Taoyuan Armed Forces General 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.

Purpose: Fetal bovine serum (FBS) is widely used in cell culture due to its rich nutrient and growth factor content, but it poses ethical concerns, biosafety risks, and cost limitations. This study investigates plasma-depleted lyophilized (freeze-dried) porcine platelet lysate (pPL) as a potential alternative to FBS for use in cell-based research and biomanufacturing. Materials and Methods: Fresh porcine blood was processed to obtain plasma-depleted pPL using double centrifugation and repeated freeze–thaw cycles. The lysate was analyzed for growth factor content via ELISA, then freeze-dried and sterilized with gamma irradiation. Endotoxin levels and cytotoxicity were evaluated. The ability of plasma-depleted lyophilized pPL to promote cell proliferation was assessed using L929 fibroblast cultures and compared with FBS. Results: Plasma-depleted lyophilized pPL contained significantly higher levels of TGF-β1 than FBS. The freeze-dried product remained stable for at least three months at room temperature. Gamma irradiation effectively sterilized the lysate without degrading key growth factors. Plasma-depleted lyophilized pPL showed no cytotoxicity and promoted greater proliferation of L929 cells compared to FBS, indicating enhanced mitogenic activity. Conclusions: Plasma-depleted lyophilized pPL is a stable, safe, and growth factor-rich alternative to FBS. It supports fibroblast proliferation, retains bioactivity after sterilization and storage, and may provide a scalable, ethical option for cell culture in biomedical research, regenerative medicine, and therapeutic product development.

BACKGROUND Concomitant infected aortic aneurysm and liver abscess is extremely rare and potentially fatal. Their simultaneous occurrence suggests an aggressive disease course and presents substantial diagnostic and therapeutic challenges. Because symptoms are often nonspecific, diagnosis is frequently delayed, which can lead to worse outcomes. Early recognition through timely imaging and a coordinated multidisciplinary approach are essential for optimizing clinical results. CASE REPORT A 65-year-old woman with a history of hypertension and diabetes mellitus presented with a 1-week history of epigastric pain, fever, and constipation. Laboratory studies showed leukocytosis and elevated inflammatory markers. Chest radiography showed an opacity in the left lower lung field. Contrast-enhanced CT demonstrated a focal aneurysmal dilatation of the descending thoracic aorta measuring 8.0×7.1×5.0 cm with an irregular wall and surrounding fat stranding, consistent with a mycotic aneurysm, and a hypodense hepatic lesion with peripheral enhancement, suggestive of a liver abscess. Empirical antibiotic therapy with piperacillin-tazobactam and vancomycin was initiated. Given the patient's and family's preference, comorbidities, and high surgical risk, thoracic endovascular aortic repair (TEVAR) was selected as the primary intervention. Blood cultures grew Klebsiella pneumoniae sensitive to piperacillin-tazobactam, prompting discontinuation of vancomycin. She improved steadily and was discharged after 40 days. Follow-up CT at 2 months showed no recurrence. CONCLUSIONS This case highlights the critical role of early imaging in detecting rare co-infections and supports TEVAR with targeted antibiotics as an effective, less invasive treatment for high-risk patients.

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.

Background: Myocardial perfusion scintigraphy (MPS) is an important tool for evaluating ischemia in diabetic populations. However, applications of advanced predictive models like multivariate adaptive regression splines (MARS) to estimate summed stress scores (SSS) are lacking. Methods: In this study, 1028 diabetic women undergoing Thallium-201 MPS were analyzed. The dataset was split into training (80%) and testing (20%) subsets. MARS and multiple linear regression (MLR) models were constructed to predict SSS, and their performance was evaluated using root mean square error (RMSE), relative absolute error (RAE), root relative squared error (RRSE), Mean Absolute Percentage Error (MAPE), and Symmetric Mean Absolute Percentage Error (SMAPE). Results: On the testing dataset, the MARS model outperformed the MLR model across all metrics, with an RMSE of 3.25 compared to 3.89 for MLR, an RAE of 0.52 vs. 0.64, and an RRSE of 0.53 vs. 0.67. Similar trends were observed in MAPE (18.7% vs. 22.1%) and SMAPE (17.3% vs. 20.5%). Conclusions: The superior predictive accuracy of the MARS model suggests its potential to enhance non-invasive myocardial risk stratification in diabetic women.

Herpes zoster (HZ) has emerged as a post-viral complication in COVID-19 survivors, but its long-term clinical impact remains uncertain. This retrospective cohort study utilized the TriNetX Global Collaborative Network to evaluate whether HZ reactivation after COVID-19 is associated with increased risks of mortality, cardiovascular, and renal outcomes. Adults diagnosed with HZ within one year of COVID-19 were propensity score–matched 1:1 with controls without HZ. A total of 48,442 matched patients were followed for three years. Compared with controls, HZ patients had significantly higher risks of major adverse cardiovascular events (HR: 1.38, 95% CI: 1.30–1.46), acute kidney injury (HR: 1.67, 95% CI: 1.55–1.80), and renal function decline defined by eGFR < 60 mL/min/1.73 m² (HR: 1.28, 95% CI: 1.20–1.37). Although no significant difference in overall all-cause mortality was observed across the full follow-up period, time-stratified analysis revealed a biphasic pattern: patients with HZ had lower mortality risk during the first 90 days but showed significantly higher mortality from day 91 to three years post-COVID-19 (HR: 1.33, 95% CI: 1.24–1.44). Subgroup analyses consistently identified older age, chronic comorbidities, impaired renal function, and systemic inflammation as risk enhancers across outcomes. These findings suggest that HZ reactivation after COVID-19 signals a vulnerable subgroup predisposed to cardiorenal complications. Targeted follow-up and risk-based interventions are warranted in this population.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-16398-3.

Background: Obesity is a global health challenge associated with metabolic and cardiovascular diseases. Traditional Chinese Medicine (TCM) body constitution theory offers a unique perspective on individual susceptibility to obesity; however, its integration into public health strategies remains underexplored. Objective: To examine the associations between vegetarian dietary patterns, TCM body constitution types (Phlegm stasis, Yang deficiency, and Yin deficiency), and overweight/obesity in a large-scale national cohort. Methods: Data were obtained from 3597 participants enrolled in the Taiwan Biobank. Socio-demographic variables, lifestyle behaviors (diet, smoking, physical activity), and anthropometric indicators (BMI and waist circumference) were assessed. Participants were categorized by weight status and TCM body constitution. Polytomous logistic regression models were used to evaluate associations between vegetarian dietary patterns, constitution types, and overweight/obesity, adjusting for potential confounders. Results: Among participants (mean age, 50.1 ± 9.4 years), 55.6% had normal BMI, 27.3% were overweight, and 17.1% were obese. Vegetarian dietary patterns were significantly associated with lower odds of Phlegm stasis (OR: 0.96; p < 0.001), Yang deficiency (OR: 0.97; p < 0.001), and Yin deficiency (OR: 0.97; p < 0.001), as well as with lower odds of overweight (OR: 0.72; p < 0.05) and obesity (OR: 0.67; p < 0.05). Physical activity was also associated with lower odds of all three constitution types and obesity. Phlegm stasis constitution was associated with higher odds of obesity (range of ORs: 1.18-1.58; p < 0.001). Conclusions: Vegetarian dietary patterns and regular physical activity were associated with lower odds of obesity and TCM constitution imbalances, particularly Phlegm stasis. These findings suggest a potential role for constitution-informed strategies in obesity-related public health approaches. Longitudinal studies are warranted to clarify temporal relationships and mechanisms. Clinical Trials Registration: ClinicalTrials.gov NCT03938207 (Study Start: 1 October 2022).

Background: Carpometacarpal thumb arthritis causes pain and functional limitations. Methods: This study evaluated the efficacy of arthroscopic partial trapeziectomy with free palmar longus tendon suspension and interpositional arthroplasty, combined with a soft anchor internal brace, for the treatment of thumb basal joint arthritis. Between August 2010 and April 2020, 60 thumbs with symptomatic basal joint arthritis (Eaton stage II–III) were treated using this minimally invasive technique. Results: The cohort included 52 female and 8 male patients (mean age, 62.6 ± 4.3 years), who underwent clinical follow-up for 28.7 ± 3.0 months. VAS pain scores decreased from 5.7 ± 0.5 to 1.0 ± 0.7 and 7.1 ± 0.6 to 1.4 ± 0.9 (p < 0.001) during rest and activity, respectively. Thumb range of motion increased from 43.3 ± 11.3 to 54.2 ± 9.8 degrees, while pinch strength improved from 47.3 ± 9.5% to 88.8 ± 17.3% of the contralateral side (p < 0.001). Patients with Eaton stage II disease demonstrated better outcomes than those with stage III disease. Radiographically, minimal proximal migration of the first metacarpal (mean, 1.2 mm) was observed, with no cases of scaphotrapezial joint arthritis. Conclusions: Arthroscopic partial trapeziectomy with tendon suspension/interposition and an internal brace is an effective treatment for Eaton stage II–III basal joint arthritis, offering significant pain relief, functional improvement, and joint stability, while preserving the scaphotrapezial joint.

The benefit of high-dose trimethoprim/sulfamethoxazole (trimethoprim component ≥ 8 mg/kg/day) treatment for Stenotrophomonas maltophilia infections remains unclear. We aimed to evaluate the effect of high-dose trimethoprim/sulfamethoxazole treatment on outcomes in patients with S. maltophilia bacteraemia. We conducted a single-centre retrospective cohort study (2004-23) that included patients treated with trimethoprim/sulfamethoxazole for monomicrobial S. maltophilia bacteraemia. The patients were categorized into two groups based on the trimethoprim/sulfamethoxazole dose: high-dose (trimethoprim component ≥ 8 mg/kg/day) and low-dose (trimethoprim component < 8 mg/kg/day) groups for comparison. The primary endpoint was 30-day mortality. Adverse drug events between groups were also compared. Multivariable logistic regression and inverse probability of treatment weighting (IPTW) analysis were performed. A total of 143 patients treated with trimethoprim/sulfamethoxazole for S. maltophilia bacteraemia were included: 41 (28.7%) received the high-dose regimen, and 102 (71.3%) received the low-dose regimen. There was no significant difference in 30-day mortality between the high- and low-dose group (39.0% versus 26.5%; P = 0.139). Multivariable regression revealed that high-dose trimethoprim/sulfamethoxazole therapy was not associated with mortality (adjusted OR 1.96, 95% CI 0.75-5.10; P = 0.167) after adjustment. The IPTW-adjusted regression yielded consistent results. More adverse drug events were reported in the high-dose group (31.7% versus 12.7%, P = 0.008). High-dose trimethoprim/sulfamethoxazole for S. maltophilia bacteraemia was not associated with improved outcomes while more frequent adverse drug events were observed. The sample size and retrospective design limit the study's conclusions. Future studies that address these limitations are needed to confirm the results.