Introduction: Triphala, an Ayurvedic polyherbal formulation composed of Terminalia chebula Retz., Terminalia bellirica (Gaertn.) Roxb., and Phyllanthus emblica L., is associated with metabolic regulation. This study evaluated the lipid-lowering effects of Triphala aqueous extract (TPL) in a therapeutic rat model of hypercholesterolemia and explored a potential mechanism involving 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition. Methods: Male Wistar rats received cholesterol (2 g/kg, intragastric) in corn oil for 3 weeks to induce hypercholesterolemia. After biochemical confirmation, rats were assigned to six groups (n = 6 each): normal diet, hypercholesterolemic control, atorvastatin (10 mg/kg), or TPL (250, 500, and 1000 mg/kg). Cholesterol administration continued throughout the 6-week treatment period. Serum lipid profiles and body weight were monitored. HMG-CoA reductase inhibition by TPL and individual fruit extracts was assessed. Results: TPL 250 and 500 mg/kg significantly reduced total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), whereas TPL 500 mg/kg significantly increased high-density lipoprotein cholesterol (P<0.05). TPL 1000 mg/kg produced lipid-lowering effects comparable to atorvastatin and significantly decreased the atherogenic index of plasma at week 6. In vitro, TPL inhibited HMG-CoA reductase by 36.4±1.5% (5 µg/mL), compared with 82.5 ± 2.4% for pravastatin (0.5 µg/mL). Among individual fruit extracts, P. emblica exhibited the strongest inhibitory activity, followed by T. chebula and T. bellirica, while the combined TPL retained appreciable activity. TPL 1000 mg/kg also attenuated diet-induced body weight gain. Conclusion: TPL exerts significant lipid-lowering and weight-regulating effects under sustained cholesterol challenge, partly mediated by HMG-CoA reductase inhibition, supporting its potential as a natural adjunct for dyslipidemia.

Background/Objectives: Periductal fibrosis (PDF) is a common hepatobiliary abnormality associated with chronic Opisthorchis viverrini infection and may represent an ultrasonographic marker of chronic biliary injury in liver fluke-endemic regions. This systematic review and meta-analysis evaluated the association between ultrasound-defined PDF and cholangiocarcinoma (CCA)-related outcomes and summarized the prevalence of overall PDF and advanced periductal fibrosis (APF) in endemic populations. Methods: PubMed, Embase, and Scopus were searched from database inception to April 2026, supplemented by manual screening of reference lists. Observational studies reporting PDF prevalence and/or the association between PDF and CCA-related outcomes were included. Pooled odds ratios (ORs) and prevalence estimates were calculated using random-effects models. Five studies met the inclusion criteria. Results: Three studies involving 758,686 participants were included in the pooled association analysis. Ultrasound-defined PDF was associated with higher odds of CCA-related outcomes, including confirmed CCA, incident CCA, and clinically suspected CCA, with a pooled OR of 2.77 (95% CI: 2.24–3.44; I² = 0%). Because outcome definitions, effect measures, adjustment status, and PDF exposure categories varied across studies, this estimate should be interpreted as a summary association rather than as a precise estimate of confirmed CCA risk. Four studies involving 759,117 participants contributed to the overall PDF prevalence analysis, whereas three studies reported APF prevalence data. Prevalence estimates varied substantially across endemic settings, with extreme between-study heterogeneity. Conclusions: Overall, ultrasound-defined PDF may help identify individuals who warrant closer surveillance or further evaluation; however, it should not be interpreted as a definitive histopathological diagnosis or a proven causal precursor of CCA. Further prospective studies using standardized fibrosis definitions, blinded ultrasonographic assessment, confirmed or incident CCA outcomes, and adjustment for O. viverrini infection-related factors and other key confounders are needed to validate the role of PDF in CCA risk stratification.

Background and Objectives: Hereditary medullary thyroid carcinoma (hMTC) exhibits substantial clinical heterogeneity according to the underlying germline RET pathogenic variant. Although the germline RET M918T pathogenic variant is associated with aggressive disease, its associations with clinical outcomes have not been comprehensively quantified. We aimed to evaluate the associations between the M918T variant and adverse clinical outcomes in patients with hMTC. Materials and Methods: PubMed, Scopus, and Embase were searched from database inception to May 2026 in accordance with PRISMA 2020. Eligible studies compared patients with the germline RET M918T pathogenic variant with those harboring other germline RET pathogenic variants. Random-effects models were used to pool odds ratios (ORs) and 95% confidence intervals (CIs) for lymph node metastasis, metastatic disease, advanced-stage disease, and mortality. Risk of bias was assessed using the Quality in Prognosis Studies tool. The protocol was prospectively registered in PROSPERO (CRD420261377120). Results: Nine cohort studies involving 1485 participants were included, with outcome-specific sample sizes varying. Three studies had a low overall risk of bias and six had a moderate risk. The M918T variant was associated with increased odds of lymph node metastasis (OR 7.86, 95% CI 2.58–23.94), metastatic disease (OR 6.50, 95% CI 3.72–11.37), advanced-stage disease (OR 4.88, 95% CI 2.30–10.33), and mortality (OR 7.32, 95% CI 3.14–17.10). The association was stronger for disease-specific than all-cause mortality, although the subgroup difference was not statistically significant. Conclusions: The germline RET M918T pathogenic variant was associated with adverse clinical outcomes compared with other germline RET pathogenic variants. However, heterogeneous comparator groups and residual confounding preclude causal interpretation.