Rapid identification of chemical constituents and dynamic metabolic profile of Shenqi-Tiaoshen formula in rat plasma based on UPLC-Q-TOF/MSE.

Shenqi-Tiaoshen formula (SQTSF) is a traditional Chinese medicine (TCM) prescription that has been employed in the treatment of chronic obstructive pulmonary disease (COPD). Clinical practice has demonstrated that SQTSF is an effective prescription for stable COPD. However, owing to the complexity of TCM prescription, there is a lack of in-depth understanding of the chemical components of SQTSF and its in vivo metabolism studies. In this study, a comprehensive analytical strategy based on ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was established to identify the chemical components, the absorbed components, and the metabolites of SQTSF given by gavage in rats, and analyze their dynamic changes. As a result, 86 chemical components of SQTSF were characterized, which were mainly categorized into flavonoids, saponins, organic acids, terpenoids, etc. Among them, 13 compounds were confirmed unambiguously by reference standards. Furthermore, 20 prototype components and 46 metabolites were detected in rat plasma at different time points. It was found that one prototype component and thirteen metabolites could be detected during the entire 24 h, indicating that these compounds were slowly eliminated and thus accumulated in vivo over a prolonged duration. Interestingly, the phenomenon that three prototype components and fourteen metabolites reappeared after a period of disappearance from the plasma was found. It was also observed that different prototype components may generate the same metabolite. The metabolic processes of SQTSF in rats mainly included oxidation, reduction, hydration, demethylation, deglycosylation, methylation, acetylation, glucuronidation, glutathionylation, and associated combination reactions. Overall, the present study identified the chemical components of SQTSF and their dynamic metabolic profile in rat plasma, which provided a systematic and applicable strategy for screening and characterization of the prototype components and metabolites of TCM compound preparations.

Inducing the Abscopal Effect in Liver Cancer Treatment: The Impact of Microwave Ablation Power Levels and PD-1 Antibody Therapy.

Microwave ablation (MWA) is an effective treatment for liver cancer (LC), but its impact on distant tumors remains to be fully elucidated. This study investigated the abscopal effects triggered by MWA treatment of LC, at different power levels and with or without combined immune checkpoint inhibition (ICI). We established a mouse model with bilateral subcutaneous LC and applied MWA of varied power levels to ablate the right-sided tumor, with or without immunotherapy. Left-sided tumor growth was monitored to assess the abscopal effect. Immune cell infiltration and distant tumor neovascularization were quantified via immunohistochemistry, revealing insights into the tumor microenvironment and neovascularization status. Th1- and Th2-type cytokine concentrations in peripheral blood were measured using ELISA to evaluate systemic immunological changes. It was found that MWA alone, especially at lower power, promoted distant tumor growth. On the contrary, combining high-power MWA with anti-programmed death (PD)-1 therapy promoted CD8+ T-cell infiltration, reduced regulatory T-cell infiltration, upregulated a Th1-type cytokine (TNF-α) in peripheral blood, and inhibited distant tumor growth. In summary, combining high-power MWA with ICI significantly enhances systemic antitumor immune responses and activates the abscopal effect, offering a facile and robust strategy for improving treatment outcomes.