Objective To investigate SIAH′s role in α-synuclein degradation, formation of Lewy bodies and neuronal death. Methods Proliferative activity of PC12 cells was measures by MTT assay after treatment with MPP and Rapamycin. Western Blot was applied determine the protein expression of LC3-Ⅱ, E1, SIAH-1, P53 and α-synucleinto. PCR was applied to measure protein related mRNA levels. Immunofluorescent techniques were used to detect the distribution of α-synuclein, SIAH-1 and LC3 in cells after SIAH antibody processing. Results MPP+ treatment increased α-synuclein, E1 expression and SIAH-1 activity, however, LC3-Ⅱ, P53 and α-synuclein protein levels decreased significantly. Anti-SIAH-1 antibody treatment reversed this trend, with E1 significantly increased. Rapamycin treatment reduced SIAH-1 and α-synuclein levels in the MPP+ group. SIAH-1 antibody significantly decreased the positive immuno-stain of α-synuclein, SIAH-1 and LC3, suggesting loss of co-localization. Conclusions Anti-SIAH-1 supports the clearance of non-aggregated α-synuclein by the UPS. SIAH plays a key role in the pathogenesis of Parkinson′s disease and is a potential therapeutic target of neurodegenerative diseases.

Objective To explore the specific role of autophagy and ubiquitin-proteasome pathway in apoptosis, specific protease inhibitor and (or) macroautophagy inhibitors.Methods The stimulators were selected to work on the pheochromocytoma (PC12) cell lines transfected with human mutant α-synuclein (A53T).Cell activity and apeptosis rate were detected by MTT law and flow cytometry.NO energy, heat shock protein 70 (Hsp70) and Caspase-3 expression were determined in cell culture.Results A53T cell survival rate significantly decreased 24 hours after handling with the protease inhibitor (100 nmol/L) and (or) autophagy inhibitors 3-MA (10 mmol/L, A =0.23±0.01,0.19±0.01 and 0.17±0.01 respectively; P <0.05) compared with the control group (A =0.32±0.06).Cell survival rate was significantly higher than the other drug group after 24 hours handling with autophagy stimulators (A =0.44±0.08).Compared with the control group or autophagy stimulator of rapamycin (0.2 μg/ml) group (1.55%±1.15%), A53T cells apeptosis percentage rate was significantly higher after treated with proteasome inhibitor and macroautophagy inhibitors 24 hours (4.74%±0.91%, 4.59%±1.18% and 5.40%±1.75%respectively, P <0.05); and a slight decrease with stimulators.Protein Hsp70 and NO were significantly higher in proteasome inhibitor groups than the control group.But in antophagy inhibitor and stimulator group, NO and Hsp70 protein was similar to the control group.Conclusion The inhibition of macroautophagy and proteasome can promote apoptosis.Inhibiting or stimulating autophagy has less impact on Hsp70 and NO than proteasome pathway.

Objective To study the impact of Paeoniflorin (PF) on α-synuclein degradation pathway. Methods PC12 cells were treated with or without MPP+ (0.5mM) for 24 h, then treated with Paeoniflorin (50 uM) or Rapamycin (0.2 μg/ml) for 24 h. The proliferative activity of cells was detected with the MTT method , and then the protein expression levels of α-synuclein, microtubule-associated protein light chain 3 (LC3-II) and E1 were detected by Western Blot. The expressions of α-synuclein and LC3 were detected by confocal microscopy. Results (1) CAT and SOD activity were significantly decreased after PF and RAPA treatment compared with MPP+ (P < 0.001). (2)MPP+ activated both LC3-Ⅱand E1. MPP+ promoted the increase ofLC3-Ⅱ but inhibited E1. PF significantly upregulated both LC3-Ⅱ (autophagy) and E1 expression (ubiquitin-proteasome pathway) (P < 0.001), promoted degradation of α-synuclein, and reduced cell damage. (3) MPP+enhanced immunofluorescence signal of intracellular α-synuclein and LC3. Fluorescence intensity of α-synuclein decreasedafter PF treatment. Conclusion PF may significantly upregulate both autophagy and ubiquitin proteasome pathways, promote the degradation of α-synuclein and reduce cell damage. These findings suggest Paeoniflorin may be a potential therapy for neurodegenerative diseases.

Posterior circulation ischemic stroke (PCIS) is caused by the infarction of the blood supply area of vertebrobasilar artery system, accounting for about 20% of all ischemic strokes. The clinical manifestations of PCIS are different and usually lack specificity. The commonly used pre-hospital stroke scale can not fully reflect signs and symptoms of PCIS, and even imaging examination is not easy to detect PCIS. As a result, it is difficult to correctly identify PCIS in the early stage in emergency settings, and the rates of misdiagnosis and missed diagnosis are significantly higher than those of the anterior circulation ischemic stroke. Early and correct identification of PCIS is of great significance to improve the prognosis of patients. By summarizing the relevant literature at home and abroad, this article discusses the diagnostic error factors of PCIS in emergency room from different angles, and summarizes the strategies and methods to improve the speed and accuracy of PCIS recognition and early management.

ObjectiveToinvestigatethecorrelationbetweenbloodpressurevariabilityandcognitive impairment in ischemic stroke. Methods The inpatients with acute ischemic stroke were enroled. The demographic and clinical data were colected. The coefficient of variation of blood pressure within 7 days after onset w as calculated. Montreal Cognitive Assessment w as used to evaluate the cognitive function at three month after onset. Multivariate logistic regression analysis w as used to identify the relationship betw een the coefficient of variation of blood pressure w ithin 7 days and the cognitive impairment at 3 months after onset. Results A total of 708 patients w ith acute ischemic stroke w ere enrol ed in the study. At 3-month folow-up, 510 patients (72.0%) had cognitive impairment and 198 (28.0%) had normal cognitive function. The coefficient of variation for systolic blood pressure ( 8.3 ±1.2 vs.8.7 ±1.4; t= -3.299, P=0.001) and coefficient of variation for diastolic blood pressure ( 7.8 ±1.3 vs.8.0 ±1.5; t= -2.529, P=0.012) in the cognitive impairment group w ere significantly higher than those in the normal cognitive function group. With the first quintile as a reference, after adjusting other confounding factors, multivariate logistic regression analysis show ed that cognitive impairment at 3 months after onset w as significantly associated w ith coefficient of variation for systolic blood pressure. The odds ratios and 95 % confidence intervals for the 2-5 quantile groups w ere 2.33 (1.18-4.6), 2.31 (1.15-4.66), 2.70 (1.29-5.65), and 4.82 (1.92-12.1), respectively ( al P<0.05 ). Conclusion Systolic blood pressure variability in the acute phase of ischemic stroke is associated w ith cognitive impairment.

Objective To evaluate the relationship between short-term blood pressure variability and poor outcome and hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke.Methods The Databases such as Wanfang,CNKI,Cochrane,Pubmed,EMBASE,and Web of Science were retrieved.The randomized controlled trials,cohort studies and case-control studies about blood pressure monitoring after intravenous thrombolytic therapy in patients with acute ischemic stroke and calculation and analysis of blood pressure variability were enrolled.The deadline for retrieval was December 2017.STATA 13.0 software was used to conduct Meta-analysis.Results A total of 9 non-randomized controlled trials with 19 161 patients were included.Four of them were prospective studies and 5 were retrospective studies.The relationship between short-term blood pressure variability and poor outcome (defined as a modified Rankin scale score ＞2) were investigated in 8 studies (a total of 19 045 patients).The relationship between short-term blood pressure variability and hemorrhagic transformation were investigated in 6 studies (with 18 456 patients).The results of Meta-analysis showed that short-term systolic blood pressure variability (every 10 mmHg change;1 mmHg =0.133 kPa) and poor outcome (odds ratio [OR] 1.55,95％ confidence interval [CI] 1.22-1.86;P ＞0.001),hemorrhagic transformation (OR 2.39,95％ CI 1.71-3.35;P =0.025),and symptomatic intracranial hemorrhage (OR 2.49,95％ CI 1.39-4.39;P =0.048) had significant correlations.Conclusion The increased short-term blood pressure variability after intravenous thrombolysis in patients with acute ischemic stroke is associated with poor outcome,hemorrhagic transformation,and symptomatic intracranial hemorrhage.

Objective: To investigate the value of Baduanjin combined with balance pad exercise in improving the balance ability and motor function of elderly Parkinsonundefineds patients. Methods: Totally 120 elderly patients with Parkinsonundefineds disease admitted in our hospital from March 2017 to March 2018 were divided into two groups according to different exercise methods: the balance pad training group (60 cases) and the Baduanjin combined balance pad group (60 cases). After 2 months of continuous exercise, Fugl-Meyer lower limb motor function scale and Berg Balance Scale (BBS) were used to evaluate the recovery of lower limb motor ability and the changes of somatic balance control. Before training and 2 months after training, Parkinsonundefineds Scale (UPDRS) was used to evaluate the motor impairment of the patients. Results: There were no significant differences between the two groups in the Fugl-Meyer score, BBS score, 6mWD and UPDRS scores before training (P>0.05). After 2 months of training, the BBS score of the observation group was (45.5±4.0) points and Fugl-Meyer score. (25.5±3.2) points and 6mWD scores (362.2±44.9) points, the control group was (42.3±3.8) points, (22.7±3.6) points, (337.3±51.0) points, the difference was statistically significant (t=4.493, 4.503, 2.839, P<0.05). After 2 months of training, the UPDRSII and III scores of the observation group were (11.8±3.0) points and (15.8±1.9) points, respectively, which were significantly better than the control group (14.7±2.6) points, (17.2 ± 1.4) points, the difference was statistically significant (t=5.658, 4.595, P<0.05).; the observation group patients had a fall rate of 16.67% (10/60), no fracture cases, the control group was 41.67% (25/60), 6.67% (4/60), the difference was statistically significant (χ²=9.076,-, P<0.05). Conclusion Bazuanjin combined with balance pad training can significantly improve lower limb motor function, restore gait, improve body balance control and improve quality of life in elderly patients with Parkinsonundefineds disease.