Biomedical Journal最新文献

{"title":"Drug repurposing targeting miRNA–mRNA networks to mitigate areca nut-induced head and neck cancer","authors":"Hung-Han Huang ,&nbsp;Joseph T. Chang ,&nbsp;Guo-Rung You ,&nbsp;Yi-Chen Li ,&nbsp;Yi-Fang Huang ,&nbsp;Yu-Chen Huang ,&nbsp;Eric Yi-Liang Shen ,&nbsp;Yin-Ju Chen ,&nbsp;Ching-Chi Chiu ,&nbsp;Ann-Joy Cheng","doi":"10.1016/j.bj.2025.100886","DOIUrl":"10.1016/j.bj.2025.100886","url":null,"abstract":"<div><h3>Background</h3><div>Areca nut is a significant risk factor for head and neck cancer (HNC), yet its molecular mechanisms, particularly miRNA-mediated regulation, remain poorly understood. This study investigates the regulatory networks underlying areca nut-induced HNC and explores therapeutic strategies through computational drug repurposing.</div></div><div><h3>Materials and methods</h3><div>Arecoline was used to assess its effects on invasion, migration, and cisplatin resistance in HNC cells and normal keratinocytes. Differentially expressed miRNAs and mRNAs were identified using high-throughput profiling, followed by integrative network analysis using the TCGA-HNSC dataset and multiMiR. OncoPredict was used for drug repurposing to identify therapeutic agents targeting dysregulated miRNA–mRNA networks.</div></div><div><h3>Results</h3><div>Arecoline exposure promoted invasion and cisplatin resistance, with more pronounced effects in normal keratinocytes, indicating a potential role in early tumorigenesis. Integrative transcriptomic analysis revealed a miRNA–mRNA regulatory network comprising 1971 oncogenes, 604 tumor suppressors, 35 oncogenic miRNA (OncomiRs), and 36 tumor suppressor miRNA (TSmiRs) regulating pathways related to cell motility and stress response. A tumor-suppressive network with <em>miR-212-3p</em> as a central hub and an oncogenic network modulated by <em>miR-410</em> and <em>miR-1-3p</em> as critical hubs were identified. Drug repurposing analysis identified four potential therapeutic candidates (MK-2206, BYL-719, MG-132, and FGIN-1-27), with MK-2206 emerging as the most promising. MK-2206 effectively reversed arecoline-induced miRNA–mRNA dysregulation, mitigated malignant phenotypes, and selectively targeted HNC cells while sparing normal keratinocytes.</div></div><div><h3>Conclusions</h3><div>This integrative approach elucidates areca nut-driven carcinogenesis through miRNA–mRNA interactions and highlights MK-2206 as a promising therapeutic strategy for areca nut-associated HNC.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100886"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photodynamic therapy-induced inflammation and adverse effects: An updated review","authors":"Kave Moloudi,&nbsp;Heidi Abrahamse,&nbsp;Blassan P. George","doi":"10.1016/j.bj.2025.100889","DOIUrl":"10.1016/j.bj.2025.100889","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) is a non-invasive medical treatment that uses a photosensitizing agent and light to treat various medical conditions and ophthalmology including chronic central serous chorioretinopathy, cancer, skin disorders, and infections. Local inflammation in tumor environment after PDT can be effective in eliciting an immune response to improve treatment efficiency but it causes some early and long-term side effects in local and surround tissues, resulting leads to incidental effects and unwilling consequences such as pain, erythema and infection. Moreover, the mechanism of inflammation in PDT is not clear. Employment of non-optimized protocol including cytotoxic photosensitizer (PS) and fluence and fluence rate during PDT can bring biased outcomes for patients in terms of inflammation and treatment. In PDT, the minimum cytotoxicity and side effects of normal tissue depend on several factors, including the type and location of the tumor to be treated, the PS used, laser power, oxygen level, tumor properties and the patient's individual characteristics. Therefore, careful consideration and adjustment of these parameters are essential for achieving successful PDT outcome. However, in this topical review, various databases, including PubMed, ScienceDirect, and Google Scholar, were used to find relevant studies for this purpose. We highlighted various parameters that influence on cytotoxicity and inflammation response of normal tissue after PDT. Additionally, various pathways that PDT induced inflammation summarized as well as associated side effects have been categorized and finally, we proposed some factors to reduce the side effects and cytotoxicity to the normal tissue in future.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100889"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrepant treponemal test results: Identification of associated risk factors through machine learning technology in 18-year electronic medical records and national claims data","authors":"Hsin-Yao Wang ,&nbsp;Ru-Fang Hu ,&nbsp;Ting-Wei Lin ,&nbsp;Wan-Ying Lin ,&nbsp;Yu-Chiang Wang ,&nbsp;Jang-Jih Lu ,&nbsp;Yi-Ju Tseng","doi":"10.1016/j.bj.2025.100890","DOIUrl":"10.1016/j.bj.2025.100890","url":null,"abstract":"<div><h3>Background</h3><div>Syphilis is a prevalent disease diagnosed primarily through serological tests. Although one confirmatory treponemal tests (TT), including <em>Treponema pallidum</em> particle agglutination (TPPA) or fluorescent treponema antibody absorption (FTA-Abs), is required for syphilis diagnosis, multiple TTs are commonly administered throughout the disease course. Discrepant TT results can cause confusion and delay treatment. In this study, we identified the clinical characteristics of patients with discrepant TT results and developed a machine learning tool to evaluate the risk of TT discrepancies.</div></div><div><h3>Materials and methods</h3><div>In this retrospective cohort study, electronic health records were linked to national claims records collected from 2001 to 2018. Variables of interest in risk factor identification and machine learning model development included medical histories and demographic characteristics. The association between syphilis treatment and discrepant TT results was further assessed.</div></div><div><h3>Results</h3><div>Among 5780 eligible patients tested for syphilis, 133 (2.30 %) had discrepant TT results. HIV and AIDS were identified as prominent risk factors associated with discrepant TT results (adjusted odds ratio = 2.6, 95 % confidence interval = 1.4–4.7). Patients with a top 5 % risk probability in the LightGBM model were 10 times more likely than others to have discrepant TT results. TPPA was more likely than FTA-Abs to become negative after treatment among patients with discrepant TT results (odds ratio = 14.7, 95 % confidence interval = 1.9–115.4).</div></div><div><h3>Conclusions</h3><div>Risk factor identification and machine learning model development can support the interpretation of serological tests for syphilis, enabling accurate diagnosis and clinical decision-making.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100890"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clockwork macrophage: Timing in innate immunity","authors":"Siyu Chen ,&nbsp;Nick Ciccone ,&nbsp;David Ray","doi":"10.1016/j.bj.2025.100872","DOIUrl":"10.1016/j.bj.2025.100872","url":null,"abstract":"<div><div>The circadian clock enables organisms to predict daily environmental changes and synchronise their physiology and behaviour accordingly. Macrophages, key sensor cells in the innate immune system, exhibit cell-autonomous circadian rhythmicity. This circadian rhythmic behaviour is synchronised to the central clock in the hypothalamus as a result of neural, and hormonal signals. Macrophage rhythms and responses involve sensing temporal cues, integrating information from tissue-specific environments, and initiating context-appropriate, time-gated responses. On a broader scale, monocytes and macrophages communicate and synchronise with other immune cells, migrate throughout the body, and infiltrate tissues, collectively contributing to circadian regulation in both health and disease. While the field of macrophage circadian biology is rapidly advancing, it is equally important to reflect on its historical development, which has been shaped by over two centuries of accumulating knowledge and technological progress. This review traces key milestones in macrophage and circadian research, examining how recent discoveries have refined our understanding of early foundational questions and setting the stage for future inquiries. Notably, many intriguing questions remain unresolved, including the circadian regulation of macrophage function under steady-state conditions, the tissue-specific heterogeneity of macrophage circadian rhythms, and the role of macrophage circadian clocks in disease pathogenesis and their potential clinical implications.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100872"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages of the heart: Homeostasis and disease","authors":"Koketso C. Mabatha ,&nbsp;Pheletso Letuka ,&nbsp;Olukayode Aremu ,&nbsp;Michael Z. Zulu","doi":"10.1016/j.bj.2025.100867","DOIUrl":"10.1016/j.bj.2025.100867","url":null,"abstract":"<div><div>Cardiac macrophages (CMs) are the most abundant immune cell type in the heart. They are critical for maintaining cardiac homeostasis and in the orchestration of immune responses to ischemic and non-ischemic cardiomyopathies. Their functions are highly heterogeneous and regulated by their tissue microenvironment. CMs have high plasticity, which allows them to perform various functions in the myocardium to bring about homeostasis within the cardiovascular system (CVS). CMs also play critical roles in coronary development and angiogenesis, tissue repair and remodeling, cardiac conduction and in the clearance of necrotic and apoptotic cells. However, there is a paucity of studies on the biology of cardiac macrophages in both steady state and disease, especially in humans. In this review, we discuss the multifaceted roles of CMs in the heart, focusing on their ontogeny, homeostatic functions and immunological responses during inflammation and reparative processes post-injury. We highlight the heterogeneity of CMs in their ontogeny, phenotypes and functions as well as their roles in the pathogenesis of pathological conditions such as myocarditis, myocardial fibrosis and heart failure. Understanding the unique characteristics of cardiac macrophages in the cardiac milieu is critical for the development of macrophage-specific therapeutic interventions to alleviate the global burden of cardiovascular disease (CVD). Therefore, future studies should focus on further improving the understanding of the biology of cardiac macrophages to harness their potential as therapeutic targets for cardiovascular disorders.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100867"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of vertical facial patterns on three-dimensional surgical outcomes and stability in skeletal Class II malocclusion","authors":"Wasuthorn Poolsin ,&nbsp;Ellen Wen-Ching Ko ,&nbsp;Carol Yi-Hsuan Chen ,&nbsp;Cheng-Hui Lin","doi":"10.1016/j.bj.2025.100894","DOIUrl":"10.1016/j.bj.2025.100894","url":null,"abstract":"<div><h3>Background</h3><div>The surgical outcomes and stability of patients with skeletal Class II malocclusion determine the success of treatment. Variations in surgical interventions, patient responsiveness, and growth patterns across vertical facial morphologies result in varying treatment outcomes and postoperative stability.</div></div><div><h3>Methods</h3><div>This retrospective study recruited 52 adults diagnosed with skeletal Class II malocclusion treated with bimaxillary surgery; these adults were divided into two groups according to their vertical facial patterns. Cone-beam computed tomography images were collected before surgery (T0), after surgery (T1), and after orthodontic treatment (T2). Reconstructed three-dimensional images were used for cephalometric measurements and analysis.</div></div><div><h3>Results</h3><div>From T0 to T1, the Frankfort-mandibular plane angle decreased in the high-angle group but increased in the low–medium-angle group. The mandible advanced 9.02 and 6.21 mm in the high-angle and low–medium-angle groups, respectively. From T1 to T2, significant changes were observed in the anterior mandible horizontal movement of the high-angle group (−1.91 ± 3.63 mm) compared with the low–medium-angle group (−0.57 ± 1.04 mm). There were more patients exhibit clinically significant relapse (&gt;2 mm) in the high-angle group (44 %) than in the low–medium-angle group (20 %).</div></div><div><h3>Conclusion</h3><div>The relapse patterns in the two groups were similarly upward and backward. However, the high angle group exhibited greater average postoperative changes. The proportion of patients who exhibited a clinically significant relapse was higher in the high angle group.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100894"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Odyssey of macrophages","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2026.100967","DOIUrl":"10.1016/j.bj.2026.100967","url":null,"abstract":"<div><div>This issue brings together reviews and original research addressing diverse aspects of immune regulation, disease mechanisms, and clinical management. Several reviews focus on macrophages as integrative regulators across physiological systems, including their circadian control of immune activity, their role in coordinating endocrine signaling within the hypothalamic–pituitary axes, and their functions in cardiac tissue homeostasis and repair. Additional contributions revisit the development of regulatory T cells as a central mechanism of peripheral immune tolerance, examine the potential of artificial intelligence for infectious disease surveillance, and discuss emerging roles of long non-coding RNAs in cardiac regeneration. Further reviews evaluate multidisciplinary care strategies for pelvic floor disorders and analyze the inflammatory consequences of photodynamic therapy. Original studies in this issue investigate areca nut–associated head and neck carcinogenesis, determinants of persistent carbapenem-resistant <em>Klebsiella pneumoniae</em> bacteremia, treatment outcomes in hepatocellular carcinoma with portal vein tumor thrombus, protective effects against gastric ulceration, machine-learning–assisted interpretation of syphilis serology, and relapse patterns following orthognathic surgery.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100967"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anisomeles indica enriched with ovatodiolide protects against aspirin-induced gastric ulcers through gut microbiota modulation","authors":"Hsiu-Man Lien ,&nbsp;Yu-Yen Wang ,&nbsp;Shiao-Wen Li ,&nbsp;Hwai-Jeng Lin ,&nbsp;Hui-Yu Wu ,&nbsp;Yu-Tsen Huang ,&nbsp;Chun-Ya Chen ,&nbsp;Chia-Chang Chen ,&nbsp;Cheng-Hsun Chiu ,&nbsp;Chih-Ho Lai","doi":"10.1016/j.bj.2025.100893","DOIUrl":"10.1016/j.bj.2025.100893","url":null,"abstract":"<div><h3>Background</h3><div>Gastric ulcers are commonly caused by improper use of aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or <em>Helicobacter pylori</em> infection. <em>Anisomeles indica</em> (L.) <em>Kuntze</em>, a traditional herbal medicine enriched with ovatodiolide, possesses potent anti-bacterial and anti-inflammatory properties and has demonstrated efficacy in improving gastric ulcers in animal models. However, its impact on the gut microbial ecosystem remains unclear. This study aimed to evaluate the therapeutic effects of <em>A. indica</em> fractions enriched with ovatodiolide on aspirin-induced gastric ulcers and to investigate their influence on gut microbiota composition.</div></div><div><h3>Materials and methods</h3><div>Aspirin-induced gastric ulcers were established in mice, followed by treatment with various <em>A. indica</em> fractions. The severity of gastric ulceration was assessed using histopathological analysis. Additionally, 16S rRNA V3–V4 sequencing and 16S amplicon library construction were performed to characterize gut microbiota composition.</div></div><div><h3>Results</h3><div>Our results showed that mice treated with ovatodiolide-enriched <em>A. indica</em> fractions exhibited significant amelioration of gastric ulcers compared to untreated controls. The treatment also enhanced the relative abundance of beneficial gut microbiota, including <em>Lactobacillus</em> and <em>Adlercreutzia</em>. Furthermore, histopathological examination revealed that <em>A. indica</em> treatment significantly upregulated mucin expression in ulcerated gastric tissues, suggesting a protective role in gastric mucosal integrity.</div></div><div><h3>Conclusions</h3><div>This study provides insights into the mechanisms by which <em>A. indica</em> alleviates gastric ulcers, highlighting its ability to modulate gut microbiota and enhance mucosal protection.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100893"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory T cells from concept to clinic: The 2025 Nobel Prize and its implications for immune-mediated diseases and cancer","authors":"Chien-Hao Huang ,&nbsp;Wei-Ting Ku ,&nbsp;Yung-Chang Lin ,&nbsp;Chun-Yen Lin","doi":"10.1016/j.bj.2026.100959","DOIUrl":"10.1016/j.bj.2026.100959","url":null,"abstract":"<div><div>The 2025 Nobel Prize in Physiology or Medicine, awarded to Shimon Sakaguchi, Mary E. Brunkow, and Fred Ramsdell, recognizes the discovery and molecular definition of regulatory T cells (Tregs) as the cornerstone of peripheral immune tolerance. This recognition honors a transformative journey marked by Sakaguchi's identification of CD4⁺CD25⁺ T cells as a regulatory population (1995), followed by Brunkow and Ramsdell's discovery that mutations in the <em>FOXP3</em> gene cause both the <em>scurfy</em> mouse phenotype and human IPEX syndrome (2001), and culminating in the demonstration that FOXP3 governs Treg development and function (2003).</div><div>This achievement crowns a turbulent half-century arc. The suppressor T-cell (Ts) hypothesis of the 1970s proposed an active T-cell brake on immunity but collapsed in the 1980s due to phenotypic ambiguity and reproducibility failures. Following this “dark age,” the concept of active suppression was kept alive through functional studies in organ-specific autoimmunity (Parish, Kong, Rose) and transplantation tolerance (Waldmann). However, it was Sakaguchi's discovery of CD25 as a specific marker that finally provided the physical identity of these cells, bridging the gap between functional observation and cellular definition. The subsequent identification of FOXP3 as the lineage-defining transcription factor transformed a disputed concept into a reproducible, engineerable immune module.</div><div>Today, this molecular precision drives broad clinical translation, ranging from Treg-based therapies in autoimmunity and transplantation to targeted Treg modulation in cancer immunotherapy. This Short Review traces the trajectory—from controversy to molecular definition—and frames a forward path for context-dependent modulation of Tregs in clinical medicine.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100959"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and genomic insights into persistent carbapenem-resistant Klebsiella pneumoniae bacteremia: risk factors, resistance mechanisms, and treatment challenges","authors":"Shian-Sen Shie ,&nbsp;Ya-Han Yang ,&nbsp;Yin-Hsiang Kung ,&nbsp;Chih-Jung Chen","doi":"10.1016/j.bj.2025.100905","DOIUrl":"10.1016/j.bj.2025.100905","url":null,"abstract":"<div><h3>Introduction</h3><div>Carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) is a major cause of nosocomial infections with high mortality rates. Persistent bacteremia, indicative of treatment failure, poses significant clinical challenges. This study aimed to identify clinical parameters for persistent CRKP bacteremia while exploring microbial and genetic characteristics.</div></div><div><h3>Materials and methods</h3><div>A case-control study was conducted on patients with CRKP bacteremia from January 2016 to July 2019 at a tertiary hospital in Taiwan. Clinical, demographic, and microbiological data were collected for 61 cases of persistent bacteremia and 122 matched controls without persistent infections. Conditional logistic regression was used to evaluate risk factors for persistent bacteremia. Whole-genome sequencing (WGS) was used to identify genotypes and factors mediating resistance and virulence in the strains.</div></div><div><h3>Results</h3><div>Persistent CRKP bacteremia was independently associated with mechanical ventilation (adjusted odds ratio [aOR] 11.007, 95 % confidence interval [CI] 2.137–56.693), a lower Pitt bacteremia score (aOR 0.642, 95 % CI 0.494–0.835), and the use of colistin (aOR 11.18, 95 % CI 2.988–41.787) and tigecycline (aOR 16.42, 95 % 4.495–60.0) in definitive therapy. Strains from either group shared similar capsular types. WGS identified three dominant multidrug-resistant clones, ST11, ST307, and ST15, harboring carbapenemase and virulence factors encoding yersiniabactin. A strain of hypervirulent clone ST23 exhibited high virulence but lacked carbapenemase genes, suggesting alternative resistance mechanisms of CR phenotype.</div></div><div><h3>Conclusions</h3><div>Antimicrobial regimens with tigecycline and colistin were insufficient for effectively managing CRKP bacteremia. The convergence of resistance and virulence in prevalent clones demands the urgent introduction of novel therapeutics. Aggressive and tailored strategies are critical for improving outcomes in high-risk patients.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 2","pages":"Article 100905"},"PeriodicalIF":4.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}