Objective To evaluate the role of Toll-like receptor 4 (TLR4) in mitigation of inflammatory responses following myocardial ischemia-reperfusion (I/R) injury by sufentanil postconditioning in rats.Methods Thirty Wistar rats were randomly divided into 3 groups (n =10 each):sham operation group (S group); I/R group; sufentanil postconditioning group (SP group).Myocardial I/R was produced by temporary ligation of left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion.In group SP,sufentanil 0.6 μg/kg was injected intravenously at 5 min before reperfusion.The myocardial specimens and blood samples were taken at the end of 120 min reperfusion for determination of the interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations and TLR4 content (by ELISA).Results Compared with S group,the levels of TLR4,IL-6 and TNF-α were significantly increased in the other two groups.Comparedwith I/R group,the levels of TLR4,IL-6 and TNF-α were significantly decreased in group SP.Conclusion The mechanism by which sufentanil postconditioning mitigates inflammatory responses following myocardial I/R injury may be related to downregulation of TLR4 expression in myocardial tissues of rats.

Objective To discuss the expressions and clinicopathologic significances of insulin-like growth factor Ⅱ mRNA binding protein 3 (IMP3)in squamous intraepithelial lesion (SIL)and cervical squa-mous cell carcinoma (CSCC)before and after the therapy of radiation and chemotherapy.Methods The expressions of IMP3 in 80 cases of CSCC,90 cases of SIL (60 cases of HSIL,30 cases of LSIL)and 30 cases of cervicitis were detected by immunobistochemistry.The relations between IMP3 and clinicopathological cha-racteristics of CSCC were analyzed.Results The expression rates of IMP3 in CSCC,HSIL,LSIL and cervici-tis were 86.3%(69 /80),78.3%(47 /60),33.3%(10 /30)and 0(0 /30),and the difference among the four groups was statistically signicant (χ2 =87.01,P <0.01).The positive expression rate of IMP3 declined by radiation or chemotherapy (60.0% vs.85.0%,χ2 =5.79,P =0.013).The expression of IMP3 was related with lymph node metastasis (χ2 =3.97,P =0.046),differentiated degree (χ2 =5.95,P =0.018),clinical stage (χ2 =5.82,P =0.016)and invasion depth (χ2 =5.73,P =0.017).There was nothing to do with age (χ2 =0.11,P =0.745).Conclusion IMP3 expresses excessively in CSCC,and is associated with pathologi-cal grade and invasion progress.Radio-chemotherapy can reduce the expression of IMP3.

Cancer pain is the most important factor affecting the cancer patients' quality of life, and the approach to relieve and control cancer pain is becoming the focus. Pain mechanism research can offer solutions to pain treatment, such as blocking the happening and conduction of analgesia. The earliest μ, κ, σopioid receptors were found in the research of morphine and opioid peptides, especially μ receptor's leading role in pain treatment. Currently, μ opioid agonist is basically used in clinical pain treatment. Morphine, the third level drug, is still the classic pain therapy drugs. Novel drugs such as fentanyl transdermal and controlled-release oxycodone provide new ideas for the pain ease. Opioid combined with non-opioid drugs, the change of opioid drugs delivery way and joint application of controlled release drug and relievers, have dramatically reduced opioid drugs' side effects.

Objective To evaluate the effects of inhalation sevoflurane in the early ischemia and reperfusion on pulmonary inflammatory response in patients undergoing cardiac surgery with extracorporeal circulation (ECC). Methods Forty patients with rheumatic heart disease scheduled for elective valve replacement were randomly assigned into 2 groups (20 patients in each group): control group and sevoflurane group. In sevoflurane group, 2% sevoflurane was inhaled for 15 min before and after the ascending aorta was blocked, and also before and after the ascending aorta was opened. Paitents in control group didn′t inhale sevoflurane. Time was defined as the followings: after anesthesia and before skin incision (T0), immediately before ECC (T1), immediately after ECC (T2), 2 h after ECC (T3), 6 h after ECC (T4) and 24 h after ECC (T5). At T0, T2, T3, T5, the radial artery blood was obtained to detect the levels of plasma tumor necrosis factor-α(TNF-α), interleukin-8(IL-8) and soluble intercellular adhesion molecule-1(sICAM-1). At T1, T2, the pulmonary artery and pulmonary vein blood was obtained to detect the neutrophil count and calculate the differences between the vein and artery. At T0, T2, T3, T4, T5, the arterial blood gas was detected and differences of alveoli-arterial oxygen pres [P(A- a)O2], oxygenation index (OI), static compliance (Cst) were calculated. Results The levels of plasma TNF-α, IL-8 and sICAM-1 were higher at T2, T3, T5 than those at T0 in two groups (P<0.05). The levels of plasma TNF-α, IL-8 and sICAM-1 were decreased in sevoflurane group at T2 and T3, compared with those in control group (P<0.05). The neutrophil counts of pulmonary artery, pulmonary vein and the differences between the vein and artery were higher at T2 than those at T0 in two groups (P<0.05). The neutrophil counts of pulmonary artery, pulmonary vein and the differences between the vein and artery were decreased in sevoflurane group at T2 compared with those of control group (P<0.05). The level of P(A- a)O2 was higher at T2, T3, T4 and T5 than that at T0 in two groups (P<0.05). The level of OI was decreased at T2, T3, T4 and T5 compared with that at T0 in two groups (P<0.05). The level of Cst was decreased at T2, T3 and T4 compared with that at T0 in two groups (P<0.05). The level of P(A-a)O2 was decreased in sevoflurane group at T2, T3 and T4 compared with that in control group (P<0.05). The levels of OI and Cst were higher in sevoflurane group at T2, T3 and T4 compared with those in control group (P<0.05). Conclusions Severe pulmonary inflammation often occurs during cardiac surgery with ECC, and it can be relieved by inhalation of sevoflurane in the early ischemia and reperfusion.

Objective To investigate the effects of post-propofol anesthesia on cognitive function and hippocampus proteome expressions in aged rats.Methods Thirty healthy male Wistar rats aged 20 months were randomly divided into control group(n =15) and propofol group(n =15).The control group was injected with normal saline of 6 ml/kg intraperitoneally and propofol was injected intraperitoneally with propofol 60 mg/kg.The rats in both groups underwent Step-down Test to assess cognitive function at the first day and at the seventh day after the termination of drug administration.Five rats were decapitated randomly each time after the two step-down tests and their hippocampi were removed for two-dimensional gel electrophoresis and mass spectrometric analysis.Results In the step-down test,aged rats in the propofol group showed significantly learning impairment and decreased memory abilities at the 1st day after propofol anesthesia as compared with those in the control group.In learning phase of the 1st day,the latency of the propofol group is (29.5 ± 7.6)s as compared with(19.7 ± 7.0)s of the control group,while the error time is 3.6±1.2 vs.1.6 ±0.8 in the propofol group vs the control group,and the total time of electric shock is(65.2 t 10.6)s vs.(42.7 ± 10.3)s in the propofol group vs the control group(all P＜0.01).The latency of the memory phase in the propofol group is also decreased as compared with that in the control group(31.4±14.3)s vs.(111.2± 23.7) s,(P＜0.01).On the 7th day after anesthesia,there was no significant difference between the two groups.There were 17 differentially expressed proteins on the 1st day after propofol anesthesia,6 of them were up-regulated and 11 proteins were down-regulated (P ＜ 0.05).On the 7th day,there were 10 differentially expressed proteins,and the expression of 5 proteins was down-regulated (P ＜ 0.01).Conclusions Aging rats receiving propofol anesthesia show cognitive function decline,but do not show a long-term decline.The mechanism may be related to the different expressions of hippocampal proteins.

Objective:To compare the effect of the frequency of transcatheter arterial chemoembolization (TACE) on preventing tumor recurrence after hepatectomy. Methods:A total of 45 post-operative patients who had received prophylactic TACE once or thrice were retrospectively examined between January 2008 and June 2009. Of the 45 patients, 23 underwent TACE once, and the others un-derwent it thrice. TACE was administered to all patients via the hepatic artery one to two months after operation and was repeated every two to four months with patients who underwent TACE three times. All cases were followed up for 36 to 40 months after surgery. The rates of cumulative recurrence between the two groups were compared. Results:In the group that underwent TACE once, the 1-, 2-and 3-year cumulative recurrence rates were 30.43%, 47.83%, and 47.83%, respectively. In the group that underwent TACE thrice, the 1-, 2-and 3-year cumulative recurrence rates were 4.55%, 27.27%, and 36.36%, respectively. Statistical analysis showed that the relapse rate within one year was lower in the group that underwent TACE thrice than in the group that underwent TACE only once (P=0.022). How-ever, no significant difference in the cumulative recurrence rate was found between the two groups in two and three years (P=0.086, 0.225). Conclusion:Hepatocellular carcinoma patients who undergo preventive TACE three times after hepatectomy exhibit reduced re-currence rates during the peak time of tumor recurrence and extended disease-free survival intervals.

Objective To investigate the role of Janus kinese 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by sufentanil postconditioning in dogs.Methods Twenty-four healthy dogs of either sex,weighing 10-15 kg,were randomly divided into 4 groups (n =6 each):sham operation group (group S); I/R group; sufentanil postconditioning group (group PO) and sufentanil postconditioning + specific JAK2 inhibitor AG490 group (group AG).In groups I/R,PO and AG,myocardial I/R was produced by occlusion of left anterior descending coronary artery for 30 min followed by 120 min reperfusion.In groups PO and AG,sufentanil 0.6 μg/kg was infused intravenously over 5 min before reperfusion and in addition in group AG,AG490 1 mg/kg was injected intravenously before sufentanil infusion.Myocardial specimens were taken at the end of 120 min reperfusion for microscopic examination and determination of the expression of caspase-3 and p-STAT3 by immuno-histochemistry and myocardial cell apoptosis index (AI) by TUNEL.Results AI and the expression of caspase-3 and p-STAT3 were significantly higher in groups I/R,PO and AG than in group S ( P ＜ 0.05).Compared with group I/R,AI and the expression of caspase-3 were significantly decreased in groups PO and AG,the expression of p-STAT3 was significantly increased in group PO,and the expression of p-STAT3 was significantly decreased in group AG ( P ＜ 0.05).AI and the expression of caspase-3 were significantly higher and the expression of p-STAT3 was significantly lower in group AG than in group PO (P ＜ 0.05).The pathologic changes were significantly attenuated in group PO compared with groups I/R and AG.Conclusion JAK2-STAT3 pathway is involved in reduction of myocardial I/R injury by sufentanil postconditioning in dogs.

Objective To evaluate the effect of sufentanil postconditioning on the level of cathepsin B in the myocardium during ischemia-reperfusion (I/R) in the rats.Methods Eighteen healthy adult male Sprague-Dawley rats,weighing 250-300 g,were divided into 3 groups (n=6 each) using a random nunber table:shamn operation group (group S),group I/R and sufentanil postconditioning group (group SP).The rats were anesthetized with intraperitoneal 20％ urethane 5 ml/kg.Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion.At 5 min before reperfusion,sufentanil 1.0 μg/kg was intravenously injected in group SP,and the equal volume of normal saline was given instead in S and I/R groups.At the end of reperfusion,blood samples from the abdominal aorta were collected for determination of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) concentrations,and myocardial specimnens were obtained for examination of the ultrastructure of cardiomyocytes (using transmission electron microscopy) and for determination of Beclin1,microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) and cathepsin B expression (by Western blot) and cathepsin B activity (by fluorometric assay).Results Compared with group S,the serum cTnI and CK-MB concentrations were significantly increased,the expression of Beclin-1,LC3 Ⅱ and cathepsin B was up-regulated,and the activity of cathepsin B was enhanced in I/R and SP groups (P＜0.05).Compared with group I/R,the serum cTnI and CK-MB concentrations were significantly decreased,the expression of Beclin-1 and LC3 Ⅱ was down-regulated,the expression of cathepsin B was up-regulated,and the activity of cathepsin B was enhanced (P＜0.05),the pathological changes of myocardial tissues were signifieantly attenuated,and autophagosomes were reduced in group SP.Conclusion The mechanism by which sufentanil postconditioning inhibits cardiomyocyte autophagy during myocardial I/R is probably related to increased expression and activity of cathepsin B in rats.

Objective To establish a tibial cancer pain model with MADB-106 mammary gland carcinoma cell line and to conduct therapeutic research through the behavior pain, X-ray, histological observation of the model. MethodsA rat model of bone cancer pain was established by intra-tibial inoculations of MADB-106 rat mamnary gland carcinoma cells in SD rats. Spontaneous pain was assessed by the reflection of spontaneous paw withdraw, move-evoked pain was observed by the extent of lower extremity claudication when the rats walked and heat hyperalgesia was evaluated by using a thermal dolorimeter. The structural damage of the bone was monitored by X-ray and histology.ResultsThe model group spontaneously withdrawed their paws (14.42±1.24) times on the 15th day after operation (P ＜0.001), (18.33±1.37) times on the 22nd day (P ＜0.001), (21.25±1.54) times on the 25th day (P ＜0.001). The radiant pain thresholds of the model group was (1 1.86±1.63) s on the 15th day after operation (P ＜0.001), (8.38±1.05) s on the 22nd day (P ＜0.001), (7.47±1.25) times on the 25th day (P ＜0.001). The move-evoked pain score of the model group was (1.25±0.62) on the 15th day after operation (P ＜0.001), (2.00±0.95) on the 22nd day (P ＜0.001), (2.33±1.07)on the 25th day (P ＜0.001). The results showed that rats of the model group displayed the gradual development of spontaneous pain, heat hyperalgesia and move-evoked pain on the 15-25 days after injection of the tumor cells. The X-ray of the tibia showed clear bone destruction. The histology of the bone showed the bone marrow cavity was full of tumor cells and the cortical bone had been destroyed. ConclusionThe bone cancer model has been built well and it will be useful to evaluate the therapy of cancer pain after two weeks.

Objective To investigate the mechanism underlying sufentanil postconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in rats through evaluating the relationship between phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) signaling pathway and mitochondrial permeability transition pore (mPTP).Methods Forty-eight pathogen-free healthy male SpragueDawley rats,aged 3 months,weighing 250-300 g,were divided into 4 groups (n=12 each) using a random number table:sham operation group (group S),group I/R,sufentanil postconditioning group (group SP) and snfentanil postconditioning plus PI3K inhibitor wortmannin group (group SP +W).The rats were anesthetized with 20％ urethane 5 ml/kg.Myocardial I/R was induced by ligation of the anterior descending branch of left coronary artery for 30 min,followed by 120 min reperfusion.Sufentanil 1.0 μg/kg was injected via the sublingual vein at 5 min before reperfusion in SP and SP+W groups.Wortmannin 15 pμg/kg was injected via the sublingual vein at 5 min before reperfusion,and then sufentanil 1.0 μg/kg was given in group SP+W.Blood samples were taken from the abdominal aorta at the end of reperfusion for detection of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) concentrations.The rats were then sacrificed and hearts were removed for determination of cell apoptosis (by TUNEL),nicotinamide adenine dinueleotide (NAD+) content (by speetrophotometry),and expression of phosphorylated Akt (p-Akt) in myocardial tissues (by Western blot).Apoptosis index (AI) was calculated.The myocardial mitochondria and cytoplasm were isolated for detection of the expression of cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) using Western blot.Results Compared with group S,the serum cTnI and CK-MB concentrations and AI were significantly increased,the content of NAD+ was decreased,the expression of p-Akt was up-regulated,the expression of Cyt e and AIF in mitochondria was down-regulated,and the expression of Cyt c and AIF in cytoplasm was up-regulated in I/R,SP and SP+W groups (P＜0.05).Compared with group I/R,the serum cTnI and CK-MB concentrations and AI were significantly decreased,the content of NAD+ was increased,the expression of p-Akt was up-regulated,the expression of Cyt c and AIF in mitochondria was up-regulated,and the expression of Cyt c and AIF in cytoplasm was down-regulated in group SP (P＜0.05).Compared with group SP,the serum cTnI and CK-MB concentrations and AI were significantly increased,the content of NAD+ was decreased,the expression of p-Akt was down-regulated,the expression of Cyt c and AIF in mitochondria was down-regulated,and the expression of Cyt c and AIF in cytoplasm was up-regulated in group SP+W (P＜0.05).Conclusion Sufentanil postconditioning can activate PI3K/Akt signaling pathway,inhibit mPTP opening,mitigate mitochondrial injury and inhibit apoptosis in cardiomyocytes,thus attenuating myocardial I/R injury in rats.