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关键词： 足三里   炎症性肠病   3型固有淋巴细胞   白细胞介素-22   小鼠  

摘要： 目的 观察电针“足三里”对炎症性肠病（IBD）小鼠结肠中分泌白细胞介素（IL）-22的3型固有淋巴细胞（ILC3s）和肠胆碱能神经元等的影响，探讨电针改善IBD的效应机制。方法 24只C57BL/6J雄性小鼠按照随机数字表法分为正常组（n=8）和造模组（n=16）。造模组小鼠给予4%硫酸葡聚糖钠盐溶液自由饮用7 d，制备IBD小鼠模型。造模后第4天，将造模组小鼠按随机数字表法分为模型组和电针组，每组8只。对电针组小鼠双侧“足三里”行电针干预，每日1次，每次20 min，连续7 d。干预结束后，观察各组小鼠粪便，检测粪便隐血情况；对各组小鼠疾病活动指数（DAI）进行评分；测定结肠长度；苏木精-伊红染色法观察小鼠结肠组织形态，并进行组织病理学评分；流式多重蛋白定量检测结肠组织中IL-1β、肿瘤坏死因子-α（TNF-α）和IL-6的含量；流式细胞术检测结肠组织固有层淋巴细胞中IL-22+ILC3s比例；酶联免疫吸附测定法检测结肠组织中IL-22含量；免疫荧光法检测结肠组织中乙酰胆碱转移酶（ChAT）+/原癌基因Fos（c-Fos）+共标神经元数量。结果 与正常组比较，模型组小鼠出现不同程度的稀便，粪便隐血呈强阳性，DAI评分升高，结肠长度缩短，结肠组织病理学评分增加，结肠组织中IL-1β、TNF-α和IL-6含量增加，结肠组织固有层淋巴细胞中IL-22+ILC3s比例减少（P＜0.05）。与模型组比较，电针组小鼠粪便性状得到改善，粪便隐血呈弱阳性，DAI评分降低，结肠长度增加，结肠组织病理学评分减少，结肠组织中IL-1β、TNF-α和IL-6含量降低，结肠组织固有层淋巴细胞中IL-22+ILC3s比例增加，结肠组织IL-22含量升高，结肠组织ChAT+/c-Fos+共标神经元数量增多（P＜0.05）。结论 电针“足三里”能够明显改善IBD小鼠结肠损伤，降低炎症反应，其机制可能与激活肠胆碱能神经元、增强结肠ILC3s功能有关。

关键词： apoptosis   GATA-binding protein 3   IFN-alpha 2b   Kaposi's Sarcoma   proliferation  

摘要： Previous studies have established that interferon (IFN) can inhibit the occurrence and progression of various tumors, particularly those associated with viral infections. However, the specific molecular mechanisms underlying its effects remain a key research focus. This study aims to elucidate how interferon inhibits Kaposi's sarcoma (KS), ultimately to improve its therapeutic efficacy against this condition. The role of IFN-alpha 2b in treatingKS has been extensively studied, especially regarding its antiviral properties and immune regulatory functions. In this study, we demonstrate that IFN-alpha 2b suppresses LANA expression in KSHV-infected cells, thereby reducing cell proliferation and increasing apoptosis. Further investigation into the molecular mechanisms revealed that IFN-alpha 2b enhances the expression of GATA3, and that overexpression of GATA3 inhibits the phosphorylation of STAT5B. In summary, IFN-alpha 2b exerts its inhibitory effects on KS by regulating GATA3 expression. Additionally, exploring the interactions between IFN-alpha 2b and other molecules may uncover more complex tumor-suppressing mechanisms.

关键词： HLA-DQA1   next-generation sequencing   novel allele  

摘要： HLA-DQA1*01:140 differs from the HLA-DQA1*01:02:01:01 allele by one nucleotide substitution in exon 4.

关键词： brain-derived neurotrophic factor (BDNF)   cognition disorders   elastography   fatigue   fibrosis   hepatic encephalopathy   inflammation   Interleukin-6   Interleukin-18   liver   liver cirrhosis   liver function tests   primary biliary cholangitis   ultrasonography  

摘要： Background and Aims: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease frequently associated with fatigue and mild cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays key roles in neuroplasticity, immune regulation, and metabolism. This study aimed to evaluate plasma BDNF levels in early-stage PBC and examine their clinical and biochemical associations. Methods: In this observational study, plasma BDNF, IL-6, and IL-18 concentrations were measured by ELISA in 45 patients with early-stage PBC and 31 age- and sex-matched healthy controls (mean age 60.5 years;96% women). All participants underwent liver elastography using point shear wave elastography (ElastPQ), Doppler ultrasound, laboratory testing, and assessment of cognitive function (PHES) and fatigue severity (MFIS). Non-invasive fibrosis scores (APRI, FIB-4) were calculated. Results: Median plasma BDNF concentrations were significantly higher in PBC patients than in controls [median: 21.04 ng/mL (IQR: 10.68-38.07) vs. 5.80 ng/mL (IQR: 4.58-7.54);p < 0.0001]. In PBC patients, higher BDNF levels correlated inversely with liver stiffness measured by ElastPQ (R = -0.39, p = 0.0258), spleen dimensions, splenic vein flow volume (R = -0.49, p = 0.0018), suggesting an association with milder liver fibrosis and early hemodynamic alterations. A trend toward association between BDNF and IL-6 levels was observed in multivariate analysis. No significant associations were found between BDNF concentrations and markers of hepatocellular injury, cognitive performance, or fatigue severity. Conclusions: Plasma BDNF concentrations are elevated in early-stage PBC and inversely correlate with liver fibrosis severity. No significant associations were found with hepatocellular injury, cognitive function, or fatigue. These findings suggest that BDNF may play a protective role against hepatic fibrogenesis, or alternatively, that BDNF concentrations may decline with advancing liver disease. Further s

关键词： Atopic dermatitis   JAK inhibitors   Body mass index   Obesity   Real-world study   Upadacitinib   Abrocitinib   Baricitinib   Treatment efficacy   Dermatology  

摘要： Introduction: Janus kinase (JAK) inhibitors are effective systemic treatments for moderate-to-severe atopic dermatitis (AD), rapidly controlling symptoms and improving quality of life. However, the impact of body mass index (BMI) on therapeutic response remains unclear. Methods: This multicenter retrospective study analyzed data from 388 adult AD patients treated with upadacitinib, abrocitinib, or baricitinib across 25 Italian dermatology centers between May 2022 and July 2024. Patients were classified as overweight (BMI >= 25) or non-overweight (BMI < 25), with disease severity assessed using EASI, IGA, and Numerical Rating Scales (NRS) for pruritus and sleep disturbance over 104 weeks. The effect of different treatment dosages was also evaluated. Results: No significant BMI-related differences in clinical outcomes were noted at most timepoints. However, in the upadacitinib 15 mg group, non-overweight patients showed greater EASI and pruritus improvements at Week 4 (p = 0.037, p = 0.039), although these differences resolved subsequently. At Week 104, higher BMI modestly reduced EASI improvement (p = 0.045) in multivariable analysis. Conclusions: Treatment dosage consistently influenced clinical improvement regardless of BMI. These findings confirm the efficacy of JAK inhibitors across BMI categories, suggesting minimal short-term BMI influence but highlighting potential long-term considerations in overweight patients, emphasizing personalized dosing strategies and prolonged monitoring.

关键词： HBsAg   RIPK1   TNFα   Ubiquitination   cIAP1  

摘要： Tumor necrosis factor α (TNFα) is a highly pleiotropic cytokine with a variety of biological functions such as cell proliferation, metabolic activation, inflammatory response and cell death. TNFα can induce a variety of mechanisms to initiate hepatocyte apoptosis, resulting in subsequent liver damage. HBsAg is the most abundant HBV protein in the hepatocyte during chronic virus infection. However, its role in TNFα-mediated apoptosis of hepatocytes has not been revealed. We report here that HBsAg promotes TNFα-mediated hepatocyte apoptosis through inhibiting TNFα-mediated anti-apoptotic complex I dependent NF-κB activation and enhancing TNFα-mediated pro-apoptotic complex II assembly. Mechanistically, HBsAg-mediated inhibition of complex I assembly was associated with down-regulation of K63-linked RIPK1 ubiquitination through repression of cIAP1 expression. Secretion-deficient HBsAg variants S204R enhance their proapoptotic abilities via further inhibition of RIPK1 ubiquitination. Expression of HBsAg in mice injected with recombinant adenovirus-associated virus 8 promoted D-galactosamine/lipopolysaccharide- induced TNFα-mediated liver injury and damage by a mouse model. In conclusion, HBsAg may predispose hepatocytes to TNFα-mediated apoptosis and mice to acute liver injury by switching TNFα-mediated anti-apoptotic complex I to pro-apoptotic complex II, showing novel insights into the underlying mechanisms of HBV-associated liver injury.

关键词： Buzhongyiqi granules   Blood-absorbed components   Ulcerative colitis   IL-6/STAT3 axis   Traditional Chinese medicine  

摘要： Ethnopharmacological relevance: Buzhongyiqi Granules (BZYQ), a classical herbal formulation derived from Pi Wei Lun, is traditionally used to regulate Qi and blood circulation while enhancing immune function, particularly for gastrointestinal disorders. However, its protective effects and mechanisms on ulcerative colitis (UC) remain unclear. Aim of the study: This study aimed to identify the blood-entering bioactive components of BZYQ and elucidate its immune-modulatory mechanisms in UC using an integrated strategy combining medicinal chemistry, bioinformatics analysis, molecular docking, and experimental validation. Materials and methods: The chemical profile and serum pharmacochemistry components (SPCs) of BZYQ were identified via UPLC-QE-Orbitrap mass spectrometry. Network pharmacology and molecular docking predicted UC-related targets and pathways. In vivo, experimental colitis was induced via 3 % dextran sulfate sodium solution administration for 7 days, followed by 10-day BZYQ treatment. Anti-inflammatory effects were validated through flow cytometry, qPCR, Western blotting, and in vitro bone marrow-derived macrophage (BMDM) cultures. Results: Fifty-four compounds were identified in BZYQ, with seven SPCs (astragaloside IV, licoflavone A, 18 beta glycyrrhizinic acid, glabrolide, ganoderic acid X, complanatuside, and isosakuranin) directly related to UC pathogenesis. Molecular docking confirmed high-affinity interactions between glabrolide and IL-6. BZYQ alleviated colitis by suppressing IL-6/STAT3 axis, reprogramming macrophage polarization, increasing regulatory T cell frequency, and suppressing naive CD4+ T cell differentiation. Conclusions: This study is the first to define BZYQ's component basis and cellular immunological mechanisms in UC alleviation. These findings contribute to the development and application of traditional Chinese medicine prescriptions.

摘要： Class I major histocompatibility complex (MHC-I) molecules present peptides derived from intracellular antigens on the cell surface for immune surveillance. Proteins that recognize peptide-MHC-I (pMHCI) complexes with specificity for diseased cells could have considerable therapeutic utility. Specificity requires recognition of outward-facing amino acid residues within the disease-associated peptide as well as avoidance of extensive contacts with ubiquitously expressed MHC. We used RFdiffusion to design pMHCI-binding proteins that make extensive contacts with the peptide and identified specific binders for 11 target pMHCs starting from either experimental or predicted pMHCI structures. Upon incorporation into chimeric antigen receptors, designs for eight targets conferred peptide-specific T cell activation. Our approach should have broad utility for both protein- and cell-based pMHCI targeting.

关键词： HLA-DRB1   MinION   new allele   NGS  

摘要： The novel HLA-DRB1*13:368 allele differs from HLA-DRB1*13:01:01:01 by one nucleotide substitution G -> T in exon 3.