To establish a population pharmacokinetic (PPK) model of digoxin in older Chinese patients to provide a reference for individual medication in clinical practice. Serum concentrations of digoxin and clinically related data including gender, age, weight (WT), serum creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), albumin (ALB), and co-administration were retrospectively collected from 119 older patients taking digoxin orally for more than 7 d. NONMEM software was used to get PPK parameter values, to set up a final model, and to assess the models in clinical practice. Spironolactone (SPI), WT, and Cr markedly affected the clearance rate of digoxin. The final model formula is Cl/F=5.9×[1–0.412×SPI]×[1–0.0101×(WT–62.9)]×[1–0.0012×(Cr–126.8)] (L/h); Ka=1.63 (h⁻¹); V_d/F=550 (L). The population estimates for Cl/F and V_d/F were 5.9 L/h and 550 L, respectively. The interindividual variabilities (CV) were 49.0% for Cl/F and 94.3% for V_d/F. The residual variability (SD) between observed and predicted concentrations was 0.365 μg/L. The difference between the objective function value and the primitive function value was less than 3.84 (P>0.05) by intra-validation. Clinical applications indicated that the percent of difference between the predicted concentrations estimated by the PPK final model and the observed concentrations were −4.3%–+25%. Correlation analysis displayed that there was a linear correlation between observated and predicted values (y=1.35x+0.39, r=0.9639, P<0.0001). The PPK final model of digoxin in older Chinese patients can be established using the NONMEM software, which can be applied in clinical practice.

Backgroud: To analyze the correlation between gene polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR) and risk of unexplained recurrent pregnancy loss (URPL) in Chinese women. Methods: Eligible studies were searched in Pubmed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Established inclusion criteria were used to screening articles, subsequently evaluate the quality of the included studies, Stata 16.0 PM and RevMan 5.3 software were conducted for meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was determined to assess the relationship between MTHFR and risk of URPL in Chinese women. Results: For MTHFR C677T, fifty studies were included, involving 6677 URPL cases and 8111 controls. The overall results showed that MTHFR C677T was significantly correlated with URPL risk, especially in the homozygous model (TT vs CC; OR 3.06; 95% CI 2.56–3.66). For MTHFR A1298C, twenty-first studies were included, involving 3439 URPL cases and 3155 controls. The results showed that MTHFR A1298C was also significantly correlated with URPL risk in recessive (CC vs AC + AA; OR 1.55; 95% CI 1.25–1.93) and homozygous (CC vs AA; OR 1.53; 95% CI 1.22–1.91) models. In addition, sub-group results showed that no significant difference between north and south China populations in the MTHFR gene polymorphisms and URPL risk. Of note, the patients carrying MTHFR C677T and MTHFR A1298C joint mutants had no synergistic effect (OR 2.71; 95% CI 0.84–8.70) on the occurrence of URPL compared with the wild-type homozygous genotype (MTHFR 677CC/ MTHFR 1298AA). Conclusion: Studies included in this meta-analysis suggested that MTHFR 677T allele and 677TT genotype and MTHFR 1298CC genotype were both associated with URPL; testing MTHFR C677T gene polymorphism was a more appropriate target compared with other mutations in the prediction of URPL.

Background: Granulocyte colony-stimulating factors (G-CSFs) include long-acting ones and short-acting ones. They have been mainly applied in Chinese clinical practice for years to prevent neutropenia. However, which type of G-CSF is more superior has not been conclusively determined. Methods: A systematic literature search was conducted using the PubMed, Embase, Cochrane Library, clinical trials.gov, China National Knowledge Infrastructure, and WAN FANG databases for related studies published till August 2021. Revman 5.3 software was used to assess the effectiveness and safety of these 2 types of G-CSFs in patients undergoing chemotherapy. Results: Ten studies involving 1916 patients were included in our meta-analysis to compare the effectiveness and safety of long-acting G-CSFs and short-acting G-CSFs. We found that the incidence of febrile neutropenia (relative risk [RR] 0.82; 95% confidence interval [CI] 0.57–1.17), the recovery time of the absolute neutrophil count (mean difference –0.23; 95% CI –0.49 to 0.03), and the fatigue rate (RR 0.82; 95% CI 0.62–1.07) were similar between the long- and the short-acting G-CSFs. However, the long-acting G-CSFs significantly decreased the incidence (RR 0.86; 95% CI 0.76–0.96) and shortened the duration (mean difference –0.19; 95% CI –0.38 to 0.00) of severe (grade ≥3) neutropenia, and decreased the rate of bone and/or muscle pain (RR 0.75; 95% CI 0.58–0.98). Conclusion: Primary prophylaxis with long-acting G-CSFs was more effective and safer than primary prophylaxis with short-acting G-CSFs in Chinese adults undergoing chemotherapy.