Annals of medicine最新文献

{"title":"Early combination of sotrovimab with nirmatrelvir/ritonavir or remdesivir is associated with low rate of persisting SARS CoV-2 infection in immunocompromised outpatients with mild-to-moderate COVID-19: a prospective single-centre study.","authors":"I Gentile, G Viceconte, F Cuccurullo, D Pietroluongo, A D'Agostino, M Silvitelli, S Mercinelli, R Scotto, F Grimaldi, S Palmieri, A Gravetti, F Trastulli, M Moccia, A R Buonomo","doi":"10.1080/07853890.2024.2439541","DOIUrl":"10.1080/07853890.2024.2439541","url":null,"abstract":"<p><strong>Background: </strong>Immunocompromised patients are at high risk of developing persisting/prolonged COVID-19. Data on the early combined use of antivirals and monoclonal antibodies in this population are scarce.</p><p><strong>Research design and methods: </strong>We performed an observational, prospective study, enrolling immunocompromised outpatients with mild-to-moderate COVID-19, treated with a combination of sotrovimab plus one antiviral (remdesivir or nirmatrelvir/ritonavir) within 7 days from symptom onset. Primary outcome was hospitalization within 30 days. Secondary outcomes were: needing for oxygen therapy; development of persistent infection; death within 60 days and reinfection or relapse within 90 days.</p><p><strong>Results: </strong>We enrolled 52 patients. No patient was hospitalized within 30 days of disease onset, required oxygen administration, died within 60 days, or experienced a reinfection or clinical relapse within 90 days.The clearance rates were 67% and 97% on the 14th day after the end of therapy and at the end of the follow-up period, respectively.Factors associated with longer infection were initiation of therapy 3 days after symptom onset and enrollment for more than 180 days from the beginning of the study. However, only the latter factor was independently associated with a longer SARS-CoV-2 infection, suggesting a loss of efficacy of this strategy with the evolution of SARS-CoV-2 variants.</p><p><strong>Conclusions: </strong>Early administration of combination therapy with a direct antiviral and sotrovimab seems to be effective in preventing hospitalization, progression to severe COVID-19, and development of prolonged/persisting SARS-CoV-2 infection in immunocompromised patients.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2439541"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive value of three nutritional indexes for disease activity in patients with inflammatory bowel disease.","authors":"Zhuoyan Chen, Liuwei Zeng, Weimin Cai, Xian Song, Qian Xu, Jun Xu, Luying Zhao, Yuan Zeng, Xiangting Zhang, Xiao Wu, Ruoru Zhou, Huiya Ying, Kanglei Ying, Yuhao Chen, Fujun Yu","doi":"10.1080/07853890.2024.2443256","DOIUrl":"https://doi.org/10.1080/07853890.2024.2443256","url":null,"abstract":"<p><strong>Background: </strong>Malnutrition is prevalent in patients with inflammatory bowel disease (IBD); however, its ability to predict the disease activity in IBD remains unexplored. Therefore, this study aimed to explore the association between malnutrition and disease activity in IBD.</p><p><strong>Methods: </strong>In this retrospective study, we enrolled 1006 patients diagnosed with IBD from the First Affiliated Hospital of Wenzhou Medical University from 2011 to 2022. Malnutrition was assessed based on the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) scores. Logistic regression analyses were performed to identify predictors for disease activity. Restricted cubic spline analysis was performed to evaluate the possible nonlinear relations, and subgroup analysis was performed to explore potential interactions. Additionally, prediction performances were compared through receiver operating characteristic curves, net reclassification improvement, and integrated discrimination improvement.</p><p><strong>Results: </strong>The prevalence of malnutrition calculated by the PNI, GNRI, and CONUT scores in IBD was 16.9%, 72.1%, and 75.6%, respectively and significant correlations were observed among them. Multivariate logistic regression analysis showed that PNI, GNRI, and CONUT were independent risk factors for disease activity, and no significant nonlinear relationship was observed between disease activity and all three indexes. No statistically significant interactive effect was found in nearly all the subgroups. GNRI showed the highest predictive value compared with PNI and CONUT. Additionally, combining any of the three indexes improved the ability of C-reactive protein to predict IBD activity.</p><p><strong>Conclusions: </strong>All three nutritional indexes evaluated malnutrition to be an independent risk factor for IBD activity.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2443256"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe postoperative complications after minimally invasive esophagectomy reduce the long-term prognosis of well-immunonutrition patients with locally advanced esophageal squamous cell carcinoma.","authors":"Chao Chen, Shao-Jun Xu, Zhi-Fan Zhang, Cheng-Xiong You, Yun-Fan Luo, Rui-Qin Chen, Shu-Chen Chen","doi":"10.1080/07853890.2024.2440622","DOIUrl":"10.1080/07853890.2024.2440622","url":null,"abstract":"<p><strong>Background: </strong>While severe postoperative complications (SPCs) impact cancer prognosis, their effect on locally advanced esophageal squamous cell carcinoma (ESCC) patients with varying immunonutritional statuses after minimally invasive esophagectomy (MIE) is unclear.</p><p><strong>Methods: </strong>This retrospective study analyzed 442 patients with locally advanced ESCC who underwent MIE, investigating the relationship between SPCs and survival based on preoperative immunonutritional status, determined by the prognostic nutritional index (PNI). Nomograms were developed for patients with preserved immunonutritional status using Cox regression, and their performance was assessed.</p><p><strong>Results: </strong>Of the patients, 102 (23.1%) experienced SPCs after MIE. Five-year overall survival (OS) and disease-free survival (DFS) were significantly different between SPCs and non-SPCs groups (<i>p</i> < 0.001). In the preserved immunonutritional group, SPCs significantly reduced 5-year OS (<i>p</i> = 0.008) and DFS (<i>p</i> = 0.011), but not in the poor immunonutritional group (OS <i>p</i> = 0.152, DFS <i>p</i> = 0.098). Multivariate Cox regression identified SPCs as an independent risk factor for OS (HR = 1.653, <i>p</i> = 0.013) and DFS (HR = 1.476, <i>p</i> = 0.039). A nomogram for predicting OS and DFS in preserved immunonutritional patients demonstrated excellent performance.</p><p><strong>Conclusions: </strong>SPCs significantly affect prognosis in ESCC patients with preserved immunonutritional status after MIE. Nomograms based on SPCs can predict OS and DFS in these patients.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2440622"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The predictive value of thyroid hormone sensitivity parameters for cervical lymph node metastasis in patients with differentiated thyroid cancer.","authors":"Jingcheng Bi, Tianqi Yao, Yu Yao, Zhengcai Zhu, Qiucheng Lei, Lianghe Jiao, Tao Li","doi":"10.1080/07853890.2024.2443564","DOIUrl":"https://doi.org/10.1080/07853890.2024.2443564","url":null,"abstract":"<p><strong>Objective: </strong>To comprehensively investigate the predictive value of thyroid hormone sensitivity parameters for cervical lymph node metastasis in patients diagnosed with differentiated thyroid cancer (DTC) undergoing total thyroidectomy and neck lymph node dissection.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted involving patients diagnosed with DTC and evaluated for cervical lymph node metastasis. Relevant demographic, tumour, lymph node and thyroid hormone sensitivity parameter data were extracted from medical records and laboratory reports. Thyroid hormone sensitivity parameters including thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroglobulin antibodies (TgAbs), thyroid peroxidase antibody, thyroid hormone receptor α and TSH receptor antibody were assessed. Statistical analyses including descriptive statistics, comparative analysis, Pearson's correlation analysis, logistic regression analysis, receiver operating characteristic (ROC) analysis and construction of a multivariable prediction model based on machine learning using the xgbTree method were employed to evaluate the associations and predictive value of thyroid hormone sensitivity parameters for cervical lymph node metastasis.</p><p><strong>Results: </strong>The study revealed significant associations between several thyroid hormone sensitivity parameters and cervical lymph node metastasis in patients with DTC. Specifically, higher levels of T4, T3, Tg, TgAbs and TSH receptor antibody were associated with lymph node metastasis. Pearson's correlation analysis, logistic regression analysis and ROC analysis further underscored the predictive performance of these parameters, with strong overall discriminative abilities. The machine learning-based prediction model demonstrated promising performance with a high area under the curve (AUC) of 0.979.</p><p><strong>Conclusions: </strong>The findings provide compelling evidence for the predictive value of thyroid hormone sensitivity parameters, particularly T3, T4, Tg, TgAbs and TSH receptor antibody, in identifying and evaluating the likelihood of cervical lymph node metastasis in patients with DTC. These parameters hold potential implications for risk stratification, clinical decision-making and personalized management strategies, contributing to improved outcomes for patients at risk of lymph node metastasis.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2443564"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital learning strategies in residency education.","authors":"Helena Vallo Hult, Adam Abovarda, Christian Master Östlund, Paul Pålsson","doi":"10.1080/07853890.2024.2440630","DOIUrl":"10.1080/07853890.2024.2440630","url":null,"abstract":"<p><strong>Background: </strong>New digital learning environments have transformed medical education and training, allowing students and teachers to engage in synchronous, real-time interactions and asynchronous learning activities online. Despite extensive research on the role of digital technologies in education, understanding the interplay between digital technology, work, and learning, especially in complex fields like healthcare, remains a challenge.</p><p><strong>Objective: </strong>The objective of this study is to examine resident physicians' perceptions and experiences of using a digital learning environment as part of their specialist medical training. The paper focuses on digital learning through video conferencing (virtual lectures and seminars) and related learning technologies. It aims to understand how resident physicians perceive pedagogical opportunities and challenges in digital learning environments during their medical training and what strategies they use to address these.</p><p><strong>Materials and methods: </strong>The methodological approach is qualitative, aiming to capture and understand participants' experiences and views of digital learning. The empirical data gathered from open-ended responses to four course evaluation surveys and semi-structured interviews with nine physicians from a cohort of participants enrolled in two or more digital courses were analyzed through thematic analysis. The analysis revealed three main themes related to digital transformation of learning: sociotechnical, educational and administrative.</p><p><strong>Results: </strong>The results suggest that (i) sociotechnical aspects and understanding of the context in which the learning takes place contribute to enhancing digital learning for resident physicians; (ii) insights into participants' perceptions of digital learning emphasize that interactive communication and group discussions are significant for their learning, and (iii) administrative aspects related to course design, lecture management, and instructional support are more important in digital learning environments compared to traditional teaching and learning.</p><p><strong>Conclusion: </strong>Findings from this study confirm and extend prior studies on digital learning in healthcare, contributing to a better understanding of how digital learning environments, especially virtual lectures and seminars, can be developed and integrated into residency programs and health professions education to increase their usefulness.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2440630"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour necrosis factor inhibitors in Ulcerative colitis: real-world data on Therapeutic drug monitoring and evaluation of current treatment targets (STRIDE II).","authors":"Jonas Andre Lundekvam, Marte Lie Høivik, Karoline Anisdahl, Milada Cvancarova Småstuen, David J Warren, Nils Bolstad, Asle Wilhelm Medhus","doi":"10.1080/07853890.2024.2424447","DOIUrl":"10.1080/07853890.2024.2424447","url":null,"abstract":"<p><strong>Background: </strong>The benefit of therapeutic drug monitoring (TDM) and implementation of recommendations from the Selection of Therapeutic Targets in Inflammatory Bowel Disease (IBD, STRIDE) are discussed in the IBD community. We report real-world data in ulcerative colitis patients receiving first-line tumour necrosis factor inhibitor (TNFi) treatment followed by TDM, and assess how implementation of the STRIDE II recommendations might affect clinical practice.</p><p><strong>Methods: </strong>Adult, biologically naïve UC patients starting TNFi between 2014 and 2021 at Oslo University Hospital were included in a medical chart review study, and data were collected at three and twelve months after the start of treatment. Target serum drug levels were defined as ≥7.5 mg/L for adalimumab and ≥5 mg/L for infliximab.</p><p><strong>Results: </strong>Of 141 included patients, 36% were in clinical and biochemical (combined) remission after twelve months. Among 102 treatment persistent patients, 54% were in combined remission after twelve months. Target drug level at three months was associated with clinical remission at twelve months (OR = 2.97, 95% CI [1.24-7.12]) and biochemical remission at twelve months (OR = 2.64, 95% CI [1.03-6.77]). In total, 56% of recorded dosage adjustments were related only to serum drug levels.</p><p><strong>Conclusions: </strong>Combined remission rates at twelve months for treatment persistent patients suggest that 46% should have been considered for a change of treatment according to the STRIDE II recommendations. A majority of dosage adjustments were made proactively. Target drug level at three months was associated with remission at twelve months and supports the use of proactive TDM.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2424447"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using network pharmacology and molecular docking technology, proteomics and experiments were used to verify the effect of Yigu decoction (YGD) on the expression of key genes in osteoporotic mice.","authors":"Kun Yan, Rui-Kun Zhang, Jia-Xin Wang, Hai-Feng Chen, Yang Zhang, Feng Cheng, Yi Jiang, Min Wang, Ziqi Wu, Xiao-Gang Chen, Zhi-Neng Chen, Gui-Jin Li, Xin-Miao Yao","doi":"10.1080/07853890.2024.2449225","DOIUrl":"https://doi.org/10.1080/07853890.2024.2449225","url":null,"abstract":"<p><strong>Background: </strong>Yigu decoction (YGD) is a traditional Chinese medicine prescription for the treatment of osteoporosis, although many clinical studies have confirmed its anti-OP effect, but the specific mechanism is still not completely clear.</p><p><strong>Methods: </strong>In this study, through the methods of network pharmacology and molecular docking, the material basis and action target of YGD in preventing and treating OP were analyzed, and the potential target and mechanism of YGD in preventing and treating OP were clarified by TMT quantitative protein and experiment.</p><p><strong>Results: </strong>Network pharmacology and molecular docking revealed that the active components of YGD were mainly stigmasterol and flavonoids. Molecular docking mainly studied the strong binding ability of stigmasterol to the target. Animal proteomics verified the related mechanism of YGD in preventing and treating OP. Based on the KEGG enrichment of network pharmacology and histology, our animal experiments <i>in vivo</i> verified that YGD may play a role in the treatment of OP by mediating hif1- α/vegf/glut1 signal pathway.</p><p><strong>Conclusions: </strong>YGD prevention and treatment of OP may be achieved by interfering with multiple targets. This study confirmed that it may promote osteoblast proliferation and protect osteoblast function by up-regulating the expression of proteins related to HIF signal pathway.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2449225"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of Naples prognostic score in predicting long-term mortality in heart failure patients.","authors":"Sidar Şiyar Aydın, Selim Aydemir, Murat Özmen, Emrah Aksakal, İbrahim Saraç, Faruk Aydınyılmaz, Onur Altınkaya, Oğuzhan Birdal, İbrahim Halil Tanboğa","doi":"10.1080/07853890.2024.2442536","DOIUrl":"10.1080/07853890.2024.2442536","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) remains a significant health problem despite advances in diagnosis and treatment options. Malnutrition and increased inflammation predict poor disease prognosis. The parameters of the Naples prognostic score (NPS) include albumin, total cholesterol, neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). We aimed to assess the potential of NPS as a predictor of long-term mortality in patients with HF.</p><p><strong>Methods: </strong>A total of 1728 patients with HF who applied to our center between 2018 and 2022 were included in this study. The NPS was computed and the patients were divided into three groups according to their NPS values as follows: NPS = 0 (Group 1), NPS = 1-2 (Group 2), and NPS = 3-4 (Group 3). We also evaluated the association between NPS value and HF mortality.</p><p><strong>Results: </strong>The patients were followed for a mean follow-up duration of 30 months. The mortality rate was 8.3% (145 patients). We carried out Model-1 and -2 Cox regression analyses to identify long-term mortality determinants. Model-2 was constructed by adding NPS to Model-1. NPS was significantly associated with HF mortality (Hazard Ratio: 2.194, 95% Confidence Interval: 1.176-4.091, <i>p</i> = 0.014). According to the Kaplan-Meier plot and log-rank analyses, there was a statistically significant difference in the long-term mortality of patients with HF and their NPS values for the entire cohort.</p><p><strong>Conclusion: </strong>Based on our findings, NPS showed promise as an independent predictor of long-term mortality in individuals with HF.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2442536"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive characterization of the molecular feature of T cells in laryngeal cancer: evidence from integrated single-cell and bulk RNA sequencing data using multiple machine learning approaches.","authors":"Jie Cui, Yangpeng Ou, Kai Yue, Yansheng Wu, Yuansheng Duan, Genglong Liu, Zhen Chen, Minghui Wei, Xudong Wang","doi":"10.1080/07853890.2025.2477287","DOIUrl":"10.1080/07853890.2025.2477287","url":null,"abstract":"<p><strong>Background: </strong>The clinical relevance of T cell-related molecules at single-cell resolution in laryngeal cancer (LC) has not been clarified.</p><p><strong>Materials and methods: </strong>Three LC tissues and matching adjoining normal tissues from the hospital were used to perform 10X single-cell RNA sequencing. Hub T cell-related genes (TCRGs) were detected by applying ten machine learning (ML) techniques based TCGA and GEO databases, which were also utilized to create a prediction model (TCRG classifier) and a multicenter validation model. Lastly, we conducted a comprehensive analysis of the TCRG's correlation with immunological properties.</p><p><strong>Results: </strong>The analysis of single-cell RNA-seq data revealed that T cells are the primary components of the tumor microenvironment (TME), are significantly involved in cell differentiation pathways, and play a considerable role in intercellular communication. Based on 10 ML approaches, TCRG classifier were identified to develop and validate. The TCRG classifier exhibited excellent prognostic values with a mean C-index of 0.66 in six cohorts, serving as an independent risk factor (<i>p</i> < 0.01). Additionally, the TCRG exhibited a significant relationship with immune score, immune cell infiltration, immune-associated pathways, immune checkpoint inhibitors, human leukocyte antigen, and immunogenicity. Lastly, IPS, TCIC, TIDE, and IMvigor210 cohort analysis illustrated that the immunotherapy response may be accurately predicted using TCRG.</p><p><strong>Conclusion: </strong>A TCRG classifier is an excellent resource for predicting a patient's prognosis, potentially guiding the preservation of laryngeal function, and identifying patients who may have a positive response to immunotherapy, which might have profound effects on therapeutic practice.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2477287"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circKCNQ5 promotes the proliferation of DNA-methyltransferase 3A R882 mutated acute myeloid leukemia cells by elevating high-mobility group box 1 expression.","authors":"Yijian Chen, Xiaodan Zhu, Chuanming Lin, Rong Xu, Pengxiang Xu, Liuyan Xin, Lin Li, Liqun Zhang","doi":"10.1080/07853890.2025.2478309","DOIUrl":"10.1080/07853890.2025.2478309","url":null,"abstract":"<p><strong>Background: </strong>Patients with acute myeloid leukemia (AML) harboring the DNA-methyltransferase 3 A (DNMT3A) R882 mutation (DR882MUT) usually have a high recurrence rate and poor prognosis. circKCNQ5 levels were aberrantly elevated in patients with AML according to the microarray platform. Therefore, the purpose of this study is to investigate the effect and mechanism of circKCNQ5 on DR882MUT AML cell proliferation.</p><p><strong>Methods: </strong>A DR882MUT cell line model was established. circKCNQ5 expression in AML cells expressing wild-type DNMT3A (DNMT3A-WT) or DR882MUT was analyzed using RT-qPCR. The proliferation of DNMT3A-WT and DR882MUT AML cells after transfection was measured using a CCK-8 assay. High-mobility group box 1 (HMGB1) protein expression was assessed by western blotting. The regulatory mechanism of circKCNQ5 on HMGB1 expression was studied using RNA pull-down and co-immunoprecipitation assays.</p><p><strong>Results: </strong>circKCNQ5 expression increased gradually in HS-5, DNMT3A-WT, and DR882MUT AML cells. circKCNQ5 overexpression facilitated the proliferation of DNMT3A-WT KG-1a and HL-60 cells, whereas circKCNQ5 silencing blocked DR882MUT KG-1a and HL-60 cell proliferation. CircKCNQ5 interacts with HMGB1 and enhanced HMGB1 protein levels by inhibiting HMGB1 ubiquitination. HMGB1 protein levels increased gradually in HS-5, DNMT3A-WT, and DR882MUT AML cells. Furthermore, circKCNQ5 overexpression elevated HMGB1 protein levels in DNMT3A-WT KG-1a and HL-60 cells, whereas circKCNQ5 silencing reduced HMGB1 protein levels in DR882MUT KG-1a and HL-60 cells. HMGB1 overexpression remarkably increased the proliferative ability of DR882MUT KG-1a and HL-60 cells and circKCNQ5 silencing.</p><p><strong>Conclusions: </strong>These findings verified that circKCNQ5 promotes the proliferation of DR882MUT AML cells by increasing HMGB1 expression.</p>","PeriodicalId":93874,"journal":{"name":"Annals of medicine","volume":"57 1","pages":"2478309"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}