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关键词： 化痰通络法   咳嗽变异性哮喘   气道重塑   白细胞介素-17   转化生长因子β1   血管内皮生长因子   血小板衍生生长因子  

摘要： 目的：研究化痰通络法对咳嗽变异性哮喘（cough variant asthma，CVA）豚鼠气道重塑相关细胞因子的影响，探讨化痰通络法治疗CVA的作用机制，为临床治疗提供依据。方法：将40只豚鼠随机分为正常组、模型组、孟鲁司特钠组及化痰通络组，以卵蛋白、氢氧化铝致敏并吸入卵蛋白激发法复制CVA豚鼠模型，观测肺组织病理形态学表现、白细胞介素-17(interleukin-17，IL-17)、转化生长因子β1(transform growth factor β1，TGF-β1)、血管内皮生长因子（vascular endothelial growth factor，VEGF）及血小板衍生生长因子（platelet-derived growth factor，PDGF)水平。结果：肉眼观察：模型组肺组织颜色暗红，个别可见瘀点、瘀斑，边缘较钝，充血水肿，体积增大，药物干预组豚鼠肺组织颜色较模型组浅，充血水肿程度较轻；HE染色：模型组肺组织支气管基底膜明显增厚，充血水肿明显，管腔变小，内可见黏液栓，炎性细胞浸润明显，支气管上皮细胞排列紊乱，肺泡壁破坏；药物干预组豚鼠肺组织支气管基底膜较模型组薄，充血水肿程度较轻，黏液栓减少，管腔相对完整且通畅，炎性细胞浸润较轻，肺泡腔较透亮；各组气道形态学参数：各组支气管基底膜周径（Pbm）组间比较无统计学差异（P＞0.05），模型组总管壁面积（Wat）较正常组增加（P＜0.05），化痰通络组较模型组Wat减小（P＜0.05），模型组管壁平滑肌面积（Wam）较正常组增加（P＜0.05），化痰通络组较模型组减小（P＜0.05），模型组Wat/Pbm、Wam/Pbm较正常组增大（P＜0.05），化痰通络组较模型组减小（P＜0.05）；细胞因子：模型组血清及支气管肺泡灌洗液（BALF）中IL-17、TGF-β1、VEGF及PDGF水平较正常组升高（P＜0.05），化痰通络组较模型组降低（P＜0.05）。结论：化痰通络法可能通过调节IL-17、TGF-β1、VEGF及PDGF水平，从而减轻气道重塑。

关键词： Chronic kidney disease   Metal nephrotoxicity   Tumor necrosis factor-alpha   Gene polymorphism   Transmembrane TNF-alpha  

摘要： Chronic kidney disease (CKD) is a progressive disorder often aggravated by environmental exposure to waterborne metal pollutants, such as lead (Pb), cobalt (Co), copper (Cu), and zinc (Zn).These metals induce renal injury predominantly through oxidative stress and inflammatory pathways, with tumor necrosis factor-alpha (TNF-alpha) serving as a key mediator. The study aimed to investigate the association of the TNF-alpha -308 G/A (rs1800629) gene polymorphism and transmembrane(Tm)-TNF-alpha expression with the risk and severity of metal-induced CKD. A case-control study was conducted, including 80 patients with CKD (40 with early-stage and 40 with late-stage disease) and 40 age- and sex-matched healthy controls, selected according to stringent inclusion criteria. Metal concentrations were quantified using inductively coupled plasma mass spectrometry (ICP-MS), TNF-alpha genotyping was performed via amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), and Tm-TNF-alpha levels were assessed by flow cytometry. The findings revealed that the A allele was significantly associated with increased CKD risk across dominant, recessive, and allelic genetic models. In a co-dominant model, the AA genotype conferred a fourfold and 15-fold higher risk for early- and late-stage CKD, respectively, compared to those with the GG genotype. Moreover, elevated Tm-TNF-alpha expression was significantly associated with the GA and AA genotypes and was most pronounced in late-stage CKD patients (p < 0.001). These findings suggest that the TNF-alpha -308 G/A polymorphism markedly enhances susceptibility to metal-induced CKD, driven by increased Tm-TNF-alpha expression. Understanding this genetic variation elucidates the pathogenesis of metal-induced nephropathy and offers new opportunities for early diagnosis and targeted therapeutic development.

关键词： IL-10   IL-10R   lung inflammation   interstitial macrophages   monocyte-derived macrophages   Th1 and Th17 cells   commensal bacteria   Delftia acidovorans   Rhodococcus erythropolis   gut-lung axis  

摘要： Crosstalk between the immune system and the microbiome is critical for maintaining immune homeostasis. Here, we examined this communication and the impact of immune-suppressive IL-10 signaling on pulmonary homeostasis. We found that IL-10 sensing by interstitial macrophages (IMs) is required to prevent spontaneous lung inflammation. Loss of IL-10 signaling in IMs initiated an inflammatory cascade through the activation of classical monocytes and CD4+ T cell subsets, leading to chronic lung inflammation with age. Analyses of antibiotic-treated and germ-free mice established that lung inflammation in the animals lacking IL-10 signaling was triggered by commensal bacteria. 16S rRNA sequencing revealed Delftia acidovorans and Rhodococcus erythropolis as potential drivers of lung inflammation. Intranasal administration of these bacteria or transplantation of human fecal microbiota elicited lung inflammation in gnotobiotic Il10-deficient mice. These findings highlight that IL-10 sensing by IMs contributes to pulmonary homeostasis by preventing lung inflammation caused by commensal dysbiosis.

关键词： macrophage   cancer therapy   immune suppression   Treg cell   cytokines   cell death   lymph node  

摘要： Apoptotic cells are immunosuppressive, creating a barrier in cancer treatment. Thus, we investigated immune responses to dying tumor cells after therapy in the tumor draining lymph node (TDLN). A key population responsible for clearing tumor material in the TDLN was medullary sinus macrophages (MSMs). Tumor debris phagocytosis by MSMs induces the cytokine IL-33, and blocking the IL-33 receptor (ST2) or deletion of Il33 in MSMs enhances therapy responses. Mechanistically, IL-33 activates T regulatory cells in TDLNs that migrate to the tumor to suppress CD8+ T cells. Therapeutically combining ST2 blockade, targeted kinase inhibitors, and anti-PD-1 immunotherapy increases CD8+ T cell activity promoting tumor regression. Importantly, we observe similar activity in human macrophages, and IL-33 expression in sentinel lymph nodes correlates with disease stage and survival in melanoma. Thus, our data identifies an IL-33-dependent immune response to therapy that attenuates therapy-induced anti-tumor immunity.

关键词： 新生儿   ABO   溶血病   用药剂量   免疫球蛋白   总胆红素  

摘要： 探讨免疫球蛋白不同剂量治疗新生儿ABO溶血病的疗效及安全性。方法 选取我院收治的120例新生儿ABO溶血病患者,分为对照组和观察组。对照组采用常规剂量人免疫球蛋白分三天注射法,观察组则实施单次给予高剂量免疫球蛋白的注射方案。对比分析不同剂量下的临床应用效果。结果 相较于对照组,观察组在黄疸消退时长、光疗时长、住院天数以及换血治疗的应用比例上均有显著降低(P<0.05)。观察组的HCT、Hb以及RBC的水平均显示出低于对照组的趋势(P<0.05)。观察组患者的IgG1与IgG3水平相较于治疗前及对照组均有显著提升(P<0.05)。比较两组间的不良反应发生率无显著差异(P>0.05)。结论 单次给予大剂量免疫球蛋白的注射策略,通过调节IgG1和IgG3水平能显著提高ABO溶血病新生儿的疗效,展现出较高的临床应用价值。

关键词： 心肌梗死   心力衰竭   参蛤散   纤维化   赖氨酰氧化酶样蛋白2/转化生长因子β1/IL-11信号通路   Sprague Dawley大鼠  

摘要： 目的:基于赖氨酰氧化酶样蛋白2(LOXL2)/转化生长因子β1(TGF-β1)/IL-11信号通路探讨参蛤散对心肌梗死后心力衰竭大鼠心肌纤维化的影响。方法:将SD大鼠分为空白对照组、模型对照组、参蛤散小剂量组、参蛤散大剂量组、阳性对照组、参蛤散大剂量+LOXL2激活剂组，每组12只。除空白对照组外，其他组均通过冠状动脉缩窄法构建心肌梗死后心力衰竭模型。建模成功后立即给药，1次/d，持续4周。彩色多普勒超声显像仪检测大鼠左心室短轴缩短率（LVFS）和左心室射血分数（LVEF）;ELISA法分析血清中IL-1β和IL-6水平；Masson染色评估大鼠心肌胶原容积分数（CVF）；免疫组织化学染色检测心肌组织中Ⅰ型胶原蛋白、α平滑肌肌动蛋白（α-SMA）平均光密度值；qRT-PCR检测心肌组织中基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制剂1(TIMP-1)mRNA表达；蛋白质印迹法检测心肌组织中LOXL2、TGF-β1、IL-11蛋白表达。结果:与空白对照组比较，模型对照组LVFS、LVEF降低，血清中IL-6和IL-1β水平升高，CVF、心肌组织中Ⅰ型胶原蛋白、α-SMA平均光密度值、MMP-9和TIMP-1 mRNA表达以及LOXL2、TGF-β1、IL-11蛋白表达均增加（均P<0.05）。与模型对照组比较，参蛤散小剂量组、参蛤散大剂量组、阳性对照组LVFS、LVEF升高，血清中IL-6和IL-1β水平降低，CVF、心肌组织中Ⅰ型胶原蛋白、α-SMA平均光密度值、MMP-9和TIMP-1 mRNA表达以及LOXL2、TGF-β1、IL-11蛋白表达减少（均P<0.05）。LOXL2激活剂可逆转大剂量参蛤散对心肌梗死后心力衰竭大鼠心肌纤维化的改善作用。结论:参蛤散可能通过调控LOXL2/TGF-β1/IL-11通路抑制心肌梗死后心力衰竭大鼠心肌纤维化。

关键词： adalimumab   adverse effects   Crohn's disease   dosage   drug interactions   efficacy   Entyvio   guselkumab   Humira   infliximab   lactation   mirikizumab   Omvoh   Otulfi   pregnancy   Pyzchiva   Remicade   Rinvoq   risankizumab   safety   Selarsdi   Skyrizi   Stelara   Steqeyma   TNF inhibitors   Tremfya   upadacitinib   ustekinumab   vedolizumab   Wezlana   Yesintek  

关键词： TNF   TNFR1   TNFR2   Tuberculosis   Anti-TNF therapy  

摘要： Tumor necrosis factor (TNF) is a key immunoregulatory cytokine with a dual role in the host response to Mycobacterium tuberculosis. While essential for granuloma formation, macrophage activation, and containment of latent infection, TNF can also contribute to tissue damage and immune pathology. This review systematically analyzes over 300 peer-reviewed studies published between 1980 and 2024, highlighting the molecular and cellular mechanisms of TNF action in tuberculosis (TB). Particular attention is given to TNF receptor signaling pathways, the balance between protective and pathological immune responses, and the modulation of TNF activity during anti-TNF therapy in patients with autoimmune diseases. We discuss how different TNF inhibitors vary in their capacity to interfere with host defense mechanisms, with monoclonal antibodies carrying a higher reactivation risk than receptor-based agents. To enhance conceptual clarity, we provide newly developed schematic representations that integrate current knowledge on TNF-driven immune dynamics, including its interaction with other cytokines, effects on granuloma stability, and role in intracellular bacterial control. Understanding the pleiotropic functions of TNF in tuberculosis pathogenesis is crucial for developing safe immunomodulatory strategies and optimizing the clinical management of patients at risk of latent TB reactivation.