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Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver injury. However, the underlying mechanisms appear to be multifaceted and there are few effective treatments. In this study, we used the 2′-Hydroxycinnamaldehyde (HCA), an active ingredient extracted from cinnamon stem bark to evaluate the therapeutic effect against APAP-induced ALI. The results indicated that pyruvate kinase M2 (PKM2)-mediated aerobic glycolysis may activate NLRP3 inflammasome in APAP-induced ALI, However, this process was prevented by HCA. Additionally, overexpression of PKM2 by adeno-associated virus (AAV9-PKM2) in vivo and plasmid (PKM2-OE) in vitro reversed the inhibition of NLRP3 inflammasome by HCA. Intriguingly, the HCA-triggered repressive pyroptosis was mediated through dephosphorylation and nuclear translocation of PKM2. Furthermore, the therapeutic effect of HCA on APAP-induced ALI was achieved by partially stimulating the Akt-mTOR signaling pathway, thus inhibiting the PKM2-NLRP3 axis. These findings elucidate that a potential drug to the clinical treatment of APAP overdose by HCA.

Abstract Background Hepatocellular Carcinoma (HCC) is a common malignant neoplasm with limited treatment options and poor outcomes. Thus, there is an urgent need to find sensitive biomarkers for HCC. Methods Gene expression and clinicopathological information were obtained from public databases, based on which a pyroptosis-related gene signature was constructed by the least absolute shrinkage and selection operator Cox regression. The applicability of the signature was evaluated via Kaplan–Meier curve and time-dependent ROC curve. TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT, ssGSEA, and ESTIMATE were employed to assess the immune status. Comparisons between groups were analyzed with Wilcoxon test. Pearson and Spearman correlation analyses were adopted for linear correlation analysis. Genetic knockdown was conducted using siRNA transfection and the mRNA expression levels of interest genes were measured using quantitative reverse transcription PCR. Finally, protein levels in 10 paired tumor tissues and adjacent non-tumor tissues from HCC patients were measured using immunohistochemistry. Results A pyroptosis-related gene signature was established successfully to calculate independent prognostic risk scores. It was found that survival outcomes varied significantly between different risk groups. In addition, an attenuated antitumor immune response was found in the high-risk group. Meanwhile, multiple immune checkpoints were up-regulated in high-risk score patients. Cell cycle-related genes, angiogenesis-related genes and tumor drug resistance genes were also markedly elevated. Knockdown of prognostic genes in the signature significantly inhibited the expression of immune checkpoint genes and angiogenesis-related genes. Besides, each prognostic gene was expressed at a higher level in HCC tissues than in adjacent normal tissues. Conclusions We successfully established a novel pyroptosis-related gene signature which could help predict the overall survival and assess the immune status of HCC patients.

Objective: This study aimed to explore the effect of ward-noise-reduction management on the mental health and quality of life of patients with inflammatory bowel disease. Methods: The medical records of 275 patients with inflammatory bowel disease admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2020 to January 2023 were retrospectively analyzed. Routine care was performed for such hospitalized patients from January 2020 to July 2021. Thus, 124 patients were enrolled in the control group. From August 2021 to January 2023, our hospital implemented ward-noise-reduction management for such inpatients, and 151 patients were included in the observation group. The Athens Insomnia Scale (AIS), the State-Trait Anxiety Inventory, the Inflammatory Bowel Disease Questionnaire (IBDQ), and the noise level at the time of admission and discharge were compared. Results: No significant difference in the State Anxiety Scale (S-AI), Trait Anxiety Scale (T-AI), and AIS and IBDQ scores at baseline existed between the two groups (P >0.05). After nursing, the S-AI, T-AI, and AIS scores of the observation group were lower than those of the control group, and the IBDQ score of the observation group was higher than that of the control group (P < 0.05). The noise level of the observation group was lower than that of the control group during hospitalization in maximum sound level and average intermediate (P < 0.05). Conclusions: The application of ward-noise-reduction management in the nursing of patients with inflammatory bowel disease can improve their negative mood, improve their sleep quality, and quality of life, and reduce the ward noise level in maximum sound level and average intermediate, which has high clinical value. [ABSTRACT FROM AUTHOR]