CXCR2 Activated JAK3/STAT3 Signaling Pathway Exacerbating Hepatotoxicity Associated with Tacrolimus.

Purpose: Tacrolimus could induce hepatotoxicity during clinical use, and the mechanism was still unclear, which posed new challenge for the prevention and treatment of tacrolimus-induced hepatotoxicity. The aim of this study was to investigate the mechanism of tacrolimus-induced hepatotoxicity and provide reference for drug development target.

Methods: In this study, biochemical analysis, pathological staining, immunofluorescent staining, immunohistochemical staining, transcriptomic analysis, Western blotting was used to investigate the mechanism of tacrolimus-induced hepatotoxicity in gene knockout mice and Wistar rats.

Model-informed precision dosing of quetiapine in bipolar affective disorder patients: initial dose recommendation.

Objective: Bipolar affective disorder (BAD) is a mood disorder with high morbidity and mortality. Quetiapine can be used in the treatment of patients with BAD; however, the precise administration regimen of quetiapine in these patients is still unknown. In this study, a population pharmacokinetic (PPK) model of quetiapine in patients with BAD was constructed based on model-informed precision dosing (MIPD) and real-world clinical data and an optimal initial dose of quetiapine in these patients was recommended.

Optimization of initial dosage of quetiapine in schizophrenic patients: effects of fluvoxamine or duloxetine coadministration.

Objective: Although quetiapine has been approved for use in schizophrenic patients, its individualized dosage regimen remains unclear, especially with respect to drug-drug interactions (DDIs). Thus, we investigated the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on population pharmacokinetics (PPK).

Methods: Ninety-six schizophrenic patients treated with quetiapine were included to establish the PPK model, which also includes coadministration of multiple drugs.

Interface-Engineered CuO@BiMoO Heterojunctions to Inhibit Piezoelectric Screening Effect and Promote Double-Nanozyme Catalysis for Antibacterial Treatment.

Sonodynamic therapy is confronted with the low acoustic efficiency of sonosensitizers, and nanozymes are accompanied by intrinsic low catalytic activity. Herein, to increase the piezopotential of N-type piezoelectric semiconductors, the P-N heterojunction is designed to inhibit the piezoelectric screening effect (PSE) and increase electron utilization efficiency to enhance nanozyme activity. P-type CuO nanoparticles are in situ grown on N-type piezoelectric BiMoO (BMO) nanoflakes (NFs) to construct heterostructured CuO@BMO by interface engineering.

Targeting CXCR2 ameliorated tacrolimus-induced nephrotoxicity by alleviating overactivation of PI3K/AKT/mTOR pathway and calcium overload.

Objectives: The purposes of this study were to (i) verify the role of CXCR2 in tacrolimus-induced nephrotoxicity, (ii) explore the specific mechanism of CXCR2-mediated tacrolimus nephrotoxicity, and (iii) target the antagonism of CXCR2 and provide a potential target for the treatment of tacrolimus-induced nephrotoxicity in children.

Methods: CXCR2 knockout (CXCR2-KO) mice were used to evaluate the role of CXCR2 in tacrolimus-induced nephrotoxicity. Wistar rats were used to explore the underlying mechanism.

Initial dosage optimization of olanzapine in patients with bipolar disorder based on model-informed precision dosing: a study from the real world.

Objectives: Olanzapine is used for treating bipolar disorder (BPD); however, the optimal initial dosing regimen is unclear. The present study aimed to investigate the optimal olanzapine initial dosage in patients with BPD via model-informed precision dosing (MIPD) based on a real-world study.

Methods: Thirty-nine patients with BPD from the real-world study were collected to construct the MIPD model.

Weight, Genotype, and Voriconazole Co-administration Influence Tacrolimus Initial Dosage in Pediatric Lung Transplantation Recipients with Low Hematocrit based on a Simulation Model.

Objective: The method of administering the initial doses of tacrolimus in recipients of pediatric lung transplantation, especially in patients with low hematocrit, is not clear. The present study aims to explore whether weight, genotype, and voriconazole co-administration influence tacrolimus initial dosage in recipients of pediatric lung transplantation with low hematocrit based on safety and efficacy using a simulation model.

Methods: The present study utilized the tacrolimus population pharmacokinetic model, which was employed in lung transplantation recipients with low hematocrit.

Effects of dapagliflozin on body weight in patients with type 2 diabetes mellitus: Evidence‑based practice.

The dose-dependent pharmacological response to dapagliflozin in patients with type 2 diabetes mellitus (T2DM) with regard to weight loss remain unknown. The aim of the present study was to investigate the effects of dapagliflozin on weight loss in patients with T2DM. A total of 8,545 patients with T2DM from 24 randomized controlled trials reported in the literature were selected for inclusion in the study.

Effects of Aripiprazole on Olanzapine Population Pharmacokinetics and Initial Dosage Optimization in Schizophrenia Patients.

Objective: Olanzapine has already been used to treat schizophrenia patients; however, the initial dosage recommendation when multiple drugs are used in combination, remains unclear. The purpose of this study was to explore the drug-drug interaction (DDI) of multiple drugs combined with olanzapine and to recommend the optimal administration of olanzapine in schizophrenia patients.

Methods: In this study, we obtained olanzapine concentrations from therapeutic drug monitoring (TDM) database.

Optimizing the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels.

Background: The appropriate initial dosage of tacrolimus is undefined in Chinese pediatric lung transplant patients with normal hematocrit values. The purpose of this study is to optimize the initial dose of tacrolimus in Chinese children who are undergoing lung transplantation and have normal hematocrit levels.

Methods: The present study is based on a published population pharmacokinetic model of tacrolimus in lung transplant patients and uses the Monte Carlo simulation to optimize the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels.

Syk/BLNK/NF-κB signaling promotes pancreatic injury induced by tacrolimus and potential protective effect from rapamycin.

Background: The treatment of tacrolimus-induced post-transplantation diabetes mellitus (PTDM) has become a hot topic to improve the long-term survival of organ transplant patients, however whose pathogenesis has not been fully elucidated. In pancreas, the up-regulation of NF-κB has been reported to stimulate cytokine IL-1β/TNF-α secretion, inducing pancreatic injury, meanwhile other studies have reported the inhibitory effect of rapamycin on NF-κB.

Purpose: The aim of this study was to clarify the mechanism of tacrolimus-induced pancreatic injury and to explore the potential effect from small dose of sirolimus.

The Dosage Recommendation of Cyclosporin in Children with Hemophagocytic Lymphohistiocytosis based on Population Pharmacokinetic Model.

Objectives: Cyclosporin is one of the therapeutic regimens for hemophagocytic lymphohistiocytosis (HLH); however, the optimal dosage of cyclosporine in children with HLH is unknown. It has been found that piperacillin-tazobactam affects the cyclosporine pharmacokinetic process in pediatric HLH patients. Thus, the purpose of the present study was to recommend cyclosporin dosage for pediatric HLH with and without piperacillin- tazobactam.

Quantitative effects of sodium-glucose cotransporter-2 inhibitors on liver functions in patients with nonalcoholic fatty liver disease.

Background: The present study aimed to explore the quantitative effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on liver functions in patients with nonalcoholic fatty liver disease (NAFLD).

Research Design And Methods: A total of 4771 patients with NAFLD were included for analysis by means of nonlinear mixed effect modeling, where the change rates of liver functions were taken as the evaluation indexes so as to eliminate the potential baseline effects.

Results: For ALT and AST, the E of SGLT-2 inhibitors was -17.

Analyze and simulate an individualized nutritional computing system for multidisciplinary teams in nutritional support therapy.

To explore the efficiency of nutritional support therapy . Pharmacists led the construction of an individualized nutritional computing system and were involved in the process of treatment. After obtaining relevant professional knowledge and instruction on how to operate the system, MDT members intervened in the incorrect treatment process during nutritional support therapy.

Therapeutic effect and rebound evaluation of dapagliflozin on glycated hemoglobin (HbA1c) in type 1 diabetes mellitus patients.

Dapagliflozin has been used to treat patients with type 1 diabetes mellitus; however, the actual drug efficacy of dapagliflozin on glycated hemoglobin (HbA1c) and whether there is a rebound from dapagliflozin efficacy on HbA1c remain unknown. The present study aimed to explore the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients. A total of 1,594 type 1 diabetes mellitus patients were enrolled for analysis using a non-linear mixed effect model from randomized controlled trials from published literature works including two 5 mg/day dapagliflozin dosage groups and three 10 mg/day dapagliflozin dosage groups.

Quantitative effects of sodium-glucose cotransporter-2 inhibitors dapagliflozin and empagliflozin on quality of life in heart failure patients.

The aim of the present study is to investigate the quantitative effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the quality of life in heart failure (HF) patients. A total of 14,674 HF patients from two dapagliflozin and three empagliflozin studies is included for analysis the nonlinear mixed-effect modeling (NONMEM) software, among which the change rate of the Kansas City Cardiomyopathy Questionnaire (KCCQ) score is used as the evaluation index. There is no significant difference in the pharmacodynamics influencing the quality of life in HF patients between the SGLT-2 inhibitors: 10 mg/day dapagliflozin and 10 mg/day empagliflozin.

Predicting the effect of sirolimus on disease activity in patients with systemic lupus erythematosus using machine learning.

What Is Known And Objectives: The present study aimed to predict the effect of sirolimus on disease activity in patients with systemic lupus erythematosus (SLE) using machine learning and to recommend appropriate sirolimus dosage regimen for patients with SLE.

Methods: The E model was selected for machine learning, where the evaluation indicator was the change rate of systemic lupus erythematosus disease activity index from baseline value.

Results: A total 103 patients with SLE were included for modelling, where the E , ET were -53.

A machine-learning approach for predicting the effect of carnitine supplementation on body weight in patients with polycystic ovary syndrome.

The present study aimed to explore the effect of carnitine supplementation on body weight in patients with polycystic ovary syndrome (PCOS) and predict an appropriate dosage schedule using a machine-learning approach. Data were obtained from literature mining and the rates of body weight change from the initial values were selected as the therapeutic index. The maximal effect (E) model was built up as the machine-learning model.

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Urine Albumin to Creatinine Ratio in Type 2 Diabetes Mellitus Patients and Medication Care.

Objectives: The purpose of this study was to explore the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on urine albumin to creatinine ratio (UACR) in type 2 diabetes mellitus (T2DM) patients and to recommend appropriate medication care scheme.

Methods: 8371 T2DM patients from four dapagliflozin studies and two canagliflozin studies were collected for analyzing with nonlinear mixed effect model (NONMEM). The change rates of UACR from baseline were intended to be evaluation indicators.