Search

Abstract Background Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed to provide further insight into the integrated transcriptomic and proteogenomic landscape and identify a new target involved in HCC progression following iRFA. Methods Peripheral blood and matched tissue samples were collected from 10 RFA-treated HCC patients. Multiplex immunostaining and flow cytometry were used to assess local and systemic immune responses. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. Proteinase-3 (PRTN3) was identified in these analyses. And then, the ability of PRTN3 to predict overall survival (OS) was assessed in 70 HCC patients with early recurrence after RFA. In vitro CCK-8, wound healing and transwell assays were conducted to observe interactions between Kupffer cells (KCs) and HCC cells induced by PRTN3. The protein levels of multiple oncogenic factors and signaling pathway components were detected by western blotting. A xenograft mouse model was built to observe the tumorigenic effect of PRTN3 overexpression on HCC. Results Multiplex immunostaining revealed no immediate significant change in local immune cell counts in periablational tumor tissues after 30 min of iRFA. Flow cytometry showed significantly increased levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127− Tregs and significantly decreased the levels of CD16+CD56+ natural killer cells on day 5 after cRFA (p

Background and aimsMethamphetamine (MA) is a psychostimulant associated with a high relapse rate among patients with MA use disorder (MUD). Long-term use of MA is associated with mental disorders, executive dysfunction, aggressive behaviors, and impulsivity among patients with MUD. However, identifying which factors may be more closely associated with relapse has not been investigated. Thus, we aimed to investigate the psychological factors and the history of MA use that may influence MA relapse.MethodsThis cross-sectional study included 168 male MUD patients (MUD group) and 65 healthy male residents (control group). Each patient was evaluated with self-report measures of executive dysfunction, psychopathological symptoms, impulsiveness, aggressiveness, and history of MA use. Data were analyzed with t-tests, analyses of variance, and correlation and regression analyses.ResultsThe MUD group reported greater executive dysfunction, psychopathological symptoms, impulsivity, and aggression than the control group. Lower age of first MA use was associated both with having relapsed one or more times and with having relapsed two or more times; greater executive dysfunction was associated only with having relapsed two or more times.ConclusionPatients with MUD reported worse executive function and mental health. Current results also suggest that lower age of first MA use may influence relapse rate in general, while executive dysfunction may influence repeated relapse in particular. The present results add to the literature concerning factors that may increase the risk of relapse in individuals with MUD.