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关键词： 型过敏反应   GPMT   豚鼠   细胞因子   免疫球蛋白  

摘要： 目的 研究豚鼠Ⅳ型过敏反应过程中细胞因子和免疫球蛋白的变化规律，为临床合理用药提供参考依据。方法 采用二硝基氯苯建立Ⅳ型过敏反应模型（豚鼠最大化过敏性试验），激发后1、5、24、48、72 h不同时间点评价豚鼠背部皮肤红斑、水肿及其致敏率，并测定豚鼠血清中白介素-2(IL-2)、干扰素-γ(IFN-γ)、免疫球蛋白E(IgE)和免疫球蛋白M(IgM)的含量。结果 激发后不同时间点，实验组动物背部皮肤均可见红斑、水肿，评分在5～24 h达峰值；致敏率在1～48 h达100%。激发后实验组与对照组相比，IL-2、IgE、IgM含量在各时间点升高或显著升高，但达峰时间并不一致；而IFN-γ含量逐渐降低或显著降低。结论 Ⅳ型过敏反应过程涉及多种免疫途径的相互作用，IL-2、IgE、IgM与IFN-γ的含量随时间变化而呈现不同的规律。

摘要： Interleukin-1 (IL-1) is a pro-inflammatory cytokine that exerts a wide range of neurological and immunological effects throughout the central nervous system (CNS) and is associated with the etiology of affective and cognitive disorders. The cognate receptor for IL-1, Interleukin-1 Receptor Type 1 (IL-1R1), is primarily expressed on non-neuronal cells (e.g., endothelial cells, choroidal cells, ventricular ependymal cells, astrocytes, etc.) throughout the brain. However, the presence and distribution of neuronal IL-1R1 (nIL-1R1) has been controversial. Here, for the first time, a novel genetic mouse line that allows for the visualization of IL-1R1 mRNA and protein expression (Il1r1GR/GR) was used to map all brain nuclei and determine the neurotransmitter systems which express nIL-1R1 in adult male mice. The direct responsiveness of nIL-1R1-expressing neurons to both inflammatory and physiological levels of IL-1 beta in vivo was tested. Neuronal IL-1R1 expression across the brain was found in discrete glutamatergic and serotonergic neuronal populations in the somatosensory cortex, piriform cortex, dentate gyrus, and dorsal raphe nucleus. Glutamatergic nIL-1R1 comprises most of the nIL-1R1 expression and, using Vglut2-Cre-Il1r1r/r mice, which restrict IL-1R1 expression to only glutamatergic neurons, an atlas of glutamatergic nIL-1R1 expression across the brain was generated. Analysis of functional outputs of these nIL-1R1-expressing nuclei, in both Il1r1GR/GR and Vglut2-Cre-Il1r1r/r mice, reveals IL-1R1+ nuclei primarily relate to sensory detection, processing, and relay pathways, mood regulation, and spatial/cognitive processing centers. Intracerebroventricular (i.c.v.) injections of IL-1 (20 ng) induces NF kappa B signaling in IL-1R1+ non-neuronal cells but not in IL-1R1+ neurons, and in Vglut2-Cre-Il1r1r/r mice IL-1 did not change gene expression in the dentate gyrus of the hippocampus (DG). GO pathway analysis of spatial RNA sequencing 1mo following restoration of n

关键词： Besoin de traitement   Compliance   Divergence   Dysmorphose   Faible revenu   IOTN   Niveau socio-économique   Version incisive  

摘要： Introduction: Patients from low socioeconomic backgrounds are empirically considered more difficult to treat. The objectives were to evaluate low socioeconomic status of patients as a factor associated with increased treatment need and the correlation between socioeconomic status and dysmorphosis on one hand, and cooperation level on the other. Material and Methods: This was a retrospective comparative monocentric observational cohort study. Included subjects were under 16 years old at the time of orthodontic braces placement and were beneficiaries of the complémentaire santé solidaire (C2S) or not (non-C2S). Evaluated criteria included treatment need (IOTN-DHC), antero-posterior and vertical dysmorphosis (FMA, ANB, IMPA, I/F), and compliance. Fisher and Wilcoxon tests were performed. A 5% threshold was retained. Results: Overall, 173 patients were included and divided into two groups: C2S/non-C2S. Neither treatment need nor skeletal and alveolar-dental dysmorphosis are correlated with socioeconomic status. Cooperation is correlated with low socioeconomic status across all evaluated criteria: three times more bracket debondings, three times more remarks about failure to wear elastics, 1.25 times more missed appointments, ten times more treatment abandonments. Conclusion: It may not be dysmorphosis that makes orthodontic treatment of low socioeconomic status patients more difficult, but rather a lack of cooperation. This calls for clinical and policy interventions to increase patient involvement in treatment. Randomized trials are needed to corroborate the results.;Introduction: Les patients de faible niveau socio-économique sont empiriquement considérés plus difficiles à traiter. Les objectifs de cette étude étaient d’évaluer le faible niveau socio-économique des patients comme facteur associé à un besoin de traitement augmenté et la corrélation entre le niveau socio-économique et la dysmorphose, d’une part, et le niveau de coopération d’autre part. Matériel et méth

关键词： 造血干细胞   造血干细胞移植   造血干细胞动员   细胞因子   血小板生成素   CXCR4拮抗剂   整合素拮抗剂   化疗   动员效能  

摘要： 背景：造血干细胞移植是一种广泛应用于血液系统恶性和非恶性疾病的重要治疗手段，动员和收集足够的造血干细胞是保证患者移植后快速、持续造血功能重建的前提，但最常用的粒细胞集落刺激因子联合或不联合化疗的经典方案仍有10%-40%的动员失败率。目的：综述近年来造血干细胞动员现状，分析不同方案的优缺点，展望未来动员新方案。方法：以“造血干细胞，造血干细胞移植，造血干细胞动员，细胞因子，血小板生成素，CXCR4拮抗剂，整合素拮抗剂，化疗，动员效能”为中文关键词，以“hematopoietic stem cell,hematopoietic stem cell transplantation,hematopoietic stem cell mobilization,cytokines,thrombopoietin,CXCR4 antagonists,integrin antagonist,chemotherapy,mobilization efficiency”为英文关键词，在CNKI、PubMed、万方数据库进行检索，文献语种限制为中文、英文，检索年限为1990-2024年，共检索到300多篇文献，最终纳入68篇文献进行分析。结果与结论：越来越多的研究发现粒细胞集落刺激因子联合普乐沙福、白细胞介素、血小板生成素及整合素拮抗剂等能够更加有效地动员造血干细胞，联合使用可以减少粒细胞集落刺激因子的使用剂量，减少相关不良反应。一些新药如可溶性重组flt3-配体(简称CDX-301)、双重α9β1/α4β1整合素抑制剂BOP等可与粒细胞集落刺激因子联合，促进造血干细胞动员。此外还发现一些潜在的动员靶点如前列腺素E2受体及1-磷酸鞘氨醇等，尚在研究阶段。除固有的患者特征、治疗特征外，开发纳入生物标志物的预测模型，有助于有效预测造血干细胞动员失败，提升干细胞动员技术。

关键词： Alzheimer’s disease   Bioinformatics analysis   HLA   Immunoinflammation   Molecular docking  

摘要： Alzheimer's disease (AD) is a common neurodegenerative disease, neuroinflammation is an early pathological feature of AD. However, the alteration of the immune microenvironment in asymptomatic AD was not fully explained. In this study, we aimed to utilize the transcriptome data of AD patients in public databases to reveal the change of immune microenvironment in asymptomatic AD and screen the potential anti-AD drug. Through a series of bioinformatics analyses, differentially expressed genes (DEGs) screening, enrichment analysis, PPI network construction, and hub gene identification were done. Meanwhile, the hub genes were validated in APP/PS-1(AD) mice. Importantly, seven enrichment pathways and eight hub genes associated with inflammation were identified in asymptomatic AD. Early AD patients presented infiltration of immunoinflammatory cells to varying degrees in the four representative brain regions. Correspondingly, more hub genes changed in the hippocampus in AD mice compared to the other four brain regions. Accompanied by the activation of microglia and astrocytes, the inflammation cytokines were increased in the hippocampus of AD mice. Moreover, HLA-C was correlated with the activation of microglia, HLA-DRB1 with IL-6 and OAS2 with TGF-β1 in the hippocampus. Five FDA-approved drugs (Itrazole, Dfo, Syrosingopine, Cefoperazone and Pradaxa) were predicted as the common drug-targeted HLA-C and HLA-DRB1 by molecular docking. Taken together, the changes in the immune microenvironment of asymptomatic AD, and provided a new perspective for the development of anti-inflammatory drugs for AD early treatment.

关键词： IL-10   Pleural remodeling   Systemic lupus erythematosus (SLE)  

摘要： BackgroundInterleukin-10 (IL-10), a pivotal anti-inflammatory cytokine, has gotten attention for its involvement in tissue remodeling and organ fibrosis. Pleurisy and subsequent pleural remodeling are recognized as quantifiable indicators of systemic lupus erythematosus (SLE) activity. However, the role of IL-10 in SLE-associated pleural remodeling remains unknown. In this study, we investigated role of IL-10 in SLE-associated pleural remodeling and the underlying *** data and serum specimens were obtained from SLE patients, while pleural mesothelial cells and mouse models served as primary experimental subjects. The protein expression-related technologies, histopathological staining, and other experimental methods were used in the *** investigation got several key findings. Firstly, serum obtained from SLE patients with pleural thickening was found to induce pleural mesothelial cell remodeling. Subsequently, heightened levels of IL-10 were found in serum from SLE patients with pleural thickening compared to that of SLE patients without pleural thickening. Secondly, administration of recombinant IL-10 was confirmed its ability to induce pleural mesothelial cell remodeling, on the contrary, this remodeling was effectively mitigated by IL-10 inhibition. Notably, blockade of IL-10 significantly prevented collagen deposition and prevented thickening in pleura of SLE mouse models. Lastly, the IL-10/JAK2/STAT3/HIF1 alpha/TMEM45A/P4HA1 signaling axis was elucidated to mediate pleural remodeling and *** study uncovered that IL-10 mediated pleural remodeling in SLE. We suggested that serum IL-10 level exceeding 6.32 pg/mL was a potential reference threshold for predicting pleural thickening in SLE patients.

关键词： HIV   CD4   T淋巴细胞   病毒载量   老年人   感染状况  

摘要： 目的 分析2023年上海市黄浦区新发现HIV感染者CD4+T淋巴细胞与病毒载量检测结果，探究两者相关性，为制定有针对性的预防控制措施和抗病毒治疗方案提供科学依据。方法 收集2023年上海市黄浦区新发现HIV感染者CD4+T淋巴细胞计数、病毒载量、人口学特征等数据并运用描述性流行病学方法进行分析。结果 黄浦区67例HIV新发现感染者CD4+T淋巴细胞计数均值为301.22±235.19个/μl，病毒载量均值为5.15×105±1.28×105拷贝/mL，不同年龄人群CD4+T淋巴细胞计数和病毒载量差异有统计学意义（P＜0.05），但性别和婚姻状况差异无统计学意义（P均＞0.05），CD4+T淋巴细胞计数和CD4/CD8比值与病毒载量log值呈负相关（r=-0.29，r=-0.378）。结论 2023年黄浦区新发现HIV感染者CD4+T淋巴细胞计数普遍偏低，高病毒载量感染者比例较高，老年感染者风险较大，老年群体已经逐渐成为黄浦区艾滋病防控的重点人群。建议扩大提高老年人群HIV筛查，降低HIV传播风险，提高早发现早治疗率。

关键词： Cytokines   Immunology   Infectious disease   T cells   Th1 response  

摘要： CD4+ T helper 1 (TH1) cells coordinate adaptive immune responses to intracellular pathogens, including viruses. Key to this function is the ability of TH1 cells to migrate within secondary lymphoid tissues, as well as to sites of inflammation, which relies on signals received through the chemokine receptor CXCR3. CXCR3 expression is driven by the TH1 lineage-defining transcription factor T-bet, and the cytokine-responsive Signal Transducer and Activator of Transcription (STAT) family members STAT1 and STAT4. Here, we identify the Ikaros zinc finger (IkZF) transcription factor Aiolos (Ikzf3) as an additional positive regulator of CXCR3 both in vitro and in vivo using a murine model of influenza virus infection. Mechanistically, we find that Aiolos-deficient CD4+ T cells exhibit decreased expression of key components of the IFNγ/STAT1 signaling pathway, including JAK2 and STAT1. Consequently, Aiolos deficiency results in decreased levels of STAT1 tyrosine phosphorylation and reduced STAT1 enrichment at the Cxcr3 promoter. We further find that Aiolos and STAT1 form a positive feedback loop via reciprocal regulation of each other downstream of IFNγ signaling. Collectively, our study demonstrates that Aiolos promotes CXCR3 expression on TH1 cells by propagating the IFNγ/STAT1 cytokine signaling pathway.

关键词： HLA class I   vaccine   epitope   CD8+T cell   immune response   correlate of protection   immuno-dominant   coverage metric  

摘要： Vaccines have historically played a pivotal role in controlling epidemics. Effective vaccines for viruses causing significant human disease, e.g., Ebola, Lassa fever, or Crimean Congo hemorrhagic fever virus, would be invaluable to public health strategies and counter-measure development missions. Here, we propose coverage metrics to quantify vaccine-induced CD8+ T cell-mediated immune protection, as well as metrics to characterize immuno-dominant epitopes, in light of human genetic heterogeneity and viral evolution. Proof-of-principle of our approach and methods are demonstrated for Ebola virus, SARS-CoV-2, and Burkholderia pseudomallei (vaccine) proteins.