Comparisons of different methods of anesthesia and analgesia on the levels of glycometabolism rate-limiting enzymes in erythrocytes and plasma glucose and stress hormones in patients undergoing esophagus surgery

Objective： To compare the effects of different methods of anesthesia and analgesia on the activities of phosphofructokinase（PFK）, glucose-6-phosphate dehydrogenase（G-6PD） and aldose reductase（AR） in erythrocytes and levels of plasma glucose and stress hormones in patients undergoing esophagus surgery. Methods： Sixty-two patients scheduled for esophagus surgery were randomly divided into three groups： group Ⅰ （n = 20） receiving only general anesthesia（GA） followed by intravenous patient controlled analgesia（PCA） with fentanyl 15 μg/kg. The other two groups receiving both general anesthesia combined with thoracic epidural anesthesia （GEA） and either intravenous PCA with fentanyl 15 μg/kg （group Ⅱ, n = 21） or thoracic epidural analgesia（TEA） with 0.125% ropivacaine and 0.0002% fentanyl mixture（group Ⅲ, n = 21） after the operation. Venous blood samples were collected for measurements of PFK, G-rPD and AR activities in erythrocytes and plasma glucose, cortisol, epinephrine and norepinephrine before induction （T1）, 60 min following the incision （T2）, 60 min（T3） after operation, on the lst（T4） and 2nd postoperative day（T5）. Results： The activities of PFK decreased（P 〈 0.01 or P = 0.004） and the activities of G-6PD and AR increased（P 〈 0.01） in groups Ⅰ and Ⅱ on T4 compared with those on T1 Between the two groups, the activities of these enzymes in group Ⅱ changed less than those of group Ⅰ （P 〈 0.01 or P 〈 0.05）. These enzymes activities changed slightly in group Ⅲ on T4（P 〉 0.05）. There were significant differences between group Ⅲand the other two groups（P 〈 0.0l or P 〈 0.05）. The levels of plasma glucose increased significantly on T2（P 〈 0.01）, reached peak values on Ta（P 〈 0.01） and fell on T5 in the three groups. Compared to those of groups Ⅰ and Ⅱ, the values of plasma glucose in group Ⅲwere lower on T4 and T5（P 〈 0.05 or P 〈 0.01）. The cortisol concentration in each group increased significantly at T2（P 〈 0.01 or P 〈 0.05）, and remained elevated on T5（P 〈 0.01 or P 〈 0.05）, while on T2 and T3 the cortisol levels＇ of group I were higher than that of groups Ⅱand Ⅲ （P 〈 0.05）. The levels of group Ⅲ were lower than those of the other groups on T4 and T5（P 〈 0.01 or P 〈 0.05）. The levels of epinephrine and norepinephrine were also significantly higher in group Ⅰ than those of the other two groups on T2（P 〈 0.01 or P 〈 0.05）, and their levels in group Ⅰ and Ⅱ were higher than that of group Ⅲ on T4. The patients of the three groups obtained satisfactory pain relief, with all Vidual Analogue Scale（VAS） scores less than 3. VAS scores of group I were much greater 4h after operation. Group m VAS scores were the lowest 24h after operation. However, the number of times patients pressed the bolus switch was higher in group Ⅱ （P 〈 0.01）. Conclusion： Compared with GA and intravenous PCA, general anesthesia combined with thoracic epidural anesthesia and analgesia obtain better pain relief and could markedly alleviate the stress response and improve these erythrocyte glucose metabolism changes after esophagus surgery.

Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions

Autoimmune diseases are characterized by an imbalance between regulatory T cells and effector T-cell subsets, such as Thl and Th17 cells. Studies have confirmed that natural CD4＋Foxp3＋ Tregs were unstable and dysfunctional in the presence of pro-inflammatory cytokines. In the current study, human CD39hi Tregs and CD39low Tregs were sorted from Tregs in vitro after 7 days of expansion. The functions of both Treg subsets were investigated under inflammatory conditions in vitro and in vivo. In the presence of IL-1β and IL-6, cultured CD4＋CD39hi Tregs maintained stable forkhead box protein 3 expression, whereas CD4＋CD39low Tregs lost Foxp3 expression and trans-differentiated into Thl or Th17 cells. Decreased IL-1βR and IL-6R expression on the CD39hi Tregs was the primary mechanism responsible for Treg stability. In addition, reduced activation of downstream molecules, such as STAT1 and STAT3, through the modulation of CpG demethylation played an important role. Finally, human CD4＋CD39hi Tregs but not CD4＋CD39low Tregs protected against xenograft versus host disease in model mice. These results strongly implied the physiological importance of CD39 expression and suggested that manipulation of CD39hi Tregs might represent a novel strategy for the treatment of autoimmune diseases.