Pharmacokinetics and pharmacodynamics of antibiotics in septic children treated with extracorporeal membrane oxygenation / 中华儿科杂志

Objective: To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibacterial agents in children with sepsis treated by extracorporeal membrane oxygenation (ECMO). Methods: In this prospective cohort study, 20 children with sepsis (confirmed or suspected) who were treated with ECMO and antimicrobial in the Department of Critical Medicine of Hunan Children's Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through therapeutic drug monitoring (TDM), the PK-PD parameters of antibacterial agents were analyzed. Twenty five children with sepsis in the same department who were treated with vancomycin but no ECMO at the same time were enrolled as the control group. The individual PK parameters of vancomycin were calculated by Bayesian feedback method. The PK parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison. Results: Twenty patients in the ECMO group, included 6 males and 14 females, with an onset age of 47 (9, 76) months. In the ECMO group, 12 children (60%) were treated with vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases; AUC/minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11 children (55%) who were treated with β-lactam antibiotics, there were 10 cases with drug concentration at 50% dosing interval (CT50)>4 MIC and 9 cases with trough concentration>MIC, both CT50 and trough concentration of cefoperazone reached the target. Among the 25 cases of control group, 16 were males and 9 females, with an onset age of 12 (8, 32) months. There was a positive correlation between vancomycin trough concentration and AUC (r2=0.36, P<0.001). The half-life of vancomycin and the 24-hour AUC (AUC0-24 h) in the ECMO group were higher than those in the control group (5.3 (3.6, 6.8) vs. 1.9 (1.5, 2.9) h, and 685 (505, 1 227) vs. 261 (210, 355) mg·h/L, Z=2.99, 3.50, respectively; both P<0.05), and the elimination rate constant and clearance rate was lower than those in the control group (0.1 (0.1, 0.2) vs. 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) vs. 2.0 (1.1, 2.8) L/h, Z=2.99, 2.11, respectively; both P<0.05). Conclusion: The PK-PD parameters in septic children treated by ECMO varied with a longer half-life, higher AUC0-24 h, lower elimination rate constant and clearance rate.

Expression and regulation of XBP1 in mouse uterus during early pregnancy / 生理学报

The transcription factor X-box binding protein-1 (XBP1) plays a key role in unfolded protein reaction. This study was aimed to investigate the expression pattern and regulation of XBP1 in the mouse uterus during early pregnancy. The methods of immunohistochemistry (IHC) and real time quantitative RT-PCR were used to test XBP1 expression in early pregnancy, artificial decidualization, oestrous cycle and hormone-regulated mouse models. The results showed that XBP1 was spatiotemporally expressed in mouse uterus during early pregnancy. The XBP1 protein was mainly detected in the luminal and glandular epithelia on days 1-4 of pregnancy, and was strongly detected in the decidual area on days 5-8 of pregnancy. Similarly, XBP1 expression was also mainly expressed in decidual cells following artificial decidualization. During the oestrous cycle, Xbp1, Xbp1u, and Xbp1s mRNA was predominantly present in proestrus. In the ovariectomized uterus, the expression of XBP1 in luminal and glandular epithelia was up-regulated after estrogen treatment. These results suggest that XBP1 is associated with embryo implantation and decidualization during early pregnancy in mice, and the expression of XBP1 in luminal and glandular epithelia may be regulated by estrogen.