Opioid peptides and their receptors play an important r ole in the pathophysiologic process of stroke. The concentration of endogenous o pioid peptides elevates, while the density of opioid receptors decreases in CNS during cerebral ischemia; on the other hand, opioids influence the development o f stroke through regulating the contraction of cerebral vessel, immuno-endocrin e system and neuroprotection against injury. Thus, drugs that regulate the opioi d system may be a new therapeutic approach for prevention and treatment of cereb ral ischemia.

Voltage-gated sodium channels (NaV1.1-NaV1.9) play important roles in the generation and maintenance of electrical excitability. NaV1.7 is preferentially expressed in peripheral somatic sensory neurons and sympathetic ganglion neurons. ln humans, gain-of-function mutations of SCN9A gene, which encodes NaV1.7, cause inherited neuropathic pain, whereas loss-of-function mutations result in a congenital indifference to pain without motor, cognitive and cardiac deficits. The effects of some analge-sics are associated, at least in part, with the NaV1.7 and selective NaV1.7 inhibitors have also been demonstrated to be analgesic in animal models. NaV1.7 has emerged as a potential target for the treat-ment of pain.

Objective To explore the characteristics of gait and surface electromyography (sEMG) of underwater treadmill training (UWTT). Methods From January to September, 2015, gait and sEMG parameters of ten healthy adults were synchronously collected using three-dimensional gait analysis system and sEMG systems on land and UWTT. Results When walking in self comfortable speed, compared with walk on land, there was significant increase in gait cycle (t=-11.411, P<0.001) and percentage of the swing phase (t=-5.252, P<0.05), significant reduction in walking speed (Z=-2.803, P<0.01) and step frequency (t=7.421, P<0.001). There was no significant difference in step strength (Z=-0.357, P>0.05). The integral electromyography of biceps femoris, gastrocnemius, tibialis anterior muscle were significant less than iEMG on land (t>3.984, P<0.01), but no significant difference of rectus femoris (t=0.054, P>0.05). Conclusion There are signifi-cant differences in gait and muscle contraction intensity between land walking and UWTT. The dynamic physiology and neural control of UWTT need further study.

ObjectiveTo explore the relationship among the aggressive behavior,hostile attribution bias and childhood trauma in schizophrenic patients.Methods 135 schizophrenic patients were tested with Modified Overt Aggression Scale (MOAS),the Chinese-version of the Ambiguous Intentions Hostility Questionnaire (AIHQ-C) and Childhood Trauma Questionnaire (CTQ).According to the score of the MOAS,the patients were divided into the aggressive group ( n =58 ) and the non-aggressive group ( n =77 ).The hostile attribution bias and the childhood trauma were compared between the two groups,and correlation and hierarchical regression analysis were used to investigate the relationships of the variables.ResultsCompared with the non-aggressive patients,the aggressive patients had significantly higher AIHQ-C total hostility bias score (6.27 ± 1.20 vs 5.90 ± 0.97,P ＜0.05 ),total blame bias score (8.04 ± 1.97 vs 6.91 ± 2.10,P ＜ 0.01 ) and total aggression bias score ( 6.17 ±1.02 vs 5.59 ± 1.04,P ＜ 0.01 ).Correlation analysis showed that the MOAS score,AIHQ scores and the total score of CTQ were significantly positively correlated with each other ( r =0.171 ～ 0.350,P ＜ 0.05 ～0.01 ).Regression analysis indicated the hostile attribution bias directly predicted the aggressive behavior( β =0.342,P ＜0.05) and completely mediated the relationship between the childhood trauma and the aggressive behavior.ConclusionThe aggressive behavior in schizophrenic patients is associated with the experience of childhood trauma and the attribution style.The childhood trauma indirectly influences the aggressive behavior by the mediating of the hostile attribution bias.

Summary: The homocysteine (Hcy)-induced tissue factor (TF) expression in human vascular smooth muscle cells (VSMCs) and the effect of Hey on the activity of nuclear factor-kappaB (NF-κB) and the expression of inducible nitric oxide synthase (iNOS) were investigated. Human umbilical artery VSMCs were cultured by tissue explanting method, identified by α-actin immunohistochemistry, and incubated with different concentrations of Hcy/PTDC (NF-κB inhibitor). Semi-quantitative RT-PCR was performed to detect the expression of TF mRNA in VSMCs. Flow cytometry was used to assay the expression of TF protein on the surface of VSMCs and the expression of iNOS in VSMCs. Westem blot was carried out to detect the expression of NF-κB protein in nuclei. The results showed that Hcy could induce VSMCs expressing TF mRNA significantly after the VSMCs were incubated with Hey at concentrations of 10, 100, 500 μmol/L respectively. There was low expression level of TF protein on the surface of the resting VSMCs and Hcy could also induce VSMCs expressing TF protein on the cell surface in different concentrations. Additionally, Hcy could rapidly induce the activation of NF-κB and this effect could be significantly inhibited by PDTC. Hcy alone could not induce the expression of iNOS in VSMCs. It was concluded that Hey could significantly induce the expression of TF in VSMCs and enhance the activation of NF-κB, subsequently mediate TF gene expression and protein synthesis. NF-κB-mediated expression of TF in VSMCs might be the important mechanism of atherosclerosis and thrombosis induced by Hcy.

Objective To explore the effects of self-efficacy theory on coping style and quality of life of patients with bladder cancer underwent the targeted therapy.Methods A total of 84 advanced bladder cancer patients in our hospital from May 2011 to May 2016 were selected in the study using convenience sampling method. All patients were randomly divided into control group and observation group,each 42 cases. Patients in both groups were given the combination of conventional chemotherapy and targeted therapy with trastuzumab intravenous injection. The therapy was observed for 4 cycles. Patients in the control group were given routine nursing during the treatment, while patients in the observation group received additional nursing intervention based on self-efficacy. The prognosis and curative effect, coping style and quality of life scores of patients were recorded in the two groups.Results The total curative effective rate of patients in the observation group was 52.38%, which was higher than that in the control group (28.57%). The difference was statistically significant between two groups (P<0.05). After the intervention, the positive coping scores of two groups significantly increased (P<0.05), while the negative coping scores significantly decreased (P<0.05). The changes in the observation group was significantly better than that in the control group (P<0.05). The average quality of life score of the observation group after the intervention was significantly higher than that of the control group (P<0.05).Conclusions The application of self-efficacy theory in the bladder cancer patients underwent the targeted therapy can promote the transformation of positive coping style and improve the quality of life of patients, which is beneficial to the improvement of the overall total effectiveness.

Objective To observe the intervention effect of acupuncture at"Zusanli"(ST36)or"Neiguan"(PC6)on the ulcerative colitis(UC)model mice.And to analyze the similarities and differences of gene transcription expression between the diseased colon and the non-diseased heart after acupuncture intervention by using transcriptomics,to explore whether there are efficacy differences between the two acupoints.Methods The UC mouse model was established by inducing dextran sulfate sodium salt(DSS).After successful modeling,the mice were randomly divided into model group,Zusanli group,and Neiguan group,with 9 mice in each group.Zusanli group and Neiguan group intervened with acupuncture at"Zusanli"and"Neiguan",respectively,30 min each time,once a day,for 5 consecutive days.The control and model groups were only bound without acupuncture.Observe the general situation of mice in each group,calculate the disease activity index(DAI),observe the morphological changes of colon tissue by HE staining.Use transcriptome sequencing technology to sequence and biologically analyze the colon tissue of mice in each group,and compare and study whether the two acupoints have differences in acupoint efficacy from the perspective of diseased tissue.At the same time,take the heart tissues of each group for comparative analysis,and discuss whether the effects of the two acupoints are different from the perspective of non-diseased tissue.Results Compared with control group,the DAI score of the model group increased significantly(P<0.001),and HE staining results showed significant pathological damage;after acupuncture at Zusanli or Neiguan,the DAI scores of UC mice were reduced considerably(P<0.05),and the pathological damage was significantly improved.The results of transcriptome sequencing and bioinformatics analysis showed that the effects of acupuncture at Zusanli or Neiguan on the colon of diseased tissue involved multiple genes,and 825 differential genes with similar changes(co-DEGs)were mainly enriched in white blood cells and chemokine pathways;there were 168 differentially expressed genes(ST36 only-DEGs)affected only by Zusanli,which were enriched to gastric acid secretion and other pathways;there were 325 differentially expressed genes(PC6 only-DEGs)only affected by Neiguan,which were enriched in cytokine-cytokine receptor interaction and other pathways.There were 95 co-DEGs in the heart of non-diseased tissue,which were mainly enriched in positive regulation of defense response and response to interleukin-1;there were 28 ST36 only-DEGs;there were114 PC6 only-DEGs,which were enriched in cardiovascular diseases and other pathways.Conclusion Acupuncture of"Zusanli"and"Neiguan"could improve UC mice's symptoms and pathological colon changes.However,through transcriptomic analysis,it was found that the two acupoints had differences in gene transcription effects on the colon of diseased tissue and the heart of non-diseased tissue,suggesting that acupoints with different distribution positions had some similarities in macro efficacy.Still,there were some differences at a micro level.

Objective This study aims to compare the accuracy of self-developed universal implant guide(SDG),3D printed digital guide(DG),and free hand(FH)simulated implantation in the posterior tooth area of dental models.Methods Ten junior dentists were selected to place three implants in the 35,37,and 46 tooth sites of the mandibular models(35,36,37,and 46 missing teeth)by using SDG,DG,and FH,and the process was repeated again to take the av-erage value.Cone beam computed tomography(CBCT)was used to evaluate the global coronal deviation,global apical deviation,depth deviation,and angular deviation between the actual position and preoperative planned position.Re-sults The coronal deviation and apical deviation of the three implant sites in the SDG group were not significantly dif-ferent from those in the two other groups(P>0.05).The depth deviation and angular deviation in the SDG group were smaller than those in the DG group(P<0.05)and FH group(P<0.05),respectively.All deviations at site 37 in the SDG group were not different from those at site 35(P>0.05),while the depth and angular deviation at site 37 in the DG group were higher than those at site 35(P<0.05).Conclusion The precision of the self-developed universal dental im-plant guide can meet the requirements of clinical posteri-or implantation.

OBJECTIVE To evaluate the psychological dependence of the extrasynaptic GABAA receptor(GABAAR)agonist gaboxadol and compare it with the synaptic GABAAR modulator midazolam in the two-bottle free-choice model of mice.METHODS ① Male C57BL/6J mice were ig administered with vehicle,midazolam(59.0,73.7,92.2,115.2,144.0 and 180.0 mg·kg-1)or gaboxadol(8.4,10.5,13.1,16.4,20.5,25.6 and 32.0 mg·kg-1),and the loss of righting reflex was observed.The median effective dose(ED50)was obtained from the dose-response curve.② A two-bottle free-choice model was used to find out whether gaboxadol and midazolam induced preference behavior in mice.The mice were divided into normal control,gaboxadol or midazolam groups.During the habituation stage(the first day to the third day,D1-D3),both test and vehicle bottles contained water.During the trail stage(D4-D5),4%sucrose solution was provided in both bottles.During the test stage(D6-D15),test bottles contained vehicle,gaboxadol(3.9×10-6 mol·L-1)or midazolam(1.4×10-5 mol·L-1)in sucrose solu-tions,while other bottles contained the corresponding vehicle in sucrose solutions.Bottles were placed on the two sides of the home cage,to which mice had free access,and their consumption from each bottle was recorded daily.Total consumption,accumulated daily consumption,relative consumption,and accumulated relative consumption during the test stage were calculated.The weight of the mice was also recorded.RESULTS ① Midazolam and gaboxadol dose-dependently increased the rate of loss of right reflex in mice,with ED50 of 105.3 mg·kg-1(95%CI:96.4-115.2 mg·kg-1,R2=0.9796),13.7 mg·kg-1(95%CI:12.6-15.0 mg·kg-1,R2=0.9773),respectively.② Compared with the normal control group,there was no significant difference in the total consumption in the gaboxadol and midazolam groups.Compared to the vehicle bottles,the daily consumption from test bottles in the midazolam group increased significantly on D11-D15 of the test stage(P<0.05),while daily consumption from gaboxadol test bottles was significantly higher than that of vehicle bottles(P<0.01).Compared with the normal control group,the daily relative consumption in the gaboxadol group was significantly increased on D9(P<0.05),and the accumulative relative consumption was significantly higher than in the normal control group(P<0.01).There was no significant change in body weight across the groups over the test stage.CONCLU-SION Like midazolam,gaboxadol exhibits psychological dependence potential in a two-bottle free-choice model.

Objective To discover 5-HT2A receptor antagonist molecules with novel structures and explore their structure-activity relationship through structure-and mechanism-based drug design,synthesis and activity evaluation.Methods The way in which pimovanserin interacted with 5-HT2A receptor was analyzed via molecular docking,molecular dynamics simulation and binding free energy calculations.Based on the results of this study,the 5-HT2A receptor antagonist target compounds with novel structures were designed using pimovanserin as the lead molecule.According to the structures of target compounds,corresponding synthetic routes were designed.The heterocyclic methylamine intermediates were obtained by reductive amination or reduction reaction from heterocyclic formaldehyde or heterocyclic methanonitrile before being reacted with 4-(4-fluorobenzylamino)-1-methylpiperidine to obtain the target compounds using CDI urea synthesis method.The inhibitory activity of the target compounds against 5-HT2A receptor was tested at the cellular level,and the anti-hallucinogenic effects of the target compounds were tested in the mouse head twitch response model.Results Twelvenovel compounds were synthesized and their structures were confirmed by HR-MS,1H-NMR and 13C-NMR.The results of the activity assay showed that compounds 6a,6c and 6d exhibited better 5-HT2Areceptor inhibitoryactivity with IC50 values of 120,152 and 285 nmol/L,respectively while compounds 6c and 6d exhibited better anti-hallucinogenic activity in mice with inhibition rates of 97.0％and 82.9％(10 mg/kg),respectively.Conclusion The novel compound 6c and 6d have shown strong 5-HT2A receptor inhibitoryactivity and anti-hallucinogenic activity and deserve more research.Structure-activity relationship analyses of target compounds indicate that the repulsion of the heterocyclic ring with basic N atoms and the accommodation of the heterocyclic ring without basic N atoms by the side extended pocket of the 5-HT2A receptor could significantly affect the ex vivo and in vivo effects of antagonists.