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关键词： 单采献血   T淋巴细胞亚群   免疫功能   流式细胞术   频次  

摘要： 分析不同频次单采献血者T淋巴细胞亚群对比及相关性。方法 选取在某献血站进行献血的志愿者60例,分为低频献血组和高频献血组。并分析献血者T淋巴细胞亚群对比及相关性。结果 高频献血组和低频献血组在T细胞亚群的比例上存在显著差异(P<0.05)。高频献血者的CD4^+/CD8^+比值显著降低。结论 频繁单采献血可能导致T淋巴细胞亚群的失衡,需进一步关注献血者免疫功能的长期影响,并为献血频次的合理设置提供数据支持。

关键词： 脓毒症   急性肾损伤   连续性肾脏替代治疗   细胞因子   抗凝功能  

摘要： 评估多种抗凝策略与连续性肾脏替代治疗(CRRT)协同应用于脓毒症相关急性肾损伤(AKI)患者的临床效果,重点分析其对炎症介质表达谱及凝血功能相关生物标志物的调控作用。方法 本研究选取2022年4月至2024年10月在南京市溧水区中医院纳入120例确诊为脓毒症相关急性肾损伤(AKI)的病例作为研究样本。通过随机数字表法将受试者均衡分配至两个组别,其中观察组60例,对照组60例,所有入组患者均接受连续性肾脏替代治疗(CRRT)。在常规治疗基础上,本研究采用不同抗凝方案:对照组(n=60)实施全身肝素抗凝治疗,观察组(n=60)则采用枸橼酸钠局部抗凝策略。通过对比分析两组患者治疗前后的临床疗效,重点观察细胞因子谱及抗凝相关指标的变化情况。结果 观察组临床疗效显著优于对照组(90.50% vs 75.00%,P=0.031)。在实验室指标方面,虽然两组患者的肾功能指标(BUN、Scr、β2-MG)和心肌损伤标志物(CK-MB)均较治疗前改善,但观察组的改善幅度更为显著(P<0.05)。炎症指标分析表明,两组IL-6、hs-CRP及MCP-1水平均呈现下降趋势,其中观察组的下降幅度更具统计学意义(P<0.05)。在凝血功能方面,两组PT和APTT均出现延长,且对照组延长更为显著;同时,PLT计数和Fib水平均有所降低,对照组降低幅度更大(P<0.05)。安全性评估显示,观察组不良反应发生率显著低于对照组(8.33% vs 25.00%,P=0.014)。此外,观察组滤器使用时间明显长于对照组[(36.45±4.54)h vs(29.48±4.69)h,P<0.001]。结论 采用连续性肾脏替代治疗(CRRT)结合枸橼酸钠区域抗凝方案治疗脓毒症相关急性肾损伤(AKI),在临床实践中展现出多重优势:该治疗方案不仅能够显著抑制炎症反应,有效调控促炎因子表达,同时可最大限度地维持机体凝血功能的稳定性,且具有较低的不良反应发生率,展现出良好的临床应用安全性。

关键词： CAR-T cell   hepatocellular carcinoma   immunoactivation   tumor microenvironment   vitality backpacks  

摘要： Chimeric antigen receptor (CAR)-T-cell therapy achieves considerable success in the treatment of malignant tumors, but clinical relapse due to the tumor microenvironment (TME) is very common. The TME of solid tumors is characterized by weak acidity, hypoxia, and elevated reactive oxygen species (ROS) levels, which collectively impair the function and persistence of infiltrating CAR-T cells. In this study, acid-sensitive responsive CaMnCO3 nanoparticles (CMC NPs), are developed that simultaneously mitigate TME acidosis and hypoxia. IL-21 is encapsulated within CMC NPs (denoted as CMC-21), which are then surface-conjugated to CAR-T cells as functional 'vitality backpacks' to enhance cellular activity. The CMC-21 backpack enables sustained release of IL-21, persistently enhancing CAR-T cell antitumor immunity across both low- and high-dose infusion regimens. Furthermore, CMC NPs exert dual modulatory effects on the TME by: 1) consuming protons to neutralize acidic conditions, and 2) catalytically converting endogenous H2O2 to O2 to relieve hypoxia. This multimodal remodeling of the immunosuppressive TME significantly enhances the infiltration and activity of adoptively transferred CAR-T cells while simultaneously boosting endogenous T cell and NK cell recruitment in vivo. These findings establish a novel CAR-T cell enhancement strategy through sustained IL-21 release from CMC-21 backpacks, offering new possibilities for solid tumor immunotherapy.

摘要： Neutralizing anti-interferon-gamma (IFN-gamma) autoantibodies (nAIGAs) impair IFN-gamma-mediated immunity, predisposing patients with nAIGAs to infection by nontuberculous mycobacteria, Talaromyces marneffei, and other intracellular pathogens. Current clinical management relies on continuous antimicrobial therapy, with no treatment offering sustained benefits. Here, we developed human chimeric autoantibody receptor (CAAR) T cells targeting autoreactive B cells expressing nAIGA B cell receptors (BCRs) using an IFN-gamma receptor-irresponsive IFN-gamma variant as bait. By exploiting a mouse model of nAIGA BCR-expressing B cell leukemia, we found that IFN-gamma CAAR T cells lack off-target toxicity, including IFN-gamma receptor cross-reactive toxicity and Fc-redirected toxicity. IFN-gamma CAAR T cells substantially reduced circulating AIGAs secreted from target cells in vivo. Further, IFN-gamma CAAR T cells effectively eliminated autoreactive B cells in ex vivo cultures of peripheral blood mononuclear cells from patients with nAIGAs. Together, these results demonstrate that IFN-gamma CAAR T cells may be a promising strategy to ameliorate nAIGA-associated infections by eliminating autoreactive B cells.

关键词： 康妇炎胶囊   硝酸咪康唑   阴道炎   外阴瘙痒  

摘要： 探讨康妇炎胶囊联合硝酸咪康唑在阴道炎伴外阴瘙痒中的临床疗效。方法 选择2023年4月-2024年4月河北省承德市隆化县韩麻营中心卫生院收治阴道炎伴外阴瘙痒患者80例进行研究,随机分组,对照组给予硝酸咪康唑治疗,观察组在此基础上给予康妇炎胶囊治疗,同时根据观察组患者病原体类型分为霉菌性阴道炎组(22例)以及细菌性阴道炎组(18例),比较治疗疗效。结果 观察组治疗后阴道微生态平衡、Th1/Th2细胞因子谱、治疗疗效均优于对照组(P<0.05),霉菌性阴道炎组与细菌性阴道炎组比较无明显差异(P>0.05)。结论 联合药物治疗方式在阴道炎伴阴道瘙痒中疗效显著,可临床应用。

关键词： rheumatoid arthritis   exosome   C22:6   TLR4   IL-1 beta  

摘要： Introduction: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by significant disability and teratogenic effects, for which there are few effective curative therapies. Exosomes derived from mesenchymal stem cells (MSCs) exhibit anti-inflammatory and tissue regenerative properties. This study aimed to investigate the therapeutic potential of exosomes derived from human classical interscapular brown adipocytes (hcBAC-exos) in alleviating symptoms of RA in a mouse model. Methods: We established a mouse model of collagen-induced arthritis (CIA) to evaluate the efficacy of hcBAC-exos. Specifically, we assessed the degree of RA remission by applying vitamin E emulsion, as well as a mixture of vitamin E emulsion and hcBAC-exos, to the foot paws of CIA mice. Additionally, the effects of hcBAC-exos on pro-inflammatory cytokines in macrophages (RAW264.7 cells) were investigated at the cellular level. The active components of hcBAC-exos were analyzed via lipidomics, and the mechanism of their ability to inhibit inflammation was explored. Results: Administration of hcBAC-exos significantly reduced the expression of pro-inflammatory cytokines in macrophages. In the CIA mouse model, transdermal application of hcBAC-exos led to notable decreases in ankle swelling and the serum levels of IL-1 beta and TNF alpha (P < 0.5). Mechanistically, lipidomic analysis showed that Docosahexaenoic acid (C22:6) is highly enriched in hcBAC-exos. Furthermore, we found that C22:6 specifically inhibits IL-1 beta expression by binding to the amino acids Y183, S210, E265, S182, and R223 of TLR4, mutating these amino acids results in the loss of C22:6 binding activity to TLR4. Discussion: Our findings suggest that the hcBAC-exos-C22:6-TLR4-IL-1 beta signaling pathway plays a crucial role in the context of RA, indicating the potential clinical applications of hcBAC-exos in the treatment of inflammatory conditions such as rheumatoid arthritis.

关键词： gypenosides   ferroptosis   chronic stress   lipid peroxidation   iron homeostasis  

摘要： Chronic stress can lead to nervous system dysfunction and depression-like behaviors in animals. Gypenosides can improve chronic stress-induced neuronal damage, but the protective mechanism remains poorly understood. This study aims to investigate the effect and mechanism of gypenosides on chronic stress-induced neuronal ferroptosis. Therefore, we established a chronic stress-induced neuronal damage model in vitro using corticosterone to induce PC12 cell injury. We demonstrated that ferroptosis inhibitors DFO and Ferrostatin-1 alleviated corticosterone-induced cell death in PC12 cells by reducing iron accumulation, lipid peroxidation, and increasing cell viability. Meanwhile, gypenosides attenuated ferroptosis agonist Erastin-induced ferroptosis in PC12 cells. Then, gypenosides ameliorated corticosterone-induced ferroptosis in PC12 cells. In terms of molecular mechanisms, gypenosides decreased the expression of Hepcidin and DMT1, and increased the expression of Ferritin and FPN1, thereby improving corticosterone-induced iron homeostasis disorders and iron accumulation. Moreover, gypenosides improved corticosterone-induced lipid peroxidation by inhibiting GLS2 expression, upregulating the expression of SLC7A11 and glutathione peroxidase 4, and reducing glutamate accumulation and GSH depletion. Gypenosides also reduced corticosterone-induced release of inflammatory cytokines, the expression of TNFR1, and the phosphorylation of NF-kappa B and p53 in PC12 cells. These findings indicate that gypenosides attenuate corticosterone-induced ferroptosis by inhibiting TNF-alpha/NF-kappa B signaling pathway in PC12 cells.

关键词： 系统性红斑狼疮   回顾性研究   ENA抗体检验   血清体液免疫检验   健康体检人群   诊断有效性  

摘要： 讨论分析SLE临床诊断中ENA抗体检验和血清体液免疫检验的效果。方法 研究选取我院2024年1-12月收治的系统性红斑狼疮患者100例为实验组,其中活动期50例,非活动期50例。选取同阶段健康体检人群100例为体检组。两组患者均进行ENA抗体和血清体液免疫检验。比较患者ENA抗体和血清体液免疫指标的差异。结果 实验组ENA抗体和血清体液免疫阳性率增高,P<0.05,差异显著。结论 在系统性红斑狼疮患者中采用ENA抗体检验联合血清体液免疫检验的方式诊断效果更好。

关键词： 单克隆抗体   抗体制备   杂交瘤技术   单个B细胞技术   AI辅助技术   联合应用   技术进展   应用研究  

摘要： 基因工程(Genetic engineering)与人工智能(Artificial Intelligence,AI)的发展极大推动了单克隆抗体制备技术的革新与优化,但当前如何利用这些前沿技术高效制备单克隆抗体仍亟待解决。本文将对比传统与现代单克隆抗体制备技术,深入探讨单个B细胞制备技术与AI辅助单抗制备技术这两大创新领域。通过解析单抗的结构特点,重点阐述两种技术的作用机理,并讨论单B测序技术与AI预测技术在单抗制备、疾病治疗等方面的最新研究进展。对这两种技术的协同应用进行前瞻性展望,期望通过它们的整合,实现单克隆抗体制备过程的全面自动化与个性化医疗发展,加速商业化进程。

关键词： Fibrosis   Heart failure   LOXL2/ TGF-β1/IL-11 signaling pathway   Myocardial infarction   Shenge powder   Sprague Dawley rats  

摘要： OBJECTIVES:To investigate the effect of Shenge powder (SGP) on myocardial fibrosis in rats with heart failure after myocardial infarction and its relation with lysyl oxidase like protein 2 (LOXL2)/transforming growth factor-β1 (TGF-β1)/IL-11 signaling pathway. METHODS:Seventy-two SPF male SD rats were divided into blank control group, model control group, SGP small dose group, SGP large dose group, positive control group, SGP large dose+LOXL2 activator group, with 12 rats in each group. Except for blank control group, post-myocardial infarction heart failure was induced by coronary constriction in all groups. Corresponding treatments were given immediately after successful modeling, once a day for 4 weeks. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in rats were detected by Color Doppler ultrasound imaging. Levels of IL-1β and IL-6 in serum were analyzed by ELISA method, Myocardial collagen volume fraction (CVF) was evaluated by Masson staining. Expressions of collagen Ⅰ and α-smooth muscle actin (α-SMA) in myocardial tissue were detected by immunohistochemical staining. The mRNA expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in myocardial tissue were detected by qRT-PCR. Expression of LOXL2, TGF-β1, and IL-11 proteins in myocardial tissue were detected by Western blotting. RESULTS:Compared with the blank control group, the LVFS and LVEF of the model control group decreased, the levels of serum IL-6 and IL-1β elevated, the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, expressions of - and - mRNA, and expressions of LOXL2, TGF-β1, and IL-11 proteins increased (all <0.05). Compared with the model control group, the LVFS and LVEF of SGP small dose group, SGP large dose group and positive control group increased, the levels of serum IL-6 and IL-1β decreased, the CVF value, the expressions of Collagen Ⅰ and α-SMA in myocardial tissue, express