Objective To evaluate the influence of dexmedetomidine（Dex） on sedation and requirement of propofol during anesthesia induction. Methods Thirty patients（ASA Ⅰ or Ⅱ） undergoing selective operation were randomly divided into 2 groups：Dexmedetomidine group （group D,n=15） or control group （group C,n=15）. Patients in the group D received 1 μg/kg dex diluted to 10ml over 10 min by pumped infusion and patients in the group C was simply recieved normol saline at the same way.Twenty minutes after administrating the drug,patients in both groups were pumped propofol at the speed of 0.4 mg·kg-1·min-1. When holding up jaw without movement,patients received 1 μg/kg fentanyl and 0.6 mg/kg rocuronium,and endotracheal intubated 1.5 minutes later. RE,SE,Ramsay sedation scale of the patients were recorded before（T0） and after 5,10,20 minutes（T1-T3） of drug adminstration.The minimum dose and total dose of propofol during induction were recorded.Results Compared with group C and T0,RE and SE in group D decreased obviously at T1-T3 （P0.01）,while Ramsay sedation scale rised significantly （P0.01）. Compared with group C,the minimum dose and the total dose of propofol decreased obviously in group D during induction （P0.01）.Conclusion Dexmedetomidine causes sadetive without respiratory depression,and has the propofol sparing effect during anesthesia induction.

Objective To evaluate the role of interlukin-6 and signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway in the up-regulation of high mobility group box 1 (HMGB1) expression in lung tissues in septic rats.Methods Ninety healthy male Wistar rats,aged 10-14 weeks,weighing 250-300 g,were randomly divided into 3 groups (n =30 each):sham operation group (group S),cecal ligation and puncture (CLP) group and anti-IL-6 monoclonal antibody group (group IL-6).Sepsis was induced by CLP.Anti-IL-6 monoclonal antibody 0.5 mg/kg was injected intraperitoneally 1 h before CLP,while the equal volume of normal saline was given in groups S and CLP.Six rats in each group were sacrificed at 6,12,24,48 and 72 h after CLP and lungs were removed for determination of HMGB1 content (by RT-PCR),HMGB1 mRNA expression (by ELISA) and STAT3-DNA binding activity (by electrophoretic mobility shift assay) in lung tissues.Results Compared with S group,HMGB1 content,HMGB1 mRNA expression and STAT3-DNA binding activity were significantly increased in groups CLP and IL-6 (P ＜ 0.05).HMGB1 content,HMGB1 mRNA expression and STAT3-DNA binding activity were significantly lower in group IL-6 than in group CLP (P ＜ 0.05).Conclusion IL-6/STAT3 signaling pathway is involved in the up-regulation of HMGB1 expression in lung tissues in septic rats.

Objective To evaluate the effect of lovastatin on shedding of heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC-1) in the lung tissues of rats with sepsis-induced acute lung injury.Methods One-hundred and twenty male Wistar rats aged 8-12 weeks,weighing 325-425 g,were randomly divided into 3 groups (n =40 each) using a random number table:sham operation group (group S),cecal ligation and puncture (CLP) group and lovastatin group (group L).Lovastatin 4 mg/kg was injected once a day for 5 consecutive days in S and L groups,while the equal volume of 0.5％ CMC (the solvent) was given in CLP group.Sepsis was produced by CLP on 5th day of administration in CLP and L groups.The left lung was lavaged at 24 h after operation.The broncho-alveolar lavage fluid (BALF) was collected for determination of protein concentrations,white blood cell (WBC) count and percentage of neutrophils.Blood samples were collected for determination of the concentrations of HSPG and SDC-1 in serum (by ELISA).Evans blue was injected at 24 h after operation in the remaining 20 rats of each group.The lungs were removed for examination of the pathological changes and for measurement of HSPG and SDC-1 mRNA and protein expression (using Western blot and PCR),and Evans blue content (reflecting pulmonary capillary permeability) in the lung tissue.Results Compared with group S,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly increased,and HSPG and SDC-1 mRNA and protein expression was down-regulated in CLP and L groups.Compared with group CLP,the protein concentrations,WBC count and percentage of neutrophils in BALF,Evans blue content in lung tissues and the concentrations of HSPG and SDC-1 in serum were significantly decreased,and HSPG and SDC-1 mRNA and protein expression was up-regulated in group L.The pathological changes of lungs were significantly attenuated in group L as compared with group CLP.Conclusion The mechanism by which lovastatin attenuates acute lung injury induced by sepsis may be related to reduced shedding of HSPG and SDC-1 in lung tissues and improved function of pulmonary vascular endothelium in rats.

Objective To observe the protective effects of lovastatin against lung injury and the expression changes of adiponectin in the septic rats.Methods Fifty four male Wistar rats weighting 250-300g were randomly divided into the three groups:sham operation group ( group Sham) ,sepsis group ( group CLP) and lovastatin interven tion group (group LOV).Rats were injected with lovastatin (4mg/kg) or 0.5%CMC (vehicle) for five days and then subjected to CLP.At 4h,12h and 24h after operation.BALF was collected to determine the levels of TNF-αand IL-6,lung tissue was obtained to observe histopathological changes,and to detect the content of MPO and MDA,the blood sample was obtained to detect the level of adiponectin.Results In the group Sham,at 4h,12h and 24h time points,the levels of TNF-αwere (1.80 ±0.13)pg/mL,(2.04 ±0.15)pg/mL and (1.930.19)pg/mL;the levels of IL-6 were (20.56 ±0.23)pg/mL,(18.35 ±0.15) pg/mL and (21.23 ±0.20) pg/mL;the contents of MPO were (2.82 ±0.14) U/g tissue,(2.88 ±0.07) U/g tissue and (2.76 ±0.18) U/g tissue;and the levels of MDA were (3.32 ±0.12)nmol/mg,(3.09 ±0.11)nmol/mg and (3.21 ±0.08)nmol/mg;the concentrations of adiponectin were (2.68 ±0.14)μg/mL,(2.80 ±0.07)μg/mL and (2.86 ±0.18)μg/mL.Compared with group Sham,both LOV group and CLP group had increased pulmonary damage:(1)the levels of TNF-α[4h,12h and 24h were (4.23 ± 0.18)pg/mL,(5.62 ±0.24)pg/mL and (5.14 ±0.10)pg/mL,t=28.41,30.98 and 36.62]and IL-6[4h,12h and 24h were (39.12 ±0.17) pg/mL,(47.25 ±0.21) pg/mL and (44.690.27) pg/mL,t =158.90,273.40 and 127.28] of the CLP group in BALF were both increased,and MPO[4h,12h and 24h were (4.85 ±0.13) U/g tissue, (6.17 ±0.08)U/g tissue and (7.84 ±0.10)U/g tissue,t=26.39,79.40 and 60.43]and MDA[4h,12h and 24h were (6.24 ±0.06)nmol/mg,(7.56 ±0.15)nmol/mg and (8.43 ±0.10)nmol/mg,t=53.31,58.86 and 90.06] concentrations in lung homogenate were raised with the decreased expression of serum adiponectin[4h,12h and 24h were (1.35 ±0.10)μg/mL,(1.17 ±0.07)μg/mL and (1.24 ±0.11)μg/mL,t=19.86,12.75 and 18.81](all P<0.05);(2) meanwhile the levels of TNF-α[4h,12h and 24h were (2.85 ±0.17) pg/mL,(3.720.13) pg/mL and (3.240.09)pg/mL,t=12.02、20.73 and 16.68]and IL-6[4h,12h and 24h were (30.75 ±0.22)pg/mL, (37.52 ±0.29)pg/mL and (32.43 ±0.26)pg/mL,t=78.42,68.29 and 83.67]in BALF of the LOV group were all increased,the contents of MPO[4h,12h and 24h were(3.59 ±0.05)U/g tissue,(4.67 ±0.11)U/g tissue and (5.33 ± 0.05)U/g tissue,t=12.03,33.63 and 33.70]and MDA[4h,12h and 24h were (4.45 ±0.10)nmol/mg,(5.01 ± 0.11)nmol/mg and (5.83 ±0.04) nmol/mg,t =17.72,30.23 and 71.75] were also increased with the serum adiponectin concentrations[4h,12h and 24h were (2.09 ±0.08)μg/mL,(2.07 ±0.05)μg/mL and (2.03 ± 0.10)μg/mL,t=8.96,20.79 and 6.30]dicreased(all P<0.05).There were less histopathological changes in the LOV group,and the levels of TNF-α(t=13.46,17.05 and 15.43),IL-6(t=73.70,64.10 and 80.12),MPO(t=22.16,27.01and 32.86) and MDA(t=37.59,42.72 and 59.13) were lower than those in CLP group,also the level of adiponectin(t=14.15,8.10 and 3.19) increased siginificantly(all P<0.05).Conclusion Administration of lovastatin could attenuate lung injury of the sepsis by down-regulate the level of TNF-αand IL-6,with reduced inflam-matory response and oxidative stress,and could upregulate the level of adiponectin in serums of rats with sepsis.

Objective To evaluate the effects of rapamycin combined with rosiglitazone on lung injury in septic rats.Methods One hundred and twenty healthy male Wistar rats were randomly divided into 5 groups (n =6 each):sham operation group (group S); cecum ligation and punture (CLP) group; rapamycin group (group RPM) ; rosiglitazone group (group RGZ) ; rapamycin plus rosiglitazone group (group RPM + RGZ).The rats were anesthetized with intraperitoneal 10% chloral hydrate 100 mg/kg.Sepsis was induced by CLP in groups CLP,RPM,RGZ and RPM + RGZ.At 30 min before CLP,rapamycin 0.4 mg/kg was injected subcutaneously in RPM group,rosiglitazone 0.3 mg/kg was injected via the femoral vein in RGZ group,and rapamycin 0.4 mg/kg was injected subcutaneously and rosiglitazone 0.3 mg/kg was injected via the femoral vein in group RPM + RGZ.While the equal volume of normal saline was given instead in CLP group.Six rats were sacrificed at 2,6,24 and 48 h after CLP in each group,and lungs were removed and cut into sections which were stained with haematoxylin and eosin and examined under microscope.The pathological changes of lungs were scored.The myeloperoxidase (MPO) activity and signal transducer and activator of transcription 3 (STAT3)-DNA binding activity in lung tissues were measured.Results Compared with group S,the pathological scores,MPO activity and STAT3-DNA binding activity were significantly increased in groups CLP,RPM,RGZ,RPM + RGZ (P ＜ 0.05).The pathological scores,MPO activity and STAT3-DNA binding activity were significantly lower in groups RPM,RGZ and RPM +RGZ than in group CLP,and in group RPM + RGZ than in groups RPM and RGZ (P ＜ 0.05).Conclusion Rapamycin combined with rosiglitazone offers additional benefit to attenuating lung injury induced by sepsis over rapamycin or rosiglitazone alone,and inhibition of activation of STAT3 pathway is involved in the mechanism.

Objective To evaluate the effect of dexmedetomidine on the expression of 8-Oxoguanine DNA glycosylase 1 (OGG1) mRNA in rat hippocampal neurons subjected to oxygen-glucose deprivation/reoxygenation and restoration (OGD/R).Methods Hippocampal neurons isolated from pathogen-free neonatal Sprague-Dawley rats born within 3 days,were cultured primarily and seeded in 96-well plates (100 μl/well) or 6-well plates (2 ml/well) at the density of 1 × 106 cells/ml.The cells were randomly divided into 5 groups (n=30 each):control group (group C),group OGD/R,and different concentrations of dexmedetomidine groups (DEX1-3 groups).The cells were cultured in normal culture medium in group C and the cells were subjected to OGD/R in the other groups.In DEX1-3 groups,dexmedetomidine with the final concentrations of 0.1,1.0 and 10.0μmol/L were added,respetively,at 2h before OGD.At 24h of restoration,hippocampal neurons were stained with haematoxylin and eosin (H.E) for examination of pathological changes,the cell survival rate was detected by MTT method,the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) were detected by colorimetric method,and the expression of OGG1 mRNA was detected by RT-PCR.Results The pathological changes of neurons were obvious in group OGD/R,and the pathological changes of neurons were significantly mitigated in DEX1,DEX2 and DEX3 groups.Compared with group C,the cell survival rate and SOD activity were significantly decreased,MDA content was increased,and the expression of OGG1 mRNA was down-regulated in OGD/R,DEX1,DEX2 and DEX3 groups (P ＜ 0.05).Compared with group OGD/R,the cell survival rate and SOD activity were significantly increased,MDA content was decreased,and the expression of OGG1 mRNA was up-regulated in DEX1,DEX2 and DEX3 groups (P ＜ 0.05).There was no significant difference in the indices mentioned above between DEX1,DEX2 and DEX3 groups (P ＞ 0.05).Conclusion Dexmedetomidine may protect hippocampal neurons against oxidative stress injury by up-regulating the expression of OGG1 mRNA in rat hippocampal neurons subjected to OGD/R.

Objective To explore the predictive capability of different methods for difficult la-ryngoscopy and analyze its optimal cutoff value.Methods Three hundred consecutive patients (aged 18-65 years,weighing 42-88 kg,ASA physical status Ⅰ or Ⅱ)scheduled to undergo general anesthe-sia and surgery were invited to participate.Difficult airway assessments were performed by thyromen-tal height (TMH),thyromental distance (TMD),sternomental distance (SMD),modified Mallam-pati test (MMT)and ratio of height and TMD (RHTMD)before anesthetic induction.Cormack-Le-hane (C-L)grade of laryngoscopy view was assessed after induction.Sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV)and accuracy of these tests were calculated. Receiver operator characteristic (ROC)curve of TMH was performed to determine the optimal cutoff value of TMH.Results There were 22 patients diagnosed as difficult airway.Sensitivity,specificity, PPV,NPV and accuracy of TMH were higher than those of TMD,SMD and MMT tests.Sensitivity of RHTMD was lower than that of TMH test,and specificity,PPV,NPV and accuracy of RHTMD were similar to that of TMH.The optimal cutoff value of TMH was 4.9 cm through ROC curve. Conclusion The optimal cutoff value of TMH detecting difficult laryngoscopy was 4.9 cm.Similar to RHTMD,TMH appears to be more effective for prediction of difficult laryngoscopy than TMD, SMD and MMT.

Objective To evaluate the effect of exogeneous adiponectin on hippocampal advanced glycation end products (AGEs)-reactive oxygen species (ROS)-endoplasmic reticulum stress (ERS) pathway in aged mice with postoperative cognitive dysfunction (POCD).Methods Thirty-two healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were randomly divided into 4 groups (n=8 each) using a random number table: control group (group C), POCD group, exogeneous adiponectin group (group APN), and vehicle group (group Veh).Splenectomy was performed to establish the POCD model in aged mice anesthetized with intraperitoneal pentobarbital sodium.In group APN, adiponectin 0.1 μg/g (in 2 μl of phosphate buffer solution) was injected into the lateral cerebral ventricle at 30 min before establishing the model.Phosphate buffer solution 2 μl was given at 30 min before establishing the model in group Veh.Cognitive function was assessed on day 7 after surgery.The mice were then sacrificed, and the hippocampus was harvested for determination of the area of AGE deposition (by immunohistochemistry), levels of ROS (by flow cytometry), and levels of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), caspase-12 and ROS (using Western blot).Results Compared with group S, the freezing time in the contextual fear conditioning test was significantly shortened, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were increased, and the level of GRP78 was decreased in POCD, APN and Veh groups.Compared with POCD and Veh groups, the freezing time in the contextual fear conditioning test was significantly prolonged, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were decreased, and the level of GRP78 was increased in group APN.Conclusion Exogeneous adiponectin decreases the occurrence of POCD probably by blocking hippocampal AGEs-ROS-ERS pathway in aged mice.

Objective To investigate the role of hippocampal cyclophilin D (CypD) in sepsis-associated encephalopathy in rats.Methods A total of 36 adult male Sprague-Dawley rats,aged 3-4 months,weighing 300-400 g,were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (Sham group),sepsis group (S group),and sepsis + CypD inhibitor cyclosporin A group (CsA group).Sepsis was induced by cecal ligation and puncture (CLP).Cyclosporin A 6 mg/kg was injected intraperitoneally at 30 min before CLP in group CsA.All the animals underwent Morris water maze test on 4th day after CLP.The animals were sacrificed after the test,and the hippocampus was isolated for determination of the expression of cytochrome c (Cyt c),CypD,caspase-3,brain-derived neurotrophic factor (BDNF),phosphorylated protein kinase A (p-PKA),and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB).Results Compared with group Sham,the escape latency was significantly prolonged,the space exploration time was shortened,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was up-regulated,and the expression of BDNF was down-regulated in S and CsA groups (P＜0.05).Compared with group S,the escape latency was significantly shortened,the space exploration time was prolonged,the expression of Cyt c,CypD,caspase-3,p-PKA and p-CREB was down-regulated,and the expression of BDNF was up-regulated in group CsA (P＜0.05).Conclusion Hippocampal CypD may be involved in the pathophysiological mechanism of sepsis-associated encephalopathy,and the downstream mechanism is probably related to promotion of activation of PKA/CREB signaling pathway in rats.

Objective To investigate the influence of low-dose ketamine and dexmedetomidine on cardiovascular response during. sedative amnesia fiberoptic nasotracheal intubation. Methods Ninety ASA Ⅰ or Ⅱ patients scheduled to recerve general anesthesia were evenly random-ized to dexmedetomidine and ketamine (group DK),dexmedetomidine and propofol (group DP)and dexmedetomidine and remifentanil (group DR).Ten minutes before intubation,the patients in group DK received intravenously dexmedetomidine 1.0 μg/kg plus ketamine 0.5 mg·kg-1 ·h-1 ;those in group DP received intravenously dexmedetomidine 1.0 μg/kg plus propofol 2.0 mg · kg-1 · h-1 ;those in group DR received intravenously dexmedetomidine 1.0 μg/kg plus remifentanil 5.0μg·kg-1 ·h-1 .Nasotracheal intubation was performed with fiberoptic bronchoscopy after dexemeto-midine injection and complete topical anesthesia.HR,MAP,SpO 2 and Ramsay sedation score were re-corded before anesthesia (T0 ,baseline),before intubation (T1 ),immediately intubated (T2 )and five minutes after intubation (T3 ).Side effects such as restlessness,bucking,respiratory depression and cardiovascular event during intubation and awareness of intubation were also recorded.Results All pa-tients in three groups were performed successfully.HR and MAP were significantly decreased in groups DP and DR at T1 (P <0.05),SpO 2 was significantly decreased in group DP at T1 (P <0.05);MAP in group DR were higher than those in group DP,HR in groups DP and DR were significantly increased than those in group DK at T3 (P < 0.05 );Ramsay score were significantly decreased in groups DP and DR at T2 ,significantly lower in group DR at T3 than those in groups DK and DP (P<0.05).The incidences of bradycardia and respriatory depression were significantly higher in group DP than those in group DK,and bucking,restlessness,tachycardia incidence rate in group DR were significantly higher than those in groups DK and DP (P <0.05).Conclusion Dexmedetomidine com-bined with low dose ketamine together with topical anesthesia is an ideal method for sedative amnesia fiberoptic nasotracheal intubation with slighter cardiovascular response and less side effects.