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关键词： D-二聚体   白细胞介素-5   重症肺结核   预后   预测价值  

摘要： 目的 检测重症肺结核患者血清D-二聚体（D-D）、白细胞介素-5（IL-5）的水平,并探讨其在重症肺结核患者预后评估中的应用价值。方法 选取本院96例在2020年6月-2023年6月期间收治的重症肺结核患者为重症组,重症肺结核患者入院治疗28d后依据预后情况分为预后良好组（n=57）,预后不良组（n=39）。另选同期于本院治疗的96例轻症肺结核患者为轻症组。采用酶联免疫吸附测定法检测所有患者血清D-D、IL-5水平;对比预后不良组和预后良好组一般资料;构建Logistic回归模型分析影响重症肺结核患者预后结局的潜在因素;绘制受试者工作特征（Receiver operating characteristic,ROC）曲线评估血清D-D、IL-5水平在预测重症肺结核患者预后方面的效能。结果 重症组患者血清D-D、IL-5水平均高于轻症组（P<0.05）;预后不良组肺部感染评分（CPIS）评分、血清D-D、IL-5水平均显著高于预后良好组（P <0.05）;IL-5、DD水平升高、CPIS评分升高均为重症肺结核患者预后不良的危险因素（P <0.05）;血清D-D、IL-5水平、CPIS评分单独预测重症肺结核患者不良预后的AUC分别为0.847（95%CI:0.759～0.913）、0.843（95%CI:0.755～0.910）、0.842（95%CI:0.754～0.909）,血清D-D、IL-5水平联合预测重症肺结核患者不良预后的AUC为0.942 （95%CI:0.874～0.979）,二者联合优于血清D-D (Z二者联合-D-D=1.992,P=0.046)、IL-5 (Z二者联合-IL-5=2.007,P=0.045)、CPIS评分(Z二者联合-CPIS评分=2.063,P=0.039)单独预测价值。结论 D-D、IL-5水平在重症肺结核患者血清中均升高,二者水平变化与重症肺结核患者预后不良显著相关,且二者联合在预测重症肺结核预后不良方面展现出更高效能,可作为预测重症肺结核患者预后的生物标志物。

关键词： 细胞因子类   变应性鼻炎   嗜酸性粒细胞   诊断  

摘要： 目的 本研究旨在通过分析过敏性鼻炎（AR）和非过敏性鼻炎（NAR）患者的血浆12项细胞因子水平及鼻腔局部嗜酸性粒细胞水平，探讨其在AR诊断中的临床价值，并构建基于Logistic回归的诊断模型，为AR的快速、精准诊断提供新方法。 方法 收集2024年1月1日至12月31日在北京同仁医院就诊的具有AR症状并进行血浆细胞因子检测的患者进行回顾性横断面研究。根据血清学检测结果对患者进行分组，分为AR组（395例）和NAR组（185例），其中儿童患者205例（<18岁），成人患者375例（≥18岁）。通过多重微球流式免疫荧光法检测血浆中12项细胞因子的水平，包括白细胞介素（IL）-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12P70、IL-17A、肿瘤坏死因子α、干扰素（IFN）α和γ，并通过鼻分泌物细胞检测评估鼻腔局部嗜酸性粒细胞水平。采用Mann-Whitney U 检验分析AR和NAR患者人群的临床特征并使用Spearman检验分析细胞因子水平与鼻腔局部嗜酸性粒细胞的相关性。采用Logistic回归分析筛选预测因子，构建AR诊断模型，并通过受试者工作特征曲线及列线图展示模型的预测能力与评估效能。 结果 AR患者与NAR患者在总IgE（tIgE）（儿童组 U =‒7.799， P <0.001；成人组 U =‒12.630， P <0.001）和吸入混合型过敏原（儿童组 U =‒8.296， P <0.001；成人组 U =‒13.810， P <0.001）中差异有统计学意义。AR患者的鼻腔局部嗜酸性粒细胞水平高于NAR患者（ Z =‒4.592， P <0.001）。在儿童中，AR患者和NAR患者相比IL-4、IL-5和IL-10水平差异有统计学意义（ P <0.05），而在成人中AR患者与NAR患者 相比仅IL-10水平差异有统计学意义（ P <0.05）。鼻腔局部嗜酸性粒细胞水平与血浆中的IL-5（ ρ =0.166， P <0.001）及IFN-γ（ ρ =0.132， P =0.002）弱正相关。基于Logistic回归分析，年龄、局部嗜酸性粒细胞水平和IL-10被纳入成人AR诊断模型，该模型的曲线下面积为0.709，敏感度为73.9%，特异度为57.4%。其中嗜酸性粒细胞中、高水平为AR的危险因素（以低水平为参照，中水平 OR =3.072， P <0.001；高水平 OR =15.136， P <0.001），年龄和IL-10水平为AR的保护因素（年龄 OR =0.572， P =0.002；IL-10 OR =0.535， P =0.003）。 结论 AR患者表现出以辅助性T细胞2（Th2）型细胞因子（IL-4、IL-5）升高，IL-10降低为特征的免疫反应，且鼻腔局部嗜酸性粒细胞水平高于NAR患者。基于年龄、局部嗜酸性粒细胞水平和IL-10和的Logistic回归模型对AR的精准诊断具有一定的价值。

关键词： 狂犬病人免疫球蛋白   国家药品抽检   质量评价  

摘要： 目的 评价国内上市不同企业生产的狂犬病人免疫球蛋白的质量状况。方法 对13家生产企业50批次狂犬病人免疫球蛋白依据法定质量标准进行检验，同时开展了狂犬病抗体效价、比活性及效价稳定性、质量可比性及可能引起不良反应的影响因素［免疫球蛋白A（immunoglobulinA，IgA）残留量、渗透压］等4个方面的探索性研究。对检验及探索性研究所得的结果进行统计分析，综合评价狂犬病人免疫球蛋白的质量现状。结果 50批样品的合格率为100%。采用细胞法测定狂犬病抗体效价，通过半数有效量(medianeffectivedose，ED50)法计算，结果为101～237 IU·mL-1。比活性结果为0.88～2.78 IU·mg-1蛋白质。成品透光率结果为92.3%～98.7%，热稳定性试验后样品透光率结果为3.1%～97.5%，IgA残留量结果为5～1 017 μg·mL-1，渗透压结果为118～858 mOsmol·kg-1，企业间差异明显。亚可见微粒结果为每毫升13 406～2 185 154个，两家企业显著较高。结论 本品总体质量状况较好。但不同企业间产品的透光率、亚可见微粒、IgA 残留量、渗透压等指标上有较大差异，值得进一步关注。质量标准需进一步完善，可对狂犬病抗体效价增订统计分析要求。

关键词： comorbidity   dendritic cells   inflammation mediators   psoriasis   psychological stress  

摘要： Background Psychological stress often accompanies psoriasis, and both conditions involve an overactive IL-23/Th17 inflammatory axis. However, the mechanism behind the comorbidity of psoriasis and psychological stress remains unclear. This study established a mouse model of comorbid psoriasis and psychological stress to investigate the impact on skin inflammation and the IL-23/Th17 axis. Chronic restraint stress and imiquimod cream were used to induce psychological stress and psoriasis. Behavioural tests included the open-field test and elevated plus maze, while psoriasis severity was assessed using the Psoriasis Severity Index and histopathology. Flow cytometry measured cDC2 populations in the lesion and spleen, and ELISA quantified levels of key inflammatory factors in serum and lesions. Mice with psoriasis alone showed anxiety symptoms, which were significantly exacerbated in the comorbid group. The comorbid group exhibited more severe lesions, with elevated levels of IL-23 and IL-17A in both serum and lesions compared to the psoriasis-only group. The number of CD11c + cDCs in the dermis and the proportion of cDC2s in the lesion and spleen were also significantly higher in the comorbid group. Psychological stress intensifies anxiety symptoms and exacerbates the inflammatory response in the skin and systemic tissues of mice with comorbid psoriasis and psychological stress. This occurs via the overactivation of the IL-23/Th17 inflammatory axis, leading to increased mobilisation of cDC2s and higher levels of inflammatory mediators like IL-23 and IL-17A, thus chronicling inflammation. These findings enhance our understanding of the mechanisms linking psoriasis and psychological disorders, paving the way for identifying potential therapeutic targets.

关键词： Knockout   NLRC5   NOD-like receptor   VHSV   Zebrafish  

摘要： Nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) have complex and diverse functions. Studies in mammalian models have indicated a clear role of NLRC5 in the regulation of MHC-I gene expression. The nlrc5 KO zebrafish model was generated using CRISPR/Cas9 technology to understand its function with respect to VHSV. The VHSV infection experiment demonstrated higher mortality in nlrc5 KO fish with higher VHSV copy numbers. Virus-infected pathology, such as tissue swelling, hemorrhage, and eye bulging, was significantly higher in the nlrc5 KO fish. Expressional analysis of ifn system genes indicated the significant upregulation of ifnφ1 . Gene expression analysis during VHSV infection indicated a significant downregulation of MHC-I genes in the nlrc5 KO model compared to the wild-type (WT). Owing to the impact of MHC-I, the viral copy number may increase with higher mortality under VHSV infections. For neutrophil migration analysis, a nlrc5 KO and a neutrophil-labeled model were developed ( nlrc5 -/- Tg(mpx:mcherry) ). Injury was generated in the caudal fin, and the injury site was stimulated with poly I: C. The number of neutrophils were reduced in the nlrc5 KO fish. Levels of critical cytokines responsible for neutrophil migration were significantly reduced in nlrc5 KO fish during VHSV infection. The data from the current study in zebrafish reconfirm the observations in mammalian models, and neutrophil migration analysis suggests that Nlrc5 may be associated with inflammatory activation in the presence of VHSV.

关键词： 过敏反应   血清免疫球蛋白G4   免疫治疗  

摘要： 变应原特异性免疫球蛋白G4（IgG4）在过敏性疾病中的临床意义复杂。作为IgG抗体的一个亚类，IgG4具有独特的抗原结合片段，能够以单价方式与双特异性抗原结合，但与补体C1q和结晶片段γ受体结合的亲和力较低，通常表现出非炎症特征。IgG4在过敏性疾病中的作用存在争议，在变应原免疫治疗中，IgG4作为一种耐受诱导剂，通过竞争变应原结合来阻断IgE的活性，发挥保护作用，但食物特异性IgG4在不应作为食物过敏的诊断工具。此外，IgG4在嗜酸性粒细胞性食管炎等疾病中的致病作用也得到了关注。本文综述了IgG4的结构、功能及其在过敏性疾病中的作用，以期加深临床医务工作者对IgG4价值的认识，并为IgG4的正确应用提供指导。

关键词： MT: Regular Issue   adenovirus   high-capacity vectors   dendritic cell   gene therapy   cancer vaccination   tumor vaccination   targeted transduction   lymph node   IL-2v   IL-21  

摘要： Adenoviral vectors demonstrate encouraging clinical outcomes for B and T cell vaccines. With such approaches, multiple payloads can be delivered, beyond the antigen itself. Nevertheless, the human adenoviral vector serotype C5 (HAdV5) exhibits limited transduction efficiency to dendritic cells (DCs), therefore necessitating very high viral loads. Targeting antigen-presenting cells (APCs) has remained challenging. To solve this problem, we developed a versatile platform that employs modular retargeting adapters to enhance transduction of specific cell types, including challenging host cells. By rational design, we constructed a dual-adapter for DC-SIGN and CD11c and demonstrate successful targeting of HAdV5 to human and murine DCs. Our in vivo characterization highlights improved and specific transduction of DCs in draining lymph nodes. Moreover, a tumor vaccination study demonstrates the advantageous co-expression of T cell stimulatory cytokines (interleukin [IL]-2v or IL-21) locally in lymph nodes alongside a potent tumor antigen. Lymph node-directed gene therapy at significantly reduced vector loads may circumvent systemic toxicity of stimulating payloads. Our proposed low-dosage DC-targeted vaccine may offer an effective solution for patients and potentially minimize adenovirus-related side effects. The robust immunogenicity of HC-HAdV5, with its large coding capacity (37 kbp DNA), opens up exciting possibilities for future therapeutic combination strategies.

摘要： BACKGROUND AND OBJECTIVES:Takayasu arteritis (TAK) is a rare large-vessel vasculitis primarily affecting young female patients, with pediatric cases being even rarer. Biologic therapies, such as anti-tumor necrosis factor (anti-TNF) and anti-interleukin-6 (anti-IL-6) agents, have become integral to TAK treatment; however, their use in children is not well supported by robust data due to the rarity of the disease. This systematic review aimed to evaluate the use, effectiveness, and safety of anti-TNF drugs and tocilizumab in the treatment of pediatric TAK. METHODS:We conducted a systematic literature search in PubMed/MEDLINE and Scopus databases from their inception until 15 December 2024. Studies were eligible if they included pediatric patients with TAK (diagnosed before 18 years of age) treated with anti-TNF or anti-IL-6 drugs and reported clinical outcomes. Clinical trials, observational studies, case series, and reports were included. Data were extracted independently by two reviewers. Only English articles were analyzed. Due to heterogeneity in study designs and reporting, a narrative synthesis was performed. RESULTS:A total of 94 reports involving 225 pediatric patients with TAK who received 262 treatment courses of biologic treatment were included. Anti-TNF drugs were more frequently used than tocilizumab (74.2% versus 36.9%, p < 0.001). Both groups showed comparable effectiveness, with clinical improvement observed in 64.9% of anti-TNF drug and 70.9% of tocilizumab treatment courses (p = 0.438). The frequency of relapse was also similar between the two groups (~50% in both groups, p = 0.472). Hypertension was more prevalent in the anti-TNF group (p = 0.004), while concurrent glucocorticoid administration was more frequent in the tocilizumab group (p = 0.024). Infliximab was the most frequently used anti-TNF drug, with a higher proportion of patients showing improvement compared with adalimumab (71.1% versus 45.5%). Adverse events were only reported with infl

关键词： Heavy metals   PANSS   Schizophrenia   Severity   Stroop test   TNF-α  

摘要： The presence of hazardous heavy metals (HMs) in the environment is well established, and numerous studies have explored their involvement in brain-related disorders. However, their potential impact on neuroinflammation, disease severity, and cognitive function in schizophrenia (SZ) remains largely unexplored. Therefore, this study aimed to investigate the potential pathophysiological role of environmental HMs in SZ. A total of 40 SZ patients and 40 healthy controls (HCs) were recruited from AIIMS Jodhpur, India. Blood samples were analyzed for lead (Pb), cadmium (Cd), arsenic (As), aluminium (Al), and TNF-α using atomic absorption spectroscopy and ELISA, while TNF-α gene expression was quantified using RT-qPCR. Patients exhibited notably elevated concentrations of Cd and Pb while decreased levels of As with median (IQR), 0.9 (0.40-1.72); 1.11 (0.59-1.26); and 0.73 (0.46-0.89) compared to HCs with median (IQR), 0.75 (0.46-1.06); 0.11 (0.04-0.18); and 0.92 (0.65-1.60) respectively. A significant positive relationship between TNF-α gene expression and blood As (ρ = 0.33, p < 0.05) and a negative association between Pb and Al (ρ = -0.34; p < 0.05) were reported in the patient group. Cognitive focus test scores were significantly lower in patients than in controls (p < 0.001). Cd levels negatively correlated with Stroop Word, Stroop Color, Color-Word, and Stroop Total scores (ρ =  - 0.28, - 0.36, - 0.28, - 0.33), indicating cognitive dysfunction. Additionally, PANSS score correlated negatively with Stroop Word (ρ =  - 0.36) and Stroop Total (ρ =  - 0.35), while PANSS Total scores showed negative correlations with Stroop Total (ρ =  - 0.33) and Stroop Color (ρ =  - 0.34), linking higher disease severity to poorer cognitive performance. In conclusion, these findings provide novel insights into SZ pathophysiology, highlighting the neurotoxic impact of heavy metals on TNF-α regulation, neuroinflammation, and cognition. The relationship between cognitive function with Cd and

关键词： Interleukin-6   Kiss1 gene   Maternal high-fat diet   Methylation   Ten-eleven translocation methylcytosine dioxygenase 2  

摘要： Maternal high-fat diet (HFD) is known to impair the reproductive function of female offspring, but the underlying epigenetic mechanisms of this developmental programming remain unclear. In this study, female rats were fed either a control diet (CD; 10% kcal from fat) or an HFD (60% kcal from fat) prior to and during gestation and lactation. After weaning, female offspring were randomly assigned to continue on either a CD or HFD, resulting in four groups: C/C, C/HF, HF/C, and HF/HF. Maternal HFD significantly reduced primordial follicle numbers, increased follicular atresia and granulosa cell apoptosis, and disrupted sex hormone levels in female offspring at 3 months of age. Female offspring from HFD-fed dams exhibited reduced Kiss1 gene expression and increased promoter methylation in both the ovaries and hypothalami. Additionally, the IL-6/STAT3 pathway was activated, and the expression of Ten-eleven translocation methylcytosine dioxygenase 2 (TET2), a key regulator of DNA demethylation, was downregulated. Post-weaning exposure to a normal diet partially attenuated these effects by 6 months of age. Furthermore, in vitro experiments demonstrated that IL-6/STAT3 signaling downregulated the expression of TET2 and Kisspeptin. Overall, our study demonstrates that maternal HFD consumption reduces TET2 expression in the ovaries and hypothalami of female offspring via the IL-6/STAT3 pathway, leading to Kiss1 promoter hypermethylation and a subsequent decrease in Kisspeptin levels. These findings highlight a potential epigenetic mechanism linking maternal diet to long-term reproductive toxicity in female offspring.