{"title":"Beyond disease treatment and prevention: From geroscience and molecular hallmarks to gerotherapeutics and precision geromedicine.","authors":"Li-Ning Peng, Fei-Yuan Hsiao, Liang-Kung Chen","doi":"10.1097/JCMA.0000000000001374","DOIUrl":"10.1097/JCMA.0000000000001374","url":null,"abstract":"<p><p>Geroscience-the interdisciplinary field investigating the causal relationship between the biology of aging and age-related chronic disease-has undergone a remarkable evolution since its formalization within the United States National Institutes of Health in the early 2010s. Grounded in the recognition that aging is the paramount modifiable risk factor for most noncommunicable diseases, geroscience has produced a coherent molecular taxonomy of aging processes (12 hallmarks), delineated proaging and antiaging molecular pathways (gerogenes, gerosuppressors, and gerozymes), and catalyzed a new clinical vocabulary-geroprotection, gerodiagnostics, and gerotherapeutics. Two institutional milestones anchor the field's translational ambitions: the World Health Organization's (WHO) codification of Ageing-Associated Decline in Intrinsic Capacity as International Classification of Disease (ICD)-11 code MG2A; and the United States Food and Drug Administration's (FDA) acceptance of the Targeting Aging with Metformin (TAME) trial-the first prospective clinical trial designed to delay aging as a composite multidisease outcome, currently underway. The biomarker science of aging has advanced in parallel, from first-generation DNA methylation clocks to organ-specific plasma proteomic signatures capable of predicting various age-related diseases with clinical-grade precision. The gerotherapeutic landscape has expanded substantially. Metformin, which engages more aging hallmarks than any other candidate gerotherapeutic, provided the regulatory impetus for TAME; in a rigorous 40-month multiomics study in cynomolgus monkeys, it decelerated plasma proteomic biological age by 6.41 years-the strongest pharmacological evidence to date for systemic biological age modification in a primate model. Senolytics and senomorphics target senescent cell burden; SGLT-2 inhibitors are notable for their indirect senolytic mechanism, enhancing immunosurveillance of senescent cells glucagon-like peptide-1 (GLP-1) receptor agonists attenuate inflammaging; NAD + precursors restore mitochondrial and sirtuin function; and the gerozyme (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) inhibitor offers a mechanistically distinct proregenerative approach with emerging relevance as an adjunct to GLP-1 receptor agonist therapy. Multidomain lifestyle programs address multiple aging hallmarks simultaneously and have demonstrated measurable intrinsic capacity improvement in randomized trials. Building on these foundations, this review proposes the Geroscience-Responsive Aging Care Ecosystem (GRACE)-a three-element service model operationalizing geroscience and gerotherapeutic evidence within the WHO Integrated Care for Older People (ICOPE) framework.</p>","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":" ","pages":"323-333"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Male- and female-factor infertility and partners' quality of life during assisted reproductive technology: A dyadic actor-partner analysis.","authors":"Po-Hung Pan, Yu-Chen Hsu, Chun-Han Tseng, Ting-Chien Lin, Tasheng Chen, Yu-Hsien Wu, Chih-Wei Lin, Meng-Hsing Wu","doi":"10.1097/JCMA.0000000000001380","DOIUrl":"10.1097/JCMA.0000000000001380","url":null,"abstract":"<p><strong>Background: </strong>Infertility constitutes a dyadic stressor, as it inherently involves both members of a couple; nevertheless, its psychological impact is frequently evaluated from an individual perspective. We tested whether etiologic diagnosis (male and female factors) is associated with both partners' quality of life (QoL) during assisted reproductive technology (ART).</p><p><strong>Methods: </strong>We conducted a retrospective cross-sectional study at the assisted reproduction center of a tertiary university hospital in southern Taiwan, enrolling married heterosexual couples undergoing ART who completed the Fertility Quality of Life questionnaire during treatment. Using a distinguishable-dyads actor-partner interdependence model (APIM), we estimated actor effects (one's diagnosis on one's QoL) and partner effects (one's diagnosis on the partner's QoL) in all domains. Sensitivity analyses of the APIM adjusted for age, body mass index, infertility duration, and prior embryo transfer attempts.</p><p><strong>Results: </strong>A total of 105 couples were eligible to be enrolled. Men reported higher QoL than women across domains ( p < 0.01). The APIM showed a significant, asymmetric partner effect: female-factor infertility was associated with lower Mind-Body ( β = -17.54, p = 0.017) and Core ( β = -10.15, p = 0.045) scores in male partners. No partner effect of male-factor infertility on women's QoL was detected, and actor effects were not significant for either partner. Adjusted models yielded directionally consistent results.</p><p><strong>Conclusion: </strong>Infertility etiology relates to the couple's well-being in an asymmetric pattern. Female-factor infertility is linked to poorer QoL in male partners, consistent with distress from witnessing treatment and sociocultural expectations, underscoring the need for dyadic, couple-centered support during ART. Limitations include the cross-sectional design and potential selection bias arising from a high exclusion rate of incomplete dyads, which restricts generalizability.</p>","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":" ","pages":"340-346"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proposed study design for estimating COVID-19 vaccine effectiveness in post-pandemic Taiwan.","authors":"Long-Sheng Chen, Cheng-Yi Lee, Hung-Wei Kuo, Yu-Lun Liu, Jen-Hsiang Chuang","doi":"10.1097/JCMA.0000000000001372","DOIUrl":"10.1097/JCMA.0000000000001372","url":null,"abstract":"<p><p>Post-licensure observational studies are used to assess vaccine effectiveness (VE) when clinical randomized controlled trials are not feasible. Although vaccination engenders various effects at the individual and population levels, few studies have specifically examined the types of effects estimated in the VE study. The test-negative design (TND) is more commonly used to evaluate direct vaccine performance against the influenza virus, rotavirus, and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is preferably used within a standard sentinel surveillance platform, and certain constraints may affect its validity. After the World Health Organization declared that coronavirus disease 2019 (COVID-19) is no longer a public health emergency, developing robust methodologies for evaluating VE is critical. Accordingly, this study aims to (1) clarify the types of vaccine effects typically captured by current observational VE studies, and (2) propose a scientifically rigorous and operationally feasible study design for estimating seasonal COVID-19 VE against severe outcomes after the pandemic. After reviewing various VE methodological issues, including vaccine effect, study design, outcomes, and exposures of interest, key covariates, and Taiwan's post-pandemic context. We propose a refined population-based retrospective cohort design. This design enables estimating direct VE against severe COVID-19 outcomes in the post-pandemic era by utilizing Taiwan's integrated national databases and incorporating validated health-seeking behavior and healthcare access markers, evidence-based underlying conditions, and advanced statistical models. The proposed design provides a scientifically valid and feasible alternative to the TND for direct COVID-19 VE assessment in the absence of a sentinel surveillance platform. It is also applicable to other respiratory-pathogen-related vaccines, such as the seasonal influenza vaccine, and to countries with similar settings.</p>","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":" ","pages":"398-403"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu-Sheng Chen, Hua-Ching Chang, Sheng-Chu Chi, Koji Tanaka, Shih-Jen Chen, Tai-Chi Lin
{"title":"Different aflibercept regimens for wet age-related macular degeneration: A systematic review and network meta-analysis.","authors":"Yu-Sheng Chen, Hua-Ching Chang, Sheng-Chu Chi, Koji Tanaka, Shih-Jen Chen, Tai-Chi Lin","doi":"10.1097/JCMA.0000000000001379","DOIUrl":"10.1097/JCMA.0000000000001379","url":null,"abstract":"<p><strong>Background: </strong>Intravitreal aflibercept injection for wet age-related macular degeneration (AMD) was initially approved with a regimen consisting of three monthly loading doses followed by maintenance doses every 8 weeks. Alternative regimens with a reduced treatment burden have been explored. The treat-and-extend (TAE) regimen involves gradually extending the treatment interval in accordance with disease activity, and the pro-re-nata (PRN) regimen involves administering injections only when signs of disease activity are observed during follow-up visits. This study evaluated these alternative regimens aimed at reducing treatment burden in real-world clinical practice.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant randomized controlled trials (RCTs). A random-effects model was adopted for network meta-analysis. Results are presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs). Methodological quality of the included RCTs was assessed using the Cochrane risk-of-bias 2.0 tool.</p><p><strong>Results: </strong>Seven RCTs (1683 patients with wet AMD) were included in the network meta-analysis. No significant inter-regimen differences were observed in visual acuity or central retinal thickness. The TAE and PRN regimens required significantly fewer injections than did bimonthly and monthly regimens, respectively (TAE vs bimonthly: SMD -1.091, 95% CI -2.030 to -0.153; TAE vs monthly: SMD -3.024, 95% CI -4.584 to -1.465; PRN vs bimonthly: SMD -1.919, 95% CI -3.307 to -0.532; PRN vs monthly: SMD -3.852, 95% CI -5.717 to -1.988). However, injection count did not differ significantly between the TAE and PRN regimens (TAE vs PRN: SMD 0.828, 95% CI -0.847 to 2.503). Nonetheless, the TAE regimen was associated with fewer clinic visits than the PRN regimen.</p><p><strong>Conclusion: </strong>The TAE regimen maintains efficacy while reducing treatment burden in patients with wet AMD receiving intravitreal aflibercept.</p>","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":" ","pages":"347-353"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical presentations and prognostication of HER2-low and HER2-zero early breast cancer in Taiwan.","authors":"Yen-Jen Grace Chen, Pei-Ju Lien, Ling-Ming Tseng, Chi-Cheng Huang","doi":"10.1097/JCMA.0000000000001376","DOIUrl":"10.1097/JCMA.0000000000001376","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor II (HER2)-low breast cancer has emerged as a clinically relevant subset of HER2-negative disease, but its prognostic significance in early-stage, real-world populations remains uncertain. We aimed to compare clinicopathological features and outcomes of HER2-low vs HER2-zero early breast cancers using a nationwide registry and to clarify the impact of hormone receptor (HR) status.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using the Taiwan Cancer Registry (2011-2020). Eligible cases were stages 0 to III HER2-negative breast cancers managed with upfront surgery. We compared clinical characteristics , overall survival (OS) and relapse-free survival (RFS). All analyses were stratified by HR (positive vs negative) and by pathological stage.</p><p><strong>Results: </strong>We analyzed 38 773 patients; 65.4% were HER2-low and 34.6% were HER2-zero. HER2-low tumors were diagnosed at a slightly younger age (median 56.3 vs 57.1 years; p < 0.001) and were more often HR-positive. Across HR- and stage-defined strata, pathological stage and HR status remained the principal determinants of prognosis. Compared with HER2-zero, HER2-low showed modestly higher hazards, with small but consistent separations in OS (91.8%, 93%, 83.3%, and 86.2% for HR-positive/HER2-low, HR-positive/HER2-zero, HR-negative/HER2-low, and HR-negative/HER2-zero breast cancers; p < 0.0001) and RFS (95.6%, 97.1%, 89.6%, and 91.1% for HR-positive/HER2-low, HR-positive/HER2-zero, HR-negative/HER2-low, and HR-negative/HER2-zero breast cancers; p < 0.0001) within strata, with the exception of stage 0.</p><p><strong>Conclusion: </strong>In Taiwanese early-stage breast cancer, HER2-low is common and associated with greater HR positivity and modestly inferior OS/RFS relative to HER2-zero after HR and stage stratification. Further studies are warranted to understand the biological and therapeutic relevance of this newly established taxonomy.</p>","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":" ","pages":"354-363"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Causal links of 233 metabolic markers to benign prostatic hyperplasia: Mendelian randomization and RNA-sequencing insights.","authors":"Pengfei Zhou, Zaisheng Zhu","doi":"10.1097/JCMA.0000000000001377","DOIUrl":"10.1097/JCMA.0000000000001377","url":null,"abstract":"<p><strong>Background: </strong>Benign prostatic hyperplasia (BPH) is a common urological condition affecting middle-aged and elderly men, and it significantly impairs their quality of life. Although metabolic disorders are suspected to contribute to BPH, the causal relationship between metabolic markers and BPH remains unclear due to the limitations of traditional observational studies.</p><p><strong>Methods: </strong>In this study, Mendelian randomization (MR) analysis was performed by integrating genome-wide association study (GWAS) data from European populations, integrating metabolites from the GWAS Catalog, BPH-related GWAS data from OpenGWAS, and gene expression data from GEO. Five regression models were used for two-sample MR analysis, with reverse MR analysis also performed. Sensitivity analyses were carried out through stringent instrumental variable selection criteria, including heterogeneity tests, horizontal pleiotropy tests, and leave-one-out analysis. Additionally, differential gene expression analysis, consensus clustering of BPH subtypes, characteristic gene screening, diagnostic model construction, immune infiltration analysis, and single-gene Gene Set Enrichment Analysis (GSEA) were performed.</p><p><strong>Results: </strong>MR analysis identified several metabolic markers, including total cholesterol, valine, and alanine in HDL, that were significantly associated with BPH, all acting as risk factors. Reverse MR analysis revealed no evidence of reverse causal effects of BPH on most metabolic markers. Additionally, distinct BPH subtypes were identified, along with three key genes (GRAMD2B, HEBP2, and STRADB). A highly accurate diagnostic model was constructed based on these genes.</p><p><strong>Conclusion: </strong>This study elucidates the causal relationship between metabolic markers and BPH, offering new insights into the etiology, diagnosis, and treatment of the disease. However, limitations include the lack of in vitro experimental validation. Future research should address these limitations, further explore the pathogenesis of BPH, and facilitate the development of more effective prevention and treatment strategies.</p>","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":" ","pages":"383-392"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chinese herbal medicine and acupuncture reduce mortality after intracerebral hemorrhage.","authors":"Dai-Ying Lin, Ming-Jen Wang, Ying-Hsiu Shih, Chiu-Lin Tsai, Yow-Wen Hsieh, Fuu-Jen Tsai, Hsien-Yin Liao, Ching-Mao Chang","doi":"10.1097/JCMA.0000000000001381","DOIUrl":"10.1097/JCMA.0000000000001381","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage (ICH) is the second most common stroke worldwide and is associated with high mortality rates. Despite established guidelines for ICH treatment, the prognosis of ICH remains poor. Traditional Chinese Medicine (TCM), including Chinese herbal medicine (CHM) and acupuncture, has been used as a complementary therapy; however, its long-term survival benefits remain uncertain.</p><p><strong>Methods: </strong>This study aimed to evaluate the effectiveness of TCM, including CHM and acupuncture, in reducing mortality among patients with ICH, using data from Taiwan's National Health Insurance Research Database. This retrospective cohort study analyzed patients with ICH (ICD-9-CM: 430-432; ICD-10-CM: I60-I62) between 2000 and 2018. Patients who received TCM or acupuncture (≥2 outpatient or ≥1 inpatient visits) were matched 1:1 with non-TCM patients based on age, sex, urbanization, and income. Mortality was the primary outcome, analyzed using Cox proportional hazards models.</p><p><strong>Results: </strong>Among 6450 patients (3225 TCM; 3225 control), TCM, including CHM and acupuncture, was significantly associated with reduced all-cause mortality in patients with ICH (adjusted hazard ratio [aHR] = 0.42; 95% CI, 0.39-0.46; p < 0.001), with CHM alone showing aHR = 0.40 (95% CI, 0.35-0.45; p < 0.001) and CHM combined with acupuncture showing aHR = 0.43 (95% CI, 0.39-0.47; p < 0.001) compared with non-TCM users. Among the top 10 single herbs used, Di-Long exhibited the greatest reduction in mortality risk (aHR = 0.36; 95% CI, 0.28-0.47; p < 0.001). Among formulas, Xue-Fu-Zhu-Yu-Tang and Chai-Hu-Jia-Long-Gu-Mu-Li-Tang demonstrated the strongest protective associations with mortality (aHR = 0.35; p < 0.001). Network core pattern analysis identified the key components of treatment, including Bu-Yang-Huan-Wu-Tang, Yuan-Zhi, Shi-Chang-Pu, Tian-Ma, and Gou-Teng. Acupuncture exhibited a similar dose-response effect, with mortality risk decreasing progressively with more sessions (aHR: for ≥18 sessions: 0.45; 95% CI, 0.40-0.49; p < 0.001).</p><p><strong>Conclusion: </strong>CHM and acupuncture are associated with lower mortality in patients with ICH. Further research is needed to confirm these findings and explore the underlying mechanisms.</p>","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":" ","pages":"364-377"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13193293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive review of current management and precision medicine in pancreatic cancer.","authors":"Hung-Yuan Yu, Le-Gin Lin, Yee Chao, Chung-Pin Li","doi":"10.1097/JCMA.0000000000001365","DOIUrl":"10.1097/JCMA.0000000000001365","url":null,"abstract":"<p><p>Pancreatic cancer is one of the most lethal malignancies, with an increasing incidence and limited improvement in survival despite therapeutic advances. Surgical resection remains the only curative option; however, recurrence is frequent, and long-term outcomes remain dismal. Major risk factors include smoking, obesity, diabetes, chronic pancreatitis, and pathogenic germline variants such as BRCA1/2, ATM, and mismatch repair genes. Routine population screening is not recommended; instead, surveillance using endoscopic ultrasonography and magnetic resonance cholangiopancreatography is recommended for high-risk individuals. Diagnosis relies on multiphasic pancreatic protocol computed tomography and histological confirmation. Treatment strategies are determined based on resectability: upfront surgery with adjuvant chemotherapy for resectable disease, neoadjuvant chemotherapy for borderline resectable or high-risk patients, and palliative chemotherapy with or without chemoradiation for locally advanced cases. Systemic therapies, including FOLFIRINOX, gemcitabine plus nab-paclitaxel, and NALIRIFOX, remain the cornerstone of therapies for metastatic disease, with precision medicine offering targeted options such as PARP inhibitors for BRCA-mutated tumors. Modern radiotherapy techniques including stereotactic body radiation therapy and particle therapy enhance local control and reduce toxicity. The integration of next-generation sequencing and multidisciplinary management is essential for improving pancreatic cancer outcomes.</p>","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":"89 4","pages":"263-270"},"PeriodicalIF":2.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan-Jie Su, Guang-Yuh Chiou, Chih-Ling Yeh, Hou-Kai Hu, Teh-Ia Huo, Yuan-Tzu Lan, Ping-Hsing Tsai, Yi-Ping Yang
{"title":"Tumor-suppressive circRNAs in colorectal cancer spheroids and patients.","authors":"Yan-Jie Su, Guang-Yuh Chiou, Chih-Ling Yeh, Hou-Kai Hu, Teh-Ia Huo, Yuan-Tzu Lan, Ping-Hsing Tsai, Yi-Ping Yang","doi":"10.1097/JCMA.0000000000001361","DOIUrl":"10.1097/JCMA.0000000000001361","url":null,"abstract":"<p><strong>Background: </strong>Cancer stem cells pose significant clinical challenges in patients with colorectal cancer, as they complicate chemotherapy treatment and reduce survival rates. Investigating cancer stem cells may help elucidate the mechanisms driving therapeutic resistance and disease progression. Recent studies suggest that circular RNAs (circRNAs) play crucial roles in tumor formation and may offer potential for early diagnosis and novel treatment strategies. However, comprehensive validations of these circRNAs remain limited to date. The aim of this study was to elucidate the molecular roles of circRNAs that are downregulated in colorectal cancer stem-like cell populations.</p><p><strong>Methods: </strong>We established 3D spheroid cultures using HCT-15 and WiDr cell lines as cancer stem cell models. Bulk RNA sequencing profiled circRNA and mRNA expression, followed by bioinformatic analyses using CircInteractome, CircBank, miRDB, and TargetScan to construct circRNA-miRNA-mRNA interaction networks.</p><p><strong>Results: </strong>CircRNA sequencing revealed predominant downregulation of circRNAs in spheroid cultures. Integration with clinical datasets comprising 788 colorectal cancer patients identified 15 circRNAs consistently downregulated in both spheroid models and metastatic tissues. Among these, hsa_circ_0039776 and hsa_circ_0067353 emerged as key tumor-suppressive candidates, predicted to regulate three oncogenic miRNAs-hsa-miR-614, hsa-miR-645, and hsa-miR-4689-significantly upregulated in advanced-stage patients. Cross-validation confirmed circRNA-miRNA and miRNA-mRNA interactions, and four tumor-suppressive genes ( CCL5 , INSC , SLC9A1 , SLC34A1 ) were associated with improved survival. Gene set enrichment analysis suggested these networks modulate cancer stem cell phenotypes, including inhibition of differentiation, resistance to apoptosis, and enhancement of DNA damage repair.</p><p><strong>Conclusion: </strong>This study identifies hsa_circ_0039776 and hsa_circ_0067353 as novel tumor-suppressive circRNAs reduced in colorectal cancer spheroids and metastatic lesions. The circRNA-miRNA-mRNA regulatory network implicates oncogenic miRNAs and downstream tumor-suppressive targets correlating with favorable survival and cancer stemness. These findings underscore the potential of circRNAs as diagnostic biomarkers and therapeutic targets in colorectal cancer.</p>","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":" ","pages":"301-311"},"PeriodicalIF":2.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"After Eprex ® discontinuation: Multicenter evidence for a biosimilar erythropoietin and health system resilience in Taiwan.","authors":"Chih-Yu Yang","doi":"10.1097/JCMA.0000000000001362","DOIUrl":"10.1097/JCMA.0000000000001362","url":null,"abstract":"","PeriodicalId":94115,"journal":{"name":"Journal of the Chinese Medical Association : JCMA","volume":" ","pages":"261-262"},"PeriodicalIF":2.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}