Objective To explore the neuroprotective effect and mechanism of picroside II on ERK1/2 signal transduction pathway after cerebral ischemia injury in rats.Methods The focal cerebral is-chemic models were established by inserting a monofilament threads into middle cerebral artery occlusion (MCAO) in 100 Wistar rats and treated by injecting picroside II (20 mg/kg) intraperitoneally.The neu-robehavioral function was evaluated by modified neurological severity score points ( mNSS) test.The cerebral infarct volume was measured by tetrazolium chloride ( TTC) staining.The apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling ( TUNEL) assay.The expression of pERK1/2 in cortex was determined by the immunohistochemistry ( IHC) and Western Blot ( WB) .Results mNSS test showed that severe neurological dysfunction was found in model and LPS groups,and the scores of mNSS were significantly increased;meanwhile the scores of mNSS in treatment group and U0126 group were signifi-cantly lower than that in model and LPS groups (P<0.05).TUNEL assay showed that the apoptotic cell inde-xes (ACI) in different groups were (0.06±0.02),(0.27±0.03),(0.07±0.02),(0.26±0.03)and(0.09± 0.05) ,and the ACI in treatment and U0126 groups was obviously lower than that in model and LPS groups (P<0.05) .With IHC and WB,pERK1/2 level in model group was the highest,which was slightly higher than that of LPS group,and pERK1/2 expression in treatment and U0126 groups was significantly decreased com-pared with that in model and LPS groups (P<0.05) .Conclusion The activation of ERK1/2 by cerebral is-chemia could induce the cell apoptosis.Picroside II might reduce cell apoptosis by inhibiting the activation of ERK1/2 in ischemic brain injury.

Objective To investigate medical students' cognitive status and attitude toward urban-rural integration and to find the influencing factors in an aim to provide information for the process of urban and rural integration.Methods Sampling survey was conducted among the junior students who were major in eight-year clinical medicine,five-year clinical medicine and nursing (undergraduate) with self-made questionnaire.The data entry was done by 19.0 SPSS software and descriptive statistical analysis and ONE-WAY ANOVA were used to do statistical analysis.Results Students who didn't know urban-rural integration accounted for 53.2％,while 80.7％ students supported urban-rural integration.Students' major and residence were two influencing factors of working in the countryside.Conclusion Measures should be taken to raise students' awareness of urban-rural integration based.Targeted measures should be adopted based on students' majors and residences.

Objective To explore the relationship between the level of serum stem cell factor (SCF) and the activity of lupus nephritis (LN). Methods Sixty LN patients who had underwent routine renal biopsy were selected from March 2014 to September 2016. According to the systemic lupus erythematosus disease activity index (SLEDAI), the LN patients were divided into two groups: active nephritis group (30 cases) and stable nephritis group(30 cases). Meanwhile 30 healthy controls were selected as normal control group. Spearman correlation analysis test was used for correlations between the level of serum SCF and the activity of LN. Results The serum level of SCF was significantly higher in active nephritis group [(357.29 ± 63.85) ng/L] than that in stable nephritis group [(310.03 ± 40.17) ng/L] , the serum level of SCF in stable nephritis group was significantly higher than that in normal control group [(154.06 ± 22.49) ng/L], and there were significant differences (P<0.01). In the LN patients, the level of SCF was positively related to SLEDAI, anti ds-DNA, 24 h urinary total protein(UTP), erythrocyte sedimentation rate (ESR), activity index (AI), and tubulointerstitial lesions (TIL)(r=0.469, 0.353, 0.297, 0.312, 0.390, 0.317;P<0.01 or<0.05), but negatively correlated to C3 (r=-0.321, P<0.05), while the chronicity index (CI) had no correlation with the level of SCF (r=-0.181, P>0.05). Conclusions The level of SCF may play an important role in the occurrence and development of LN. It could reflect clinical and pathology changes and emerg as a potential serum biomarkers of LN.

Objective To explore the prevalence and risk factors of hyperuricemia(HUA) in patients with chronic kidney disease(CKD) on stages 3-5 and to investigate the effect of uric acid on renal function during the past 15 years.Methods Patients with CKD on stages 3-5 who admitted to the Nephrology Department of Affiliated Hospital of Qingdao University from January 2000 to December 2014 were recruited.The prevalence of HUA in patients with CKD on stages 3-5 were analyzed statistically,the risk factors of HUA and the effect of uric acid on the estimated glomerular filtration rate(eGFR) were analyzed by regression analysis.Results (1)The prevalence of HUA was 55.6%,and there was no significant difference between male and female in the 3 547 patients who met the inclusion criteria(χ2=0.184,P=0.683).The prevalence of HUA for CKD on stage 3,4,5 was 42.6%,59.1%,61.2%,respectively.(2)The independent risk factors of HUA in patients with CKD on stages 3-5 were hypertension(OR:1.209(95%CI:1.002-1.458)),increased BMI(OR:1.039(95%CI:1.015-1.062)),increased total cholesterol(OR:1.411(95%CI:1.274-1.564)),increased CKD stage(OR:1.891(95%CI:1.515-2.359),OR:1.898(95%CI:1.481-2.431)) and decreased HDL-C(OR:0.178(95%CI:0.134-0.238))(P<0.05).(3)In patients with CKD on stages 3-5,multiple regression analysis showed that after adjusting for confounding factors,each 100 mol/L-higher uric acid at baseline led to a change in the rate of the baseline eGFR decline of 1.49 ml.min-1.(1.73 m2)-1[95% CI:-2.20--1.05).(4)In 348 hyperuricemic patients with CKD on stage 3,Logistic regression analysis showed that persistent HUA was associated with a higher risk for eGFR decreasing more than 10 ml/min/(1.73 m2) 1 year later(hazard ratio(HR)=2.645,95%CI:1.388-5.039,P=0.003).Conclusion The prevalence of HUA in patients with CKD stages 3-5 is high.Hypertension,hyperlipidemia and overweight are risk factors of HUA.HUA is an independent risk factor for renal function deterioration.

Objective To investigate the emotional memory impairment in patients with primary insomnia (PI) and explore the neurobiological mechanisms underlying primary insomnia through emotional memory tasks involving different valance of emotional pictures.Methods Thirty patients with primary insomnia(PI group) and twenty healthy controls(HC group) were given emotional memory tasks using positive,neutral and negative valence images.The emotional memory was evaluated by the recognition of emotional pictures.Results Compared with healthy controls (positive (11.60±4.00) , neutral (11.05± 3.73) and negative (12.60± 2.06) , respectively), patients with PI (positive (11.30±3.75),neutral (11.47±3.21) and negative (11.43±4.12) ,respectively) showed no significant difference in appraisal of the emotional pictures (P＞0.05).Compared with healthy controls (43.40± 4.88) for the emotional images memorizing task,patients with PI (39.40±6.43) exhibited evident deficit of all emotional images (P＜0.05).Furthermore, the accuracy in recognizing both positive (12.60± 2.42) and neutral (12.87±3.18) valence pictures were significantly lower in patients with P1 than those in healthy controls(positive (14.05±2.19) and neutral (14.75± 1.80)) (P＜0.05).There was no significant difference in negative stimulus between PI group(13.93±1.76) and HC group(14.70±1.59) (P＞0.05).Conclusion The results suggest thant emotional memory is impaired in patients with PI.Moreover,the emotional memory for positive and neutral vanlence pictures is impaired but the emotional memory for negative is relatively spared in patients with primary insomnia.The results also indicate that impaired emotional memory with different valences may relate with distinct neuromechanisms.

Aim To investigate the neuroprotective effect of picroside Ⅱ(PIC)on cyto C/caspase-9/caspase-3 signal pathway following ischemia/reperfusion(I/R)injury in rats.Methods Atractyloside(Atr)was selected as negative control,cyclosporin A(CsA)was selected as positive control,and PIC was selected as the treatment medicine.The I/R model was made by inserting a monofilament suture into internal carotid artery for 2 h,and then reperfused for 24 h.The cerebral infarction volume was detected by TTC staining,and the expression of cyto C,caspase-9 and caspase-3 were determined by immunohistochemical assay and Western blot.Results In model group,the cerebral infarct volume was obviously large;the expression of cyto C,caspase-9 and caspase-3 was increased significantly more than that in sham group(P<0.05).In PIC group,the cerebral infarct volume was significantly improved;the expression of cyto C,caspase-9 and caspase-3 was significantly decreased than that in model group(P<0.05).In Atr+PIC group,the rat infarction volume was reduced,and the expression of cyto C,caspase-9 and caspase-3 was significantly decreased than that in Atr group(P<0.05).Conclusion The mechanism of PIC inhibiting neuron apoptosis in focal cerebral I/R rats might be through down-regulating the expression of cyto C,caspase-9 and caspase-3.

Objective To assess the effectiveness of initial Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) as predictors for clinical outcomes in patients with top of the basilar syndrome (TOBS).Methods A total of 64 patients with TOBS were selected from Nanjing Stroke Registration Program (NSRP). Initial GCS and NIHSS were retrospectively evaluated by reviewing patients' records for details of clinical presentation and outcomes at 30 days measured by modified Rankin Scale (mRS) score. Patients were categorized as favorable outcome group (mRS 0-3) and unfavorable outcome group (mRS 4-6).Results The mean GCS was lower in the cases with mRS of 4-6 compared with those with mRS of 0-3 (P<0.01) and the mean NIHSS score was higher in favorable outcome group compared with unfavorable outcome group (P=0.011). In multivariate logistic regression analysis, after adjusting for age, gender and treatment approaches, the GCS OR was 0.301(95% CI 0.167～0.542), NIHSS OR was 1.436(95% CI 1.147～1.796), and both of them turned out to be the independent predictors of outcome at 30 days. ROC curve analysis suggested that GCS score of 10 represented a good cut-off point for predicting the outcome with the prognostic sensitivity of 87.9% and specificity of 83.9%. NIHSS score of 14 could also serve as a good cut-off point with the prognostic sensitivity of 63.6% and specificity of 77.4%.Conclusions Conclusions Both GCS and NIHSS can predict outcomes in patients with acute TOBS with GCS score ≤10 and NIHSS score ≥14 as the cutoff points of poor outcome. GCS cutoff point is more strongly predictive of outcome than that of NIHSS.

Objective To investigate the effect ofpicroside Ⅱ on mitochondria cytochrome C (CytC) expression and its significance in rats after ischemia/reperfusion.Methods Ninety-six Wistar rats were randomly divided into sham-operated group,model group,picroside Ⅱ group,Cyclosporin A (CsA,specific antgonist of CytC) group,CsA+picroside Ⅱ group,atractyloside (Atr,selective agonist of CytC) group,Atr+picroside Ⅱ group and DMSO group (n=12);the middle cerebral artery occlusion/reperfusion models referring to Longa's method with medications were adopted,which were established by inserting a monofilament suture into the internal carotid artery for 2 h and then reperfusion for 24 h.After 24 h of ischemia/reperfusion,modified neurological severity scale (mNSS) scores were observed,contents of reactive oxygen species (ROS) in brain tissues were measured by enzyme-linked immunosorbent assay (ELISA),morphology of brain tissues was observed by hematoxylin-eosin staining,ultrastructures ofmitochondria were observed by transmission electron microscopy,apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL),and CytC expression was determined by immunohistochemical assay and Western blotting.Results As compared with the sham-operated group,the model group had significantly increased mNSS scores,ROS contents,number ofapoptotic cells and CytC expression (P＜0.05),and the mitochondria structure was seriously destroyed.The picroside Ⅱ group had obviously decreased mNSS scores,ROS contents,number of apoptotic cells and CytC expression,and the morphology of brain tissue was improved and the mitochondria damage was reduced as compared with the model group,with significant differences (P＜0.05).The Atr+picroside Ⅱ group had significantly decreased mNSS scores,ROS contents,number of apoptotic cells and CytC expression (P＜0.05),and the mitochondria damage in the Atr+picroside Ⅱ group was reduced as compared with that in the Atr group with significant difference (P＜0.05).Conclusion The mechanism of picroside Ⅱ protecting against focal cerebral ischemia reperfusion might attribute to decrease of ROS contents,protection of mitochondria structure and down-regulation of CytC expression in middle cerebral artery occlusion/reperfusion rats.

Objective To investigate the urate-lowering efficacy and renal effect of febuxostat in hyperuricemic patients with chronic kidney disease (CKD) stages 3-5. Methods A prospective, randomized, controlled trial of CKD stages 3-5 patients with hyperuricemia was conducted from June 2015 to June 2016. Patients were randomly assigned to either febuxostat group (treatment group) or allopurinol group (control group). Patients in treatment group received febuxostat 40 mg/d after study initiation, and the dosage was changed to 20 mg/d if serum uric acid (sUA)<360 μmol/L. Patients in control group were administered a dose of 100 mg/d of allopurinol. Serum uric acid, serum creatinine and other clinical parameters were measured at baseline and 1-6 months after treatment. The rate of achieving target sUA level and the change of eGFR in two groups were performed using SPSS 21.0. Results A total of 98 patients met the inclusion criteria and completed the trial. The treatment group and the control group had 51 cases and 47 cases, respectively. There was no significant difference between the two groups in age, sex, body mass index (BMI), blood pressure, serum creatinine, eGFR, sUA and renal diseases (P>0.05). At month 1-6, there were significant differences between treatment group and control group in the rate of achieving target sUA level (P<0.01). At month 1 and month 3, no statistical difference was observed in the change of eGFR between the two groups (P=0.624, P=0.319). At month 6, the changes in eGFR were +2.23 ml·min-1·(1.73 m2)-1 and-4.36 ml·min-1·(1.73 m2)-1 in the treatment and control group, respectively, and the difference between the two groups was significant (P=0.037). In patients with CKD stages 3-5, generalized estimating equation showed that after adjusting for confounding variables, the eGFR increased 1.149 ml·min-1·(1.73 m2)-1 (P=0.003) and 24-hour urinary protein decreased 0.019 g/d (P=0.037) when per 60 μmol/L decreased in sUA. Febuxostat 20 mg/d was able to keep target sUA levels in 90.2% patients with CKD stages 3-5 within half a year and no serious adverse effects appeared. Conclusions Febuxostat performs better than allopurinol in lowering urate and delaying progression of renal function in patients with CKD stages 3-5 and HUA. Febuxostat 20 mg/d may be the effective and safe maintenance dose to maintain target sUA level in patients with CKD stages 3-5, but whether it can be used as the best long-term maintenance dose needs to be further studied.

Objective To evaluate the effectiveness of swallowing training supplemented with neuromuscular electrical stimulation to provide a reference for clinical treatment and further study.Methods Reports of randomized and controlled trials of surface neuromuscular electrical stimulation in treating post-stroke dysphagia were sought in the Cochrane library,the PubMed and Embase databases,the Cumulative Index to Nursing and Allied Health Literature (CINAHL),and also in the ProQuest,PsycARTICLES,CBMdisc,China National Knowledge Infrastructure (CNKI),CQVIP database and Wanfang databases.All of the literature found was evaluated by 2 researchers according to predefined inclusion and exclusion criteria and the data were extracted and combined.Then meta-analysis was performed using version 5.3 of the RevMan software package.Results Eleven randomized and controlled trials involving 576 patients were included in the meta-analysis.Together,the data showed that swallowing training supplemented by neuromuscular electrical stimulation is significantly more effective than swallowing training alone in improving swallowing function.It reduces the risk of aspiration and improves quality of life.It does not,however,generally shorten the pharyngeal transmit time.Conclusions Swallowing training supplemented with neuromuscular electrical stimulation is a promising approach for treatment of post-stroke dysphagia and warrants further study.