Objective:To evaluate the effect of lipoxin A4 on lipopolysaccharide (LPS)-induced activation of microglia and role of silent information regulator sirtuin 1 (SIRT1)/NF-κB signaling pathway.Methods:This experiment was performed in two parts.PartⅠ The well-growth BV2 microglia were divided into 4 groups ( n=30 each) using a random number table method: control group (group C), LXA4 group (group LXA4), LPS group (group LPS) and LPS+ LXA4 group (group LLI). PartⅡ The well-growth BV2 microglia were divided into 2 groups ( n=30 each) using a random number table method: LPS+ LXA4 group (group LL2) and LPS+ LXA4+ SIRT1 inhibitor EX527 group (group LLE). Cells in group C were commonly cultured without any treatment. In LXA4 group and LPS group, LXA4 (final concentration 100 nmol/L) and LPS (final concentration 100 ng/ml) were added respectively, and then the cells were incubated for 24 h. In LL1 group and LL2 group, LXA4 (final concentration 100 nmol/L) was added at 1 h before treatment with LPS, and the other treatments were similar to those previously described in LPS group. EX527 (final concentration of 5 μmol/L) was added at 30 min before treatment with LXA4, and the other treatments were similar to those previously described in LL2 group.The expression of inducible nitricoxide synthase (iNOS), CD32, arginine synthase 1 (Arg-1), CD206, interleuckin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and IL-10 mRNA was detected by real-time polymerase chain reaction. The concentrations of IL-1β, IL-6, TNF-α and IL-10 in the supernatant were measured using enzyme-linked immunosorbent assay. The content of ROS was detected by DCFH-DA. The activity of SOD was measured by WST-8 assay. The expression of NADPH oxidase 2 (NOX2), superoxide dismutase 1 (SOD1), heme oxygenase-1 (HO-1), SIRT1 and acetylated NF-κB p65 was detected by Western blot. Results:Compared with group C, the expression of iNOS, CD32, IL-1β, IL-6 and TNF-α mRNA was significantly up-regulated, the concentrations of IL-1β, IL-6 and TNF-α in the supernatant were increased ( P<0.05), no significant change was found in the expression of Arg-1, CD206 and IL-10 mRNA and IL-10 concentrations in the supernatant, the expression of NOX2 and HO-1 was up-regulated, SOD1 expression was down-regulated, the activity of SOD was decreased, the content of ROS was increased, the expression of SIRT1 was down-regulated, and the expression of acetylated NF-κB p65 was up-regulated in group LPS ( P<0.05). Compared with group LPS, the expression of iNOS, CD32, IL-1β, IL-6 and TNF-α mRNA was significantly down-regulated, the expression of Arg-1, CD206 and IL-10 mRNA was up-regulated, concentrations of IL-1β, IL-6 and TNF-α in the supernatant were decreased, the concentration of IL-10 was increased, the expression of NOX2 was down-regulated, the expression of HO-1 and SOD1 was up-regulated, the activity of SOD was increased, the content of ROS was decreased, the expression of SIRT1 was up-regulated, and the expression of acetylated NF-κB p65 was down-regulated in group LL1 ( P<0.05). Compared with group LL2, the concentrations of IL-1β, IL-6 and TNF-α in the supernatant were significantly increased, the activity of SOD was decreased, the content of ROS was increased ( P<0.05), and no significant change was found in the IL-10 concentration in the supernatant in group LLE ( P>0.05). Conclusions:LXA 4 can inhibit LPS-induced polarization of microglia to M1 phenotype, and the mechanism may be related to enhancement of SIRT1 activity and inhibition of NF-κB transcriptional activity.

Objective:To determine the optimal concentration of inhaled oxygen in pediatric patients undergoing laparoscopic choledochal cyst resection under general anesthesia.Methods:Seventy-five pediatric patients of both sexes, aged 1-3 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with body mass index of 15-18 kg/m 2, with expected operation time≥3 h, scheduled for elective laparoscopic choledochal cyst resection with general anesthesia, were divided into 3 groups ( n=25 each) using a random number table method: C 40 group (FiO 2=40%), C 30 group (FiO 2=30%) and C 21 group (FiO 2=21%). Blood samples were collected from the radial artery for blood gas analysis after operation for determination of oxygenation index (OI), respiratory index (RI), alveolar-arterial oxygen partial pressure difference (PA-aO 2) and arterial-alveolar oxygen partial pressure ratio (PaO 2/PAO 2). The occurrence of high risk events of hypoxia (SpO 2<94%), extubation time, and occurrence of pneumonia and atelectasis at day 7 after operation were recorded. Results:Compared with C 21 group, PaO 2, PAO 2, PA-aO 2 and RI were significantly increased, PaO 2/PAO 2 was decreased, and the incidence of high risk events of hypoxia was decreased in C 30 and C 40 groups, and the incidence of atelectasis in C 30 group and pneumonia and atelectasis in C 40 group was increased at day 7 after operation ( P<0.05). Compared with C 30 group, PaO 2, PAO 2, PA-aO 2 and RI were significantly increased, and PaO 2/PAO 2 was decreased in C 40 group ( P<0.05). Conclusions:The optimal concentration of inhaled oxygen recommended is 21%-30% in the pediatric patients undergoing laparoscopic choledochal cyst resection under general anesthesia.

Objective:To evaluate the relationship between early postoperative cognitive dysfunction and neuromodulator protein 1β(NRG1β) in aged rats.Methods:Pathogen-free healthy male Sprague-Dawley rats, aged 18-20 months, weighing 600-700 g, were divided into 3 groups ( n=10 each) using a random number table method: control group (group C), operation group (group O) and NRG1β group (group N). Exploratory laparotomy was performed in group O and group N. NRG1β 0.5 μg/kg was slowly injected into the lateral ventricle on 1 day before surgery in group N, while the equal volume of 0.1 mol/L phosphate buffer solution was given instead in C and O groups.Learning and memory function was assessed using Morris water maze test performed at day 3 after operation.The rats were then sacrificed, and the hippocampi were removed for determination of the expression of nuclear factor kappa B (NF-κB) p65 (by Western blot) and contents of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay). Results:Compared with group C, the postoperative escape latency was significantly prolonged, the expression of NF-κB p65 was up-regulated, and the contents of IL-1β and TNF-α were increased in group O and group N ( P<0.05). Compared with group O, the postoperative escape latency was significantly shortened, the expression of NF-κB p65 was down-regulated, and the contents of IL-1β and TNF-α were decreased in group N ( P<0.05). Conclusion:NRG1β is involved in the endogenous protective mechanism of early postoperative cognitive dysfunction probably by inhibiting the activation of NF-κB pathway and inhibiting inflammatory responses in aged rats.

Objective:To evaluate the changes in the expression of hippocampal HSP70 during postoperative cognitive dysfunction in aged rats.Methods:Twelve pathogen-free healthy male Sprague-Dawley rats, aged 18 weeks, weighing 500-650 g, were divided into 2 groups ( n=6 each) using a random number table method: old control group (group O) and old surgery group (group OS). Another 12 pathogen-free healthy male Sprague-Dawley rats served as control and divided into 2 groups ( n=6 each) according to a random number table method: adult control group (group A) and adult surgery group (group AS). Exploratory laparotomy was performed in group AS and group OS.Morris water maze test was performed at 3 days after operation, and then the rats were sacrificed, and the hippocampi were removed for determination of the expression of heat shock protein 70 (HSP70) (by Western blot) and contents of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay). Results:Compared with group A, the expression of HSP70 was significantly up-regulated ( P<0.05), and no significant change was found in the other indices in group AS ( P>0.05). Compared with group O, the escape latency was significantly prolonged, the frequency of crossing platform was decreased, the contents of IL-1β and TNF-α were increased, and the expression of HSP70 was up-regulated in group OS ( P<0.05). Compared with group AS, the escape latency was significantly prolonged, the frequency of crossing platform was decreased, the contents of IL-1β and TNF-α were increased ( P<0.05), and no significant change was found in the expression of HSP70 in group OS ( P>0.05). Conclusion:HSP70 expression in hippocampi is up-regulated during postoperative cognitive dysfunction and is helpful in inhibiting the inflammatory response and exerting endogenous neuroprotective effect in aged rats.

Objective To determine the median effective concentration(EC50)of sevoflurane in?hibiting responses to laryngeal mask airway(LMA)removal in pediatric patients under comprehensive clin?ical conditions. Methods Twenty?six pediatric patients of both sexes, aged 1-5 yr, with body mass index of 15-20 kg∕m2, of American Society of Anesthesiologists physical statusⅠ, scheduled for elective minor surgery, were enrolled in this study. Anesthesia was induced by inhaling 8% sevoflurane and injecting dezocine 0.1 mg∕kg. The LMA painted with Teracainum Plasmagel was inserted. Anesthesia was maintained by sevoflurane inhalation and target?controlled infusion of remifentanil. Remifentanil infusion was stopped at 5 min before the end of surgery. At the end of surgery, the end?tidal concentration of sevoflurane was main?tained at the target concentration for at least 10 min and then the laryngeal mask airway was removed. The end?tidal concentration of sevoflurane was determined by using Dixon′s up?and?down sequential method. The end?tidal concentration of sevoflurane was set at 0.8% in the first pediatric patient. Each time the concen?tration of sevoflurane increased∕decreased by 0.1% in the next pediatric patient according to patient′s re?sponses to LMA removal. Results The EC50of sevoflurane inhibiting responses to LMA removal was 0.59%, and the 95% confidence interval was 0.55%-0.63% in pediatric patients under comprehensive clinical conditions. Conclusion The EC50of sevoflurane inhibiting responses to LMA removal is 0.59% in pediatric patients under comprehensive clinical conditions.

Objective To evaluate the role of conventional protein kinase Cγ (cPKCγ)/growthassociated protein-43 (GAP-43) signaling pathway in ketamine-induced apoptosis in hippocampal neurons of developing rats in an in vitro experiment.Methods Primarily cultured hippocampal neurons were seeded in culture plates at a density of 1×10.6 cells/ml and divided into 2 groups (n=10 each) using a random number table:control group (C group) and ketamine group (K group).Group C received no treatment.Ketamine was added with the final concentration of 300 μmol/L in group K.At 12 h of culture or incubation,the apoptosis in hippocampal neurons was detected by flow cytometry.The apoptotic rate was calculated.The expression of cPKCγ,GAP-43 and phosphorylated GAP-43 in hippocampal neurons was measured by Western blot.Results Compared with group C,the apoptotic rates of hippocampal neurons were significantly increased,and the expression of cPKCγ,GAP-43 and phosphorylated GAP-43 was down-regulated in group K (P<0.01).Conclusion The mechanism by which ketamine induces apoptosis in hippocampal neurons of developing rats may be related to inhibition of cPKCγ/GAP-43 signaling pathway activation in an in vitro experiment.

Objective To observe the effects of obesity on dose-response curve of rocuronium in female patients and calculate ED9 5 of rocuronium.Methods Eighty female patients,aged 18-45 years, falling into ASA grade Ⅰ or Ⅱ,schedualed for elective surgery under general anesthesia,undergoing surgery less than 1.5 h,were included in the study.The patients with body mass index of 20-25 kg/m2 as group N were randomized to divided group N1,group N2,group N3 and group N4.Anoth-er 40 patients with body mass index of 30-35 kg/m2 as group B were randomized to divided group B1, group B2,group B3 and group B4.When the first twitch height of TOF (T1)was 100%,groups N1-N4 and groups B1-B4 patients were injected rocuronium 0.075,0.1,0.1 5,0.3 mg/kg respectively. The first dose of rocuronium in each group,T1 maximum inhibition degree and onset time were re-corded.The relationship between probit-transformed depression of T1 and the logarithm dose of rocu-ronium was analyzed by linear regression.ED50 and ED9 5 of rocuronium in obese and normal body weight patients were calculated.Results Dose-response curve equation of each group were Y1 =3.464X1 -2.23 and Y2 = 3.843X2 - 2.750 respectively(P < 0.05 ).The ED50 and ED9 5 (95% CI)of rocuronium were 0.122 (0.092-0.1 65 )mg/kg and 0.324 (0.242-0.433 )mg/kg in group N,and were 0.103 (0.078-0.133)mg/kg and 0.25 1 (0.1 93-0.326)mg/kg in group B.Conclusion Obesity significantly affects the dose-response curve of young women and can enhance the sensitivity of them to the rocuronium.The ED9 5 of obese patients is 0.25 1 mg/kg.

Objective To evaluate the role of Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway in propofol-induced neuroapoptosis in the hippocampus of newborn rats.Methods Experiment Ⅰ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1×106 cells/ml and divided into 2 groups (n=6 each) using a random number table:solvent control group (C group) and propofol group (P group).Propofol was added with the final concentration of 60 μg/ml in group P.Dimethyl sulfoxide was added with the final concentration of 0.04％ in group C.The expression of RhoA and ROCK2 in hippocampal neurons was measured by Western blot at 24 h of incubation.Experiment Ⅱ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1 × 106 cells/ml and divided into 3 groups (n =6 each) using a random number table:solvent control group (C group),propofol group (P group) and propofol plus specific RhoA/ROCK2 signaling pathway blocker Y27632 group (P+Y group).Propofol was added with the final concentration of 60 μg/ml in group P.Propofol at the final concentration of 60 μg/ml and Y27632 at the final concentration of 10 μmol/L were added in group P+Y.Dimethyl sulfoxide was added with the final concentrauon of 0.04％ in group C.At 24 h of incubation,the neuroapoptosis in hippocampi was detected by flow cytometry,and the expression of activated caspase-3 in hippocampal neurons was measured by Western blot.The apoptotic rate was calculated.Results Experiment Ⅰ Compared with group C,the expression of RhoA and ROCK2 in hippocampal neurons was significantly up-regulated in group P (P＜0.05).Experiment Ⅱ Compared with group C,the apoptotic rate of hippocampal neurons was significantly increased,and the expression of activated caspase-3 was up-regulated in P and P+Y groups (P＜0.05 or 0.01).Compared with group P,the apoptotic rate of hippocampal neurons was significantly decreased,and the expression of activated caspase-3 was down-rcgulatcd in group P + Y (P＜ 0.05).Conclusion Activation of RhoA/ROCK2 signaling pathway is involved in propofol-induced neuroapoptosis in hippocampi of newborn rats.

Objective To evaluate the relationship between the mechanism underlying propofol-induced inhibition of migration of human breast cancer cells and glyc olysis.Methods Human breast cancer cell line MDA-MB-231 cells were inoculated in 12-well culture plates at a density of 3× 105 cells/well.After being cultured for 24 h,the cells were divided into 2 groups (n=12 each) by using a random number table:control group (group C) and propofol group (group P).Propofol at the final concentration of 5 μg/ml was added to the culture medium in group P,and the equal volume of phosphate buffer solution was added to the culture medium in group C.At 6 h of incubation,the culture media were changed to the common culture media containing no drugs,and the cells were then incubated for another 24 h.The culture media were collected for determination of glucose concentrations (by oxidase mnethod) and lactate concentrations (by chemical colorimetry).Glucose consumption and lactate production were calculated according to glucose and lactate concentrations.Cells were collected,the expression of lactate dehydrogenase A was detected by Western blot,and the migration of cells was determined by cell scratch test.Results Compared with group C,the consumption of glucose and production of lactate were significantly decreased,the expression of lactate dehydrogenase A was down-regulated,and the migration rate was decreased in group P (P＜0.05).Conclusion The mechanism by which propofol inhibits migration of human breast cancer cells may be associated with inhibition of glycolysis.

Objective To observe the effect of multiple monitoring of total intravenous anes-thesia on postoperative cognitive function in elderly patients.Methods Elective 100 patients undergo-ing general anesthesia for abdominal operation,56 males,44 females,aged 65-80 years,ASA physi-cal status Ⅱ or Ⅲ.All patients were divided into multiple monitoring group (group M)and routine monitoring group (group R)by random digital table method,n =50 each.In group M,the anesthesi-ologists modulated anesthetic drugs to make NTI of 37-56 and rSO 2 higher than 50% or not lower than the baseline value by 20%,while in group R the infusion rate of propofol,remifentanil and cisa-tracurium was adjusted by anesthesiologists according to anesthesiologist’s experiences by the pa-tients’monitoring index.Cognitive function of patients in the two groups were evaluated using MMSE 1 d before surgery and 1 d,3 d,7 d,1 month and 3 months after surgery.The occurrence of cognitive dysfunction 7 d,1 month and 3 months after surgery,the postoperative recovery and the dosage of propofol,remifentanil and cisatracurium were recorded.Blood was randomly selected from each group to determine the serum content of S100βand Aβ1-42 by ELISA method at the time point of before surgery (T0 ),one hour after starting surgery (T1 ),the end of surgery (T2 )and postopera-tive 24 hours (T3 ).Results The incidence of postoperative cognitive decline in group M on 1 d (8%vs.22%),3 d (2% vs.1 6%)after surgery were significantly lower than that in group R (P <0.05). Postoperative cognitive dysfunction between the two groups 7 d and 1 month,3 months after surgery has no statistical significance.The dose of propofol [(3.3 ± 0.8)mg · kg-1 · h-1 vs.(3.7 ± 0.7 ) mg·kg-1 ·h-1 ,P < 0.05 ] and cisatracurium [(104 ± 47 )μg · kg-1 · h-1 vs.(124 ± 68 )μg·kg-1 ·h-1 ,P <0.05]in group M was less than that in group R.The time of eye-opening [(10 ±3)min vs.(1 6±6)min,P <0.01],extubation [(13±3)min vs.(22±7)min,P <0.01]and lo-cation [(1 7±4)min vs.(27 ±9)min,P <0.01 ]was shorter in group M.Compared with T0 ,the serum level of S100βprotein was significantly increased in group M at T1 ,T2 and group R at T1-T3 (P <0.05);The level of serum S100βprotein in group M was significantly lower than that in group R (P <0.05).Compared with T0 ,Aβ1-42 protein level was significantly reduced in two groups at T1 and T2 (P <0.05),but there was no significant difference between the two groups.Conclusion Total intravenous anesthesia with multiple monitoring can reduce neural injury and reduce the incidence of early postoperative cognitive decline in elderly patients with abdominal surgery,but has no significant effect on the incidence of POCD.