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关键词： 分枝杆菌，结核   干扰素类   白细胞介素2   诊断，鉴别   肺外结核  

摘要： 目的：评估结核分枝杆菌（Mycobacterium tuberculosis，MTB）特异性细胞因子[γ-干扰素（IFN-γ）和白细胞介素2（IL-2）]检测联合常见实验室指标对肺外结核的辅助诊断价值。方法：采用前瞻性研究方法，连续纳入2023年8月至2024年9月在西安市胸科医院住院治疗的158例肺外结核患者作为肺外结核组；选取同时期在西安市胸科医院住院治疗的107例非结核性肺外疾病患者作为对照组。对所有研究对象行MTB特异性双因子检测、分枝杆菌培养、实时荧光定量PCR检测（qRT-PCR）、实时荧光RNA恒温检测（SAT-TB）、MTB核酸检测（恒温扩增DNA）、GeneXpert MTB/RIF检测（简称“GeneXpert”）和抗酸杆菌涂片镜检检测，以及降钙素原（PCT）、C反应蛋白（CRP）、全身免疫炎症指数（SII）、中性粒细胞/淋巴细胞比值（NLR）和血小板/淋巴细胞比值（PLR）检测，评价MTB特异性双因子单独及联合常见实验室指标（PCT、CRP、SII、NLR和PLR）对肺外结核的辅助诊断价值。结果：以临床诊断为参照标准，MTB特异性双因子检测的敏感度、特异度、阳性预测值、阴性预测值分别为：78.48%（124/158）、71.96%（77/107）、80.52%（124/154）和69.37%（77/111），敏感度均高于其他6种方法，约登指数（0.504）和一致性检验Kappa值（0.501）均高于其他6种检测方法。方法学比较中，血清学组（MTB特异性双因子）技术的检测阳性率为78.48%（124/158），明显高于分子生物学组（qRT-PCR、SAT-TB、Xpert和恒温扩增DNA）技术和细菌学组（分枝杆菌培养和抗酸杆菌涂片镜检）技术的检测阳性率[分别为：39.87%（63/158）和26.58%（42/158）]，差异均有统计学意义(χ2值分别为48.743和85.333，P均＜0.001)。实验室指标比较中，肺外结核组的PCT、CRP、SII、PLR水平分别为0.00（0.00，0.09）pg/ml、24.08（3.56，71.69）mg/L、976.76（571.92，2159.82）和190.66（135.02，267.31）；对照组的PCT、CRP、SII、PLR水平分别为0.06（0.00，0.18）pg/ml、10.05（0.39，63.44）mg/L、784.56（401.14，1409.55）和151.54（108.23，218.47）；两组比较差异有统计学意义（U值分别为-2.592、-2.024、-2.484和-3.285，P值分别为0.010、0.043、0.013和0.001）。受试者操作特征曲线结果显示，MTB特异性双因子联合常见实验室指标（PCT、CRP、SII、NLR和PLR）检测的曲线下面积为0.801（95%CI：0.720～0.881）。结论：MTB特异性双因子检测在肺外结核的诊断中具有较好的敏感度，尤其联合常见实验室指标（PCT、CRP、SII、NLR和PLR），可提高对肺外结核诊断的准确率。

关键词： Asthma   Computed tomography   COPD   Microbiome   Mucus   ABPA   allergic bronchopulmonary aspergillosis   ACO   asthma-COPD overlap   CFTR   cystic fibrosis transmembrane conductance regulator   COPD   chronic obstructive pulmonary disease   CT   computed tomography   DPP1   dipeptidyl peptidase-1   EGFR   epidermal growth factor receptor   FEV   1   forced expiratory volume in 1 s   FEF   25-75   forced expiratory flow between 25 % and 75 % of forced vital capacity   FeNO   fractional exhaled nitric oxide   FVC   forced vital capacity   IL   interleukin   ILC2   type 2 innate lymphoid   NETs   neutrophil extracellular traps (NETs)   SCFA   short-chain   fatty acid   T2   type 2  

摘要： Airway mucus plugs are the main pathological and computed tomography (CT) findings that affect clinical outcomes in patients with asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap. Despite the introduction of biologics targeting type 2 inflammation, mucus plug removal remains challenging and understanding its pathogenesis is critical for improved management. In eosinophilic airways, elevated MUC5AC and eosinophil-derived molecules (galectin-10 and extracellular traps) cause highly viscoelastic plugs detectable as high-density regions on ultra-high-resolution CT. In neutrophilic airways, where phylum Proteobacteria and genus Haemophilus are predominant, excessive neutrophil elastase impairs mucociliary clearance, induces neutrophil extracellular traps (NETs), and promotes mucus overproduction. Since mucus plugs could be reservoirs for bacterial colonization, an altered airway microbiome and airway inflammation may be associated with mucus plugging. Phylum Firmicutes and genus Streptococcus are positively and genus Fusobacterium is negatively associated with mucus plugging in severe eosinophilic inflammation. Anaerobic commensals produce short-chain fatty acids, which suppress eosinophilic inflammation. In moderate eosinophilic inflammation, anaerobic commensals may be replaced by pathogenic bacteria of the phylum Proteobacteria and genus Haemophilus , which triggers severe neutrophilic inflammation and exacerbates mucus plugging. Finally, in eosinophilic inflammation, mucus plugs containing aggregated eosinophils may induce mechanical dilation of the airways. In contrast, the presence of mucus plugs in a neutrophilic milieu may reflect severe inflammation characterized by excessive neutrophil extracellular traps and degenerative tissue remodeling, which is consistent with the pathological features of bronchiectasis. This review provides clues regarding how inflammation and microbiome alterations interact with mucus plugging in chronic airw

摘要： Allopurinol remains the first-line treatment for gout; however, it carries a risk of severe cutaneous adverse reactions (SCARs), particularly among carriers of the HLA-B*58:01 allele. In the Asia-Pacific region, screening practices vary widely due to infrastructure gaps, cost concerns, and differing health policies. For example, while cost-effectiveness analyses have influenced screening decisions in some countries, they often overlook long-term health system burdens and ethical imperatives. Therefore, screenings should not be withheld solely on economic grounds, especially when they can prevent life-threatening outcomes. For that reason, a targeted, risk-based approach that integrates genetic and clinical factors could offer a practical and equitable path forward, improving pharmacogenomic literacy, expanding access to testing, developing regional data-sharing platforms, and involving patients in co-designing screening strategies. Rapid point-of-care testing and integration of screening process with existing care pathway may further support this implementation. However, a coordinated regional effort is needed to ensure safer prescribing and equitable access to pharmacogenomic screening across diverse healthcare settings.

关键词： itch   neurogenic inflammation   intraepidermal nerve fiber density   claudin-1   sensitization   AD   Atopic dermatitis   DLQI   Dermatology Life Quality Index   DRKS   Deutsches Register Klinischer Studien (German Clinical Trials Register)   FPL   Former pruritic lesional/healed   FU   Follow up   HADS   Hospital Anxiety and Depression Scale   IA   Initial assessment   IENF(D)   Intraepidermal nerve fiber (density)   IL   Interleukin   IL-R   Interleukin receptor   NGF   Nerve growth factor   NPNL   Non-pruritic non-lesional   PL   Pruritic lesional   QoL   Quality of life   SEMA3A   Semaphorin 3A   TH2   T-helper-cell 2   TJ   Tight junction  

摘要： Itch is the dominant symptom in atopic dermatitis (AD). Cutaneous neuronal alterations underlying this symptom are still poorly understood. Therefore, we aimed at deciphering cutaneous neuronal alterations during AD treatment with dupilumab. Skin biopsies and blood from 49 adult patients with severe AD receiving dupilumab 300mg subcutaneously every two weeks over a period of 16 weeks were analyzed at initial assessment (IA) and at follow-up (FU) for intraepidermal nerve fiber density (IENFD), alloknesis and biomarker. Decreased IENFD and increased alloknesis in pruritic lesional (PL) and non-pruritic non-lesional (NPNL) skin at IA improved following dupilumab treatment. Formation of tight junctions (claudin-1 staining) was correlated to the epidermal level of IENF growth. Expression of targeted interleukin receptors ( IL4R, IL13RA1, IL13RA2 ) and mediators related to innervation density (NGF, SEMA3A) were increased in IA-PL compared to IA-NPNL and FU-FPL (former pruritic lesional/healed). Blood CD8+ central memory T-cells and CD4+ CD25+ CD127- cells including regulatory T-cells increased at FU, CD8 T-effector cells and CLA+ activated CD4+ cells decreased. In conclusion, treatment with an IL4Rα-antibody is paralleled by an improvement of neuroanatomy and reduction of neuronal sensitization paralleled by relevant biomarker improvement.

关键词： Aging   Inflammation   Periodontitis   SIRT1   Taurine  

摘要： Aging is a progressive decline in physiological & immunological functions, leading to an increased risk of chronic diseases. Taurine is a semi-essential amino acid, reduces inflammation by apoptosis, and oxidative stress by lowering inflammatory factors and decreases oxidative stress. The aim of this pilot study is to evaluate the saliva and serum levels of taurine and interrelated proteins in patients with periodontitis in different age groups. The study included systemically healthy young (25–44 years old) and old (≥ 65 years old) periodontally healthy and stage III grade B periodontitis patients. Periodontal parameters and salivary flow rates were recorded. Serum and saliva samples were collected to measure the taurine, sirtuin 1(SIRT1), and TNF-α using ELISA kits. Taurine levels in saliva and serum were significantly elevated in the young periodontally healthy group compared to other groups (p < 0.05). SIRT1 levels in serum were also higher in the young healthy group (p < 0.05), while no significant difference was found in saliva. TNF-α positively correlates with the local inflammatory burden of periodontal disease (bleeding on probing and clinical attachment loss). TNF-α was found the most accurate biomarker (AUC = 0.711). According to data of this pilot study, young individuals have higher levels of taurine compared to older individuals, and that this variation may be suggested as more strongly associated with age than with periodontal condition. NCT06635369 – 10/10/2024—Retrospectively registered.

关键词： CD4 T cells   MHC II   Mycobacterium tuberculosis   Pyrazinamide   interferon-gamma   oxidative burst  

摘要： Antibacterial drug mechanisms have traditionally been examined through a drug-pathogen lens, often overlooking the host's role in shaping drug activity. However, growing evidence suggests that the host environment is crucial for antibacterial efficacy. Pyrazinamide (PZA), a key component of modern tuberculosis therapy, exemplifies this complexity-exhibiting potent activity despite its inability to reduce viability in standard culture. Here, using macrophage and murine infection models, we identify a critical role for host cell-mediated immunity in PZA's antitubercular action. Through the use of MHC II knockout mice, we demonstrate that CD4 T cell help is essential for PZA efficacy. Notably, while IFN-γ is required for PZA-mediated clearance of at extrapulmonary sites, bacterial reduction in the lungs occurs independently of IFN-γ signaling. Additionally, we show that PZA leverages cell-mediated immunity in part through activation of the oxidative burst. Our findings underscore the need to incorporate host factors into antibacterial drug evaluation and highlight potential avenues for host-directed therapies and adjunctive antibiotics in first- and second-line tuberculosis treatment.

关键词： 孤独症谱系障碍   神经炎症   小胶质细胞   细胞因子   免疫调节  

摘要： 孤独症谱系障碍（ASD）是一种出现在儿童发育早期，以社会交往及交流障碍、重复刻板行为和兴趣狭窄为核心特征的神经发育障碍疾病。ASD患病率呈逐年上升趋势，给患儿身心、家庭及社会带来了巨大压力及负担。ASD发病机制及病因尚未完全明确，神经炎症在其中的作用逐渐受到关注。越来越多研究发现ASD是一种中枢神经系统慢性炎症性疾病，ASD动物模型脑组织中小胶质细胞激活、炎症细胞因子如白细胞介素-1（IL-1）、白细胞介素-6（IL-6）等水平改变均与ASD发生发展相关。本文综述了神经炎症与ASD之间的关联，探讨了小胶质细胞、细胞因子等在ASD发生发展中的作用。这将为进一步阐明孤独症的发病机制，为临床治疗孤独症的研究提供新的策略。

关键词： Diffuse large B-cell lymphoma, ITK   Immune microenvironment   Rituximab   TCR signaling pathway  

摘要： Diffuse Large B-Cell Lymphoma (DLBCL) is the most prevalent pathological subtype of non-Hodgkin lymphoma (NHL). Patients with DLBCL often experience extremely poor prognoses due to drug resistance or relapse, and the limitations of existing treatment regimens are evident. This study focuses on the mechanistic role and clinical significance of interleukin-2-inducible T-cell kinase (ITK) in DLBCL. Through bioinformatics analysis, it was found that ITK, as a key molecule in the T Cell Receptor (TCR) signaling pathway, is significantly underexpressed in DLBCL. This underexpression is associated with a poorer overall survival (OS) of patients and exhibits a negative correlation with the expression of the immune checkpoint molecule Programmed Death Ligand 1 (PD-L1), suggesting its potential involvement in the regulation of T cell exhaustion. In vitro experiments demonstrated that overexpression of Itk significantly enhanced the immunological activity of mouse T lymphocytes (CTLL-2), activating the TCR-Ca-Calcineurin-NFAT-IFN-γ signaling pathway. This led to improved calcium ion responsiveness in T cells, increased calcineurin activity, and nuclear translocation of Nuclear Factor of Activated T Cells (NFAT). It also enhanced cytokine secretion levels and proliferative capacity of cytotoxic T lymphocytes (CD8 T cells), thereby driving an anti-tumor immune response. In a co-culture model, overexpression of Itk significantly augmented the killing effect of CTLL-2 cells on DLBCL, inducing apoptosis in DLBCL cells. Furthermore, T cells overexpressing Itk exhibited a synergistic effect when combined with Rituximab, significantly enhancing the inhibition of DLBCL cell proliferation. This provides a clinically feasible approach to address the challenge of drug resistance in DLBCL treatment. This study unveils the molecular mechanism by which ITK enhances anti-tumor immunity through remodeling the T cell receptor signaling pathway, offering new theoretical grounds for the developme

关键词： HLA-B gene   HLA-B*58:01   PSORS1C1 gene   gout patients   paraclinical characteristics   rs9263726 SNP  

摘要： : The allele is strongly linked to severe cutaneous adverse reactions (SCARs) during allopurinol treatment, and it has been associated with the A allele of rs9263726 (G>A). Paraclinical characteristics of gout are indicative of associated comorbid conditions. This study investigated the genotype frequency of and its association with paraclinical characteristics and rs9263726 in gout patients from Northeast Vietnam. : A total of 133 unrelated gout patients were randomly recruited by the clinician. BioEdit sequence alignment editor version 7.2.5 software (Raleigh, Raleigh, NC, USA) was used for the analysis of nucleotide sequence data of gene alleles from the IPD-IMGT/HLA Database, which showed that the allele can be distinguished from reference and other alleles by specific nucleotide positions: 387C, 379C, 368A, 355A, and 353T (in exon 3); and 319C, 285G, and 209A (in exon 2). and rs9263726 genotypes were identified using Sanger sequencing of PCR products, analyzed with BioEdit software, and verified using the NCBI dbVar database. Statistical analyses were performed using SPSS version 25.0. : Our study revealed a significant age difference between male and female gout patients ( < 0.001). Male gout patients had an average age of 51.44 ± 14.59 years, whereas female gout patients were notably older, with an average age of 70.33 ± 10.64 years. Positive correlations were observed between platelet count, serum creatinine, and uric acid levels (r = 0.174, = 0.045; r = 0.195, = 0.025) in male gout patients, while only high-density lipoprotein cholesterol showed a statistically significant negative correlation with uric acid levels (r = -0.885, = 0.002) in female patients. The allele frequency among study subjects was 6.02%, with 12.03% being heterozygous individuals (, N = 16). The allele was not detected in female gout patients. White blood cell counts were significantly higher in male gout patients with the genotype compared to those with the genotype ( =