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关键词： allergic disease   birth cohort   HLA   phenome-wide association study   polygenic score   atopic march   immunoglobulin E   food allergy   atopic dermatitis   genetic predisposition  

摘要： The atopic march lacks early identification methods for high-risk children. In this study, we assessed whether the risk of atopic diseases in infants could be predicted using a polygenic score (PGS) for total immunoglobulin E (IgE) levels. The PGS estimated using the poly-genic model generated by PRS-CS was significantly correlated with log-transformed IgE levels (rho = 0.200, p < 2.2 x 10(-16)). Assessment of the risk from birth to 2 years of age in a Japanese birth cohort (n = 17,154) applying the estimated PGS revealed significantly elevated incidence risk ratios in the highest PGS quintile (Q5) compared with those in the reference quintiles (Q1-Q3) for food allergy (1.51-fold;95% confidence interval: 1.30-1.76), atopic dermatitis (1.30-fold;1.12-1.51), and both conditions (1.88-fold;1.46-2.43). These findings address critical gaps in allergy and PGS research among non-European populations, suggesting the contribution of genetic predisposition to IgE production in early-onset allergic diseases and supporting the use of PGS in early intervention.

关键词： Interleukin-1 receptor 2   Colorectal cancer   Immune checkpoint   CTLA-4   PD-1  

摘要： Colorectal cancer (CRC) continues to be a major global health challenge due to its high incidence and mortality rates, emphasizing the critical need for innovative therapeutic strategies. IL-1R2, a member of the IL-1 receptor family, plays a pivotal role in both tumorigenesis and antitumor immunity. However, its precise role in tumor development and its impact on immune checkpoint inhibitors (ICIs) therapy in CRC remain poorly understood. We examined tumor progression in wild-type and IL-1R2-deficient mice using an AOM/DSS-induced colitis-associated colorectal cancer model treated with combined ICIs therapy. Our findings revealed that IL-1R2 deficient mice exhibited a significant reduction in tumor burden, accompanied by alterations in the carcinogenic program and enhanced immunogenicity of tumor cells. Furthermore, the deletion of IL-1R2 resulted in an increased proportion of exhausted CD8+ T cells, a population commonly enriched for tumor antigen-specific T cells, suggesting an augmentation of tumor-specific immune responses. Moreover, IL-1R2 deletion upregulated genes linked to antigen presentation in dendritic cells, indicating enhanced activation of the adaptive immune system. Collectively, these findings position IL-1R2 as a promising therapeutic target for improving the efficacy of treatment strategies in CRC.

关键词： 自身免疫病   嵌合抗原受体T细胞疗法   中医药优势  

摘要： 自身免疫病（AID）目前主要依赖系统性免疫抑制治疗，虽可缓解症状，但需长期甚至终生用药，伴随较高的不良反应发生率及复发风险。嵌合抗原受体T(CAR-T)细胞疗法近年来在AID中的应用取得积极进展，展现出重塑免疫系统的潜力，为AID的潜在治愈性带来可能。在CAR-T细胞疗法的强大疗效背景下，传统中医药如何实现精准协同、发挥特色优势，成为值得探讨的课题。笔者梳理CAR-T细胞疗法治疗AID的最新进展与挑战，探索中医药的潜在切入点，旨在为未来两者协同应用提供理论依据与参考。

关键词： antitumor immunity   antiviral immunity   CD8+ T cells   dendritic cells   galectin-4  

摘要： Galectin-4 (Gal-4), a member of the beta-galactoside-binding galectin family, plays a role in various physiological processes, including tumor progression and intestinal disorders. However, its contribution to adaptive immunity remains poorly understood. In this study, Gal-4 is identified as a critical factor for effective generation of CD8+ T cell responses against tumors and viral infections. Gal-4-deficient mice exhibit significantly enhanced tumor growth in syngeneic mouse cancer models, attributed to impaired CD8+ T cell responses. Similarly, antiviral CD8+ T cell responses against lymphocytic choriomeningitis virus (LCMV) are profoundly diminished in Gal-4-deficient mice. This is not due to CD8+ T cell-intrinsic defects but instead linked to decreased surface expression of antigen-MHC-I complexes on dendritic cells. Building on these findings, the therapeutic potential of Gal-4 is investigated. Administration of Gal-4 enhances the efficacy of cancer vaccines and PD-1 blockade cancer therapy to improve outcomes in tumor-bearing mice. Additionally, systemic administration of Gal-4 markedly amplifies antiviral CD8+ T cell responses against LCMV. Collectively, these results underscore the pivotal role of Gal-4 in modulating CD8+ T cell immunity and highlight its promise as a therapeutic target for the development of novel immunotherapeutics against cancer and viral diseases.

关键词： spondyloarthritis   HLA-B*27-negative   immunogenetics   Romanian cohort   cross-reactivity  

摘要： This study examined the distribution and disease associations of non-HLA-B*27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B*27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping was performed at two-digit resolution, and allele distributions were compared with two Romanian HLA-B*27-negative control groups (n = 335 and n = 1705 cases), using chi-square testing and logistic regression. Compared to controls, HLA-B*47 (p = 0.0007) and HLA-B*54 (p = 0.0013) were significantly enriched, while HLA-B*40 was underrepresented (p = 0.0287). Notably, HLA-B*54 was observed exclusively in axial SpA. Within the cohort, both HLA-B*13 and HLA-B*57 alleles were associated with psoriasis, while HLA-B*37 and HLA-B*41 alleles were clustered within the reactive arthritis group. The HLA-B*35 and HLA-B*18 alleles were the most frequently observed alleles across most clinical phenotypes. When comparing the frequency of HLA-B associations, the most common genotypes among SpA patients were B*08-B*18, B*13-B*35, and B*35-B*51. Notably, B*08-B*18 was more frequent in patients with radiographic sacroiliitis grade >= 2, while B*35-B*51 was more frequent in those with confirmed systemic inflammation, as indicated by elevated CRP or ESR levels. Analysis of peptide-binding patterns revealed a cluster of risk alleles, HLA-B*08, B*18, B*35, B*40, and B*54, sharing similar features, distinct from the canonical profile of B*27. These findings highlight the contribution of non-B*27 HLA-B alleles to SpA susceptibility in an Eastern European population and support the notion that HLA-B*27-negative SpA may represent a distinct clinical and immunological entity, driven by alternative pathogenic mechanisms. They also emphasize the importance of population-specific immunogenetic profiling and support expanding genetic characterizat

关键词： advanced cardiac imaging   Castleman disease   giant coronary artery aneurysm   interleukin-6   AAA   abdominal aortic aneurysm   CAA   coronary artery aneurysm   CD   Castleman disease   CMR   cardiac magnetic resonance   CT   computed tomography   ECG   electrocardiogram   ECM   extracellular matrix   IL   interleukin   MMP   matrix metalloproteinase   RCA   right coronary artery   TAA   thoracic aortic aneurysm  

摘要： Background Giant coronary artery aneurysms (CAAs), defined as aneurysms exceeding 20 mm, are rare vascular anomalies with potentially life-threatening complications such as thrombosis, embolization, and rupture. CCAs are typically linked to atherosclerosis and vasculitis, and their occurrence in Castleman disease (CD), a rare lymphoproliferative disorder, is exceedingly rare. Case Summary A 68-year-old man presented with a large right atrial mass on echocardiography, later identified on coronary computed tomography angiography and cardiac magnetic resonance imaging as a giant right coronary artery aneurysm with thrombus. Discussion This case highlights a rare presentation of a giant CAA associated with CD and the potential role of interleukin-6 (IL-6) in aneurysm pathogenesis in CD. Additionally, this case underscores the importance of multimodal imaging in diagnosis and management. Further research is needed to explore the link between IL-6 dysregulation in CD and vascular abnormalities. Take-Home Messages CD may contribute to vascular abnormalities via IL-6-mediated inflammation. Multimodal imaging is essential for diagnosing giant CAAs and guiding appropriate intervention.

关键词： 天麻钩藤饮   血管性痴呆   星型胶质细胞   TNF-α/STAT3/α1ACT通路  

摘要： 目的：探究天麻钩藤饮对血管性痴呆模型大瘤坏死因子-α（TNF-α）/信号转导与转录激活因子3（STAT3）/α1-抗胰蛋白酶C末端尾片段?（α1ACT）通路及A1星型胶质细胞的影响。方法：将72只雄性SD大鼠随机分为假手术组，模型组，天麻钩藤饮高、中、低剂量组（5.13、10.26、20.52 g·kg?1）及尼莫地平西药组（8.1 mg·kg?1），每组12只。采用永久性双侧颈总动脉闭塞法造模后干预4周。通过新物体识别实验评估学习记忆能力；强迫游泳实验观察行为症状；酶联免疫吸附测定?检测海马组织白细胞介素6（IL-6）、CC趋化因子配体2（CCL2）水平；尼氏染色观察海马神经元形态；TUNEL染色检测细胞凋亡；免疫组化检测脑源性神经营养因子（BDNF）、胶质纤维酸性蛋白（GFAP）、髓鞘碱性蛋白（MBP）阳性表达；蛋白免疫印迹法测海马组织TNF-α、TNF受体1（TNFR1）、磷酸化STAT3（p-STAT3）、α1ACT、IL-6、补体C3（Complement Component 3）、BDNF、S100钙结合蛋白A10（S100A10）、GFAP蛋白表达。结果：与假手术组比较，模型组大鼠新物体相对识别指数显著降低（P<0.01），被动漂浮时间延长、次数增多（P<0.01）；海马组织IL-6、CCL2表达升高（P<0.01），尼氏染色显示神经元数量减少、尼氏小体丢失（P<0.01），MBP阳性表达降低（P<0.01），细胞凋亡增多（P<0.01），BDNF阳性表达减少（P<0.05），GFAP阳性表达升高（P<0.01），TNF-α、TNFR1、p-STAT3、α1ACT、IL-6、C3蛋白表达升高（P<0.01），BDNF、S100A10降低（P<0.01）。与模型组比较，天麻钩藤饮各剂量组新物体相对识别指数显著升高（P<0.05），被动漂浮时间缩短、次数减少（P<0.01，P<0.05），IL-6、CCL2表达降低（P<0.01），神经元数量增加（P<0.01，P<0.05），MBP阳性表达增加（P<0.01），细胞凋亡减少（P<0.01），BDNF阳性表达增加（P<0.05），GFAP阳性表达降低（P<0.01），TNF-α、TNFR1、p-STAT3、α1ACT、IL-6、C3蛋白表达降低（P<0.01），BDNF、S100A10蛋白表达升高（P<0.01）。结论：天麻钩藤饮治疗可以通过TNF-α/STAT3/α1ACT通路抑制血管性痴呆大鼠A1型星型胶质细胞激活，减轻神经元凋亡，提高学习记忆能力。

关键词： HLA-DQB1*03:570   new allele   NGS  

摘要： HLA-DQB1*03:570 differs from HLA-DQB1*03:02:01:02 by a single nucleotide polymorphism in exon 4, codon 207.

关键词： IL-17A   cardiopulmonary bypass   endoplasmic reticulum stress   neuronal apoptosis  

摘要： Cardiopulmonary bypass (CPB) is associated with significant neurological complications, yet the mechanisms underlying brain injury remain unclear. This study investigated the role of interleukin-17A (IL-17A) in exacerbating CPB-induced neuronal apoptosis and identified vulnerable brain regions. Utilizing a rat CPB model and an oxygen-glucose deprivation/reoxygenation (OGD/R) cellular model, we demonstrated that IL-17A levels were markedly elevated in the hippocampus post-CPB, correlating with endoplasmic reticulum stress (ERS)-mediated apoptosis. Transcriptomic analysis revealed the enrichment of IL-17 signaling and apoptosis-related pathways. IL-17A-Neutralizing monoclonal antibody (mAb) and the ERS inhibitor 4-phenylbutyric acid (4-PBA) significantly attenuated neurological deficits and hippocampal neuronal damage. Mechanistically, IL-17A activated the Act1-IRE1-JNK1 axis, wherein heat shock protein 90 (Hsp90) competitively regulated Act1-IRE1 interactions. Co-immunoprecipitation confirmed the enhanced Hsp90-Act1 binding post-CPB, promoting IRE1 phosphorylation and downstream caspase-12 activation. In vitro, IL-17A exacerbated OGD/R-induced apoptosis via IRE1-JNK1 signaling, reversible by IRE1 inhibition. These findings identify the hippocampus as a key vulnerable region and delineate a novel IL-17A/Act1-IRE1-JNK1 pathway driving ERS-dependent apoptosis. Targeting IL-17A or Hsp90-mediated chaperone switching represents a promising therapeutic strategy for CPB-associated neuroprotection. This study provides critical insights into the molecular crosstalk between systemic inflammation and neuronal stress responses during cardiac surgery.

关键词： Cell death   Fenpropathrin   Inflammation   Sambucus Nigra   TNF-alpha   NF-kappa B  

摘要： This research assessed the effectiveness of Sambucus nigra (SN) in alleviating hepatorenal injury caused by fenpropathrin (FNP) in rodents. Six equal groups were created from the 30 Wistar rats: Group 1 was the negative control, Groups 2 and 3 were the SN control groups, Group 4 was the FNP group, and Groups 5 and 6 were the FNP + SN combination groups. The hepatoprotective and renoprotective effects of SN were assessed by quantifying serum enzyme markers, including ALT, AST, ALP, blood urea nitrogen, and creatinine. Oxidative stress indicators, RT-PCR analysis, histological examination, and immunohistochemistry studies were conducted on the liver and kidneys to confirm the previously indicated parameters. The rats administered FNP injections displayed increased blood marker enzyme levels, altered oxidant-antioxidant equilibrium, and significant pathogenic changes in hepatic and renal tissues. Furthermore, these rats exhibited elevated levels of caspase-3 and iNOS, linked to the triggered expression of TNF-alpha and NF-kappa B genes in these tissues. Administering SN enhanced all the aforementioned toxicological parameters. The prospective hepato-renal therapeutic benefits of SN against impairment of the liver and kidneys induced by FNP have been evidenced through its anti-inflammatory, antioxidant, and anti-apoptotic pathways.