Objective To study the influence of Erythropoietin(Epo) on cognition,brain protection and ?-tubulin expression in hippocampus in rat models of vascular dementia(VD).Methods VD rat models were established by two-vessel occlusion and salium nitroprusside.Epo group was treated by intraperitoneal injection of Epo.Morris labyrinth test was performed to detect the cognition of rats.Nissle staining and ?-tubulin immunohistochemistry staining were used to observe the cellular morphous.Western blot method was used to assay ?-tubulin contents in hippocampus.The results of Epo group were compared with those of VD models(VD group) and sham-operative group.Results Compared with VD group,Epo group had significantly shorter the escaping latency of Morris labyrinth(excepting the first day of the test)(all P

Objective To investigate the influence of the different degree of internal carotid stenosis on the white matter lesion and cognition of Binswanger disease.Methods A total of 108 elderly patients with Binswanger disease from Department of Geriatric Neurology of Qilu Hospital were recruited during December 2013 and June 2014.At the end of follow-up,6 cases showed acute eerebrovaseular disease,39 (＜ 10 ％) had no internal carotid stenosis,31 (10 ％-49 ％) had mild internal carotid stenosis,32 (50％-70％)had moderate internal carotid stenosis through B ultrasound examination and MRI and MRA examination on internal carotid artery and brain.The B ultrasound examination of internal carotid artery included intima-media thickness (IMT),plaque index and the peak systolic velocity (PSV).Cognitive function of Binswagner disease was assessed by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA).The white matter lesion was assessed by reformed visual Scheltens scale.The relationship among IMT,plaque index,PSV,white matter lesion,and cognitive function was investigated.The variation of cognition was observed after 1 year.Results There were statistically significant differences in IMT,PSV,plaque index,reformed Scheltens scale scores between groups of non,mild,moderate internal carotid stenosis (all P ＜0.05).The IMT was thicker in moderate internal carotid stenosis group than in mild internal carotid stenosis group (P＜0.05).The differences in PSV,plaque index,and reformed Scheltens scale scores between mild and moderate internal carotid stenosis groups were not significant (P＞0.05).There were positive correlation between PSV and reformed Scheltens scale scores (r=0.630,P =0.020).There were negative correlation between PSV and MMSE scores (r=-0.970,P=0.040).The scores of MMSE and MOCA both were declined after 1 year in three groups (0.61 ± 0.60,0.68 ± 0.81),(0.70±0.60,0.93±0.69),(1.06±0.68,1.13±0.76).The declination of MMSE and MOCA of BD patients was higher in moderate internal carotid stenosis group than in non internal carotid stenosis group (P＜0.05).The differences in the declination of MMSE and MOCA between moderate and mild internal carotid stenosis groups were not significant (P＞ 0.05).Conclusions Internal carotid stenosis is one of risk factors for the cognitive impairment of BD,the abnormal IMT and PSV are both correlated with white matter lesion and cognitive impairment in BD.Early standardized therapy can postpone the rate of cognitive impairment in BD.

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Objective To detect the relationship of blood pressure variability (BPV) and angiotensinogen(AGT) T235M polymorphism with Binswanger's disease (BD).Methods Totally 122 cases with BD and 108 cases with essential hypertension had been enrolled.Ambulatory blood pressure monitoring was used to get the data of BPV and mean blood pressure (MBP).PCR-RFLP was applied to detect genotype of AGT T235M.Results Distribution of MM+MT genotype and frequency of M allelic were higher in BD group (51.6％,29.9％) than in hypertension group(27.8％,16.2％)(x2 ＝13.543,11.995,P＜0.01).The variability of night time blood pressure (11.8±2.8,9.1±2.5) and 24 hours diastolic blood pressure(11.6±6.0) in BD group were increased compared with those in hypertension groups(10.9±2.4,8.2±3.2,10.1±4.6)(t＝2.59,2.64,2.09,all P＜0.05).Prevalence of anti-dipper was higher in BD group (32.8％) than in EH group (16.7％)(x2 ＝7.894,P＜0.01).Among BD patients,anti-dipper who carried MM or MT genotypes (44.4 ％) was more than that who carried TT genotype (20.3％) (x2 ＝ 8.760,P＜ 0.01).Conclusions Fluctuations of nighttime blood pressure and diastolic pressure are higher in patients with BD,and the relative frequency of MM or MT genotype is higher.Moreover,among patients with BD who carried MM or MT genotypes are apt to have anti-dipper.MM or MT genotype is related to BD by means of affecting blood pressure circadian rhythms probably.

Objective To evaluate the relationships of the serum levels of matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1) and adiponectin with the mild cognitive impairment (MCI) in senile metabolic syndrome (MS)patients. Methods The 74 cases with MS and 30 health controls (control group) were enrolled. Mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), digit-symbol test (DST), auditory verbal memory test (AVMT), trail making test(TMT), sunderland clock drawing test (CDT) and verbal fluency test (VFT) were applied to evaluate cognitive function. Based on the cognitive assessment, MS patients were divided into two groups: 39 cases with MCI (MS+MCI group) and 35 cases without cognitive impairment (MS group). The levels of MMP-9, ICAM-1 and adiponectin were measured by ELISA. Biochemical variables were measured by routine methods in all subjects. Results (1)MS+MCI group showed the higher levels of BMI, SBP, FBG and MMP-9 (all P＜0.05) and lower level of adiponectin (P＜0.05) than did the MS group. And MS group had higher levels of MMP-9 and ICAM-1 (P＜0.01) and lower adiponectin level (P＜0.01) than did the control group. (2)Spearman's correlation analysis showed that the serum levels of MMP-9 (r=-0.794, P＜0.001) and ICAM-l (r=-0.501, P＜0.001) were negatively correlated with adiponectin. However, MMP-9 was positively correlated with ICAM-1 (r=0.481, P=0.006). (3)Multiple linear regression analysis indicated that there was linear relationship of MoCA with MMP-9 (β=-3.438, P=0.0019), adiponectin (β=1.337, P=0.006), SBP (β=-0.058, P=0.003) and FBG (β=-0.227, P=0.049). (4)Stepwise logistic analysis showed that both high MMP-9 (OR=1.007) and low adiponectin (OR=0.359) were risk factors for the decline of cognitive function. Conclusions Elderly patients with MS may show deterioration in memory, calculation and visuospatial perception. Elevated inflammatory factors might contribute, in combination with abnormal metabolism, to MCI. MMP-9 might contribute to neuronal degeneration. However, adiponectin could strongly counteract the risk factors for cognitive impairment.

Objective To observe the changes of behavior,blood cortisol level,glucocorticoid receptors (Grs) and mineralocorticoid receptors (MRs) in hippocampus area after four weeks of unpredictable chronic mild stress,and to investigate the probable role of hypothalamus-pituitary-adrenal (HPA) axis in the pathogenesis of depression in aged people.Methods Aged male Wister rats were randomly assigned to control group and model group.The model group received unpredictable mild stress,including food and water deprivation,restrain,tail clipping,forced swimming,white noise,cage titling and cage rotating for 4 weeks,while the control group was undisturbed unless routine feeding and cage changing.After 4 weeks of procedure,the behavior changes were assessed by sucrose intake test,open-field test and state evaluation,serum cortisol level was measured by chemiluminescent assay,the qualitation and quantitation of GRs and MRs in hippocampus area were evaluated by immunohistochemistry and Western blotting respectively.All data were analyzed by using t-test.Results Body weight,the grooming score,activities in openfield test,food intake and sucrose intake were decreased in model group as compared with control group after 2 weeks of chronic mild stress (all P＜0.01),suggesting the stress induced depressive-like behavior effects on aged rats.Serum cortisol level was elevated in model group as compared with control group after 4 weeks of chronic mild stress (P＜0.01).A decrease of the neurons was found in CA3 of hippocampus,but not in DG area.In CA3 area,GR positive neurons were decreased,but no significant decrease was found in MR positive neurons.Conclusions The chronic mild stress leading to depressive-like behavior effects in aged rats induces overall HPA axis dysfunction,elevation of serum cortisol level,impairment of hippocampus neurons and decrease of GR positive neurons.The HPA axis dysfunction induced by chronic mild stress may play an important role in the pathogenesis of depression.

Hereditary spastic paraplegia type 58 is rare, caused by pathogenic variations in KIF1C gene. Here, a case diagnosed in Qilu Hospital, Shandong University, was reported. The 15-year-old female suffered tremor in bilateral upper limbs which was aggravated gradually since age 8. Cerebellar ataxia, positive pyramidal tract sign and dystonic tremor were prominent on physical examination. The brain magnetic resonance imaging showed T 2-hyperintense signals in bilateral pyramidal tracts, optic radiations and superior cerebellar peduncles, with mild cerebellar atrophy. Whole exon sequencing revealed the unreported homozygous c.425_426delTG (p.V142Gfs*10) mutation which was presumed pathogenic.

To investigate the inhibitory effect of sildenafil on Caco-2 cell proliferation and its anti-inflammatory effect on menadione-induced NCM460 cell inflammation model, MTT assay was used to determine cell proliferation. Intracellular reactive oxygen species(ROS)and nitric oxide(NO)levels were detected by fluorescent probe. Western blot was used to detect the expression of eNOS/ERK/JNK pathway related proteins in Caco-2 cells and correlated inflammatory cytokines in NCM460 cells. The effect of sildenafil on the growth of two probiotics was determined by spectrophotometry. Results showed that sildenafil signi-ficantly inhibited the proliferation of Caco-2 cells and enhanced the expression levels of eNOS, p-eNOS, p-JNK1/2 and p-ERK1/2 proteins in Caco-2 cells; while after adding NG-nitro-L-arginine methyl ester(L-NAME), the expression levels of eNOS, p-eNOS, p-JNK1/2 and p-ERK1/2 proteins were significantly lower than those of the sildenafil group. Compared with the menadione group, sildenafil significantly reduced ROS levels in NCM460 cells and inhibited the expression levels of IL-6, IL-1β, p62, and TNF-α. Moreover, high concentrations of sildenafil had no obvious toxic effects on Lactobacillus casei and Lactobacillus rhamnosus. Thus, the results indicated that sildenafil could effectively inhibit the intestinal inflammatory response without affecting the balance of the intestinal flora, and prevent colorectal cancer by reducing the oxidative stress responses in the intestinal cells.

Objective:To investigate the early- and mid-term clinical, functional and radiographic outcomes of patellofemoral arthroplasty (PFA).Methods:A retrospective analysis was conducted in 64 patients (80 knees) who suffered from severe patellofemoral osteoarthritis (PFOA) and underwent PFA from January 2013 to December 2020. These patients were aged 60.50±8.82 (range from 27 to 82) years, including 9 males (12 knees) and 55 females (68 knees). All enrolled individuals presented typical PFOA. Unilateral PFA was performed in 48 cases, bilateral PFA in 16 cases, including one-stage PFA in 9 cases and two-stage PFA in 7 cases. The visual analogue scale (VAS), Hospital for Special Surgery (HSS) knee score and Oxford knee score (OKS) of patients with more than 5 years' follow-up were assessed to evaluate the clinical effects of PFA at the time before surgery, 1 year and 5 years after surgery. In addition, the patellar tilt angle (PTA) and hip-knee-ankle (HKA) angle were measured and analyzed to evaluate the improvement of patellar tracking and progression of tibiofemoral osteoarthritis, based on axial X-ray imaging (skyline view) of knee and the full length standing X-ray imaging of the lower limbs at before surgery and 5 years after surgery. Meanwhile, the complications of all patients that related to the operation were recorded.Results:A total of 64 patients were followed up for 4.31±1.79 (range, 1.5 to 8.2) years. Twenty-five patients (32 knees) who followed up more than 5 years were analyzed. The VAS, HSS and OKS improved from 5.91±0.82, 68.06±6.03 and 21.22±3.46 preoperatively to 0.88±1.01, 90.09±3.30 and 39.06±3.37 at 1 year after surgery, and to 0.41±0.76, 94.53±2.99 and 42.13±3.17 at 5 years after surgery, respectively ( F=89.38, 81.47, 56.73, P<0.001). Additionally, comparing to the preoperative radiological data, the patellar tract was improved with the PTA decreased from 8.21°±3.14° preoperatively to 3.58°±4.48°at 5 years after surgery ( t=4.96, P<0.001). The HKA angle changed from 179.01°±1.43° preoperatively to 178.77°±1.67° at 5 years follow up ( t=1.71, P=0.096). There was no case of prosthesis loosening or wear and no case of obvious progression of tibiofemoral osteoarthritis that needed revision in all patients. Conclusion:Satisfied early- and mid-term clinical outcomes could be achieved by PFA in treating severe PFOA patients. PFA could relieve pain and improve function of knee joint.