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摘要： In our recent research on AIDS Elite controllers, we demonstrated that the HLA-B*57:01 allele is part of an extensive MHC haplotype associated with impaired MICA/MICB function. Considering the pivotal role of natural killer (NK) cells and innate immunity in fighting cancer and infectious diseases, we investigated whether this allele could also influence human longevity. To this end, we performed a multinational European study including 2,597 centenarians and 9,973 controls. We found that HLA-B*57:01 was consistently less frequent in the European centenarian cohorts compared with the corresponding controls (OR ≈ 0.68, p &;lt 0.0005). These findings provide the first in vivo genetic evidence that innate immunity and NK cell function are key components of human longevity.

关键词： 重症肺炎   辅助性T淋巴细胞1/辅助性T淋巴细胞2   肺炎程度评分   模型   预后  

摘要： 目的 构建重症肺炎的外周血辅助性T淋巴细胞1/辅助性T淋巴细胞2(helper T lymphocyte 1/helper T lymphocyte 2,Th1/Th2)细胞因子与肺炎程度指数(pneumonia degree index,PSI)评分的联合模型,探讨该联合模型对重症肺炎患者预后的评估价值。方法 选取2021年1月至2023年8月收治的120例重症肺炎患者,并对其进行为期1年的随访,根据随访期间患者的生存状态分为生存组(n=82)和死亡组(n=38)。比较两组患者的一般资料、实验室指标及PSI评分,采用多因素logistic回归分析重症肺炎患者预后的影响因素,根据结果构建logistic回归预测模型,并绘制受试者工作特征(receiver operating characteristic curve,ROC)曲线,采用ROC曲线下面积(area under curve,AUC)评估预测模型对重症肺炎患者预后的预测价值。结果 死亡组平均年龄[(80.62±10.41)岁]、中性粒细胞与淋巴细胞比值(neutrophil-to-lymphocyte ratio,NLR)水平(13.60±2.45)及PSI评分(127.64±22.18)均高于生存组[(70.18±18.30)岁、10.79±6.12、113.59±20.61](t=3.275、2.726、3.299,P<0.05),住院时间[(11.15±10.03)d]、外周血Th1/Th2细胞因子水平(4.02±1.02)均低于生存组[(18.45±11.26)d、5.01±1.62](t=3.146、3.458,P<0.05)。多因素logistic回归分析结果显示,年龄(OR=1.613,95%CI:1.744～3.498)、住院时间(OR=1.603,95%CI:1.729～3.525)、NLR(OR=1.793,95%CI:1.837～3.844)、Th1/Th2(OR=1.840,95%CI:1.806～4.200)、PSI评分(OR=1.817,95%CI:1.818～4.034)均为影响重症肺炎患者死亡的危险因素。基于外周血Th1/Th2细胞因子、PSI评分构建logistic回归预测模型:logistic(P)=-4.516+0.610(Th1/Th2)+0.597(PSI评分),其对重症肺炎患者死亡预测的敏感度、特异度、AUC分别为79.85%、90.65%、0.912。结论 外周血Th1/Th2细胞因子与PSI评分的联合模型对重症肺炎患者死亡预测的敏感度、特异度及AUC水平均较高,预测效能好,对临床评估重症肺炎患者预后有一定指导价值。

关键词： Human metabolism   proteomics  

摘要： Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are widely used to manage type 2 diabetes mellitus (T2DM) to ameliorate hyperglycemia, albuminuria, and obesity, with established cardiorenal benefits. However, predictive biomarkers for therapeutic responses remain limited. In this study, seventy patients initiating SGLT2i therapy were evaluated clinically and through plasma proteomics and transcriptomics. Treatment significantly improved HbA1c (71.2%), albuminuria (47.5%), and weight (58.6%), with benefits in insulin resistance, beta-cell function, blood pressure, uric acid, and body composition. Proteomic analysis identified IL-18R1 reduction linked to improved glycemic control, albuminuria, fat mass, and liver function. Transcriptomic profiling revealed genetic alterations in blood mononuclear cells, reinforcing anti-inflammatory changes. Receiver operating characteristic analysis indicated high baseline IL-18/IL-18R1 predicted overall response (area under the curve: 0.75, p = 0.005;cutoffs: IL-18 = 244.29 pg/mL, IL-18R1 = 325.97 pg/mL). IL-18/IL-18R1 signaling emerges as a promising biomarker for predicting therapeutic responses, guiding clinical decisions regarding SGLT2i use in T2DM management.

关键词： Natural sciences   biological sciences   Immunology   systems biology   cancer systems biology  

摘要： Interference by tumor-associated macrophages may significantly reduce the efficacy of therapeutic viruses designed to infect cancer cells and activate anti-tumor T cells. Using a computational model, we hypothesized that viruses encoding a T cell-stimulating signal, like interferon-gamma (IFN-gamma), could overcome this barrier. We engineered an alphavirus-based replicon expressing IFN-gamma and evaluated its effect in various human-derived tumor-immune coculture systems and an in vivo murine model. While alphavirus replicons do not replicate in macrophages, macrophages acted as a barrier, limiting tumor infection in afrequency-depen-dent but phenotype-independent manner. Nonetheless, T cell activation occurred even when only a fraction of infected tumor cells expressed IFN-gamma, regardless of macrophage presence, frequency, or phenotype. Additionally, viral stimulation drove macrophage repolarization toward a pro-inflammatory phenotype favoring T cell activation. These findings highlight a strategy for optimizing virotherapy in macrophage-rich tumors by designing viruses that stimulate T cell activation, ensuring therapeutic efficacy.

关键词： 抗狂犬病病毒单克隆抗体   狂犬病   暴露预防   专家共识  

摘要： 抗狂犬病病毒单克隆抗体（anti-rabies virus monoclonal antibody,RmAb）是利用现代基因工程技术开发和生产的一种新型狂犬病被动免疫制剂，其可以特异性地与狂犬病病毒表面G蛋白上的抗原位点结合，阻断病毒与细胞表面受体的结合，从而起到预防作用。与传统的狂犬病免疫球蛋白相比，RmAb具有产量可控、质量稳定、安全性高、比活性好等优势。目前，全球已有4种RmAb产品获批上市。针对临床医生对RmAb认识相对不足的现状，中华预防医学会狂犬病预防控制工作委员会、中国医学救援协会动物伤害救治分会组织中国专家，收集最新证据，参考国内外相关规范、指南和共识，结合专家临床经验等，撰写本共识，为临床工作提供科学和规范的建议。

关键词： 小鼠细小病毒   单克隆抗体   双抗体夹心ELISA   抗原检测  

摘要： 制备小鼠细小病毒（MVM）VP2蛋白单克隆抗体，建立一种基于双抗体夹心ELISA的实验动物小鼠MVM抗原检测方法。应用原核表达质粒表达VP2蛋白，纯化蛋白免疫雌性BALB/c小鼠制备单克隆抗体，以获得的单抗1C5作为捕获抗体，HRP标记的单抗8B9作为检测抗体，优化条件建立双抗体夹心ELISA检测方法，并对其灵敏性、特异性和重复性进行系统评价并与qPCR检测进行比对分析。结果显示，表达纯化了MVM VP2 蛋白，免疫雌性BALB/c小鼠，免疫程序结束后筛选获得2株单克隆抗体，命名为1C5和8B9，Western-blot和间接免疫荧光鉴定发现这2株抗体可与MVM病毒和重组蛋白特异性结合。以1C5作为捕获抗体，HRP标记的8B9作为检测抗体建立了双抗体夹心ELISA方法，其对MVM病毒和重组蛋白最低检测限分别为103.4TCID50/mL和50 ng/mL；与4种常见病毒感染的小鼠血清均无交叉反应，包被ELISA板条的批间变异系数均小于10%，与qPCR检测结果相比总符合率为100%。结果表明，成功制备了2株MVM单克隆抗体，应用这2株抗体建立的MVM双抗体夹心ELISA方法具有较好的灵敏性和特异性，与qPCR检测法相比一致性较好，为实验动物小鼠的临床诊断、高通量筛查监测提供了有效的检测方法，从而保障实验动物的SPF状态，为生命科学研究提供健康可靠的实验动物。

关键词： Gastric cancer   Gut microbiota   TNF   Ginsenoside Rh2   3-Indolepropionic acid   Systems biology   Dose-weighted network pharmacology  

摘要： IntroductionGastric cancer (GC) remains a formidable global health issue with limited therapeutic options. ShenXia KuanZhong Decoction (SXKZD), a classical traditional Chinese medicine (TCM) formula, is used to manage GC;however, its anti-tumor mechanisms remain poorly *** and MethodsThe anti-GC effects of SXKZD were investigated in a GC model using dose-weighted network pharmacology, molecular docking, molecular dynamics (MD) simulations, and pharmacokinetic profiling. Its impacts on tumor metabolism, immunity, and gut microbiota were assessed. A gut microbiota-substrate-metabolite (GM-S-M) network was constructed, and key targets and pathways were analyzed using computational and experimental *** treatment significantly alleviated tumor progression in GC models. Network analysis revealed upregulated TNF and IL6 expression in GC, which SXKZD reduced, alongside enrichment in IL-17 and TNF signaling pathways. Molecular docking and MD simulations confirmed stable binding of Ginsenoside Rh2 and 3-Indolepropionic acid to TNF, with binding energies of -147.63 kJ/mol and - 98.63 kJ/mol, respectively. Pharmacokinetic profiling showed 3-Indolepropionic acid's high bioavailability, while GM-S-M analysis identified key microbial taxa (e.g., Lactobacillus plantarum, Akkermansia muciniphila) modulated by SXKZD, enhancing anti-tumor immunity and *** further confirm these computational predictions, in vitro CCK-8 assays revealed that GRh2 and IPA inhibited AGS cell growth in a concentration-dependent manner, with IC50 values of 68.74 +/- 1.27 mu g/mL and 780.60 +/- 24.40 mu g/mL at 24 hours, respectively. Western blot analysis demonstrated that GRh2 more effectively suppressed TNF alpha expression, whereas CETSA showed that IPA provided superior thermal stabilization of TNF *** mitigates GC by modulating gut microbiota and inhibiting TNF signaling, offering a mechanistic basis for its therapeutic potential in GC manage

关键词： Disease management   IL-6 inhibition   juvenile idiopathic arthritis   pediatric rheumatology   treatment   unmet needs  

摘要： INTRODUCTION:Medical management of juvenile idiopathic arthritis (JIA) presents a significant challenge in pediatric rheumatology. Ideally, the treatment target is remission, though achieving this remains complex. Interleukin-6 (IL-6) inhibitors (IL-6is) play an important role, targeting the inflammatory pathways central to JIA pathogenesis. However, their optimal use is debated. AREAS COVERED:This narrative review examined JIA care needs and IL-6 inhibition. A SPIDER-based literature search of PubMed/MEDLINE, Semantic Scholar, WorldCat, Cochrane Library, Embase, CINAHL, ICTRP, and *** (to May 2025), identifying 56 studies from 246 records published between 2018-2025. Key unmet needs include difficulty controlling the disease, diagnostic delay, shortcomings in biomarker research, and multidisciplinary support. Tocilizumab, a well-studied IL6i, showed efficacy in symptom reduction, disease control, and reduced glucocorticoid use. EXPERT OPINION:Addressing gaps in JIA management, such as delayed diagnosis and inadequate disease control, is essential. Experts advocate for early IL6i use within a treattotarget framework, optimizing outcomes and minimizing glucocorticoid use. Recognizing benefits for highrisk JIA subtypes, experts support earlier tocilizumab integration into treatment algorithms, offering valuable options for refractory oligoarthritis and uveitis. Ultimately, bridging gaps in JIA management and reshaping real-world outcomes hinges on integrating clinical insight and research outcomes - a process driven by precision medicine.

关键词： IL-10   Lactobacillus paracasei   Pichia membranifaciens   Saccharomyces cereviciae   atopic dermatitis   dendritic cells  

摘要： : In this study, we focused on a mixed microbial culture of , , and (LS) as a new probiotic and examined the therapeutic and preventive effects of topical treatment with LS in a mouse model of atopic dermatitis (AD). : Immunomodulatory effects of LS were examined with murine dendritic cell lines (DC2.4) by measuring the interleukin (IL)-10 and tumor necrosis factor (TNF) α levels. The anti-inflammatory effects of LS were evaluated in stimulated human epidermal keratinocytes (HaCaTs) by focusing on the production of IL-8 and thymus and activation-regulated chemokine (TARC). Therapeutic and preventive properties of topical treatment with LS (10%) were finally examined in a mouse model of AD developed by topical sensitization to house dust mite ointment. Clinical symptoms, back skin thickness, and transepidermal water loss (TEWL) were monitored weekly, and the immune responses in the auricular lymph nodes were analyzed after necropsy. : LS treatment significantly enhanced the secretions of IL-10 and TNFα by DC2.4 cells. IL-8 and TARC production by stimulated HaCaT cells was significantly decreased by co-culturing with LS. Although there were no significant changes in clinical symptoms, skin thickness, or TEWL in the therapeutic setting of the AD mouse model, the number of IgE-positive B cells and IL-4 levels in the local lymph nodes significantly decreased in the LS treatment group. Preventive treatment with LS significantly decreased AD symptoms compared to those in AD control mice. : Our findings indicate that the immunomodulatory and anti-inflammatory effects of LS prevent the development of AD.

关键词： MDA5   interferon   juvenile dermatomyositis   muscle   myositis-specific auto-antibodies  

摘要： OBJECTIVES:This study aimed to establish the role of myositis-specific antibodies (MSAs) in the association between type I interferon (IFN-I) plasma levels and disease activity in juvenile dermatomyositis (JDM). METHODS:We prospectively obtained 400 samples from 101 JDM patients from 2 independent cohorts. Autoantibody levels were determined for all patients. Muscle activity was assessed using the Childhood-Myositis Assessment Scale (CMAS). Two characterized homebrew digital ELISAs measuring respectively, all 12 IFN-alpha subtype proteins (IFN-α), and IFN-beta (IFN-β) were used to quantify IFN-I in patient plasma. Receiver operating characteristic (ROC) curve analysis was used to identify IFN-I thresholds associated with CMAS changes. Correlations between IFN-I levels and CMAS were assessed at recruitment using Spearman's test, and longitudinally using mixed-effects models to account for repeated measures. RESULTS:IFN-α levels were higher in melanoma differentiation-associated gene 5 (MDA5)-positive patients while IFN-β levels were comparable across MSA subgroups. IFN-β was found to be more effective than IFN-α in distinguishing between active and inactive muscle disease, and between severe and non-severe disease status. Over the disease course, we identified IFN-β as a reliable biomarker of muscle disease activity regardless of MSA expression. In contrast, IFN-α levels showed a specific association with CMAS only MDA5-positive patients. CONCLUSIONS:This exclusive association of IFN-α levels with muscle clinical score in anti-MDA5-positive patients suggests a subgroup-specific pathophysiological mechanism. These findings underscore potentially distinct roles for IFN-I subtypes (IFN-α and IFN-β) as circulating biomarkers of muscle disease activity in JDM according to the MSA expression.