Objective:To establish a practical patient-based internal quality control method for valproic acid drug concentration monitoring.Methods:Observational Study. A PBRTQC model based on the exponentially weighted moving average (EWMA) method was established using Python. All results of a total of 28, 757 valproic acid concentration data from February 1, 2023 to January 31, 2024 were collected and split into training set and validation set at a ratio of 80% and 20% respectively. The truncation limit (TL) was optimized by using the winsorized mean method and the trimmed mean method. Different weighting coefficients λ were set. Different TL and different λ were combined with the EWMA algorithm into different patient-based real-time quality control (PBRTQC) models. The optimized models were verified by introducing simulated constant errors (CE) and proportional errors (PE) respectively. The false positive alarm rate (FAR) was used to evaluate specificity, and the average number of patients before error detection (ANPed) was used to evaluate sensitivity. According to the daily test volume and quality target requirements, we comprehensively judged whether the performance evaluation indicators of FAR and ANPed meet the laboratory requirements. Bias detection curve was used for determination of the best model.Results:The parameters of the best PBRTQC model for valproic acid drug concentration monitoring are: trimmed mean method with 1.5 standard deviations (i.e., truncating data outside 1.5 standard deviations of the data mean), λ=0.01. The performance verification result shows that ANPed of CE and PE of this model are both less than 100. The comparison between the EQA results and the EWMA results show that the EWMA method results are comparable to the EQA results.Conclusion:A PBRTQC model for the valproic acid drug concentration monitoring project based on the EWMA method has been successfully established. It is comparable with both IQC and EQA results, which means PBRTQC may be used as a supplement to the quality control of daily quality control products.

Psychotropic medication plays a crucial role in the field of mental illness,and the issues of drug efficacy and safety due to individual differences cannot be ignored.Genetic factors,especially the genetic poly-morphisms related to drug-metabolizing enzymes,drug action targets,and risk,have a significant impact on drug responses.Pharmacogenomics,by detecting genetic polymorphisms,can reveal a patient's inherited tend-encies towards drug efficacy,pharmacokinetic characteristics,and potential toxicity,thereby predicting the therapeutic effects and adverse reactions of drug treatment,and providing guidance for personalized therapy.Therefore,individualized medication based on pharmacogenomics helps to improve cure rates,reduce relapse rates,and decrease medical costs,which is of great significance to clinical medication in mental illness.

Objective To investigate the interference of varying degrees of lipemia on serum lithium(Li)measurement using the phosphatase method and explore effective mitigation strategies.Methods A pooled sample of severe lipemic serum without lithium was collected and concentrated to obtain lipemic serum concentrate.A pooled serum sample from patients with normal lipid levels taking lithium carbonate was used for triglyceride(TG)interference experiments.Additionally,28 serum samples from patients not taking lithium carbonate were collected.Based on the results of TG interference experiments,the maximum TG concentration that did not interfere with serum lithium measurement was determined as the target concentration for dilution,and the corresponding dilution factor was calculated.Lithium solution was added to each sample to determine the theoretical lithium concentration.Samples were divided into three groups and analyzed using direct detection,physiological saline dilution,and high-speed centrifugation(13 000 r/min,10 min).The results obtained from different methods were compared.Results Lipemic serum with TG concentrations>4.77mmol/L interfered with lithium measurement by the phosphatase method.The physiological saline dilution method showed the largest deviation(t=10.87,P<0.000 1)and significant differences from theoretical values,making it unsuitable for accurate measurement.In contrast,the high-speed centrifugation method provided results closest to the theoretical values(t=2.97,P=0.036 9)with higher accuracy.Although the direct detection method was highly correlated with the high-speed centrifugation method(r=0.976 5,P<0.000 1),with a significant mean difference remained(t=5.37,P<0.000 1).Conclusion For lipemic serum samples with TG concentrations>4.77mmol/L,the physiological saline dilution method should be avoided due to its inaccuracy.High-speed centrifugation effectively removes lipemic interference,yielding results closer to theoretical values,and is recommended as the optimized method for serum lithium measurement in lipemic samples.

Objective To investigate the interference of varying degrees of lipemia on serum lithium(Li)measurement using the phosphatase method and explore effective mitigation strategies.Methods A pooled sample of severe lipemic serum without lithium was collected and concentrated to obtain lipemic serum concentrate.A pooled serum sample from patients with normal lipid levels taking lithium carbonate was used for triglyceride(TG)interference experiments.Additionally,28 serum samples from patients not taking lithium carbonate were collected.Based on the results of TG interference experiments,the maximum TG concentration that did not interfere with serum lithium measurement was determined as the target concentration for dilution,and the corresponding dilution factor was calculated.Lithium solution was added to each sample to determine the theoretical lithium concentration.Samples were divided into three groups and analyzed using direct detection,physiological saline dilution,and high-speed centrifugation(13 000 r/min,10 min).The results obtained from different methods were compared.Results Lipemic serum with TG concentrations>4.77mmol/L interfered with lithium measurement by the phosphatase method.The physiological saline dilution method showed the largest deviation(t=10.87,P<0.000 1)and significant differences from theoretical values,making it unsuitable for accurate measurement.In contrast,the high-speed centrifugation method provided results closest to the theoretical values(t=2.97,P=0.036 9)with higher accuracy.Although the direct detection method was highly correlated with the high-speed centrifugation method(r=0.976 5,P<0.000 1),with a significant mean difference remained(t=5.37,P<0.000 1).Conclusion For lipemic serum samples with TG concentrations>4.77mmol/L,the physiological saline dilution method should be avoided due to its inaccuracy.High-speed centrifugation effectively removes lipemic interference,yielding results closer to theoretical values,and is recommended as the optimized method for serum lithium measurement in lipemic samples.

Objective:To establish a practical patient-based internal quality control method for valproic acid drug concentration monitoring.Methods:Observational Study. A PBRTQC model based on the exponentially weighted moving average (EWMA) method was established using Python. All results of a total of 28, 757 valproic acid concentration data from February 1, 2023 to January 31, 2024 were collected and split into training set and validation set at a ratio of 80% and 20% respectively. The truncation limit (TL) was optimized by using the winsorized mean method and the trimmed mean method. Different weighting coefficients λ were set. Different TL and different λ were combined with the EWMA algorithm into different patient-based real-time quality control (PBRTQC) models. The optimized models were verified by introducing simulated constant errors (CE) and proportional errors (PE) respectively. The false positive alarm rate (FAR) was used to evaluate specificity, and the average number of patients before error detection (ANPed) was used to evaluate sensitivity. According to the daily test volume and quality target requirements, we comprehensively judged whether the performance evaluation indicators of FAR and ANPed meet the laboratory requirements. Bias detection curve was used for determination of the best model.Results:The parameters of the best PBRTQC model for valproic acid drug concentration monitoring are: trimmed mean method with 1.5 standard deviations (i.e., truncating data outside 1.5 standard deviations of the data mean), λ=0.01. The performance verification result shows that ANPed of CE and PE of this model are both less than 100. The comparison between the EQA results and the EWMA results show that the EWMA method results are comparable to the EQA results.Conclusion:A PBRTQC model for the valproic acid drug concentration monitoring project based on the EWMA method has been successfully established. It is comparable with both IQC and EQA results, which means PBRTQC may be used as a supplement to the quality control of daily quality control products.

A 66-year-old female patient received oral sertraline (initial dose 25 mg once daily,gradually increased to 100 mg once daily on day 10),zopiclone (7.5 mg once per night),lorazepam (0.5 mg thrice daily),and amlodipine (2.5 mg once daily) following the doctor's advice due to recurrent depressive disorder,sleep disorder,and hypertension.Before administration,the patient's serum levels of aspartate aminotransferase (AST),alanine aminotransferase (ALT),and γ-glutamyl transpeptidase (γ-GT)were 21 U/L,16 U/L and 50 U/L,respectively.On day 16 after the medication,the patient's serum levels of AST,ALT,and-γ-GT were 114 U/L,134 U/L,and 192 U/L,respectively,but the treatment protocol was not adjusted.On day 21 after the medication,her serum levels of AST,ALT,and γ-GT turned to be 178 U/L,242 U/L,and 362 U/L,respectively.Then hepatoprotective drugs were given,sertraline was discontinued by gradual reduction (oral escitalopram 5 mg once daily was added when sertraline was reduced to 25 mg once daily,but escitalopram was changed to oral mirtazapine 15 mg at bedtime finally due to the patient's leg discomfort),and the other drugs were continued.The liver function of the patient gradually improved and her serum levels of AST,ALT,and γ-GT were 35 U/L,36 U/L,and 108 U/L,respectively about 50 days after sertraline withdrawal.

A 66-year-old female patient received oral sertraline (initial dose 25 mg once daily,gradually increased to 100 mg once daily on day 10),zopiclone (7.5 mg once per night),lorazepam (0.5 mg thrice daily),and amlodipine (2.5 mg once daily) following the doctor's advice due to recurrent depressive disorder,sleep disorder,and hypertension.Before administration,the patient's serum levels of aspartate aminotransferase (AST),alanine aminotransferase (ALT),and γ-glutamyl transpeptidase (γ-GT)were 21 U/L,16 U/L and 50 U/L,respectively.On day 16 after the medication,the patient's serum levels of AST,ALT,and-γ-GT were 114 U/L,134 U/L,and 192 U/L,respectively,but the treatment protocol was not adjusted.On day 21 after the medication,her serum levels of AST,ALT,and γ-GT turned to be 178 U/L,242 U/L,and 362 U/L,respectively.Then hepatoprotective drugs were given,sertraline was discontinued by gradual reduction (oral escitalopram 5 mg once daily was added when sertraline was reduced to 25 mg once daily,but escitalopram was changed to oral mirtazapine 15 mg at bedtime finally due to the patient's leg discomfort),and the other drugs were continued.The liver function of the patient gradually improved and her serum levels of AST,ALT,and γ-GT were 35 U/L,36 U/L,and 108 U/L,respectively about 50 days after sertraline withdrawal.

Objective To study the differences in retinoic acid receptor γ(RARγ) mRNA expression levels in blood leukocytes between antipsychotic-free and antipsychotic-naive schizophrenic patients and healthy control,especially in different genders. Methods Forty-three acute schizophrenic patients who were antipsychotic-naive or antipsychotic-free for at least three months (male = 34, female = 9) and 39 age- and sex-matched healthy subjects (male =25 ,female = 14) were included for blood leukocytes expression of RAR γ mRNA ,using real-time PCR technique. Results Kolmogorov-Smirnov Z analysis showed a significant increase of RARγ mRNA (P =0.041) level in blood leukocytes of pooled schizophrenic patients(0. 027 ± 0. 003) than in the healthy subjects (0. 020 ± 0.002). The elevation was mainly found in the female patients (0. 030 ± 0.003). Within-sex analysis showed that the female schizophrenic patients showed a trend increase (P = 0. 166) of RAR γmRNA expression compared with the male patients (0. 026 ± 0. 001) and exhibited greater RARγ mRNA expression (P = 0. 014)when compared with the female healthy subjects(0. 018 ±0.004). Conclusions The present findings showed an abnormal expression of leukocyte RARγ mRNA level in antipsychotic-free and antipsychotic-naive schizophrenia especially in the female patients. Blood RARγ markers could add to the diagnosis and individualized pharmacotherapy of schizophrenic patients ,especially the female patients.