Background: Type 2 diabetes mellitus (T2DM) is a complex, multifactorial disease with a significant global burden. Although genome-wide association studies (GWAS) have identified many T2DM-associated variants, most lie in non-coding regions, making it difficult to interpret their functional roles. Methods: We aimed to identify genetically regulated Cytosine–phosphate–Guanine (CpG) sites associated with T2DM by conducting a methylome-wide association study (MWAS), followed by Mendelian randomization (MR) and functional validation using human pancreatic cells and mouse models. MWAS was performed using summary statistics from large-scale GWAS and a DNA methylation (DNAm) prediction model to test associations between genetically predicted DNAm and T2DM. Results: We identified 111 CpG sites significantly associated with T2DM in Europeans, including 8 novel sites near genes not previously linked to T2DM. These findings were replicated in independent datasets. Many CpGs also showed associations with cardiometabolic traits, highlighting shared epigenetic mechanisms. Trans-ethnic MR analysis confirmed consistent effects for six CpGs in East Asians. Functional analysis revealed that several CpGs regulate gene expression in human pancreatic α- and β-cells. Among them, 2´-5´-oligoadenylate synthetase like (OASL) expression, regulated by a significant CpG, was differentially expressed in α-cells of T2DM cases compared to controls. Supporting evidence from mouse models suggests a role for OASL in glucose regulation. Conclusion Our study identifies novel genetically regulated CpG sites associated with T2DM risk and highlights OASL as a potential epigenetic regulator of glucose metabolism in α-cells. These findings provide mechanistic insights into the epigenetic architecture of T2DM and suggest potential targets for cross-ethnic biomarker development and therapeutic intervention.

Purpose: Transarterial chemoembolization (TACE) delivers cytotoxic drugs intra-arterially and induces ischemic necrosis by arterial embolization. Embolization is achieved using a variety of agents that differ widely in particle size and range, deformation, and in vivo arterial distribution. The clinical significance of these differences has not been thoroughly characterized. The present study is to compare the efficacy of Embosphere and Embozene microspheres in TACE therapy for hepatocellular carcinoma. Materials and Methods: This retrospective study includes 108 hepatocellular carcinoma (HCC) patients who received TACE/doxorubicin with Embozene (70 patients) or Embosphere (38 patients) at a single medical center. Patient outcomes, including liver function, tumor size, tumor response, and complications after treatment, were analyzed. The change in total target lesion size and tumor response was evaluated according to embolization agent and clinical characteristics. Results: The postoperative glutamate oxaloacetate transaminase (mean, 194.5 vs. 147.5; p=0.032) and bilirubin (mean, 1.11 mg/dL vs. 0.73 mg/dL; p=0.016) were higher among patients treated with Embozene, the decrease in the number (55.86±25.55% vs. 41.81±38.51%, p=0.027) and size (56.37±25.91 mm vs. 43.44±37.89 mm, p=0.001) of liver tumors relative to baseline was greater in these patients than in those treated with Embosphere. These greater antitumor effects were achieved using lower doses of doxorubicin than for treatment with Embozene. Minor complications were more common among patients treated with Embosphere than with Embozene. Conclusion These results suggest that Embozene is more efficacious than Embosphere for HCC treatment using TACE/doxorubicin.

Background: Liver regeneration is dependent on the proliferation of hepatocytes. Hepatic progenitorcells are intra-hepatic precursor cells capable of differentiating into hepatocytes or biliary cells.Although liver progenitor cell proliferation during the regenerative process has been observed in animalmodels of severe liver injury, it has never been observed in vivo in humans because it is unethicalto take multiple biopsy specimens for the purpose of studying the proliferation of liver progenitorcells and the roles they play in liver regeneration. Associating liver partition and portal vein ligationfor staged hepatectomy (ALPPS) is a staged procedure for inducing remnant liver hypertrophy sothat major hepatectomy can be performed safely. This staged procedure allows for liver biopsyspecimens to be taken before and after the liver begins to regenerate. Case presentation: The liverprogenitor cell proliferation is observed in a patient undergoing ALPPS for a metastatic hepatictumour. Liver biopsy is acquired before and after ALPPS for the calculation of average number ofliver progenitor cell under high magnification examination by stain of immunomarkers. This is thefirst in vivo evidence of growing liver progenitor cells demonstrated in a regenerating human liver.

OBJECTIVETo compare the differences of two recommended diagnostic criteria for metabolic syndrome (MS) in a health check-up population aged 12-19 years in Taiwan province.

METHODThe study data were supplied by the MJ Health Screening Center, which is a private membership chain clinic with 4 health screening centers around the Taiwan Island and provides periodic health examination to its members. The database included a self-administered questionnaire for health history, asking about demographic, socioeconomic, medical, and lifestyle information, and clinical and laboratory measures for every member. A total of 1629 members (873 boys and 756 girls, respectively) received a health check-up first time at MJ centers were recruited from 2005 to 2006. MS detection rate and agreement rate was calculated according to two definitions, respectively. The distributions of MS components and the aggregation of risk factors were further analyzed.

RESULT(1) The range of age-adjusted detection rate of MS for two definitions were 4.05% (5.84% for boys, 1.98% for girls) and 8.35% (10.42% for boys, 5.95% for girls), respectively. It was 0.94% , 14.20% and 36.59% for criterion I among adolescents who were overweight (BMI over 95th percentile), at risk of overweight (BMI between 85th and 95th percentile) and normal weight (BMI below the 85th percentile), respectively; while 3.61%, 25.93% and 53.66% for criterion II. (2) The range of five MS components were 9.09% (low-HDL-C)-16.39% (high blood pressure) for definition I, while 0.98% (high FBG)-27.13% (high WC) for definition II. (3) Of the total subjects, 2.76%, 1.04% and 0.25% were presented with three, four and five MS risk factors for definition I; while 6.69%, 1.60% and 0.34% for definition II, separately. (4) The most common clinical symptom complex of MS was "obesity, hypertension and low-HDL-C" for criterion I, "high TG, obesity and low-HDL-C" for criterion II. (5) The MS diagnostic criterions of I and II were in moderate accordance with agreement rate of 94.35%, Kappa index was 0.518.

CONCLUSIONOur findings reveal that there were relatively large differences in detection and aggregation of risk components on MS when using two recommended definitions, the detection rate of MS in adolescents depends strongly on the parameters chosen and their respective cut-off points. In order to avoid possible relevant under- or over-estimation of the prevalence, it seems advisable that the use of unversally specific cut-off values seems to be more appropriate to give more reliable results.

Adolescent ; Adult ; Child ; Cross-Sectional Studies ; Diagnostic Techniques and Procedures ; standards ; Female ; Humans ; Male ; Metabolic Syndrome ; diagnosis ; Reference Standards ; Taiwan