OBJECTIVETo explore permeability of artificial blood-brain barrier (aBBB) by oxygen-glucose deprivation combined (OGD)-induced using tetramethylpyrazine combined with puerarin in vitro.

METHODRats were divided into normal control group, model group, tetramethylpyrazine group, puerarin group, tetramethylpyrazine-puerarin group and nimodipine group. Culture rat brain microvascular endothelial cells and astrocytes in vitro and build the OGD-induced aBBB damage model. Evaluate aBBB damage characteristics by TEER, gamma-GT, AKP and LDH. Determine contents of tetramethylpyrazine, puerarin, nimodipine and calculate drug permeating concentration of OGD-induced aBBB model by HPLC.

RESULTCompared with the model, the level of TEER was lower than the control group with significant difference (P < 0.01). The levels of gamma-GT, AKP in tetramethylpyrazine group, tetramethylpyrazine-puerarin group and nimodipine group were higher than the model group, the differences were significant (P < 0.01). Compared with tetramethylpyrazine group or puerarin group, the level of AKP of tetramethylpyrazine-puerarin group increased significantly (P < 0.01). The differences of levels of TEER, gamma-GT, AKP and LDH between tetramethylpyrazine-puerarin group and nimodipinthe group were significant (P < 0.05). Tetramethylpyrazine-puerarin group has a synergistic effect of increasing TEER, gamma-GT, AKP and reducing LDH. The permeating rate in tetramethylpyrazine-puerarin group was higher than tetramethylpyrazine group and puerarin group.

CONCLUSIONTetramethylpyrazine-puerarin can permeate aBBB more easily and protect aBBB. The cause may relate to reducing the permeability of the OGD-induced aBBB.

Animals ; Blood-Brain Barrier ; drug effects ; Drug Combinations ; Glucose ; physiology ; Isoflavones ; administration & dosage ; pharmacology ; Male ; Oxygen ; physiology ; Permeability ; Pyrazines ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley

Objective To compare the cost-utility of tislelizumab and sorafenib in the first-line treatment of advanced unresectable hepatocellular carcinoma,and to provide a reference for the selection of treatment regimens from the perspective of pharmacoeconomics.Methods A partitioned survival model was used to simulate the survival status of patients using tislelizumab or sorafenib within 10 years,and the cost and health output were calculated respectively to obtain the incremental cost-utility ratio(ICUR).The 3 times China's per capita gross domestic product(GDP)in 2022 was taken as the threshold for willingness to pay(WTP).Results During the simulation period,the ICER of tislelizumab versus sorafenib was 280 691.4 yuan/quality-adjusted life year(QALY),which was significantly higher than that of the sorafenib group,which had obvious economic performance.Univariate sensitivity analysis showed that the incidence of grade 3 or above adverse reactions in the tislelizumab group,the cost of tislelizumab,and the incidence of grade 3 or higher adverse reactions in the sorafenib group were important factors affecting ICUR.Probabilistic sensitivity analysis showed that tislelizumab had a significant cost-utility advantage when WTP was 3 times GDP,with an economic probability of 81.4％,and the results were robust.Conclusion For the first-line treatment of advanced unresectable hepatocellular carcinoma,tislelizumab has a significant cost-utility advantage over sorafenib.