Cardinal Tien Hospital

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Despite advances in targeted therapies, 2drug resistance and limited efficacy in KRAS-mutant CRC continue to present clinical challenges. Antrodia cinnamomea, a medicinal fungus, demonstrates antitumor properties; however, the mechanisms of its triterpenoid compound, 4-acetylantrocamol LT3 (LT4), remain unclear. The present study investigated the effects of LT4 on KRAS-mutant HCT116 CRC cells using cell viability, colony formation and migration assays. Western blotting was also employed to examine key signaling pathways. Transcriptome profiling via RNA sequencing was followed by Kyoto Encyclopedia of Genes and Genomes/Gene Ontology enrichment and protein-protein interaction network analyses using STRING, CytoHubba and Molecular Complex Detection (MCODE). Molecular docking with PI3Kγ (PDB: 1E7U) was conducted to evaluate the predicted binding position and docking energy of LT4. The results indicated that LT4 significantly inhibited HCT116 cell proliferation and migration, induced a mesenchymal-to-epithelial transition, suppressed PI3K/AKT/mTOR and ERK signaling and activated the GSK3β/FOXO and phosphorylated-p38/p21 axes. LT4 also reduced the levels of cyclooxygenase-2 and anti-apoptotic proteins (Bcl-2 and Bcl-XL) and reduced the expression of the mitochondrial respiratory chain protein cytochrome c oxidase subunit IV. Transcriptomic analysis identified the PI3K/AKT pathway as the most significantly enriched signaling cascade. Network topology analyses highlighted solute carrier family 3 member 2, Cyclin D1, phosphoserine aminotransferase 1 and ChaC glutathione-specific γ-glutamylcyclotransferase 1 as central nodes, linking the effects of LT4 to nutrient signaling, redox homeostasis and serine metabolism. Molecular docking confirmed that LT4 stably occupied the ATP-binding pocket of PI3Kγ with a binding energy comparable to wortmannin and a conformation similar to antroquinonol. In conclusion, to the best of our knowledge, the present study is the first to comprehensively demonstrate the multi-target anti-CRC effects of LT4, highlighting its potential as a therapeutic agent, especially in KRAS-mutant CRC.

The palatine tonsils and adenoids are critical inductive sites for the mucosa-associated lymphoid tissue (MALT) system, educating B cells for salivary defense. While their removal is common, the long-term impact on mucosal autoimmunity remains unclear. We hypothesized that disrupting this lymphoid network increases susceptibility to Sjögren's syndrome (SS). Using the TriNetX US Collaborative Network (2006-2023), we conducted a retrospective cohort study matching 302,737 patients who underwent tonsillectomy/adenoidectomy with 302,737 non-surgical controls (propensity score-matched 1:1). Hazard ratios (HR) for incident SS were estimated using Cox proportional hazards models. The surgical cohort exhibited a significantly elevated risk of SS (HR 1.52; 95% CI 1.23-1.87; p<0.001) compared to controls. This risk was most profound in individuals operated on before age 18 (HR 2.27) and in African American patients (HR 2.26). Sensitivity analyses using negative outcome controls (e.g., burns, injuries) confirmed the specificity of the association. Tonsillectomy is independently associated with an increased risk of SS. These findings suggest that early-life removal of nasopharyngeal lymphoid tissue may disrupt the MALT axis, impairing oral tolerance and predisposing to salivary autoimmunity.

Oropharyngeal squamous cell carcinoma (OPSCC) is increasing worldwide, with a well-established link to human papillomavirus (HPV). However, evidence on how lifestyle risk factors-particularly smoking, alcohol consumption, and betel-quid chewing-modify the prognostic impact of HPV-associated disease remains limited, especially in regions with high exposure burden such as Taiwan. Understanding the interplay between viral and lifestyle determinants is essential for accurate prognostication and treatment planning. We conducted a retrospective cohort study of 5,671 OPSCC patients using data from the Taiwan Cancer Registry between 2018 and 2021. p16 status was used as a surrogate marker for HPV infection. Overall survival and cancer-specific survival were compared across p16 status, age, sex, tumor location, cancer stage, lifestyle risk factors and treatment pattern using Kaplan-Meier method and multiple Cox models. Treatment-stratified analyses were additionally performed to evaluate whether lifestyle risk factors modified prognosis within p16-positive disease. Overall, 23.2% of OPSCC cases were p16-positive, with substantially higher p16 positivity among females (52.5%) and in tonsillar subsites. p16-positive patients had significantly better 5-year overall survival (69.0%; 95% CI, 66.0%-71.8%) than p16-negative patients (37.9%; 36.1%-39.6%). However, among p16-positive individuals, the presence of multiple lifestyle risk factors markedly attenuated the survival advantage, reducing 5-year overall survival from 78.6% (74.0%-82.5%) in those without lifestyle exposures to 57.6% (52.6%-62.4%) in those with smoking plus other risks. These gradients persisted after multivariable adjustment and across treatment modalities. In contrast, lifestyle risk factors were not independently associated with survival in p16-negative OPSCC, where prognosis was primarily driven by tumor stage, subsite, and treatment. This nationwide study provides novel evidence that the prognostic benefit associated with p16 positivity is substantially attenuated by multiple lifestyle risk factors. These findings highlight the importance of integrating viral and behavioral determinants into prognostic assessment and treatment planning. They also underscore the need to pair HPV-associated prevention strategies with efforts to reduce tobacco, alcohol, and betel-quid use in regions with high burdens of these exposures.

Glaucoma is a leading cause of irreversible blindness worldwide. Current diagnostic methods often fail to detect disease at early stages. MicroRNAs (miRNAs), owing to their regulatory role in gene expression, have been investigated as potential biomarkers, although their diagnostic utility and clinical feasibility remain under evaluation. The aim of this work is to systematically review and synthesize evidence on the diagnostic significance of microRNAs and related genetic markers in glaucoma and its subtypes. A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including 16 studies with 17,300 participants. Odds ratios (ORs) and log ORs with 95% confidence intervals (CIs) were pooled using fixed-effects models. Subgroup analyses were performed by sample type, glaucoma subtype, and molecular pathway. Specific miRNAs (e.g., miR-143-3p, miR-182) were significantly associated with glaucoma (OR 6.32, 95% CI 5.31-7.54, p < 0.001). Stronger correlations were observed in aqueous humor samples (OR 13.79, 95% CI 6.81-27.94, p < 0.001). Dysregulation of miRNAs was linked to increased retinal ganglion cell apoptosis and altered aqueous humor osmolality. Genetic analysis showed that common alleles in ATOH7 (OR 1.55, 95% CI 1.40-1.72) and CDKN2B (OR 1.66, 95% CI 1.55-1.78) significantly increased glaucoma risk, while miR182 variants also showed strong associations. The autotaxin (ATX)-lysophosphatidic acid (LPA) pathway was consistently implicated (OR 3.94, 95% CI 2.46-6.32). MiRNAs, particularly in blood samples, show promise as feasible biomarkers for early glaucoma detection, while aqueous-humor-based testing remains clinically limited owing to invasiveness. Genetic variants such as ATOH7, CDKN2B, and miR182 modestly but consistently contribute to glaucoma susceptibility. Large-scale longitudinal studies are warranted to validate these findings and translate them into routine clinical practice.

Background: Chronic periodontal disease (CPD) may contribute to systemic inflammation and adverse outcomes in patients undergoing maintenance hemodialysis, but age-specific risks remain unclear. We aimed to evaluate the association between CPD and clinical outcomes in hemodialysis patients, stratified by age.Methods: We conducted a retrospective cohort study using the TriNetX Research Network. Adults aged 45-64 or ≥65 years initiating maintenance hemodialysis were included. CPD exposure was defined using ICD-10-CM codes documented within 6 months before or up to 5 years after hemodialysis initiation. Outcomes included all-cause mortality, pneumonia, fracture, and major adverse cardiovascular events (MACE) over a 5-year follow-up period. Propensity score matching was conducted within each age group using a comprehensive model that included age, sex, race, comorbidities, medications, and laboratory values. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox models. Subgroup and sensitivity analyses were conducted to assess robustness and effect modification.Results: CPD was significantly associated with increased risks of all-cause mortality in both younger (aHR = 1.313, 95% CI: 1.129-1.527; p<0.001) and older patients (aHR = 1.126, 95% CI: 1.048-1.209; p=0.001), with stronger associations in the younger group. Subgroup analysis showed elevated mortality risks in younger males, females, and non-diabetic individuals. Pneumonia risk was significantly increased across both age groups, with particularly high risks in younger females and older males. CPD was also associated with a higher risk of fracture, particularly among older adults (aHR = 1.673, 95% CI: 1.375-2.036; p<0.001), with consistent findings across subgroups. No significant associations were observed between CPD and MACE in either age stratum. Sensitivity analyses adjusting for comorbidities and inflammatory markers supported the primary findings.Conclusion: CPD is associated with increased risks of mortality, pneumonia, and fractures among hemodialysis patients, with variation by age and clinical subgroup. These findings support integrating periodontal screening and preventive strategies into hemodialysis care. Younger patients may benefit from early intervention to reduce infection and mortality risk, while older adults may require targeted skeletal protection.

IntroductionBronchiectasis exhibits substantial heterogeneity across geographic locations and includes a diverse range of aetiologies. Limited large-scale data are available for Southeast Asian countries.MethodsThis was a multicentre, retrospective, observational cohort study. Between January 2017 and June 2020, comprehensive clinical data were collected on enrolment, and 1-year follow-ups were conducted using an electronic case report form.ResultsA total of 2753 patients were enrolled. The mean age of the patients was 67 years. Forty-two per cent (1150/2753) of patients were male. The mean modified Reiff score was 5.0±3.3. The proportions of bacteria, tuberculosis and nontuberculous mycobacteria cultured from sputum within 1 year of follow-up were 46% (381/829), 1% (10/829) and 24% (202/829), respectively. The most prevalent bacterial isolate was Pseudomonas aeruginosa (22%), followed by Klebsiella pneumoniae (11%). Airflow obstruction was observed in 32% of patients, and 39% used inhaled bronchodilators. A substantial proportion (57%) of the patients were prescribed mucolytics. Seventeen per cent of the patients experienced severe exacerbations within a year. One-year all-cause mortality rate was 2% (52 of 2563 patients). Female patients demonstrated more severe imaging findings than male patients (modified Reiff score, 5.2 vs 4.6, p<0.001). However, they exhibited less obstructive lung function impairment (26% vs 40%, p<0.001), experienced fewer severe exacerbations (15% vs 20%, p=0.002) and had lower mortality rates (2% vs 5%, p<0.001). The risk of severe exacerbation and mortality increased significantly among patients older than 80 years.ConclusionAlthough female patients with bronchiectasis exhibited more severe imaging findings, their prognoses were better in Taiwan. Elderly patients older than 80 years had worse prognosis.

To compare corneal deflection characteristics during air-puff before and after keratorefractive procedures using a mathematical method. The authors collected Corvis ST (Oculus Optikgeräte GmbH) corneal images from 86 eyes after photorefractive keratectomy (PRK), 93 eyes after laser in situ keratomileusis (LASIK), and 76 eyes after small incision lenticule extraction (SMILE). Using these images, corneal deflection was quantified and modal coefficients obtained over time through a decomposition method. The results were then compared among individual patients to identify differences before and after surgery. SMILE surgery increased corneal deflection by a quantifiable amount with less dependence on the depth of removed tissue, demonstrating up to 1.46 times (maximum) greater modal deflection changes compared with other surgeries. In contrast, in PRK and LASIK, corneal deflection was increased with greater ablation depth. Inter-patient variability was the largest in PRK, particularly in lower-order modes, which affected a large central area. Higher-order modes of the decomposition method in the central area demonstrated that SMILE and PRK exhibited similar patterns before air-puff, whereas SMILE and LASIK exhibited similar deflection patterns during air-puff. A significant difference between LASIK and SMILE was observed in transient deflection during the early air-puff phase and the ending phase. This computational method could comprehensively analyze the overall corneal bending over time. The results suggest the use of LASIK and PRK for patients with low myopia and SMILE for patients with high myopia.

Intrinsic radioresistance in non-small-cell lung cancer (NSCLC) is partially driven by adaptive redox mechanisms that prevent oxidative cell death. Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a potential therapeutic vulnerability in tumors with elevated antioxidant capacity. However, its mechanistic integration with radiotherapy remains incompletely understood. We compared the effects of three clinically approved VEGFR-targeting tyrosine kinase inhibitors (TKIs), cabozantinib, lenvatinib, and ripretinib, on NSCLC cell viability with and without radiation. Subsequent mechanistic studies focused on cabozantinib and included ferroptosis rescue assays (ferrostatin-1, deferoxamine), lipid ROS quantification, glutathione assays, clonogenic survival, co-immunoprecipitation of BECN1-SLC7A11 complexes, and BECN1 knockdown by siRNA and shRNA. All three TKIs were evaluated for cytotoxicity, but only cabozantinib significantly reduced NSCLC cell viability in combination with radiation in a ferroptosis-dependent manner. Cabozantinib inhibited STAT3 phosphorylation and downregulated MCL1, resulting in the release of BECN1. This allowed BECN1 to bind and suppress SLC7A11, disrupting system Xc- function, depleting glutathione, and promoting lipid ROS accumulation. Genetic silencing of BECN1 reversed these effects and restored redox balance and clonogenic capacity. Lenvatinib and ripretinib failed to elicit similar responses, indicating that the inhibition of non-VEGFR targets (e.g., MET, AXL) may be essential for ferroptosis induction by cabozantinib. Cabozantinib enhances the radiosensitization of NSCLC cells through ferroptosis induction mediated by the suppression of the STAT3/MCL1/BECN1/SLC7A11 axis. These findings uncover a novel mechanism linking kinase inhibition to redox imbalance and suggest that the pharmacologic modulation of ferroptosis using multi-target TKIs may represent a rational approach to overcome radioresistance in NSCLC.