International Journal of Medical Sciences最新文献

{"title":"Molecular Subtyping and Prognostic Prediction in Pancreatic Cancer Based on Mitophagy-Related Genes.","authors":"Yunlong Cai, Taohua Yue, Yongchen Ma, Guanyi Liu, Jixin Zhang, Long Rong","doi":"10.7150/ijms.121350","DOIUrl":"10.7150/ijms.121350","url":null,"abstract":"<p><p><b>Background:</b> Pancreatic cancer (PaC) is characterized by poor prognosis. This study aimed to identify mitophagy-related clusters and develop a prognostic model for PaC. <b>Methods:</b> Differentially expressed genes (DEGs) between PaC and normal tissues were identified from the TCGA and GTEx cohorts. Mitophagy-related genes (MRGs) were sourced from Reactome, GO, and KEGG databases. The intersection of DEGs and MRGs identified differentially expressed MRGs (DeMRGs). Consensus clustering identified PaC subtypes based on DeMRG expression. Univariate Cox analysis was used to find prognosis-related genes, and LASSO regression analysis was employed to develop the prognostic model. A nomogram was constructed to predict survival probabilities. <b>Results:</b> A total of 7,240 DEGs were identified between PaC tissues and normal controls. From these, 12 DeMRGs were identified, and consensus clustering revealed three distinct molecular clusters. A prognostic model based on six significant genes (PAPPA, NBPF12, CXCL11, CKLF-CMTM1, CCDC6, AHNAK) was developed using LASSO regression analysis. This model demonstrated good predictive performance for overall survival in the TCGA cohort, with AUC values of 0.78, 0.74, and 0.82 for 1-, 2-, and 3-year survival in the training set, and 0.73, 0.82, and 0.73 in the validation set. External validation in independent GEO cohorts demonstrated moderate predictive performance. The nomogram demonstrated good calibration and accuracy in predicting survival. Significant correlations were found between the risk model and immune cell infiltration. High-risk patients showed higher sensitivity to dasatinib and staurosporine. <b>Conclusions:</b> The study identified mitophagy-related molecular clusters and developed a prognostic model for PaC. This model may help predict overall survival and guide personalized treatment strategies for PaC patients.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 2","pages":"620-635"},"PeriodicalIF":3.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12825130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051791","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":"Artificial Intelligence-Enabled Electrocardiography for Preoperatively Detecting Atrial Fibrillation and Mortality Risk in Patients with Sinus Rhythm.","authors":"Chiao-Chin Lee, Chin-Sheng Lin, Wen-Yu Lin, Chiao-Hsiang Chang, Wei-Ting Liu, Dung-Jang Tsai, Cheng-Chung Cheng, Jun-Ting Liou, Wei-Shiang Lin, Tien-Ping Tsao, Chien-Sung Tsai, Yung-Tsai Lee, Chin Lin","doi":"10.7150/ijms.123598","DOIUrl":"10.7150/ijms.123598","url":null,"abstract":"<p><p><b>Background:</b> Pre-existing atrial fibrillation (AF) and postoperative new-onset AF (NOAF) are independent perioperative risk factors associated with increased short-term mortality and adverse events. This study aimed to develop and validate an artificial intelligence (AI) model capable of detecting hidden AF, including both pre-existing AF and NOAF, from sinus rhythm electrocardiograms, to improve perioperative risks assessment. <b>Methods:</b> We trained and validated an AI model to detect hidden AF. Subsequent analysis confirmed the prognostic relevance of both pre-existing AF and NOAF in patients receiving non-cardiac surgery. The AI model was applied to patients without known AF to evaluate its predictive capability for NOAF and to stratify short-term clinical outcomes. <b>Results:</b> The AI model demonstrated an area under the receiver operating characteristic curve of 0.87 during the development phase for predicting AF. In an independent validation cohort, pre-existing AF and postoperative NOAF were significantly correlated with increased 30-day all-cause mortality. Patients without pre-existing AF who were classified as high-risk by the AI model had substantially higher 30-day all-cause mortality than their low-risk counterparts (HR 17.33, 95% CI 5.29-56.75). Furthermore, the model scores surpassed conventional clinical risk scores in predicting NOAF and 30-day all-cause mortality. <b>Conclusions:</b> This AI-based approach facilitated the accurate identification of patients with elevated perioperative AF-related risk. It will facilitate focused interventions that may enhance clinical outcomes.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 2","pages":"684-694"},"PeriodicalIF":3.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12825122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052038","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":"AMIGO2 as a Novel Biomarker Predicting Poor Prognosis and Associated with Adhesion-Driven Metastasis in Pancreatic Adenocarcinoma.","authors":"Ze-Syuan Chen, Tsung-Shun Chang, Wan-Jou Shen, Shan-Ju Liu, Chih-Yang Wang, Yung-Kuo Lee, Wen-Hsin Hsu, Wei-Jan Wang","doi":"10.7150/ijms.121794","DOIUrl":"10.7150/ijms.121794","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PAAD), the predominant form of pancreatic cancer, is highly aggressive and refractory to current therapies. The Amphoterin-Induced Gene and ORF (AMIGO) family encodes three structurally related type I transmembrane proteins (AMIGO1-3) containing leucine-rich repeat and immunoglobulin-like domains, which mediate cell adhesion and signaling. Although AMIGO proteins have been implicated in neural development and tumor progression, their functional relevance in PAAD remains unclear. Here we identify AMIGO2 as a key driver of PAAD progression through integrated transcriptomic, proteomic, and functional analyses. Multi-cohort datasets (ONCOMINE, TCGA) and immunohistochemistry revealed marked AMIGO2 overexpression in PAAD tissues, with recurrent genetic alterations (~11%) and strong association with poor relapse-free and overall survival. Functional enrichment of AMIGO2-correlated genes indicated activation of focal adhesion and PI3K/AKT signaling. Consistently, inhibition of AMIGO2 expression in pancreatic cancer cells reduced migration and invasion while restoring E-cadherin expression, indicating inhibition of epithelial mesenchymal transition. Protein profiling from the Human Protein Atlas further confirmed elevated AMIGO2 expression in tumors. Together, these findings demonstrate that AMIGO2 promotes PAAD aggressiveness by enhancing adhesion- and EMT-associated pathways, establishing it as a potential prognostic biomarker and therapeutic target in pancreatic cancer.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 2","pages":"695-710"},"PeriodicalIF":3.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12825146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051981","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":"Intrahepatic Lymphangiogenesis Is Associated with Early Post-Hepatectomy Liver Regeneration, in Part via IL-6/STAT3 Signaling.","authors":"Shudong Xie, Xiaofei Fan, Yang Liu, Hao Li, Chen Zhou, Chen Guo, Xiongzhuo Tang, Yingzi Ming, Pengpeng Zhang","doi":"10.7150/ijms.106849","DOIUrl":"10.7150/ijms.106849","url":null,"abstract":"<p><p><b>Background:</b> Insufficient liver regenerative capacity poses life-threatening risks to patients following partial hepatectomy (PHx), and existing clinical treatments provide limited options for enhancing regeneration. Lymphatic vasculature plays essential roles in the immune response through the uptake and transport of pathogens, antigens, inflammatory mediators, and antigen-presenting cells. Recent research has shown that lymphangiogenesis may contribute to both heart and bone regeneration. However, the role and underlying mechanisms of intrahepatic lymphangiogenesis in liver regeneration remain unclear. <b>Methods:</b> Single-cell RNA sequencing was employed to identify dynamic changes in lymphatic endothelial cells (LyECs) in liver tissues following 70% PHx. A mouse model of liver regeneration was utilized to assess the contribution of intrahepatic lymphangiogenesis to the regenerative process after 70% PHx. Additionally, an adeno-associated virus overexpressing vascular endothelial growth factor-C (AAV-VEGF-C) was used to confirm the role of intrahepatic lymphangiogenesis in liver regeneration. qRT-PCR, western blotting and immunofluorescence staining were performed to investigate the potential underlying mechanisms. Furthermore, a neutralizing rat anti-murine anti-IL-6 antibody (anti-IL-6) was used to verify signaling pathway. <b>Results:</b> Single-cell RNA sequencing analysis revealed dynamic changes of LyECs in liver tissues following 70% PHx. Consistent with these findings, the number and area of intrahepatic lymphatic vessels (LVs) around the portal tract significantly decreased on postoperative day 3 (POD3) in the mouse model of 70% PHx compared to the sham group, but the number and area recovered by POD7. Additionally, vascular endothelial growth factor-C(VEGF-C), a pro-lymphangiogenic growth factor, was found to increase in the liver of the 70% PHx mouse model. Stimulation of lymphangiogenesis with AAV-VEGF-C significantly accelerated liver regeneration and repair. Mechanistically, intrahepatic lymphangiogenesis might accelerate liver regeneration by the activation of the IL-6/STAT3 pathway. Blocking IL-6 reversed lymphangiogenesis-accelerated liver regeneration. <b>Conclusions:</b> Intrahepatic lymphangiogenesis may contribute to early liver regeneration after PHx, with partial dependence on IL-6/STAT3 signaling. These findings support further investigation of lymphatic-modulating approaches as potential adjuncts to enhance postoperative recovery after PHx, particularly in selected contexts.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 2","pages":"646-660"},"PeriodicalIF":3.2,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12825147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051445","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":"Transcriptomic Profiling Reveals Divergent Immune Responses to AAV1 and AAV-ie in Mice Inner Ear.","authors":"Dazhi Shi, Lei Han, Can Li, Guannan Geng, Luoying Jiang, Xiaoyun Chen, Fengzhao Yang, Yong Feng, Junli Luo, Yilai Shu","doi":"10.7150/ijms.121060","DOIUrl":"10.7150/ijms.121060","url":null,"abstract":"<p><p>Adeno-associated virus (AAV) unequivocally emerges as one of the most powerful and promising delivery vectors for gene therapy targeting hereditary hearing loss. Following AAV transduction in the inner ear, varying degrees of natural immune responses are triggered, primarily characterized by macrophage activation and the secretion of pro-inflammatory factors. Additionally, the production of neutralizing antibodies may affect the efficacy of gene therapy. To evaluate immune dynamics, we injected AAV1 and AAV-ie (capsids with distinct transfection efficiencies) into murine cochleae and analyzed temporal transcriptomic profiles. Our results demonstrate that both capsids induce immune activity but with critical temporal and intensity differences that AAV1 elicits significantly later and milder immune reactions compared to AAV-ie. These findings establish that dynamic cochlear gene expression profiles directly inform the selection of immunologically optimized AAV vectors to minimize adverse responses in future hereditary hearing loss gene therapies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 2","pages":"611-619"},"PeriodicalIF":3.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12825142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046599","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 Sleep Connection: Exploring the Role of Composite Dietary Antioxidant Index in Sleep Quality Based on NHANES 2007-2014.","authors":"Xiang Xu, Xin Wei, Hong Chen, Hao Gao, XingHua Chen","doi":"10.7150/ijms.114874","DOIUrl":"10.7150/ijms.114874","url":null,"abstract":"<p><p><b><i>Background</i></b> : Growing evidence has highlighted the critical role of oxidative stress in the pathogenesis of sleep problems. The Composite Dietary Antioxidant Index (CDAI), a holistic metric designed to assess the cumulative antioxidant capacity of dietary components, may be intricately linked to sleep quality. This study aimed to investigate the association between CDAI and sleep parameters using data from the National Health and Nutrition Examination Survey (NHANES). <b><i>Methods</i></b> : Participants with complete data on CDAI, sleep parameters, and other essential covariates were included in this study. Weighted multivariable linear or logistic regression models were employed to examine the association between CDAI and sleep parameters (sleep duration, sleep trouble, and sleep disorder). Subgroup analyses, smooth curve fitting, threshold/saturation effect analyses, and sensitivity analyses were conducted to characterize the association's features. <b><i>Results</i></b> : A total of 10,491 participants were finally included in the analysis. After adjusting for all potential covariates, higher CDAI levels were associated with increased sleep duration (CDAI_T3 vs. CDAI_T1, β=0.16, 95% CI: 0.08-0.24), while exhibiting no significant correlation with sleep trouble (CDAI_T3 vs. CDAI_T1, OR=1.03, 95% CI: 0.88-1.20) or sleep disorder (CDAI_T3 vs. CDAI_T1, OR=1.01, 95% CI: 0.79-1.28). Subgroup analyses and interaction tests indicated a more pronounced association among individuals with depression (P interaction<0.0001) and those taking sleep-modulating medications (P interaction=0.0014). Smooth curve fitting analyses identified an inverted \"L\"-shaped association between CDAI and sleep duration, with the inflection point of CDAI determined to be 3.2. Within this threshold, each 1-unit increase in CDAI was associated with a 0.04-hour (95% CI: 0.02-0.05) increase in sleep duration, whereas no association was observed beyond this point. Finally, sensitivity analyses, which excluded individuals with extreme energy intakes or depression, confirmed a consistent and robust association between CDAI and sleep duration. <b><i>Conclusion</i></b> : The association between CDAI and sleep duration exhibits a positive, inverted \"L\"-shaped pattern with a saturation effect. Further prospective or longitudinal cohort studies with larger sample sizes and longer follow-up periods are needed to evaluate its practical value for clinical interventions.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 1","pages":"227-242"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12702126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762176","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":"Betel-quid Use Is Associated with Depression.","authors":"Perl Han Lee, Jiun-Hung Geng, Szu-Chia Chen, Chien-Hung Lee, Chih-Hung Ko","doi":"10.7150/ijms.119520","DOIUrl":"10.7150/ijms.119520","url":null,"abstract":"<p><p><b>Background:</b> Betel-quid use is linked to cancer and other adverse health effects. However, its potential impact on depression has not been well studied. <b>Objective:</b> To investigate the association between betel-quid use and depression. <b>Methods:</b> We analyzed the data of 43,636 men from the Taiwan Biobank. Participants were divided into two groups on the basis of betel-quid use: never-user and ever-user groups. Depression was defined according to self-reported medical history in the questionnaire. Logistic regression was used to assess the association between betel-quid use and depression. <b>Results:</b> The average age of the participants was 49.89 ± 11.36 years. Among them, 16.31% were ever-users of betel quids. In the never-user group (n = 36,521), 828 participants (2.27%) reported a history of depression. However, 75 of 2,592 participants in the ever-user group (2.89%) reported a similar history. The adjusted odds ratio for depression in the ever-user group compared with the never-user group was 1.265, indicating its association with depression. Daily consumption of 11-30 betel quids was associated with depression compared with consumption of ≤10 betel quids. However, no association was found for those consuming more than 30 betel quids daily. <b>Conclusions:</b> Betel-quid use is associated with depression. The association between betel-quid use and depression may not be linear, suggesting a complex dose-response effect.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 1","pages":"126-132"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12701964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762592","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":"Sex-Specific Associations Between Hyperuricemia and Kidney Stone Disease in a Large Taiwanese Cohort.","authors":"Meng-Shiang Liu, Shuo-Hung Wang, Jia-In Lee, Szu-Chia Chen, Shu-Pin Huang, Jiun-Hung Geng","doi":"10.7150/ijms.109742","DOIUrl":"10.7150/ijms.109742","url":null,"abstract":"<p><p><b>Background:</b> Kidney stone disease (KSD) is a growing global health issue, while hyperuricemia has been linked to various health conditions. This study aimed to explore the association between hyperuricemia and KSD. <b>Methods:</b> This study analyzed the data of 118,963 generally healthy participants aged 30-70 years from the Taiwan Biobank. KSD was defined based on self-reported diagnoses, and hyperuricemia was defined as a serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women. Key variables including age, sex, body mass index, lifestyle factors, presence of hypertension, diabetes, and chronic kidney disease were recorded. Statistical analysis was conducted using descriptive statistics and logistic regression to evaluate the association between hyperuricemia and KSD. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were reported, with statistical significance set at p < 0.05. An additional causal mediation analysis was performed to assess the mediating role of gout. <b>Results:</b> Among the 118,963 participants, 23,094 (19.4%) had hyperuricemia. Those with hyperuricemia were older, had a higher body mass index, and were more likely to smoke, consume alcohol, and have elevated blood pressure. They also had higher rates of comorbidities such as hypertension, diabetes, metabolic syndrome, chronic kidney disease, and gout, along with worse laboratory profiles. Multivariable analysis revealed that hyperuricemia was significantly associated with an increased risk of KSD (OR: 1.155, 95% CI: 1.089-1.224, p < 0.001). When stratified into four exposure groups, the prevalence of KSD was 5.4% in participants without hyperuricemia or gout, 8.5% in those with hyperuricemia alone, 17.0% in those with gout alone, and 15.7% in those with both conditions; the adjusted ORs were 1.178, 1.522, and 1.505, respectively, compared with the reference group. The risk was more pronounced in females, particularly those in higher uric acid quartiles, whereas in males, the association was weaker and became nonsignificant after full adjustments. Mediation analysis further indicated that gout explained approximately 24% of the association between hyperuricemia and KSD, while the direct effect of hyperuricemia on KSD remained significant. <b>Conclusion:</b> Hyperuricemia was an independent risk factor for KSD in this large Taiwanese cohort study, with a stronger association observed in females. Gout partially mediates this relationship, suggesting overlapping yet distinct pathways linking hyperuricemia to kidney stone formation. These findings underscore the importance of sex-specific management strategies for KSD. Routine monitoring of serum uric acid levels is recommended to mitigate KSD risk, especially among high-risk individuals. Future research should focus on elucidating the long-term impact of hyperuricemia on KSD and tailoring prevention strategies to regional and population-specific needs.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 1","pages":"53-62"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12702031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762650","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":"Kisspeptins inhibit ectopic endometrial cell invasion and angiogenesis by suppressing PI3K/AKT signaling pathway via CREB5 in endometriosis.","authors":"Lingnan Kong, Suliya Yushanjiang, Li Nie, Yiran Pan, Lei Jin, Zun Wang, Man He, Gao Zhang, Ziyang Ma, Rongqian Zhao, Dongzhi Yuan, Changlong Li","doi":"10.7150/ijms.112890","DOIUrl":"10.7150/ijms.112890","url":null,"abstract":"<p><p>Endometriosis (EMs) is a common gynecological disorder. According to the most widely recognized theory of retrograde menstruation, endometrial cells require completion of three key steps during ectopic implantation: adhesion, invasion, and angiogenesis. Although kisspeptin exerts anti-invasive and anti-angiogenic effects in multiple tumors, its potential inhibitory effects mediated through the KISS1 receptor (KISS1R) on EMs-related invasion and angiogenesis remain uncharacterized. This study aimed to identify regulatory genes in EMs pathogenesis via RNA sequencing and elucidate underlying molecular mechanisms. We performed a comparative transcriptomic analysis of ectopic endometrium (EC) and eutopic endometrium (EU) in 5 patients with EMs and control endometrium in 3 women without EMs. Then, we screened for genes that showed significant differences between EU and group, and even more pronounced differences between EC and EU, indicating a progressive change. Moreover, we identified the top 20 progressively altered genes during EMs development, including KISS1R. Furthermore, KEGG pathway analysis revealed that these progressively altered DEGs were mainly enriched in the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. Previous studies suggest that the PI3K/AKT signaling pathway may mediate cell invasion and angiogenesis in EMs. Additionally, substantial evidence indicates that cAMP-response element binding protein (CREB5), a transcriptional regulator, can regulate the PI3K/AKT pathway. However, the mechanism of functional changes of CREB5 and PI3K/AKT in EMs is unclear. Our study validated the functional role of KISS1/KISS1R in EMs through animal experiments and cell experiments. It may suppress the cell invasion and angiogenesis of endometrial cells by reducing the phosphorylation levels of PI3K and AKT mediated by increasing CREB5. This mechanistic insight provides novel pathogenic explanations for EMs.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 1","pages":"334-349"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12702097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762691","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":"Polycystic Ovary Syndrome Revisited: Novel Insights and Updates.","authors":"Wenwen Zhao, Jiayi Zhou, Yanhua Song, Miao He, Xudong Zhu, Bianfang Yu, Wenxiao Gao","doi":"10.7150/ijms.119968","DOIUrl":"10.7150/ijms.119968","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting approximately 10% of middle-aged women worldwide. The main clinical features of PCOS include hirsutism, anovulation, irregular menstruation, and polycystic ovaries. However, the exact etiology and underlying mechanisms of PCOS remain incompletely understood. Increasing evidence suggests that a variety of factors-including environmental toxins, chronic low-grade inflammation, oxidative stress, and dysregulated insulin secretion-are involved in the onset and progression of PCOS. Additionally, abnormalities in neurotransmitter metabolism play a significant role in the pathophysiology of PCOS, particularly in relation to weight gain, hyperandrogenemia, and mood disorders. Patients with PCOS often exhibit neuroendocrine system dysfunction, characterized by altered levels of neurotransmitters such as serotonin, norepinephrine, and dopamine. These changes are closely associated with clinical symptoms such as anxiety, depression, obesity, and metabolic disturbances. Current treatment strategies for PCOS primarily focus on lifestyle modifications and pharmacological interventions. These include dietary changes, nutritional supplementation, physical activity, and ovulation induction, all aimed at alleviating symptoms and improving quality of life. Notably, interventions targeting neurotransmitter metabolism are emerging as a novel area of research. The use of antidepressants, anxiolytics, and insulin-sensitizing agents has shown potential in alleviating symptoms and regulating neuroendocrine function. Furthermore, PCOS is significantly associated with metabolic dysfunction, particularly in hormone metabolism, lipid metabolism, and glucose metabolism, which exacerbates the risk of obesity, hyperandrogenemia, and type 2 diabetes. Therefore, understanding alterations in neurotransmitter metabolism and developing new therapeutic strategies may offer novel perspectives and intervention approaches for the diagnosis and treatment of PCOS.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"23 1","pages":"271-282"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12702132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762660","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}