Objective To investigate the changes in the expression of calcitonin gene-related peptide (CGRP), substance P (SP) and brain-derived neurotrophic factor (BDNF) in dorsal root ganglion (DRG) and the effect of electroacupuncture (EA) on morphine tolerance in rats with chronic inflammatory pain (CIP) and morphine tolerance. Methods Twenty-five 8-month-old male SD rats weighing 230-250 g in which intrathecal (IT)catheters were successfully implanted without complications were randomly divided into 5 groups ( n = 5 each):groupA CIP + normal saline (NS) 10 μl IT twice a day for 7 consecutive days; group B CIP + morphine 10 μg/kg ( 10 μl) IT twice for the first day only; group C CIP + morphine 10 μg/kg ( 10 μl) IT twice a day for 7 consecutive days; group D CIP + EA (intensity 2 mA, frequency 2 Hz, wave length 0.6 ms) + morphine 10 μ g/kg (10 μl) IT twice a day for7 consecutive days; group E CIP + EA (intensity 2 mA, frequency 15 Hz,wave length 0.4 ms) + morphine 10μg/kg (10 μl) IT twice a day for7 consecutive days. CIP was induced by injecting complete Freund's adjuvant (CFA) into the ankle joint of the left hindlimb. IT morphine or NS was started on the 4th day after induction of CIP. EA of Yanglingquan and Zusanli lasting 30 min was performed once a day after first IT administration of morphine for 7 days. Paw withdrawal latency (PWL) to a thermal nociceptive stimulus was measured before induction of CIP, 1 day before (baseline) and at day 1-7 after administration (T0-8) . The animals were sacrificed after the last PWL measurement. The DRGs of the lumbar segment (L4-6) were removed for determination of CGRP, SP and BDNF mRNA expression using RT-PCR. Results PWL was significantly shorter at T1 than at T0 in all groups, and at T3-8 than at T2 in group B-E, while longer at T2 than at T1 in group B-E ( P ＜0.05). PWL was significantly longer in group B-E and CGRP, SP and BDNF mRNA expression higher in group C than in group A ( P ＜ 0.05). PWL was significantly longer in group C-E than in group B ( P ＜ 0.05). PWL was significantly longer and CGRP, SP and BDNF mRNA expression lower in group D and E than in group C ( P ＜0.05). PWL was significantly lower and CGRP, SP and BDNF mRNA expression higher in group E than in group D ( P ＜ 0.05). Conclusion Up-regulation of the expression of CGRP, SP and BDNF mRNA in DRG is involved in the devepopment of morphine tolerance. EA can inhibit the devepopment of morphine tolerance by inhibiting the expression of CGRP2 SP and BDNF mRNA.

Objective To evaluate the relationship between pharmacodynamics of sufentanil-induced respiratory depression and age factors. Methods Forty ASA Ⅰ or Ⅱ patients scheduled for elective abdominal surgery were randomly divided into 2 groups according to the age: young and middle-aged group (25-64 yr, group M) and elderly group (65-80 yr, group E). EC50 was determined by up-and-down sequential trail. The initial target effect-site concentration (Ce) of sufentanil was set at 0.40 and 0.35 μg/ml in group M and E respectively.Each time Ce decreased/increased by 10% in the next patient depending on whether or not the respiratory depression occurred. Respiratory depression was defined as VT ≤ 5 ml/kg, RR ≤ 8 bpm/min, SpO2 ≤ 94%,PET CO2 ≥ 55 mm Hg, and/or apnea ≥ 15 s. Results The EC50 and 95 % confidence interval of sufentanil causing respiratory depression were 0.61 (0.54-0.70) μg/ml and 0.41 (0.38-0.45) μg/ml in group M and E respectively with the significant difference. Conclusion The efficacy of sufentanil-induced respiratory depression is related to age factors and the elderly patients are more sensitive to sufentanil-induced respiratory depression.

Objective To investigate the effect of different concentrations of sevoflurane inhalation combined with pro?pofol anesthesia on rocuronium pharmacodynamics. Methods Sixty-seven patients, who underwent elective abdominal op?eration in Tianjin Medical University General Hospital from Nov. 2014 to Feb. 2015, were randomly allocated to three groups:propofol combined 0.5 minimum alveolar concentration (MAC) end-tidal concentration of sevoflurane (group Ⅰ, 24 cases), propofol combined 0.75 MAC end-tidal concentration of sevoflurane (group Ⅱ, 20 cases) and propofol combined 1 MAC end-tidal concentration of sevoflurane (groupⅢ, 23 cases). All those patients were given midazolam 0.05 mg/kg, sufen? tanil 0.3μg/kg, etomidate 0.3 mg/kg for anesthesia induction. Rocuronium was given through the T1 mode of Closed-loop muscle relaxant infusion system and infused by 2ED95(0.6 mg/kg). The following variables were recorded:average consump?tion dosage of rocuronium, recovery index, averaged consumption dosage of propofol and remifentanil. Results The aver?aged consumption dosage of rocuronium was decreased in the three groups in turn[(9.71 ± 2.38 vs 7.50 ± 0.98 vs 6.90 ± 1.14)μg·kg-1·min-1,F=18.562,P<0.05]. There was no significant difference in recovery index between the three groups [(8.92± 2.62 vs 8.95 ± 2.58 vs 10.30 ± 3.65)min,F=1.577, P>0.05]. The average consumption dosage of propofol and remifentanil were lower in groupⅢthan those of groupⅠand groupⅡ(P<0.05). Conclusion High concentration of sevoflurane can enhance neuromuscular blockage effect of rocuronium, and decrease the consumption dosage of propofol and remifentanil.

Objective To explore the role of excitatory amino acid carrier 1 (EAAC1)in dorsal root ganglion (DRG) in the mechanism of developing morphine tolerance. Methods Thirty male SD rats were implanted intrathecal catheters and randomized into 6 groups with 5 rats each. The rats of 4 groups were made into the model of adjuvant-induced arthritis in the left hind limb and were administered intrathecally, morphine 10 μg(group M_(10)), morphine 20μg(group M_(20)), morphine 20 μg plus naloxone 10 μg(group MN) ,or saline(group C) respectively. The other 2 groups without were administered intrathecally saline (group C_0) or morphine 20 μg (group M0). The drugs were administered twice daily for 7 days. Mechanical withdrawl threshold(MWT) of the left hind limb was examined to evaluate the behavior. Immunohistochemistry was used to detect the expression of EAAC1 in the left L_(3-4) and L_(4-5) DRG. Results Morphine tolerance was formmed stably in the arthritis rats of group M_(10) and group M_(20) after administering morphine for 7 days. The expression of EAAC1 in DRG was downregulated. Conclusion DRG EAAC1 may be involved in the mechanism of developing morphine tolerance in rats with inflammatory pain.

Objective To investigate the changes in the expression of glutamate-aspartste transporter in spinal dorsal horn in rats with inflammatory pain and chronic morphine tolerance. Methods Thirty healthy male SD rats in which intrathecal (IT) catheters were successfully placed without complications were randomized into 3 groups ( n = 10 each): normal saline group ( group NS), arthritis group ( group A), and arthritis + morphine group (group AM). NS 50 μl was injected into the ankle joint of the left hindlimb in group NS, while complete Freund's adjuvant was injected in the other two groups instead. After 3 days, group NS and A received IT NS 10 μl twice a day for 7 consecutive days, group AM IT morphine 10 μg (10 μl) twice a day for 7 consecutive days. Mechanical pain threshold (MPT) was measured before IT administration and at day 2, 4, 6 and 8 after IT administration (T0-4). The animals were sacrificed after the last MPT measurement. The spinal cords were isolated for determination of GLAST expression in spinal dorsal horn. Results Compared with group NS, MPT was significantly decreased in the other groups and GLAST expression was down-regulated in group AM (P ＜ 0.05). Compared with group A, no significant change was found in MPT at T3,4 (P ＞ 0.05), while GLAST expression was down-regulated in group AM ( P ＜ 0.05). Conclusion The development of chronic morphine tolerance is related to the decrease in the function of GLAST in spinal dorsal horn in rats with inflammatory pain.

To fulfill the performance optimization for database of HIS, the shortest query response time and the highest throughput of database server are realized through the minimization of the network flow, disc I/O and CPU time. The performance optimization should exist throughout the development of HIS, so the requirements of HIS applications, the logical construction and physical structure of data, the balance of conflicting databases should be involved in.

Objective To investigate the role of JNK in intestinal barrier dysfunction in severe septic mice treated by hydrogen. Methods Eighty male ICR mice were randomly divided into four groups (n=20 each):sham operation group, hydrogen control group, sepsis group and hydrogen treatment group. Severe sepsis rat model was reproduced by cecal ligation and puncture (CLP). Laparotomy without CLP was performed in sham operation group and hydrogen control group. The mice in hydrogen control group and hydrogen treatment group received 1-hour inhalation of 2%hydrogen at 1 hour and 6 hours after sham operation or CLP, respectively. Ten mice of each group were selected at 20 h after CLP operation and were gavaged with fluorescein-isothiocyanate-conjugated dextran (FITC-dextran). Blood samples were obtained by cardiac puncture to measure the serum concentration of FITC-dextran 4 h after treatment with FITC-dextran . Ten mice in each group were sacrificed at 24 h after CLP operation. The colony-forming unit (CFU) numbers in the peritoneal lavage fluid were counted. The middle intestinal tissues were obtained for the measurement of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1βand high mobility group box 1(HMGB1) by ELISA. The level of phosphorylated JNK (p-JNK) and the expression of tight junction protein ZO-1 and Occludin were detected by Western blot assay. The intestinal pathological changes and epithelial ultrastructure changes were observed by light microscope and transmission electron microscope (TEM). Results There was no statistical significance in clinical variables between sham operation group and hydrogen control group. Compared with sham operation group, the serum FITC-dextran concentration, the CFU numbers in the peritoneal lavage fluid, the levels of TNF-α, IL-1βand HMGB1 in intestine, and the expression of p-JNK were significantly increased, the expression of ZO-1 and Occludin were down-regulated in sepsis group(P < 0.05). There was a significant intestinal pathological injury along with epithelial ultrastrcture injury in sepsis group. Compared with sepsis group, the serum FITC-dextran concentration, the CFU numbers in the peritoneal lavage fluid, the levels of intestinal TNF-α, IL-1β and HMGB1, and the expression of p-JNK were significantly decreased, the expression of ZO-1 and Occludin were up-regulated in hydrogen treatment group(P < 0.05), and the pathological and ultrastructure damage was significantly reduced. Conclusion Hydrogen can decrease levels of proinflammatory factors and up-regulate the expression of tight junction to improve intestinal barrier dysfunction caused by severe sepsis, which is related with the inhibition of JNK signaling pathway.

Objective To evaluate the role of signal transducer and activator of transcription 3 (STAT3) signal transduction pathway in diazoxide cardioplegic solution-induced reduction of ischemia-reperfusion (I/R) injury in isolated rat hearts.Methods Sixty adult male Sprague-Dawley rats,aged 2-3 months,weighing 240-260 g,were used in this study.Their hearts were excised and perfused in a Langendorff apparatus and then randomly divided into 5 groups (n=12 each):control group (group C),group I/R,cardioplegic solution group (group P),diazoxide cardioplegic solution group (group DZX),and STAT3 signal transduction pathway blocker Stattic group (group Stattic).The hearts were continuously perfused for 90 min after 15 min of equilibration in group C.Perfusion was stopped after 15 min of equilibration and restored 30 min later in I/R,P,DZX and Stattic groups.In P and DZX groups,the hearts were perfused with the cardioplegic solution containing 0.4％ dimethyl sulfoxide and 50μmol/L diazoxide,respectively,before perfusion was stopped.In group Stattic,the hearts were perfused with 10μmol/L Stattic for 5 min before perfusion with diazoxide.At 60 min of reperfusion,the hearts were sliced and stained for determination of myocardial infarct size (IS) as a percentage of area at risk (AAR) (IS/AAR),cell apoptosis and expression of phosphorylated STAT3 (p-STAT3) protein (by Western blot) and STAT3 mRNA (using RT-PCR).Apoptotic index (AI) was calculated.Results Compared with group C,the IS/AAR and AI were significantly increased in the other four groups,the expression of p-STAT3 and STAT3 mRNA was down-regulated in I/R and Stattic groups,and the expression of p-STAT3 was down-regulated and STAT3 mRNA was up-regulated in P and DZX groups (P ＜ 0.05).Compared with group I/R,the IS/AAR and AI were significantly decreased,and the expression of p-STAT3 and STAT3 mRNA was up-regulated in P and DZX groups (P ＜ 0.05),and no significant changes were found in the parameters mentioned above in Stattic group (P ＞ 0.05).The IS/AAR and AI were significantly lower,and the expression of p-STAT3 and STAT3 mRNA was higher in DZX group than in P group (P ＜ 0.05).Conclusion STAT3 signal transduction pathway is involved in diazoxide cardioplegic solution-induced reduction of I/R injury in isolated rat hearts.

Objective To evaluate the role of ERK1/2 signaling pathway in mitigation of myocardial ischemia-reperfusion (I/R) injury by diazoxide postconditioriing in rats.Methods Sixty adult male SpragueDawley rats,aged 3 months,weighing 240-260 g,were randomly divided into 5 groups (n =12 each) using a random number table:sham operation group (S group),I/R group,vehicle group (Ⅴ group),diazoxide postconditioning group (D group),and ERK1/2 signaling pathway inhibitor U0126 group (U group).Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion.In V and D groups,0.4％ DMSO and diazoxide 7 mg/kg (in 1 ml 0.4％ DMSO) were administrated,respectively,through the femoral vein at the onset of the reperfusion.In U group,U0126 was given through the femoral vein at 10 min before reperfusion,and the following procedures were similar to those previously described in group D.At 120 min of reperfusion,myocardial specimens were obtained for detection of myocardial infarct size,cell apoptosis (using TUNEL),and expression of ERK1/2 mRNA (by RT-PCR),total ERK1/2 (t-ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) (by Western blot).Apoptosis index was calculated.Results Compared with S group the myocardial infarct size and apoptosis index were significantly increased in the other groups,the expression of ERK1/2 mRNA and p-ERK1/2 was down-regulated in I/R,V and U groups,and no significant change was found in the expression of ERK1/2 mRNA and p-ERK1/2 in Dgroup.Compared with I/R group,the myocardial infarct size and apoptosis index we re significantly decrcaed,and the expression of ERK1/2 mRNA and p-ERK1/2 was up-regulated in D group,and no significant change was foundin the parameters mentioned above in V and U groups.Compared with D group,the myocardial infarct sizeand apoptosis index were significantly increased,and the expression of ERK1/2 mRNA and p-ERK1/2 was down-regulated in U group.There was no significant difference in t-ERK1/2 expression between five groups.Conclusion Diazoxide postconditioning mitigates myocardial I/R injury possibility through activating ERK1/2 signaling pathway in rats.

Objective To evaluate the relationship between delta opioid receptors (DORs) and activity of glycogen synthase kinase-3β (GSK-3β) in the spinal cord during hyperalgesia induced by remifentanil in a rat model of incisional pain (IP).Methods Twenty-four male Sprague-Dawley rats,aged 240-260 g,weighing 2-3 months,were randomly divided into 3 groups (n =8 each) using a random number table:control group (group C),remifentanil+IP group (group R+I) and DOR antagonist naltrindole group (group N).A 1-cm longitudinal incision was made in the plantar surface of the left hindpaw in anesthetized rats.In group C,the equal volume of normal saline was injected intraperitoneally,and normal saline was then infused for 60 min at the same rate.In group R+I,the equal volume of normal saline was injected intraperitoneally,remifentanil was infused for 60 min at 1.2 μg · kg-1 · min-1,and IP was produced immediately after onset of remifentanil infusion.In group N,naltrindole 0.1 mg/kg was injected intraperitoneally,remifentanil was infused for 60 min at 1.2 μg · kg-1 · min-1,and IP was produced immediately after onset of remifentanil infusion.At 24 h before infusion of normal saline or remifentanil and 2,6,24 and 48 h after iv administration (T0-4),the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.The rats were sacrificed after the last measurement of pain threshold,the lumbar segment (L4-6) of the spinal cord was removed for determination of the expression of GSK-3β,phosphor-GSK-3β (pGSK-3β) (by Western blot) and GSK-3β mRNA (realtime PCR).The ratio of pGSK-3β /GSK-3β was calculated.Results Compared with group C,the MWT was significantly decreased,and the TWL was shortened at T1 4,the expression of GSK-3β,pGSK-3β and GSK-3β mRNA was up-regulated,and pGSK-3β/GSK-3β ratio was decreased in R + I and N groups.Compared with group R + I,thc MWT was significantly incrcased,and the TWL was prolonged at T1-4,the expression of GSK-3β,pGSK-3β and GSK-3β rmRNA was down-regulated,and pGSK-3β/GSK-3β ratio was increased in group N.Conclusion Activation of DOR is involved in enhancement of activity of GSK-3β in the spinal cord during hyperalgesia induced by remifentanil in a rat model of IP.