{"title":"Large Language Models in Medicine: Applications, Challenges, and Future Directions.","authors":"Erlan Yu, Xuehong Chu, Wanwan Zhang, Xiangbin Meng, Yaodong Yang, Xunming Ji, Chuanjie Wu","doi":"10.7150/ijms.111780","DOIUrl":"10.7150/ijms.111780","url":null,"abstract":"<p><p>In recent years, large language models (LLMs) represented by GPT-4 have developed rapidly and performed well in various natural language processing tasks, showing great potential and transformative impact. The medical field, due to its vast data information as well as complex diagnostic and treatment processes, is undoubtedly one of the most promising areas for the application of LLMs. At present, LLMs has been gradually implemented in clinical practice, medical research, and medical education. However, in practical applications, medical LLMs still face numerous challenges, including the phenomenon of hallucination, interpretability, and ethical concerns. Therefore, in-depth exploration is still needed in areas of standardized evaluation frameworks, multimodal LLMs, and multidisciplinary collaboration in the future, so as to realize the widespread application of medical LLMs and promote the development and transformation in the field of global healthcare. This review offers a comprehensive overview of applications, challenges, and future directions of LLMs in medicine, providing new insights for the sustained development of medical LLMs.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2792-2801"},"PeriodicalIF":3.2,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302053","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}
Ru-Yin Tsai, Sheng-Yi Lin, Chin-Chang Chen, Yao Hsiao
{"title":"Efficacy of Acupuncture in Managing Radiation-Induced Xerostomia: An Updated Meta-Analysis.","authors":"Ru-Yin Tsai, Sheng-Yi Lin, Chin-Chang Chen, Yao Hsiao","doi":"10.7150/ijms.110366","DOIUrl":"10.7150/ijms.110366","url":null,"abstract":"<p><p><b>Background:</b> Xerostomia, or dry mouth, frequently affects head and neck cancer patients receiving radiotherapy, leading to discomfort and impacting daily functions such as speaking and swallowing. Conventional treatments may offer limited relief and are often accompanied by undesirable side effects. Acupuncture, as a non-pharmacological intervention, is increasingly explored for its potential to mitigate xerostomia symptoms. <b>Objective:</b> This systematic review and meta-analysis aim to assess the effectiveness of acupuncture in improving symptoms and quality of life in patients experiencing radiation-induced xerostomia. <b>Methods:</b> A thorough literature search was conducted across several databases, including MEDLINE, Embase, Cochrane Central, and Web of Science, up to the current year. We included randomized controlled trials (RCTs) that evaluated acupuncture's impact on salivary flow and symptom relief in adults with radiation-induced xerostomia. Primary outcomes were changes in salivary flow, with secondary outcomes including patient-reported symptom severity and quality of life metrics. The risk of bias was evaluated, and data were synthesized using a random-effects model. <b>Results:</b> A total of 11 RCTs involving 1271 participants were included in the analysis. The pooled data showed a moderate increase in salivary flow in the acupuncture group, effective in both resting and stimulated conditions. Additionally, acupuncture demonstrated significant benefits in reducing xerostomia symptoms and improving quality of life scores compared to control interventions. Subgroup analysis revealed that traditional acupuncture was more effective than Transcutaneous Electrical Nerve Stimulation (TENS). <b>Conclusions:</b> The findings suggest that acupuncture may be an effective complementary treatment for radiation-induced xerostomia, offering relief from dry mouth symptoms and potentially improving quality of life. Further research should focus on standardizing acupuncture protocols to confirm these benefits across diverse patient populations.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2802-2815"},"PeriodicalIF":3.2,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302036","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}
Limin Zhang, Guoxiu Xiao, Duyao Su, Xun Wang, Cuiting Lv, Chunchun Li, Mingsheng Fu, Liang Song
{"title":"Diagnostic Value of the Combined Detection of Microbiota, Multiple Inflammation-Related Indicators, Serum Lipid Indices, and Tumour Markers in Colorectal Polyps: A Case-Control Study.","authors":"Limin Zhang, Guoxiu Xiao, Duyao Su, Xun Wang, Cuiting Lv, Chunchun Li, Mingsheng Fu, Liang Song","doi":"10.7150/ijms.108819","DOIUrl":"10.7150/ijms.108819","url":null,"abstract":"<p><p><b>Purpose:</b> Colorectal polyps have few clinical symptoms, and related tumor markers are unclear; therefore, developing a simple and economical tumor detection index for auxiliary diagnosis is necessary. We aimed to investigate differences in salivary and fecal microbiota, inflammation-related indicators, serum lipid indices, and tumor markers between patients with colorectal polyps and healthy controls, to identify novel non-invasive biomarkers for colorectal polyps. <b>Patients and methods:</b> This case-control study enrolled 47 patients with colorectal polyps and 59 age- and sex-matched healthy controls between 13 May 2022 and 20 November 2023. From each participant, we collected salivary and fecal samples, fasting venous blood samples, polyp tissues, and normal intestinal tissues. We then evaluated the diagnostic performance of multiple markers, including salivary and fecal microbiota, routine blood tests, blood lipids, serum tumor markers, and the NOD-like receptor protein 3 (NLRP3) inflammasome, both individually and in combination. The assessment was based on metrics such as the Youden index, sensitivity, and specificity. <b>Results:</b> There were statistically significant differences in several markers between patients and controls. The receiver operating characteristic curve analysis showed that the areas under the curve for the diagnosis of colorectal polyps using the individual and combined detection of the neutrophil-to-lymphocyte ratio, mean corpuscular haemoglobin (MCH), MCH concentration, cystatin C, triglycerides, low-density lipoprotein cholesterol, carcinoembryonic antigen, <i>Porphyromonas gingivalis</i>, <i>Fusobacterium nucleatum</i>, <i>Prevotella intermedia</i>, <i>Ruminococcus gnavus</i>, <i>Bacteroides ovatus</i>, and <i>Parabacteroides distasonis</i> were 0.696, 0.726, 0.742, 0.771, 0.829, 0.731, 0.785, 0.759, 0.738, 0.786, 0.739, 0.764, 0.757, and 0.996, respectively. Combining 13 markers was better than a single marker regarding the diagnostic effect. Compared to that in normal mucosal tissues, the ratio of positively stained areas for NLRP3, apoptosis-associated speck-like proteins containing a caspase recruitment domain, and interleukin-1β was higher in polyp tissues. <b>Conclusion:</b> Detection of salivary and fecal microbiota, multiple inflammation-related indicators, serum lipid indices, and tumor markers can non-invasively and effectively improve the diagnosis of colorectal polyps.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2757-2770"},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302034","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":"ABCG1 promotes the proliferation and migration of clear cell renal cell carcinoma and reduces its apoptosis.","authors":"Yihan Dong, Qiufang Qiao, Shaomin Guo, Ruibing Chen, Tianyu Lin, Xinyu Liu, Jiaxin Li, Shiming Liu, Huamao Jiang, Yong Wang, Dan Yue, Rui Wang","doi":"10.7150/ijms.107055","DOIUrl":"10.7150/ijms.107055","url":null,"abstract":"<p><p><b>Background and Aims:</b> In this study, we analyzed the expression levels of ATP-binding cassette transporter G1 (ABCG1) in clear cell renal cell carcinoma (ccRCC) to assess its significance for early diagnosis and its role in the disease's biological processes. <b>Materials and Methods:</b> ABCG1 expression levels in ccRCC were determined by analyzing The Cancer Genome Atlas (TCGA) database, as well as immunohistochemical staining and western blot. The correlation between the ABCG1 expression level and the clinicopathological stage and diagnostic prognosis of ccRCC were analyzed by the TCGA database. The ABCG1 stable knockout cell line and functional experiments using ABCG1 inhibitors were constructed to verify the effect of reduced ABCG1 expression on the ccRCC cell function. In addition, the pathways and genes affected by ABCG1 were analyzed by RNA-seq. <b>Results:</b> Analysis of the TCGA database demonstrated, as well as immunohistochemical staining and western blot detection, confirmed that ABCG1 was significantly elevated in ccRCC. The expression level of ABCG1 was correlated with the clinicopathological stage of ccRCC. The Cox regression analysis showed that ABCG1 could be used as an independent prognostic marker for ccRCC. And decreasing ABCG1 expression decreased the proliferation, migration, and invasion abilities of ccRCC cells, with increased apoptosis. In addition, analysis of ABCG1-related differentially expressed genes (DEGs) showed that ABCG1 positively regulates specific proliferation-related genes and negatively affects those associated with apoptosis. <b>Conclusions:</b> In summary, these findings highlight the critical role of ABCG1 in ccRCC progression and suggest its potential as a biomarker for diagnosis and prognosis.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2721-2737"},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302029","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":"Expert Consensus on the Diagnosis and Management of Carotid Atherosclerotic Plaque: Pathophysiology, Clinical Management, and Preventive Approaches.","authors":"Xing Chang, Hang Zhu, Zhijiang Guo, Hongshuo Shi, Yingjie Tian, Qianying Hao, Hui Zhang, Rongjun Zou, Xiaoping Fan, Qihui Zhang, Sang-Bing Ong, Qingyong He, Hao Zhou","doi":"10.7150/ijms.107479","DOIUrl":"10.7150/ijms.107479","url":null,"abstract":"<p><p>To standardize and harmonize pharmacist-led cholesterol-lowering medication therapy management (MTM) for patients with carotid atherosclerosis and plaque, the Expert Consensus on Lipid-Lowering Pharmacotherapy Management in Patients with Carotid Atherosclerosis and Plaque was developed under the leadership of the PLA General Hospital. This consensus establishes a systematic framework spanning the full-cycle management process: data collection, analytical evaluation, intervention implementation, and long-term follow-up, supported by standardized protocols, documentation forms, and assessment tools. It prioritizes seven evidence-based evaluation domains: therapeutic efficacy, drug selection, dosing appropriateness, adverse reactions, drug-drug/food interactions, cost-effectiveness, and medication adherence. By integrating practical workflows with clinical decision-support tools, the consensus aims to optimize therapeutic outcomes, mitigate safety risks, and provide actionable guidance for healthcare professionals managing this high-risk population.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2738-2756"},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302050","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}
Sijia Liu, Wanqing Zhao, Yusen Qie, Na Liu, Qing Liu
{"title":"Efficacy of Laser Therapy for Grade C Periodontitis in Young Individuals.","authors":"Sijia Liu, Wanqing Zhao, Yusen Qie, Na Liu, Qing Liu","doi":"10.7150/ijms.107543","DOIUrl":"10.7150/ijms.107543","url":null,"abstract":"<p><p>Grade C periodontitis in young individuals is characterized by its early onset and rapid progression, resulting in swift periodontal tissue destruction in systemically healthy individuals. The application of laser technology in periodontal therapy has gradually increased in recent years. Laser therapy offers several advantages over traditional antibiotics, such as reduced patient discomfort, minimized postoperative edema, and a lower risk of drug-resistant strains. Recent studies suggest that laser-assisted treatments can significantly augment the clinical efficacy in managing grade C periodontitis. However, available evidence has not drawn distinct conclusions. This review aims to present the research progress in laser and antibacterial photodynamic therapy as the adjuvant treatment of grade C periodontitis in young individuals over the past decade, offering references for clinical practice.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2653-2662"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302037","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":"Neutrophil Percentage-to-Albumin Ratio as a Prognostic Marker for Mortality in Ischemic Stroke Patients.","authors":"Yue-Xin Lu, Bao-Jie Mao, Ming Wang, Shu Wan","doi":"10.7150/ijms.108493","DOIUrl":"10.7150/ijms.108493","url":null,"abstract":"<p><p><b>Background:</b> The neutrophil percentage-to-albumin ratio (NPAR) is an emerging inflammatory biomarker that has demonstrated a significant association with poor outcomes in patients with cardiovascular diseases. However, the existing evidence regarding its prognostic value in ischemic stroke (IS) patients remains limited. Our study aimed to investigate the potential of the NPAR as a prognostic indicator for all-cause mortality in patients with IS. <b>Methods:</b> This study screened IS patients from the Medical Information Mart for Intensive Care (MIMIC-IV) database and categorized them into two groups based on NPAR values, employing propensity score matching to mitigate confounding factors. The primary outcome assessed was 90‒day mortality, and the secondary outcomes included in-hospital mortality, ICU mortality, and mortality at 30‒day and 1‒year after admission. Cox proportional hazards regression analysis and restricted cubic splines were used to explore the relationship between the NPAR and all-cause mortality in critically ill IS patients, whereas Kaplan‒Meier analysis was used to estimate survival curves. Subgroup analysis and interaction tests were performed to evaluate the robustness of the results. Receiver operating characteristic curves were computed to assess the diagnostic value of the NPAR in predicting outcomes. <b>Results:</b> A total of 706 patients (53.3% male) were included in the study, with in-hospital and ICU mortality rates of 18.2% and 12.6%, respectively. The mortality rates at 30‒day, 90‒day, and 1‒year were 19.2%, 29.7%, and 37.8%, respectively. Restricted cubic splines indicated a nonlinear increase in all-cause mortality as the NPAR increased. Multivariate Cox regression analysis revealed a significant association between a high NPAR and all-cause mortality at 90‒day (hazard ratio [HR]: 1.99; 95% confidence interval [95% CI]: 1.44-2.76, p < 0.001), 30‒day (HR: 2.09; 95% CI: 1.39-3.13, p < 0.001), and 1‒year (HR: 1.77; 95% CI: 1.32-2.37, p < 0.001). The subgroup analysis indicates that a significant interaction was observed between hypertension and mortality risk in IS patients (p for interaction = 0.012), suggesting that hypertension may be an important predictor of poor prognosis in these patients. Receiver operating characteristic curves demonstrated that the NPAR provides a modestly greater ability to predict the risk of death in patients with IS compared to the individual indices of neutrophil percentage and albumin levels, although the specificity (0.567) and sensitivity (0.684) of NPAR were not outstanding overall. <b>Conclusion:</b> Our study revealed an independent association between a high NPAR and increased all-cause mortality at 30‒day, 90‒day, and 1‒year and during hospitalization in patients with IS, reinforcing its status as an independent determinant of mortality risk.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2663-2675"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302054","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}
Anni Shi, Na Chen, Qin Ma, Yaxuan Wang, Xiaoling Liu, Jun Lu, Jianyou Guo
{"title":"A Bibliometric Analysis of Neuroinflammation in Depression from 2004 to 2023: Global Research Hotspots and Prospects.","authors":"Anni Shi, Na Chen, Qin Ma, Yaxuan Wang, Xiaoling Liu, Jun Lu, Jianyou Guo","doi":"10.7150/ijms.100888","DOIUrl":"10.7150/ijms.100888","url":null,"abstract":"<p><p><b>Background:</b> Neuroinflammation lays a prominent impact in the pathophysiology of depression, and numerous studies have been conducted in recent decades. Bibliometric analysis is of important for understanding the hot spots and research trends in a certain subject field. However, no systematic bibliometric study exists in this field to date. The purpose of the study focused on the trends and hotspots in neuroinflammation of depression and provided future researchers with guidance and sights. <b>Methods:</b> Publications (2004-2023) were obtained from the WoSCC, and analyzed by HistCite, VOSviewer, CiteSpace, and Bibliometrix. The impact of publications was assessed by TGCS. <b>Results:</b> We analyzed 1,496 articles published in 409 journals and authored by 46,533 researchers across 72 countries and regions. The most prolific countries were China, the USA, and Brazil, and the most cited countries were the USA, followed with China and the UK, while the most prolific and cited institution was University Toronto (records=34, TGCS=2,137). Brain Behavior and Immunity is the leading journal that regularly published research in this field (records=93, TGCS=6,247). NLRP3 inflammasome, microglia, TNF-α, and brain-derived neurotrophic factor (BDNF) were the basis of neuroinflammation in depression. C-reactive protein, an important marker of inflammation, has been discussed for the longest time in this disease. In recent five years, two most frontier potential areas in studying depression were gut microbiota dysbiosis and BDNF. <b>Conclusions:</b> There remains a strong research basis for neuroinflammation in depression from this bibliometric analysis. Microglial activation, gut microbiota, cytokine signaling, and oxidative stress were research hotspots in recent years. In the future, chronic stress, hippocampal structure, and gut microbiota will continue to be studied in the field of neuroinflammation in depression. This study may benefit scientists in identifying potential directions for future study and providing clinicians with new ideas for treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2700-2720"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302028","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":"Establish VO<sub>2</sub>max prediction models based on exercise and body parameters from the step test.","authors":"Chia-An Ho, Hung-Chih Yeh, Hei-Tung Lau, En-Yu Chang, Chih-Wen Hsu, Chun-Hao Chang, Chi-Chang Huang, Wen-Sheng Chang Chien, Chin-Shan Ho","doi":"10.7150/ijms.109977","DOIUrl":"10.7150/ijms.109977","url":null,"abstract":"<p><p>This study addresses the challenge of cardiorespiratory fitness (CRF) assessment by proposing predictive models for maximal oxygen uptake (VO₂max) based on step test parameters. Recognizing VO₂max as a gold standard for CRF evaluation, this study aims to develop a VO₂max prediction model based on a step test, providing a simple and practical alternative for primary healthcare and health monitoring. This model enables clinicians and health management professionals to efficiently assess patients' cardiorespiratory fitness. Through the recruitment of 200 healthy Taiwanese adults, the research combined direct VO₂max measurements with step test heart rate (HR) data and variables like age, sex, percentage body fat (PBF), body mass index (BMI), and resting heart rate (RHR) to develop six predictive models. This method is applicable for clinical health monitoring, cardiorespiratory fitness assessment in patients with chronic diseases, and exercise capacity monitoring in cardiac rehabilitation programs. The study identified that PBF-based models consistently outperformed BMI-based ones, with Model<sup>PBF3</sup>, which incorporates HR responses during exercise, achieving the highest accuracy (R² = 0.689; SEE = 4.6971 ml·kg⁻¹·min⁻¹). These results indicate that the model can effectively estimate VO₂max and be applied in primary healthcare, remote health monitoring, and cardiac rehabilitation settings, providing a simple and practical tool for cardiorespiratory fitness assessment in clinical practice. Validation via PRESS cross-validation and Bland-Altman plots confirmed the stability and reliability of the models across diverse subgroups. By bridging the gap between laboratory-grade precision and everyday practicality, the study introduces a robust, low-cost, and user-friendly tool for CRF assessment, adaptable for non-athletes and those unable to perform high-intensity exercises. This research advances the feasibility of CRF self-management in varied settings, while future iterations could extend its applicability to broader demographics and integrate additional physiological variables for universal adoption.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2676-2685"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302049","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":"Notable influences of estrogen and sex-specific microenvironment in colorectal cancer revealed by single-cell transcriptome analysis.","authors":"Yihui Zheng, Chaoxin Yang, Guozhong Xiao, Mingyuan Lei, Pengfei Qin, Huaxian Chen, Hongcheng Lin","doi":"10.7150/ijms.106133","DOIUrl":"10.7150/ijms.106133","url":null,"abstract":"<p><p><b>Background:</b> Colorectal cancer (CRC), the third most common malignancy worldwide, exhibits notable sex-specific prognostic differences, yet the underlying biological mechanisms remain poorly understood. <b>Methods:</b> In this study, we conducted single-cell sequencing on 32 CRC samples, followed by pathway enrichment analysis, cell-cell interaction analysis, and transcription factor analysis. The co-expression of GZMB and the transcription factor EOMES in CD8+ T cells was detected using multiplex immunohistochemistry. Western blot and TUNEL assays were employed to validate estrogen-induced apoptosis in CRC cell lines. <b>Results:</b> After quality control, we obtained a total of 167,437 cells across 9 cell types from all samples. Specifically, our analysis revealed sex-based variations in cellular composition, functionality, and intercellular interactions within CRC. Notably, female CRC samples exhibited significant positive correlation between estrogen signaling pathway activation and apoptotic activity, with validation through Western blot and TUNEL assays confirming estrogen-mediated apoptosis induction in CRC cell lines. The immune response was notably enhanced in female CRC, with CD8+ T cells showing increased expression of the EOMES gene regulatory network, thereby boosting T cell immunity. Moreover, B cells of female CRC demonstrated improved capabilities in antigen-presenting and MHC-I interactions with T cells. Additionally, Macro_CCL4 cells engaged in sex-specific TNF-TNFRSF1B crosstalk with CD8+ T cells, potentially leading to enhanced antitumor immunity in females. Conversely, CAF_MMP11 cells exhibiting a myofibroblastic CAF phenotype interacted with malignant epithelial cells via signaling pathways such as THBS, MK, and FN1, likely promoting CRC progression. <b>Conclusions:</b> Our research highlights the distinct immunological and hormonal responses in CRC by sex, which may explain the observed prognostic disparities. These findings may offer additional further biological insights for targeted therapies in CRC.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 11","pages":"2637-2652"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302055","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}