Multi-target drugs attract increasing attentions for the therapy of complicated neurodegenerative diseases. In this study, a computer-assisted strategy was applied to search for multi-target compounds by the pharmacophore matching. This strategy has been successfully used to design dual-target inhibitor models against both the acetylcholinesterase (AChE) and poly (ADP-ribose) polymerase-1 (PARP-1). Based on two pharmacophore models matching and physicochemical properties filtering, one hit was identified which could inhibit AChE with IC50 value of (0.337 +/- 0.052) micromol x L(-1) and PARP-1 by 24.6% at 1 micromol x L(-1).

Objective To investigate the clinical effect of different surgical approaches on multi-level cervical spondylosis in elderly patients.Methods A total of 53 aged patients with multi-level cervical spondylosis (≥70 years old) who received operation in our department during May 2007 to May 2014 were retrospectively studied, and divided into anterior cervical surgical group (n=22) and posterior cervical group (n=31), according to the surgical approach.The operation duration, intraoperative blood loss, hospitalization time, postoperative complications, Japanese orthopedics association (JOA) scores, Neck disability index (NDI), postoperative subjective improvement of clinical symptoms and spinal fusion of the two groups were evaluated and compared respectively.Results The mean operative time was longer in the anterior surgical group than in the posterior surgical group [(2.7±0.5)h vs.(1.9±0.3) h, P＜0.05].The average blood loss of the anterior surgical group was less than that of posterior surgical group [(90.0±50.4) ml vs.(160.7±40.5)ml, P＜0.05].The hospitalization time of the anterior surgical group was less than that of posterior surgical group [(10.3±2.5) d vs.(15.7±3.6) d, P＜0.05].Postoperative JOA score of anterior surgical group was higher than that of posterior surgical group 6 months after surgery [(14.7 ±0.8)vs.(13.8±1.2), P＜0.05], while there was no significant difference in JOA score between the two groups up to the last follow-up [(14.8±1.2) vs.(14.7±1.8), P＞0.05].NDI score was lower in anterior surgical group than in posterior surgical group 3, 6, 12 months after operation and at the last follow-up.Among the 41 patients, radiographic outcomes showed that there were 16 cases of anterior surgical group with no bony fusion at the follow-up 3 months after operation, and all the 16 patients achieved bony fusion at the follow-up 1 year after operation, and there were 4 cases with titanium mesh subsidence (＜ 3 mm).Conclusions Both anterior cervical decompression and fusion and posterior cervical single open-door laminoplasty have good efficacy in the treatment of multilevel cervical spondylosis in elderly patients, which have advantages on the limb functional recovery time and cervical function assessment.When anterior cervical surgical contraindications were excluded, the anterior cervical decompression and fusion may be a good choice for the treatment of multilevel cervical spondylosis in aged patients.

Objective To investigate the effects of long intergenic non-coding RNA 467(linc00467)on the proliferation,apoptosis and migration,invasion ability of endometrial carcinoma cells.Methods Human endometrial carcinoma cells HC1A,Ishikawa,KLE and RL-95-2 were cultured in vitro,the expression level of linc00467 in the four cells was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Endometrial carcinoma cell lines HEC-1A and Ishikawa with the highest linc00467 expression levels were selected for subsequent experiment.Two Iinc00467 lentivirus silencing expression vectors of sh-linc00467#1 and sh-linc00467#2,and empty lentivirus plasmids were constructed,respectively;the HEC-1A and Ishikawa cells in logarithmic growth phase were divided into sh-NC group,sh-linc00467#1 group,and sh-linc00467#2 group.The cells in the sh-NC group were transfected with empty lentivirus plasmids,the cells in the sh-linc00467#1 group and sh-linc00467#2 group were transfected with sh-linc00467#1 and sh-linc00467#2,respectively;the relative expression level of linc00467 in cells of the three groups was detected by RT-qPCR,the proliferation ability of cells in the three groups was detected by 5-ethynyl-2-deoxyuridine(EdU)assay and colony formation assay,the migration ability of cells in the three groups was detected by scratch assay,the invasion ability of cells in the three groups was detected by Transwell assay,and the cell apoptosis in the three groups was detected by flow cytometry.Results The relative expression level of linc00467 mRNA in HEC-1A cells was significantly higher than that in KLE and RL-95-2 cells(P＜0.05);the relative expression level of linc00467 mRNA in Ishikawa cells was significantly higher than that in KLE and RL-95-2 cells(P＜0.05);there was no statistically significant difference in the relative expression level of linc00467 mRNA between HEC-1A and Ishikawa cells(P＞0.05);the relative expression level of linc00467 mRNA in KLE cells was significantly lower than that in RL-95-2 cells(P＜0.05).The relative expression levels of linc00467 mRNA in HEC-1A and Ishikawa cells in the sh-linc00467#1 group and sh-linc00467#2 group were significantly lower than those in the sh-NC group(P＜0.01);there was no statistically significant difference in the relative expression level of linc00467 mRNA in HEC-1A and Ishikawa cells between the sh-linc00467 # 1 group and the sh-linc00467#2 group(P＞0.05).The number of EdU positive HEC-1A and Ishikawa cells in the sh-linc00467#1 group and sh-linc00467#2 group was significantly lower than that in the sh-NC group(P＜0.01);there was no statistically significant difference in the number of EdU positive HEC-1A and Ishikawa cells between the sh-linc00467#1 group and sh-linc00467#2 group(P＞0.05).The number of cloned HEC-1A and Ishikawa cells in the sh-linc00467#1 group and sh-linc00467#2 group was significantly lower than that in the sh-NC group(P＜0.01);there was no statistically significant difference in the number of cloned HEC-1A and Ishikawa cells between the sh-linc00467#1 group and sh-linc00467#2 group(P＞0.05).The apoptosis rates of HEC-1A and Ishikawa cells in the sh-linc00467#1 group and sh-linc00467#2 group were significantly higher than that in the sh-NC group(P＜0.01);there was no statistically significant difference in the apoptosis rates of HEC-1A and Ishikawa cells between the sh-linc00467#1 group and sh-linc00467 #2 group(P＞0.05).The scratch healing rates of HEC-1A and Ishikawa cells in the sh-linc00467#1 group and sh-linc00467#2 group were significantly lower than those in the sh-NC group(P＜0.01);there was no statistically significant difference in the scratch healing rates of HEC-1 A and Ishikawa cells between the sh-linc00467#1 group and sh-linc00467#2 group(P＞0.05).The number of invasive cells of HEC-1 A and Ishikawa in the sh-linc00467#1 group and sh-linc00467#2 group was significantly lower than that in the sh-NC group(P＜0.01);there was no statistically significant difference in the number of invasive cells of HEC-1 A and Ishikawa between the sh-linc00467#1 group and sh-linc00467#2 group(P＞0.05).Conclusion Down-regulation of linc00467 expression can inhibit the proliferation,migration and invasion,and promote apoptosis of endometrial carcinoma cells.

Objective To evaluate the efficacy of biofeedback combined with swallowing function training at different times on post-stroke dysphagia. Methods 124 patients with post-stroke dysphagia were randomly divided into observation group and control group. The observation group was given biofeedback combined with swallowing function training for 2 weeks and 4 weeks of treatment. The control group was given routine swallowing function training for 2 weeks and 4 weeks of treatment. Kubota drinking water test was used to evaluate the swallowing function before treatment, 2 weeks and 4 weeks after treatment in both groups. Results There was no statistically significant difference in the scores of swallowing function between the two groups before treatment (P=0. 401). After 2 weeks of treatment, there was also no statistically significant difference in the evaluation of swallowing function between the observation group and the control group (P=0. 138). After 4 weeks of treatment, the evaluation of swallowing function in the observation group was significantly better than that in the control group(P=0. 003). Conclusion Biofeedback combined with swallowing function training is better than the routine swallowing function training. After 4 weeks of treatment, the efficacy of biofeedback combined with swallowing function training is better than the biofeedback combined with swallowing function training after 2 weeks, indicating that there is a correlation between the treatment effect and the length of treatment time.

Objective To investigate the roles of neutral sphingomyelinase-2 (nSMase2) pathway on cerebral edema and cerebral injury in cerebral ischemia-reperfusion injury in rats. Methods Seventy-six adult male SD rats were randomly divided into sham operation group (n = 12), modeling group (n = 16), vehicle group (n = 16), SB203580 (a p38 mitogen activated protein kinase [MAPK] inhibitor) treatment group (n = 16) , and MRS1754 (a selective adenosine A2B receptor [A2B AR] antagonist) treatment group (n = 16) according to the random number table. A suture-occluded method was used to induce a middle cerebral artery ischemia-reperfusion model. Vehicle, SB203580, and MRS1754 were injected into the lateral ventricles 30 min before model preparation, the neurological function score was performed after ischemia-reperfusion for 24 h. 2,3,5 triphenyltetrazolium staining was used to detect the infarct volume. The water content of brain tissue was detected by dry-wet weight method. Western blot analysis was used to detect the expression of nSMase 2 and p38 MAPK in ischemic brain tissue. Immunohistochemical staining was used to detect the expression of nSMase 2 in ischemic brain tissue. Results MRS1754 significantly decreased neurobehavioral score (P < 0. 05) and reduced cerebral infarction volume (P < 0. 05) in rats. Both MRS1754 and SB203580 significantly decreased the water content of ischemic brain tissue (all P < 0. 05). In addition, MRS1754 also significantly decrease the phosphorylation of p38 MAPK after ischemia-reperfusion and decreased the expression level of nSMase 2 (P < 0. 01). Conclusion Regulation of A2BAR and p38 MAPK of nSMase upstream may play a neuroprotective role after cerebral ischemia-reperfusion injury.