Background Several cytokines,especially interleukin-1β (IL-β) involve in the breakdown of blood-retina barrier,and the signal of cytokine is transduced through protein tyrosine kinase (PTK) pathway.Objective This study was to investigate the effects of PTK inhibitor,Genistein,on IL-1β-induced blood-retinal barrier breakdown and possible mechanism.Methods The animal models of blood-retinal barrier breakdown were induced through intravitreal injection of IL-1β(10ng) in 24 clean healthy SD rats and assigned to IL-1β group and Genistein group.5μl IL-1β+1μl Genistein with 0.2,1,5μg were intravitreally injected in 12 model rats and 5μl IL-1β (2mg/L)+1μl DMSO was used at the same way in other 12 models.Evans Blue was injected in rats via jugular vein in 1 hour before sacrifice of animals and the arterial blood was collected for the detect of serum Evans Blue.The retinas of the rats were obtained in 4 and 48 hours after injection of vitreous cavity to assay the content of Evans Blue in retina.The changes of vessels and infiltration of inflammatory cells were observed with hematoxylin-eosin stain.RT-PCR was employed to determine the expression of IL-8 and MCP-1mRNA in neuroretina after intravitreal injection.Expression of MCP-1 protein was localized by immunohistochemistry.Results The ratio of retinal Evans Blue and plasma Evans Blue was significantly decreased after intravitreal injection of different doses of Genistein among Genistein groups and IL-8 group with a statistical difference (4 hours:F=7.510,P=0.010;48 hours:F=5.960,P=0.019).With the increase of time after injection of Evans Blue,the ratio of retinal Evans Blue and plasma Evans Blue was gradually reduced in comparison to IL-1β group (P＜0.05).After injection of IL-1β,the dilation of retinal vessel and adhesion of leukocyte to vessel wall were seen under the light microscope,but infiltration of less inflammatory cells was found in Genistein group.The expressions of IL-8 and MCP-1mRNA were obviously declined in retina of rats in Genistein groups compared with IL-8 group (P＜0.05).Immunochemistry indicated that the expression of MCP-1 protein in neuroretina tissue was weaker in Genistein group compared with IL-8 group.Conclusion PTK inhibitor,Genistein,can decrease IL-1β-induced permeability of vessel and maintain the integrity of blood-retinal barrier by downregulating the expression of chemokines and infiltration of leukostasis in retinal vessels.This study imply that PTK pathway plays an important role in IL-1β-induced blood-retinal barrier breakdown.

Objective To determine the median effective target effect-site concentration (EC50) of sufentanil when intraoperative wake-up test was successful in patients undergoing scoliosis surgery.Methods Ninety ASA Ⅰ or Ⅱ patients,aged 18-64 yr,with body mass index ＜ 30 kg/m2,scheduled for scoliosis surgery under sevoflurane and sufentanil anesthesia,were randomly divided into Ⅰ-Ⅵ groups (n =15 each).Anesthesia was induced with sufentanil,etomidate and cisatracurium,and maintained with sevoflurane,sufentanil and cisatracurium.The patients were tracheal intubated and mechanically ventilated.Before the wake-up test,infusion of cisatracurium was stopped and the end-tidal concentration of sevoflurane was adjusted to 0.The EC50 was determined by the K(a)rber method.The target effect-site concentration of sufentanil was set at 0.19 ng/ml in group Ⅰ,0.18 ng/ml in group Ⅱ and gradually decreased in decrements of 0.01 ng/ml.The wake-up test was performed 5 min later.The EC50 and 95 ％ confidence interval of sufentanil were calculated by the K(a)rber method.Results EC50 of sufentanil obtained was 0.164 ng/ml and 95％ confidence interval of sufentanil obtained was 0.157-0.172 ng/ml when the wake-up test was successful.Conclusion The EC50 of sufentanil is 0.164 ng/ml when the intraoperative wake-up test is successful in the patients undergoing scoliosis surgery.

Objective To observe the effect of treadmill training on metabotropic glutamate receptor of a middle cerebral artery occlusion model in rat and its underlying mechanisms. Methods Sprague-Dawley male rats of 2 or 3 months old were randomly divided into 3 groups: a sham operation group, an iscbemia-reperfnsion group and a treadmill training group (subject to 2 weeks of training after the ischemia-reperfusion). All the animals were sacri-ficed after 2 weeks of training and their brains were sampled for measurement of the expression level of the striatum mGluR Ⅰ-mRNA, using RT-PCR technique. Results The striatum mRNA of mGluR1 and mGluR5 was signifi-cantly elevated in the ischemia-reperfusion group(P<0.01), but treadmill training significantly suppressed the ele-vation of the expression of mRNA of mGluR1 and mGluR5 (P<0.01). Conclusions Treadmill training can signif-icantly downregulate mGluR Ⅰ-mRNA expression. This might be one of the important mechanisms for inhibition of the excitatory glutamate production.

BACKGROUND:It is wel-known that mechanical stimulation could promote fracture healing. However, what kind of mechanical stimulation induced by treadmil exercise can increase the bone conductibility of bone material and promote the healing of bone defect is stil unclear.
OBJECTIVE:To evaluate the influence of indirect mechanical stimulation produced by treadmil exercise on bone defect healing and osteogenesis of bone materials.
METHODS:Sprague-Dawley rats at 12 weeks old were used in this study to establish a bone defect of 3 mm in diameter and height at the left distal femur. Afterwards, calcium sulphate scaffolds were implanted into the defects. The rats were divided into treadmil exercise group and control group. Treadmil exercise was began at 1 week postoperatively, 10 m/min, 45 minutes per day, 5 days per week, for 3 weeks. Control group did not receive any exercise. Micro-computed tomography was used to determine bone formation in the bone defects at 1, 2, 3, and 4 weeks after surgery. The sections of left distal femur were subject to hematoxylin-eosin staining, the new bone formation and degradation of bone materials in the bone defects were observed.
RESULTS AND CONCLUSION:Micro-CT analysis showed that, a smal amount of new bone formed in both treadmil exercise group and control group at 1 week after surgery. In treadmil exercise group, new bone formation was significantly higher than the control group at 2, 3, 4 weeks (P<0.05). At 4 weeks, histological results also confirmed the difference of new bone formation in bone defect between treadmil exercise group and control group. In addition, bone mineral density of treadmil exercise group was higher than that of control group at 2, 3, 4 weeks, but no significant difference was found (P>0.05). The results suggest that moderate treadmil exercise could promote bone defect healing and enhance osteoconductivity of bone substitute.

Objective To evaluate the overall failure rate of one or two-stage exchange arthroplasty for infections in total knee arthroplasty (TKA) and the predictors affecting the outcome of exchange.Methods Thirty-nine cases received one or two-stage exchange arthroplasty for periprosthetic joint infections after primary TKA in Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine and Southeast Hospital affiliated to Xiamen University from January 2012 to November 2014 were reviewed.Periprosthetic tissue and articular fluid of all patients were analyzed by bacterial culture.All patients were followed up for more than one year.C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),procalcitonin (PCT) and blood routine were tested every four weeks,and the evaluation on pain,total periprosthetic function,range of motion and deformation of arthroplasty were conducted.Differences between groups were analyzed using chi-square test or Student's t test when appropriate.A stepwise selection approach in logistic regression analysis was used to screen key predictors for outcome of one or two-stage exchange for infections in TKA.Results There were 39 patients who had undergone one or two-stage exchange for infections in TKA,including 20 males (51.3％) and 19 females (48.7％) with an average age of (62.4±11.7) years.Among the 39 patients,18 gram-positive strains were isolated from specimens,and 6 gram negative strains,2 Mycobacterium tuberculosis and 1 candida albicans.Ten of 39 reimplantations developed reinfection.Between the success and failure groups,there were significant differences in the time from primary TKA to revision (P =0.023),operative time (P =0.029),multidrug resistant organisms (P =0.045),the preoperative and post-operative ESR (P=0.002 and P＜0.001,respectively) and post-operative CRP (P=0.018).Multivariable logistic regression analysis demonstrated that time from primary TKA to revision (OR =0.96,95％CI:0.92-1.00,P=0.025),preoperative ESR (OR=0.97,95％CI:0.95-1.00,P=0.045) and post-operative ESR (OR =0.94,95％ CI:0.91-0.98,P =0.002) were independent indicators associated with the outcome of one or two-stage revision.Conclusions The failure rate after revision for infected TKA is relatively high.The time from primary TKA to revision,preoperative and post-operative ESR could predict the outcome of one or two-stage revision effectively.

Objective To investigate the influence of lipid metabolic markers on hip osteoarthritis (OA) and the correlation with the pain of hip.Methods In this retrospectively cross sectional analysis,393 subjects fufilling the inclusive criteria were continuously included from June 2013 to September 2014.The presentation of hip X-ray of subjects were classified into OA group and non-OA group in terms of Kellgren-Lawrence grading scale,the subjects with Kellgren-Lawrence (K-L)≥2 was classified into OA group.The average of age in total was (62±9) years.There were 183 males and 210 females,the number of patients with OA was 182.There were 210 patients with hypertension and 118 patients with diabetes while the number of smoking patients was 74.The demographic information,risk factors,blood pressure,blood glucose,lipid metabolic markers were analyzed.Differences in proportions were compared using the Chi-square test.Difterences in continuous variables were tested for statistical significance using t test analysis.VAS score was used to evaluate the severity of hip pain.Independent risk factors were confirmed by using multiple logistic regression analysis.The correlation between the risk factors and severity of hip pain was analyzed by Spearman correlation analysis.Results Statistically significance existed in age (t=-4.849),sex (x2=8.946),BMI (t=-4.794),hypertension (x2=4.751),smoking (x2=7.062),metabolic syndrome (x2=34.406),apolipoprotein A1 (t=2.352),apolipoprotein B (t=-6.870),high density lipoprotein cholesterol (t=2.519),triglyceride (t=-4.652) and ApoB/ApoA1 ratio (t=-4.901) between OA group and non OA group.Age [OR =1.060(1.033,1.086)],metabolic syndrome [OR=3.682(2.284,5.938)] and ApoB/ApoA1 ratio [OR=5.743(2.393,13.785)] were the independent risk factors.The ApoB/ApoA1 ratio had positive correlation with the severity of hip pain(r=0.379).Conclusion ApoB/ApoA1 ratio is the independent risk factor of hip osteoarthritis,and has positive correlation with the severity of hip pain.The ApoB/ApoA1 ratio should be monitored in hip osteoarthritis patients in clinical work,to get the relief of pain and improve hip osteoarthritis.

Objective To explore the expression of PRR11(Proline-rich protein 11) in human osteosarcoma and investigate the effect of PRR11 on the proliferation of human osteosarcoma cells.Methods Immunohistochemical staining was applied to detect the PRR11 expression in 75 cases of osteosarcoma and corresponding normal tissues.Western blotting was used to examine PRR11 protein expression levels in osteosarcoma cell lines.We used siRNA to knock down the expression of PRR11 and tested the effects of PRR11 down-regulation on the proliferation in SaOS2 cells.Results PRR11 was overexpressed in osteosarcoma specimens compared to their paired normal tissues,the over expression rate of PRR11 in osteosarcoma and corresponding paracancerous tissues were 76％(57/75) and 9.33％(7/75) with statistical difference(P<0.05).The high expression of PRR11 was correlated with tumor pathological grade and lymphatic metastasis(P<0.05).PRR11 was expressed in 4 osteosarcoma cell lines which were SaOS2,143B,U2OS and MG63 respectively,the expression was highest in SaOS2 cells.Silencing PRR11 inhibited cell growth as compared with control cells(P<0.05).Conclusion PRR11 is overexpression in human osteosarcoma and promotes its progression by enhancing proliferation.The increased expression of PRR11 in osteosarcoma is a new target for treatment and early diagnosis of human osteosarcoma patients.

Drug dependence has been a severe social and health problem,which has caused serious economic losses and social disorder in China.The critical problem in drug dependence is repeated relapse even after detoxification.We have been contributed to the research of neurobiological mechanisms,clinical characteristics,and interventions of craving after withdrawal from addicting drugs.We have systemati-cally studied the change of drug seeking behavior and craving after withdrawal from cocaine,and further investigated the neural anatomic pathway,long-term neuroplasticity,and neural signal pathways which involved in the change of drug seeking behavior.According to the situation of dug abuse in China,we investigated the characteristics in the expression of incubation of craving after withdrawal from opiate.We have primarily found the neural anatomic pathways and neural plasticity mechanisms which contribute to the process.We have also demonstrated the psychological characteristics and neurobiological mechanisms of craving induced by opiate and its long-term maintenance resulting from learning and memory,chronobiology and imaging.Our findings have provided evidence for effective inventions on preventing relapse after abstinence in addicts.Abstract:SUMM ARY Drug dependence has been a severe social and health problem,which has caused serious e-conom ic losses and social d isorder in China.The critical problem in drug dependence is repeated relapse even after detoxification.W e have been contributed to the research of neurobiologicalmechanisms,clini-cal characteristics,and interventions of craving afterwithdrawal from add icting drugs.W e have systemati-cally stud ied the change of drug seeking behavior and craving afterwithdrawal from cocaine,and further investigated the neural anatom ic pathway,long-term neuroplasticity,and neural signal pathways which involved in the change of drug seeking behavior.Accord ing to the situation of dug abuse in China,we in-vestigated the characteristics in the expression of incubation of craving after withdrawal from opiate.W e have primarily found the neural anatom ic pathways and neural plasticity mechanisms which contribute to the process.W e have also demonstrated the psychological characteristics and neurobiologicalmechanisms of craving induced by opiate and its long-term maintenance resulting from learning and memory,chrono-biology and imaging.Our find ings have provided evidence for effective inventions on preventing relapse after abstinence in add icts.

Objective To assess the effect of simvastatin on secretion of VEGF in blood serum and sputum of elderly chronic ob-structive pulmonary disease(COPD)combined with PAH patients and the pulmonary function.Methods Seventy cases of elderly COPD patients combined with PAH patients were randomized in two groups,namely the normal treatment group and combined sim-vastatin group (35 cases in each group),then compare the changes of the VEGF in blood serum,sputum and lung function.Results VEGF in blood serum and sputum showed significant changes after therapies of simvastatin (P <0.05).After 4 weeks′therapy, the FEV1% pre and FEV1/FVC increased significantly (P <0.05).Conclusion Normal treatment combine with simvastatin could decrease VEGF in blood serum and sputum of elderly COPD combined with PAH patients,meanwhile improve pulmonary function.