AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

Objective:To investigate the value of tumor volume to uterine volume ratio (N/U) combined with the expression of alpha-fetoprotein (AFP), sugar antigen 199 (CA199) and human epididymal secretory protein 4 (HE4) in evaluating the pathologic grade and prognosis of endometrial carcinoma (EC) .Methods:A total of 160 EC patients admitted to Linyi Central Hospital from Jan. 2021 to Dec. 2023 were divided into low-grade group and high-grade group according to FIGO grading method, and were divided into poor prognosis group and good prognosis group according to cancer death, recrudescence. The levels of N/U, AFP, CA199 and HE4 in patients with different pathologic grades and prognosis were compared. COX regression was used to analyze the influencing factors of EC adverse prognosis, ROC curve was used to analyze the value of N/U combined with serum AFP, CA199 and HE4 in predicting EC adverse prognosis, and a nomogram model was constructed.Results:Pathological examination of 160 EC patients showed that 12 cases were non-endometrioid adenocarcinoma, 148 cases were endometrioid adenocarcinoma, 41 cases were high-grade and 119 cases were low-grade.According to the follow-up, 94 of the 160 EC patients had good prognosis and 66 had poor prognosis. The levels of N/U, AFP, CA199 and HE4 in the poor prognosis group were higher than those in the good prognosis group ( P<0.05). COX regression analysis showed that high levels of N/U, AFP, CA199 and HE4 were all factors affecting the poor prognosis of EC patients ( P<0.05). The AUC value of combined detection of N/U, AFP, CA199 and HE4 in predicting adverse prognosis of EC patients was higher than that of single detection ( Z=3.140, 3.658, 4.277, 4.378, P<0.05) .The ROC curve AUC (95% CI) of the training set and the validation set were 0.84 (0.77-0.92) and 0.90 (0.81-0.98) respectively for the training set and the validation set to predict the adverse prognosis of EC patients. Calibration curve results showed that the calibration curve for EC patients predicted by the nomogram model was close to the ideal curve ( P=0.521, 0.743). The DCA curve shows that the probability threshold of the nomogram model has a higher positive net return at 20%~100%. Conclusion:The levels of N/U, AFP, CA199 and HE4 in EC patients are related to the pathologic grade, and the combined detection of these indicators can predict the poor prognosis of EC patients, and the nomogram model constructed based on these indicators has high predictive value.

Objective:To investigate the value of tumor volume to uterine volume ratio (N/U) combined with the expression of alpha-fetoprotein (AFP), sugar antigen 199 (CA199) and human epididymal secretory protein 4 (HE4) in evaluating the pathologic grade and prognosis of endometrial carcinoma (EC) .Methods:A total of 160 EC patients admitted to Linyi Central Hospital from Jan. 2021 to Dec. 2023 were divided into low-grade group and high-grade group according to FIGO grading method, and were divided into poor prognosis group and good prognosis group according to cancer death, recrudescence. The levels of N/U, AFP, CA199 and HE4 in patients with different pathologic grades and prognosis were compared. COX regression was used to analyze the influencing factors of EC adverse prognosis, ROC curve was used to analyze the value of N/U combined with serum AFP, CA199 and HE4 in predicting EC adverse prognosis, and a nomogram model was constructed.Results:Pathological examination of 160 EC patients showed that 12 cases were non-endometrioid adenocarcinoma, 148 cases were endometrioid adenocarcinoma, 41 cases were high-grade and 119 cases were low-grade.According to the follow-up, 94 of the 160 EC patients had good prognosis and 66 had poor prognosis. The levels of N/U, AFP, CA199 and HE4 in the poor prognosis group were higher than those in the good prognosis group ( P<0.05). COX regression analysis showed that high levels of N/U, AFP, CA199 and HE4 were all factors affecting the poor prognosis of EC patients ( P<0.05). The AUC value of combined detection of N/U, AFP, CA199 and HE4 in predicting adverse prognosis of EC patients was higher than that of single detection ( Z=3.140, 3.658, 4.277, 4.378, P<0.05) .The ROC curve AUC (95% CI) of the training set and the validation set were 0.84 (0.77-0.92) and 0.90 (0.81-0.98) respectively for the training set and the validation set to predict the adverse prognosis of EC patients. Calibration curve results showed that the calibration curve for EC patients predicted by the nomogram model was close to the ideal curve ( P=0.521, 0.743). The DCA curve shows that the probability threshold of the nomogram model has a higher positive net return at 20%~100%. Conclusion:The levels of N/U, AFP, CA199 and HE4 in EC patients are related to the pathologic grade, and the combined detection of these indicators can predict the poor prognosis of EC patients, and the nomogram model constructed based on these indicators has high predictive value.

Objective:To analyze the research hotspots and trends in the stigmatization of adolescents living with HIV/AIDS.Methods:Relevant literature was retrieved from the Web of Science Core Collection database, with the search covering from database inception to May 1, 2024. CiteSpace software was used to conduct bibliometric analysis, including the distribution of countries, institutions, authors, keywords, and cited references. Knowledge maps were generated to visualize the findings.Results:A total of 414 articles were included in the analysis. The number of publications has shown an overall upward trend. The United States had the highest number of publications (244 articles), the most productive institution was University of Cape Town (31 articles), and the most productive author was Linda-Gail Bekker (9 articles). Research hotspots mainly focused on stigmatization, behavioral patterns, mental health, treatment adherence, social support, and intervention models.Conclusions:Research on the stigmatization of adolescents living with HIV/AIDS is currently at a critical stage. Future studies should continue to explore the multidimensional impact of stigma and focus on the development of region-specific and individualized intervention models, while actively constructing a comprehensive support system within the field of public health.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

Objective:To analyze the research hotspots and trends in the stigmatization of adolescents living with HIV/AIDS.Methods:Relevant literature was retrieved from the Web of Science Core Collection database, with the search covering from database inception to May 1, 2024. CiteSpace software was used to conduct bibliometric analysis, including the distribution of countries, institutions, authors, keywords, and cited references. Knowledge maps were generated to visualize the findings.Results:A total of 414 articles were included in the analysis. The number of publications has shown an overall upward trend. The United States had the highest number of publications (244 articles), the most productive institution was University of Cape Town (31 articles), and the most productive author was Linda-Gail Bekker (9 articles). Research hotspots mainly focused on stigmatization, behavioral patterns, mental health, treatment adherence, social support, and intervention models.Conclusions:Research on the stigmatization of adolescents living with HIV/AIDS is currently at a critical stage. Future studies should continue to explore the multidimensional impact of stigma and focus on the development of region-specific and individualized intervention models, while actively constructing a comprehensive support system within the field of public health.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective: To investigate the impact of immediate cessation of antiviral therapy on postpartum liver function and the factors influencing postpartum abnormality in mothers with chronic hepatitis B virus infection. Methods: A retrospective cohort study was conducted. One hundred eighty-eight pregnant women with HBV DNA level > 2×106 IU/ml were enrolled from June 2014 to June 2018. Demographic information and clinical data of liver function and HBV DNA load during gravidity, intrapartum and postpartum period were collected. According to the antiviral treatment recommendations during pregnancy, the women were divided into three groups, namely, tenofovir (TDF), telbivudine (LdT) and control group. Liver function abnormalities among the three groups were compared within 6 months after delivery, and the factors influencing abnormal liver function were analyzed by unconditional logistic regression. Results: Of the 188 cases, 72 cases were in the TDF group, 80 cases in the LdT group, and 36 cases in the control group. Pregnant women in the TDF and LdT groups received oral TDF (300 mg/d) and LdT (600 mg/d) from 28 ± 4 weeks of gestation till delivery. Among the 188 patients, 30 (16.0%) had abnormal postpartum liver function abnormality. The incidence of postpartum liver function abnormality [alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN)] in the TDF, LdT, and control groups was 19.4%, 12.5%, and 16.7%, respectively. The postpartum peak levels of ALT (median, range) in the three groups were 34.5 (12.0-946.0) U/L, 37.5 (12.0-733.8) U/L, and 39.0 (7.0-513.0) U/L, respectively. There was no significant difference between the two indexes among the three groups (P > 0.05). There was no statistically significant difference in the degree of postpartum liver function abnormalities between the three groups (P = 0.944). Most of the liver function abnormalities were mild to moderate (2 × ULN≤ALT < 10 × ULN), and usually resolved spontaneously or by treatment. Univariate and multivariate analysis showed that baseline ALT level during pregnancy was an independent factor associated with postpartum liver function abnormality (OR = 1.031, CI 95%: 1.005-1.058; χ² = 5.340, P = 0.021), whereas age, antiviral therapy, HBeAg-positivity, baseline HBV DNA levels, gravidity, parity, preterm delivery and delivery mode were not significantly associated with postpartum liver function abnormality. Conclusion Cessation of antiviral therapy after delivery did not significantly increase the risk of postpartum liver function abnormality in pregnant women with chronic HBV infection. The ALT level during pregnancy is a factor influencing postpartum liver function abnormality.