Journal of Inflammation Research最新文献

{"title":"RNA-Based Therapies in Kidney Diseases.","authors":"Liang Hu, Ting Jin, Ning Zhang, Jin Ding, Lina Li","doi":"10.2147/JIR.S505252","DOIUrl":"10.2147/JIR.S505252","url":null,"abstract":"<p><p>Kidney diseases are major global health challenges, affecting over 750 million people worldwide. Despite significant efforts, effective treatment strategies are still insufficient. In recent years, RNA therapeutics have made substantial progress, and an increasing number of nucleic acid-based therapies have been approved, showing potential for treating various diseases (including kidney diseases). These therapies can target proteins, transcripts, and genes that were previously considered \"undruggable\", allowing for the regulation of their expression and the expansion of therapeutic targets. Among RNA therapeutics, mRNA-based therapies are particularly promising because they can rapidly express therapeutic proteins, along with their design flexibility and potential to target previously inaccessible disease mechanisms. This review discussed various RNA-based strategies for developing new treatments, including antisense and RNA interference technologies, mRNA-based approaches, and CRISPR-Cas-mediated genome editing. Additionally, we highlighted the opportunities and challenges associated with the widespread application of these therapies in kidney disease treatment.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3143-3160"},"PeriodicalIF":4.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Biomarkers in Coronary Artery Disease: Insights From Mendelian Randomization and Transcriptomics.","authors":"Zhilin Xiao, Xunjie Cheng, Yongping Bai","doi":"10.2147/JIR.S507274","DOIUrl":"10.2147/JIR.S507274","url":null,"abstract":"<p><strong>Background: </strong>The identification of inflammatory genes linked to coronary artery disease (CAD) helps to enhance our understanding of the disease's pathogenesis and facilitate the identification of novel therapeutic targets.</p><p><strong>Methods: </strong>Inflammation-related genes (IRGs) were downloaded from the Msigdb database. Differentially expressed genes (DEGs) were determined by comparing CAD group with the control group in the GSE113079 and GSE12288 datasets. Key module genes associated with CAD were identified through weighted gene co-expression network analysis (WGCNA). Differentially expressed IRGs (DE-IRGs) were established by intersecting the DEGs, key module genes, and IRGs. Feature genes were derived using machine learning techniques. Mendelian randomization (MR) analysis was conducted to explore the causal relationship between CAD and the identified feature genes. Subsequently, a logistic regression model and an alignment diagram model were developed to predict the incidence of CAD.</p><p><strong>Results: </strong>In the given datasets, a total of 92 DE-IRGs were identified. Furthermore, twelve feature genes were discerned utilizing four distinct machine learning algorithms. Notably, two pivotal genes, HIF1A (odds ratio (OR) = 1.031, <i>P</i> = 0.024) and TNFAIP3 (OR = 1.104, <i>P</i> = 0.007), exhibited a causal relationship with coronary artery disease (CAD). Additionally, logistic regression and alignment diagram models demonstrated their efficacy in predicting the incidence of CAD. Ultimately, TNFAIP3 and HIF1A were significantly associated with T-cell receptor and NOD-like receptor signaling pathways.</p><p><strong>Conclusion: </strong>The identification of <i>TNFAIP3</i> and <i>HIF1A</i> as causal inflammatory biomarkers of CAD offers novel insights with significant clinical potential, which may provide valuable targets for the management and treatment of CAD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3177-3200"},"PeriodicalIF":4.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Olink Targeted Proteomics Identifies IL-17A as a Prospective Inflammatory Marker for the Prediction and Diagnosis of Kawasaki Disease.","authors":"Xueli Tu, Xueqi Chen, Liyan Xu, Chenxi Yang, Jingjing Li, Yiwen Liu, Bin Zhou","doi":"10.2147/JIR.S506154","DOIUrl":"10.2147/JIR.S506154","url":null,"abstract":"<p><strong>Purpose: </strong>Kawasaki disease (KD) is an acute febrile vasculitis and the leading cause of acquired heart disease in children. However, early diagnosis of KD remains challenging, and its pathogenic mechanisms are yet to be fully elucidated. This study utilized Olink Targeted Proteomics to analyze serum protein profiles and identify potential early diagnostic biomarkers for patients with KD.</p><p><strong>Methods: </strong>Based on febrile children final diagnosis, they were categorized into either the KD group or the febrile control (FC) group. Serum samples from each group were randomly selected and analyzed using the Olink Target 96 Inflammation panel. A retrospective analysis of clinical data was also conducted. By integrating the results of the Olink analysis with clinical data, receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic potential and critical thresholds of the identified biomarkers.</p><p><strong>Results: </strong>This study identified 25 differentially expressed proteins, with 18 upregulated and 7 downregulated proteins in the KD group. Using LASSO regression analysis, we identified 5 protein biomarkers, IL-17A, CCL23, SCF, TWEAK, and NT-3, that could be used to distinguish KD from FC. Among these, IL-17A exhibited the greatest fold change. Additionally, a subset of the participants underwent serum cytokine testing within the first 5 days of fever onset during hospitalization. Our retrospective analysis of this clinical data found that IL-17 levels were significantly elevated in children subsequently diagnosed with KD.</p><p><strong>Conclusion: </strong>Our results suggest that inflammation-associated serum proteins are strongly linked to KD. Among the identified biomarkers, IL-17 family, especially IL-17A, showed the best correlation, providing clinicians with a new potential biomarker for early diagnosis of KD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3093-3103"},"PeriodicalIF":4.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Interleukin-6 Family Cytokines and the Role in Respiratory Diseases.","authors":"Tuo Ji, Guanhong Huang, Yudie Cao, Yuzhi Gao, Xuzhu Gao","doi":"10.2147/JIR.S508031","DOIUrl":"10.2147/JIR.S508031","url":null,"abstract":"<p><p>The interleukin-6 (IL-6) family of cytokines includes IL-6, IL-11, IL-27, IL-31, etc. These cytokines are intimately linked with inflammatory diseases and exhibit pleiotropic properties. Several factors, including air pollution, smoking, and an aging population, are contributing to the changing epidemiology of respiratory diseases. A high incidence of respiratory disease represents a significant burden on society and the economy. The prominent role of IL-6 family members in respiratory diseases has been extensively studied, and they influence the disease process through multiple mechanisms and has significant clinical relevance in respiratory diseases. Here, we describe the role of IL-6 family cytokines and their signaling pathways on various immune cells, as well as the research progress on IL-6 family cytokines in respiratory diseases in recent years. The aim of this review is to provide an in-depth analysis of the key role of the IL-6 family in respiratory diseases and to provide a solid theoretical basis for further research and clinical practice in this field.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3125-3141"},"PeriodicalIF":4.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Multi-Level Investigation of Friend Leukemia Integration 1 Transcription Factor as a Novel Immune-Inflammatory Biomarker in Rheumatoid Arthritis: Bridging Bioinformatics, Clinical Cohorts, and Mechanistic Validation.","authors":"Mengyu Zhang, Lei Wan, Haoxiang Fang, Xiaojun Zhang, Siyu Wang, Feng Li, Dawei Yan","doi":"10.2147/JIR.S507941","DOIUrl":"10.2147/JIR.S507941","url":null,"abstract":"<p><strong>Introduction: </strong>Friend Leukemia Integration 1 Transcription Factor (FLI1) has attracted attention due to its involvement in rheumatoid arthritis (RA). Nevertheless, the precise mechanism through which FLI1 contributes to RA remains elusive. We investigated the potential role of FLI1 in RA through integrated bioinformatics, clinical experiments, and cellular experiments.</p><p><strong>Methods: </strong>Based on the GSE1919 and GSE12021 datasets, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses identified <i>FLI1</i> as a differential gene in RA. Clinical validation was performed by measuring the FLI1 expression in the serum collected from RA patients. Correlational analysis between FLI1 and immune-inflammatory markers confirmed its association with RA inflammation. WGCNA analysis, along with the KnockTF, JASPAR, and ENCODE databases, was employed to predict the potential target genes of FLI1. Receiver operating characteristic analysis and gene-set enrichment analysis-KEGG were conducted to elucidate the biological functions of these target genes. Finally, cellular experiments were performed to validate FLI1's regulatory effects on its target genes and its impact on synovial cell viability and apoptosis in RA.</p><p><strong>Results: </strong>FLI1 was upregulated in RA. FLI1 exhibited positive correlations with CRP, ESR, CCP, RF, IL-6, IL-10, IL-8, and TNF-α. The combined detection of FLI1 with CRP, ESR, CCP, and RF demonstrated the highest efficacy in evaluating RA disease activity. The target genes most strongly associated with FLI1 were AGA, DCK, LRRC15, MAN2A1, and TES, all of which exhibited positive correlations with FLI1. The suppression of FLI1 expression led to a decreased expression of AGA, DCK, LRRC15, MAN2A1, and TES. Furthermore, the inhibition of FLI1 reduced the viability of RA synovial cells and promoted their apoptosis.</p><p><strong>Discussion: </strong>FLI 1 is upregulated in RA and can promote inflammation, increase RA synovial cell viability, or inhibit synovial cell apoptosis. This finding suggests that FLI 1 and its target genes may serve as novel therapeutic targets in RA. The present findings integrate bioinformatics and experimental approaches to advance our current understanding of RA and open new avenues for targeted therapies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3105-3123"},"PeriodicalIF":4.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of TPT-260 in Ischemic Stroke: An Investigation Into Its Anti-Inflammatory Effects and Impact on Microglial Activation.","authors":"Jun Qian, Xiaoming Guo, Qian Xu, Zhidong Huang","doi":"10.2147/JIR.S497030","DOIUrl":"10.2147/JIR.S497030","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is characterized by a high incidence and elevated mortality. Ischemic events trigger neuroinflammation, leading to severe brain edema and neuronal necrosis. Microglia are the primary mediators of neuroinflammation. Inhibition of M1 microglia effectively alleviate neuronal damage in mild stroke. TPT-260 is a minimally cytotoxic, small molecule chaperone of the retromer complex, which mediates the recycling and trafficking of membrane protein receptors. This study explores the therapeutic effects and related mechanisms of TPT-260 in stroke model mice from an anti-inflammatory perspective, aiming to evaluate the efficacy and mechanism of TPT-260 in treating stroke.</p><p><strong>Methods: </strong>In this study, a middle cerebral artery occlusion (MCAO) animal model was established to simulate ischemic stroke. Primary microglia were cultured for lipopolysaccharides treatment to construct M1 microglia. Both animals and cells were treated with TPT-260. Nuclear factor-κB (NF-κB) nuclear translocation and the expression of downstream pro-inflammatory factors Interleukin 1β (IL-1β) and Tumor necrosis factor-α (TNF-α) were determined.</p><p><strong>Results: </strong>In vivo results revealed that TPT-260 significantly reduced the brain infarct area and inflammation as well as improved the neurological function of the stroke model mice. The potential mechanism of TPT-260 involved the marked inhibition of the lipopolysaccharides-induced M1 microglia by suppressing NF-κB nuclear translocation and attenuating the expression IL-1β and TNF-α. Moreover, TPT-260 inhibited NOD-like receptor protein 3 and reduced inflammasome formation, thereby decreasing the release of mature IL-1β and alleviating neuroinflammation.</p><p><strong>Conclusion: </strong>TPT-260 attenuated M1 microglia via repression of NF-κB signaling, thus preventing neuroinflammation and neuronal injuries in stroke model mice.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3055-3066"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis of Multi-Omics Data on RNA Polymerase as an Adverse Factor in Head and Neck Squamous Cell Carcinoma.","authors":"Yu-Jia Gu, Jie Zhang, Yuan-Jie Liu, Qian Zhang, Qi-Feng Geng","doi":"10.2147/JIR.S496748","DOIUrl":"10.2147/JIR.S496748","url":null,"abstract":"<p><strong>Background: </strong>High transcription levels are essential for cancer cells to maintain their malignant phenotype. While RNA polymerases (POLRs) have been implicated in various transcriptional mechanisms, their impact on the tumor microenvironment (TME) remains poorly understood.</p><p><strong>Methods: </strong>We analyzed publicly available pan-cancer cohorts to evaluate the expression and genomic alterations of POLRs. Focusing on head and neck squamous cell carcinoma (HNSC), we integrated bulk RNA sequencing, single-cell, and spatial transcriptome data to identify POLR2C expression patterns and its potential regulation by Yin Yang 1 (YY1). In vitro and in vivo experiments were conducted to validate the functional role of the YY1-POLR2C axis in cancer proliferation and immune modulation.</p><p><strong>Results: </strong>POLRs were found to be aberrantly expressed in cancers and associated with genomic alterations. In HNSC, POLR up-regulation was linked to poor prognostic features. POLR2C was significantly up-regulated in malignant cells, and its expression appeared to be transcriptionally regulated by YY1. Functional studies demonstrated that the YY1-POLR2C axis drives cell-cycle dysregulation and malignant proliferation in HNSC. Additionally, high POLR expression negatively correlated with immune cell infiltration and facilitated immune evasion. Mechanistically, POLRs mediated frequent interactions between malignant and immune cells, potentially contributing to resistance to immunotherapy.</p><p><strong>Conclusion: </strong>This study highlights the dual role of POLRs in promoting malignant proliferation and shaping an immunosuppressive TME. POLR2C, regulated by YY1, emerges as a critical mediator in HNSC and a promising target for precision therapies.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3067-3091"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Channels and Transporters in Ischemic Brain Edema.","authors":"Jianping Yu, Bozhi Zhang, Xin Yang, Yongjun Tan, Yuanfeng Zhou, Jiexin Li, Xinyue Mu, Yu Ren, Li Zhou, Qin Yang","doi":"10.2147/JIR.S503231","DOIUrl":"10.2147/JIR.S503231","url":null,"abstract":"<p><p>Brain edema is one of the most devastating consequences of acute ischemic stroke, but an effective and preventive therapy targeting the formation of ischemic brain edema has not yet to be validated. Ischemic brain edema is primarily caused by damage to the blood-brain-barrier, leading to the leakage of ions and water into the brain tissue. Ion channels and transporters play a crucial role in ischemic brain edema. Understanding their function and regulation mechanism could provide valuable insights into new therapeutic targets for ischemic brain edema. Recently, significant progress has been made in the study about ion channels and transporters as therapeutic targets for ischemic brain edema. In this review, we summarize ion channels and transporters involved in the formation of ischemic brain edema, including trigger force, physiological function, regulatory mechanisms, and detection technologies. Especially, we will focus on the roles of these ion channels and transporters in ischemic brain edema, as well as recent advances in therapeutic strategies targeting these transporters.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3025-3038"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updating on the Dual Role of Salivary Gland Epithelial Cell (SGEC) in Sjögren's Disease.","authors":"Wen Zhu, Yun Lu, Yifan Zhu, Xiaohan Huang, Yue Wang","doi":"10.2147/JIR.S509220","DOIUrl":"10.2147/JIR.S509220","url":null,"abstract":"<p><p>Sjögren's disease, an autoimmune inflammatory disease, currently lacks effective treatment options. The salivary gland, a crucial exocrine organ responsible for saliva production and local immune responses on mucous membranes, is frequently impaired in individuals with Sjögren's disease. Restoring salivary gland function poses a significant challenge for researchers. Salivary epithelial cells, recognized as pivotal components of the salivary gland, have been increasingly implicated as key initiators of inflammation and exhibit innate immune cell-like properties. On the whole, SGEC plays a protective role in the physiological state, and can also participate in the persistence of inflammation as an initiating factor in the pathological state. In the review, we explore the interplay between Ca+, endoplasmic reticulum (ER), and mitochondrial homeostasis imbalance in salivary epithelial cells. Additionally, we provide an overview of current literature on research advancements related to Pattern Recognition Receptors (PRRs), programmed cell death, posttranslational modification (PTM), and oral microecology, etc. specifically focusing on their implications in salivary epithelial cells. Given the crucial role of salivary gland epithelial cells in the onset of Sjögren's disease, a treatment based on salivary gland epithelial cells may have the potential to alleviate the condition by addressing the inflammatory response in the salivary glands.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3039-3053"},"PeriodicalIF":4.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying and Validating Prognostic Hyper-Inflammatory and Hypo-Inflammatory COVID-19 Clinical Phenotypes Using Machine Learning Methods.","authors":"Xiaojing Ji, Yiran Guo, Lujia Tang, Chengjin Gao","doi":"10.2147/JIR.S504028","DOIUrl":"10.2147/JIR.S504028","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 exhibits complex pathophysiological manifestations, characterized by significant clinical and biological heterogeneity. Identifying phenotypes may enhance our understanding of the disease's diverse trajectories, benefiting clinical practice and trials.</p><p><strong>Methods: </strong>This study included adult patients with COVID-19 from Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, between December 15, 2022, and February 15, 2023. The k-prototypes clustering method was employed using 50 clinical variables to identify phenotypes. Machine learning algorithms were then applied to select key classifier variables for phenotype recognition.</p><p><strong>Results: </strong>A total of 1376 patients met the inclusion criteria. K-prototypes clustering revealed two distinct subphenotypes: Hypo-inflammatory subphenotype (824 [59.9%]) and Hyper-inflammatory subphenotype (552 [40.1%]). Patients in Hypo-inflammatory subphenotype were younger, predominantly female, with low mortality and shorter hospital stays. In contrast, Hyper-inflammatory subphenotype patients were older, predominantly male, exhibiting a hyperinflammatory state with higher mortality and rates of organ dysfunction. The AdaBoost model performed best for subphenotype prediction (Accuracy: 0.975, Precision: 0.968, Recall: 0.976, F1: 0.972, AUROC: 0.975). \"CRP\", \"IL-2R\", \"D-dimer\", \"ST2\", \"BUN\", \"NT-proBNP\", \"neutrophil percentage\", and \"lymphocyte count\" were identified as the top-ranked variables in the AdaBoost model.</p><p><strong>Conclusion: </strong>This analysis identified two phenotypes based on COVID-19 symptoms and comorbidities. These phenotypes can be accurately recognized using machine learning models, with the AdaBoost model being optimal for predicting in-hospital mortality. The variables \"CRP\", \"IL-2R\", \"D-dimer\", \"ST2\", \"BUN\", \"NT-proBNP\", \"neutrophil percentage\", and \"lymphocyte count\" play a significant role in the prediction of subphenotypes. Use the identified subphenotypes for risk stratification in clinical practice. Hyper-inflammatory subphenotypes can be closely monitored, and preventive measures such as early admission to the intensive care unit or prophylactic anticoagulation can be taken.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"3009-3024"},"PeriodicalIF":4.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}