Aim To investigate the apoptosis of lung cancer cells A549 induced by quercetin and the regulation of survivin and Bcl-2 on A549 cells induced by quercetin.Methods MTT,fluorescence stain,flow cytometric analysis and immunocytochemistry stain were carried out.Results Quercetin had a significant inhibition on growth and proliferation of A549 cell in a concentration-and time-dependent manner.Evidence was provided that apoptosis occurred in A549 cells treated with quercetin using fluorescence microscopy.Quercetin arrested A549 cells at the G0/G1 phase by FCM analyses.Expression of survivin and Bcl-2 protein were decreased,and activity of caspase-3 were enhanced.Conclusion Quercetin could induce apoptosis of A549 cells.The arrested cell cycle and the down-regulation of survivin and Bcl-2 protein could activate caspase-3 resulting in cells apoptosis,which may contribute to the apoptosis mechanisms.The down-regulated survivin and Bcl-2 may play an important role in A549 cells apoptosis induced by quercetin.

Objective:To analyze the influencing factors of achieving textbook outcome (TO) after pancreaticoduodenectomy (PD) in patients with pancreatic ductal adenocarcinoma, and to construct a nomograph model to explore its predictive value in TO.Methods:The clinical data of 205 patients with pancreatic ductal adenocarcinoma treated by PD in Henan University People's Hospital from January 2019 to December 2022 were analyzed retrospectively, including 88 males and 117 females with the age of (61.3±9.8) years old. Patients were divided into two groups based on whether they achieved TO after surgery: TO group ( n=113) and non-TO group ( n=92). Clinical data such as age, gender, intraoperative blood loss, operation time, blood transfusion volume, pancreatic CT value, and tumor differentiation degree were collected. Logistic regression analysis screened the influencing factors of PD postoperative TO and built a nomogram model. The performance of the nomogram model was evaluated using receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis. Results:Multivariate logistic regression analysis showed that the higher the degree of tumor differentiation was in patients with pancreatic ductal adenocarcinoma (high differentiation to medium differentiation: OR=7.20, 95% CI: 1.20-43.28; high differentiation to low differentiation: OR=16.55, 95% CI: 2.01-136.11), CT value>38.45 Hu ( OR=0.29, 95% CI: 0.13-0.65), blood transfusion volume ≤350 ml ( OR=8.05, 95% CI: 2.94-22.01) and operative time ≤407.5 min ( OR=10.88, 95% CI: 3.90-30.41), the easier it was to achieve TO after PD (all P<0.05). Based on the above influencing factors, a nomogram model of the postoperative effect of PD on TO was established, and the consistency index of this column graph model was 0.863 (95% CI: 0.816-0.911). The sensitivity and specificity of ROC curve were 0.804 and 0.752, respectively. The calibration diagram showed that the calibration curve fits well with the ideal curve, and the decision curve showed that the model had obvious positive net benefit. Conclusion:The degree of tumor differentiation, CT value, blood transfusion volume, and operation time are independent influencing factors for the achievement of TO after PD in patients with pancreatic ductal adenocarcinoma, and the nomogram model constructed based on which has good predictive performance for TO.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.