International Journal of Medical Sciences最新文献

{"title":"Decoding Pancreatic Cancer Pain: From Tumor-Nerve Crosstalk to Targeted Analgesic Strategies.","authors":"Daqiang Zhao, Qingwen Hu, Hanxuan Wang, Yu Huang, Yuqian Li, Yu Qian, Li Gao, Qian Ding, Yi Zhun Zhu","doi":"10.7150/ijms.134090","DOIUrl":"10.7150/ijms.134090","url":null,"abstract":"<p><p>Pancreatic cancer (PC) remains one of the most lethal malignancies, with pain being a prevalent and debilitating symptom that severely impairs patients' quality of life and independently predicts poorer survival. While historically attributed to tumor mass effects, the mechanisms driving PC pain are far more complex. This review aims to synthesize the current understanding of the intricate biological underpinnings of PC-associated pain and discuss the paradigm shift towards mechanism-based therapeutic strategies. The pathogenesis of PC pain is fundamentally driven by dynamic tumor-nerve interactions. A central mechanism is perineural invasion (PNI), a pathologic hallmark wherein cancer cells infiltrate the perineural space, establishing a specialized \"neural niche.\" Within this niche, bidirectional crosstalk involving cancer cells, Schwann cells, immune cells, and stromal components, which is mediated by neurotrophins, chemokines, and neurotransmitters, drives neural remodeling, neuroinflammation, and peripheral nociceptor sensitization. These peripheral signals subsequently induce central sensitization within the spinal cord and brain, perpetuating chronic, refractory pain. While conventional analgesics and interventions like celiac plexus neurolysis remain the mainstay, their relief is often incomplete and transient, as they fail to address these underlying biological drivers. A therapeutic paradigm shift is underway, moving from symptomatic palliation towards mechanism-based interventions. Emerging strategies, including molecularly targeted inhibitors, neuromodulation, and precision nanomedicine platforms, aim to directly disrupt the fundamental neurobiological pathways of pain. By targeting tumor-nerve crosstalk, neuroinflammation, and pathological neural plasticity, these approaches hold the potential to achieve more effective and durable analgesia, ultimately improving the lives of patients suffering from pancreatic cancer.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2847-2873"},"PeriodicalIF":3.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887463","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":"ALDH2 regulates oxaliplatin sensitivity via PDE4B in p53-mutant colorectal cancer.","authors":"Po-Li Wei, Chien-Yu Huang, Cheng-Chin Lee, Uyanga Batzorig, Kuei-Yen Tsai, Yu-Jia Chang","doi":"10.7150/ijms.133461","DOIUrl":"10.7150/ijms.133461","url":null,"abstract":"<p><strong>Background: </strong>Chemoresistance remains a major limitation in the treatment of colorectal cancer (CRC), particularly in tumors harboring TP53 mutations. Although aldehyde dehydrogenase 2 (ALDH2) has been implicated in cancer biology, its role in regulating platinum sensitivity and the underlying molecular context remain incompletely understood.</p><p><strong>Methods: </strong>Public transcriptomic and proteomic datasets (TCGA, GEO, CPTAC) were analyzed to evaluate ALDH2 expression patterns, prognostic relevance, and associations with chemotherapy response in CRC. Functional studies were performed in p53-mutant and p53-wild-type CRC cell lines using pharmacological inhibition and genetic silencing of ALDH2, complemented by p53 knockout and reconstitution approaches. Downstream signaling was interrogated by gene set enrichment analysis, quantitative PCR, and pharmacological inhibition of phosphodiesterase 4B (PDE4B). Oxaliplatin sensitivity was assessed using cell viability and apoptosis assays.</p><p><strong>Results: </strong>ALDH2 expression was significantly reduced in CRC tissues and was associated with unfavorable clinical outcomes and diminished oxaliplatin responsiveness. Functional experiments revealed that inhibition or knockdown of ALDH2 selectively induced oxaliplatin resistance in p53-mutant CRC cells, while p53-wild-type cells were largely unaffected. Mechanistically, loss of ALDH2 led to upregulation of PDE4B in a p53 status-dependent manner. Elevated PDE4B expression correlated with chemoresistance and poor recurrence-free survival in patients with p53-mutant CRC. Importantly, pharmacological inhibition of PDE4B using the clinically approved drug roflumilast effectively restored oxaliplatin-induced apoptosis and reversed chemoresistance in ALDH2-deficient, p53-mutant CRC cells.</p><p><strong>Conclusions: </strong>This study identifies a previously unrecognized, p53 status-dependent ALDH2-PDE4B regulatory axis that governs oxaliplatin sensitivity in colorectal cancer. Our findings highlight ALDH2 as a potential predictive biomarker for oxaliplatin response in p53-mutant CRC and suggest that targeting PDE4B may represent a promising strategy to overcome chemoresistance in this molecular context.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2835-2846"},"PeriodicalIF":3.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887384","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":"Potential impact of <i>NUCB2</i> genetic variants with the clinicopathological characteristics of prostate cancer.","authors":"Yung-Shu Lee, Tien-Huang Lin, Chia-Yen Lin, Shun-Fa Yang, Chiao-Wen Lin, Chih-Hsin Tang","doi":"10.7150/ijms.135299","DOIUrl":"10.7150/ijms.135299","url":null,"abstract":"<p><p>The most prevalent illness in men is prostate cancer, which risk increases with age and obesity. The precursor <i>NUCB2</i> gene produces the adipokine nesfatin-1, which was first found in hypothalamic neurons. It is currently unclear how <i>NUCB2</i> polymorphisms, cancer-promoting lifestyle factors, and prostate cancer are related. We investigated the relationship between clinicopathological features and 4 <i>NUCB2</i> gene polymorphisms in prostate cancer when compared to healthy individuals. Compared with the wild-type T/T genotype, carriage of at least one G allele (T/G or G/G genotypes) at the <i>NUCB2</i> SNP rs10766383 was linked with a declined risk of clinical T3+T4 stage, pathologic T3+T4 stage, and perineural invasion. In addition, the TG/GG genotypes at rs10766383 were also associated to a lower risk of clinical T3+T4 stage and perineural invasion in patients with biochemical recurrence. Importantly, GTEx data indicated that the wild-type TT homozygous genotype was linked with markedly higher <i>NUCB2</i> levels compared to the GG allele of variant rs10766383 variant in mucosa and whole blood tissues. Thus, the <i>NUCB2</i> SNP rs10766383 may play a protective function against prostate cancer progression.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2828-2834"},"PeriodicalIF":3.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887228","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":"Comparison of Emergence Agitation Between Remimazolam- and Propofol-Based Anesthetic Induction in Patients Undergoing Transurethral Endoscopic Urologic Surgery: A Propensity Score-Matched Retrospective Study.","authors":"Ji-Yoon Jung, Hwang-Ju You, Woojin Kwon, Junho Kim, Tae-Yun Sung","doi":"10.7150/ijms.137664","DOIUrl":"10.7150/ijms.137664","url":null,"abstract":"<p><strong>Background: </strong>Emergence agitation is a clinically relevant phenomenon during recovery from general anesthesia. This study aimed to compare the effects of remimazolam and propofol as anesthetic induction agents on emergence agitation.</p><p><strong>Methods: </strong>This retrospective propensity score-matched study included adult patients undergoing elective transurethral endoscopic urologic surgery under general anesthesia. Patients were divided into remimazolam- or propofol-based induction groups. The primary outcome was the incidence of emergence agitation, defined as a Ricker Sedation-Agitation Scale (RSAS) score ≥ 5 during emergence. Secondary outcomes included the severity of emergence agitation, extubation time, postoperative pain scores, use of analgesics or antiemetics in the post-anesthesia care unit (PACU) and risk factor identification.</p><p><strong>Results: </strong>A total of 239 patients were analyzed before matching, and 99 matched pairs were generated. After matching, the incidence of emergence agitation was significantly lower in the remimazolam group compared with the propofol group (13.1% vs. 36.4%; P = 0.001). Remimazolam-based induction was independently associated with a reduced risk of emergence agitation (odds ratio 0.23, 95% confidence interval 0.09-0.56; P < 0.001). The distribution of RSAS scores demonstrated reduced severity of agitation in the remimazolam group. Extubation time, postoperative pain scores, and PACU medication did not differ between groups. Younger age and male sex were identified as independent risk factors.</p><p><strong>Conclusions: </strong>Remimazolam-based anesthetic induction reduced incidence and severity of emergence agitation compared with propofol, without delaying extubation or impairing early postoperative recovery. Remimazolam may represent a favorable induction agent for adult patients at risk for emergence agitation.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 8","pages":"2739-2746"},"PeriodicalIF":3.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619915","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":"CLEC3B (tetranectin) expression is associated with vascular localization and tumor aggressiveness in breast cancer.","authors":"Ching-Ting Wei, Teng-Hung Yu, Chia-Chang Hsu, Chin-Feng Hsuan, Wei-Chin Hung, Chao-Ping Wang, Wei-Hua Tang, Fu-Mei Chung, Yau-Jiunn Lee, Chi-Chang Chang, Chia-Chi Chen","doi":"10.7150/ijms.132030","DOIUrl":"10.7150/ijms.132030","url":null,"abstract":"<p><strong>Background: </strong>C-type lectin domain family 3 member B (CLEC3B), also known as tetranectin, is a secreted protein associated with extracellular matrix remodeling and tumor microenvironment regulation. However, its expression pattern and clinical significance in breast cancer tissues remain unclear. This study aimed to investigate CLEC3B expression in breast cancer tissues and its associations with clinicopathological characteristics and the tumor microenvironment.</p><p><strong>Methods: </strong>Ninety-eight women with newly diagnosed breast cancer who underwent surgical treatment at our hospital between September 2023 and December 2024 were included in this study. Tumor and adjacent non-tumorous tissues, including vascular regions, were obtained from the enrolled patients and processed for immunohistochemical analysis. CLEC3B expression was semiquantitatively graded from 1 to 4. Associations between CLEC3B expression, clinicopathological and biochemical variables were analyzed using the chi-square test, Spearman correlation, and multivariable logistic regression. Double immunofluorescence staining was performed to assess colocalization of CLEC3B with CD68 (macrophages) and CD31 (endothelial cells).</p><p><strong>Results: </strong>The expression of CLEC3B was identified in both tumor cell membrane and cytoplasm, and was significantly higher in breast cancer tissues than in adjacent non-tumorous tissues. CLEC3B expression was also significantly higher in blood vessels than in tumor parenchyma (p < 0.0001), indicating predominant vascular localization. High CLEC3B expression (grade 3-4) was associated with a tumor size of 2-5 cm, Ki-67 ≥14%, and the luminal B HER2-positive subtype. Spearman analysis showed that a high CLEC3B expression was correlated with larger tumor size, higher Ki-67 index, higher carcinoembryonic antigen level, and shorter prothrombin time. Multivariable logistic regression analysis further demonstrated that tumor size ≥2 cm and high Ki-67 (≥14%) were independently associated with high CLEC3B expression, whereas molecular subtype was not. CLEC3B was colocalized with CD68 and CD31, confirming its expression in macrophages and endothelial cells. CD4⁺ and CD8⁺ T-cell infiltration was abundant regardless of CLEC3B expression level.</p><p><strong>Conclusion: </strong>The expression of CLEC3B was upregulated in breast cancer tissues and predominantly localized to the tumor vasculature and macrophages. Its expression was associated with aggressive clinicopathological features and certain biochemical parameters. No apparent differences in CD4⁺ or CD8⁺ T-cell infiltration were observed across different levels of CLEC3B expression. These findings suggest that CLEC3B expression may be associated with vascular and microenvironment-related characteristics of breast cancer.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 8","pages":"2715-2727"},"PeriodicalIF":3.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619890","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":"Risk of Peripheral Artery Disease and Venous Thromboembolism in Patients with Neuromyelitis Optic Spectrum Disorder: A Nationwide Population-Based Cohort Study.","authors":"Xin-An Chen, Chun-Nan Wu, Tung-Han Tsai, Chien-Yu Lin, Hsuan Chang, Shuo-Yan Gau, Kuang-Hua Huang, Chien-Ying Lee","doi":"10.7150/ijms.130836","DOIUrl":"10.7150/ijms.130836","url":null,"abstract":"<p><strong>Background: </strong>The relationship between Neuromyelitis optica spectrum disorder (NMOSD) and specific cardiovascular outcomes, particularly macrovascular events such as peripheral artery disease (PAD) and venous thromboembolism (VTE), has not been examined in a population-based study. The current study investigated the association between NMOSD and the risks of PAD and VTE.</p><p><strong>Materials and methods: </strong>This retrospective cohort study used data from the Taiwan National Health Insurance Research Database. Patients with new-onset NMOSD between 2003 and 2020. Patients with previous PAD or VTE were excluded. Each patient was matched to five general patients for comparison using propensity score matching. In total, the study included 2,027 patients with NMOSD and 10,135 matched general population controls. A Cox proportional hazards model was used to investigate PAD and VTE risk, with relevant variables controlled for. NMOSD was stratified by severity to further verify the association between disease severity and macrovascular event risk. The control variables considered in this study were sex, age, insured salary, urbanization, Charlson comorbidity index (CCI), and related comorbidities.</p><p><strong>Results: </strong>The average follow-up of all participants was 7.01 person-years. After adjustments for relevant variables, patients with NMOSD had significantly higher risks of PAD (adjusted hazard ratio [aHR] = 1.40; 95% confidence interval [CI]: 1.02-1.92) and VTE (aHR = 4.81; 95% CI: 3.08-7.52). The risk of vascular events was strongly associated with disease severity. Severe NMOSD was associated with markedly increased risks of PAD (aHR = 2.26; 95% CI: 1.41-3.61) and VTE (aHR = 11.69; 95% CI: 6.86-19.90), whereas mild and moderate disease did not significantly increase PAD risk.</p><p><strong>Conclusion: </strong>NMOSD is a significant risk factor for PAD and VTE. These findings highlight the importance of proactive vascular risk assessment and preventive management in patients with NMOSD.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 8","pages":"2747-2757"},"PeriodicalIF":3.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620060","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 Marine Triterpene Stellettin B Triggers Mitochondrial-to-Nuclear Translocation of AIF/EndoG and Reverses Epithelial-Mesenchymal Transition to Inhibit Oral Cancer Progression.","authors":"Peng-Yu Chen, Pin-Chen Kuo, Yi-Lung Ling, Yen-Yun Wang, Shyng-Shiou F Yuan, Jyh-Horng Sheu, Wan-Chi Tsai","doi":"10.7150/ijms.134063","DOIUrl":"10.7150/ijms.134063","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is associated with aggressive clinical behavior and poor outcomes. In this study, we investigated the anticancer efficacy and underlying mechanisms of Stellettin B, an isomalabaricane triterpene isolated from the marine sponge <i>Jaspis stellifera,</i> in OSCC cells. Our results demonstrate that Stellettin B significantly inhibited the proliferation of HSC-3 and OC-2 cells while sparing normal oral keratinocytes. Mechanistically, Stellettin B triggers a predominantly caspase-independent apoptotic program, evidenced by the pronounced mitochondrial-to-nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) following DNA damage, whereas classical caspase activation functions as a dispensable, secondary event. Furthermore, Stellettin B suppressed migration and invasion by reversing epithelial-mesenchymal transition (EMT), characterized by E-cadherin upregulation and downregulation of Vimentin, Snail, Slug, and β-catenin. Transcriptomic profiling further revealed significant suppression of mTORC1 signaling and EDIL3 expression. In conclusion, these findings demonstrate that Stellettin B exerts multimodal antitumor activity in OSCC and highlight its therapeutic potential as a marine-derived anticancer agent.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 8","pages":"2758-2766"},"PeriodicalIF":3.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619986","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":"Long-Term Trends in Microbiology and Outcomes of Pediatric Deep Neck Infections: An 18-Year Study.","authors":"Fang-Ching Liu, Pei-Rung Yang, Yao-Te Tsai, Yao-Hsu Yang, Chia-Yen Liu, Geng-He Chang","doi":"10.7150/ijms.131187","DOIUrl":"10.7150/ijms.131187","url":null,"abstract":"<p><strong>Importance: </strong>Pediatric deep neck infection (DNI) is a potentially life-threatening condition. However, contemporary large-scale data describing microbial etiology and outcomes remain limited. Understanding long-term pathogen trends is essential for guiding empiric antibiotic therapy and improving outcomes.</p><p><strong>Objective: </strong>To investigate temporal changes in bacterial pathogens, treatment strategies, and outcomes of pediatric DNI across an 18-year period.<b>Design, Setting, and Participants</b>: Retrospective multicenter cohort study using the Chang Gung Research Database (CGRD), a de-identified nationwide database from Taiwan's largest medical system. Hospitalized patients younger than 18 years with DNI from 2006 to 2023 were identified and divided into two 9-year periods (2006-2014 and 2015-2023).</p><p><strong>Main outcomes and measures: </strong>Demographics, comorbidities, treatment modalities, disease severity, and microbiological profiles were analyzed. Bacterial isolates were evaluated at genus and species levels, with methicillin-sensitive <i>Staphylococcus aureus</i> (MSSA) and methicillin-resistant <i>S. aureus</i> (MRSA) assessed separately.</p><p><strong>Results: </strong>Among 1,743 pediatric DNI cases (1,017 in 2006-2014; 726 in 2015-2023), antibiotic-only therapy increased (91.5% to 94.4%), surgical intervention decreased (8.5% to 5.7%), and no tracheostomies were performed. ICU admission declined (8.9% to 6.8%), mediastinal complications decreased (0.6% to 0%), and mortality remained 0.1%. <i>Staphylococcus</i> increased while <i>Streptococcus</i> decreased; <i>Veillonella</i> replaced <i>Peptostreptococcus</i> among anaerobes. MRSA became the predominant facultative anaerobic/aerobic pathogen, and <i>Veillonella parvula</i> emerged as the leading anaerobic species.</p><p><strong>Conclusions and relevance: </strong>Over 18 years, pediatric DNI in Taiwan demonstrated a marked shift toward conservative, antibiotic-based management with sustained excellent outcomes. Concurrently, MRSA and anaerobes such as <i>Veillonella</i> emerged as dominant pathogens in culture-positive patients, highlighting the need to consider empiric regimens that adequately cover these evolving bacterial profiles specifically in severe, refractory, or surgically managed cases.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 8","pages":"2728-2738"},"PeriodicalIF":3.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620009","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":"Mapping the Evolutionary Landscape of Solid Tumor Immunotherapy: A Quarter-Century Bibliometric Analysis of the Title-Defined Core Literature (2000-2025).","authors":"Ender Eren Ozcelik, Gul Akin, Hulya Odabasi Bukun, Mursel Sali, Ahmet Bilgehan Sahin, Adem Deligonul, Erdem Cubukcu, Turkkan Evrensel","doi":"10.7150/ijms.137251","DOIUrl":"10.7150/ijms.137251","url":null,"abstract":"<p><p>Cancer immunotherapy has evolved from an experimental niche to the established fourth pillar of oncological care. While the clinical success of checkpoint inhibitors is well-documented, the macro-level evolutionary trajectory of the field remains unmapped. This study provides a quarter-century bibliometric analysis of the core title-defined research landscape in solid tumor immunotherapy. Data from the Web of Science Core Collection were utilized as the primary source via a title-restricted search strategy, and core thematic structures were cross-compared against a high-impact Scopus subset. While this strategy ensures high clinical specificity, it represents a primary methodological limitation by inherently reducing search sensitivity and potentially excluding relevant studies with non-descriptive titles. The final data retrieval was conducted on January 1, 2026. The study covered the period from January 1, 2000, to December 31, 2025, utilizing advanced network visualization techniques via VOSviewer and Biblioshiny to identify spatiotemporal trends. 54,546 documents were identified, revealing a rapid and sustained expansion in publication volume, a descriptive trend that chronologically aligns with major clinical milestones such as the 2011 FDA approval of ipilimumab. Geopolitically, a distinctive divergence emerged: while China has surpassed the USA in total publication volume, the USA maintains higher integration in global collaboration networks and greater per-article citation counts. Network analysis visualized a decisive conceptual evolution from the \"Cytokine Era\" (2000-2010) to the \"Checkpoint Revolution\" (2011-2019). Most critically, recent trends (2020-2025) indicate a clear shift in research toward the \"Tumor Microenvironment\" and \"Neoadjuvant Therapy\" with the latter emerging as a predominant focus of recent translational research. The field's research focus is currently undergoing a structural transition from monotherapy in metastatic settings to combinatorial and perioperative strategies in early-stage disease. Current bibliometric trends indicate a growing academic focus on overcoming resistance mechanisms in \"cold\" tumors, reflecting strong translational interest in combining and sequencing immunotherapies with next-generation modalities, such as antibody-drug conjugates.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2810-2827"},"PeriodicalIF":3.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887263","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":"TNFSF13 Drives Atherosclerosis Progression by Targeting Macrophage Senescence.","authors":"Xiao Lin, Mintong Liang, Shenglan Zeng, Kaiye Chen, Ying Yang, Fei Yu, Jiahui Zhou, Hui Tang, Hanqing Tang, Pengju Wen, Shulin Tang, Yueheng Wu","doi":"10.7150/ijms.130617","DOIUrl":"10.7150/ijms.130617","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis (AS), a complex age-related disease characterized by arterial lipid plaque formation, remains poorly understood at the molecular level. Senescent cells, particularly macrophages, drive plaque progression, but key senescence-inducing genes and their mechanisms are unclear.</p><p><strong>Method: </strong>Senescence-related DEGs (SR-DEGs) were identified by intersecting differentially expressed genes (DEGs) from GSE28829 with senescence-related genes (SRGs) in CellAge genes. Machine learning algorithms prioritized hub genes, whose expression and diagnostic performance were subsequently visualized with box plots and receiver operating characteristic (ROC) curves in the training dataset GSE28829, and validation sets GSE163154 and GSE100927. Immune infiltration analysis compared early and advanced plaques. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) mapped hub gene expression across cell types and plaque regions. TNFSF13 was further validated in clinical atherosclerosis samples using Quantitative Real-time PCR (RT-qPCR), immunohistochemistry (IHC) and multiplex Immunohistochemistry (mIHC).</p><p><strong>Results: </strong>Advanced plaques exhibited 74 SR-DEGs compared to early plaques. Machine learning identified six senescence-related hub genes. ScRNA-seq revealed macrophage enrichment of all six hub genes, aligning with immune infiltration results. Bayesian deconvolution confirmed macrophage compositional shifts. Cell-cell communication analysis implicated TNFSF13-associated pathways. Spatial transcriptomics localized TNFSF13 upregulation specifically to the plaque core region, rich in SPP1+ macrophages and foam macrophages. Critically, TNFSF13 upregulation was robustly validated in human coronary artery tissues.</p><p><strong>Conclusion: </strong>This study identifies TNFSF13 as a master regulator of macrophage senescence driving atherosclerosis progression. By leveraging multi-omics and machine learning, we pinpoint the spatial and cellular context of TNFSF13 within plaques and validate its clinical relevance. TNFSF13 represents a promising therapeutic target to disrupt senescence-mediated plaque advancement in AS.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 9","pages":"2780-2795"},"PeriodicalIF":3.7,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887362","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}