Objective To explore the enzymatic reaction kinetics of metoprolol tartrate in an in vitro human liver microsome incubation experiment and to explore the effect of famotidine on the metabolism of metoprolol tartrate.Methods An LC-MS/MS method was developed to accurately measure the concentration of metoprolol tartrate in a human liver microsomal incubation system.A human liver microsome incubation system was established to determine the optimal incubation time and protein concentration;using the substrate depletion method,the enzymatic reaction kinetics parameters of metoprolol tartrate(such as Vmax and Km).Series concentrations of famotidine were co-incubated with metoprolol tartrate,and the concentration of metoprolol tartrate was measured to evaluate the effect of famotidine on its metabolism.Results The optimal incubation time for metoprolol tartrate in human liver microsomes was found to be 60 minutes,with an optimal protein concentration of 1.0 mg/mL.The enzymatic reaction kinetics parameters were Vmax=0.07 μmol/min/mg protein and Km=7.84 μmol/L.Conclusion The results indicated that famotidine did not produce a significant inhibitory effect on the metabolism of metoprolol tartrate in human liver microsome incubation system,suggesting that the combination of these two drugs may be relatively safe.

Non-small cell lung cancer(NSCLC)is a prevalent and aggressive global malignancy.Conventional sur-gical treatments,radiotherapy,chemotherapy,and targeted therapies often fall short in halting disease progression due to inher-ent limitations,resulting in suboptimal prognosis.Despite the advent of immunotherapy drugs offering new hope for NSCLC treatment,current efficacy remains insufficient to meet all patient needs.Therefore,actively exploring novel immunotherapeu-tic approaches to further reduce mortality rates in NSCLC patients has become a crucial focus of NSCLC research.This article aims to systematically review the anti-tumor effects ofinterleukin-21 and follicular helper T cells in NSCLC immunotherapy by summarizing and analyzing relevant literatures from both domestic and international sources,as well as exploring the potential for enhancing NSCLC treatment prospects through immune checkpoint regulation via immunotherapeutic means.

Objective To investigate the expression of histamine in the cardiac sympathetic fibers from the guinea pig superior cervical ganglion and its coexistence with norepinephrine so as to provide morphological evidence for histamine as a cardiac sympathetic neurotransmitter.Methods Biotinylated dextranamine(BDA) anterograde tracing and immunofluorescence histochemical staining for histamine/norepinephrine were applied.Results After injection of BDA into the superior cervical ganglion,BDA labeled sympathetic fibers in the left and right atria and ventricle were observed.Meanwhile,the tracing fibers proved histamine-like immunoreactive or both histamine and norepinephrine-like immunoreactive.Conclusion Histamine is expressed in the cardiac sympathetic fibers from the guinea pig superior cervical ganglion and coexisted with norepinephrine.