Cerebral Small Vessel Disease Is Associated with Motor, Cognitive, and Emotional Dysfunction in Multiple System Atrophy.

BACKGROUND: Cerebral small vessel disease (CSVD) has not been systematically studied in patients with multiple system atrophy (MSA). OBJECTIVE: We sought to explore whether MSA patients suffer from a heavier CSVD burden relative to healthy individuals and whether CSVD has a relationship with motor, cognitive, and emotional dysfunction in patients with MSA. METHODS: This study consecutively recruited 190 MSA patients and 190 matched healthy controls whose overall CSVD burden and single CSVD imaging markers (including white matter hyperintensity (WMH), microbleeds, lacunes, and enlarged perivascular spaces (EPVS)) were measured. Of the MSA patients, 118 completed multi-dimensional outcome assessments. Spearman's correlations and multivariable linear regressions were performed. RESULTS: We observed a greater burden of overall CSVD, WMH, and EPVS in MSA patients compared with controls, but not for microbleeds and lacunes. Motor dysfunction and cognitive impairment were significantly worse in subjects with severe CSVD than those with none-to-mild CSVD. In patients with MSA, the severity of CSVD burden was positively associated with motor impairments as measured by the Unified Multiple System Atrophy Rating Scale-II (ß= 2.430, p = 0.039) and Scale for the Assessment and Rating of Ataxia (ß= 1.882, p = 0.015). Of CSVD imaging markers, different associations with MSA outcomes were displayed. WMH was associated with motor, cognitive, and emotional deficits, while the EPVS in the centrum semiovale, basal ganglia, and hippocampus regions was correlated only with motor severity, anxiety, and cognition, respectively. Similar findings were noted in MSA-cerebellar and MSA-parkinsonian patients. CONCLUSIONS: Concomitant CSVD may be correlated with worse multi-dimensional dysfunction in patients with MSA.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

Association of Cerebral Microbleeds with Cognitive Decline: A Longitudinal Study.

BACKGROUND: The role of cerebral microbleeds (CMBs) in cognitive impairment remains controversial. OBJECTIVE: To investigate the possible links between the presence, progression, number, and location of CMBs and cognition. METHODS: We assessed 792 subjects from the Alzheimer's Disease Neuroimaging Initiative who underwent both brain 3 Tesla MRI scans and cognitive testing. The association between CMBs and cognitive change was explored using linear mixed-effects models (LME). RESULTS: Presence and number of CMBs were associated with memory (ß= -0.03, p = 0.015; ß= -0.01, p = 0.003), executive function (ß= -0.04, p = 0.010; ß= -0.01, p = 0.014), and global cognitive function (ß= -0.06, p = 0.025; ß= -0.03, p < 0.001). Progression of CMBs showed significant negative associations with executive function (ß= -0.05, p = 0.025) and global cognitive function (ß= -0.12, p = 0.015). The relations with cognitive performance (memory, executive function and global cognitive function) were mainly driven by lobar CMBs (ß= -0.03, p = 0.041; ß= -0.04, p = 0.010; ß= -0.07, p = 0.029, respectively), especially those located in temporal lobe (ß= -0.08, p = 0.027; ß= -0.13, p = 0.001; ß= -0.26, p < 0.001, respectively). Furthermore, white matter hyperintensities may mediate the association between CMBs and cognition. CONCLUSION: The presence, progression, number, and location of CMBs, especially those located in temporal lobe, are associated with cognitive decline. These findings suggest CMBs play a role in cognitive impairment.

Bioinformatic analysis of long non-coding RNA-associated competing endogenous RNA network in adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a malignant tumor with poor prognosis and unclear pathogenesis. This study aimed to explore the role of long non-coding RNAs (lncRNAs) in ACC. METHODS: We obtained the lncRNA expression profiles of 10 ACC samples and 6 normal control samples from the GEO database and identified differentially expressed RNAs using the limma package in R. RESULTS: We obtained a total of 391 differentially expressed lncRNAs (DElncRNAs) and 1,313 differentially expressed mRNAs (DEmRNAs) between ACC samples and normal control samples. Using Cytoscape v3.7.0, we then constructed a lncRNA-miRNA-mRNA (competing endogenous RNA, or ceRNA) network consisting of 87 lncRNAs, 31 miRNAs, and 78 mRNAs. Applying GO and KEGG enrichment analysis for 78 mRNAs in the ceRNA network, we identified 9 GO terms and 21 significantly enriched pathways. A PPI network was constructed using STRING online tools and Cytoscape v3.7.0, identifying 10 key genes. Finally, through Kaplan-Meier survival analysis, we identified five lncRNAs (LINC00887, MEIS1-AS2, MIR29B2CHG, MIR503HG, and SREBF2-AS1) associated with prognosis in patients with ACC. CONCLUSIONS: In summary, we constructed a ceRNA network and propose a new method for lncRNA research in ACC. Our results provide new clues for further exploration of lncRNAs in the pathogenesis of ACC.

Association of neck circumference and cognitive impairment among Chinese elderly.

Objectives: To investigate the association between neck circumference (NC) and cognitive impairment and interactions between relevant variables to the risk of cognitive impairment. Methods: A population-based survey was conducted among elderly inhabitants aged 60 years and over from a community in Shanghai suburb. Multivariate logistic regression analyses were performed to evaluate associations and log likelihood ratio tests to examine interactions. Results: Cognitive impairment was identified in 269 (10.8%) subjects from 2,500 participants. Higher BMI (OR = 1.55; 95% CI = 1.11-2.16), higher WHR (OR = 1.44; 95% CI = 1.07-1.95), and higher total cholesterol (TC) (OR = 1.52; 95% CI = 1.09-2.13) were significantly associated with the increased risk of cognitive impairment. Significant interactions were observed between TC and a few other relevant variables, respectively. Conclusions: NC was associated with the high risk of cognitive impairment. Additive effects of NC with TC on cognitive impairment were observed.

An electrochemical immunosensor based on enzyme-encapsulated liposomes and biocatalytic metal deposition.

A novel electrochemical immunosensor based on double signal amplification of enzyme-encapsulated liposomes and biocatalytic metal deposition was developed for the detection of human prostate specific antigen (PSA). Alkaline phosphatase (ALP)-encapsulated and detection antibody-functionalized liposomes were first prepared and used as the detection reagent. In the sandwich immunoassay, the model analyte PSA was first captured by anti-PSA capture antibody immobilized on the electrode and then sandwiched with the functionalized liposomes. The bound liposomes were then lysed with surfactant to release the encapsulated ALP, which served as secondary signal amplification means. ALP on the electrode surface initiated the hydrolysis of ascorbic acid 2-phosphate (AA-p) to produce ascorbic acid. The latter, in turn, reduced silver ions on the electrode surface, leading to deposition of the metal silver on the electrode surface. Linear sweep voltammetry (LSV) was chosen to detect the amount of the deposited silver. The results showed that the anodic stripping peak current was linearly dependent on the PSA concentration in the range of 0.01-100 ng mL(-1), and a detection limit as low as 0.007 ng mL(-1) can be obtained. Since the cut-off value of human PSA is 4 ng mL(-1), the proposed electrochemical immunosensor would be expected to gain widespread applications for the detection of PSA in clinical diagnosis.

Febrile seizures are associated with mutation of seizure-related (SEZ) 6, a brain-specific gene.

Genetic factors contribute significantly to the etiology of febrile seizures (FS), the most common type of seizures in childhood. However, in most patients with FS, the causative gene is unknown. The purpose of this study was to explore the relationship between human brain-specific gene SEZ-6 and FS. Through amplification of genomic DNA by PCR and sequencing of the resulting products, we screened 75 subjects for mutations in the coding region (17 exons) of the SEZ-6 gene. Fifteen subjects were healthy individuals and 60 subjects had FS. Patients with FS could be divided into sub-groups based on seizure type (42 simple and 18 complex) and family history (41 had a positive family history). All patients have been followed to date to evaluate seizure recurrence and the development of epilepsy. No mutations were found in healthy controls, but 21 of the patients with FS had mutations in SEZ-6, and the most common type of mutation was a heterozygous, cytosine insertion (frame shift mutation) at position 1435 of the cDNA. The mutation incidence was significantly higher in patients with complex FS (vs. simple FS) and in patients with a positive family history. Sixteen of 42 patients with simple FS experienced seizure recurrence during the 1-5-year follow-up period. Fifteen of 18 patients with complex FS also experienced a recurrence during this period. Among these patients with recurrences, five patients with simple FS and six patients with complex FS have developed epilepsy. The mutation incidence among these epileptic patients is 72.7%. The human SEZ-6 gene is related to the occurrence and development of FS and may be a novel candidate gene for epilepsy. Screening for mutations in SEZ-6 may be valuable in predicting FS recurrence or the development of epilepsy.