Exploring blood metabolites and thyroid disorders: a bidirectional mendelian randomization study.

Background: Human blood metabolites have demonstrated close associations with thyroid disorders in observational studies. However, it's essential to determine whether these correlations imply causation. Mendelian Randomization (MR) offers a promising approach to investigate these patterns. Aims: The primary aim of our investigation is to establish causality between blood metabolites and three thyroid disorders: TC, GD, and HT. Methods: We employed a two-sample bidirectional MR analysis approach to assess the relationships between 452 blood metabolites and the three aforementioned thyroid disorders. Causal links were estimated using the IVW method, with sensitivity analyses conducted via MR-Egger, Weighted Median, and MR-PRESSO. We assessed potential heterogeneity and pleiotropy using MR-Egger intercept and Cochran's Q statistic. Additionally, we conducted pathway analysis to identify potential metabolic pathways. Results: We found 46 metabolites that showed suggestive associations with thyroid disease risk, especially Aspartate (ORIVW=7.41; 95%CI: 1.51-36.27; PIVW=0.013) and C-glycosyltryptophan (ORIVW=0.04; 95%CI: 0.00-0.29; PIVW=0.001) impacted TC, Kynurenine (ORIVW=2.69; 95%CI: 1.08-6.66; PIVW=0.032) and 4-androsten-3beta,17beta-diol disulfate 2 (ORIVW=0.78; 95%CI: 0.48-0.91; PIVW=0.024) significantly impacted GD, and Alpha-ketoglutarate (ORIVW=46.89; 95%CI: 4.65-473.28; PIVW=0.001) and X-14189-leucylalanine (ORIVW=0.31; 95%CI: 0.15-0.64 PIVW=0.001) significantly impacted HT. We also detected 23 metabolites influenced by TC and GD. Multiple metabolic pathways have been found to be involved in thyroid disease. Conclusion: Our MR findings suggest that the identified metabolites and pathways can serve as biomarkers for clinical thyroid disorder screening and prevention, while also providing new insights for future mechanistic exploration and drug target selection.

MiR-3677-3p promotes development and sorafenib resistance of hepatitis B-related hepatocellular carcinoma by inhibiting FOXM1 ubiquitination.

Being encoded by hepatitis B, hepatitis B X (HBx) protein plays crucial roles in hepatitis B-related hepatocellular carcinoma (HCC) occurrence, development, and metastasis. miRNAs also function in the progression of hepatitis B-related HCC. Hence, the objective of this study was to explore the impacts of miR-3677-3p on tumor progression and sorafenib resistance in hepatitis B-related HCC and the related underlying mechanisms. Our research revealed that miR-3677-3p and FOXM1 was up-regulated and FBXO31 was down-regulated in HBV+ HCC cells and tumor tissues from nude mice. After miR-3677-3p overexpression, cell proliferative, invasive, and migrating potentials and stemness-related protein (CD133, EpCAM, and OCT4) levels were enhanced, and cell apoptosis was reduced in Huh7 + HBx/SR cells and HepG2.2.15/SR cells. Besides, miR-3677-3p promoted the drug resistance of Huh7 + HBx/SR cells and HepG2.2.15/SR cells to sorafenib and lifted IC50. In vivo experiments, miR-3677-3p down-regulation suppressed the tumor growth in the hepatitis B HCC nude mouse models. Mechanistically, miR-3677-3p targeted and negatively-regulated FBXO31 and FBXO31 could enrich FOXM1 protein. miR-3677-3p down-regulation or FBXO31 overexpression promoted the ubiquitylation of FOXM1. In a word, miR-3677-3p bound to FBXO31 and inhibited FBXO31 expression, thus curtailing the ubiquitylation degradation of FOXM1, contributing to HCC development and sorafenib resistance.

Tension-free hiatal hernia repair with biological mesh: A real-world experience.

Laparoscopic Nissen fundoplication and esophagoplasty are the standards for gastroesophageal reflux disease (GERD) and hiatal hernia (HH) repair. Biologically derived mesh is also associated with reduced recurrence. This study attempted to evaluate the effectiveness of a biological mesh in the 4K laparoscopic repair of HH. This retrospective study reviewed patients with a severe GERD complicated with HH from August 2019 to August 2020. All patients underwent the HH repair using a biological mesh under a 4K laparoscope accompanying Nissen fundoplication. Up to 16 months postoperatively, GERD-health-related quality-of-life (GERD-HRQL) scale, radiologic studies on HH recurrence, and symptoms were recorded. The mean surgical time and postoperative hospital stay were 70.9 ±â€…8.72 min, 4.8 ±â€…0.76 days, respectively. The postoperative symptom relief rate was 96.5%, and no recurrence exhibited during follow-up. Dysphagia occurred in 10 (9.43%) patients. There were no intraoperative vagus nerve injury or postoperative complications, mesh infection, and reoperation for mesh. The tension-free repair of HH with the biological mesh is an option for clinical use, with effectiveness and few short-term complications being reported.