Jinqi Xue, Xudong Zhu, Xinbo Qiao, Yulun Wang, Jiawen Bu, Xiaoying Zhang, Qingtian Ma, Lu Liang, Lisha Sun, Caigang Liu
{"title":"Erratum: <i>CEMIP</i> as a potential biomarker and therapeutic target for breast cancer patients: Erratum.","authors":"Jinqi Xue, Xudong Zhu, Xinbo Qiao, Yulun Wang, Jiawen Bu, Xiaoying Zhang, Qingtian Ma, Lu Liang, Lisha Sun, Caigang Liu","doi":"10.7150/ijms.114765","DOIUrl":"https://doi.org/10.7150/ijms.114765","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/ijms.58067.].</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 15","pages":"3938"},"PeriodicalIF":3.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between Disorders of Lipid Metabolism and Oculopathy: An Overview.","authors":"Yuanting Yang, Ruixue Zhang, Miao Zhang, Zhaohui Yang, Zhongyu Ma, Yinqiao Zhang, Mengke Wu, Dadong Guo, Hongsheng Bi","doi":"10.7150/ijms.116512","DOIUrl":"10.7150/ijms.116512","url":null,"abstract":"<p><p>Lipid metabolism disorders, which lead to lipid deposition or changes in blood lipid composition, play a significant role in inducing or exacerbating the pathogenesis of diseases such as hypercholesterolemia and diabetes. Moreover, these disorders are closely associated with the development and progression of ocular diseases, including corneal degeneration, cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy. Studies have shown that lipid metabolism disorders critically impact the structure and function of ocular tissues through mechanisms such as lipid deposition, disrupted cholesterol synthesis, abnormal lipid concentrations, or impaired lipid transport. These disorders can damage cellular structures, induce oxidative stress, disrupt signal transduction, and lead to apoptosis of ocular tissue cells, mitochondrial dysfunction, and osmotic imbalance, ultimately impairing normal physiological functions and contributing to the onset of various eye diseases. This article reviews the association between lipid metabolism disorders and the development of various ocular diseases and explores the mechanisms underlying the interaction between lipid metabolism abnormalities and eye diseases, as well as the preventive role of lipid metabolism regulation in ocular diseases.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 15","pages":"3878-3894"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cheng-Peng Li, Yuan Chu, Wei-Wei Jia, Priska Hakenberg, Flavius Șandra-Petrescu, Christoph Reißfelder, Cui Yang
{"title":"Punching Above Its Weight: A Head-to-Head Comparison of Deepseek-R1 and OpenAI-o1 on Pancreatic Adenocarcinoma-Related Questions.","authors":"Cheng-Peng Li, Yuan Chu, Wei-Wei Jia, Priska Hakenberg, Flavius Șandra-Petrescu, Christoph Reißfelder, Cui Yang","doi":"10.7150/ijms.118887","DOIUrl":"10.7150/ijms.118887","url":null,"abstract":"<p><p><b>Objective:</b> This study aimed to compare the performance of DeepSeek-R1 and OpenAI-o1 in addressing complex pancreatic ductal adenocarcinoma (PDAC)-related clinical questions, focusing on accuracy, comprehensiveness, safety, and reasoning quality. <b>Methods:</b> Twenty PDAC-related questions derived from the up-to-date NCCN guidelines for PDAC were posed to both models. Responses were evaluated for accuracy, comprehensiveness, and safety, and chain-of-thought (CoT) outputs were rated for logical coherence and error handling by blinded clinical experts using 5-point Likert scales. Inter-rater reliability, evaluated scores, and character counts by both models were compared. <b>Results:</b> Both models demonstrated high accuracy (median score: 5 vs. 5, p=0.527) and safety (5 vs. 5, p=0.285). DeepSeek-R1 outperformed OpenAI-o1 in comprehensiveness (median: 5 vs. 4.5, p=0.015) and generated significantly longer responses (median characters: 544 vs. 248, p<0.001). For reasoning quality, DeepSeek-R1 achieved superior scores in logical coherence (median: 5 vs. 4, p<0.001) and error handling (5 vs. 4, p<0.001), with 75% of its responses scoring full points compared to OpenAI-o1's 5%. <b>Conclusion:</b> While both models exhibit high clinical utility, DeepSeek-R1's enhanced reasoning capabilities, open-source nature, and cost-effectiveness position it as a promising tool for complex oncology decision support. Further validation in real-world multimodal clinical scenarios is warranted.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 15","pages":"3868-3877"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deep Learning Based on Automated Breast Volume Scanner Images for the Diagnosis of Breast Lesions: A Multicenter Diagnostic Study.","authors":"Hui Liu, Ying Zhang, Bin Tan, Yi-Fei Yin, Li-Xia Yan, Li-Hua Xiang, Dan-Dan Shan, Yun-Yao Zhang, Shi-Si Ding, Guang Xu, Bo-Yang Zhou, Yi-Lei Shi, Xiao-Xiang Zhu, Jing-Liang Hu, Li-Ping Sun, Hui-Xiong Xu, Yi-Feng Zhang","doi":"10.7150/ijms.118430","DOIUrl":"10.7150/ijms.118430","url":null,"abstract":"<p><p><b>Objectives:</b> To develop a deep learning (DL) model for the automated detection and diagnosis of breast cancer utilizing automated breast volume scanner (ABVS) images, and to compare its diagnostic performance with that of radiologists in screening ABVS examinations. <b>Methods:</b> In this multicenter diagnostic study, ABVS data from 1,368 patients with breast lesions were collected across three hospitals between November 2019 and April 2024. The DL model (VGG19, DenseNet161, ResNet101, and ResNet50) was developed to detect and classify lesions. One-tenth of the cases from Hospital A were randomly selected as a fixed internal test set; the remaining data were randomly divided into training and validation sets at an 8:2 ratio. External test sets were derived from Hospitals B and C. Pathological findings served as the gold standard. Clinical applicability was assessed by comparing radiologists' diagnostic performance with and without DL model assistance. <b>Results:</b> For breast cancer detection, the DL model achieved an area under the receiver operating characteristic curve (AUC) of 0.984 (95% CI: 0.965-0.995) on the internal test set, 0.978 (95% CI: 0.951-0.994) on the external test set 1 (Hospital B), and 0.942 (95% CI: 0.902-0.978) on the external test set 2 (Hospital C). The model demonstrated significantly higher sensitivity (98.2%) and specificity (90.3%) than junior radiologists (P < 0.05), while exhibiting comparable diagnostic reliability and accuracy to senior radiologists. Interpretation time was significantly reduced for all radiologists when using the DL model (P < 0.05). <b>Conclusion:</b> The DL model based on ABVS images significantly enhanced diagnostic performance and reduced interpretation time, particularly benefiting junior radiologists.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 15","pages":"3924-3937"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting LC3B/MCL-1 expression by Protodioscin induces autophagy and apoptosis in human glioblastoma cells <i>in vitro</i> and <i>in vivo</i>.","authors":"Ching-Ting Tai, Yi-Hsien Hsieh, Hsiang-Lin Lee, Pei-Ni Chen, Hui-Ling Chiou, Tsai-Yun Wu, Chia-Liang Lin, Yi-Chen Lin, Chien-Min Chen","doi":"10.7150/ijms.116656","DOIUrl":"10.7150/ijms.116656","url":null,"abstract":"<p><p>Protodioscin (PD), a natural steroidal saponin extracted from Dioscorea and Tribulus terrestris, has been shown to exhibit anticancer, antimetastatic, and pro-autophagic and apoptotic activities in various malignant tumor cells. However, its antitumor potential and molecular mechanisms in glioblastoma remain unclear. This study aimed to investigate the effects of PD on apoptosis and autophagy in human glioblastoma cells using both <i>in vitro</i> and <i>in vivo</i> models. Our results suggested that PD significantly inhibited the proliferation, induced mitochondrial dysfunction and apoptosis of human GBM8401 and M059K cells, as evidenced by the activation of cleaved-PARP (c-PARP) and MCL-1 expression. However, PD also enhanced autophagic activity, as indicated by the upregulation of LC3B expression. Silencing LC3 expression using siRNA markedly attenuated PD-induced autophagy and apoptosis, these results demonstrated the crucial regulatory role of LC3 in mediating cell death pathways. In an <i>in vivo</i> GBM8401 xenograft model, PD treatment significantly suppressed GBM8401 tumor growth without affecting body weight or causing organ toxicity in PD-treated mice. Immunohistochemical analysis further suggested that PD reduced the expression of the Ki67 expression in glioblastoma tumor tissues and molecular docking finding that PD strong interaction with LC3B and MCL-1. In summary, PD induces both apoptosis and autophagy in glioblastoma cells through LC3B/MCL-1 modulation, demonstrating strong antitumor potential against human glioblastoma. These findings suggest that PD may serve as a novel therapeutic strategy and a promising candidate for glioblastoma treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 15","pages":"3828-3838"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The natural compound n-butylidenephthalide suppresses type II ovarian cancer cell growth by inducing ferroptosis.","authors":"Shinn-Zong Lin, Chih-Yang Huang, Yueh-Min Lin, Rathinasamy Baskaran, Yu-Jung Lin, Wei-Wen Kuo, Dah-Ching Ding","doi":"10.7150/ijms.114086","DOIUrl":"10.7150/ijms.114086","url":null,"abstract":"<p><p>Type II high-grade serous ovarian cancer (HGSOC) accounts for 80% of all ovarian cancers. Tumor metastasis and chemotherapy resistance are predominantly caused by cancer stem cells (CSCs). n-butylidenephthalide (BP) has showed promise as an anti-tumor drug in a variety of malignancies. The purpose of this study was to examine the ferroptosis influence of BP on HGSOC. CSCs were isolated from the HGSOC cell lines KURAMOCHI and OVSAHO by employing the CSC marker ALDH. The study assessed cell survival, proliferation, IC<sub>50</sub> (the concentration at which 50% growth suppression occurs), terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay, and Western blot analysis of ovarian cancer cells and CSCs. qPCR was performed to assess ferroptosis-related gene expression. Furthermore, animal studies were carried out using a mouse model with subcutaneous xenografted stemness-enriched ovarian CSCs and evaluated with an IVIS scan. In this <i>in vivo</i> investigation, control, BP with or without taxol or ferrostatin were intended as cancer treatments. The findings indicated that BP inhibits HGSOC growth via ferroptosis mediated by the GPX4 conventional and HMBOX-1 noncanonical pathways. Furthermore, the anti-tumor effects of BP and Taxol were significantly improved when tumor-bearing mice were treated with both simultaneously, compared to their sole therapy. BP may increase the susceptibility of ovarian cancer cells to Taxol, implying its potential to improve the therapeutic effects of this standard ovarian cancer treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 15","pages":"3854-3867"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kuang-Yu Chou, An-Chen Chang, Thomas I-Sheng Hwang, Te-Fu Tsai, Chao-Yen Ho, Hsiu-Wen Liu, David Achudhan, Chih-Hsin Tang, Yen-You Lin
{"title":"ABCC6 Transporter Contributed to Cisplatin Resistance on Bladder Cancer.","authors":"Kuang-Yu Chou, An-Chen Chang, Thomas I-Sheng Hwang, Te-Fu Tsai, Chao-Yen Ho, Hsiu-Wen Liu, David Achudhan, Chih-Hsin Tang, Yen-You Lin","doi":"10.7150/ijms.115487","DOIUrl":"10.7150/ijms.115487","url":null,"abstract":"<p><p>Bladder cancer (BLCA) is one of the most common urological malignancies worldwide, including in Taiwan, where its incidence has been increasing. It accounts for approximately 3% of all newly diagnosed cancer cases. Drug resistance remains a major challenge in BLCA treatment, particularly at the metastatic stage, where only 35% of metastatic BLCA patients respond to cisplatin chemotherapy, and most eventually develop resistance. In the present study, we established cisplatin-resistant BLCA cell models (T24 and UMUC3) and analyzed ATP-binding cassette (ABC) transporters. We identified ABC transporter C member 6 (ABCC6) as a crucial transporter upregulated in cisplatin-resistant BLCA cells. Further analysis showed that ABCC6 knockdown affected autophagy-related markers, and inhibition of autophagy using bafilomycin A1 (BafA1) and chloroquine (CQ) reversed cisplatin resistance. These findings suggest that ABCC6 contributes to cisplatin resistance in BLCA through autophagy regulation. Our study highlights ABCC6 as a crucial factor in BLCA cisplatin resistance, with autophagy playing a significant role in this mechanism. Targeting autophagy may offer a potential strategy to overcome chemoresistance in BLCA. Future research should focus on validating these findings in clinical samples and exploring ABCC6 inhibitors or autophagy modulators as therapeutic options.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 15","pages":"3895-3905"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weijia Wen, Jiaying Li, Li Yuan, Yan Liao, Caixia Shao, Dingze Xu, Hongye Jiang, Yuandong Liao, Pan Liu, Chunyu Zhang, Shuzhong Yao, Wei Wang
{"title":"PRDX3 Promotes Lymph Node Metastasis in Cervical Cancer by Activating NF-κB Signaling Pathway and Anoikis Resistance.","authors":"Weijia Wen, Jiaying Li, Li Yuan, Yan Liao, Caixia Shao, Dingze Xu, Hongye Jiang, Yuandong Liao, Pan Liu, Chunyu Zhang, Shuzhong Yao, Wei Wang","doi":"10.7150/ijms.118912","DOIUrl":"10.7150/ijms.118912","url":null,"abstract":"<p><p>Lymph node metastasis (LNM) confers significant treatment failure and adverse clinical outcomes in cervical cancer (CCa). However, large unknown lies in the mechanisms underlying LNM in CCa. In this study, we discovered that PRDX3 is elevated in CCa with LNM and associates with poor prognosis in CCa patients. Moreover, multivariate logistic analysis revealed that PRDX3 is an independent predictor of LNM in CCa. Functional investigations demonstrated that PRDX3 promotes invasion, lymphangiogenesis, and LNM of CCa. Mechanistically, PRDX3 activates NF-κB signaling pathway and upregulates the downstream pro-metastatic molecules VEGF-C and MMP-9 in CCa cells. Furthermore, PRDX3 could inhibit the anoikis of detached CCa cells by reducing the ROS level and hence promote LNM in CCa. Importantly, genetic inhibition of PRDX3 potently slows LNM of CCa. These findings highlight a novel PRDX3-mediated mechanism of LNM in CCa and recognize PRDX3 as a promising predictive marker and target of clinical intervention for LNM in CCa.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 15","pages":"3839-3853"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decoding Endoplasmic Reticulum Stress on Chondrocyte Driving Osteoarthritis Development through Integrating Single-Cell and Transcriptomic Profiling.","authors":"Zhao Zhang, Debin Cheng, Jingyi Dang, Xiaohe Wang, Hongbin Fan, Dong Liu","doi":"10.7150/ijms.119573","DOIUrl":"10.7150/ijms.119573","url":null,"abstract":"<p><p><b>Background:</b> Endoplasmic reticulum stress (ERS) as a potent disease regulator has been proven to be engaged in the pathogenesis and progression of numerous disorders. Osteoarthritis (OA) is a widespread degenerative disease of the joints with chondrocyte damage as the main pathologic mechanism. However, the specific role of ERS in chondrocytes during OA development remains poorly understood. <b>Methods:</b> Integration of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq analyses to thoroughly assess the landscape of ERS in chondrocytes from OA samples. The WGCNA and unsupervised cluster analysis were integrated to identify ERS patterns. Furthermore, we screened ERS key regulators for diagnosis and prediction of OA development by three algorithms (LASSO, Random Forest, and PPI analysis). Finally, we constructed <i>in vitro</i> OA models for validating the biological roles of the identified ERS key regulators. <b>Result:</b> scRNA-seq analysis revealed a robust association between ERS and OA progression. Unfolded protein responses, TNFA signaling via NF-κB, and apoptosis were significantly activated in the high ERS risk subpopulation. Cellular communication analysis demonstrated markedly enhanced cell-cell interactions and signaling pathways in high ERS risk subpopulations compared to low ERS risk subpopulations. Unsupervised cluster analysis identified two ERS patterns exhibiting distinct metabolic and inflammation signaling sceneries. Additionally, we identified two key ERS regulators, IGFBP3 and S100A4, and developed a novel nomogram based on these markers, which demonstrated excellent clinical predictive and guiding capabilities. Finally, we found that suppressing IGFBP3 expression <i>in vitro</i> could maintain chondrocyte metabolic homeostasis and inhibit PERK/ATF4/CHOP cascade-mediated ERS to reduce chondrocyte apoptosis. <b>Conclusion:</b> The present study integrated scRNA-seq and bulk RNA-seq to delve into the pathogenesis of ERS driving the progression of OA and identify ERS key regulators for OA diagnosis and therapeutic intervention.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 15","pages":"3906-3923"},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Ke, Shuang Wu, Hongyang Xu, Fengming Liang, Jing Tian, Qiuhui Wang, Yang Chen
{"title":"Role of Estimated Glucose Disposal Rate in Staging and Death Risk of Cardiovascular-Kidney-Metabolic Syndrome: Insights from NHANES 1999-2018.","authors":"Jin Ke, Shuang Wu, Hongyang Xu, Fengming Liang, Jing Tian, Qiuhui Wang, Yang Chen","doi":"10.7150/ijms.116708","DOIUrl":"10.7150/ijms.116708","url":null,"abstract":"<p><p><b>Background:</b> The concept of cardiovascular-kidney-metabolic syndrome (CKM) was recently proposed by the American Heart Association. Insulin resistance (IR) is closely linked to metabolic disorders, chronic kidney disease, and cardiovascular disease, which are the key components of CKM. As a surrogate IR marker, estimated glucose disposal rate (eGDR) may help identify high-risk patients. However, the specific role of eGDR in CKM progression and outcomes remains undefined. We aimed to evaluate the associations between eGDR and CKM progression, as well as its association with death in patients with CKM. <b>Methods:</b> Data was obtained from the National Health and Nutrition Examination Survey 1999-2018. Adults aged ≥ 20 years with complete data on CKM components and eGDR were included. Study outcomes were CKM progression and death outcomes. Multinomial logistic regression was used to evaluate the association between eGDR and CKM staging. Kaplan-Meier curves and Cox proportional hazard models assessed death outcomes, with restricted cubic splines exploring non-linear relationships. Stratified and sensitivity analyses tested the robustness of results. The predictive performance of eGDR was compared with the Homeostasis Model Assessment of Insulin Resistance and triglyceride-glucose index for death outcomes. <b>Results:</b> 29,290 participants were included (median age: 53.00 years, 51.96% males), with 27,769 classified as having CKM. Higher eGDR was also associated with lower odds of progression to advanced CKM stages. In CKM patients, over a median follow-up of 8.92 years, 4,926 deaths occurred (17.7%), with 1,330 (4.8%) cardiovascular deaths and 3,596 (12.9%) non-cardiovascular deaths. Compared with the lowest eGDR quartile, CKM patients in the highest quartile had lower risk of all-cause death (HR=0.59, 95%CI: 0.52-0.66), cardiovascular death (HR=0.52, 95%CI: 0.41-0.66), and non-cardiovascular death (HR=0.60, 95%CI: 0.53-0.69) (all <i>P</i><0.001). Non-linear relationships between eGDR and death outcomes were observed (all <i>P for nonlinear</i><0.001). Subgroup and sensitivity analyses confirmed the robustness of these associations. Additionally, eGDR predicted death in CKM patients better than other IR markers. <b>Conclusions:</b> Our findings support the utility of eGDR as a risk stratification tool in CKM populations. Lower eGDR levels were associated with more advanced CKM stages and higher long-term mortality, suggesting its potential role in identifying high-risk individuals.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 14","pages":"3779-3788"},"PeriodicalIF":3.2,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}