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关键词： Repeated exposures   Fine particles   Antiviral signalling pathways   Interferons   Mitochondria   Autophagy   AhR   Aryl hydrocarbon Receptor   AIM2   Absent In Melanoma 2   ALI   Air-Liquid Interface   ATG5   Autophagy protein 5   ATG12   Autophagy protein 12   BAL   BronchoAlveolar Lavage   BNIP3   BCL2-interacting protein 3   CCL5   Chemokine C-C Ligand 5   cGAS-independent STING   cyclic GMP-AMP synthase independent Stimulator of Interferon Genes   COPD   Chronic Obstructive Pulmonary Disease   CXCL9   C-X-C motif chemokine Ligand 9   CXCL10   C-X-C motif chemokine Ligand 10   CXCL11   C-X-C motif chemokine Ligand 11   CYP1A1   Cytochrome P450 family 1 subfamily A member 1   DEP   Diesel Exhaust Particles   DPPC   1,2-Dipalmitoyl-rac-glycero-3-phosphocholine   DRP1   Dynamin-Related Protein 1   ELISA   Enzyme Linked ImmunoSorbent Assay   FCCP   carbonyl cyanide-4(trifluoromethoxy)-phenylhydrazone   FDR   False Discovery Rate   FIS1   Mitochondrial Fission 1 protein   IAV   Influenza A Virus   IFN   Interferon   IFNA2   Interferon α 2   IFNAR   Interferon α/β Receptor   IFNB/IFN-β   Interferon-β   IL-6   InterLeukin-6   IL-8   InterLeukin-8   IRF   Interferon Regulatory Factor   ISG   Interferon-Stimulated Gene   JAK   Janus Kinase   KEGG   Kyoto Encyclopedia of Genes and Genomes   LC3   microtubule-associated protein 1A/1B-Light Chain 3   M2   Matrix 2   MAVS/IPS-1   Mitochondrial AntiViral Signalling   MDCK   Madin-Darby Canine Kidney   MDA-5   Melanoma Differentiation-Associated protein 5   MFF   mitochondrial fission factor   MFN2   Mitofusin-2   MOI   Multiplicity Of Infection   NF-κB   Nuclear Factor kappa B   OCR   Oxygen Consumption Rate   OPA1   Optic Atrophy 1   MiD49   mitochondrial dynamics protein of 49 kDa   MiD51   mitochondrial dynamics protein of 51 kDa   p62/SQSTM1   Ubiquitin-binding protein 62/Sequestosome-1   PAHs   Polycyclic Aromatic Hydrocarbons   pfu   plaque-forming units   p.i.   post-infection   PINK1   PTEN-induced putative Kinase 1   PM   2.5   Particulate Matter 2.5   PM   10   Particulate Matter 10   RIG-I/DDX58   Retinoic acid-Inducible Gene I   RLR   RIG-I-Like Receptor   ROS   Reactive Oxygen Species   RSV   Respiratory Syncytial Virus   SARS-CoV-2   Severe Acute Respiratory Syndrome Coronavirus 2   STAT   Signal Tr  

摘要： Humans are exposed to various contaminants, including fine atmospheric particles (PM 2.5 ) and respiratory viruses. Epidemiological studies have demonstrated a positive association between exposure to PM 2.5 and the severity of viral infections, including those caused by influenza viruses. Nevertheless, there is a paucity of in vitro studies investigating the underlying mechanisms, especially in the context of repeated exposures to PM 2.5 , which more realistically reflect human exposure. This study aimed to perform repeated exposures to PM 2.5 collected in Paris on an in vitro bronchial epithelium model at the air-liquid interface (ALI) prior to infection with influenza A virus (IAV), and assessed modulations of antiviral responses. This work firstly demonstrated particle internalisation and a sustained pro-inflammatory response during repeated exposures to PM 2.5 . Repeated exposures to PM 2.5 prior to IAV infection revealed a downregulation of the interferon (IFN) pathway without modulation of the pro-inflammatory response. Furthermore, mitochondrial dysfunction was observed following repeated PM 2.5 exposures, as well as an accumulation of autophagic vesicles and p62 protein. This suggests the involvement of mitochondrial alteration and/or blockage of autophagic flux in the modulation of the IFN signalling pathway, and warrants further investigation.

关键词： T淋巴细胞亚群   慢性阻塞性肺疾病急性加重期   老年   短期预后   再住院  

摘要： 目的 评价T淋巴细胞亚群分布对老年AECOPD病人短期预后和出院后1年内再次住院的预测价值。方法 回顾性分析2022年1月-2023年9月在我院住院治疗的104例老年AECOPD患者的临床资料,根据预后情况分为预后良好组和预后不良组,根据出院后1年内再住院情况分为再住院组和非再住院组。比较各组的一般资料以及T淋巴细胞亚群水平,并采用受试者工作特征（ROC）曲线分析T淋巴细胞亚群对老年AECOPD患者短期预后及1年内再住院的预测效能。结果 单因素分析显示预后良好组血清CD8+百分比明显低于预后不良组,CD3+、CD4+百分比以及CD4+/CD8+显著高于预后不良组（P<0.05）;再住院组血清CD8+百分比明显高于非再住院组,CD3+、CD4+百分比以及CD4+/CD8+显著低于非再住院组（P<0.05）。Logistic回归分析结果显示CD3+、CD4+是影响AECOPD患者短期预后及1年内再住院的潜在因素（P<0.05）。ROC分析显示CD3+和CD4+预测预后不良的AUC分别为0.751 （95%CI:0.659～0.843）和0.737（95%CI:0.632～0.842）,最佳预测值分别为63.25%和35.61%;CD3+和CD4+预测1年内再住院的AUC分别为0.870（95%CI:0.801～0.938）和0.635 （95%CI:0.527～0.743）,最佳预测值分别为63.25%和38.48%。结论 CD3+和CD4+对AECOPD患者短期预后和1年内再住院有一定的预测价值,CD3+预测效能更高。

关键词： 肾小球肾炎，膜性   自身抗体   靶抗原   疾病诊断  

摘要： 抗磷脂酶A2受体抗体发现以来，借助不断发展和改进的检验方法学，原发性膜性肾病由最初的依赖肾组织活检穿刺确诊，逐渐演变为部分患者可通过血清学诊断。检测手段的演进和新抗原的发现推动原发性膜性肾病走向个性化诊疗。本文对原发性膜性肾病相关抗原抗体检测方法学做一综述，旨在探讨方法学的优缺点及未来可能的发展方向。

关键词： TNFα   autoimmune diseases   inflammation   protein–protein interactions   small molecules  

摘要： Most diseases are accompanied by an inflammatory response, making effective pharmacological control highly desirable. Tumor necrosis factor alpha (TNFα) is a key cytokine driving inflammatory and autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease. Although biological TNFα inhibitors revolutionized treatment, they have drawbacks including lacking blood-brain barrier penetration, parenteral administration, and immunogenicity. Recent studies highlight the potential of small-molecule approaches to target TNFα by stabilizing an asymmetrical, receptor-incompetent trimer conformation. Balinatunfib (also known as SAR441566) is an orally available small molecule designed to exploit this mechanism, thereby preventing TNFα from effectively binding to its receptors. In preclinical models, balinatunfib reduces inflammation comparably to biologic therapies, yet avoids the complexities of large protein therapeutics. This allosteric strategy involves capturing a sampled but distorted state of TNFα, thereby blocking receptor clustering and downstream proinflammatory signaling. The oral route of administration confers practical advantages in terms of patient compliance and could facilitate drug access to sites traditionally less amenable to biologics, such as the central nervous system. By demonstrating that small molecules can achieve high-affinity, conformation-based inhibition of TNFα, balinatunfib, and related compounds may result in a new area of orally administered therapies that advance the management of TNFα-mediated diseases.

摘要： Encephalitis, an inflammatory disorder of the brain caused by infections or autoimmune responses, is still a major global health concern due to its high morbidity, mortality, and long-term neurological consequences. The available therapy alternatives are usually confined, and conventional drug discovery procedures are both resource-intensive and time-consuming. These challenges underscore the critical need for novel tools to speed up therapy development, which could revolutionize treatment regimens and enhance results for impacted people globally. To identify, optimize & selection of TNF-α inhibitors as anti-encephalitis candidates by using in silico assisted drug design approach. Computer-aided drug design (CADD) is a revolutionize tool for identifying potential anti-encephalitis candidates through its ability to simulate molecular interactions, predict drug-target affinities, and optimize pharmacokinetic properties with molecular dynamics simulation. In this study, we have employed comprehensive in silico method to find effective therapeutic compounds that targets the TNF-α receptor in encephalitis. An in silico screening of nearly 600 isatin derivatives were conducted by using data from the PubChem database. It was carried out using the Lipinski rule of five in addition to other criteria. After filtering, 48 Isatin derivatives were selected, and six compounds with binding affinities exceeding −8.0 kcal/mol were identified as potential candidates. Additionally it was subjected to ADME analysis using Swiss ADME software. Every contender demonstrated greater binding affinity and actively crossed the BBB. Protein–ligand complexes were subjected to molecular dynamics (MD) simulations using CABS-flexV2.0 and the iMOD server in order to assess the root-mean-square fluctuations (RMSFs) and quantify protein stability respectively. Hence, it is concluded that compounds with higher binding affinity and actively cross BBB values showed effective anti-encephalitis ag

关键词： BK virus   HLA genotype   T cell donors   Virus-specific T cells  

摘要： PURPOSE:The increasing application of virus-specific T cell therapy for treating BK virus infections in immunocompromised patients highlights the necessity for rapid identification of compatible cell donors with optimal BK-specific T cell response. This study aims to characterize the BK virus-specific T cell response in relation to demographic factors, blood group, serological status, and HLA genotypes using samples from a cell donor registry. METHODS:Peripheral blood mononuclear cells from cell donors were stimulated with peptide pools derived from VP1 and LTA proteins, and the IFN-γ production was analyzed using ELISpot and validated by flow cytometry. RESULTS:Our findings provide an overview of the T cell response to BK virus proteins in healthy donors, revealing associations with demographic characteristics, RhD status, CMV or EBV serological status, and HLA alleles. Remarkably, RhD-negative, CMV-seronegative, and EBV-seronegative donors showed a major T cell response against BK virus proteins. Notably, certain HLA alleles were associated with either enhanced or diminished T cell response. Furthermore, our results suggest that HLA-B leader dimorphism, specifically the presence of threonine at position 2, influences the VP1-specific immune response, resulting in enhanced T cell activation. CONCLUSION:This study, beyond advancing our understanding of the relationship between donor characteristics and BK virus-specific T cell response, has significant implications for improving the selection of optimal cell donors for patient-specific adoptive therapy.

摘要： Interleukin-18 has broad immune regulatory functions. Genomic data and enhanced Magnetic Resonance Imaging data related to LGG patients were downloaded from The Cancer Genome Atlas and Cancer Imaging Archive, and the constructed model was externally validated using hospital MRI enhanced images and clinical pathological features. Radiomic feature extraction was performed using “PyRadiomics”, feature selection was conducted using Maximum Relevance Minimum Redundancy and Recursive Feature Elimination methods, and a model was built using the Gradient Boosting Machine algorithm to predict the expression status of IL18. The constructed radiomics model achieved areas under the receiver operating characteristic curve of 0.861, 0.788, and 0.762 in the TCIA training dataset (n = 98), TCIA validation dataset (n = 41), and external validation dataset (n = 50). Calibration curves and decision curve analysis demonstrated the calibration and high clinical utility of the model. The radiomics model based on enhanced MRI can effectively predict the expression status of IL18 and the prognosis of LGG.

关键词： psoriasis   psoriasis treatment   skin diseases  

关键词： HLA-DPB1*1156:01:02   next-generation sequencing   novel allele  

摘要： HLA-DPB1*1156:01:02 differs from HLA-DPB1*1156:01:01 by a single nucleotide substitution at position 262 C>A.

关键词： anti-IL-5R   anti-IL4Ra   anti-IL5   anti-IgE   biological treatment   chronic rhinosinusitis with nasal polyps   network meta-analysis   sinus surgery