Objective To investigate the effect of parecoxib on hippocompal inflammation following partial hepatectomy in aged rats.The effects of selective COX-2 inhibitor (parecoxib) on hippocampal inflammation were also evaluated.Methods Seventy male rats,aged 20 months,weighing 500-600 g,were randomly divided into three groups: control (n=10),surgery (n=30),and parecoxib (n=30).Control animals received sterile saline to control for the effects of injection stress.Rats in the surgery group received partial hepatectomy under isoflurane anesthesia and sterile saline injection.Rats in the parecoxib group received surgery and anesthesia similar to surgery group rats,and parecoxib treatment.On postanesthetic day 1,3 and 7,animals were euthanized to assess the hippocampal COX-2 expression,PGE2 production and caspase-3 expression.Results Surgery significantly increased the expression of COX-2 mRNA and protein expression,PGE2 production and caspase-3 protein expression on day 1 postoperatively (P<0.01),until day 3 (P<0.05) compared to control group.Parecoxib treatment group significantly suppressed COX-2 mRNA and protein expression,PGE2 production and caspase-3 protein expression on postoperative day 1 and day 3 (P<0.05 or P<0.01),in comparison with the surgery group.There was no significant difference between control group and other groups of the expression of COX-2 mRNA and protein expression,PGE2 production and caspase-3 protein expression on day 7.Conclusion Partial hepatectomy induces a short-term hippocampal inflammatory response in the rats.Parecoxib suppressed the hippocampal inflammation via the down-regulation of COX-2 mRNA and protein,PGE2 and caspase-3 protein in rats following partial hepatectomy.

ObjectiveTo compare the roles of Toll-like receptor-4 (TLR-4) in the acute lung injury (ALI) induced by lipopolysaccharide (LPS) and by hemorrhagic shock and resuscitation (HSR) and LPS (twohit) in mice.MethodsTwo types of mice were used in this study:free wild type mice (C3H/HeN) and TLR4 gene mutation type ( C3H/HeJ).Each type of mice was randomly divided into 2 groups ( n ＝ 18):group sham operation+ LPS (group S/LPS) and group HSR + LPS (group HSR/LPS).Hemorrhagic shock was induced by blood withdrawal until MAP was reduced to 35-45 ram Hg and maintained for 60 min (first hit).The animals were then resuscitated by infusion of shed blood and lactated Ringer' s solution.LPS 30 tμg/kg was instilled into trachea at 24 h after HSR (second hit).Arterial blood gas analysis was performed and the animals were then sacrificed by exsanguination at 0,3 and 6 h after LPS(T,,T2,T3 ).The lungs were removed.W/D lung weight ratio and MPO activity,IL-6 and 1L-10 contents in the lung tissue were determined.The changing rate of the abovementioned variables at T2,T3 based on the values at T1 were calculated.ResultsIn C3H/HeN animals the changing rate of PaO2 was significantly lower while the changing rate of W/D ratio,MPO activity and IL-6,IL-10 contents in the lung tissue were significantly higher in HSR/LPS group than in S/LPS group at T2.3.But in C3H/HeJ animals the above-mentioned variables were changed at T2.ConclusionThe role of TLR-4 in the two-hit-induced ALI is stronger than that in the LPS-induced ALI in mice.

Objective To evaluate the role of p38MAPK signaling pathway in the up-regulation of heme oxygenase-1 (HO-1) expression during hemorrhagic shock and resuscitation (HSR)-induced acute lung injury (ALI) in mice. Methods Thirty-two C3H/HeN (wild-type) mice, aged 10-12 weeks, weighing 20-25 g, were randomly divided into 4 groups (n = 8 each): sham operation group (group S); group HSR; FR167653 (a p38MAPK inhibitor) group (group FR) and FR167653 + HSR group (group FR + HSR). HSR was induced according to the methods described by Ayala et al. MAP was reduced to 35-45 mm Hg and maintained for 60 min.Then the animals were resuscitated with transfusion of the shed blood and lactated Ringer's solution equivalent to the volume of shed blood. FR167653 5 mg/kg was injected intravenosly in group FR. FR167653 5 mg/kg was injected intravenously 30 min before blood-letting in group FR + HSR. The animals were sacrificed by exsanguination at 6 h after resuscitation. The lungs were immediately removed for microscopic examination. The W/D lung weight ratio was calculated and the levels of myeloperoxidase (MPO), IL-10, IL-6 and HO-1 and activated p38MAPK were determined (by ELISA).Results Compared with group S, the pathological score, W/D ratio, the levels of MPO, IL-10, IL-6 and HO-1 and the level of activated p38MAPK were significantly increased in group HSR, the pathological score, W/D ratio and the level of HO-1 were significantly increased in group HSR + FR ( P ＜ 0.01) .Compared with group HSR, the pathological score, W/D ratio, the levels of MPO, IL-10, IL-6 and HO-1 and activated p38MAPK were significantly decreased in group HSR + FR ( P ＜ 0.01 ). Conclusion p38MAPK signaling pathway mediates the up-regulation of HO-1 expression during HSR-induced ALI in mice.

Objective To investigate the effect of surgical trauma on the expression of COX-2 and PGE2in the hippocampus in aged rats. Methods Forty-five 18-month-old male SD rats weighing 500-600 g were randomly divided into 3 groups (n = 15 each): group Ⅰ control (group C); group Ⅱ anesthesia (group A) and group Ⅲ surgery + anesthesia (group S). Anesthesia was induced by intraperitoneal 1% pentobarbital sodium 50 mg/kg in group A and S. The animals underwent appendectomy and splenectomy under anesthesia in group S.Cognitive function was assessed by open field test and Y-mase test on the 1st, 3rd and 7th day after anesthesia and surgery (T1-3). The animals were sacrificed after behavior tests at T1.2.3 and the hippocampi were removed for determination of the expression of COX-2 mRNA (by RT-PCR) and PGE2 content (by ELISA). Results The time the animal spent in the central square was significantly prolonged, the number of crossing grid and standing on the back legs and the number of right response were decreased, the total reaction time was prolonged and the COX-2mRNA expression at T1 and PGE2 content in the hippocampus were increased at T1,2 in group S as compared with group C and A. There was no significant difference in the variables mentioned above between group C and A. Conclusion Surgical trauma can induce early postoperative cognitive dysfunction through up-regulation of COX-2 mRNA expression and by increasing PGE2 content in the hippocampus in aged rats.

Objective To investigate the risk factors for early postoperative cognitive function in the patients with peritoneal surface malignancies after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy(CRS-HIPEC).Methods Fifty-one patients(21 men and 30 women), ranged from 25 to 65 years,42-80 kg,ASA Ⅰ-Ⅲ,undergoing CRS-HIPEC under combined intrave-nous-inhalational anesthesia,were studied.Patients were assigned into postoperative cognitive dys-function (POCD)group or non-POCD group according to their performances of visual verbal learning test,concept shifting task,letter-digit coding test and stroop color-word test 1 day before operation and 7 days after operation.Years of education,medical history,duration of operation,intraoperative blood loss,frequency of cardiovascular events,amount of fluid infused per hour and VAS scores were recorded.Venous blood samples were taken at five time points:before surgery(T0 ),30 minutes after the beginning of the procedure(T1 ),30 minutes after the beginning of HIPEC(T2 ),at the end of the surgery(T3 )and 24 hours after the surgery(T4 ),to determine the concentration of serum amyloid A (SAA).pH,PaCO 2, Hb,blood glucose were recorded at T0-T2.Then the data was statistically analyzed.Results According to the diagnostic criteria,twenty patients developed POCD 20 (39.2%). There were significant differences between POCD and non-POCD groups on age,gender, pre-operative complications and the origin of tumor(P <0.05).The concentration of SAA increased from T2 and reached the peak at T4 ,and SAA concentration for patients in POCD group was higher than that for patients in non-POCD group(P <0.05).Compared with non-POCD group,the levels of blood glucose were significantly increased in POCD group at T2 (P <0.05).Conclusion CRS-HIPEC resul-ted in exaggerated and prolonged inflammatory response.Advanced age,female,diabetes,hyperten-sion,peritoneal carcinomatosis from ovarian cancer and endometrial cancer are associated with early POCD in the patients undergoing CRS-HIPEC.

Objective To investigate the adjuvant effect of intravenous immunoglobulin on patients with sepsis-associated thrombocytopenia. Methods A total of 229 patients with sepsis with platelet count less than 3 × 109/L, were included in this prospective, randomized, controlled study. The patients were divided into the intervening group and the control group. Conventional treatments were applied in the two both groups , while in the intervening group, intravenous immunoglobulin with a dose of 0.4 g/(kg·d) for 5 consecutive days was administered. The end-points were the platelet counts on day 1,day 3,day 5,and day 7 post-intravenous immunoglobulin, patients’ in-ICU time and the 28-day in-hospital mortality. Results Compared with the control group, the platelet count recovered dramatically after 5-day intravenous immunoglobulin in the intervening group. Moreover , the 28-day in-hospital mortality and in-ICU time were also dramatically improved in the intervening group. Conclusion Intravenous immunoglobulin can enhance the recovery of platelet counts , shorten the in-ICU time and reduce the hospital mortality in patients with sepsis- associated thrombocytopenia (PLT count < 30 × 109/L).

Objective To investigate the effect of continuous venous-venous hemofiltration (CVVH) and continuous venous-venous hemodialysis (CVVHD) on patients with lactic acidosis.Methods A total of 137 cases with lactic acidosis were included in this prospective randomized control study.lhe patients were collected from the University of Hong Kong-shenzhen Hospitall and the First Affiliated Hospital of Shantou University Medical College from April 2009 to April 2013.Inclusion criteria were patients with lactic acidosis.Exclusion criteria were patients with end-stage malignancy or terminal stage of illnesses.The patients were randomly divided into two groups:CVVH group and CVVHD group,and patients of both group were intervened with conventional treatments as well.For each group,the lactic acid and blood gas analysis were tested before CRRT,and at 4 hours,8 hours,12 hours,24 hours,and 48 hours of CRRT.The patients' mortality and length of ICU stay time were analysed and recorded.Statistical analysis was performed using SPSS 15.0software.Results When the length of time for treatment was the same,the efficacy between CVVH group and CVVHD group showed no difference in blood lactic acid level [4 h:(11.65 ± 3.39) mmol/L vs.(11.12±2.65) mmol/L; 8 h:(8.78±2.35) mmol/L vs.(8.59±2.09) mmol/L; 12 h:(6.91 ±1.67)mmol/Lvs.(6.74±1.76) mmol/L;24h:(1.66±0.39) mmol/Lvs.(1.51±0.30) mmol/L; 48 h:(0.95 ±0.24) mmol/L vs.(0.66 ±0.20) mmol/L,P ＞ 0.05) and pH value [4 h:(6.93 ±0.14) vs.(7.05±0.09);8h:(7.04±0.10)vs.(7.12±0.05); 12h:(7.13±0.07)vs.(7.20±0.04);24h:(7.30±0.03) vs.(7.38±0.04); 48h:(7.41 ±0.03) vs.(7.46±0.02),P＞ 0.05].There are also no difference in the hospital mortality (11.4％ vs.10.4％,P=0.854) and length ofICU stay time [(9.5 ±2.4) d vs.(8.8 ± 2.9) d,P =0.329].Conclusions Both CVVH and CVVHD can effectively correct hyperlactemia,enhance acid-base balance,contributing no differences in length of ICU stay time and patients' hospital mortality.

Objective To evaluate the effects of postconditioning with propofol on lipopolysaccharide (LPS)-induced inflammatory responses of microglial cells in rat brain tissues.Methods The primary cultured microglial cells in brain tissues of Sprague-Dawley rats were seeded in 24 multi-well plates at a density of 1 × 105 cells/ml,and the microglial cells of 100 wells were randomly divided into 5 groups (n =20 each) using a random number table:control group (group C),LPS group (group L),and propofol 25,50 and 100 μmol/L groups (P25,P50,P100 groups).The cells were cultured routinely in group C.LPS 1 μg/ml was added and the cells were incubated for 24 h in group L.In P25,P20,and P100 groups,when the cells were incubated for 24 h with LPS 1 μg/ml,propofol with the final concentrations of 25,50 and 100 μmol/L was added,respectively.The cells were collected at 1 h of incubation with propofol for determination of the expression of inducible nitric oxide synthase (iNOS) mRNA,cyclooxygenase-2 (COX-2) mRNA,tumor necrosis factor-α (TNF-α) mRNA and interleukin-1β (IL-1β) mRNA (by RT-PCR).The supematant was separated for determination of the concentrations of nitric oxide (NO) (by Griess method) and pmstaglandin E2 (PGE2),TNF-α and IL-1β (by ELISA).Results Compared with group C,the expression of iNOS mRNA,COX-2 mRNA,TNF-α mRNA and IL-1β mRNA was significantly up-regulated and the concentrations of NO,PGE2,TNF-α and IL-1β in the supematant were increased in group L (P ＜ 0.01).Compared with group L,the expression of iNOS mRNA,COX-2 mRNA,TNF-α mRNA and IL-1β mRNA was significantly down-regulated and the concentrations of NO,PGE2,TNF-α and IL-1β in the supernatant were decreased in P50 and P100 groups (P ＜ 0.05 or 0.01),while no significant change in the indexes mentioned above was found in P25 group (P ＞ 0.05).Conclusion Postconditioning with propofol 50 and 100 μmol/L can inhibit LPS-induced inflammatory responses of microglial cells in rat brain tissues.

Objective To investigate the changes in expression of hippocampal neuronal gap function protein connexin 36 (Cx36) induced by postoperative cognitive dysfunction (POCD) in aged rats.Methods Ninety male SD rats aged 20 months weighing 500-600 g were randomly divided into 3 groups ( n =30 each):group normal control (group C); group sham operation (group S) and group POCD.POCD was induced by splenectomy.Cognitive function was assessed by using open field test and maze test on the 1st,3rd and 7th day after operation (T1,T2,T3 ).The ultrastructure of gap junction in the CA1 region of hippocampas was examined with thin-section transmission electron microscope.The expression of Cx36 was detected by immuno-histochemical method.Results POCD significantly decreased the number of grid cross,the rearing and correct responses and increased the time the animab spent in the central square and total reaction time at T1 in group POCD as compared with group C.Cx36 expression was significantly decreased at T1 in group POCD as compared with group C.The ultrastructure of gap junctions underwent significant change at T1 in group POCD.Conclusion Hippocampal neuronal Cx36 may be involved in the cognitive dysfunction after splenectomy in aged rats.

Objective To investigate the effects of repeated intraperitoneal dexmedetomidine on the cognitive function in rats with chronic cerebral ischemia.Methods Forty-eight male Sprague-Dawley rats,aged 3-4months,weighing 250-300 g,were randomly divided into 4 groups (n =12 each) ∶ sham operation group (group S),chronic cerebral ischemia group (group IS),dexmedetomidine treatment 1 group (group DXM1) and dexmedetomidine treatment 2 group (group DXM2).Dexmedetomidine 5 μg/kg was injected intraperitoneally at 30 min before occlusion of bilateral common carotid arteries and 3,12,24 and 48 h after occlusion in group DXM1,and at 3,12,24 and 48 h after occlusion in group DXM2.The cognitive function was assessed by Morris water maze 2 weeks after occlusion.The apoptosis was examined by TUNEL.The expression of Bcl-2 protein in hippocampus was detected by Western blot.Results Compared with group S,the escape latency was significantly prolonged from 2nd day to 5th day after the place navigation test in group IS and on 2nd day after Morris water maze test in groups DXM1 and DXM2,and the time of staying in 1 st quadrant was significantly shortened,the apoptotic rate was increased,and the expression of Bcl-2 was up-regulated in groups IS,DXM1 and DXM2 (P ＜ 0.05).Compared with group IS,the escape latency was significantly shortened from 3rd day to 5th day after the place navigation