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Aerobic glycolysis is a typical metabolic rearrangement for tumorigenesis. Arecoline is of explicit carcinogenicity, numerous works demonstrate its mutagenicity, genotoxicity, and cytotoxicity. However, the effects of arecoline on aerobic glycolysis of esophageal epithelial cells remain unclear. In the present study, 5 μM arecoline efficiently increased HK2 expression to induce aerobic glycolysis in Het‐1A‐Are and NE2‐Are cells. The mechanistic analysis showed that arecoline activated the Akt‐c‐Myc signaling pathway and reduced the GSK3β‐mediated phosphorylation of c‐Myc on Thr58 to prevent its ubiquitination and destruction, subsequently promoting HK2 transcription and expression. Taken together, these results suggest that arecoline can induce aerobic glycolysis of esophageal epithelial cells and further confirm that arecoline is a carcinogen harmful to human health. [ABSTRACT FROM AUTHOR]

Background: Cholelithiasis or cholecystectomy may contribute to the development of gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) through bile reflux; however, current observational studies yield inconsistent findings. We utilized a novel approach combining meta-analysis and Mendelian randomization (MR) analysis, to assess the association between them., Methods: The literature search was done using PubMed, Web of Science, and Embase databases, up to 3 November 2023. A meta-analysis of observational studies assessing the correlations between cholelithiasis or cholecystectomy, and the risk factors for GERD, BE, and EACwas conducted. In addition, the MR analysis was employed to assess the causative impact of genetic pre-disposition for cholelithiasis or cholecystectomy on these esophageal diseases., Results: The results of the meta-analysis indicated that cholelithiasis was significantly linked to an elevated risk in the incidence of BE (RR, 1.77; 95% CI, 1.37-2.29; p  < 0.001) and cholecystectomy was a risk factor for GERD (RR, 1.37; 95%CI, 1.09-1.72; p  = 0.008). We observed significant genetic associations between cholelithiasis and both GERD (OR, 1.06; 95% CI, 1.02-1.10; p  < 0.001) and BE (OR, 1.21; 95% CI, 1.11-1.32; p  < 0.001), and a correlation between cholecystectomy and both GERD (OR, 1.04; 95% CI, 1.02-1.06; p  < 0.001) and BE (OR, 1.13; 95% CI, 1.06-1.19; p  < 0.001). After adjusting for common risk factors, such as smoking, alcohol consumption, and BMI in multivariate analysis, the risk of GERD and BE still persisted., Conclusion: Our study revealed that both cholelithiasis and cholecystectomy elevate the risk of GERD and BE. However, there is no observed increase in the risk of EAC, despite GERD and BE being the primary pathophysiological pathways leading to EAC. Therefore, patients with cholelithiasis and cholecystectomy should be vigilant regarding esophageal symptoms; however, invasive EAC cytology may not be necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Cai, Chen, Zhu, Feng, Jin and Ma.)

Enhanced protein synthesis is a crucial molecular mechanism that allows cancer cells to survive, proliferate, metastasize, and develop resistance to anti-cancer treatments, and often arises as a consequence of increased signaling flux channeled to mRNA-bearing eukaryotic initiation factor 4F (eIF4F). However, the post-translational regulation of eIF4A1, an ATP-dependent RNA helicase and subunit of the eIF4F complex, is still poorly understood. Here, we demonstrate that IBTK, a substrate-binding adaptor of the Cullin 3-RING ubiquitin ligase (CRL3) complex, interacts with eIF4A1. The non-degradative ubiquitination of eIF4A1 catalyzed by the CRL3 IBTK complex promotes cap-dependent translational initiation, nascent protein synthesis, oncogene expression, and cervical tumor cell growth both in vivo and in vitro. Moreover, we show that mTORC1 and S6K1, two key regulators of protein synthesis, directly phosphorylate IBTK to augment eIF4A1 ubiquitination and sustained oncogenic translation. This link between the CRL3 IBTK complex and the mTORC1/S6K1 signaling pathway, which is frequently dysregulated in cancer, represents a promising target for anti-cancer therapies., Competing Interests: DJ, HS, XZ, YC, ZL, QS, YL, CW, KG No competing interests declared, (© 2023, Jiao, Sun et al.)

Objectives: To explore the basic clinical characteristics and relevant factors affecting the early postoperative prognosis in patients with infective endocarditis (IE)., Methods: A total of 702 patients with IE, who underwent surgery in Xiangya Hospital, Central South University from January 1981 to June 2019, were studied and the data were collected through the paper records and the hospital information system. The patients from January 1981 to June 2010 served as an early group ( n =224), and other patients from July 2010 to June 2019 served as a recent group ( n =478). Independent risk factors for early postoperative death were determined by logistic regression analysis., Results: The mean age of the 702 patients was 36.7±16.1 years, and the male accounted for 68.1%. Preoperative stroke occurred in 71 patients (10.1%), and dialysis was done in 14 patients (2%) preoperatively. Streptococcus were the pathogenic bacteria in 172 patients, accounting for 59.5% of all positive blood culture results. In the early group, the percentage of IE combined with congenital heart disease was significantly higher than that in the recent group [77 patients (34.4%) in the early group vs 22 patients (4.6%) in the recent group; P <0.05]. Postoperative stroke occurred in 15 patients (2.1%), while 59 patients (7%) required new dialysis postoperatively because of renal insufficiency. Twenty-nine patient died in the post-operation, with 4.1% in 30-day mortality. Logistic regression analysis revealed that the high preoperative New York Heart Association (NYHA) grade of cardiac function (OR=3.22, 95% CI 1.50-6.88; P <0.01), postoperative stroke (OR=5.75, 95% CI 1.22-27.07; P <0.05), postoperative dialysis (OR=15.53, 95% CI 3.50-68.82; P <0.01), perivalvular abscess (OR=13.19, 95% CI 3.83-45.42; P <0.01) and multivalve involvement (OR=3.57, 95% CI 1.24-10.30; P <0.05) were the independent risk factors for early mortality., Conclusions: Streptococcus is the most common pathogenic bacteria in the patients with IE. Surgery for IE can obtain a satisfactory early outcomes. High preoperative NYHA grade of cardiac function, postoperative stroke, postoperative dialysis, perivalvular abscess and multivalve involvement are the independent risk factors for early mortality.

Objective: To observe the results of different treatment of congenital heart disease (CHD) complicated with severe pneumonia in infants.
 Methods: A total of 27 infants with CHD and severe pneumonia were admitted to the Department of Pediatrics, Xiangya Hospital from January 2014 to December 2014, of whom 18 were male and 9 were female. The average age was 2.0-19.0(5.9±4.3) months, with an average body weight of 3.3-10.0 (5.8±1.8) kg. Infants were treated with a strategy of complete control of the lung infection before surgery (internal medicine group). From January 2015 to December 2015, 29 infants with same condition were admitted, of whom 15 were males and 14 females. The average age was 2.0-27.0 (6.1±3.9) months, with an average body weight of 3.1-8.0 (4.8±1.0) kg. Infants were treated with a strategy of combined treatment (combined treatment group), in which early surgical treatment were performed after a short time antibiotics and supportive treatment.
 Results: One nosocomial death in internal medicine group, with an average hospital stay for 3-26 (11±6) d. Further surgeries were performed in 5 patients after discharge with no surgical death. The mean preoperative hospital stay in combined treatment group was 1-21 (10±6) d. The mean total hospital stay for combined treatment group was 14-48 (24±9) d and the mean postoperative hospital stay was 6-35 (14±7) d. One patient died soon after surgery in combined treatment group. Thirty-day follow-up found that no other patient died in combined treatment group, and 6 patients died in internal medicine group. The 30-day mortality was 3.4% in combined treatment group and 22.2% in internal medicine group (P<0.01).
 Conclusion: Infant congenital heart disease complicated with severe pneumonia requires early surgical treatment, which contributed to the control of pulmonary infection and reduce mortality.