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.

Background: Chemoradiotherapy is the standard treatment for esophageal cancer, but the optimal radiation dose remains undetermined. A dose of 50.4 Gy is commonly used in both neoadjuvant and definitive settings. This study evaluates the outcomes of using 50.4 Gy in neoadjuvant chemoradiotherapy (nCRT). Methods: Patients with esophageal cancer who underwent nCRT with 50.4 Gy radiation followed by surgery between 2010 and 2023 were retrospectively analyzed. They were categorized as achieving pathological complete response (pCR patients) or not (non-pCR patients). Oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS), were assessed. Results: Among 258 patients treated with nCRT, 96.5% completed the treatment protocol, and 74.4% (n=192) proceeded to surgery. These 192 patients formed the analysis cohort. The overall complication rate was 70.3%, with 19.3% classified as major complications. The 30-day and 90-day postoperative mortality rates were both 0.5%. The pCR rate was 45%. Patients with pCR had a 3-year OS rate of 72.7% and a median survival of 125 months, whereas non-pCR patients had a 3-year OS rate of 49.6% and a median survival of 35 months (p=0.002). Additionally, pCR patients had a 3-year RFS rate of 62.0% and a median RFS of 68 months, compared to 33.6% and 20 months, respectively, for non-pCR patients (p<0.001). Conclusion This study reports the outcomes of using 50.4 Gy in nCRT for locally advanced esophageal cancer. The findings affirm the efficacy of 50.4 Gy neoadjuvant chemoradiotherapy in achieving favorable long-term outcomes, particularly among patients with complete pathological response.

Objective: To construct a prognostic model for unsuccessful removal of nasogastric tube (NGT) was the aim of our study. Methods: This study examined patients with swallowing disorders receiving NGT feeding due to stroke or traumatic brain injury in a regional hospital. Clinical data was collected, such as age, sex, body mass index (BMI), level of activities of daily living (ADLs) dependence. Additionally, gather information regarding the enhancement in Functional Oral Intake Scale (FOIS) levels and the increase in food types according to the International Dysphagia Diet Standardization Initiative (IDDSI) after one month of swallowing training. A stepwise logistic regression analysis model was employed to predict NGT removal failure using these parameters. Results: Out of 203 patients, 53 patients (26.1%) had experienced a failed removal of NGT after six months of follow-up. The strongest predictors for failed removal were age over 60 years, underweight BMI, total dependence in ADLs, and ischemic stroke. The admission prediction model categorized patients into high, moderate, and low-risk groups for removal failure. The failure rate of NGT removal was high not only in the high-risk group but also in the moderate-risk groups when there was no improvement in FOIS levels and IDDSI food types. Conclusion Our predictive model categorizes patients with brain insults into risk groups for swallowing disorders, enabling advanced interventions such as percutaneous endoscopic gastrostomy for high-risk patients struggling with NGT removal, while follow-up assessments using FOIS and IDDSI aid in guiding rehabilitation decisions for those at moderate risk.

AIMThe structure of the human penile venous system has been well studied, but disappointing outcomes of penile venous surgery in certain patients have called into question on the anatomy. We planned to extend the anatomic knowledge with the ultimate goal of improving operative success.

METHODSThirty-five patients, who had undergone penile venous surgery, complained of poor erection developed gradually 6 months to 7 years postoperatively. Cavernosography was performed again during their return visit. Seven new patients underwent spongiosography followed by immediate cavernosography. Eleven male cadavers were carefully dissected. The anatomical findings were applied to venous surgery in 155 patients, who were then followed with the International Index of Erectile Function Questionnaire-5 (IIEF-5).

RESULTSImaging observation demonstrated that the deep dorsal vein served as a common vessel of the corpora cavernosa and corpus spongiosum. A prominent cavernosal vein was found coursing along each corpus cavernosum distally to the glans, in contrast to its reported description as a short segment at the penile hilum. All cadavers had two sets of para-arterial veins sandwiching the dorsal artery. In 148 men available for follow-up, their mean IIEF-5 score was 9.3 preoperative and increased to 22.7 after the operation. The 88.5% (131/148) of the patients believed that venous stripping was a worthy treatment modality. Five cases required sildenafil to maintain their potentia, which was not working preoperatively.

CONCLUSIONSThe failure of penile venous surgery has traditionally been ascribed to penile vein regeneration. However, our finding of a long and independent cavernosal vein and an independent set of para-arterial veins may be the principal cause in patients experiencing poor postoperative results.

Aged ; Dissection ; Erectile Dysfunction ; surgery ; Humans ; Male ; Penis ; blood supply ; diagnostic imaging ; surgery ; Phlebography ; Veins ; anatomy & histology ; surgery