The therapeutic use of glimepiride and gliclazide shows substantial inter-individual variation in pharmacokinetics and pharmacodynamics in human populations, which might be caused by genetic differences among individuals. The aim of this study was to assess the effect of CYP2C9 and OATP1B1 genetic polymorphisms on the metabolism and transport of glimepiride and gliclazide. The uptake of glimepiride and gliclazide was measured in OATP1B1*1a, *5 and *15-HEK293T cells, and their metabolism was measured using CYP2C9*1, *2 and *3 recombinase by LC-MS. Glimepiride in OATP1B1*1a, *5 and *15-HEK293T cells had Vmax values of 155 ± 18.7, 80 ± 9.6, and 84.5 ± 8.2 pmol/min/mg, while gliclazide had Vmax values of 15.7 ± 4.6, 7.2 ± 2.5, and 8.7 ± 2.4 pmol/min/mg, respectively. The clearance of glimepiride and gliclazide in OATP1B1*5 and *15 was significantly reduced compared to the wild-type. Glimepiride in the presence of CYP2C9*1, *2 and *3 recombinase had Vmax values of 21.58 ± 7.78, 15.69 ± 5.59, and 9.17 ± 3.03 nmol/min/mg protein, while gliclazide had Vmax values of 15.73 ± 3.11, 10.53 ± 4.06, and 6.21 ± 2.94 nmol/min/mg protein, respectively. The clearance of glimepiride and gliclazide in CYP2C9*2 and *3 was significantly reduced compared to the wild-type. These findings collectively indicate that OATP1B1*5 and *15 and CYP2C9*2 and *3 have a significant effect on the transport and metabolism of glimepiride and gliclazide.

Objective: To assess the clinical utility of the ratio of CD4+CD25+CD127 low regulatory T cells (Tregs) in subjects at high risk of HCC, investigate the relationship between the percentage of Tregs and the expression of transforming growth factor (TGF)-β1 and interleukin (IL)-10 in patients with hepatocellular carcinoma before and after treatment. Methods: Peripheral venous blood was collected from patients with liver cancer before and after treatment. The proportion of CD4+CD25+CD127 low Tregs was detected by flow cytometry. The levels of TGF-β1 and IL-10 in serum were detected by enzyme-linked immunosorbent assay, and were compared with healthy subjects as a control group. Results: The proportion of CD4+CD25+CD127 low to CD4+T lymphocytes in patients with hepatocellular carcinoma was significantly higher than that in healthy controls (P<0.01). The proportion of CD4+CD25+CD127 low Tregs, whose AUC of ROC curve was 0.917, could effectively separate the HCC patients from the healthy subjects with a diagnostic sensitivity of 90%, specificity of 80%. The proportion of CD4+CD25+CD127 low to CD4+T lymphocytes and the levels of TGF-β1 and IL-10 in patients with hepatocellular carcinoma after the operation and chemotherapy were significantly lower than those before treatment (P<0.05).The proportion of CD4+CD25+CD127 low Tregs was positively correlated with the concentrations of TGF-β1 and IL-10 before and after treatment of primary liver cancer (P<0.05). Conclusion: CD4+CD25+CD127 low Tregs may be a significant predictor of HCC biopsy outcome and play an inhibitory role on effector T cells by regulating cytokines.

Overall, this study indicates OATP1B1 in human and oatp1b2 in rats might participate in the hepatic uptake of OPD.

Background: Lung cancer is one of the most common cancers, the symptoms and treatment of which can cause negative emotions like anxiety, depression, and cancer-related fatigue (CRF). Nonpharmacological interventions, serving as alternative therapies, can greatly alleviate CRF in lung cancer patients. Previous meta-analyses have reported nonpharmacological interventions of CRF in lung cancer patients, but the results may be conflicting, and the reporting and methodological qualities remain unknown. Moreover, there is limited evidence to identify efficient and safe non-pharmacological interventions of CRF in lung cancer patients. This study aims to assess the therapeutic efficacy of nonpharmacological interventions of CRF in lung cancer patients through a network meta-analysis.Methods: Relevant literatures reporting non-pharmacological interventions of CRF in lung cancer patients published before June 2021 will be searched in online databases, including Wanfang, VP Information Chinese Journal Service Platform, China National Knowledge Infrastructure, Chinese BioMedicine Literature Database, PubMed, Embase, Cochrane, and Web of science. Two reviewers will be independently responsible for study selection, quality appraisal, and data extraction. Data analysis will be performed using the STATA14.0 and GEMTC 0.14.3 software.Results: This meta-analysis will provide additional and stronger evidences for nonpharmacological interventions of CRF in lung cancer patients. Our findings will be conductive to make therapeutic decisions by clinicians.Conclusion: This study will provide a reliable evidence-based basis for non-pharmacological interventions of CRF in lung cancer patients.Ethics and dissemination: Ethical approval was not required for this study. The systematic review will be published in a peerreviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peerreviewed journal or conference presentations.