Yuheng Ding, Jun Liu, Lingna Shen, Zhipeng Yan, Yonghong Huang, Yihui Huang, Rong Huang, Yunda Qian, Xiaojun Lou, Lai Wang
{"title":"The persistent risk of secondary malignancies in gastric neuroendocrine tumor survivors: a population-based analysis.","authors":"Yuheng Ding, Jun Liu, Lingna Shen, Zhipeng Yan, Yonghong Huang, Yihui Huang, Rong Huang, Yunda Qian, Xiaojun Lou, Lai Wang","doi":"10.1007/s10238-025-01706-y","DOIUrl":"10.1007/s10238-025-01706-y","url":null,"abstract":"<p><p>Gastric neuroendocrine tumors (G-NETs) are rare neoplasms with a favorable survival rate, yet they present a significant risk for second primary malignancies (SPMs). This study aims to estimate the relative risks of SPMs in G-NET survivors, exploring variations across key patient characteristics. Patients diagnosed with G-NETs were identified from the Surveillance, Epidemiology, and End Results database (2000-2021). Standardized incidence ratios (SIRs) and excess absolute risks (EARs) were calculated to assess SPM risk stratified by age at diagnosis, gender, race, latency period, marital status, and surgical intervention. Among 5072 G-NET survivors, 912 (18.0%) developed SPMs, with a median interval of 34.3 months between the diagnoses. The overall SIR for SPMs was 2.09 (95% confidence interval [CI] 1.96-2.23), corresponding to an EAR of 145.64 per 10,000 person-years. Increased risks were observed for cancers of the stomach, small intestine, thyroid, hepatobiliary system, pancreas, and esophagus. The highest risk for SPMs occurred within the first 4 years following G-NET diagnosis (SIR 2.57; 95% CI 2.11-3.1), with a gradual decline thereafter. Patients under 50 years had the highest SIRs, particularly for stomach cancer (SIR 196.28; 95% CI 160.21-238.05). Females exhibited a slightly higher SIR than males. White patients demonstrated the highest risk for stomach cancer, with an SIR of 63.88 (95% CI 57.00-71.38). G-NET survivors are at a persistently elevated risk of developing SPMs, particularly within the first 4 years of diagnosis. Age, gender, and racial factors significantly influence this risk. Personalized surveillance strategies are warranted to address these disparities and reduce SPM incidence.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"158"},"PeriodicalIF":3.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985869","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":"Haematological toxicities with immune checkpoint inhibitors in digestive system tumors: a systematic review and network meta-analysis of randomized controlled trials.","authors":"Xinpu Han, Jing Xu, Meichen Cui, Zhangjun Yun, Hongbin Zhao, Shaodan Tian, Suicai Mi, Li Hou","doi":"10.1007/s10238-025-01688-x","DOIUrl":"10.1007/s10238-025-01688-x","url":null,"abstract":"<p><p>This study aims to comprehensively evaluate the hematologic toxicity profiles, toxicity spectrum, and safety rankings of immune checkpoint inhibitors (ICIs) used for digestive system tumors. The PubMed, Cochrane Library, Web of Science, and Embase databases were systematically searched from inception to August 2024 to identify randomized controlled trials (RCTs). The primary outcome was anemia, while secondary outcomes included neutropenia, neutrophil count decreased, thrombocytopenia, platelet count decreased, leukopenia, white blood cell (WBC) count decreased, lymphocyte count decreased, and febrile neutropenia (FN). Subgroup analyses were performed based on tumor type, country category, study phase, ICI regimen, control group, chemotherapy regimen, ICI plus different chemotherapy regimens. Two reviewers independently selected the studies, extracted data according to pre-specified criteria, and assessed the risk of bias using the Cochrane Collaboration risk of bias tool. RevMan 5.4 software was utilized to visualize the risk of bias assessments. Stata 16.0 was used to conduct network meta-analysis, sensitivity analysis and meta-regression. 25 phase II and III RCTs (n = 15216) were included. The general safety of ICIs ranked from high to low for grade 1-5 anemia were as follows: avelumab, nivolumab, pembrolizumab, sintilimab, camrelizumab, and tislelizumab. For grade 3-5 anemia, the general safety profile of the ICIs were as follows, from highest to lowest: avelumab, nivolumab, pembrolizumab, sintilimab, and camrelizumab. Compared to chemotherapy, treatment-related hematologic toxicities with ICIs occurred primarily in grade 1-5 anemia, neutropenia, thrombocytopenia, leukopenia, and WBC count decreased. Taking ICI monotherapy, nivolumab plus ipilimumab were generally safer than taking chemotherapy, one ICI drug with chemotherapy, or two ICI drugs with chemotherapy. In terms of grade 1-5 hematologic toxicities, tislelizumab had the highest risk of neutropenia and leukopenia; the primary treatment-adverse events (AEs) for sintilimab was neutrophil count decreased and WBC count decreased; the primary treatment-related AE associated with nivolumab was platelet count decreased; camrelizumab posed the highest risk for lymphocyte count decreased. In terms of grade 3-5 hematologic toxicities, pembrolizumab was predominantly linked to neutropenia; sintilimab showed the greatest risk for neutrophil count decreased, platelet count decreased, and lymphocyte count decreased; avelumab was most associated with WBC count decreased. FN primarily manifested as grade 3-5, with camrelizumab having the highest risk. Among agents used in gastric or gastroesophageal junction cancer, avelumab demonstrated the most favorable safety profile for anemia. Each treatment regimen has its unique safety profile. Early identification and management of ICI-related hematologic toxicities are essential in clinical practice.Systematic Review Registration: PROSPERO CRD420245715","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"157"},"PeriodicalIF":3.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953600","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}
Agnieszka Walczyk, Danuta Gąsior-Perczak, Iwona Pałyga, Janusz Kopczyński, Artur Kuchareczko, Emilia Niedziela, Agnieszka Suligowska, Izabela Płachta, Magdalena Chrapek, Stanisław Góźdź, Aldona Kowalska
{"title":"Risk characteristics of papillary thyroid cancer > 1-4 cm is associated with increased tumour size.","authors":"Agnieszka Walczyk, Danuta Gąsior-Perczak, Iwona Pałyga, Janusz Kopczyński, Artur Kuchareczko, Emilia Niedziela, Agnieszka Suligowska, Izabela Płachta, Magdalena Chrapek, Stanisław Góźdź, Aldona Kowalska","doi":"10.1007/s10238-025-01596-0","DOIUrl":"10.1007/s10238-025-01596-0","url":null,"abstract":"<p><p>Recent guidelines recommend total thyroidectomy for papillary thyroid cancers (PTC) larger than 4 cm. For papillary macrocarcinoma with a diameter >1-4 cm, less intensive surgery can be managed, but this is still a matter for debate. The aim of our study was to assess the prevalence of risk factors such as vascular invasion, positive margin, extrathyroidal extension, aggressive histology, lymph nodes and distant metastases associated with a primary PTC tumour with a diameter >1-4 cm, and the association between tumour size and the risk of having one or more of these factors. A retrospective analysis of the medical records of 857 patients who underwent total thyroidectomy between 2000 and 2020, with a final post-operative diagnosis of a PTC >1-4 cm. Overall, less than a half (47.0%) of tumours were associated with at least one risk factor. The prevalence of analysed risk factors, except aggressive histology and a positive margin status, was significantly associated with larger tumour size (>2-4 cm). The optimal cut-off value for a cumulative risk of having one or more risk factors was estimated as 2.0 cm. Patients with a primary tumour < 2.0 cm had almost double less risk (p-value < 0.0001; OR 1.95; 95% CI 1.47-2.58) of having one or more risk factors than patients with PTC ≥ 2.0 cm. In an era of de-escalation, the cut-off value of 2 cm can be helpful in identifying patients with PTC >1-4 cm and lower risk of having aggressive disease providing less extensive treatment approach.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"155"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987218","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":"Revealing roles of PANoptosis-related genes in prognosis and molecular subtypes in lung squamous cell carcinoma by integrated bioinformatic analyses and experiments.","authors":"Ying Chen, Meihua Wang","doi":"10.1007/s10238-025-01696-x","DOIUrl":"10.1007/s10238-025-01696-x","url":null,"abstract":"<p><p>The purpose of current study was to reveal the role of PANoptosis-associated genes in lung squamous cell carcinoma (LUSC) and their potential as prognostic biomarkers. We analyzed RNA-seq data from TCGA-LUSC and GEO datasets to identify differentially expressed genes (DEGs) between LUSC and normal samples, followed by VENN analysis to reveal PANoptosis-related DEGs. Functional enrichment analyses were performed by clusterProfiler package. Distinct LUSC subtypes were identified by consensus clustering based on PANoptosis-related DEGs. Univariate Cox and LASSO regression were utilized to identify key prognostic genes, and a prognostic model was developed based on selected genes. Immune infiltration status was evaluated by CIBERSORT and ESTIMATE algorithms. Expression of key prognostic genes was tested in three LUSC cell lines by RT-qPCR and Western blot. Roles of TLR3 in LUSC progression were determined by functional experiments. A total of 76 PANoptosis-related DEGs were identified, with significant enrichment in apoptosis pathways. The clustering analysis revealed four subtypes, in which survival and immune microenvironment were dramatically different. From the 76 genes, four key prognostic genes (CHEK2, PDK4, TLR3, and IL1B) were identified to establish prognostic risk model, which could reflect the survival status and immune cells composition variations for LUSC patients. Besides, these four genes showed significant correlations with infiltrating levels of various immune cells. TLR3 was identified as a more weighted prognostic risk gene in LUSC. Functional assays demonstrated that genes like TLR3 modulated cell proliferation, migration, and inflammatory responses in LUSC cells. This study highlighted the potential of the four key PANoptosis genes as biomarkers or targets in LUSC, and the risk model based on these four genes provided novel insights to develop personalized treatment strategy for patients with LUSC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"154"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956995","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}
Huacong Cai, Jishi Wang, Zhenyu Yan, Hu Zhou, Zhenyu Li, Feng'e Yang, Pengxiang Guo, Da Gao, Jie Jin, Yun Zeng, Shujie Wang
{"title":"Efficacy and safety of a new 10% intravenous immunoglobulin (IVIG) in Chinese patients with primary immune thrombocytopenia (ITP): a multicenter, single-arm, phase III trial.","authors":"Huacong Cai, Jishi Wang, Zhenyu Yan, Hu Zhou, Zhenyu Li, Feng'e Yang, Pengxiang Guo, Da Gao, Jie Jin, Yun Zeng, Shujie Wang","doi":"10.1007/s10238-025-01658-3","DOIUrl":"10.1007/s10238-025-01658-3","url":null,"abstract":"<p><p>A novel, highly purified 10% intravenous immunoglobulin (IVIG) formulation was evaluated for both therapeutic efficacy and safety profile in adult patients diagnosed with persistent or chronic primary immune thrombocytopenia (ITP). This phase III, multicenter, open-label, single-arm clinical trial enrolled Chinese adult patients diagnosed with persistent or chronic ITP presenting with baseline platelet counts below 30 × 10<sup>9</sup>/L. Participants received intravenous administration of 10% IVIG at a standardized dosage of 1 g/kg/day for two consecutive days. The primary efficacy endpoint was defined as the proportion of subjects achieving both a platelet count elevation to ≥ 30 × 10<sup>9</sup>/L and a minimum two-fold increase from baseline values within a 7-day post-treatment observation period following the first dose administration. Seventy-two patients were enrolled and sixty patients completed the study. 52 (72.2%; 95% CI: 60.4, 82.1) patients achieved platelet count ≥ 30 × 10<sup>9</sup>/L and experienced a ≥ twofold increase from baseline within 7 days, and 52 (72.2%; 95% CI: 60.4, 82.1) patients achieved complete response (CR) or response (R) within 7 days. 64 patients (88.9%; 95% CI: 79.3, 95.1) achieved platelet count ≥ 50 × 10<sup>9</sup>/L within 7 days with a median time of 3 days. 71 patients completed the ITP bleeding scale assessment after 7 days, showing a decrease of 0.6 ± 1.07 from baseline. A total of 66 patients (91.7%) reported treatment-emergent adverse events (TEAEs) during the study, and 37 patients (51.4%) reported adverse drug reactions (ADRs). The most prevalent ADRs with an incidence exceeding 5% included headache (n = 12, 16.7%), fever (n = 10, 13.9%), decreased white blood cell count (n = 5, 6.9%), and nausea (n = 5, 6.9%). The therapeutic regimen of 10% IVIG administered at a dosage of 1 g/kg/day for two consecutive days demonstrated both favorable safety profiles and clinical efficacy. These robust findings provide substantial evidence supporting the clinical application of this novel 10% IVIG formulation in the management of adult patients with ITP.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"153"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986768","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}
Sisi Feng, Manli Zhou, Zixin Huang, Xiaomin Xiao, Baiyun Zhong
{"title":"A machine learning-based prediction model for colorectal liver metastasis.","authors":"Sisi Feng, Manli Zhou, Zixin Huang, Xiaomin Xiao, Baiyun Zhong","doi":"10.1007/s10238-025-01699-8","DOIUrl":"10.1007/s10238-025-01699-8","url":null,"abstract":"<p><p>Colorectal liver metastasis (CRLM) is a primary factor contributing to poor prognosis and metastasis in colorectal cancer (CRC) patients. This study aims to develop and validate a machine learning (ML)-based risk prediction model using conventional clinical data to forecast the occurrence of CRLM. This retrospective study analyzed the clinical data of 865 CRC patients between January 2018 and September 2024. Patients were categorized into non-CRLM and CRLM groups. The least absolute shrinkage and selection operator regression was employed to identify key clinical variables, and five ML algorithms were utilized to develop prediction models. The optimal model was selected based on performance metrics including the receiver operating characteristic curve, precision-recall curve, decision curve analysis, and calibration curve, which collectively evaluated both the predictive accuracy and clinical utility of the model. Among the five ML algorithms evaluated, Random forest demonstrated the best performance. Leveraging the Random forest algorithm, we developed the CRLM-Lab6 prediction model, which incorporates six features: LDH, CA199, ALT, CEA, TBIL, and AGR. This model exhibits robust predictive performance, achieving an area under the curve of 0.94, a sensitivity of 0.88, and a specificity of 0.93. To enhance its practical utility, the model has been integrated into an accessible web application. This study developed a novel risk prediction model by integrating ML algorithms with conventional laboratory test data to evaluate the likelihood of CRLM occurrence. The model demonstrates excellent predictive performance and has significant clinical application potential.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"156"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963987","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}
Dong Zhou, Chunhong Li, Dan Huang, Yan Yang, Chuang Sun, Yuan Huo, Liyuan Ma, Fang Xie, Jinsong Yan
{"title":"Reduced-dose donor lymphocyte infusion is a viable therapeutic strategy for Epstein-Barr virus-related post-transplant lymphoproliferative disease after hematopoietic stem cell transplantation: a single-center experience.","authors":"Dong Zhou, Chunhong Li, Dan Huang, Yan Yang, Chuang Sun, Yuan Huo, Liyuan Ma, Fang Xie, Jinsong Yan","doi":"10.1007/s10238-025-01685-0","DOIUrl":"https://doi.org/10.1007/s10238-025-01685-0","url":null,"abstract":"<p><p>Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication of hematopoietic stem cell transplantation caused by Epstein-Barr virus (EBV) reactivation due to immunosuppression. Frontline treatment includes the reduction of immunosuppressive therapy and administration of rituximab. However, the incidence of EBV-related PTLD (EBV<sup>+</sup> PTLD) continues to increase, and patient prognosis remains poor. In this retrospective study, we designed an exploratory treatment strategy for PTLD using designated reduced-dose donor lymphocyte infusion (DLI) (CD3 + T cells: 5 × 10<sup>4</sup>/kg) for majority patients (11/14). We further analyzed the data of 27 patients with PTLD who underwent transplantation at our institutions. Our therapeutic strategy effectively treated PTLD. In this study, the DLI cohort demonstrated higher overall response and complete remission rates than rituximab monotherapy after two-week intervention. Additionally, the DLI group had a markedly higher 1-year overall survival (OS) than the rituximab group. Similarly, the reduced-dosage DLI group had a significantly higher 1-year OS than the conventional-dosage group. These results indicate that varied treatments (rituximab vs DLI) and DLI dosages (conventional vs reduced) had significant impact on OS. Finally, the reduced-dosage DLI group had a lower risk of non-relapse mortality and acute graft versus host disease than the conventional-dosage group. This study demonstrates that reduced-dosage DLI is a promising treatment for EBV<sup>+</sup> PTLD.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"152"},"PeriodicalIF":3.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979205","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":"Machine learning for the prediction of diabetes-related amputation: a systematic review and meta-analysis of diagnostic test accuracy.","authors":"Zhigang Chen, Xinliang Liu, Simeng Li, Zhenheng Wu, Haifen Tan, Fuqian Yu, Dongmei Wang, Yawen Bo","doi":"10.1007/s10238-025-01697-w","DOIUrl":"10.1007/s10238-025-01697-w","url":null,"abstract":"<p><p>Although machine learning is frequently used in medicine for predictive purposes, its accuracy in diabetes-related amputation (DRA) remains unclear. From establishing the database until December 2024, we conducted a comprehensive search of PubMed, Web of Science (WoS), Embase, Scopus, Cochrane Library, Wanfang, and the China National Knowledge Index (CNKI). The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and Fagan plot analysis were used to assess the overall test performance of machine learning. Moreover, subgroup analysis and meta-regression were performed to search for possible sources of heterogeneity. Finally, sensitivity analysis and Deeks' funnel plot asymmetry test were used to evaluate the stability and publication bias, respectively. In the end, seven publications were included in this meta-analysis. The overall pooled diagnostic data were as follows: sensitivity, 0.72 (95% CI 0.69-0.75); specificity, 0.89 (95% CI 0.84-0.93); PLR, 3.62 (95% CI 3.36-3.89); NLR, 0.32 (95% CI 0.30-0.35); DOR, 13.55 (95% CI 11.72-15.67). The AUC was 0.81 (95% CI 0.77-0.84). The Fagan plot analysis showed that the positive post-test probability is 62% and the negative post-test probability is 7%. Subgroup analysis and meta-regression showed that both the level of bias and the year of publication were sources of heterogeneity in sensitivity and specificity. Sensitivity analysis confirmed the robustness of the results after excluding three outlier studies. The Deeks' funnel plot suggests that publication bias has no statistical significance (P > 0.05). In summary, our results suggest the moderate accuracy of machine learning in predicting DRA.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"151"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062765","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}
Yuxuan Ma, Yuhao Wang, Shu Wang, Haoyuan Wang, Yan Zhao, Chaosheng Peng, Xin Liu, Jianjun Yang
{"title":"Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors.","authors":"Yuxuan Ma, Yuhao Wang, Shu Wang, Haoyuan Wang, Yan Zhao, Chaosheng Peng, Xin Liu, Jianjun Yang","doi":"10.1007/s10238-025-01667-2","DOIUrl":"https://doi.org/10.1007/s10238-025-01667-2","url":null,"abstract":"<p><p>Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, primarily driven by KIT or PDGFRA mutations. Programmed cell death (PCD), including apoptosis, autophagy, and ferroptosis, plays a crucial role in GIST pathogenesis, progression, and treatment response. Non-coding RNAs (ncRNAs) have emerged as key regulators of PCD pathways, influencing GIST proliferation, metastasis, and drug resistance, particularly in response to tyrosine kinase inhibitors (TKIs) such as imatinib. Apoptosis suppression is strongly associated with poor prognosis, while autophagy contributes to tumor dormancy and TKI resistance. Ferroptosis, a novel iron-dependent cell death pathway, represents a promising therapeutic target. Recent evidence suggests that ncRNAs modulate these PCD pathways through interactions with key molecular regulators such as miR-494, miR-30a, and lncRNAs, which affect signaling networks including PI3K/AKT, MAPK, and mTOR. Furthermore, ncRNAs have mediated secondary resistance to imatinib by promoting autophagic flux and altering ferroptosis sensitivity. Understanding the molecular interplay between ncRNAs and PCD in GIST provides novel insights into disease mechanisms and offers potential therapeutic strategies to overcome drug resistance. Targeting ncRNA-mediated regulation of apoptosis, autophagy, and ferroptosis may enhance treatment efficacy and improve patient outcomes. Future research should focus on elucidating the mechanistic roles of ncRNAs in PCD pathways to develop innovative diagnostic and therapeutic approaches for GIST.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"150"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981230","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":"LASSO regression and Boruta algorithm to explore the relationship between neutrophil percentage to albumin ratio and asthma: results from the NHANES 2001 to 2018.","authors":"Yumin Fu, Jijing Zhao, Yunpeng Wang","doi":"10.1007/s10238-025-01701-3","DOIUrl":"https://doi.org/10.1007/s10238-025-01701-3","url":null,"abstract":"<p><p>The present study aims to investigate the relationship between the neutrophil-percentage-to-albumin ratio (NPAR) and asthma using least absolute shrinkage and selection operator (LASSO) regression and Boruta algorithm. Based on the National Health and Nutrition Examination Survey database from 2001 to 2018, a total of 31,138 eligible participants were included in this study. The participants were randomly divided into a training cohort and a validation cohort in a 7:3 ratio. LASSO regression and Boruta algorithm were applied to the training cohort for assessment, selection of the optimal model, and identification of potential confounding factors. A nomogram prediction model, receiver operating characteristic curve, calibration curve, and decision curve analysis were constructed to evaluate the model's ability to predict the risk of asthma and its stability. These analyses aim to provide a reference for clinical diagnosis and treatment. The study demonstrated that after adjusting for potential confounding factors, the NPAR was positively correlated with asthma incidence (P < 0.01). The area under the curve for the training set was 0.66 for LASSO regression and 0.64 for Boruta algorithm, indicating that LASSO regression exhibited superior performance. Through LASSO regression, 10 variables were selected, including gender, race, smoking status, hypertension, diabetes, cancer, poverty-income ratio, BMI, cardiovascular disease, and age. A nomogram prediction model was constructed based on these predictors. The calibration curve showed good fit between the two groups. A higher NPAR is significantly positively correlated with an increased risk of asthma.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"149"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970831","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}