RESUMEN
Norepinephrine (NE) is often administered during the perioperative period of liver transplantation to address hemodynamic instability and to improve organ perfusion and oxygen supply. However, its role and safety profile have yet to be evaluated in pediatric living donor liver transplantation (LDLT). We hypothesized that intraoperative NE infusion might affect pediatric LDLT outcomes. A retrospective study of 430 pediatric patients (median [interquartile range] age, 7 [6.10] months; 189 [43.9%] female) receiving LDLT between 2014 and 2016 at Renji Hospital was conducted. We evaluated patient survival among recipients who received intraoperative NE infusion (NE group, 85 recipients) and those that did not (non-NE group, 345 recipients). The number of children aged over 24 months and weighing more than 10 kg in NE group was more than that in non-NE group. And children in NE group had longer operative time, longer anhepatic phase time and more fluid infusion. After multivariate regression analysis and propensity score regression adjusting for confounding factors to determine the influence of intraoperative NE infusion on patient survival, the NE group had a 169% more probability of dying. Although there was no difference in mean arterial pressure changes relative to the baseline between the two groups, we did observe increased heart rates in NE group compared with those of the non-NE group at anhepatic phase (P=0.025), neohepatic phase (P=0.012) and operation end phase (P=0.017) of the operation. In conclusion, intraoperative NE infusion was associated with a poorer prognosis for pediatric LDLT recipients. Therefore, we recommend the application of NE during pediatric LDLT should be carefully re-considered.
RESUMEN
Endothelial progenitor cell (EPC)-induced angiogenesis activity is enhanced in hepatocellular carcinoma (HCC); however, the contributing factors remain unknown. The present study aimed to investigate the factors influencing the number of EPCs and circulating progenitor cells (CPCs), as well as the expression levels of vascular endothelial growth factor receptor 2 (VEGFR-2) and CD34, in patients with HCC. The expression levels of VEGFR-2 and CD34 were assessed in 72 HCC tumor and matched adjacent tissue microarrays by immunohistochemistry. The associations between VEGFR-2 or CD34 expression in tumors, clinicopathological characteristics and overall survival rates were analyzed. The number of EPCs and CPCs were analyzed in the peripheral blood of patients with HCC. In this study, high expression levels of VEGFR-2 and CD34 were detected in the tumor tissues of 41 (56.9%) and 44 (61.1%) patients, respectively. VEGFR-2 expression was significantly associated with tumor size (P<0.001), bile acid level (P=0.014) and α-fetoprotein level (P=0.011). However, CD34 expression was associated with tumor size (P=0.009), recrudescence (P<0.001) and bile acid (P=0.009). Next, the expression levels of VEGFR-2 and CD34 in tumor and adjacent tissues were compared according to the bile acid level. VEGFR-2 and CD34 expression levels were both higher in the high bile acid group, whereas expression levels of the markers were higher in adjacent tissues compared with tumor tissues. Kaplan-Meier curve analysis identified that patients with low CD34 expression had a longer overall survival compared with patients with high CD34 expression (P=0.029). Multivariate analysis also indicated that both VEGFR-2 (P=0.020) and CD34 (P=0.035) were independent prognostic risk factors. Moreover, flow cytometry demonstrated that the number of EPCs and CPCs was negatively related with the bile acid levels in patients with HCC. In conclusion, in patients with HCC, bile acid promotes EPC-induced angiogenesis. Furthermore, EPCs and CPCs may be activated by bile acid in tumors but are more so in adjacent tissues.
RESUMEN
Physical stress is one of the most important factors affecting morphine-induced conditioned place preference (CPP). Convincing evidences demonstrate that physical stress can activate lateral habenular (LHb) neurons. However, the mechanism by which physical stress regulates morphine-induced CPP through LHb remains unclear. In this study, we examined the impact of forced swimming stress (FSS) on morphine-induced CPP in rats. We found that FSS significantly decreased the CPP scores of rats compared with the normal morphine administration rats. Meanwhile, we detected the expression of DARPP-32 phosphorylation (p-DARPP-32) in the nucleus accumbens (NAc), and CaMKII in LHb. The results show that FSS enhanced the expression of CaMΚII in LHb, while it reduced the level of p-DARPP-32 expression in the NAc. Furthermore, by microinjecting AAV-CaMKII or AAV-RNAi into LHb, we demonstrated that an overexpression of CaMKII could reduce morphine-induced CPP scores of rats, while knock-down CaMΚII could restore morphine-induced CPP scores, which were interfered by FSS. In addition, by microinjecting DiI into the ventral tegmental area (VTA) and tail of VTA (tVTA) unilaterally, and an anterograde tracing virus (AAV-CaMKII-mCherry) into LHb unilaterally, we verified the neural projections from LHb to tVTA. Taken together, our findings suggest that FSS could activate LHb neurons through CaMΚII, and inhibit morphine-induced CPP through the LHb-tVTA pathway.
