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关键词： 布鲁氏菌病   成纤维细胞生长因子21   乳糖凝集素-3   白细胞介素-33   诊断  

摘要： 目的 探讨成纤维细胞生长因子21（FGF21）、半乳糖凝集素-3（Gal-3）、白细胞介素-33（IL-33）联合检测对人布鲁氏菌病的诊断价值。方法 选取2023年1月至2025年1月在新疆维吾尔自治区人民医院收治的布鲁氏菌病患者100例设为布病组，其中急性期41例，慢性期59例；另选取同期本院的体检健康者62例为对照组。ELISA检测血清FGF21、Gal-3、IL-33水平；急性期患者给予多西环素联合利福平治疗1个疗程（≥6周），并辅以解热镇痛、营养支持及免疫调节。慢性期患者按上述抗生素联合方案治疗3个疗程，必要时联合喹诺酮类或三联抗生素方案。结果 对照组、慢性布病组与急性布病组患者肝功能指标ALT、AST、DBil及血常规指标WBC、PLT、NEUT、HGB比较，差异有统计学意义（P＜0.05）；治疗前后布病组血清FGF21、Gal-3、IL-33水平均高于对照组（P＜0.05）；急性期和慢性期患者治疗前的血清FGF21、Gal-3、IL-33水平均高于治疗后水平（P＜0.05），且急性期三者水平均高于慢性期（P＜0.05）；FGF21（OR=3.247，95%CI：1.748～6.032）、Gal-3（OR=2.853，95%CI：1.603～5.076）及IL-33（OR=2.915，95%CI：1.674～5.076）水平升高是影响布鲁氏菌病发生的危险因素（P＜0.05）；FGF21、Gal-3、IL-33三者联合诊断布鲁氏菌病的AUC为0.978，联合诊断价值优于FGF21、Gal-3、IL-33单独诊断（P＜0.05）。结论 布鲁氏菌病患者血清FGF21、Gal-3、IL-33水平均显著升高，三者联合检测对人布鲁氏菌病具有较高诊断价值。

摘要： Aberrant expression of the oncogene SALL4 is associated with stemness, more aggressive cancer phenotype, and reduced patient survival in various tumor types making SALL4 a potential target for cancer immunotherapy. We conducted a transcriptional analysis of SALL4 expression in colorectal cancer (CRC) tissues and demonstrated that SALL4 was overexpressed in primary tumor and paired liver metastasis. Then, we identified the SALL4-derived S9V peptide as a naturally processed peptide that induced specific CD8+ T-cell responses from the peripheral blood of gastrointestinal cancer patients whereas no responses were observed for the peripheral blood of healthy donors. Thereafter, we isolated a SALL4-specific T-cell receptor (TCR) that recognized this peptide in the most common HLA molecule in the Caucasian population, HLA-A2, and used this to develop TCR-engineered T cells. In vitro analysis showed that SALL4 TCR-redirected primary CD8+ T cells exhibited cytotoxic effects against SALL4-expressing tumor cells and produced effector cytokines. In vivo, SALL4-TCR T cells significantly reduced tumor growth and improved survival of tumor-bearing mice. Moreover, SALL4-TCR T cells displayed no toxicity against hematopoietic stem cells. Thus, we conclude that T cells engineered to express a SALL4-specific TCR have the potential to be effective as immunotherapy for solid cancers and pave the way for further clinical development.

关键词： 纳米材料   生物标志物   生物传感器   免疫球蛋白G(IgG)   IgG检测  

摘要： 免疫球蛋白G（IgG）作为体液免疫系统的核心效应分子，在疾病诊断、疗效评估及感染监测中发挥着不可替代的生物标志物作用，其精准检测是个性化医疗的重要技术基石。纳米材料凭借其高比表面积效应、可调控表面化学特性及多重信号转换能力，为构建新型IgG生物传感器提供了创新性解决方案，突破了传统检测方法在灵敏度、检测限及成本控制方面的技术瓶颈。该文章系统综述了基于贵金属纳米材料、金属衍生纳米材料、碳基纳米材料、量子点纳米材料和稀土掺杂上转换纳米材料等生物传感器在检测IgG中的应用现状，并进行了优劣势分析，为开发高灵敏、低成本、便携式IgG检测生物传感器提供思路和依据。

关键词： IFN-α and IFN-γ responses   Mendelian susceptibility to mycobacterial diseases   STAT1 TSD mutation   autosomal dominant STAT1 deficiency   cytokine signaling defect   hepatosplenomegaly   immune dysfunction   loss-of-function mutation   mycobacterial infection   primary immunodeficiency  

摘要： Signal transducer and activator of transcription 1 (STAT1) mutations are associated with diverse pathologies. Loss-of-function (LOF) heterozygous mutations impair interferon (IFN) signaling, predisposing to Mendelian susceptibility to mycobacterial diseases (MSMDs). This study characterizes a novel STAT1 LOF mutation in a patient with multisystem manifestations. A patient presenting with mycobacterial infection, skeletal abnormalities, and systemic inflammation underwent whole-exome sequencing. The identified STAT1 variant was analyzed via computational tools (PolyPhen-2/SIFT). Molecular biological validation included IFN-α/γ-induced STAT1 phosphorylation assays and fluorescence microscopy for subcellular localization. Clinical features included mycobacterial osteomyelitis, severe rash, dwarfism, hepatosplenomegaly, and elevated inflammatory markers (C-reactive protein/erythrocyte sedimentation rate). A heterozygous STAT1 mutation (NM_007315.4:c.2120T>C; ***707Thr) was identified and predicted as pathogenic. Mutant cells showed reduced STAT1 phosphorylation (64% versus wild-type, < 0.05) and impaired nuclear translocation post-IFN-α/γ stimulation. Antibiotic therapy achieved clinical resolution without complications. These findings indicated that the STAT1 I707T mutation disrupts IFN-α/γ immunity, expanding the MSMD genotypic spectrum. Genetic screening for STAT1 defects is critical in patients with mycobacterial infections involving skin. Molecular biological studies corroborate mutation pathogenicity, guiding therapeutic decisions.

摘要： Nanoparticles have gained prominence in the formulation of nanopesticides, leveraging their unique nanocharacteristics. This study delves into the nephrotoxic implications of CuONanoSheet (CuONS), as nanopesticide tailored for agricultural applications to understand its safety and viability in this field. The nanocharacterization of CuONS was meticulously examined using X-ray diffraction, high-resolution transmission electron microscopy, field emission scanning electron microscopy and Zeta-Sizer device, which assessed zeta-potential, hydrodynamic size, and polydispersity index. Rats treated with CuONS showed elevated levels of blood urea nitrogen, creatinine, and uric acid and a significant increase in lipid peroxidation (MDA) and reduced levels of antioxidant enzymes. CuONS treatment resulted in an imbalance in pro-apoptotic Bax and anti-apoptotic B-cell lymphoma2 (Bcl2) levels. Histologically, CuONS induced glomerulus degeneration and vacuolation in tubules lining epithelium. Immunohistochemical evaluations revealed strong expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), tumor necrosis factor-alfa (TNF-α), and the tumor suppressor gene (p53) in CuONS-treated kidneys. Ultrastructural assessments further confirmed these structural abnormalities. While CuONS exhibits potential as a nanopesticide, caution is warranted due to observed negative impacts on kidney functions, and histological architecture, in this study. Careful consideration of potential side effects on other living organisms is imperative in the utilization of CuONS in agricultural practices.

关键词： EMCV   IFN-β   antiviral   gallic acid  

摘要： Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen with global distribution, which has caused huge serious economic losses to the development of the livestock industry. Gallic acid (GA) is an active ingredient of traditional Chinese medicine with wide pharmacological and biological activities and is also a potential antiviral drug. However, its antiviral effect and mechanism of anti-EMCV are still unclear. In the present study, we found that therapeutic administration of GA could significantly reduce the viral load and viral titer of EMCV to inhibit EMCV replication in a dose-dependent manner. GA could also protect cells infected by EMCV and decrease the content of capsid protein VP1 of EMCV in HEK-293 cells. Additionally, the mechanistic investigations revealed that GA might exert antiviral effects by regulating the interaction between TBK1 and IRF3 to promote the IFN-β expression. Meanwhile, GA could also alleviate EMCV-infected mice. These results indicate that GA may serve as a novel antiviral agent against EMCV *** a zoonotic pathogen, encephalomyocarditis virus (EMCV) causes myocarditis, encephalitis, neurological disease, reproductive disorders, and diabetes in pigs, which seriously endangers the development of the swine industry worldwide. However, due to the lack of effective commercial vaccines, there is an urgent need to develop safe and effective drugs against EMCV. Gallic acid (GA) has wide pharmacological and biological activities. However, the antiviral effect and the mechanism of GA are currently unknown. Here, we demonstrated that GA had a significant anti-EMCV effect. Further research found that GA inhibited EMCV infection via targeting the interaction between TBK1 and IRF3 to promote the IFN-β expression. These findings indicate that GA could be an effective anti-EMCV drug.

关键词： 红细胞血型   同种免疫   人类白细胞抗原(HLA)   等位基因   综述  

摘要： 红细胞同种免疫是个体在输血或妊娠过程中，接触到与自身血型抗原不同的红细胞后引发的免疫反应，可引起临床输血交叉配血不合、溶血性输血反应、新生儿溶血病的发生。人类白细胞抗原（HLA）基因多态性对红细胞血型抗原引发的同种异体免疫反应具有重要作用。本文介绍了Rh、Duffy、Kell、Kidd、MNS等多个红细胞血型系统抗原同种免疫与HLA基因多态性相关性在不同地区和种族的遗传背景的研究现状及进展。其中，Rh血型系统抗原的同种免疫倍受关注。

关键词： Ageing   Genetic association study   Human leukocyte antigen   Immunogenetics   Longevity  

摘要： BACKGROUND:Prior research on the genetics of human longevity has identified only a few robust associations. While these studies highlight the importance of metabolic processes for longevity, the contribution of immune genes, specifically those in the highly polymorphic human leukocyte antigen (HLA) region, remains understudied. Here, we addressed this gap by analysing the influence of HLA variation on longevity in Europeans. METHODS:We conducted an initial case-control study, comparing imputed HLA alleles from a German longevity cohort with younger controls. Associations were evaluated with logistic regression, adjusting for multiple testing and population structure. Subsequently, significant associations (adjusted P ≤ 0.05) were tested for replication in two additional populations of similar ancestry: a Danish longevity cohort and the UK Biobank. Furthermore, epitope binding and immunogenicity predictions were performed to detect potential mechanisms linking HLA alleles to longevity. RESULTS:Our analysis revealed a novel male-specific association of HLA-DRB1*15:01:01 with longevity (adjusted P = 2.80 × 10, odds ratio = 0.64, 95% CI: 0.48-0.82). In Germans, HLA-DRB1*15:01:01 was less frequent among male cases (10%) than controls (15%), whilst female cases exhibited no substantial decrease (14%), suggesting that men carrying this allele have a lower chance of becoming long-lived. This finding was replicated in the UK Biobank and found to be consistent in the Danish cohort. Computational predictions further revealed that HLA-DRB1*15:01 is more likely to trigger an immune response against an apolipoprotein B-100 (APOB-100) epitope than other HLA-DRB1 alleles. Furthermore, the overall predicted APOB-100 immunogenicity of all HLA-DRB1 alleles was significantly associated with longevity (estimate -0.11, SE = 0.03, P = 0.005). CONCLUSIONS:The novel male-specific association between HLA-DRB1*15:01 and longevity has been observed in three independent cohorts. The anti-longev

关键词： Intervertebral disc degeneration   Paeonol   Nucleus pulposus cell   MAPK pathway  

摘要： Objectives: Our study sought to examine paeonol's effects and possible regulatory mechanism in intervertebral disc degeneration (IDD). Methods: In human nucleus pulposus (NP) cells, interleukin-1(3 (IL-1(3) was used to construct IDD cell model. Cell viability, senescence, and apoptosis were checked utilizing cell counting kit-8 assay, (3-galactosidase staining, and flow cytometry. The related indicators of cell senescence (cyclin dependent kinase inhibitor 2A, p16INK4a), apoptosis [Bcl-2-associated X protein (Bax) and cleaved caspase-3 (C-caspase-3)], inflammation [interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)], extracellular matrix (ECM) degradation [(Collagen II, matrix metallopeptidase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5)], and mitogen-activated protein kinase (MAPK) pathway (p38 and p-p38) were examined by reverse transcription-quantitative polymerase chain reaction, Western blot, or immunofluorescence staining. The possible molecular mechanism of paeonol was explored via network pharmacology analysis. Results: Under IL-1(3 treatment, paeonol enhanced NP cell viability, inhibited cell senescence and apoptosis, impeded inflammation and ECM degradation. Furthermore, paeonol reduced the levels of p16INK4a, Bax, C-caspase-3, IL-6, iNOS, COX-2, MMP13, and ADAMTS5 and increased Collagen II levels. Network and pharmacology analysis revealed that paeonol was associated with MAPK signaling pathway and there was a binding between paeonol and MAPK14 (also known as p38). The levels of p38 and p-p38 were decreased by paeonol. In addition, paeonol's promotion on NP cell viability and inhibition on NP cell apoptosis, inflammation, and ECM degradation were reversed by p38 overexpression. Conclusions: Paeonol exerted a protective role on alleviating IDD by attenuating NP cell apoptosis, inflammation, and ECM degradation through the inhibition of MAPK signaling pathway.