International Journal of Medical Sciences最新文献

{"title":"Erratum: Lentivirus-mediated shRNA Targeting CNN2 Inhibits Hepatocarcinoma <i>in Vitro</i> and <i>in Vivo</i>: Erratum.","authors":"Xueqing Kang, Feng Wang, Xiuwan Lan, Xiaolong Li, Shunxin Zheng, Zhilue Lv, Yuan Zhuang, Yongxiang Zhao, Sufang Zhou","doi":"10.7150/ijms.114964","DOIUrl":"https://doi.org/10.7150/ijms.114964","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/ijms.21113.].</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2594-2595"},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302048","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 combination of PF-429242 and chloroquine triggers pH-dependent cell death in hepatocellular carcinoma cells.","authors":"Jiunn-Chang Lin, Tun-Sung Huang, Yan-Bin Chen, Pao-Shu Wu, Tsang-Pai Liu, Pei-Ming Yang","doi":"10.7150/ijms.109069","DOIUrl":"10.7150/ijms.109069","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a significant health challenge due to its resistance to conventional treatments and high recurrence rates. Developing novel therapeutic strategies is critical for improving outcomes for HCC patients. In this study, we identified the synergistic anticancer activity of the combination of PF-429242 and chloroquine against HCC cells. Combined treatment exhibited significant cytotoxicity against HCC cell lines, which was not observed with other therapeutic drugs. Notably, this synergistic effect was not mediated through apoptosis or autophagy. Further investigation revealed that the combination induced pH-dependent cell death, distinct from the previously described alkaliptosis. Unlike alkaliptosis, this cell death mechanism did not involve intracellular alkalinization or the IKKβ/NF-κB/CA9 signaling pathway. We also found that the ATP6V0D1/STAT3 axis, implicated in alkaliptosis, was not crucial for PF-429242/chloroquine-induced cell death. Additionally, site-1 protease inhibition by PF-429242 was not responsible for the observed synergistic effect. While the exact mechanism remains unclear, combined treatment induced a necrosis-like morphology and membrane rupture, which could be prevented by acidifying the culture medium. This research highlighted a novel pH-dependent cell death mechanism in HCC cells and suggests potential therapeutic implications for combining PF-429242 and chloroquine in cancer treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2583-2593"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302067","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":"Global, regional, and national burden of gastritis and duodenitis from 1990 to 2021 with projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021.","authors":"Lufei Wang, Wei Jiang, Hui Li","doi":"10.7150/ijms.109762","DOIUrl":"10.7150/ijms.109762","url":null,"abstract":"<p><p><b>Background:</b> Gastritis and duodenitis are highly prevalent upper gastrointestinal inflammatory conditions. We estimate the most up-to-date global, regional, and national burden in incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for gastritis and duodenitis from 1990 to 2021 with projections to 2050. <b>Methods:</b> Population-based data in this study was retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021). We evaluated the temporal trends of age-standardized rates of gastritis and duodenitis prevalence (ASPR), incidence (ASIR), mortality (ASMR), and DALYs (ASDR) across 204 countries and territories, as well as estimated annual percentage changes (EAPC) from 1990 to 2021. Analyses were stratified by sex, age subgroup, socio-demographic index (SDI) at the global, regional, and national level. A Bayesian age-period-cohort model was employed to project ASPR and ASDR of gastritis and duodenitis by sex and age up to 2050. <b>Results:</b> In 2021, 27.20 million (95% UI: 21.85-33.65) individuals globally had gastritis and duodenitis, with an ASIR of 323.24 (95% UI: 261.35-398.64) per 100,000. Globally, the prevalent cases of gastritis and duodenitis in 2021 was higher in females than in males and increased with age, peaking at the fifth decade of life. The number of prevalent cases of gastritis and duodenitis is projected to reach approximately 51.24 million by 2050. In 2021, gastritis and duodenitis caused 2.81 (95% UI: 2.17-3.61) million DALYs worldwide, with an ASDR of 35.64 (95% UI: 27.56-45.77) per 100,000, while the ASMR was 0.54 (95% UI: 0.47-0.62) per 100,000. Despite global decreases in ASPR and ASIR, increasing trends were observed in the low and low-middle SDI regions from 1990 to 2021. The low SDI regions exhibited the highest ASDR of 63.44 (95% UI: 44.08-87.16) per 100,000. Among 21 GBD regions, East Asia exhibited the highest ASPR and ASIR in 2021. The ASPR of gastritis and duodenitis in 2050 is forecast to be 402.14 per 100,000, with an ASDR of approximately 22.09 per 100,000. <b>Conclusion:</b> Despite global reductions in ASPR, ASIR, ASMR, and ASDR between 1990 and 2021, the global burden of gastritis and duodenitis exhibits regional disparities, closely linked to SDI levels. The highest burden of gastritis and duodenitis was observed in East Asia and Sub-Saharan Africa. More potent measures are urgently needed in low SDI regions to forestall the increase of Gastritis and duodenitis burden.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2570-2582"},"PeriodicalIF":3.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302052","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":"Doxycycline Enhances Anticancer Activity of Zoledronic Acid via Inducing ROS and Autophagy in Osteosarcoma Cell Lines.","authors":"Yi-An Li, Hsuan-Ying Chen, Chien-Sheng Hsu, Shun-Cheng Tseng, Eric Hwang, Cheng-Pu Hsieh, Shih-Chieh Hung, Yi-Fu Huang","doi":"10.7150/ijms.108086","DOIUrl":"10.7150/ijms.108086","url":null,"abstract":"<p><p>Zoledronic acid (ZOL) is an inhibitor of osteoclast-mediated bone resorption. It is used to treat osteoporosis and skeletal complications in patients with tumor-induced osteolysis. ZOL is also demonstrated to possess anti-cancer activity in several tumors via apoptosis induction. Doxycycline is well-known antibiotic used in treatment of infections caused by bacteria and certain parasites. In this study, we evaluated the possibility if doxycycline could be used as an effective adjuvant to ZOL against osteosarcoma cells. The data showed that co-treatment with doxycycline at non-toxic dose could significantly increase the anti-viability effect of ZOL in osteosarcoma HOS and MG-63 cells in MTT assay and colony formation assay, and largely increased the levels of apoptotic markers, cleaved caspase 3 and PARP, in ZOL-treated cells. Furthermore, as co-treatment with doxycycline, the levels of ROS and autophagy were enhanced in ZOL-treated cells. Administration of <i>N</i>-acetyl-L-cysteine, a reactive oxygen species (ROS) inhibitor, or autophagy inhibitor chloroquine both reduced anti-growth effect of this combined treatment, indicating that the increased ROS and autophagy should be involved in anti-viability effect of combined treatment with ZOL and doxycycline. Taken together, our findings suggested that combined treatment with ZOL and doxycycline may serve as a potential strategy for treating osteosarcoma.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2560-2569"},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302035","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":"Unraveling the Role of N6-Methylation Modification: From Bone Biology to Osteoporosis.","authors":"Junyi Liu, Xiang Chen, Xijie Yu","doi":"10.7150/ijms.108763","DOIUrl":"10.7150/ijms.108763","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) is the most abundant and reversible epitranscriptomic modification in eukaryotes, playing a pivotal role in regulating various RNA metabolic processes, including splicing, nuclear export, translation and degradation. Emerging evidence indicates that m6A modification is indispensable in biological processes of bone cells such as proliferation, differentiation and apoptosis. Given its pivotal influence on osteoblastogenesis and osteoclastogenesis, m6A modification, particularly via METTL3, has attracted considerable attention in osteoporosis (OP). In this review, we probe the function of m6A modification in intramembranous and endochondral ossification. Furthermore, we summarize the regulatory role of m6A modification in various biological processes in osteoblasts, osteoclasts and osteocytes, focusing on its potential signaling pathways in osteoblast and osteoclast differentiation. Specifically, m6A modulates osteoblast differentiation predominantly through signaling pathways such as Wnt/β-catenin, PI3K/AKT, and BMP/Smad. Concurrently, it regulates osteoclast differentiation and maturation via the RANKL/RANK pathway and its downstream signaling mechanisms. We also discuss recent discoveries that m6A modification regulates OP and further explore its potential clinical value in diagnosing and treating OP. Collectively, m6A modification serves as a crucial regulatory factor in bone metabolism, and a comprehensive understanding of the molecular mechanisms of m6A modification in bone biology is expected to provide new targets for treating OP.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2545-2559"},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302070","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":"Identification of an Anoikis-associated LncRNA Signature to Predict the Clinical Prognosis and Immune Function of Patients with Endometrial Cancer.","authors":"Guanxiao Chen, Ting Zhou, Xiaoyu Shen, Wan Shu, Shuyang Yu, Kejun Dong, Piotr Laudański, Klaudia Gutowska, Shuangshuang Cheng, Hongbo Wang","doi":"10.7150/ijms.107243","DOIUrl":"10.7150/ijms.107243","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Endometrial cancer is a highly heterogeneous malignancy in women with high mortality, and patients diagnosed with advanced endometrial cancer have a poor prognosis. Anoikis is a form of programmed cell death that is important for cancer development and metastasis. Long non-coding RNAs (lncRNAs) are considered critical regulators of gene expression and key players in cancer biology; however, the effects of anoikis-associated lncRNAs on the prognosis and treatment of patients with endometrial cancer remain unclear. &lt;b&gt;Methods:&lt;/b&gt; Using transcriptome sequencing data and clinical information from The Cancer Genome Atlas database, we developed a novel prognostic signature for endometrial cancer based on anoikis-related lncRNAs by combining multivariate regression analysis and least absolute shrinkage and selection operator regression. The signature was validated by receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. After analyzing the relationships between the seven lncRNAs in the signature and tumor progression through gene set enrichment analysis (GSEA), we further explored the differences in immune function and drug sensitivity. Additionally, to investigate the functions of these lncRNAs in the occurrence and development of endometrial cancer, we selected &lt;i&gt;CFAP58-DT&lt;/i&gt; to conduct a series of &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; experiments to verify its partial functions. &lt;b&gt;Results:&lt;/b&gt; Seven anoikis-associated lncRNAs (&lt;i&gt;CFAP58-DT, AC004585.1, AC103563.9, AL121895.2, AC004596.1, AC010761.4,&lt;/i&gt; and &lt;i&gt;AC087564.1&lt;/i&gt;) with prognostic value were identified for signature construction. The analysis showed excellent predictive accuracy of the signature (the largest area under the ROC curve = 0.757). GSEA indicated that these lncRNAs may regulate diverse cellular processes, including intercellular interactions, cell proliferation, differentiation, apoptosis, angiogenesis, glucose and fatty acid metabolism, immune responses, and inflammatory regulation. Furthermore, immune analysis revealed a high likelihood of immune evasion and poor immunotherapy efficacy in high-risk patients. However, there were distinct differences in the immune checkpoints and anticancer drug sensitivity between the two patient groups, which may aid in guiding treatment. Finally, our experiments showed that silencing &lt;i&gt;CFAP58-DT&lt;/i&gt; significantly affected cell proliferation, promoted apoptosis, and reduced tumor malignancy. &lt;b&gt;Conclusion:&lt;/b&gt; Our study highlights the significance of anoikis-associated lncRNAs in endometrial cancer progression and their potential as prognostic markers and therapeutic targets. The signature constructed using these lncRNAs may offer new avenues for endometrial cancer treatment and immunotherapy. The function of &lt;i&gt;CFAP58-DT&lt;/i&gt; has been validated &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;, consistent with our previous analysis; however, further research into its upstream and downstream mechanisms is warrante","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 10","pages":"2502-2517"},"PeriodicalIF":3.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093560","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":"Endothelial <i>TIE2</i> Mutation Induced Contraction Deficiency of Vascular Smooth Muscle Cells via Phenotypic Transition Regulation in Venous Malformations.","authors":"Zhong Du, Fan Yu, Yuan He You, Zhi Yang Zhao, Zhuo Wei Tian, Meng Xiao, Yan An Wang","doi":"10.7150/ijms.102700","DOIUrl":"10.7150/ijms.102700","url":null,"abstract":"<p><p><b>Introduction:</b> Venous malformations (VMs) are congenital vascular malformations characterized by venous cavity enlargement and malformation. Although <i>TIE2</i> mutation is a recognized genetic landscape in VMs, the regulatory role of <i>TIE2</i> in vascular smooth muscle cell (VSMC) contraction remains unclear. <b>Materials and Methods:</b> We generated <i>Tie2-R848W^fl/fl;Tie2^Cre+</i> and <i>Tie2-R848W^fl/fl;Apln^ER+</i> mice through specific expression of <i>Tie2-R848W</i>, a typical mutation in inherited VM, in endothelial cells (ECs). Histological and transcriptome sequencing analyses were performed on vascular abnormalities in the mutant mouse model. Postnatal vascular development <i>in vivo</i> was studied through morphometric analysis of the retinal vasculature. Under <i>in vitro</i> coculture conditions, the functional abnormality of VSMCs was studied using transwell analysis, proliferation analysis, a cell contraction assay and transcriptome sequencing analysis. Markers related to the VSMC phenotypic transition were analyzed via western blotting and quantitative RT‑PCR. <b>Results:</b> <i>Tie2-R848W^fl/fl;Tie2^Cre+</i> mice developed spontaneous pulmonary vascular malformations displaying internal hemorrhage and increased vasculature with α-SMA+ enveloped VSMCs. In <i>Tie2-R848W^fl/fl;Apln^ER+</i> mice, <i>Tie2-R848W</i> mutation also induced postnatal retinal vascular malformations (higher vascular density and coverage of α-SMA+ VSMCs). According to phenotypes and molecular markers (Acta2, Cnn1, Sm22a and Opn), dysregulated phenotypic transition of VSMCs might be the pathogenic basis. Under <i>in vitro</i> coculture condition, the decreased contractile ability of synthetic VSMCs was significant in the mutant group, while downregulated ion transmembrane transport and TNFSF10 may play substantial roles in initiating this process. <b>Conclusion</b>: Endothelial <i>TIE2</i> mutation might induce an abnormal EC-VSMC regulatory relationship strongly associated with phenotypic transition of VSMCs. Weakened contractility and abnormal proliferation induce chronic cavity expansion and thickening of the muscle layer, which may be potential mechanism basis of VMs.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 10","pages":"2518-2532"},"PeriodicalIF":3.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093552","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 Tumor Differentiation Grade-related Genes Prognostic Signature Including COL5A1 Based on Single-cell RNA-seq in Gastric Cancer.","authors":"Jianming Wei, Xibo Gao, Zhufeng Li, Yangpu Jia, Chuan Li, Jian Liu","doi":"10.7150/ijms.107509","DOIUrl":"10.7150/ijms.107509","url":null,"abstract":"<p><p><b>Background:</b> Tumor differentiation grade was reported to be a prognostic factor in gastric cancer (GC). Here, we identify a novel tumor differentiation grade-related genes prognostic signature and provide new biomarkers using single-cell RNA sequencing (scRNA-seq) in GC. <b>Methods:</b> ScRNA-seq profiles of GC were analyzed by 'seurat' package. Tumor differentiation grade module was identified through a weighted gene co-expression network analysis (WGCNA). Hematoxylin and eosin (H&E) were performed to classify differentiation grade. The effects of tumor differentiation grade on prognosis were explored using the Kaplan-Meier. Tumor differentiation grade prognostic signature was constructed and validated in GC. <b>Results:</b> Using GEO database, the scRNA-seq cell differentiation, clusters, and marker genes were identified in GC. Functional enrichment analysis revealed that common differentially expressed genes (DEGs) were mainly enriched in neutrophil process. Integrating clinical factors in GC, WGCNA analysis indicated that tumor differentiation grade module was the most significant. H&E and Kaplan-Meier analysis revealed that well-differentiated had a better prognosis in GC. Subsequently, tumor differentiation grade-related genes signature was established and validated (TNFAIP2, MAGEA3, CXCR4, COL1A1, FN1, VCAN, PXDN, COL5A1, MUC13 and RGS2). Cox regression analysis showed that age, TNM stage and the risk score were significantly associated with prognosis. And then, these genes could predict prognosis in GC. Finally, the hub gene COL5A1 was obviously correlated with B cells memory, dendritic cells activated, macrophages M0, macrophages M2, plasma cells, T cells follicular helper in GC. <b>Conclusions:</b> This study reveals a novel tumor differentiation grade-related genes signature, and COL5A1 represents a promising biomarker in GC.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 10","pages":"2533-2544"},"PeriodicalIF":3.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093614","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 SNRPE to Induce Pyroptosis Enhances Antitumor Immunity in Breast Cancer.","authors":"Zaixiong Ji, Zilin Wang, Xinyu Guo, Junjian Li, Yiran Cai, Kangan Li","doi":"10.7150/ijms.109171","DOIUrl":"10.7150/ijms.109171","url":null,"abstract":"<p><p><b>Background:</b> Although SNRPE is a core spliceosomal component that guides pre-mRNA splicing in eukaryotic cells, its impact on mammary carcinoma prognosis and the immune microenvironment remains unclear. Pyroptosis, an inflammatory cell death, exerts tumor-suppressive functions and elicits antitumor immunity. Understanding the pathways that control pyroptosis will aid in developing specific antitumor strategies, while the relationship between SNRPE and pyroptosis has not been studied. <b>Methods:</b> To determine the impact of SNRPE on tumor prognosis, survival analysis and immune infiltration assessment were performed on clinical samples from patients with breast cancer. The antitumor effects and further mechanisms of SNRPE targeting were investigated via the xenograft murine model and cell biology experiments. <b>Results:</b> Here, we found that upregulation of SNRPE expression was associated with unfavorable tumor prognosis and low levels of immune infiltration. Our data identified SNRPE targeting activated natural killer (NK) cell-mediated antitumor immunity in breast cancer by triggering pyroptosis of tumor cells <i>in vivo</i>. SNRPE targeting modulated pyroptosis of tumor cells in a ROS-dependent manner. <b>Conclusion:</b> This study contributes to new insights into the interaction between spliceosome-targeted tumors and host immunity, highlighting the targeting of spliceosome to trigger pyroptosis as a comprehensive therapeutic strategy for enhanced antitumor immunity in breast cancer.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 10","pages":"2419-2433"},"PeriodicalIF":3.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093609","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":"Associations of the Total Cholesterol/high-density Lipoprotein Cholesterol Ratio with Outcomes in Lupus Nephritis.","authors":"Xiaolei Shi, Yaoyao Tang, Wang Xiang, Jianwen Yu, Xin Wang, Hongjian Ye, Zhong Zhong, Haishan Wu, Ruihan Tang, Xi Xia, Wei Chen","doi":"10.7150/ijms.106393","DOIUrl":"10.7150/ijms.106393","url":null,"abstract":"<p><p><b>Objectives:</b> Dyslipidemia is common in lupus nephritis (LN). However, the relationship between the total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio and LN remains unclear. This study was designed to investigate the association between the TC/HDL-C ratio and LN. <b>Method:</b> This study included individuals diagnosed with LN between January 1, 1996 and December 31, 2018. Split by the optimal cutoff TC/HDL-C ratio value of the primary outcome, patients were divided into lower (<6.71) and higher (≥6.71) TC/HDL-C ratio groups. Multivariate Cox regression analysis and subgroup analyses were carried out to confirm the connection of the TC/HDL-C ratio with the adverse clinical outcomes in LN. <b>Results:</b> A total of 818 patients with LN were followed up for a median of ten years and 129 (15.77%) experienced all-cause death and 119 (14.55%) reached adverse renal events. Kaplan-Meier survival analyses demonstrated that patients exhibited a higher TC/HDL-C ratio were more susceptible to all-cause death (P=0.003) and adverse renal outcomes (P=0.001) in LN. After adjustments, a higher TC/HDL-C ratio still exhibited significant correlations with all-cause death [hazard ratio (HR):1.51, 95% confidence interval (CI): 1.03-2.23; P=0.036] and adverse renal outcomes in LN patients [HR: 1.57, 95%CI: 1.05-2.36; P=0.028]. Further subgroup analyses revealed that LN patients who were male, younger than 40 years old or with estimated glomerular filtration rate under 60 ml/min/1.73m2 seemed to be more susceptible to adverse clinical outcomes (P<0.05). <b>Conclusions:</b> An elevated TC/HDL-C ratio exhibited significant associations with poor prognosis in LN. Patients with LN may benefit from further TC/HDL-C studies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 10","pages":"2398-2407"},"PeriodicalIF":3.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093784","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}