Objective:To systematically evaluate the effects of liver and kidney function on the occurrence of thrombocytopenia induced by linezolid and the population pharmacokinetic characteristics of linezolid, so as to provide guidance for the individualization of linezolid in patients with liver and renal insufficiency.Methods:Relevant databases at home and abroad have been searched up to November 2023. The literature about the influence of liver and kidney function on linezolid-induced thrombocytopenia were analyzed using the Rev Man 5.4 statistical software, and the effect sizes were odds ratio ( OR) and standardized mean difference ( SMD) with their 95% confidence interval ( CI) in the meta-analysis. The literature on population pharmacokinetic studies of linezolid were summarized and systematically reviewed. Results:A total of 32 literature were included in the meta-analysis, including 4 112 patients. Among them, 1 458 (35.5%) developed thrombocytopenia and 2 654 (64.5%) did not. The meta-analysis results showed that the risk of linezolid-induced thrombocytopenia in the renal insufficiency patients was higher than that in patients with normal renal function [47.9% (594/1 241) vs. 25.8% (493/1 912), OR=3.24, 95% CI: 2.31-4.53], and the lower baseline creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) were associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05); the risk of thrombocytopenia induced by linezolid in patients with liver dysfunction was higher than that in patients with normal liver function [47.6% (119/250) vs. 33.9% (360/1 061), OR=2.36, 95% CI: 1.73-3.22], and the higher baseline total bilirubin (TBil) was associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05). A total of 15 articles were included in the review of population pharmacokinetic study, 11 of which were based on self-built or publicly published population pharmacokinetic models and used Monte Carlo simulation to evaluate the efficacy and safety probabilities in different dosing regimens of linezolid. Among them, there were 5 and 2 articles optimized the dosing regimen of linezolid in patients with renal and liver insufficiency, respectively. Conclusions:Liver and renal insufficiency increases the risk of linezolid-induced thrombocytopenia, and baseline levels of Ccr, eGFR, and TBil can serve as sensitive indicators for predicting the risk. Patients with liver and renal insufficiency can use population pharmacokinetic models for an optimized linezolid regimen before treatment to reduce the risk of linezolid-induced thrombocytopenia.

Objective:To systematically evaluate the effects of liver and kidney function on the occurrence of thrombocytopenia induced by linezolid and the population pharmacokinetic characteristics of linezolid, so as to provide guidance for the individualization of linezolid in patients with liver and renal insufficiency.Methods:Relevant databases at home and abroad have been searched up to November 2023. The literature about the influence of liver and kidney function on linezolid-induced thrombocytopenia were analyzed using the Rev Man 5.4 statistical software, and the effect sizes were odds ratio ( OR) and standardized mean difference ( SMD) with their 95% confidence interval ( CI) in the meta-analysis. The literature on population pharmacokinetic studies of linezolid were summarized and systematically reviewed. Results:A total of 32 literature were included in the meta-analysis, including 4 112 patients. Among them, 1 458 (35.5%) developed thrombocytopenia and 2 654 (64.5%) did not. The meta-analysis results showed that the risk of linezolid-induced thrombocytopenia in the renal insufficiency patients was higher than that in patients with normal renal function [47.9% (594/1 241) vs. 25.8% (493/1 912), OR=3.24, 95% CI: 2.31-4.53], and the lower baseline creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) were associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05); the risk of thrombocytopenia induced by linezolid in patients with liver dysfunction was higher than that in patients with normal liver function [47.6% (119/250) vs. 33.9% (360/1 061), OR=2.36, 95% CI: 1.73-3.22], and the higher baseline total bilirubin (TBil) was associated with the higher risk of linezolid-related thrombocytopenia (all P<0.05). A total of 15 articles were included in the review of population pharmacokinetic study, 11 of which were based on self-built or publicly published population pharmacokinetic models and used Monte Carlo simulation to evaluate the efficacy and safety probabilities in different dosing regimens of linezolid. Among them, there were 5 and 2 articles optimized the dosing regimen of linezolid in patients with renal and liver insufficiency, respectively. Conclusions:Liver and renal insufficiency increases the risk of linezolid-induced thrombocytopenia, and baseline levels of Ccr, eGFR, and TBil can serve as sensitive indicators for predicting the risk. Patients with liver and renal insufficiency can use population pharmacokinetic models for an optimized linezolid regimen before treatment to reduce the risk of linezolid-induced thrombocytopenia.

Objective To investigate the effect and mechanism of astragalusⅣ (AS-Ⅳ) on the expression of CCL18in U937macrophages.Methods The expression of CCL18mRNA was detected by real time PCR.The expression of CCL18protein was assessed by Elisa.The expression of IL-4receptor was measured by flow cytometry.The STAT 6phosphorylation was measured by Elisa.The activity of JAK kinase was detected by Z″-LYTETMkinase assay.Results AS-Ⅳsignificantly down-regulated the expression of CCL18in U937macrophages stimulated by IL-4with a dose-dependent manner.However, AS-Ⅳhad no significant effect on IL-4receptor subunit expression.The STAT6phosphorylation was inhibited by AS-Ⅳ, but the effect was less than AS1517499;the activity of JAK1, JAK3and TYK2kinase were inhibited by AS-Ⅳ.Conclusion AS-Ⅳcould inhibit the expression of CCL18in U937macrophages stimulated by IL-4.One of the suggested mechanisms was due to inhibition of JAK kinase activity, which caused STAT6transcriptional activity down and inhibited CCL18gene expression.