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摘要： FAM210B (family with sequence similarity 210 member B) is a novel protein that has been linked to tumor development. However, its role and underlying mechanisms in lung adenocarcinoma (LUAD) progression remain largely unexplored. In this study, FAM210B was observed to be down-regulated in LUAD cells. Analyses of public datasets revealed that decreased expression of FAM210B predicts poor survival. Accordingly, in vitro and in vivo studies have confirmed the inhibitory role of FAM210B on the growth and tumor metastasis of LUAD cells. RNA-seq analysis further indicated that FAM210B plays a role in regulating innate immune-related signaling pathways in LUAD cells, particularly involving the production of type I interferon (IFN-alpha/beta). Specifically, FAM210B activates STAT1/IRF9/IFIT3 axis by upregulating IFN-alpha/beta expression, leading to the inhibition of proliferation and migration of LUAD cells. Furthermore, TOM70 (Translocase of outer mitochondrial membrane 70, also named as TOMM70) has been identified as a functional interacting partner of FAM210B in its modulation on the expression of IFN-alpha/beta, as well as the proliferative and metastatic phenotypes of LUAD cells. In conclusion, our study indicates that FAM210B is an important suppressor of cellular viability and mobility during lung cancer progression.

关键词： Hypoxia   MHC I Expression   Antigen Presentation   Autophagy   Immune Response  

摘要： Hypoxia is a common feature of solid tumors that has previously been linked to resistance to radiotherapy and chemotherapy, and more recently to immunotherapy. In particular, hypoxic tumors exclude T cells and inhibit their activity, suggesting that tumor cells acquire a mechanism to evade T-cell recognition and killing. Our analysis of hypoxic tumors indicates that hypoxia downregulates the expression of MHC class I and its bound peptides (i.e., the immunopeptidome). Hypoxia decreases MHC-I expression in an oxygen-dependent manner, via activation of autophagy through the PERK arm of the unfolded protein response. Using an immunopeptidomics-based LC-MS approach, we find a significant reduction of presented antigens under hypoxia. Inhibition of autophagy under hypoxia enhances antigen presentation. In experimental tumors, reducing mitochondrial metabolism through a respiratory complex-I inhibitor increases tumor oxygenation, as well as MHC-I levels and the immunopeptidome. These data explain the molecular basis of tumor immune evasion in hypoxic conditions, and have implications for future therapeutic interventions targeting hypoxia-induced alterations in antigen presentation.

关键词： Immunology   Inflammation   Inflammatory bowel disease   Innate immunity   Monocytes  

摘要： Preclinical and clinical observations indicate that the probiotic Lactobacillus rhamnosus GG (LGG) can modulate colonic inflammation. However, the underlying mechanisms have not been explored in depth. Here, we demonstrate that oral administration of live LGG alleviated inflammatory colitis by increasing IL-10 expression in intestinal Ly6C+ monocytes. Mechanistically, LGG induced IL-10 production via the stimulator of IFN genes (STING)/TBK1/NF-kappa B (RELA) signaling pathway in intestinal Ly6C+ monocytes, enhancing their immune-suppressive function. Elevated IL-10 subsequently activated IL-10 signaling in Ly6C+ monocytes, resulting in an IL-10-based autocrine regulatory loop and inhibition of proinflammatory cytokine production. Furthermore, LGG shifted the gut microbial community and its metabolic functions, leading to intestinal immune responses against colitis. Fecal microbiota transplantation from LGG-colonized mice alleviated immune checkpoint blockade-associated colitis. Our findings highlight the importance of STING signaling in IL-10-dependent antiinflammatory immunity and establish an empirical basis for developing oral administration of live LGG as an efficient and safe therapeutic strategy against inflammatory colitis.

摘要： In this issue of Developmental Cell, Tang et al. identify CD74high neutrophils as a subpopulation promoted by IL-8 in the tumor microenvironment of non-small lung cancer (NSCLC). These CD74high neutrophils support anti-tumor T cell responses and enhance the efficacy of anti-PD-1 immunotherapy and targeted therapy in NSCLC.

关键词： middle-aged men   hypertension   overweight-related hypertension   serum leptin   TNF-alpha   IL-6   total cholesterol   testosterone   pathophysiology  

摘要： Background/Objectives: One of the major causes of hypertension (HT) is the transition of normal weight (NW) status to overweight (OW) status and obesity in a population, which leads to cardiovascular disease (CVD) and other disorders. A variety of factors/variables are involved in the development of HT and OW-related hypertension (OHT). However, we planned to investigate the pathophysiological role of serum leptin (Lep), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), total cholesterol (TC) and serum testosterone (ST) in OHT in middle-aged men. Methods: We consulted three groups of middle-aged men (age: 51-60 years)-an HT group (n: 97, high normal weight (HNW), body mass index (BMI): 23-24.9 kg/m2);an OHT group (n: 97, high overweight (HOW), BMI: 28-29.9 kg/m2) and a normal control group (NC, n: 98, HNW)-to investigate the variations in and correlations of Lep, IL-6, TNF-alpha, ST, TC and other variables. Results: Significant variations were obtained for the comparisons of TNF-alpha, Lep, ST and TC for the patient groups. OHT vs. NC showed a significant difference for ST. OHT vs. NC and OHT vs. HT had significant variations for IL-6. Significant changes were obtained for the serum levels of TNF-alpha, Lep, IL-6, ST and TC among groups. Significant and positive linear associations were obtained for TNF-alpha, Lep, TC and IL-6. Significant and negative linear associations were found for ST plotted against Lep, TNF-alpha and IL-6. Conclusions: The current report provides pathophysiological evidence of the interactive role of serum Lep, TNF-alpha, ST, TC and IL-6 in middle-aged men with HT and OHT. We suggest that the changes we noted in the present study would be helpful for further BMI-based studies in various subcategories of NW, OW and obese subjects with/without HT.

关键词： 癌,肝细胞   中性粒细胞   淋巴细胞   存活   化学栓塞,治疗性  

摘要： 目的观察首次介入治疗肝细胞癌(HCC)前、后中性粒细胞与淋巴细胞比值(NLR)变化预测患者总生存期(OS)的价值。方法回顾性分析92例首次接受TACE或TACE+肝动脉灌注化疗(HAIC)的HCC患者,根据治疗后与治疗前NLR比值(NLRR)分为<1.29组(n=54)与≥1.29组(n=38)、治疗后与治疗前NLR差值(ΔNLR)分为<0.87组(n=60)及≥0.87组(n=32)。比较组间临床资料,进行生存分析,观察NLRR及ΔNLR预测OS的价值。结果NLRR<1.29组与≥1.29组,ΔNLR<0.87组与≥0.87组间临床资料差异均无统计学意义(P均>0.05)。92例患者中位OS为30.90个月;其中,NLRR<1.29组长(55.10个月)于≥1.29组(22.30个月,P=0.005),ΔNLR<0.87组(55.10个月)长于≥0.87组(14.20个月,P=0.003)。Cox回归分析显示,肿瘤最大径≥5 cm、远处转移、腹腔积液、NLRR≥1.29及ΔNLR≥0.87均为OS的独立危险因素(P均<0.05)。分别以1.29及0.87为最佳截断值,NLRR及ΔNLR预测OS的曲线下面积分别为0.620及0.610。结论NLRR及ΔNLR有助于预测首次介入治疗HCC后患者OS。

关键词： RNA氧化损伤   8-氧化鸟苷   血小板活化   细胞因子  

摘要： 目的探讨RNA氧化损伤的代谢产物8-oxo-Guo能否通过促进血小板活化,调控多种细胞因子的分泌。深入揭示氧化应激条件下血小板功能的变化,以及这种变化在炎症反应和免疫调控中的潜在作用,为理解氧化应激相关病理过程提供新的视角。方法本研究首先分离并纯化人血小板,然后使用8-oxo-Guo刺激血小板10分钟,以模拟氧化应激环境。然后,通过流式细胞术应用血小板膜表面活化标志物CD62P检测血小板活化状态,采用RayBio■QAH-CAA-2000试剂盒定量检测8-oxo-Guo刺激人血小板后120种细胞因子的水平变化。采用GraphPad Prism 9.0.0进行数据分析,使用Student's t检验分析两组间差异。结果与对照组相比,8-oxo-Guo显著促进了血小板活化,其特征为CD62P表达水平的显著升高。同时,8-oxo-Guo处理后的血小板分泌的多种细胞因子也发生显著变化,其中炎症趋化因子MCP-3、MIP-3α、MIP-3β和MDC的表达显著上调,生长因子EG-VEGF、FGF-4、NT-3和BMP-7的表达显著下调。GO富集分析显示变化的细胞因子主要集中在免疫调节、炎症反应和细胞迁移等方面。这些结果提示8-oxo-Guo在调控血小板功能及相关细胞因子释放方面具有重要作用。结论8-oxo-Guo可以通过促进血小板的活化影响多种细胞因子水平的变化,这一发现不仅揭示了氧化应激条件下血小板功能调控的新机制,也为开发针对氧化应激相关疾病的新型治疗策略提供了理论基础和实验依据。

关键词： 检测性能   化学发光分析仪   前列腺特异性抗原  

摘要： 目的 评价电化学发光检测系统和三种国产化学发光检测系统检测总前列腺特异抗原(TPSA)和游离前列腺特异性抗原(FPSA)结果的一致性。方法 以cobase602电化学发光免疫分析仪及配套试剂组成的检测系统作为参比系统(X),分别以CL8000i全自动化学发光分析仪、AXCEED360化学发光分析仪、NORMAN-CL5B化学发光分析仪及配套试剂组成的检测系统作为待评系统1 (Y1)、待评系统2 (Y2)、待评系统3 (Y3)。根据CNASCL02-A003:2021《医学实验室质量和能力认可准则在临床化学检验领域的要求》参考美国临床和实验室标准协会(CLSI) EP15-A3、(CLSI) EP6、美国临床实验室标准化委员会(NCCLS) C28-A2和(NCCLS) EP15-A23文件的要求设计实验比对方案,对4种检测系统的总前列腺特异抗原(TPSA)和游离前列腺特异性抗原(FPSA)两个项目的精密度、线性范围、参考区间、样本比对进行验证评估,为实验室和临床工作提供参考。结果 4个检测系统前列腺特异抗原项目精密度批内CV小于1/4 TEa,总CV小于1/3 TEa。4种方法检测TPSA、FPSA结果相关性良好(r^(2)≥0.95)。结论 在三个国产平台上对TPSA、fpsa两个检测项目进行方法学验证,精密度、参考区间、临床可报告范围均通过,实验室在选择设备时前需进行性能验证,选择满足实验室质量要求的国产设备及试剂。

关键词： 急性胰腺炎   血小板   淋巴细胞   中性粒细胞   相关性  

摘要： 目的:分析血清降钙素原(PCT)、血小板/淋巴细胞比值(PLR)、中性粒细胞/淋巴细胞比值(NLR)与急性胰腺炎患者病情严重程度的相关性。方法:回顾性分析2020年3月至2023年3月该院收治的85例急性胰腺炎患者的临床资料,设为急性胰腺炎组,根据病情严重程度将其分为轻度患者(n=35)、中度患者(n=33)、重度患者(n=17),另选取同期80名健康体检者,设为对照组。比较两组和不同病情严重程度患者的血清PCT、PLR、NLR水平、急性生理学及慢性健康状况评分系统Ⅱ(APACHEⅡ)评分,血清PCT、PLR、NLR水平与急性胰腺炎患者病情严重程度的相关性采用Pearson相关性分析。结果:急性胰腺炎组血清PCT、PLR、NLR水平均高于对照组,差异有统计学意义(P<0.05);重度患者血清PCT、PLR、NLR水平均高于中度患者和轻度患者,且中度患者高于轻度患者,差异有统计学意义(P<0.05);重度患者APACHEⅡ评分均高于中度患者和轻度患者,且中度患者高于轻度患者,差异有统计学意义(P<0.05);Pearson相关性分析结果显示,血清PCT、PLR、NLR水平与急性胰腺炎患者病情严重程度均呈正相关(r>0,P<0.05)。结论:血清PCT、PLR、NLR水平与急性胰腺炎患者病情严重程度均呈正相关。

关键词： 重度烧伤   炎症指标   死亡风险  

摘要： 目的探讨感染炎症指标联合检测对重度烧伤患者死亡风险评估的临床价值。方法收集2019年1月至2022年6月大连市第四人民医院烧伤科收治的重度烧伤患者(烧伤总面积>30%或Ⅲ度烧伤面积>10%,且伴有吸入性呼吸道烧伤患者)72例,观察90 d,其中治疗存活62例(存活组),死亡10例(死亡组)。另选择30例同期成年体检者作为健康对照组,男、女各15例。记录患者一般临床资料,分别于伤后第1、4、7、21天检测白细胞(WBC)、降钙素原(PCT)、白介素-6(IL-6)、超敏C反应蛋白(hs-CRP)及血清淀粉样蛋白A(SAA)等炎症指标,比较各组指标在不同时间点的差异;绘制炎症指标联合检测和单独检测在各个时间点的ROC曲线,进行AUC计算和ROC曲线的成对比较,评估炎症指标联合检测和单独检测对重度烧伤患者死亡风险的预测效能。结果伤后第1天,健康对照组与重度烧伤的两组比较,PCT、IL-6、hs-CRP、SAA差异均有统计学意义(P<0.05)。伤后第21天,存活组WBC计数为8.02(5.83,10.59)×10^(9)/L,明显低于死亡组13.57(12.21,15.88)×10^(9)/L;伤后第1、4、7、21天,存活组PCT、IL-6水平均明显低于死亡组;伤后第1、21天,存活组hs-CRP、SAA水平明显低于死亡组,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,伤后第1、4、7天,各指标中PCT的ROC曲线下面积(AUC)分别为0.848、0.901、0.895;伤后第21天,IL-6的AUC为0.856。联合指标在4个相应时间点的AUC分别为0.948、0.909、0.929、0.949。联合指标检测水平在4个时间点均对重度烧伤死亡结局具有评价效能(P<0.05);ROC曲线成对比较结果显示,伤后第1天,联合指标较hs-CRP和SAA的AUC更大,差异有统计学意义(P<0.05);伤后第7天,联合指标较IL-6的AUC更大,差异有统计学意义(P<0.05);伤后第21天,联合指标较hs-CRP、SAA、PCT、IL-6的AUC更大,差异有统计学意义(P<0.05)。结论血清炎症指标WBC、PCT、IL-6、hs-CRP、SAA的早期联合动态检测相对于单个指标检测,能够在烧伤后不同时间点,更准确地预测重度烧伤患者的死亡结局,可用于指导临床决策,及时调整针对性治疗方案,提高患者存活概率。