Objective To evaluate the role of phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) signaling pathway in carbon monoxide (CO)-induced up-regulation of the mitofusin-1 (Mfn1) expression in endotoxin-challenged rat alveolar macrophages.Methods Alveolar macrophages obtained from the rats aged 12-20 weeks were subcuhured and seeded in 96 well plates at a density of 4× 104 cells/ml.After being cultured for 24 h,the cells were divided into 4 groups (n=10 each) using a random number table:control group (group C),endotoxin group (group L),lipopolysaccharide (LPS) +CO-releasing molecule-2 (CORM-2) group (group L+C) and LPS+CORM-2+PI3K inhibitor LY294002 group (group L+C+LY).Cells were cultured normally in group C.Cells were stimulated by using LPS 10 μg/ml in L,L+C and L+C+LY groups.In group L+C,CORM-2 100 μmol was given at 1 h before stimulation with LPS.In group L+C+LY,LY294002 20 μg and CORM-2 100 μ mol were given at 1.5 and 1.0 h before stimulation with LPS,respectively.The cells were continuously incubated for 24 h after the end of treatment.The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in the supernatant were determined by enzyme-linked immunosorbent assay.The expression of PI3K,phosphorylated Akt (p-Akt) and Mfn1 in cells was measured by real-time polymerase chain reaction and Western blot.Results Compared with group C,the concentration of TNF-α was significantly increased,and the IL-10 concentration was decreased in L,L+C and L+C+LY groups (P＜0.05).Compared with group L,the concentration of IL-10 was significantly increased,the TNF-α concentration was decreased,and the expression of PI3K,p-Akt and Mfn1 was up-regulated in group L+C (P＜0.05).Compared with group L+C,the concentration of IL-10 was significantly decreased,the TNF-α concentration was increased,and the expression of PI3K,p-Akt and Mfn1 was down-regulated in group L+C+LY (P＜0.05).Conclusion PI3K/Akt signaling pathway is involved in CO-induced up-regulation of Mfn1 expression in endotoxin-challenged rat alveolar macrophages.

Objective To evaluate the effect of dexmedetomidine on liver injury in the rats with ob?structive jaundice. Methods Forty?five healthy male Sprague Dawley rats, weighing 250-300 g, aged 8-9 weeks, were divided into 3 groups ( n=15 each) using a random number table: sham operation group ( S group) , obstructive jaundice group ( OJ group) and dexmedetomidine group ( D group) . Obstructive jaun?dice was induced in rats by division and double ligation of the common bile duct in OJ and D groups. Dexmedetomidine 100 μg∕kg was injected intraperitoneally at 72 h after establishment of the model in group D. At 3, 5 and 24 h after administration, blood samples were collected from hearts for determination of the plasma alanine aminotransferase (ALT) and C?reactive protein (CRP) levels. After blood sampling at each time point, the specimens from the external right lobe of the liver were obtained for detection of the expres?sion of Toll?like receptor 4 ( TLR4) mRNA ( by real?time polymerase chain reaction) and TLR4 content ( by enzyme?linked immunosorbent assay) in liver tissues and for pathological examination of liver tissues ( with light microscope) . Results Compared with group S, the plasma ALT and CRP levels were significantly increased at each time point after administration, and the expression of TLR4 mRNA in liver tissues was significantly up?regulated, and TLR4 content in liver tissues was significantly increased in OJ and D groups ( P<0?05) . Compared with group OJ, the plasma ALT and CRP levels were significantly decreased at each time point after administration, and the expression of TLR4 mRNA in liver tissues was significantly down?regulated, and TLR4 content in liver tissues was significantly decreased in group D ( P<0?05) . The degree of damage to liver tissues was significantly attenuated in group D compared with group OJ, and was aggrava?ted in group D compared with group S. Conclusion Dexmedetomidine can reduce liver injury in the rats with obstructive jaundice.

Objective To evaluate the efficacy of self?made breathing circuit joint for intermittent positive pressure ventilation ( IPPV) in patients with central airway obstruction undergoing interventional fi?beroptic bronchoscopy ( FOB) . Methods Sixty?two patients of both sexes with central airway obstruction requiring tracheal intubation, aged 60-80 yr, with body mass index of 20-26 kg∕m2 , of American Society of Anesthesiologists physical status Ⅲ or Ⅳ and Medical Research Council dyspnea scale grade Ⅲ or Ⅳ, undergoing interventional FOB under general anesthesia, were divided into 2 groups ( n=31 each) using a random number table:high frequency jet ventilation ( HFJV) group and IPPV group. The patients were tra?cheally intubated after induction of general anesthesia. The self?made breathing circuit joint was connected, then the anesthesia machine was connected to perform IPPV, and the ventilator settings were adjusted to maintain the end?tidal pressure of carbon dioxide 35-45 mmHg in group IPPV, and HFJV was used in group HFJV. Before induction ( baseline) , at 10, 20, 30 and 40 min after start of operation, and at the end of operation, arterial blood samples were collected for blood gas analysis, the pH value, arterial oxy?gen partial pressure, and arterial carbon dioxide partial pressure were recorded. The development of hyper?capnia was recorded. Results Hyoxemia was not found in the two groups. The incidence of hypercapnia was 74%, and in addition the incidence of severe hypercapnia was 10% in group HFJV. The incidence of hypercapnia was 16%, and all the patients presented with permissive hypercapnia in group IPPV. Com?pared with group HFJV, the incidence of hypercapnia was significantly decreased, and the pH value and arterial oxygen partial pressure were increased, and arterial carbon dioxide partial pressure was decreased from 10 min after start of operation to the end of operation in group IPPV (P<0.05). Conclusion The self?made breathing circuit joint provides better efficacy than HFJV when used for IPPV in the patients with central airway obstruction undergoing interventional FOB.

Objective To evaluate the sedative interaction between dexmedetomidine and propofol.Methods Sixty-four American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 20-60 yr,with body mass index of 19.0-25.0 kg/m2,scheduled for elective surgery under general anesthesia,were allocated into 4 groups (n =16 each) using a random number table:different target concentrations of dexmedetomidine groups (D1-4 groups).Dexmedetomidine was administered by target-controlled infusion (TCI) with the Markku model.The target plasma concentrations of dexmedetomidine were 0,0.4,0.6 and 0.8 ng/ml in D1-4 groups,respectively.At 15 min of dexmedetomidine TCI,propofol was given by TCI with Schnider model,and the initial target effect-site concentration was set at 1.0 μg/ml.After the target effect-site and plasma concentrations were balanced,the target effect-site concentration of propofol was gradually increased in increments of 0.2 μg/ml until loss of consciousness (Observer's Assessment of Alertness/Sedation Scale score was 1).The model of pharmacodynamic interaction was used to analyze the sedative interaction between the two drugs.Results There was no statistically significant difference in residual sums of squares fitted by using the model of pharmacodynamic interaction between the target effect-site concentration of propofol and target plasma concentration of dexmedetomidine at loss of consciousness (P＞0.05).The linear dimensionless parameter of pharmacodynamic interaction was 0.The median effective effect-site concentration of propofol was 2.38 μg/ml at loss of consciousness,and the median effective plasma concentration of dexmedetomidine was 2.03 ng/ml at loss of consciousness.Conclusion Dexmedetomidine and propofol interact additively in terms of sedation.

Objective To evaluate the efficacy of closed-loop coadministration of propofol and remifentanil guided by Narcotrend index (NI) in laparoscopic cholecystectomy.Methods Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes,aged 20-64 yr,with body mass index of 18-25 kg/m2,scheduled for elective laparoscopic cholecystectomy,were randomized into 2 groups (n =30 each):program regulation group (group P) and artificial regulation group (group A).After the initial target effect-site concentration of propofol was selected,the target effect-site concentration of remifentanil was determined according to the formula.In group A,the target effect-site concentrations of propofol (2-4 μg/ml) and remifentanil (3-4 ng/ml) were adjusted artificially according to anesthesiologists' experience every 5 min to maintain NI value at 26-46.Induction time,anesthesia induction and mean maintenance doses and the initial,highest and lowest target concentrations of propofol and remifentanil,mean NI value,percentage of time with NI between 26 and 46,emergence time,and development of fluctuation in heart rate or mean arterial pressure ＞ 20％ of the baseline value and intraoperative awareness were recorded.Results No intraoperative awareness was found in the two groups.Compared with group A,the induction time was significantly shortened,the induction dose and initial target concentration of remifentanil were increased,the mean maintenance dose and lowest target concentration of propofol and remifentanil were decreased,the percentage of time with NI between 26 and 46 was increased,and the emergence time was shortened (P＜0.05 or 0.01),and no significant change was found in the induction dose and initial target concentration of propofol,the highest target concentrations of propofol and remifentanil,mean NI value,or incidence of fluctuation in heart rate or mean arterial pressure ＞ 20％ of the baseline value in group P (P＞ 0.05).Conclusion For laparoscopic cholecystectomy,NI-guided closed-loop coadministration of propofol and remifentanil produces safe and effective anesthesia,and the efficacy of precise administration is superior to that of artificially regulated target-controlled infusion.

The effects of positive end-expiratory pressure (PEEP) on pulmonary shunt were studied during gen- eral anesthesia and postoperative period.Twenty cholecystectomy patients were randomly divided into experiment group (group P) and control group (group Z). PEEP and ZEEP were used separately after induction. Artery blood and mixed blood from the right ventricle were taken for blood gas analysis and determine the amount of pulmonary shunting before anesthesia. half and hour, one and half an hour and two and half an hour after anesthesia and one hour after the operation.The results showed that shunt in group P decreased gradually during general anesthesia and returned to the level of preoperation at an hour after operation. Shunt in group Z was increased continually and the level was significantly higher than preoperation an hour after operation. Shunt between two groups was significant difference (P

The effect of transcutaneous stimulation to Hegu, Fengchi and Yuyao points with Han's Acupoint Nerve Stimulator on enflurane anesthsia and the hemodynamic changes during craniotomy were studied in 80 neurosurgical patients. The results showed that acupoint electric stimulation decreased the inhalating concentration and consumption of enflurane. The expired concentration of enflurane in HANS group was significantly lower than that in control group by a reduction of 37.8 % -47. 0%. The cardiovascular depression was lesser during operation, and the patients recovered faster and more stable after operation in HANS group. It was concluded that acupoint stimulation with HANS significantly potentiated the anesthetic effect and decraesed the side effect of enflurane.

This study was concerned about comparing the degree and process of cardiopulmonary effect of propofol and midazolam. Forty-five adult patients,ASA grade Ⅱ, scheduled for elective operation, were randomly allocated to intravenously receiving midazolam 0.28mg?kg~(-1)(group Ⅰ,n=16), 0.40mg?kg~(-1) (group Ⅱ,n=16) ,or propofol 2.5mg?kg~(-1) (group Ⅲ,n=13) ,respectively. MAP ,HR, SpO_2 ,TV ,MV ,RR and P_(ET)CO_2 were monitored continuously before and in 30 minutes following the administration ,and the arterial blood gas analysises were performed before and 1,2,3,4,5,10,15,20 and 30 minutes after the administration. The results showed that in group Ⅰ, Ⅱ and Ⅲ after the administration separately,the maximal decrease of MAP were 20.0% ,22.8% and 22.20%, and occured in 10.8, 9.3 and 3.5 minutes;HR decreased maximally by 6.3% ,8.7% and 15.5%,TV by 76.6% ,81.3% and 91.3%/00 ,MV by 87.2%,91.6% and 93.6%,RR by 60.3%,67.5% and 83.6%; the incidences and durations of apnea were 37.5%vs 57.5 seconds,31.3%vs 68. O seconds and 76.9%vs 73.0 seconds. The MV recovered to the baseline 5 minutes in group Ⅲ and more than 10 minutes in group Ⅰ and Ⅱ following the administration. The arterial blood pH reduced and PaCO_2 increased significantly in three groups (P

To assess the concentration-responses relationships of propofol, 16 adult patient,ASA grade Ⅰ-Ⅱ,scheduled for upper abdominal operation, were randomly allocated to undergoing epidural block (group Ⅰ, n = 8)or combined anesthesia (group Ⅱ, n = 8) respectively. After a bolus injection of propofol 2.5mg ?kg, blood pressure (BP), heart rate (HR) and tidal volume (TV) were recorded, and drowsiness,amnesia,cooperation and orientation were evaluated by scorring scales in both groups. The venous samples were taken before and after the administration to measure the propofol plasma concentration by spectrofluorophotometric detector. The results revealed that there were no significant differences in pharmacokinetic parameters between two groups;the plasma concentration of propofol at 2. 5rag. L~(-1) was required for adequate anesthesia,and 1.5 to 1.9rag. L~(-1) for hypnosis,the patients were fully awake at 0.94?0.3mg. L~(-1); BP,HR and TV were significantly depressed at more than 2.0rag. L~(-1), and recovered to baseline at less than 1.5mg. L~(-1). It is suggested that there are good relationships between propofol plasma concentrations and its pharmacodynamic responses.

Objective:To test the role of tumor necrosis factor-?(TNF-?)in acute lung injury and study new treatment.Method:The rabbit acid aspiration models were induced with 0.1N hydrochloric acid (HCI). Twenty rabbits were divided randomly into HCl group,verapamil and vitamin C groups.The plasma levels of TNF-? and malondialdehyde (MDA) were measured,and polymorphonuclear neutrophils (PMN)were counted in lung tissue of all animals. Result:There were increases in TNF-?,MDA and PMN after acid aspiration,which can be inhibited by verapamil and vitamin C. Conclusion:PMN can be induced by TNF-?.Vitamin C and verapamil provide a obvious protection on pulmonary tissue after acid aspiration.