International Journal of Medical Sciences最新文献

{"title":"Exploring the Multifactorial Regulation of PIEZO1 in Chondrocytes: Mechanisms and Implications.","authors":"Gongwu Yuan, Ziren Xiong, Xi Ke, Guodong Wang, Ximing Liu, Zhigang Li","doi":"10.7150/ijms.111082","DOIUrl":"10.7150/ijms.111082","url":null,"abstract":"<p><p>The mechanosensitive PIEZO1 ion channel plays a pivotal role in the regulation of chondrocyte function and is involved in various physiological and pathological processes, including cartilage degradation and osteoarthritis (OA). This review explores the regulatory mechanisms governing PIEZO1 activation and its interactions with mechanical stress, extracellular matrix (ECM) stiffness, inflammatory factors, and other ion channels. We discuss the role of PIEZO1 in calcium signaling, its modulation by ECM stiffness, and the implications for cartilage health, particularly under high mechanical load or inflammatory conditions. Additionally, the review highlights pharmacological modulators, including PIEZO1 activators such as Yoda1 and Jedi1/2, and inhibitors like GsMTx4, as potential therapeutic targets for OA treatment. The synergistic interactions of PIEZO1 with other mechanosensitive channels, such as TRPV4 and PIEZO2, are also examined, providing insights into their collective role in mechanotransduction. Further research is essential to clarify the spatiotemporal activation patterns of PIEZO1, its downstream effects, and the potential for targeting this channel in clinical interventions for degenerative cartilage diseases.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3393-3411"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788962","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":"Investigation of The Hepatoprotective Potential of Liposomal Resveratrol as Polyphenols Against Liver Damage in Streptozotocin Diabetic Rat Model.","authors":"Ahmed Z Alanazi, Mohammad M Algahtani, Faisal A Alotaibi, Salim S Al-Rejaie, Mohammed Alqinyah, Abdullah S Alhamed, Hussain N Alhamami, Ahmed Nadeem, Mohammad Raish, Khaldoon Aljerian, Adel M Alragas, Khalid Alhazzani","doi":"10.7150/ijms.109115","DOIUrl":"10.7150/ijms.109115","url":null,"abstract":"<p><p>Diabetes Mellitus is a prominent contributor to degenerative diseases globally and is often associated with hepatic injury. The dysfunction of the liver is characterized by cirrhosis, inflammation, apoptosis, and impaired antioxidant defense mechanisms. Our goal was to estimate the hepato-protecting properties of Liposomal resveratrol (LR) administered at 20 and 40 mg/kg in diabetic rat models and compare them with those of resveratrol at 40 mg/kg. The diabetes was induced in them using streptozotocin (STZ) (65 mg/kg) during a five-week long dosage. This study investigates the effects of LR and resveratrol on glucose levels, body weight, inflammatory markers (TNF-α, IL-6, NF-κB), oxidative stress parameters (MDA, catalase, GPx), apoptotic markers (caspase-3, BAX, BCL-2), liver function enzymes (SGOT, SGPT, GGT), and histopathological alterations in liver tissue. Diabetic rats infused with STZ exhibit changes in hepatic function markers, and increased inflammatory and apoptotic responses, all of which were reversed by administering LR. This reversal occurred through the downregulation of TNF-α and IL-6, inhibition of NF-κB translocation, upregulation of BCL-2, and downregulation of caspase 3 and Bax protein levels. STZ-induced diabetic rats experience a significant disruption in their antioxidant defense system, whereas LR administration notably inhibits lipid peroxidation and significantly enhances the activity of antioxidant enzymes. The histopathological analysis of liver tissue in STZ rats showed morphological changes when compared to the normal rats. This was indicative of the development of acute inflammations. In contrast, LR treatment resulted in normal liver histology with minimal presence of chronic inflammatory cells, predominantly lymphocytes. Remarkably, resveratrol alone was less effective than LR in restoring these parameters in diabetic subjects. Administration of LR effectively mitigates oxidative stress and hepatic impairment caused due to diabetes, suggesting its potential as a therapeutic agent to reduce liver dysfunction in diabetic patients.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3380-3392"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788966","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":"Psoriasis Patients are Associated with Increased Risk of New-Onset Irritable Bowel Syndrome: A Multicenter, Retrospective Cohort Study.","authors":"Shiu-Jau Chen, Hui-Chin Chang, Shuo-Yan Gau","doi":"10.7150/ijms.116551","DOIUrl":"10.7150/ijms.116551","url":null,"abstract":"<p><p><b>Background:</b> Psoriasis is a chronic systemic inflammatory disease linked to multiple comorbidities. The association between psoriasis and irritable bowel syndrome (IBS) remains insufficiently characterized. <b>Methods:</b> We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Adults with psoriasis (ICD-10-CM L40) diagnosed between 2005 and 2023 were matched 1:1 with non-psoriasis controls based on demographics, socioeconomic status, comorbidities, and healthcare utilization. IBS (ICD-10-CM K58) diagnoses within 90 days of index were excluded. Cox regression models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses varied wash-out periods, follow-up durations, and exposure definitions. <b>Results:</b> After matching (n=256,550 per group), people with psoriasis were associated with a higher risk of IBS (HR 1.244, 95% CI 1.168-1.325) in the 15-year follow-up model while comparing with non-psoriasis controls. Subgroup analyses validated elevated risks among both age groups (e.g., age ≥65 years: HR 1.325, 95% CI 1.167-1.505) and sexes (female: HR 1.291, 95% CI 1.197-1.393). All sensitivity models yielded consistent results. <b>Conclusion:</b> Psoriasis is independently associated with an increased risk of subsequent IBS. Routine gastrointestinal symptom screening in psoriasis patients may improve comprehensive care.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3422-3428"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788971","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":"Myofunctional Therapy and Its Effects on Retropalatal Narrowing and Snoring: A Preliminary Analysis of Rehabilitative Approaches.","authors":"Vitriana Biben, Fatrika Dewi, Shinta Sari Ratunanda, Nushrotul Lailiyya, Sitti Ayu Hemas Nurarifah, Nabilla Fikria Alviani","doi":"10.7150/ijms.113922","DOIUrl":"10.7150/ijms.113922","url":null,"abstract":"<p><p><b>Introduction:</b> Snoring is a common and disturbing condition that is associated with sleep apnea in some cases. Retropalatal narrowing has been reported to be often associated with the condition, as it can lead to increased air turbulence and vibration of tissues in the throat during breathing. The activation of the tongue, soft palate, lateral wall of the pharynx, and face has been shown to keep the upper muscles open during sleep, potentially improving snoring. Therefore, this study aims to determine the effects of myofunctional therapy (MT) in patients with collapsed pharynx. <b>Methods:</b> A total of 18 participants were selected based on inclusion and exclusion criteria in this one-group pre-post study. MT exercise intervention was performed for 6 weeks, and flexible nasolaryngoscopy was used to diagnose the area of pharyngeal collapse. The impact of MT was assessed using the Berlin questionnaire (to assess the frequency and intensity of snoring) and the Epworth Sleepiness Scale (to assess daytime sleepiness), which were filled out before and after exercise. <b>Results:</b> The results showed a significant decrease in the percentage of narrowing of pharyngeal area (retropalatal) (58.8%, p < 0.05) after the intervention, as well as the frequency of snoring (94.1%, p < 0.01). In addition, there was a decrease in snoring frequency, improvement in snoring intensity (100%, p < 0.01), and decline in daytime sleepiness (mean 3.59±2.740, p < 0.01). <b>Conclusion:</b> MT can effectively alleviate narrowing in pharyngeal area, leading to a reduction in snoring and daytime sleepiness.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3371-3379"},"PeriodicalIF":3.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788967","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":"Statins and Pacing-Induced Atrial Myopathy: Unraveling Their Role in Atrioventricular Block Patients with Permanent Pacemakers.","authors":"Yu-Sheng Lin, Wan-Chun Ho, Meng-Hung Lin, Ting-Yu Kuo, Chang-Min Chung, Pei-Chun Yen, Yung-Lung Chen, Huang-Chung Chen, Wei-Chieh Lee","doi":"10.7150/ijms.113087","DOIUrl":"10.7150/ijms.113087","url":null,"abstract":"<p><p><b>Background:</b> Left atrial (LA) myopathy from interventricular dyssynchrony often precedes atrial fibrillation (AF) in atrioventricular block (AVB) patients with frequent right ventricular (RV) pacing, but the role of statin therapy in preventing LA myopathy and associated arrhythmias remains debated. <b>Objectives:</b> This study investigated the mechanisms of LA myopathy and the clinical outcomes of statin therapy in AVB patients with permanent pacemakers (PPMs). <b>Methods:</b> The study comprised an animal, cell, and clinical cohort study. In the animal study, 12 Lanyu miniature pigs were divided into sham control, RV pacing, and RV pacing plus atorvastatin groups to assess cardiac effects over six months. The cellular study used HL-1 atrial myocytes to evaluate fibrosis and protein expression after cyclic stretching. The clinical study included 2338 AVB patients with PPM, comparing statin and non-statin groups for AF incidence and outcomes using inverse probability of treatment weighting (IPTW). <b>Results:</b> In the animal model, atorvastatin did not affect LA size, function, or fibrosis. The cellular study showed increased fibrosis markers in both stretch and stretch plus atorvastatin groups compared to controls. In the PPM cohort, statin use did not significantly impact LA size, AF incidence (p=0.731), or CV mortality (p=0.129) over five years, but it was associated with significantly lower all-cause mortality (p=0.004) after IPTW adjustment. <b>Conclusion:</b> Statins do not appear to improve LA myopathy or reduce the incidence of associated atrial arrhythmias in the AVB population with PPMs.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3342-3353"},"PeriodicalIF":3.2,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788987","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":"CLCN5 inhibits tumorigenesis and fatty acid accumulation in clear cell renal cell carcinoma by regulating Enoyl CoA hydratase and 3-Hydroxyacyl CoA dehydrogenase.","authors":"Tiexi Yu, Weiquan Li, Xiangui Meng, Wei Yang, Hailong Ruan, Wen Xiao, Xiaoping Zhang","doi":"10.7150/ijms.105969","DOIUrl":"10.7150/ijms.105969","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC), a globally prevalent and highly aggressive malignancy, is characterized by abnormal lipid accumulation and high morbidity. However, the complex pathological mechanisms underlying its development remain largely unexplored, necessitating further research efforts. In this study, we employed Weighted Gene Co-expression Network Analysis (WGCNA) and identified Chloride Voltage-Gated Channel 5 (CLCN5), a member of the CIC family, as a potential hub gene involved in fatty acid degradation. Our findings suggest that downregulated CLCN5 was negatively correlated with the malignant characteristics and prognosis of ccRCC. <i>In vitro</i> experiments demonstrated that CLCN5 overexpression significantly impacts fatty acid oxidation and inhibits tumor proliferation, metastasis, migration, and invasion in ccRCC. Mechanistically, CLCN5 restrains the proliferation and migration of ccRCC cells by decreasing lipid accumulation through the effects of Enoyl CoA hydratase and 3-Hydroxyacyl CoA dehydrogenase (EHHADH). Collectively, these findings suggest that CLCN5/EHHADH-mediated fatty acid metabolism could be a potential strategy for ccRCC treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3354-3370"},"PeriodicalIF":3.2,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788959","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":"Protective Role of High-Density Lipoprotein Cholesterol in Stress Urinary Incontinence with Special Emphasis on Overweight/Obese Individuals.","authors":"Junlong Huang, Ziqiao Wang, Zheng Liu, Bolong Liu, Wenshuang Li, Xiangfu Zhou","doi":"10.7150/ijms.116324","DOIUrl":"10.7150/ijms.116324","url":null,"abstract":"<p><p><b>Background:</b> Increasing evidence shows that lipid metabolism is closely related to the pathogenesis of stress urinary incontinence (SUI). This study aimed to investigate the association between high-density lipoprotein cholesterol (HDL-C) levels and female SUI, evaluate dose-response relationships, and determine the causal effect of HDL-C on SUI risk. <b>Materials and methods:</b> Utilizing cross-sectional data from the National Health and Nutrition Examination Survey (2001-2020, n = 18,415), we assessed the dose-response relationship between HDL-C and SUI using restricted cubic splines and weighted logistic regression. Mendelian randomization (MR) analyses leveraged genetic instruments from European cohorts (HDL-C: n = 9,796; SUI: 5,926 cases/211,672 controls) to infer causality. Subgroup analyses emphasized interactions between HDL-C and BMI. <b>Results:</b> A 1 mg/dL increase in HDL-C was linearly associated with a 0.5% reduction in SUI risk (OR = 0.995, 95% CI: 0.986-0.991, <i>P</i> < 0.001). Participants in the highest HDL-C quartile (Q4) exhibited a 25.1% lower SUI risk compared to Q1 (OR = 0.749, 95% CI: 0.652-0.859). Notably, the protective effect of HDL-C was markedly stronger in overweight/obese individuals (BMI ≥ 25 kg/m²: OR = 0.992, <i>P</i> = 0.006; BMI ≥ 30 kg/m²: OR = 0.991, <i>P</i> = 0.001), with significant interaction (<i>P</i> for interaction = 0.015). MR analyses confirmed a causal protective effect of HDL-C on SUI (IVW OR = 0.842, 95% CI: 0.744-0.953), and sensitivity analyses supported robustness. <b>Conclusions:</b> Elevated HDL-C levels are causally linked to reduced SUI risk, with amplified protection in overweight/obese populations. These findings highlight the importance of maintaining healthy HDL-C levels as a targeted strategy for SUI prevention, especially in high-BMI individuals.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3304-3315"},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788970","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 Artificial Intelligence Models Using CT Radiomics for Predicting Post-Vertebral Augmentation Residual Back Pain in Osteoporotic Vertebral Compression Fractures.","authors":"Chen Ge, Changwei Li, Yaoqing Zhu, Chonglin Yang, Xiangyang Xu","doi":"10.7150/ijms.114419","DOIUrl":"10.7150/ijms.114419","url":null,"abstract":"<p><p><b>Background</b>: Residual back pain (RBP) following vertebral augmentation (VA) represents a significant challenge in managing osteoporotic vertebral compression fractures (OVCFs). While conventional predictive models have shown moderate accuracy, their preoperative risk stratification capabilities remain suboptimal. CT-based radiomics has demonstrated success in vertebral fracture assessment, yet its integration with artificial intelligence (AI) for predicting RBP remains unexplored. <b>Objective</b>: This study aims to identify the optimal AI model for predicting RBP by systematically comparing multiple algorithms that integrate CT radiomics features with clinical parameters, with the goal of enabling preoperative risk stratification for improved surgical decision-making. <b>Methods</b>: This prospective study enrolled patients who underwent VA for OVCFs. Potential predictors were identified through clinical variable analysis. Radiomics features were extracted from preoperative CT images using standardized vertebral segmentation protocols. The study population was divided into training and testing cohorts at a ratio of 7:3. Five AI models were constructed through integration of clinical predictors and radiomics features. Model performance evaluation was conducted in the independent testing cohort through discrimination, calibration, and clinical utility analyses. The predictive mechanisms of the optimal model were interpreted through feature importance analysis. <b>Results</b>: Among 856 enrolled patients, RBP developed in 102 cases (11.9%). TabNet exhibited optimal performance metrics (AUROC: 0.927, Recall: 0.833) among all evaluated algorithms. Feature importance analysis revealed intravertebral vacuum cleft and bone mineral density as principal clinical predictors, complemented by wavelet-based texture parameters and quantitative intensity metrics. Ablation experiments demonstrated that clinical parameters were critical for false-positive reduction, while radiomics features enhanced specificity in non-RBP identification. The model maintained consistent clinical utility across varying threshold probabilities. <b>Conclusion:</b> The integration of clinical parameters and CT-based radiomics through a deep learning framework enabled accurate preoperative prediction of RBP.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3329-3341"},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788960","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":"Radiotherapy elicits immunogenic cell death and metabolic shifts in the tumor microenvironment: implications for immunotherapy.","authors":"Zi-Shan Hang, Yue-Ying Huang, An Song, Zhi-Jun Sun","doi":"10.7150/ijms.109515","DOIUrl":"10.7150/ijms.109515","url":null,"abstract":"<p><p>Radiotherapy, one of the most utilized strategies to combat malignancies, has been constantly explored for its effectiveness and optimized, and it is currently operating at the molecular level. The tumor microenvironment (TME), where complicated changes take place under radiotherapy and other treatments, inevitably draws our attention to metabolic alterations, immunogenic cell death (ICD) and immunological interactions. In response to radiotherapy, tumor metabolism promotes DNA and membrane repair processes and reduces oxidative stress, thereby collectively alleviating the occurrence of cell death. Moreover, the induction of pyroptosis, necroptosis and ferroptosis under radiotherapy has the potential to increase antitumor immunity. Therefore, comprehensive knowledge about how radiotherapy triggers these modalities of ICD mechanically is necessary for developing nanomedicines with more accurate targets. In addition, information on clinical advancements as well as the management of adverse events is important for investigating radiotherapy combined with immunotherapy. This review provides an overview of up-to-date findings on metabolic changes and ICD under radiotherapy and provides insight into the status of the TME.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3277-3291"},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788972","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":"Human Epididymis Protein 4 Predicted Concurrent Intermediate-high-risk Endometrial Cancer and Eligibility of Fertility-sparing Treatment for Patients Diagnosed with Endometrial Atypical Hyperplasia Before Surgery.","authors":"Yaochen Lou, Weirong Ma, Feng Jiang, Jun Guan","doi":"10.7150/ijms.115170","DOIUrl":"10.7150/ijms.115170","url":null,"abstract":"<p><p><b>Objective:</b> To investigate whether serum human epididymis protein 4 (HE4) could identify concurrent intermediate-high-risk endometrial cancer (EC) in patients diagnosed with endometrial atypical hyperplasia before definitive surgery (preoperative-EAH). <b>Methods:</b> This retrospective study analyzed preoperative-EAH patients who underwent hysterectomy at a tertiary hospital between January 2016 and December 2022. <b>Results:</b> Among 715 preoperative-EAH patients, 26.2% (187/715) were diagnosed with concurrent EC postoperatively, with 6.0% (43/715) identified as having concurrent intermediate-high-risk EC. Serum HE4 and postmenopausal status were revealed as independent predictors of concurrent EC. Receiver operator characteristic analyses determined optimal HE4 cut-off values of 43.50 pmol/L for predicting concurrent EC, 53.15 pmol/L for intermediate-high-risk EC, and 43.80 pmol/L for identifying non-candidates for fertility-sparing treatment. Multivariate analyses confirmed HE4 and postmenopausal status as key independent predictors of intermediate-high-risk EC, leading to the development of a nomogram model. It demonstrated a bootstrap-corrected C-index of 0.819 (95% confidence interval [CI] = 0.74-0.90). The calibration and decision curves highlighted its consistency and clinical utility. According to the nomogram, 41.4% (24/58) of high-score patients had concurrent intermediate-high-risk EC, compared with only 2.9% (19/657) in the low-score group (<i>P</i> < 0.001). HE4 also significantly predicted the non-candidates for fertility-preserving therapy in young preoperative-EAH women (odds ratio [OR] = 5.21, 95% CI = 2.10-12.89, <i>P</i> < 0.001). <b>Conclusion:</b> Serum HE4 was a promising predictor of concurrent intermediate-high-risk EC and suitability for fertility-sparing treatment for preoperative-EAH patients. Incorporating HE4 and menopausal status into the nomogram model significantly enhanced the risk stratification for intermediate-high-risk EC and might assist clinical decision-making.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3292-3303"},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788964","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}