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Objective:To evaluate the predictive performance of the individualized drug delivery decision-making system including Smart Dose, PharmVan and JPKD on predicting the Vancomycin plasma concentration and to analyze the related factors affecting the predictive performance.Methods:The clinical data of patients who were treated with Vancomycin and received therapeutic drug monitoring (TDM) admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2018 to July 2020 were retrospectively collected. Smart Dose and PharmVan were used to predict the plasma concentration of Vancomycin of the initial regimen. Smart Dose, PharmVan and JPKD were used to predict the plasma concentration of Vancomycin of the adjustment regimen for patients whose initial steady-state trough concentration were not qualified. The relative predictive error (PE) between the measured plasma concentration and predicted plasma concentration was calculated and box plotted. Mann-Whitney U test was used to evaluate the difference of the absolute value of PE (APE) predicted by each software for Vancomycin plasma concentration. The TDM results were divided into accurate prediction group (APE < 30%) and the inaccurate prediction group (APE≥30%) according to the APE value. Patients and disease characteristics including gender, age, body weight complication, Vancomycin medication and TDM results were collected from electronic medical records. Univariate analysis and multivariate Logistic regression analysis were used to screen the related factors that influence the predictive performance of Smart Dose, PharmVan and JPKD; and receiver operating characteristic curve (ROC curve) was drawn to evaluate its predictive value. Results:A total of 185 patients were enrolled, and 258 plasma concentration of Vancomycin were collected, including 185 concentrations of initial regimen and 73 concentration of adjustment regimen. There was no significant difference in the APE of the initial regimen of plasma concentration between Smart Dose and PharmVan. No significant difference in the APE of the adjustment regimen of plasma concentration was found among Smart Dose, PharmVan and JPKD. The accuracy of Smart Dose in predicting the plasma concentration of the adjustment regimen was better than that of the initial regimen [22.94% (10.50%, 36.24%) vs. 29.33% (13.07%, 47.99%), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of initial regimen showed that the proportion of patients with hypertension in the accurate prediction group was significantly higher than that in the inaccurate prediction group [43.3% (42/97) vs. 27.3% (24/88), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of adjustment regimen showed that the proportion of patients with valvular heart disease in the accurate prediction group was significantly lower than that in the inaccurate prediction group [23.4% (11/47) vs. 46.2% (12/26), P < 0.05]. The univariate analysis of factors affecting the performance of JPKD in predicting the concentration of adjustment regimen showed that the body weight of patients in the accurate prediction group was significantly higher than that in the inaccurate prediction group (kg: 62.8±14.9 vs. 54.8±12.8, P < 0.05). Multivariate Logistic regression analysis indicated that hypertension was a beneficial factor for Smart Dose to predict the initial plasma concentration of Vancomycin [odds ratio ( OR) = 0.526, 95% confidence interval (95% CI) was 0.281-0.983, P = 0.044], and low body weight was an independent risk factor for the inaccurate prediction of JPKD for adjustment regimen ( OR = 1.042, 95% CI was 1.001-1.085 , P = 0.043). ROC curve analysis indicated that the area underROC curve (AUC) of the body weight for evaluating the accuracy of JPKD in predicting Vancomycin plasma concentration was 0.663, and 95% CI was 0.529-0.796 ( P = 0.023). When the body weight was less than 55.95 kg, the risk of inaccurate prediction of JPKD in predicting Vancomycin plasma concentration was increased, and the predictive sensitivityand specificity were 75% and 60% respectively. Conclusions:There is no significant difference in the predictive performance of Smart Dose, PharmVan or JPKD on Vancomycin plasma concentration. Smart Dose had a better predictive performance for the Vancomycin plasma concentration of adjustment regimen than initial regimen. Smart Dose had a better predictive performance when the patient was concomitant with hypertension. JPKD had a poor predictive performance for low-body weight patients. The predictive performance of JPKD was decreased when the body weight was lower than 55.95 kg.
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OBJECTIVE To explore the antidepressant effect and the underlying mechanisms of schisandrin (SCH), a component of the fruits of Schizandra chinesis. METHODS The forced swimming test (FST) and tail suspension test (TST) in mice were used to evaluate the antidepressant activity of SCH (5, 10, and 30 mg · kg-1) following single administration intragastrically, and the locomotor activity was investigated to exclude its neural excitatory effects. Effects of SCH on neural monoamine systems were studied in two pharmacological models, including reserpine induced monoamine depletion test and yohimbine toxicity potentiation test. RESULTS In behavioral despair models, SCH (30 mg·kg-1) signif?icantly decreased the immobility time in the TST and FST (P<0.05) compared with normal control group. Results of the locomotor activity experiment showed that SCH had no excitatory or inhibitory actions on the central nervous system. In the reserpine reversal experiment, SCH (30 mg · kg-1) antagonized thepalpebral ptosis and akinesia symptoms caused by reserpine(2.5 mg · kg-1) treatment (P<0.05) compared with model group, but had little effect on the drop of the anal temperature. Moreover, SCH did not increase the lethality caused by subcutaneous injection of yohimbine (30 mg · kg-1)at the threshold lethal dosage. CONCLUSION SCH exerts potential antidepressant-like effect in mice.
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OBJECTIVE To study the influence of glycogen synthase kinase3β (GSK3β) over expres?sion in the hippocampus on the antidepressant and anxiolytic effects of total flavoids from Xiaobuxin Tang (XBXT-2). METHODS Adeno-associated virus containing GSK3β(S9A) mutation was microinjected into the hippocampus. After three weeks of recovery, GSK3βand p-GSK3βwere detected by Western blotting, and open field test (OFT) was used to evaluate the locomotor activity. Then, AAV group and GSK3β over expression group were divided into administration group and solvent group, respectively. XBXT-2 (100 mg · kg-1) and solvent were ig administered chronically. After 14 d and 16 d of administra?tion, the tail suspension test (TST) and forced swimming test (FST) were used to investigate the influence of GSK3βover expression on the antidepressant effect of XBXT-2, respectively. After 18 d and 20 d of administration, the elevated plus maze test (EPMT) and staircase test (ST) were used to investigate the influence of GSK3β over expression on the anxiolytic effects of XBXT-2, respectively. RESULTS Western blotting analysis showed that the protein level of GSK3βincreased significantly in GSK3βover expression group (P<0.01) compared with AAV group, but there was no significant difference in p-GSK3β. In OFT, the number of crossings and rearings showed no difference between AAV group and GSK3β over expression group. The results of TST and FST showed that compared with AAV group, the immobility time was significantly reduced in AAV+XBXT-2 group (P<0.05, P<0.01), but compared with GSK3β over expression group, the immobility time showed no difference in GSK3β over expression+XBXT-2 group. In EPMT, compared with AAV group, the percentage of entrances and time into open arms in AAV+XBXT-2 group was significantly increased (P<0.01, P<0.05), but compared with GSK3βover expression group, these indexes showed no difference in GSK3βover expression+XBXT-2 group. In ST, compared with AAV group, the number of rearings was significantly reduced in AAV+XBXT-2 group (P<0.05), but there was no difference between GSK3β over expression+XBXT-2 group and GSK3βover expression group. CONCLUSION GSK3βover expression in the hippocampus can reverse the antidepressant effects of XBXT-2 in the TST and FST, and the anxiolytic effects in the EPM and ST.