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关键词： 外周血   循环游离DNA   白介素10   弥漫大B细胞淋巴瘤   中枢神经系统浸润   预测价值  

摘要： 目的:探讨外周血循环游离DNA(cf DNA)联合白介素10(IL-10)对弥漫大B细胞淋巴瘤(DLBCL)中枢神经系统浸润(CNSI)的预测价值。方法:回顾性分析2021年5月至2023年4月在本院就诊的63例DLBCL患者的临床资料。根据是否发生CNSI将患者分为CNSI组(15例)和non-CNSI组(48例)。比较两组患者的年龄、性别、Ann Arbor分期、ECOG评分、IPI风险、CNS-IPI风险、累及的结外站点数量、骨髓受累、肥大性疾病、B症状、来源细胞、葡萄糖定量、潘氏试验、脑脊液氯、脑脊液有核细胞计数、脑脊液蛋白、外周血cf NDA、IL-10的情况。Pearson相关性分析外周血cf DNA、IL-10与脑脊液蛋白的相关性。ROC曲线分析外周血cf DNA、IL-10对DLBCL患者继发CNSI的预测价值。末次随访时间为2023年11月30日,Kaplan-Meier法计算non-CNSI组患者继发CNSI的时间。结果:CNSI组的IPI风险、CNS-IPI风险、累及的结外站点数量、脑脊液蛋白水平均明显高于non-CNSI组(均P<0.05)。CNSI组患者外周血cf DNA、IL-10水平均明显高于non-CNSI组(均P<0.01)。外周血cf DNA、IL-10与脑脊液蛋白均呈正相关(r=0.4024,0.3151)。ROC曲线分析结果显示,外周血cf DNA、IL-10对CNSI具有一定预测价值,其曲线下面积分别为0.829、0.742,二者联合检测的曲线下面积为0.910,敏感度为80.00%,特异度为93.70%,诊断效能明显高于二者单独检测。中位随访时间20(6-31)个月,以外周血cf DNA联合IL-10阳性或阴性对non-CNSI患者分组,阳性组患者继发CNSI的时间明显短于阴性组的患者(P<0.05)。结论:DLBCL合并CNSI患者外周血cf DNA、IL-10的水平显著升高,二者联合检测对CNSI具有良好预测价值。

关键词： 纤维胶凝蛋白-3   CD4^(+)/CD8^(+)T淋巴细胞比值   中性粒细胞与淋巴细胞比值   肺炎支原体肺炎   EB病毒   预后  

摘要： 目的研究血清纤维胶凝蛋白-3(ficolin-3)、CD4^(+)/CD8^(+)T淋巴细胞比值联合中性粒细胞与淋巴细胞比值(NLR)在肺炎支原体肺炎(MPP)合并EB病毒(EBV)感染患儿预后评估中的临床价值。方法回顾性分析2021年1月至2023年5月西北大学附属第一医院收治的146例MPP合并EBV感染患儿的临床资料。于患儿入院后(治疗前)检测血清ficolin-3、CD4^(+)/CD8^(+)T淋巴细胞比值及NLR。患儿出院后随访12个月,根据患儿预后情况将其分为预后良好组(100例)和预后不良组(46例)。采用多因素logistic回归分析MPP合并EBV感染患儿预后的影响因素。通过受试者工作特征(ROC)曲线分析ficolin-3、CD4^(+)/CD8^(+)T淋巴细胞比值、NLR对MPP合并EBV感染患儿预后的预测效能。结果与预后良好组比较,预后不良组发热时间较长,肺部阴影≥2/3肺叶占比、重症占比较高,C反应蛋白、ficolin-3水平及NLR较高,CD4^(+)/CD8^(+)T淋巴细胞比值较低,差异有统计学意义(P<0.05)。多因素logistic回归分析结果显示,较高的ficolin-3水平及NLR,较低的CD4^(+)/CD8^(+)T淋巴细胞比值以及重症MPP、肺部阴影≥2/3肺叶是MPP合并EBV感染患儿预后不良的独立危险因素(P<0.05)。ROC曲线分析结果显示,ficolin-3、CD4^(+)/CD8^(+)T淋巴细胞比值、NLR可预测MPP合并EBV感染患儿预后不良(P<0.05),且三者联合检测的预测效能[AUC(95%CI)=0.874(0.837~0.911)]优于单项指标(P<0.05)。结论血清ficolin-3、CD4^(+)/CD8^(+)T淋巴细胞比值、NLR联合检测有助于预测MPP合并EBV感染患儿的预后。

关键词： mRNA药物   IL-27   急性肺损伤   LPS   抗炎  

摘要： 目的合成编码IL-27的mRNA,制备脂质纳米颗粒(lipid nanoparticles,LNP)/IL-27 mRNA复合物,探讨其对脂多糖(lipopolysaccharide,LPS)诱导急性肺损伤(acute lung injury,ALI)小鼠模型的保护。方法体外合成IL-27mRNA,通过LNP包载形成LNP/IL-27 mRNA,注射至小鼠体内,检测LNP/IL-27 mRNA的体内表达,并进行给药后抗炎活性评价和初步安全性评价。采用气管滴注LPS建立小鼠ALI模型,给予不同剂量的IL-27 mRNA,同时设立空白对照组、模型组、地塞米松阳性药对照组,检测小鼠肺组织湿干质量比、肺匀浆中炎症因子(IL-1β、IL-6、TNF-α)蛋白和mRNA表达水平及乳酸脱氢酶(lactic acid dehydrogenase,LDH)活性,并观察分析病理切片、免疫荧光结果,评价IL-27 mRNA对LPS诱导的ALI小鼠的保护效果。对注射IL-27 mRNA的小鼠进行主要脏器的病理切片分析并检测肝肾生化指标。结果IL-27 mRNA在小鼠体内可正确表达IL-27,保护作用评价结果显示IL-27 mRNA在12.5~125.0μg/kg剂量范围内可减轻ALI小鼠肺组织湿干质量比,降低IL-1β、IL-6、TNF-α的表达及LDH活性,改善小鼠肺泡壁增厚,减少小鼠肺间质中性粒细胞浸润。初步安全性评价结果显示250.0μg/kg剂量下IL-27 mRNA安全性良好,未引起主要脏器的病理性变化。结论IL-27 mRNA在小鼠体内成功编码目的蛋白且初步安全性良好,在12.5~125.0μg/kg剂量范围下呈剂量依赖性减轻LPS诱导ALI小鼠肺部炎症,可为mRNA药物用于治疗ALI提供新的实验依据。

关键词： 4-OI   4-octyl itaconate   7-DHC   7-dehydrocholesterol   Acod1   aconitate decarboxylase 1   ACSL4   Acyl-CoA synthetase long-chain family member 4   ALI   acute lung injury   APCs   antigen-presenting cells   ASCT2   alanine-serine-cysteine transporter 2   ASS1   Argininosuccinate Synthase   BCAAs   branched-chain amino acids   BCRs   B cell receptors   CAR-T   Chimeric antigen receptor T cell   DAMPs   damage-associated molecular patterns   DC   dendritic cells   DHODH   dihydroorotate dehydrogenase   DMT1   divalent metal transporter 1   FSP1   Ferroptosis suppressor protein 1   Gln   glutamine   Glu   glutamate   GPX4   glutathione peroxidase 4   GS   glutathione synthetase   GSH   glutathione   ICIs   immune checkpoint inhibitors   IFNγ   interferon γ   HMGB1   high-mobility group box 1   MCL   Micheliolide   MDSC   myeloid-derived suppressor cell   MFN   mitoferrin   MGST1   glutathione S-transferase 1   MHC   major histocompatibility complex   MPO   myeloperoxidase   MRI   magnetic resonance imaging   NADPH   nicotinamide adenine dinucleotide phosphate   NLRs   NOD-like receptors   NK   natural killer   NOX   nicotinamide adenine dinucleotide phosphate NADPH oxidase   PGE2   prostaglandin E2   PRRs   pattern recognition receptors   PUFAs   polyunsaturated fatty acids   RBC   red blood cells   RCD   regulated cell death   ROS   reactive oxygen species   SOD2   superoxide dismutase 2   SREBP1   sterol regulatory element-binding protein 1   STEAP3   six transmembrane epithelial antigen 3   TAMs   tumor-associated macrophages   TANs   tumor-associated neutrophils   TCA   tricarboxylic acid   Tf   transferrin   Tfr   transferrin receptors   TIN   Tumor infiltrated neutrophils   TLRs   Toll-like receptors   TME   tumor microenvironment   Ferroptosis   Innate immunity   Adaptive immunity   Cancer  

摘要： Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, has emerged as a pivotal mechanism in cancer biology with significant therapeutic potential. Immune cells, both innate and adaptive, are integral in detecting and eliminating tumor cells, yet their response is intricately modulated by ferroptosis. While cancer cell ferroptosis stimulates anti-tumor immunity, ferroptosis in immune cells undermines their effectiveness, compromising overall immune surveillance. The intricate crosstalk between ferroptosis and immune responses is pivotal in tumor progression and therapeutic outcomes, shaping both cancer resistance and treatment effectiveness. This review explores the multifaceted relationship between ferroptosis and immune function in cancer, offering insights into how these processes intersect to shape tumor immunity and guide immunotherapy strategies. We highlight cutting-edge research, uncover key molecular mechanisms, and outline promising avenues for future studies and therapeutic interventions in this evolving field.

关键词： 原发性膜性肾病   抗磷脂酶A2受体抗体   免疫球蛋白G   白细胞介素   预后  

摘要： 目的探究抗磷脂酶A2受体抗体(PLA2R-Ab)、免疫球蛋白G(IgG)以及白细胞介素-6(IL-6)在原发性膜性肾病(PMN)患者中的表达及其意义。方法回顾性选取河源市人民医院2023年11月~2024年7月期间收治的127例PMN患者的临床资料,经纳入、排除标准剔除19例患者,最终纳入108例患者作为PMN组,并根据治疗3个月后的预后情况将其分为预后良好组(86例)和预后不良组(22例);同时选取医院同期收治的性别、年龄相匹配的狼疮肾炎患者及体检健康者各50例,分别纳入病例对照组和正常组。比较PMN组、病例对照组、正常组以及不同预后患者的血清PLA2R-Ab、IgG、IL-6水平差异,使用Pearson相关性分析PMN患者血清PLA2R-Ab、IgG、IL-6水平与24 h尿蛋白定量(24 h UTP)及血清白蛋白(ALB)水平的相关性;绘制受试者工作特征(ROC)曲线分析血清PLA2R-Ab、IgG、IL-6水平对PMN患者近期预后的预测价值。结果三组年龄、性别、WBC比较,差异无统计学意义(P>0.05);PMN组和病例对照组24 h UTP、BUN、Scr、UA、TC、PLA2R-Ab、IgG、IL-6水平均显著高于正常组,ALB则显著低于正常组(P<0.05);且PMN组24hUTP、PLA2R-Ab、IgG、IL-6水平显著高于病例对照组(P<0.05);预后不良组血清PLA2R-Ab、IgG、IL-6水平均高于预后良好组(P<0.05)。Pearson相关性分析结果显示,血清IgG、IL-6水平与PLA2R-Ab均呈显著正相关(r=0.821、0.525,P<0.05);血清PLA2R-Ab、IgG、IL-6水平与24hUTP均呈显著正相关(r=0.747、0.620、0.522,P<0.05);血清PLA2R-Ab、IgG、IL-6水平与ALB均呈显著负相关(r=-0.651、-0.416、-0.429,P<0.05)。ROC曲线分析结果显示,血清PLA2R-Ab、IgG、IL-6联合检测预测PMN患者近期预后的曲线下面积(AUC)为0.951,高于单一指标预测(AUC分别为0.893、0.851、0.882),且灵敏度为100.00%、特异度为90.91%。结论血清PLA2R-Ab、IgG、IL-6水平异常升高与PMN的发生、病情进展具有密切关系,三者联合检测对PMN患者近期预后具有较高的预测价值,可为PMN临床诊治提供参考。

关键词： 免疫学技术   疫苗研发   抗原筛选   免疫原性评估   免疫监测  

摘要： 随着全球新发烈性传染病的频发,疫苗研制技术的革新成为全球公共卫生体系的必然需求。传统疫苗研制是基于病原体培养和经验性筛选,存在着时间漫长、效率较底等问题。近年来,新型疫苗研制技术的发展正在改变疫苗研制思路,基于病原体全基因组数据的反向疫苗学能够鉴定出保守的表位;通过单细胞转录组学研究可发现宿主的免疫应答异质性;人工智能驱动的抗原设计平台能为候选分子结构—效应关系预测提供线索,从而缩短研发周期。本文对上述技术手段在抗体高通量筛选、免疫原性监测动态、长效抗体免疫监测方面的有机结合,以及存在的规模化推广的挑战进行总结,并讨论了疫苗研制未来的可能发展方向和有效降低成本的可行策略,即利用低成本的检测设备与建设全球病原体抗原库,将使疫苗研制从个性化疫苗到精准疫苗再到可持续控制传染病成为可能。

关键词： 嵌合抗原受体   巨噬细胞   实体瘤  

摘要： 巨噬细胞作为肿瘤微环境中重要的先天免疫细胞,凭借其强大的吞噬能力及抗原呈递功能,成为肿瘤免疫治疗的研究热点。近年来,嵌合抗原受体巨噬细胞(chimeric antigen receptor macrophage,CAR-M)技术的开发为实体瘤治疗提供了新思路。临床前研究表明,CAR-M不仅能特异性靶向杀伤肿瘤细胞,还可通过重塑免疫微环境、招募并激活其他免疫细胞,形成协同抗肿瘤效应。本文系统综述了CAR-M的作用机制、基因工程策略、临床前研究进展及面临的挑战,并展望其未来发展方向,以期为实体瘤免疫治疗提供理论参考。

关键词： AA   airway allergy   Trabid   TRAF binding domain-containing protein   BMDCs   Bone marrow derived dendritic cells   EIPA   Ethylisopropylamiloride   STAT6   signal transducer and activator of transcription 6   TIM4   T cell immunoglobulin molecule domain-4   DME   dust mite extracts   BALF   bronchoalveolar lavage fluid   ChIP   chromatin immunoprecipitation   FBXO28   F-box only protein 28   RNF20   ring finger protein 20   Airway   Allergy   Dendritic cell   Th1   Th2  

摘要： Th2 polarization is a key factor in the pathogenesis of allergic diseases, particularly airway allergy (AA). However, the mechanisms underlying the regulation of Th2 remain to be fully elucidated. Ethylisopropylamiloride (EIPA) has been shown to attenuate immune inflammation. This study aims to investigate the efficacy of EIPA in suppressing AA and to elucidate its underlying mechanisms. A mouse model of airway allergy was established to evaluate the effects of EIPA on AA. Additionally, bone marrow-derived dendritic cells (BMDCs) were generated to explore how EIPA modulates the properties of dendritic cells (DCs). We observed that administration of EIPA significantly alleviated experimental airway allergy. The expression of IL-12b in airway DCs was positively correlated with the suppressive effects of EIPA. Specifically, EIPA increased the levels of TRAF binding domain-containing protein (Trabid), a deubiquitinase, and Jmjd2d, a demethylase, at the IL-12b promoter region of DCs. These changes actively upregulated the expression of IL-12b. The elevated IL-12b subsequently led to the degradation of T cell immunoglobulin molecule domain-4 (TIM4) in DCs. Consequently, the Th2 response and airway allergy were mitigated. In conclusion, EIPA attenuates the allergic response by upregulating IL-12b production, reducing TIM4 expression in DCs, and suppressing the Th2 response.

关键词： 自身免疫性脑炎   淋巴细胞亚群   免疫球蛋白   补体   鉴别诊断   病情评估  

摘要： 目的 分析血淋巴细胞亚群、免疫球蛋白、补体在自身免疫性脑炎鉴别诊断和病情评估中的应用价值。方法 回顾性选取佛山市第一人民医院2022年1月~2024年7月儿科收治的26例脑炎患儿为研究对象,对比两组的血淋巴细胞亚群[辅助性T细胞(Th)、抑制性T细胞(Ts)]、免疫球蛋白(IgA、IgG)、补体(补体C3)水平。根据是否为自身免疫性脑炎(AE)将其分为AE组(n=15)和非AE组(n=11),以改良Rankin量表(mRS)评分评估AE患儿病情并将其划分为轻度AE组(m RS≤3分,9例)、中重度AE组(mRS > 3分,6例),采用Pearson检验Th、Ts、IgA、IgG、补体C3与AE患儿m RS评分的相关性,采用受试者工作曲线(ROC)分析淋巴细胞亚群、免疫球蛋白、补体鉴别诊断AE的效能。结果 与非AE组比较,AE组的Ts、IgA、IgG、补体C3较高,Th细胞水平较低,差异均有统计学意义(P<0.05)。相关性分析结果显示,Ts、IgA、IgG、补体C3与m RS评分呈正相关,Th与m RS评分呈负相关(P<0.05)。ROC曲线结果显示,Th、T、IgA、IgG、补体C3及联合检测对自身免疫性脑炎诊断的曲线下面积分别为0.764、0.745、0.703、0.764、0.758、0.921,联合检测诊断效能高于单一指标检测。结论 Ts、IgA、IgG、补体C3在AE患儿血清中异常升高,与AE严重程度呈正相关,Th水平下降,与其严重程度呈负相关,且联合检测对诊断AE患儿的效能较佳。

关键词： ADCC   antibody-dependent cellular cytotoxicity   BLI   bioluminescence imaging   CAR   chimeric antigen receptor   CD16V   high-affinity CD16 V158 FcγRIIIa receptor variant   DEG   differentially expressed gene   eGFP   enhanced green fluorescent protein   ELISA   enzyme-linked immunosorbent assay   fLuc   firefly luciferase   γc   common γ chain   iPSC   induced pluripotent stem cell   KIR   killer cell immunoglobulin-like receptor   mbTRAIL   membrane-bound TRAIL   MFI   mean fluorescence intensity   NK   natural killer   PBS   phosphate-buffered saline   SEM   standard error of the mean   sTRAIL   soluble TRAIL   TRAIL   TNF-related apoptosis-inducing ligand   NK cell immunotherapy   NK cell platform   Cytokine priming   Multifunctional genetic engineering   Therapeutic antibody combination  

摘要： The advancement of NK cell-based immunotherapy requires platform-specific approaches that overcome intrinsic functional limitations while enabling flexible adaptation across diverse manufacturing settings. NK101, a human NK cell line phenotypically aligned with the CD56 dim CD62L + intermediate-stage subset, retains functional plasticity and robust cytokine responsiveness, providing a versatile platform for adoptive immunotherapy development. Although baseline cytotoxicity is relatively modest, this profile allows for rational reprogramming through targeted cytokine and genetic interventions. We initiated this reprogramming by screening IL-2 family cytokines for their effects on proliferation and effector molecule production. IL-2 and IL-15 promoted proliferation and IFN-γ secretion, whereas IL-21 uniquely enhanced granzyme B levels with minimal effects on proliferation and IFN-γ. Co-stimulation with IL-2 and IL-21 proved most effective, maximizing cytotoxic potential while sustaining proliferation and enhancing IFN-γ secretion. Transcriptomic profiling further highlighted IL-21’s role in activating granzyme-mediated apoptosis, which was amplified by IL-2 co-priming. These findings were applied to genetically engineered NK101 cells expressing high-affinity CD16 (NK101-16V), where IL-2 and IL-21 co-priming enhanced both baseline cytotoxicity and antibody-dependent cellular cytotoxicity. Additional engineering to express membrane-bound TRAIL (NK101-16V-TR) significantly augmented TRAIL-mediated apoptosis, enabling greater killing of resistant tumors. In vivo , IL-2/IL-21-primed NK101-16V-TR cells in combination with rituximab achieved complete tumor regression in all Jeko-1 xenograft-bearing mice. Collectively, this study presents a broadly applicable design framework for NK cell manipulation, integrating transient cytokine priming with multi-functional genetic modification to guide the development of next-generation NK cell therapies.