Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: a randomized phase 1/2 controlled trial.

BACKGROUND: Neural stem cells (NSCs) are believed to have the most therapeutic potential for neurological disorders because they can differentiate into various neurons and glial cells. This research evaluated the safety and efficacy of intranasal administration of NSCs in children with cerebral palsy (CP). The functional brain network (FBN) analysis based on electroencephalogram (EEG) and voxel-based morphometry (VBM) analysis based on T1-weighted images were performed to evaluate functional and structural changes in the brain. METHODS: A total of 25 CP patients aged 3-12 years were randomly assigned to the treatment group (n = 15), which received an intranasal infusion of NSCs loaded with nasal patches and rehabilitation therapy, or the control group (n = 10) received rehabilitation therapy only. The primary endpoints were the safety (assessed by the incidence of adverse events (AEs), laboratory and imaging examinations) and the changes in the Gross Motor Function Measure-88 (GMFM-88), the Activities of Daily Living (ADL) scale, the Sleep Disturbance Scale for Children (SDSC), and some adapted scales. The secondary endpoints were the FBN and VBM analysis. RESULTS: There were only four AEs happened during the 24-month follow-up period. There was no significant difference in the laboratory examinations before and after treatment, and the magnetic resonance imaging showed no abnormal nasal and intracranial masses. Compared to the control group, patients in the treatment group showed apparent improvements in GMFM-88 and ADL 24 months after treatment. Compared with the baseline, the scale scores of the Fine Motor Function, Sociability, Life Adaptability, Expressive Ability, GMFM-88, and ADL increased significantly in the treatment group 24 months after treatment, while the SDSC score decreased considerably. Compared with baseline, the FBN analysis showed a substantial decrease in brain network energy, and the VBM analysis showed a significant increase in gray matter volume in the treatment group after NSCs treatment. CONCLUSIONS: Our results showed that intranasal administration of NSCs was well-tolerated and potentially beneficial in children with CP. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov (NCT03005249, registered 29 December 2016, https://www. CLINICALTRIALS: gov/ct2/show/NCT03005249 ) and the Medical Research Registration Information System (CMR-20161129-1003).

[Extraction of the EEG signal feature based on echo state networks].

The performance of an electroencephalography (EEG) automatic detection and classification system mainly depends on the feature extraction of EEG signal. This paper analyses the advantages and disadvantages of the current EEG feature extraction methods, and then presents a new EEG feature extraction method based on echo state networks (ESN). The new method is a nonlinear method, and can extract the EEG features reversibly. Therefore, the information lost in the process of feature extraction is much less than that of the traditional EEG. Additionally, the realization of this method just needs to compute the pseudo inverse of a matrix, which keeps it efficient. Experimental results have showed that the new method could well accomplish the task of automatic detection and classification of EEG signals.

[An analysis on the relationship between susceptibility to cirrhosis and polymorphisms at C-1350T and G-944C sites of CIITA gene promoter IV in chronic HBV carriers].

OBJECTIVE: To investigate the relationship between the susceptibility to cirrhosis and the single nucleotide polymorphisms (SNPs) at C-1350T and G-944C loci of class II transactivator (CIITA) gene promoter IV in chronic HBV carriers. METHODS: C-1350T and G-944C loci of CIITA gene promoter IV were analyzed by sequence-specific primer PCR (PCR-SSP) in 544 chronic HBV carriers and 125 non-HBV infected healthy blood donors. RESULTS: Among the chronic viral hepatitis B patients, there were significantly decreased frequencies of CC and TG haplotypes, and significantly increased frequency of CG haplotype among patients with liver cirrhosis (CG vs. CC: chi2=8.274, df=1, P < 0.01; CG vs. TG: chi2 = 15.027, df =1, P <0.01). There were no significant differences in the frequencies of CC and TG haplotypes between chronic hepatitis B and liver cirrhosis patients (chi2 = 1.231, df =1, P < 0.05). There were significantly increased frequencies of CC/CC (Group 1) genotype and genotypes contained CG haplotype (Group 3), and significantly decreased frequencies chi2= 7.176, df = 1, P < 0.01; Group1 vs Group 4, chi2 = 19.818, df = 1, P < 0.01; Group 3 vs Group 2, chi2 = 11.423, df = 1, P < 0.01; Group 3 vs Group 4, chi2 = 34.226, df = 1, P < 0.01; Group 1 vs Group 3, chi2 = 0.009, df = 1; Group 2 vs Group 4, chi2 = 2.176, df = 1). CONCLUSION: Polymorphisms at -1350 and -944 loci of CIITA gene promoter IV are associated with susceptibility to liver cirrhosis in chronic HBV carriers. The chronic HBV carriers bearing CC/CC genotype or genotypes containing CG haplotype progress into liver cirrhosis with more probability.

Single nucleotide polymorphisms and functional analysis of class II transactivator (CIITA) promoter IV in persistent HBV infection.

BACKGROUND/AIMS: CIITA plays a pivotal role in immune response, and the outcome of HBV infection is influenced by immune response. The aims of this study were to analyze the effect of CIITA promoter IV polymorphisms on its activity, and their association with persistent HBV infection. METHODS: The polymorphisms in promoter IV (C-1350T and G-944C) were analyzed by tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR), and four haplotypes were assigned in 1420 HBV infected subjects. The functional analysis on haplotypes of promoter IV was studied using pGL3-basic and pGL3-promoter vectors. RESULTS: There were significantly decreased-TG and increased-CC haplotype frequencies in persistent HBV infected subjects (34.8% and 41.3%), compared with spontaneously recovered subjects (46.5% and 36.2%). There were significantly higher CC/CC and lower TG/TG genotype frequencies in persistent infected subjects (20.3% and 11.1%) than in spontaneously recovered subjects (10.9% and 23.1%). The mean relative luciferase activity of promoter IV were the highest in TG haplotype (0.558+/-0.023), and the lowest in CC haplotype (0.302+/-0.016). CONCLUSIONS: The polymorphisms of CIITA promoter IV are associated with persistent HBV infection. The CC haplotype with the lowest activity of promoter and CC/CC genotype are responsible for persistent HBV infection.

[Construction of eukaryotic expression vectors containing different haplotype cDNA of human CIITA gene].

OBJECTIVE: To construct eukaryotic expression vectors containing three different haplotype cDNAs of human CIITA gene. METHOD: cDNA fragments of three different CIITA haplotypes were obtained by inducing one or two single nucleotide mutations of wild type recombinant plasmid EBS-NPL-CIITA cDNA, which correspond to two non-homonymy single nucleotide polymorphism (SNP) sites in the coding region of human CIITA gene, using overlap extension PCR site-directed mutagenesis technology. The above-mentioned three haplotype cDNAs were respectively cloned to EBS-NPL-CIITA linearized vectors. Positive clones were identified by colonial PCR and restriction endonuclease digestion and were sent to be sequenced. Then eukaryotic expression vectors containing four different haplotypes and an empty vector EBS-NPL were transfected into HepG2 cells respectively. HLA-DR was detected by indirect cell immunofluorescence technique. RESULTS: The cDNA fragments of three different human CIITA haplotypes were successfully constructed, and the eukaryotic expression vectors containing three different haplotype cDNAs of human CIITA gene were obtained. No expression of HLA-DR was observed in the original HepG2 cells and empty vector transfected HepG2 cells and the expression of HLA-DR emerged in the HepG2 cells transfected with four eukaryotic expression vectors. CONCLUSION: The eukaryotic expression vectors containing three different haplotype cDNAs of human CIITA gene were successfully constructed, and they are essential for our further study of the functional differences of them.

Selective medial temporal volume reduction in the hippocampus of patients with idiopathic generalized tonic-clonic seizures.

BACKGROUND: Different subtypes of idiopathic generalized epilepsy may indicate different mechanisms and outcomes, suggesting that it is necessary to use a 'pure sample' of a single subtype. METHODS: A volumetric study, in conjunction with cognition assessments, was performed in a pure sample of patients with idiopathic generalized tonic-clonic seizures (IGE-GTCS; 15 males and 15 females) matched with normal control subjects (15 males and 17 females). The volumetric measurements were focused on the hippocampus and its surrounding structures, including the amygdala, the parahippocampal gyrus, the entorhinal cortex and the perirhinal cortex. The Wechsler Adult Intelligence Scale-Revised in China was administered to assess cognitive status. RESULTS: A volume reduction was found only in the hippocampus, with a more severe effect on the left side than the right side. The total number and frequency of seizures had significant negative correlations with multiple cognitive measures. Furthermore, the hippocampal volume reduction was significantly correlated with some aspects of cognitive impairment. CONCLUSION: These findings suggest that compared with the other medial temporal structures, the hippocampus may be more vulnerable to the neuropathology of IGE-GTCS. The observation that cognitive deterioration was correlated with an increased frequency and total number of seizures highlights the critical importance of preventing seizures from recurrence.

A novel dynamic update framework for epileptic seizure prediction.

Epileptic seizure prediction is a difficult problem in clinical applications, and it has the potential to significantly improve the patients' daily lives whose seizures cannot be controlled by either drugs or surgery. However, most current studies of epileptic seizure prediction focus on high sensitivity and low false-positive rate only and lack the flexibility for a variety of epileptic seizures and patients' physical conditions. Therefore, a novel dynamic update framework for epileptic seizure prediction is proposed in this paper. In this framework, two basic sample pools are constructed and updated dynamically. Furthermore, the prediction model can be updated to be the most appropriate one for the prediction of seizures' arrival. Mahalanobis distance is introduced in this part to solve the problem of side information, measuring the distance between two data sets. In addition, a multichannel feature extraction method based on Hilbert-Huang transform and extreme learning machine is utilized to extract the features of a patient's preseizure state against the normal state. At last, a dynamic update epileptic seizure prediction system is built up. Simulations on Freiburg database show that the proposed system has a better performance than the one without update. The research of this paper is significantly helpful for clinical applications, especially for the exploitation of online portable devices.