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摘要： The sequence of HLA-DPA1*02:103 was identified using Oxford Nanopore sequencing in a Chinese kidney transplant patient.

关键词： coronary artery endothelial cells   dimethyl itaconate   I kappa B zeta   IVIG-resistant   Kawasaki disease  

摘要： Kawasaki disease (KD) is the most common childhood vasculitis. Approximately 25% of KD patients are refractory to standard intravenous immunoglobulin (IVIG) therapy and frequently develop coronary artery lesions (CAL) that result in long-term complications. Transcriptome studies utilizing blood cells from KD patients and reported animal model studies had identified interleukin (IL)-1 beta as a crucial component of an essential immune pathway in the formation of CAL. We previously reported that high-dose immunoglobulin G (IgG) treatment completely inhibited tumor necrosis factor (TNF)-alpha-stimulated inflammatory responses in an in vitro human coronary artery endothelial cells (HCAECs) model. Here, we show that IL-1 beta, but not TNF-alpha, stimulation markedly induced nuclear protein expression of NF-kappa-B inhibitor zeta (I kappa B zeta) in HCAECs. It is of particular significance that IL-1 beta-induced I kappa B zeta expression is entirely refractory to high-dose IgG treatment. Therefore, I kappa B zeta may be a critical factor in the IVIG-resistant vascular inflammatory responses in severe KD. Itaconate is a Krebs cycle-derived metabolite with several immunomodulatory effects. Dimethyl itaconate (DI), a membrane-permeable derivative of itaconate, can significantly suppress IL-1 beta-induced I kappa B zeta expression in HCAECs. DI is an analog of dimethyl fumarate (DMF), which is already in clinical use for some diseases. Like DI, DMF suppressed IL-1 beta-induced I kappa B zeta expression and subsequent production of inflammatory cytokines, including IL-6 and G-CSF. This study identified I kappa B zeta as an essential inflammatory factor in IVIG-resistant inflammatory responses in HCAECs. Immunomodulatory substances, such as DI and/or DMF, may be therapeutically exploited as a novel drug to alleviate inflammation in severe IVIG-resistant KD patients.

关键词： 针灸急救法   心跳骤停   血清白细胞介素-6   IL-1β  

摘要： 评价针灸急救法对于心跳骤停患者的救治效果。方法 选择两年内的69例心跳骤停患者,摸球分组,针灸组实行针灸急救法,复苏组实行徒手心肺复苏术,相比于急救效果等指标。结果 针灸组的急救总有效率、康复指标等均显著优于复苏组,即P<0.05。结论 针灸急救法可以提升心跳骤停患者的急救疗效,使患者尽快苏醒,而且可以稳定患者的血流动力学,减轻炎症反应。

关键词： fibroblast   Co2   glycolysis   aseptic loosening   proinflammatory cytokines  

摘要： Aims: The periprosthetic fibroblast-like cells (PPFs) play an important role in aseptic loosening after total hip arthroplasty (THA). However, little is known about fibroblast metabolism in aseptic loosening. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and il-6 interleukin-6 (IL-6) are involved in periprosthetic osteolysis. Cobalt (Co) ions are capable of inducing cytokines from macrophage. In this study, we investigated the effects of Co2+ on glycolysis and secretion of TNF-alpha and IL-6 in PPFs. Materials and methods: Fibroblasts were isolated from synovial tissues of osteoarthritis (OA) and rheumatoid arthritis (RA) patients, as well as from the periprosthetic pseudomembrane of patients undergoing revision surgery for aseptic loosening. Cells were cultured with or without Co2+. Following treatment, fibroblast viability was assessed using the MTT assay. To evaluate glycolysis, glucose uptake and lactate secretion were measured using specific assay kits. Furthermore, gene expression of key glycolysis enzymes (glucose transporter -1(GLUT1), hexokinase-2(HK2)) was analyzed by quantitative real-time PCR (qPCR), while protein expression of protein kinase B (AKT) and phosphorylated AKT (pAKT) was detected via Western blotting. Finally, TNF-alpha and IL-6 secretion into the culture supernatant was quantified using enzyme-linked immunosorbent assay (ELISA) kits. Results: Increased glucose uptake and lactic acid secretion occurred in PPFs. Exposure to Co2+ significantly increased glucose uptake, lactate secretion, GLUT1/HK2 mRNA expression, and TNF-alpha/IL-6 levels in PPFs. This Co2+-induced enhancement of glycolysis and cytokine secretion was dependent on glycolytic activity, as inhibition with 2-deoxy-D-glucose (2-DG) reduced all measured parameters. Furthermore, Co2+ stimulation increased pAKT protein expression in PPFs, indicating activation of the PI3K/AKT pathway. Consistent with this, treatment with the phosphatidylinositol three kina

关键词： 慢性牙周炎   IL-33   TNF-α   IL-6   检验效果  

摘要： 在慢性牙周炎的临床检验方面,分析血清白细胞介素-33(IL-33)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的临床检验价值。方法 将本院2023年1月至2024年1月收治的75例慢性牙周炎患者作为观察组,同时将同期75例健康体检者作为对照组,皆实行血清IL-33、TNF-α、IL-6水平检验,结果 进行对比,分析血清IL-33、TNF-α、IL-6检验在慢性牙周炎诊断中的价值。结果 观察组的IL-33水平较对照组更低,而IL-6、TNF-α水平较对照组更高,差异有统计学意义(P<0.05)。重度牙周炎的IL-33水平较轻度牙周炎与中度牙周炎更低,而IL-6、TNF-α水平较轻度牙周炎与中度牙周炎更高,差异有统计学意义(P<0.05)。血清IL-33与TNF-α、IL-6具有相关性,差异有统计学意义(P<0.05)。结论 针对慢性牙周炎开展血清IL-33、TNF-α、IL-6检验,能够帮助诊断疾病,并评估牙周炎病情程度,值得推广。

关键词： HLA   HLA-A*29:02:42   novel allele   sequencing-based typing  

摘要： HLA-A*29:02:42 differs from HLA-A*29:02:01:01 by one nucleotide substitution in codon 193 in exon 4.

关键词： WAS   HIES   DOCK8   STAT3   IL-6  

摘要： Wiskott-Aldrich syndrome (WAS) is an inborn error of immunity caused by loss-of-function mutations in the WAS gene, which encodes WASp, a key regulator of cytoskeletal remodeling. In addition to microthrombocytopenia, affected individuals often present with recurrent infections, eczema, eosinophilia and elevated IgE levels, suggesting a potential pathophysiological overlap with STAT3 hyper-IgE syndrome (HIES). Given these shared features, we investigated the immunogenetic characteristics of three WAS patients and explored the IL-6/STAT3 pathway as a potential underlying mechanism. Flow cytometry revealed absent WASp expression in P1 and P3, while P2 showed reduced level. Genetic analysis identified three hemizygous mutations: A56V substitution within the WH1 domain in P1, and two splice site mutations, c.360 + 1G>T and c.734 + 1G>C, in P2 and P3, respectively. Interestingly, all WAS patients showed impaired STAT3 phosphorylation in T cells following IL-6 stimulation and SOCS3 induction was markedly decreased. These results further suggest a potential link between WASp and STAT3. Considering the interaction of WASp with DOCK8-WIP in lymphocytes and the critical role of DOCK8 in regulating STAT3 phosphorylation following IL-6 stimulation, we analyzed DOCK8 expression in lymphoblastoid cell lines. We demonstrated normal DOCK8 levels suggesting that STAT3 signaling defect is due to the absence of WASp rather than DOCK8 loss. Our results demonstrate the impairment of T cell IL-6/STAT3 pathway in WAS patients which could underlie, in part, the overlapping phenotype with HIES patients.

关键词： Coronary artery   Fibrous cap thickness   Inflammation   Interleukin-6   Myocardial Infarction   Optical coherence tomography  

关键词： asciminib hydrochloride   atherosclerosis   cardio-oncology   endothelial cells   imatinib mesylate   inflammation   ponatinib hydrochloride  

摘要： BACKGROUND:Imatinib, the first Abl-tyrosine kinase inhibitor (TKI), improved leukemia outcomes without cardiovascular side effects. Newer agents, including ponatinib, addressed imatinib resistance, improving cancer remission, but substantially increased arterial thrombotic events, including myocardial infarction (MI) and stroke. The mechanism behind ponatinib-induced thrombosis and the cardiovascular effect of asciminib, a newly approved Abl-TKI, remain ***:The effect of clinically relevant plasma concentrations of imatinib, ponatinib, and asciminib were compared with vehicle in vivo using SR-BI-mut/LDLR-knockout (KO) mice to assess spontaneous MI and stroke risk. The mechanism was interrogated in C57BL/6J mice, assessing leukocyte trafficking and thromboinflammation by intravital microscopy and flow cytometry, respectively, and in ApoE-KO mice, assessing plaque phenotype by flow cytometry and histology. In vitro effects on human umbilical vein endothelial cells (ECs) and human coronary artery ECs were determined by flow cytometry, PCR, and immunoblotting. The role of TNF (tumor necrosis factor) signaling was evaluated by pharmacological inhibition and small interfering RNA ***:In SR-BI-mut/LDLR-KO mice, ponatinib significantly accelerated death from MI and stroke compared with vehicle, imatinib, and asciminib. In human ECs, only ponatinib increased expression of TNF receptors (TNFRs) and adhesion molecules (P-selectin, ICAM1 [intercellular adhesion molecule 1], and VCAM1 [vascular cell adhesion molecule 1]). Ponatinib rapidly induced TNFR2 membrane trafficking and TNF signaling in human umbilical vein ECs. TNFR inhibition or TNFR2 knockdown prevented ponatinib induction of EC adhesion molecules. In vivo, ponatinib increased mesenteric vessel adhesion molecules, leukocyte rolling and adhesion to vessels, leukocyte and platelet activation, and platelet-leukocyte aggregates. In ApoE-KO mice, ponatinib increased plaque necrotic core and inflam

摘要： comprises over 2500 serovars that are responsible for over 90 million annual infections and 100,000 deaths worldwide. Despite this diversity, our understanding of innate immune responses to is based on extensive study of a few serovars, primarily Typhimurium, including strains that cannot replicate within primary murine macrophages. Non-replicating trigger caspase-1 and -11-dependent pyroptosis. Whether the innate immune system distinguishes between replicating and non-replicating intracellular is poorly defined. Here we demonstrate that replicating induce a distinct pathway of TNF- and caspase-8-driven apoptosis via host TLR4 and Pathogenicity Island-2 activity. This pathway is independent of gasdermin D and involves the apoptotic pore protein Pannexin-1. Combined loss of Pannexin-1 and gasdermin D resulted in defective control of systemic , indicating that these pathways function together to promote anti- host defense. Altogether, our findings uncover a previously unappreciated pathway by which macrophages sense intracellular replicating bacteria.