Objective:To explore differences in dose-adjusted plasma concentrations of valproic acid between different valproate formulations in patients with mental disorders based on therapeutic drug monitoring data.Methods:A retrospective analysis was performed; clinical data, including demographic characteristics, therapeutic drug monitoring results, comorbidities, medication details (daily valproic acid dose, concomitant medications), and liver and kidney function indicators, were collected from 633 patients with bipolar disorder or schizophrenia who were hospitalized at Xi'an Mental Health Center and received different valproates from January 2024 to June 2024 (98 patients receiving sodium valproate and 535 receiving magnesium valproate). Clinical data between a sodium valproate group and a magnesium valproate group were compared. Multivariate linear regression was used to identify independent influencing factors for dose-adjusted plasma concentration of valproic acid. Valproic acid daily doses, and plasma concentrations and dose-adjusted plasma concentrations of valproic acid were compared between the two groups, with subgroup analyses conducted by gender and age categories.Results:A total of 658 measurements of plasma valproic acid concentration were obtained in 633 patients, including 104 measurements in the sodium valproate group and 554 in the magnesium valproate group. Significant differences in proportions of comorbidities and concomitant use of olanzapine, quetiapine and clozapine were observed between the sodium valproate group and magnesium valproate group ( P<0.05). After adjusting for age, gender, body mass index, comorbidities, concomitant medications, and liver and kidney function indicators, the type of valproates remained an independent influencing factor for dose-adjusted plasma concentration of valproic acid (adjusted unstandardized B coefficient=13.814, 95% CI: 8.090-19.540, P<0.001). Daily dose in the sodium valproate group (1.0[1.0, 1.0] g/d) was significantly higher than that in the magnesium valproate group (0.5[0.5, 1.0] g/d), and dose-adjusted plasma concentration of valproic acid in the magnesium valproate group (93.00 [75.60, 117.40] [μg/mL]/[g·d]) was statistically higher than that in the sodium valproate group (78.55 [57.90, 90.00][μg/mL]/[g·d], P<0.05). Subgroup analysis revealed that, among patients stratified by genders and ages (<40 years vs. ≥40 years), the daily dose in the sodium valproate group was significantly higher than that in the magnesium valproate group, while the dose-adjusted plasma concentration of valproic acid in the magnesium valproate group was significantly higher than that in the sodium valproate group ( P<0.05). Conclusion:Significant differences in dose-adjusted plasma concentrations of valproic acid are observed among different valproate formulations for the treatment of mental disorders; therefore, therapeutic drug monitoring should be performed in patients when switching valproates to facilitate precise individualized dosage adjustment.

Objective:To explore differences in dose-adjusted plasma concentrations of valproic acid between different valproate formulations in patients with mental disorders based on therapeutic drug monitoring data.Methods:A retrospective analysis was performed; clinical data, including demographic characteristics, therapeutic drug monitoring results, comorbidities, medication details (daily valproic acid dose, concomitant medications), and liver and kidney function indicators, were collected from 633 patients with bipolar disorder or schizophrenia who were hospitalized at Xi'an Mental Health Center and received different valproates from January 2024 to June 2024 (98 patients receiving sodium valproate and 535 receiving magnesium valproate). Clinical data between a sodium valproate group and a magnesium valproate group were compared. Multivariate linear regression was used to identify independent influencing factors for dose-adjusted plasma concentration of valproic acid. Valproic acid daily doses, and plasma concentrations and dose-adjusted plasma concentrations of valproic acid were compared between the two groups, with subgroup analyses conducted by gender and age categories.Results:A total of 658 measurements of plasma valproic acid concentration were obtained in 633 patients, including 104 measurements in the sodium valproate group and 554 in the magnesium valproate group. Significant differences in proportions of comorbidities and concomitant use of olanzapine, quetiapine and clozapine were observed between the sodium valproate group and magnesium valproate group ( P<0.05). After adjusting for age, gender, body mass index, comorbidities, concomitant medications, and liver and kidney function indicators, the type of valproates remained an independent influencing factor for dose-adjusted plasma concentration of valproic acid (adjusted unstandardized B coefficient=13.814, 95% CI: 8.090-19.540, P<0.001). Daily dose in the sodium valproate group (1.0[1.0, 1.0] g/d) was significantly higher than that in the magnesium valproate group (0.5[0.5, 1.0] g/d), and dose-adjusted plasma concentration of valproic acid in the magnesium valproate group (93.00 [75.60, 117.40] [μg/mL]/[g·d]) was statistically higher than that in the sodium valproate group (78.55 [57.90, 90.00][μg/mL]/[g·d], P<0.05). Subgroup analysis revealed that, among patients stratified by genders and ages (<40 years vs. ≥40 years), the daily dose in the sodium valproate group was significantly higher than that in the magnesium valproate group, while the dose-adjusted plasma concentration of valproic acid in the magnesium valproate group was significantly higher than that in the sodium valproate group ( P<0.05). Conclusion:Significant differences in dose-adjusted plasma concentrations of valproic acid are observed among different valproate formulations for the treatment of mental disorders; therefore, therapeutic drug monitoring should be performed in patients when switching valproates to facilitate precise individualized dosage adjustment.

ObjectiveTo resolve the problems related to the abnormal interpretations of real-time fluorescence polymerase chain reaction （PCR） results for tri-allele， to formulate the interpretation methods of real-time fluorescence PCR by referring to multiplex PCR fragment analysis， so as to obtain an accurate， simple and cheap detection method for ABCB1 tri-allele. MethodsA total of 2 794 DNA samples were collected from Xi'an Mental Health Center from March 2020 to March 2021， and 5% of which were selected as experiments. Real-time fluorescence PCR method and multiplex PCR fragment analysis method were performed respectively. According to the comparison of Ct values of PCR curves and the comparison of base peak intensity in multiplex PCR fragment analysis， comparison and analysis were conducted on the interpretation results of the two methods， and samples with different interpretation results were verified， thereafter， PCR interpretation method was formulated. ResultsA total of 139 samples were collected， of which 120 alleles and 19 tri-allele were detected. The results of allele detection by two methods were absolutely consistent. In combination with the results of multiplex PCR fragment analysis， a method for the interpretation of real-time fluorescence PCR for 19 cases of tri-allele was developed as follows： when ∣∣Ct._G－Ct._T∣－∣Ct._G－Ct._A∣∣ in amplification curve was less than 3， the interpretation results were the combination of the base pairs with small Ct values； when ∣∣Ct._G－Ct._T∣－∣Ct._G－Ct._A∣∣ was greater than or equal to 3， the interpretation results were homozygotes from the base pairs with minimum Ct values. According to the interpretation method， the results of real-time fluorescence PCR were revised， and it showed 1 case of G/G， 1 case of A/A， 4 cases of T/G， 5 cases of T/A and 8 cases of T/T， which were consistent with the results of multiplex PCR fragment analysis. ConclusionReferring to the multiplex PCR fragment analysis method， the interpretation of ABCB1 tri-allele by real-time fluorescence PCR is developed， and the two interpretation methods are in good agreement.

Objective To investigate the death of chondrocytes in rats which feed with T-2 toxin under selenium (Se) deficient conditions.Methods Thirty two healthy male SD rats were divided into two groups by weight which were normal diet group and Se deficiency diet group,16 rats in each group.Rats in normal diet group were fed with Se 101.5 μg/kg diet,and rats in Se deficiency diet group were fed with Se 1.1 μg/kg diet for 30 d.Normal diet group was divided into control group and T-2 toxin group,and Se deliciency diet group was randomly divided into Se-deficiency group and Se-deficiency plus T-2 toxin group,8 rats in each group.After that,rats in T-2 toxin and Se-deficiency plus T-2 toxin groups were administrated intragastrically with T-2 toxin (100 μg/kg) everyday for 30 d.Rats were put to death,the left knee was taken and stained with hematoxylin-eosin and SafraninFast green,pathological changes of rat's knee joint cartilage were observed under light microscopy,expression levels of active caspase-3 and receptor interacting protein 3 (RIP3) in rat's articular cartilage cells were determined via the immunohistochemical method.The apoptosis was also detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL).Results Red ghost outlines of chondrocyte and multiple chondral cell clusters surrounded the non-cell areas in deep zone of articular cartilage of knee joint stained with hematoxylineosin were seen in Se-deficiency plus T-2 toxin group under light microscope.In the superficial zone of cartilage,the positive percent of TUNEL and active caspase-3 in Se-deficiency plus T-2 toxin group was higher than those of control group,Se-deficiency group and T-2 toxin group [(7.47-± 0.34)％ vs (4.68 ± 0.54)％,(2.67-± 0.64)％,(2.56 ±0.54)％;(4.75 ± 0.67)％ vs (1.24 ± 0.25)％,(0.00 ± 0.00)％,(0.00 ± 0.00)％,P ＜ 0.05].In the middle zone of cartilage,the positive percent of TUNEL,active caspase-3 and RIP3 in Se-deficiency plus T-2 toxin group was significantly higher than those of control group,T-2 toxin group and Se-deficiency group [(72.06 ± 6.15)％ vs (16.10 ± 3.00)％,(19.57 ± 3.49)％,(19.33 ± 5.19)％;(51.13 ± 4.18)％ vs (10.97-± 3.01)％,(15.36 ± 4.37)％,(15.23 ± 3.13)％;(25.91 ± 13.39)％ vs (1.59 ± 1.14)％,(4.32 ± 2.91)％,(7.50 ± 5.00)％,P ＜ 0.05].The positive percents of TUNEL,active caspase-3 and RIP3 were not significantly different in the deep zone (P ＞ 0.05).Conclusion The death of the middle zone in the rat cartilage induced by T-2 toxin under selenium deficient conditions isapoptosis and necroptosis.