Objective To enhance the cyclic peptide compound's membrane permeability,structural stability,and neuroprotective activity,based on the amino acid sequence of peptides of Tat-GluA2-3Y,by designing and synthesizing a serial of cyclic peptides through strategies including polypeptide cyclization,replacement of the cell-penetrating peptide,substitution with D-amino acids,and incorporation of mini polyethylene glycol fragments.Methods The target peptides were synthesized based on standard Fmoc solid-phase method,followed by analysis and purification via reverse phase high-performance liguid chromatography(RP-HPLC).The cytoprotective activity of the peptides was evaluated by using the HT-22 cell model.The transmembrane transport efficiency of the peptides was determined based on the Caco-2 monolayer intestinal epithelial cell model.Plasmatic plasma and metabolic stability of the peptides were measured by in vitro co-incubation experiments with rat plasma and human liver microsomes.Finally,the in vivo neuroprotective activity of the peptides was validated by using a mouse middle cerebral artery occlusion model.Results Seven cyclic peptides were successfully designed and synthesized by using the standard Fmoc solid-phase method,with purities exceeding 90%as confirmed by RP-HPLC.Cytoprotective activity assay demonstrated that both Tat-GluA2-3Y and CMT-C3Y exhibited activity at concentrations above 125 nmol/L,with CMT-C3Y showing superior activity as compared to Tat-GluA2-3Y.The results of the transmembrane assay demonstrated that,compared to Tat-GluA2-3Y,CMT-C3Y exhibited significant transmembrane capabilities at all tested concentrations(P<0.001).CMT-C3Y was classified as a highly permeable compound,whereas Tat-GluA2-3Y was categorized as a moderately permeable compound.Plasma stability studies indicated that over 50%of Tat-GluA2-3Y was metabolized after 4 h of co-incubation with rat plasma.After 8 h of coincubation with CMT-C3Y,the remaining amount was 88.1%,and no obvious degradation phenomenon occurred.In human liver microsomal stability tests,the half-life of Tat-GluA2-3Y was 26.1 min,as compared to 103.8 min for CMT-C3Y,highlighting the enhanced stability of CMT-C3Y.Tat-GluA2-3Y and CMT-C3Y were classified as a fast-metabolizing drug and a moderate-metabolizing drug,respectively.Animal experiments further demonstrated that at a dose of 8 mg/kg the neuroprotective activity of CMT-C3Y was significantly superior to that of Tat-GluA2-3Y(P<0.001).Conclusion The designed bicyclic peptide CMT-C3Y demonstrates significantly higher cell-penetrating efficiency and superior plasma stability as compared to Tat-GluA2-3Y,along with enhanced neuroprotective activity at both cellular and animal levels.

Objective:To investigate the correlation between white matter hyperintensities (WMHs) and stroke etiology classification in patients with acute isolated penetrating artery territory infarction.Methods:Patients with first-ever acute isolated penetrating artery territory infarction admitted to the Department of Neurology, the Affiliated Hospital of Xuzhou Medical University from January 2017 to May 2020 were enrolled retrospectively. According to the Chinese Ischemic Stroke Subclassification (CISS) system, they were divided into large artery atherosclerosis (LAA) and perforating artery disease (PAD). According to the distribution of infarcts, they were divided into lenticulostriate artery (LSA) territory infarction and paramedian pontine artery (PPA) territory infarction. The demographics, vascular risk factors, baseline clinical data, WMHs location, and Fazekas Scale scores were documented. Multivariate logistic regression analysis was used to identify the independent influencing factors of stroke etiology classification. Results:A total of 440 patients with acute isolated penetrating artery territory infarction were enrolled, including 120 (27.3%) in the LAA group, and 320 (72.7%) in the PAD group; 213 (48.4%) with LSA territory infarction, and 227 (51.6%) with PPA territory infarction. The proportion of patients with total Fazekas score 3-6 and periventricular WMHs (PWMHs) score 2-3 in the PAD group was significantly higher than those in the LAA group (all P<0.05). In patients with LSA territory infarction, the proportion of the patients with hypertension, WMHs total Fazekas score 3-6 and PWMHs score 2-3 in PAD subgroup was significantly higher than those in the LAA subgroup, while the proportion of the patients with hyperlipidemia was significantly lower than that in LAA subgroup (all P<0.05). In patients with PPA territory infarction, the levels of low-density lipoprotein cholesterol and homocysteine in the PAD subgroup were significantly lower than those in the LAA subgroup. Multivariate logistic regression analysis showed that PWMHs score 2-3 was an independent correlation factor of PAD (odds ratio [ OR] 2.220, 95% confidence interval [ CI] 1.085-4.541; P=0.029). In patients with LSA territory infarction, hyperlipidemia was independently correlated with LAA ( OR 0.432, 95% CI 0.192-0.972; P=0.042), and PWMHs score 2-3 was independently correlated with PAD ( OR 3.846, 95% CI 1.193-12.397; P=0.024). In patients with PPA territory infarction, higher low-density lipoprotein cholesterol ( OR 0.660, 95% CI 0.494-0.883; P=0.005), homocysteine ( OR 0.958, 95% CI 0.930-0.987; P=0.005) and C-reactive protein ( OR 0.987, 95% CI 0.977-0.997; P=0.008) were independently correlated with LAA. Conclusions:WMHs are common in patients with acute isolated perforating territory infarction caused by LAA and PAD, and more severe PWMHs suggest that PAD is more likely to be the cause of the acute isolated perforating territory infarction, especially in patients with LSA territory infarction.

Serum inflammatory markers have important value for screening unstable carotid atherosclerosis plaques.The current studies tend to classify inflammatory markers into vascular specificity (such as lipoprotein-associated phospholipase A2,pentraxin-3,etc.) and non-vascular specificity (such as matrix metalloproteinase-9,pregnancy-related plasma protein A,etc.).This article reviews the relationship between serum inflammatory markers and carotid plaque stability.

After the status quo of medical treatment quality management and its relevant problems were analyzed, how to build the platform for medical treatment quality management was proposed by establishing perioperative clinical data center and intelligent management engine through data sharing, integration and reconstitution based on the present hospital information system in order to standardize perioperative medical behaviors and protect the safety of patients.

Objective To compare the clinical features between radiological isolated syndrome (RIS) and classical multiple sclerosis (CMS), in order to improve the understanding of the RIS. Methods All 35 patients with RIS and 32 patients with CMS were selected. The epidemiological and clinical findings, cerebrospinal fluid, neural electrophysiological examination and magnetic resonance imaging (MRI) data were analyzed. Results There were no statistical differences in sex ratio and onset age between RIS patients and CMS patients (P>0.05). The main symptoms of in patients with RIS were headache (45.7%, 16/35), dizziness (40.0%, 14/35), hypomnesis (20.0%, 7/35) and psychiatric disorders (11.4%, 4/35). But the main symptoms of in patients with CMS were limb weakness (75.0%, 24/32), sensory abnormalities (68.8%, 22/32) and ocular symptoms (34.4%,11/32). The incidences of limb weakness, sensory abnormalities and ocular symptoms in patients with CMS were significantly higher than those in patients with RIS:75.0%(24/32) vs. 0, 68.8%(22/32) vs. 0 and 34.4%(11/32) vs. 0, and there were statistical differences (P<0.01). The 18 patients with RIS and 21 patients with CMS underwent the examination of cerebrospinal fluid, and there was no significant difference in leukocyte between patients with RIS and patients with CMS (P>0.05). The cerebrospinal fluid protein and the incidences of IgG index>0.7 in patients with RIS were significantly lower than those in patients with CMS:0.175 (0.03-0.69) g/L vs. 0.440 (0.04-1.09) g/L and 3/18 vs. 47.6%(10/21), and there were statistical differences (P<0.05). The 15 patients with RIS and 22 patients with CMS underwent the examination of neural electrophysiological, and the abnormality rates of visual evoked potential (VEP) and brain stem auditory evoked potential (BAEP) in patients with RIS were significantly lower than those in patients with CMS:4/15 vs. 63.6%(14/22) and 3/15 vs. 54.5%(12/22), and there were statistical differences (P<0.05). But there was no statistical difference in the abnormality rate of somatosensory evoked potential (SEP) between patients with RIS and patients with CMS (P>0.05). On MRI, the demyelinating lesions of RIS and CMS were both mainly distributed in the periventricular, semi-oval center, infratentorial white matter, partly involving corpus callosum or cortical. The rates of demyelinating lesions in brainstem and cerebellum in patients with RIS were significantly lower than those in patients with CMS:5.7%(2/35) vs. 34.4% (11/32) and 2.9% (1/35) vs. 25.0% (8/32), and there were statistical differences (P<0.01 or <0.05). Comparison with CMS lesions, RIS lesions mainly showed patching and stippled, and there were statistical differences (P<0.01 or <0.05). The rates of lesions enhancement and spinal cord injury in patients with RIS were significantly lower than those in patients with CMS: 2/17 vs. 45.0% (9/20) and 1/14 vs. 43.5% (10/23), and there were statistical differences (P<0.05). Conclusions There are differences in clinical findings, cerebrospinal fluid, neural electrophysiological examination and MRI appearances between RIS and CMS.

Objective To investigate the treatment of octanol on matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein expression,cerebral water content,infarction volume after ischemia-reperfusion in rats.Methods 150 SD rats were randomly divided into sham operated group (n=24),MCAO group (n=24),DMSO solvent control group (n=24) and octanol treatment group (n=24).A model of middle cerebral artery occlusion was induced by suture method.TTC stain was used to detect the infarction volume,dry-wet weight method to determine the brain water content.The expression of MMP-9 and TIMP-1 protein was detected by immunofiuorescence and Western blot.Results At 24 h of reperfusion after ischemia for 2 h,the octanol treatment group compared with MCAO group brain infarction volume obviously decreased(P＜0.05),water content significantly reduced ((78.16± 1.47) ％ vs (80.88±0.73) ％,P＜0.05),the number of MMP-9 positive cells obviously decreased((10.67±2.16) vs (29.00±3.40),P＜0.05),the expression of MMP-9 protein significantly reduced ((0.14±0.01) vs (0.21±0.02),P＜0.05)and the number of TIMP-1 positive cells significantly increased ((27.83 ±2.13) vs (5.67± 1.03),P＜0.05),the expression of TIMP-1 protein obviously increased((0.42±0.01) vs (0.28± 0.01),P＜0.05).The difference between MCAO group and DMSO solvent control group was not statistically significant(P ＜0.05).Conclusion Octanol may reduce brain edema,brain infarction volume.Up-regulation the expression of MMP-9 and down-regulation the expression of TIMP-1 may be one of the underlying mechanisms of the octanol neuroprotection.

Objective To investigate the relationship between the serum apolipoprotein B (ApoB)/ ApoA-Ⅰ ratio and intracranial artery stenosis in young patients with ischemic stroke.Methods Patients with ischemic stroke aged from 18 to 45 were enrolled in the study.Brain CT angiography was used to evaluate the degree of intracranial artery stenosis,and the concentrations of serum total cholesterol,triglyceride,highdensity lipoprotein cholesterol,low-density lipoprotein cholesterol,ApoA-Ⅰ,and ApoB were detected.The ratio of ApoB/ApoA-Ⅰ was calculated.The Demographic and clinical characteristics of the intracranial artery stenosis group and the non-intracranial artery stenosis group were compared.Multivariate logistic regression analysis was used to identify the independent risk factors for intracranial artery stenosis in young patients with ischemic stroke.Results A total of 161 young patients with ischemic stroke were enrolled,including 89 in the intracranial artery stenosis group and 72 in the non-intracranial artery stenosis group.The constituent ratios of diabetes mellitus (20.2％ vs.6.9％;x2 =4.641,P =0.032),smoking (47.5％ vs.15.2％;x2 =15.121,P=0.001),hyperlipidermia (56.1％ vs.48.6％;x2 =4.197,P=0.040),as well as the radios in serum high-density lipoprotein cholesterol (1.29 ± 0.30 mmol/L vs.1.65 ± 0.34 mmol/L;t =7.131,P=0.002),ApoA-Ⅰ (1.49 ± 0.65 g/L vs.1.63 ± 0.23 g/L;t =2.751,P =0.001),ApoB (1.49 ± 0.65 g/L vs.1.63±0.23 g/L;t=2.751,P=0.001),and ApoB/ApoA-Ⅰ ratio (1.49±0.65 vs.1.63± 0.23;t =2.751,P=0.001) had significant differences between the two groups.Multivariate logistic regression analysis showed that diabetes (odds ratio [OR] 3.052,95％ confidence interval [CI] 1.186-7.856;P =0.021),smoking (OR 2.997,95％ Cl 1.456-6.172;P =0.003),hyperlipidemia (OR 4.745,95％ CI 2.108-10.668;P =0.001),ApoB (OR 4.861,95％ CI 3.029-7.802;P=0.001),and ApoB/ ApoA-Ⅰ ratio (OR 5.684,95％ CI 2.215-14.584;P=0.002) were the independent risk factors for intracranial artery stenosis in young patients with ischemic stroke,while HDL-C (OR 0.561,95％ CI 0.354-0.888;P=0.014) and ApoA-Ⅰ (OR 0.065,95％ CI 0.010-0.409;P=0.004) were the independent protective factors.After adjustment for hypertension,diabetes,smoking,hyperlipidemia,HDL-C,ApoA-Ⅰ,and ApoB,ApoB/ApoA-Ⅰ ratio was still an independent risk factor for intracranial artery stenosis in young patients with ischemic stroke (each increase of 1 standard deviation,OR 4.255,95％ CI 2.348-7.711;P=0.001).Conclusion ApoB/ApoA-Ⅰ ratio is an independent risk factor for intracranial artery stenosis in young patients with ischemic stroke.

After the characteristics and necessity of medical informatics experimental course were analyzed, the application of three-stage case teaching in medical informatics experimental course was described, and its steps and methods were explained with the teaching contents of hospital system module used in experimental course as an example. This teaching method can strengthen the knowledge the students have learned.

Objective To investigate the value of modified NIHSS and MRI-PC-ASPECTS for the long-term prognosis in posterior circulation ischemic stroke. Methods Seventy eight patients with posterior circulation ischemic stroke were divided into two groups depended on MRS: good outcome group and bad outcome group. General information of patients was collected and vascular risk factors, NIHSS, MRI-PC-ASPECTS of the two groups were compared. Results The scores of admission NIHSS and highest NIHSS of bad outcome group were higher than that of good outcome group. The scores of MRI-PC-ASPECTS, T admission NIHSS (42-admission NIHSS) and T highest NIHSS of bad outcome group were lower than that of good outcome group (P<0.05). The areas under the ROC curves of MRI-PC-ASPECTS+T highest NIHSS, MRI-PC-ASPECTS, T highest NIHSS and T admission NIHSS were 0.907, 0.821, 0.870, 0.744, respectively (P<0.05). Conclusion NIHSS and MRI-PC-ASPECTS can predict the functional prognosis in patients with posterior circulation ischemic stroke.

Objective To study whether abnormalities can be detected by MR diffusion tensor imaging (DTI) technology in radiologically isolated syndrome (RIS) patients with normal-appearing white matter (NAWM).Methods Twenty-seven patients who met diagnostic criteria for RIS were collected.Sixteen age-and sex-matched healthy controls with normal neurologic examination findings and no history of neurologic or psychopathic disorders were included.All subjects were examined by both conventional scan and DTI scan on GE Signa 3.0 T MRI.All the images were transmitted to the Advantage Workstation 4.2P and postprocessed using functool software.Anisotropic maps and average diffusion coefficient (ADC) maps were reconstructed.Two ROIs were selected in the genu and splenium of the corpus callosum separately at the trigone of lateral ventricle level.Other 2 ROIs were selected in the anterior and posterior body of the corpus callosum separately at the level of the lateral ventricle body,and 1 ROI was selected in the white matter of bilateral frontal and occipital lobe separately,then the FA and MD values were measured.The diffusion indices (FA and MD)were analysed by SPSS 13.0.Independent-sample t test was performed to examine the group differences in each subregion.Intraclass correlation coefficient analysis was performed to assess the diffusion indices of two measurements in each subregion.Results The ICC of 2 measurements was 0.934-0.989 (P ＜ 0.01),which showed favorable consistency.The FA values were decreased obviously in the genu,anterior and posterior body of the corpus callosum of the RIS patients compared with controls (0.705 ±0.040 vs 0.738 ±0.045,0.632 ±0.043 vs 0.675 ±0.042,0.628 ±0.043 vs 0.666 ± 0.045,t =-3.526,-4.487,-3.890,P ＜0.01),but the FA values of the two groups did not show any significant difference in the splenium,the white matter of the frontal and occipital lobe respectively (t =-1.387,-0.683,-1.243,P ＞0.05).In comparison with controls,the RIS patients had increased MD values in the genu,anterior and posterior body of the corpus callosum.(0.891 ±0.038 vs 0.874 ±0.035,0.839 ± 0.047 vs 0.794 ± 0.031,0.833 ± 0.039 vs 0.792 ± 0.057,t =2.101,5.836,5.146,P ＜ 0.05),but the MD values of the two groups did not show any significant difference in the splenium,the white matter of the frontal and occipital lobe respectively (t =1.671,1.702,1.624,P ＞ 0.05).Conclusion The NAWM abnormalities in the patients with radiologically isolated syndrome could be detected by DTI.