Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

Aim To explore the factors on behavior patterns of light/dark box(LDB)as an animal model of state anxiety in Kunming mice.Methods The behavior of adult,male,Kunming mice in LDB was recorded for five minutes,respectively.The following parameters were evaluated:percentage of time in the light area(Ltime%),percentage of squares crossing in the light area(Lcross%),percentage of rears in the light area(Lrear%),total number of squares crossing in the whole apparatus(Cross),total number of rears in the whole apparatus(Rear),total(Cross plus Rear),transitions between two areas(Transition),and number of fecal bolis in light box and dark box(Fbs).Subsequently,the factors,such as day-night rhythm,illumination area(L3/5 or L2/5 for ratio between Light box and Dark box:3:2 or 2:3,respectively),illumination color(in Dark box)and illumination intensity(in Light box),were investigated to screen the best experimental conditions.Results t-test showed that compared with night cycle,there was no significant difference in all LDB parameters during day cycle(P>0.05),while compared with 3/5 and 2/5,LDB parameters during day cycle such as Lcross%(t=5.363,P<0.01)in big area light box(L3/5),Lrear%(t=3.211,P<0.05)in small area light box(L2/5)increased statistically.The factorial design ANOVA showed that there was no significant difference in day-night rhythm on all LDB parameters(P>0.05),but a statistical influence of illumination area on Ltime%(F(1,20)=18.361,P<0.01),Lcross%(F(1,20)=49.148,P<0.01)and Lrear%(F(1,20)=8.424,P<0.01).The single factor ANOVA showed that there was significant influence of illumination color in dark box on Real(F(3,20)=3.746,P<0.05),Fbs(F(3,20)=3.585,P<0.05),and illumination intensity in light box on Cross(F(4,25)=2.569,P<0.05)and Total(F(4,25)=2.588,P<0.05).The Dunnett t test showed that compared with red color group,Rear(MD=-30.833,P<0.05)was significantly lower in yellow color group; while Cross(MD=-173.167,P<0.05)and Total(MD=-93.667,P<0.05)in 100 W group declined statistically compared with 15 W Group.Kruskal-Wallis test showed that there was no significant difference in illumination color and intensity on Fbs(P>0.05).Conclusions LDB as an animal model of state anxiety in Kunming mice can evaluate anxiety-,locomotion-exploration and emotionality- related behaviors,which cannot be affected by day-night rhythm,but illumination area(Ltime%,Lcross%,Lrear%),illumination color(Rear)and illumination intensity(Cross,Total).So it is recommended to adopt the uniform and fixed conditions,such as illumination area,color and intensity(less than 100 W).

Objective:To explore the relationship between respiratory mechanics and right heart function during ARDS mechanical ventilation through the establishment of Beagle dogs acute respiratory distress syndrome (ARDS) animal model and the application of different levels of mechanical ventilation, which will provide theoretical basis for right heart protective ventilation strategy of ARDS.Methods:Beagle dogs were anesthetized successfully and then pulmonary artery floating catheter, esophageal manometric catheter and femoral artery catheter were inserted. Under the pressure control mode, the driving pressure was fixed. After adjustment, PEEP gradually increased from 2 cmH 2O to 14 cmH 2O. The changes of respiratory mechanics, hemodynamics and right heart function were observed. ARDS model was established by injecting oleic acid into central vein, and mechanical ventilation with the same parameters was given after the model was established successfully. In contrast to itself, the changes of respiratory mechanics, hemodynamics and right heart function indexes of experimental dogs before and after modeling were analyzed. In the group, the indexes of different PEEP were compared by ANOVA, and then compared by Student-Newman-Keuls. The difference was statistically significant at a P value <0.05. Results:Before modeling, the peak airway pressure (P peak) and plateau pressure (P plat) increased with the increase of PEEP ( F=232.733,196.33, P<0.05). However, P trans-I, P trans-E, C stat and Vt decreased significantly ( F=4.524, 6.499, 64.803, 2.31, P<0.05). The area of change of right ventricle (FAC) became smaller ( F=3.09, P<0.05); SV first increased and then decreased ( F=3.24, P<0.05), and CVP and MPAP increased ( F=19.07,14.81, P<0.05). There was no significant difference in TAPSE, MAP, HR and SpO 2 ( P>0.05). After modeling, as PEEP increased, P peak, P plat, P ES-I and P ES-E increased significantly ( F=24.829, 41.95, 9.78, 87.86, P<0.05). Vt, P trans-I, P trans-E, C stat and Vt first increased and then decreased ( F=2.91, 4.29, 5.84, 48.890, P<0.05). TAPSE and SV first increased and then decreased ( F=6.22,6.54, P<0.05). CVP and MPAP increased ( F=5.23, 19.24, P<0.05). MAP increased first and then decreased ( F=5.02, P<0.05). SpO 2 increased ( F=2.77, P<0.05). FAC and HR had no statistical significance ( P>0.05). Conclusions:Trans pulmonary pressure and lung compliance can reflect the effectiveness of ARDS lung recruitment, and have good synergy; with the increase of PEEP, the right ventricular systolic function TAPSE is first affected, and SV compensatory increase, but with the increase of PEEP, TAPSE and SV decrease; pulmonary blood flow distribution is more important in improving alveolar oxygenation. Therefore, real-time monitoring of trans pulmonary pressure, TAPSE and intrapulmonary blood flow should be performed in ARDS treatment.

Objective: To determine interleukin (IL)-23 and IL-17 level in latent autoimmune diabetes in adult (LADA) patients, and to explore the relationship of IL-23, IL-17and β-cell function in these patients. Methods: Forty LADA patients from 2011 to 2016 in our hospital were selected as LADA group, and forty participants were as normal control group. Clinical and biochemical data was collected and the level of the IL-23 and IL-17 was measured with the enzyme linked immunosorbent assay (ELISA). The differences in interleukin levels among the two groups were compared. Pearson correlation analysis was used for investigating the relationship between the dependent of statistical significant interleukins and the independent data in the LADA patients, all closely related variables then were included in a stepwise multiple linear regression analysis. Results: The levels of serum IL-23 , IL-17 and IL-23/IL-17 were significantly higher in LADA group than those in control groups [3.54(2.88~5.24)μg/L vs 1.98(1.62~2.18)μg/L, P<0.05], [22.42(17.71~26.07)ng/L vs 17.97(17.15~20.70)ng/L, P<0.05], (175.79±38.67 vs 105.22±19.08, P<0.01). IL-23 and IL-17 in the LADA group were negatively correlated with fasting C peptide (FCP) (r=-0.42, r=-0.48, P<0.05), and the ratio of IL-23/IL-17 was positively correlated with fasting plasma glucose (FPG) (r=0.44, P=0.00). Stepwise multiple liner regression analysis showed that serum IL-23 and IL-17 level were independently associated with the FCP in LADA group. Conclusions IL-23 and IL-17 were possibly important proinflammatory factor in LADA patients, and can provide the new immunodiagnosis markers for LADA.

Objective: To explore the effects of vascular risk factors on cognitive function among the elderly in community. Methods: A cross-sectional study was conducted in 1 269 elderly people (aged 65 and over) who were randomly selected from three communities.Through face-to-face interview, cognitive function was assessed by mini-mental state examination(MMSE), and blood samples were collected for laboratory examination.Logistic regression analysis was used to analyze the vascular risk factors affecting cognitive function. Results: Age ((73.1±6.6), (71.3±4.9), t=4.603, P<0.05), education level (χ²=12.727, P<0.05), hypertension (χ²=9.106, P<0.05) and LDL-C (χ²=5.157, P<0.05) were significantly different in the elderly with or without mild cognitive impairment(MCI). After controlling age, gender and education, the logistic regression analysis showed that hypertension(β=0.378, P=0.006, OR(95%CI)=1.44(1.10-1.91)), systolic blood pressure ≥140 mmHg(β=0.350, P=0.011, OR(95%CI)=1.42(1.08-1.86), 1 mmHg=0.133 kPa), and high LDL-C(β=0.355, P=0.014, OR(95%CI)=1.43(1.08-1.89)) were the risk factors of MCI in the elderly in the community.Hypertension alone or high LDL-C (β=0.365, P=0.029, OR(95%CI)=1.44(1.04-2.00)) alone was risk factor for mild cognitive impairment in the elderly in the community.The risk of mild cognitive impairment in the elderly with hypertension and high LDL-C was 2.00 times higher than that in the healthy elderly (β=0.696, P<0.05, OR(95%CI)=2.00(1.36-2.97)). Conclusion Mild cognitive impairment in the elderly is closely related to hypertension and elevated LDL-C levels.Multiple vascular risk factors can further increase the risk of cognitive impairment.

Objective To investigate the effects of long non-coding RNA (SNHG1) on the autophagy and growth of human neuroblastoma cell line SH-SY5Y and their specific mechanism using a cell model of Parkinson's disease.Methods (1) After SH-SY5Y cells were cultured in vitro,the expression levels of autophagy-related proteins LC3-Ⅱ/LC3-Ⅰ and p62 were detected by Western Blotting at different time points and subjected to treatment with different dosages of 1-methyl-4-phenyl-pyridine (MPP+).The survival rate of SH-SY5Y was detected by MTT assay.(2) The expression of SNHG1 was detected by real-time quantitative PCR after SH-SY5Y treated with different concentrations of MPP+ for different time durations.(3) The expression of endogenous SNHG1 in SHSY5Y was down-regulated by specific siRNA;the expression levels ofautophagy-related proteins LC3-Ⅱ/LC3-Ⅰ and p62 were detected by Western Blotting after MPP+ treatment while the survival rate of SH-SY5Y was detected by MTT.Moreover,SH-SY5Y cells were treated with autophagy late inhibitor bafilomycin A1 (BafA1) and autophagy inducer to further clarify the role of SNHG1.(4) The expression of p27 was detected by Western blotting after treated with different concentrations of MPP+ for different time durations.In addition,after the expression of SNHG1 in SHSY5Y was down-regulated,the expression of p27 was detected by Western blotting.Results (1) The expression of LC3-Ⅱ in SH-SY5Y was significantly increased in a dose-and time-dependent manner and the expression of p62 was significantly decreased (P＜0.05).MTT results showed that MPP+ (2.5 mmol/L) significantly reduced the survival rate of SH-SY5Y (P＜0.05).(2) Compared with the control group,the expression of SNHG1 was significantly increased in SH-SY5Y cells treated with MPP+ in a dose-and time-dependent manner (P＜0.5).(3) When SNHG1 down-regulated,the expression of LC3-Ⅱ induced by MPP+ was inhibited while the expression of p62 increased (P＜0.05).In addition,when treated with Baf A 1 at the same time,the expression of LC3-Ⅱ was increased,suggesting that SNHG1 might mainly affect the autophagosome formation of SH-SY5Y.The survival rate of SH-SY5Y cells was significantly increased after SNHG1 was down-regulated,and the cell viability was further inhibited by SH-SY5Y treated with rapamycin,suggesting that SNHG1 inhibited the growth of SH-SY5Y cells through promoting the autophagy formation.(4) The expression of p27 was significantly increased in SH-SY5Y cells treated with MPP+ in a dose-and time-dependent manner (P＜0.05).Down-regulation of SNHG1 expression inhibited the expression of p27,suggesting that SNHG1 might promote the autophagy and growth of SH-SY5Y cells through the p27 signal pathway.Conclusions SNHG1 can induce the autophagy of SH-SY5Y cells and promote death of the cells,which may be related to the regulation of p27 expression.

Objective To investigate the displacement characteristics of intraoperative and postoperative positions of electrodes on CT imaging for bilateral subthalamic nucleus-deep brain stimulation (STN-DBS) in Parkinson's disease (PD).Methods A retrospective analysis on preoperative MR imaging,intraoperative and postoperative CT images of 35 patients with PD treated with STN-DBS in our hospital from January 2014 to June 2018 was performed.A three-dimensional coordinate system was established based on preoperative MR imaging.MR imaging/CT fusion technique was used to fuse intraoperative and postoperative CT images with preoperative MR imaging to locate intraoperative and postoperative electrode positions.The displacement characteristics of intraoperative and postoperative electrodes were analyzed.Results The spatial distance between intraoperative and postoperative positions of bilateral electrodes was about 1 mm,and the depth displacement was minimal.The postoperative position of the first side electrode on lateral axis was shifted outwardly from intraopemtive position,and the second side electrode was shifted internally with a small degree;on anterior-posterior axis,the first side electrode obviously shifted backward,and the second side electrode slightly shifted backward.For bilateral electrodes,corresponding coordinate deviation of three axis between intraoperative electrode-preoperative target and postoperative electrode-preoperative target,showed a significant positive linear correlation,therefore,leading out the coordinate deviation regression function model.Conclusions The displacement of electrodes between intraoperative and postoperative positions has obvious rules after STN-DBS in PD,which can guide the adjustment of intraoperative electrode position and predict the postoperative position of electrode.

Intracranial infection is a common and serious complication of acute severe traumatic brain injury, with high mortality and disability rates, which significantly affects the prognosis. In recent years, with the widespread use of antibiotics, antibiotic-resistance rates of pathogens have risen year by year, and the choice of sensitive antibiotics is less and less, sometimes even in difficulties of no drugs available. This paper reviewed the treatment process of 1 case with intracranial infection caused by multi drug-resistant Klebsiella pneumonia after severe traumatic brain injury . The aim is to summarize the clinical experience.

Objective To evaluate the efficacy and safety of using alteplase for intravenous thrombolysis combined with vascular intervention for treatment of patients with acute intracranial large arterial occlusion.Methods Clinical data of 7 patients with acute intracranial large arterial occlusion treated by using alteplase for intravenous thrombolysis combined with intravascular intervention admitted to Department of Neurosurgery in Affiliated Hospital of the Logistics University of Cinese People's Armed Police Force from July 2015 to August 2016 were retrospectively analyzed.All the 7 patients were treated by alteplase dry powder (50 mg or 20 mg each ampule),solvent dose was 0.9 mg/kg,the maximum dose being ＜ 90 mg,firstly 10％ dose was intravenously injected,and the remaining dose was continuously infused into a vein in 60 minutes,during or after intravenous thrombolysis,digital subtraction angiography (DSA) was performed immediately,and according to the results of the angiography,at least one of the 3 kinds of intravascular mechanical intervention therapy,thrombectomy,balloon dilatation or stent placement,were chosen,and 24 hours after surgery,the anti-platelet aggregation drug and calcium channel antagonists were given,The effect of interventional therapy was analyzed,and the clinical outcome of 90-day treatment was evaluated.Results The mean age of the patients was (60.0 ± 12.6) years.Seven patients all successfully completed the treatment,and satisfactory re-canalization was achieved [they all obtained grade 3 or 2b in accord with the gradation of Thrombolysis in Cerebral Ischemia Scale (TICI)] in all the 7 cases (100％),after treatment,the National Institutes of Health Stroke Scale (NIHSS) score was significantly lower than that before treatment (5.86 ±4.10 vs.19.71 ± 5.56,P ＜0.01).Clinical outcome of 90-day follow up was excellent [Modified Rankin Scale (mRS) score 0-2] in 3 cases (42.8％).Conclusion Using alteplase for intravenous thrombolysis combined with endovascular intervention for treatment of patients with acute intracranial large arterial occlusion can achieve good re-canalization rate.