Dose-Response最新文献

{"title":"DJ-1-Binding Compound Improves Peripheral Nerve Injury in the Spinal Dorsal Horn by Restraining STAT3-Mediated Neurotoxic Reactive Astrocytes.","authors":"Shengtao Wang, Jieyong Cai, Qingsong Zhou, Ming Zhao, Wei Zhou","doi":"10.1177/15593258261475493","DOIUrl":"10.1177/15593258261475493","url":null,"abstract":"<p><p>Astrocytes are significantly activated after peripheral nerve injury (PNI) and affect the nerve repair by mediating neuroinflammation. DJ-1 is highly expressed in astrocytes, and its binding compounds exert significant neuroprotective effects by regulating antioxidant and anti-inflammatory responses. This study is designed to investigate the therapeutic effects of DJ-1-binding compound P-DJ-1A in a rat PNI model induced by spared nerve injury (SNI) surgery. The results revealed that SNI surgery induced the aggregation of activated astrocytes and the phosphorylated form of STAT3 in the ipsilateral dorsal spinal horn (DSH), which was concentrated mainly in the projection area of the injured nerve. Moreover, SNI surgery led to the extensive induction of proinflammatory and neurotoxic mediators, including IL-1β, TNF-α, IL-6, IL-18, and C3, while reducing the expression of TGF-β, IL-10, and S100A10. Treatment with P-DJ-1A or AG490 alleviated mechanical hyperalgesia and thermal hyperalgesia induced by SNI surgery, reduced \"A1\" astrocyte activation, and inhibited the expression of proinflammatory cytokines but increased the levels of TGF-β, IL-10, and S100A10. Mechanistically, P-DJ-1A or AG490 inhibited STAT3 activation and the NF-κB/NLRP3/IL-18 pathway. Collectively, the DJ-1-binding compound P-DJ-1A can alleviate SNI-induced injury by modulating neurotoxic astrocyte activation and inhibiting neuroinflammation, highlighting its potential as a novel therapeutic strategy.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261475493"},"PeriodicalIF":2.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Dose Radiation-Induced Expression of Exosomal miRNAs in the Serum of Medical Radiation Workers.","authors":"Ping Wang, Leshi Wei, Yu Gao, Xianfei Niu, Jie Li, Shasha Du, Yuanbo Cheng, Yunfei Zhang, Siqi Fang, Xiaohao Li, Lin Han, Yumin Lyu","doi":"10.1177/15593258261488713","DOIUrl":"10.1177/15593258261488713","url":null,"abstract":"<p><p><b>Objective:</b> Long-term low-dose ionizing radiation may alter genomes and cause diseases. This study examined serum exosomal miRNA differences among radiation-exposed medical workers by work types. <b>Methods:</b> High-throughput sequencing screened serum exosomal miRNAs in diagnostic radiologists, interventional radiologists, and nuclear medicine doctors. qRT-PCR validated differentially expressed miRNAs. <b>Results:</b> 410 differentially expressed miRNAs, including 102 downregulated and 308 upregulated miRNAs, enriched in 15 KEGG pathways. Four miRNAs were validated. miR-30e-5p, miR-155-5p and miR-486-5p differed significantly among groups(P<0.01).The expression levels of these three miRNAs were lower in the nuclear medicine group than in the diagnostic group (0.25±0.05vs3.89±8.62,0.10±0.15vs7.03±15.75,0.37±0.39vs4.46±9.64;Z=3.542,3.335,9.859;P<0.01), whereas miR-155-5p was lower in the interventional group than in the diagnostic group(1.32±2.43vs 7.03±15.75;H=11.889,P=0.003), miR-486-5p was higher(9.54±19.39vs4.46±9.64; H=9.859,P=0.007). All four miRNAs showed higher expression in the 14-31-year work-experience group, and all four also showed age-dependent differences, with miR-30d-5p and miR-486-5p showing the age-related differences (P<0.01). Combined detection of the four miRNAs improved discrimination among occupational categories (AUC=0.784). Multiple linear regression analysis showed that sex was associated with all four miRNAs, whereas work type was associated with miR-30d-5p and miR-155-5p (P<0.05). <b>Conclusion:</b> Serum exosomal miR-30e-5p, miR-155-5p, and miR-486-5p are promising biomarkers for monitoring radiation-induced damage, supporting occupational protection and health management.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261488713"},"PeriodicalIF":2.8,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shape-Restricted Detection of Natural Product Hormesis: A Re-Analysis of Complex Botanical Mixtures.","authors":"Ying Jin, Cynthia Rider, Ruili Huang, Menghang Xia, Helene Langevin, Shanshan Zhao, Daniel Zilber","doi":"10.1177/15593258261486644","DOIUrl":"10.1177/15593258261486644","url":null,"abstract":"<p><strong>Introduction: </strong>Botanical supplements are consumed to improve health despite the mystery of their mechanisms. One possible effect is hormesis, defined as a beneficial and stimulatory health effect at a low dose and detrimental effect at a high dose, or vice versa. Hormesis is usually discovered by manually examining the shape of dose-response curves, which is not scalable to the large number of chemical-assay combinations found in high-throughput screening (HTS) results.</p><p><strong>Methods: </strong>We proposed a semi-automatic statistical testing procedure to quickly evaluate large-scale dose-response data, accompanied by an R package <i>shorm</i> for easy implementation. The nonparametric shape tests are more flexible with few assumptions. We also developed a new visualization method to represent the test conclusions and uncertainties simultaneously. This representation highlights both significant and ambiguous findings for efficient examination.</p><p><strong>Results: </strong>We applied this method to a data set of 4860 chemical-assay pairs and identified 561 (12%) dose-response curves showing statistically significant hormesis.</p><p><strong>Conclusion: </strong>Our discovery of hormetic curves is in line with estimates of hormetic behaviors in dose-response repositories like Tox21. Our proposed method has been effective in screening for hormesis from large-scale dose-response data, and the visualization method effectively facilitates the interpretation of test results.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261486644"},"PeriodicalIF":2.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on Dietary Intervention in Radiation Protection.","authors":"Jia Du, Xudong Ding, Bingbing Song, Lu Lu","doi":"10.1177/15593258261487097","DOIUrl":"10.1177/15593258261487097","url":null,"abstract":"<p><p>The application of nuclear technology in energy, healthcare, and aerospace sectors is increasingly widespread, causing radiation protection to be an important topic for public health and biomedical research. Ionizing radiation causes harm by damaging cells directly or indirectly. Traditional radiation protection adopts physical barriers and pharmacological methods, which have proved to be effective but have certain limitations. The Mediterranean diet, fasting or calorie restriction, ketogenic diet, plant-based diet, and high-fiber diet are common and reliable dietary patterns. Dietary patterns contribute to regulating key molecular pathways including oxidative stress, inflammatory responses, metabolism, and gut microbiota. Enhancing the body's resistance to radiation damage through dietary intervention represents a highly promising nutritional strategy. Understanding the mechanisms and research behind dietary interventions for radiation protection facilitates the integration of radiation protection into daily life, enabling the development of personalized, precision-based dietary intervention strategies. This review focuses exclusively on research evidence and mechanism analysis to assess the impact of dietary intervention on ionizing radiation protection and look forward to their potential and challenges for clinical radiotherapy support and radiation protection for special occupational groups.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261487097"},"PeriodicalIF":2.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daphnetin Attenuates Inflammatory and Apoptotic Responses Induced by High Glucose/High Free Fatty Acids and Lipopolysaccharide in an HK-2 Cell-Neutrophil Co-Culture System.","authors":"Hong Wu, Yuhuan Jiang, Xiaodong Zhong, Ningrui Wang, Wenjing Zhou, Yanan Chen, Yijun Nie","doi":"10.1177/15593258261486634","DOIUrl":"10.1177/15593258261486634","url":null,"abstract":"<p><strong>Objectives: </strong>The present study aimed to investigate the protective effect of daphnetin (dap) against high glucose and high free fatty acids (HGHF) and lipopolysaccharide(LPS)-induced injury in the aforementioned co-culture system under normal control conditions (normal glucose and no exogenous FFA supplementation), and to explore its potential molecular mechanisms.</p><p><strong>Methods: </strong>Neutrophils were isolated from the peripheral blood of healthy individuals. Subsequently, HK-2 cells and a neutrophil suspension were co-cultured at 1x10⁵ cells/mL to establish the experimental model. The non-cytotoxic concentration of dap for subsequent experiments was determined by Cell Counting Kit-8 (CCK-8) assay. Heparin-binding protein (HBP) concentration was measured using dry quantitative immunofluorescence assay. Inflammatory cytokines were quantified via cytometric bead array, and cell apoptotic rate was assessed by Annexin V-FITC-based flow cytometry.</p><p><strong>Results: </strong>Both HGHF treatment and LPS exposure significantly elevated the levels of the inflammatory mediator HBP, cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-10) and cellular apoptosis, whereas dap administration markedly attenuated these inflammatory and apoptotic alterations induced by HGHF or LPS (all <i>P</i><0.05).</p><p><strong>Conclusion: </strong>In this in vitro model, dap attenuated HGHF- and LPS-induced inflammatory and apoptotic responses. Further studies are needed to assess its relevance to diabetic kidney disease.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261486634"},"PeriodicalIF":2.8,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sesamoside Alleviates Inflammatory Response in Septic Shock-Associated Acute Liver Injury by Modulating the NF-κB/MAPK Signaling Pathway.","authors":"Xinjie Zhao, Xiaohua Hao, Jialu Yuan, Yanru Zhang, Shizhuo Chen, Shuaijie Wei, Haoxuan Gao, Keqing Tian, Dan Song","doi":"10.1177/15593258261484434","DOIUrl":"10.1177/15593258261484434","url":null,"abstract":"<p><strong>Objectives: </strong>Acute liver injury, a lethal septic shock complication with scarce treatments, lacks research on Sesamoside's liver-protective function. We explored its protective mechanisms against lipopolysaccharide (LPS)-induced liver injury via the nuclear factor kappa B/mitogen-activated protein kinases (NF-κB/MAPK) pathway.</p><p><strong>Methods: </strong>Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and NF-κB/MAPK pathway were screened via bioinformatic analysis, and an LPS-induced mouse model was established for <i>in vivo</i> verification. Quantitative real-time polymerase chain reaction (qPCR) detected cytokines and vasoactive factors; Western blot measured proteins; Hematoxylin and eosin (H&E) staining and Immunohistochemistry (IHC) assessed liver pathology.</p><p><strong>Results: </strong>1-, 5-, and 10 mg/kg Sesamoside suppressed LPS- triggered excess TNF-α (∼97%, <i>p</i> < 0.0001), IL-6 (∼95%, <i>p</i> < 0.0001), IL-1β (∼91%, <i>p</i> = 0.0011) and nitric oxide (NO) (∼96%, <i>p</i> < 0.0001). It reduced NOD-like receptor family pyrin domain-containing 3 (NLRP3) by ∼25% (<i>p</i> < 0.0001), and decreased nuclear factor-kappa B p65 subunit (P65), phosphorylated extracellular signal-regulated kinase/total extracellular signal-regulated kinase (p-ERK/ERK), phosphorylated c-Jun N-terminal kinase/total c-Jun N-terminal kinase (p-JNK/JNK) by 61% (<i>p</i> < 0.0001), 25% (<i>p</i> = 0.0066) and 49% (<i>p</i> < 0.0001) respectively. Liver injury and inflammatory infiltration were markedly attenuated.</p><p><strong>Conclusion: </strong>Sesamoside alleviates septic shock-related acute liver injury by inhibiting NF-κB/MAPK signaling and excessive inflammation, providing a promising natural compound for targeted therapy development.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261484434"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DYNLRB1: A Potential Prognostic Biomarker Associated With an Immunosuppressive Microenvironment in Hepatocellular Carcinoma.","authors":"Qiaoqiao Huang, Yan Gao, Runan Zhang, Mei Chen, Deying Xiao, Long Xie, Yaping Xu","doi":"10.1177/15593258261473582","DOIUrl":"10.1177/15593258261473582","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the expression pattern, prognostic significance, immune relevance, and biological function of Dynein Light Chain Roadblock-Type 1 (DYNLRB1) in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>Publicly available datasets and analytical platforms, including TCGA, GTEx, TIMER2.0, TISIDB, LinkedOmics, GEPIA2, CancerSEA, and the Human Protein Atlas, were utilized to evaluate DYNLRB1 expression, prognostic value, and immune infiltration characteristics. In vitro functional assays-including CCK-8, EdU incorporation, colony formation, wound-healing, and Transwell assays-were performed to validate the biological role of DYNLRB1 in HCC cells.</p><p><strong>Results: </strong>DYNLRB1 was significantly upregulated in HCC tissues and cell lines. Elevated DYNLRB1 expression was consistently associated with advanced clinicopathological features and poor survival outcomes across multiple metrics (including OS, DSS, DFI, and PFI). Furthermore, high DYNLRB1 expression correlated with an immunosuppressive tumor microenvironment signature, characterized by elevated inhibitory immune checkpoints. Functional enrichment suggested involvement in ribosome biogenesis and cell-cycle-associated processes. In vitro, DYNLRB1 knockdown significantly inhibited HCC cell proliferation, migration, and invasion.</p><p><strong>Conclusion: </strong>DYNLRB1 is a potential prognostic biomarker associated with tumor malignant progression and an immunosuppressive microenvironment in HCC. These findings suggest that DYNLRB1 may represent a potential therapeutic target warranting further investigation.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261473582"},"PeriodicalIF":2.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The LNT Model and ALARA in Diagnostic Imaging: A Critical Review of Scientific Evidence in the Low-Dose Range.","authors":"Khaled Soliman, Abdulaziz Alhazmi","doi":"10.1177/15593258261481921","DOIUrl":"10.1177/15593258261481921","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The Linear No-Threshold (LNT) model and the As Low As Reasonably Achievable (ALARA) principle form the cornerstone of contemporary radiation protection. Although these frameworks were designed as conservative regulatory tools, their extrapolation to the low-dose and dose-rate (LDDR) range commonly encountered in diagnostic imaging remains scientifically contentious.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This review critically examines the scientific basis for applying the LNT model and the ALARA principle in the LDDR range (1-50 mGy) routinely encountered in diagnostic imaging, with the aim of evaluating whether current regulatory practices are proportionate to demonstrated risks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a narrative review of peer-reviewed literature published between 1995 and 2025, retrieved from PubMed, Scopus, and Web of Science using the search terms \"LNT model,\" \"low-dose radiation,\" \"ALARA,\" \"radiation hormesis,\" \"adaptive response,\" and \"diagnostic reference levels.\" Priority was given to systematic reviews, large-cohort epidemiological studies, and consensus statements from professional organizations (ICRP, UNSCEAR, AAPM, HPS, IOMP). Studies were grouped thematically into radiobiological evidence, epidemiological evidence, and clinical/policy implications. We acknowledge that this is a non-systematic review and that selection bias cannot be excluded.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Multiple lines of radiobiological evidence-including DNA repair fidelity at low doses, adaptive cellular responses, apoptotic clearance of damaged cells, and immune surveillance-suggest that the dose-response relationship for stochastic effects in the LDDR range is unlikely to be linear. Large-scale epidemiological studies, including atomic bomb survivor reanalyses, occupational cohorts, and high-background radiation populations, generally fail to demonstrate statistically significant excess cancer risk below approximately 100 mGy, although confidence intervals remain wide. Case examples in scoliosis screening, mammography, and low-dose CT lung cancer screening illustrate scenarios in which overly conservative ALARA implementation may delay or deter clinically beneficial imaging.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Within the LDDR range, the available evidence does not support a linear dose-response relationship, and the indiscriminate application of ALARA based on hypothetical risks may produce net harm through deferred imaging, radiophobia, and inefficient resource allocation. We propose that radiation protection in medical imaging shift toward an evidence-informed framework that prioritizes image quality optimization, individualized risk assessment, and the adoption of complementary principles such as ASARA (As Safe As Reasonably Achievable) and AHARA (As High As Reasonably Achievable benefits). A linear-with-threshold (LT) model and the adverse outcome pathway (AOP) framework warrant further investigation as ","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261481921"},"PeriodicalIF":2.8,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cell Distribution Width-To-Albumin Ratio and 90-Day Mortality in Sepsis Patients with and Without Sepsis-Induced Coagulopathy: A Retrospective Observational Study Using the MIMIC-IV Database.","authors":"Baochang Xie, Yu Cao, Yuanyuan Xiao, Diyang Zhu, Xiaoyu Guan, Guangming Chen","doi":"10.1177/15593258261474770","DOIUrl":"10.1177/15593258261474770","url":null,"abstract":"<p><strong>Background: </strong>The red blood cell distribution width-to-albumin ratio (RAR) has emerged as a novel prognostic biomarker in critically ill patients. However, its association with mortality in sepsis patients, particularly in the context of sepsis-induced coagulopathy (SIC), remains unclear.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed adult sepsis patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) version 3.1 database. RAR was calculated from the first laboratory measurements within 24 hours of intensive care unit (ICU) admission. The primary outcome was 90-day all-cause mortality. Cox proportional hazards regression, subgroup analyses, and restricted cubic spline (RCS) regression were performed. Discriminative ability was assessed using receiver operating characteristic (ROC) curves.</p><p><strong>Results: </strong>Of 26,854 patients meeting sepsis criteria, 17,499 were excluded due to missing RDW or albumin data. A total of 9,206 sepsis patients were included, with 5,649 (61.4%) meeting SIC criteria. The overall 90-day mortality was 38.1% (absolute rates: 23.9% in the lowest RAR quartile to 55.5% in the highest). In the fully adjusted model (age, sex, SOFA, Charlson Comorbidity Index, infection source, vasopressor use, mechanical ventilation, renal replacement therapy, and lactate), each unit increase in RAR was associated with a 9% increase in mortality risk (hazard ratio [HR]=1.09, 95% confidence interval [CI]: 1.08-1.10, P<0.001). Compared with the lowest quartile, patients in the highest RAR quartile had a significantly higher mortality risk (HR=2.07, 95% CI: 1.91-2.25). The association remained consistent across subgroups. RCS analysis revealed a significant non-linear exposure-response relationship (P for non-linearity <0.001). DeLong testing confirmed that RAR (AUC=0.648) had statistically significantly higher discriminative ability than SOFA score (AUC=0.613, P<0.001) and SIC score (AUC=0.593, P<0.001) for 90-day mortality, though all AUC values indicated moderate discrimination.</p><p><strong>Conclusions: </strong>Elevated RAR was independently associated with increased 90-day mortality after comprehensive covariate adjustment (highest vs. lowest quartile: HR=2.07, 95% CI: 1.91-2.25), with modest but statistically significant incremental discriminative ability over SOFA and SIC scores. As a biomarker derived from routine blood tests, RAR may complement existing tools for early risk stratification in sepsis. These findings are hypothesis-generating and warrant prospective validation.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261474770"},"PeriodicalIF":2.8,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon Ion Irradiation Suppresses Tumor Growth, Migration and Invasion in X-ray Resistant Melanoma <i>in Vitro</i> and <i>in Vivo</i>.","authors":"Sha Li, Zhenghua Ren, Hefa Huang, Huiyan Pang, Hongyu Luo, Zhengli Wei, Xiaoyang Yin, Mengjie Xing, Xiaoqin Li, Aihong Mao","doi":"10.1177/15593258261479396","DOIUrl":"https://doi.org/10.1177/15593258261479396","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate whether carbon ion irradiation (CIR) can overcome the inherent radioresistance of melanoma and suppress metastasis, we evaluated its effects on B16F10 cells <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Methods: </strong>B16F10 cells and C57BL/6J tumor-bearing mice were irradiated with either 4-MV X-rays or 290 MeV/nucleon carbon ions at different doses. Metastatic ability was assessed by wound-healing, Transwell migration, and Matrigel invasion assays. Expression of metastasis-related proteins, including MMP2, MMP9, N-cadherin, and E-cadherin, was analyzed by Western blotting or immunohistochemistry (IHC). Tumor growth and survival were recorded, and H&E staining was performed for histopathological evaluation.</p><p><strong>Results: </strong>Under identical physical-dose conditions, CIR suppressed cell migration and invasion more effectively than XIR, especially at 2.5 and 7.5 Gy. These effects were accompanied by reduced expression of MMP2, MMP9, and N-cadherin, along with increased E-cadherin expression. Furthermore, 7.5 Gy CIR significantly suppressed tumor growth, reduced tumor volume, and prolonged survival in tumor-bearing mice, although tumor regrowth was observed after 21 days. Conversely, 0.5 Gy XIR exerted promoting effects, while 2.5 Gy XIR only had a slight impact.</p><p><strong>Conclusion: </strong>These findings highlight the antimetastatic potential of CIRT against radioresistant melanoma. However, further validation with RBE-adjusted doses, human cell models, and metastasis-related endpoints is warranted.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"24 3","pages":"15593258261479396"},"PeriodicalIF":2.8,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}