHSV-1-GM-CSF与anti PD-L1抗体联用在双侧结肠癌皮下移植瘤模型中的全身抗肿瘤活性,并初步探究该联用方案在体内的作用原理,在BALB/c小鼠上利用***细胞建立双侧结肠癌皮下移植瘤模型并进行随机分组,设置Vehicle、oHSV-1-GM-CSF、anti PD-L1以及oHSV-1-GM-CSF+anti PD-L1组。治疗结束后,取小鼠外周血淋巴细胞进行流式细胞术和体外杀伤实验,并继续观察治疗结束后的小鼠肿瘤消退情况或消退的肿瘤重新发生的情况。结果显示,oHSV-1-GM-CSF能在***细胞上表达mGM-CSF,且溶瘤作用与空载病毒相比无显著差异;在体内实验中oHSV-1-GM-CSF对治疗侧的肿瘤抑制效果强于空载病毒,与anti PD-L1抗体联用后产生更强的抑制全身肿瘤的作用;流式结果显示,联用组小鼠外周血和脾脏中与特异性免疫相关的细胞比例显著上调,且外周血淋巴细胞能在体外特异性杀伤***细胞而对同种属的4T1细胞无明显作用;生存期结果显示联用组能显著延长小鼠生存期,存活率为33.3%,且无肿瘤重新发生的情况。综上所述,oHSV-1-GM-CSF与anti PD-L1抗体联用后能加强机体的特异性免疫从而产生持久的抑瘤效果,并延长小鼠生存期,为临床对结肠癌的治疗方案提供数据支持。

关键词： 淋巴瘤   免疫检查点抑制剂   中性粒细胞与淋巴细胞比值   预后  

摘要： 目的 探讨中性粒细胞与淋巴细胞比值(NLR)对接受免疫检查点抑制剂(ICIs)治疗淋巴瘤患者预后的影响。方法 回顾性分析本中心2018年1月至2022年6月期间接受ICIs治疗的100例淋巴瘤患者的病例资料,收集患者每一次治疗前中性粒细胞数、淋巴细胞数,计算NLR值,通过受试者工作特征曲线(ROC)得到NLR的最佳截断值(Cut-off值),以此值将患者分为两组,生存分析用Kaplan-Meier曲线和Log-rank检验,危险因素用Cox比例风险回归模型,分析NLR和各种临床特征与免疫抑制剂治疗疗效、无进展生存期(PFS)和总生存期(OS)之间的关系。结果 两组患者在疗效方面有差异(P=0.041)。低NLR组第1、2、3年累计无进展生存率分别为70.4%、69.1%、64.8%,明显高于高NLR组的52.6%、15.8%、15.8%(P=0.001);低NLR组第1、2、3年累计生存率分别为85.2%、81.5%、81.5%,高于高NLR组的78.9%、57.9%、57.9%(P=0.043)。单因素分析显示年龄、首次使用免疫治疗年龄、治疗方式、治疗前NLR为PFS预后不良的危险因素(P<0.05);Cox多因素分析发现治疗前NLR和治疗方式是PFS(P=0.005,P=0.004)的独立预后预测因素。结论 对于接受ICIs治疗的淋巴瘤患者,治疗前较低的NLR可以获得较长的PFS,低NLR的患者更能从免疫抑制剂治疗中获益,因此NLR是一个简单可行的预后评价指标。

关键词： 重症肺炎   呼吸衰竭   人免疫球蛋白   肺保护性通气  

摘要： 目的探讨人免疫球蛋白联合肺保护性通气治疗重症肺炎伴呼吸衰竭的效果。方法60例重症肺炎伴呼吸衰竭患者根据治疗方法的不同分为两组各30例。对照组接受肺保护性通气治疗,观察组接受人免疫球蛋白联合肺保护性通气治疗。比较两组的呼吸相关指标、机体炎性指标、不良反应。结果治疗后,观察组的PaO_(2)、呼吸频率、心率值均高于对照组,PaCO_(2)值以及血清IL-6、IL-8、TNF-α水平均低于对照组(P<0.05)。结论人免疫球蛋白联合肺保护性通气治疗重症肺炎伴呼吸衰竭患者可有效改善其呼吸状况,减轻其机体炎性反应,安全性高。

关键词： 《蒙古消息》   《史集》   伊利汗国   旭烈兀  

摘要： 《蒙古消息》为少数成书于《史集》之前的伊利汗国史料之一,记载了成吉思汗兴起至阿合马被杀之间的史事。其中可与《史集》对应之处颇多,但也保留了大量独出材料。该文本应当有多种材料来源,其中部分内容可以被视为《史集》的同源材料。但拉施特在编纂《史集》时,并未直接采用《蒙古消息》。对于《蒙古消息》的研究或许有助于进一步理解蒙古时代的史学编纂传统。

关键词： Rheumatoid arthritis   Synovial fibroblasts   Cellular senescence   Immune infiltration   IL-6  

摘要： Background: Rheumatoid arthritis is a chronic autoimmune disease. However, the specific role of senescence in rheumatoid arthritis (RA) is unknown. This study aimed to identify potential aging-related genes that have diagnostic and therapeutic value for RA. Methods: The GSE89408 dataset was downloaded from the Gene Expression Omnibus (GEO). Aging-related genes were downloaded from the HAGR database. Differentially expressed genes (DEGs) were subsequently identified with the "edgeR" tool. Next, hub genes were identified with a PPI network and CytoHubba analysis. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of these hub genes. Immune infiltration analysis was performed with the CIBERSORT algorithm. Additionally, molecular docking was performed with CB-Dock2. Finally, correlation experiments were performed to validate the bioinformatics and molecular docking results. Results: A total of 22 ADEGs were identified. Combined PPI network and CytoHubba analyses identified a total of 7 hub genes, including IL-6, IL7R, IL2RG, CDK1, PTGS2, and LEP, which are associated mainly with inflammation and immune responses. ROC analysis revealed that the hub genes were highly predictive of RA. Analysis of immune infiltration revealed that the 6 hub genes were positively associated with M1 macrophages. Validation experiments revealed that the inhibition of IL-6 significantly decreased the degree of synovial fibroblast (FLS) senescence. Furthermore, molecular docking and validation experiments revealed that IL-6 is a potential target for drug therapy. Conclusion: This study demonstrated that RA-FLS senescence may promote the development of RA via inflammatory and immune mechanisms. Seven hub genes were identified, of which IL-6 is a reliable biomarker for the diagnosis and treatment of RA.

关键词： HLA-DPA1*02:01:01:39   novel allele   third-generation sequencing  

摘要： HLA-DPA1*02:01:01:39 differs from HLA-DPA1*02:01:01:02 by a single nucleotide change in intron 1.

摘要： Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20-30% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate T. cruzi-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of T. cruzi infected cells. Through duplicate experiments, we identified an array of unique peptides that could be traced back to 17 distinct T. cruzi proteins. Notably, six peptides were derived from Tcj2, a trypanosome chaperone protein and member of the DnaJ (heat shock protein 40) family, showcasing its potential as a viable candidate vaccine antigen with cytotoxic T cell inducing capacity. Upon testing Tcj2 as an mRNA vaccine candidate in mice, we observed a strong memory cytotoxic CD8+ T cell response along with a Th1-skewed humoral antibody response. In vitro co-cultures of T. cruzi infected cells with splenocytes of Tcj2-immunized mice restricted the replication of T. cruzi, demonstrating the protective potential of Tcj2 as a vaccine target. Moreover, antisera from Tcj2-vaccinated mice displayed no cross-reactivity with DnaJ in lysates from mouse and human indicating a decreased likelihood of triggering autoimmune reactions. Our findings highlight how immunopeptidomics can identify new vaccine targets for Chagas disease, with Tcj2 emerging as a promising new mRNA vaccine candidate.