Objective:To analyze the clinical phenotype, imaging characteristics and genetic characteristics of a family of early-onset dementia caused by a new mutation in the triggerring receptor expressing on myeloid cells 2 gene (TREM2).Methods:Clinical data were collected from a patient with early-onset dementia. Then whole exome sequencing was performed for the proband, followed by Sanger sequencing for the family members.Results:The clinical manifestations of the proband (a 49-year-old female) was personality changes, mental and behavioral abnormalities, memory loss, ataxia, and seizures. Whole-exon sequencing revealed a novel homozygous mutation in exon 2 of TREM2, namely c.154C>T (p.R52C) heterozygosity in four family members, and one patient with similar clinical manifestations was deceased. The proband′s brain magnetic resonance imaging showed bilateral frontotemporal atrophy, bilateral white matter hyperintensity, thin corpus callosum. No bone cysts of the hands and feet were found by digital radiographic imaging.Conclusions:A homozygous mutation in TREM2 gene was detected in a patient with frontotemporal dementia-like dementia, epilepsy, but without bone cysts. This mutation is probably pathogenic. This research highlights the importance of TREM2 gene mutation screening in early-onset dementia, especially in those with atypical presentations.

Purpose: To observe therapeutic effect of acupuncture plus Methadone on improvement of heroin withdrawal syndrome. Methods: Sixty cases of heroin dependence patients were divided into the treatment group and the control group. The treatment group was given acupuncture plus Methadone, and the control group was treated with Methadone.Results: The score of the withdrawal symptoms was lower in the treatment group than in the control group (P ＜ 0.05). The improvement of withdrawal symptoms was significantly better in the treatment group than in the control group (P＜ 0.05). Conclusion: Acupuncture plus Methadone can significantly improve heroin withdrawal syndrome.

Objective To analyze the imaging features of congenital spinal deformity (CSD) associated with split cord malformation (SCM) and other intraspinal abnormalities, and to investigate the relationship to neurological symptoms. Methods 105 cases CSD with SCM were retrospectively studied. Analysis the imaging features of SCM (including type of SCM, location of SCM, location and apical vertebrae, symmetry of divided cord) and other intraspinal abnormalities. To investigate the relationship of the factors and neurological symptoms using Chi?square test of one factor and multiple factors logistic regression analysis. Re?sults 28 cases (26.7%) were formation failure, 33 cases (31.4%) were segmentation failure, and 44 cases (41.9%) were combina?tion of 2 disorders. 41 cases had neurological symptoms, 64 cases were asymptomatic. The distribution of SCM combined with spi?nal deformities:thoracic (11 cases), thoracolumbar (18 cases) and lumbar (20 cases) in type I SCM, thoracic (31 cases), thoracolum?bar (20 cases) and lumbar (5 cases) in type II, none was in cervical. The location of SCM upper than apical vertebrae 29 cases, on apical vertebrae 25 cases, lower than apical vertebrae 51 cases. Spinal cord was splitted symmetric 27 cases and asymmetric 78 cases. 66 cases combined with other intraspinal abnormalities, lower conus 42 cases, syringomyelia 38 cases, meningocele 10 cas?es and sakrale zyste 5 cases. Associated with intraspinal abnormalities, the rate of neural symptoms was different. According to Chi?square test of one factor and multiple factors logistic regression analysis, lumbar SCM, spinal cord asymmetric and lower conus were related with neurological symptoms. Conclusion The predilection spinal deformity of type I is combination, type II SCM is segmentation failure. When SCM patients associated with other intraspinal abnormalities, the incidence of neurologic symptoms is increased. The lumbar SCM, hemicords asymmetry and lower lying conus have significant relationship with neurologic symptoms.

Genetic manipulation of human pluripotent stem cells (hPSCs) provides a powerful tool for modeling diseases and developing future medicine. Recently a number of independent genome-editing techniques were developed, including plasmid, bacterial artificial chromosome, adeno-associated virus vector, zinc finger nuclease, transcription activator-like effecter nuclease, and helper-dependent adenoviral vector. Gene editing has been successfully employed in different aspects of stem cell research such as gene correction, mutation knock-in, and establishment of reporter cell lines (Raya et al., 2009; Howden et al., 2011; Li et al., 2011; Liu et al., 2011b; Papapetrou et al., 2011; Sebastiano et al., 2011; Soldner et al., 2011; Zou et al., 2011a). These techniques combined with the utility of hPSCs will significantly influence the area of regenerative medicine.
Cell Line ; Chromosomes, Artificial, Bacterial ; genetics ; Deoxyribonucleases ; genetics ; Dependovirus ; genetics ; Gene Targeting ; methods ; Genetic Engineering ; methods ; Genetic Vectors ; Genome, Human ; Humans ; Mutagenesis, Insertional ; Mutation ; Plasmids ; Pluripotent Stem Cells ; cytology ; metabolism ; Zinc Fingers ; genetics

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR family consisting of ROR1 and ROR2. RORs contain two distinct extracellular cysteine-rich domains and one transmembrane domain. Within the intracellular portion, ROR1 possesses a tyrosine kinase domain, two serine/threonine-rich domains and a proline-rich domain. RORs have been studied in the context of embryonic patterning and neurogenesis through a variety of homologs. These physiologic functions are dichotomous based on the requirement of the kinase domain. A growing literature has established ROR1 as a marker for cancer, such as in CLL and other blood malignancies. In addition, ROR1 is critically involved in progression of a number of blood and solid malignancies. ROR1 has been shown to inhibit apoptosis, potentiate EGFR signaling, and induce epithelial-mesenchymal transition (EMT). Importantly, ROR1 is only detectable in embryonic tissue and generally absent in adult tissue, making the protein an ideal drug target for cancer therapy.
Animals ; Antineoplastic Agents ; pharmacology ; Embryonic Development ; Humans ; Immunotherapy ; Molecular Targeted Therapy ; Neoplasms ; drug therapy ; enzymology ; Receptor Tyrosine Kinase-like Orphan Receptors ; physiology

Ascorbic Acid ; chemistry ; pharmacology ; Cellular Reprogramming ; Genetic Vectors ; genetics ; metabolism ; Histone Deacetylases ; genetics ; metabolism ; Humans ; Induced Pluripotent Stem Cells ; cytology ; drug effects ; Protein Kinase Inhibitors ; chemistry ; pharmacology ; RNA, Small Interfering ; metabolism

Many neurodegenerative disorders such as Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and others often occur as a result of progressive loss of structure or function of neurons. Recently, many groups were able to generate neural cells, either differentiated from induced pluripotent stem cells (iPSCs) or converted from somatic cells. Advances in converted neural cells have opened a new era to ease applications for modeling diseases and screening drugs. In addition, the converted neural cells also hold the promise for cell replacement therapy (Kikuchi et al., 2011; Krencik et al., 2011; Kriks et al., 2011; Nori et al., 2011; Rhee et al., 2011; Schwartz et al., 2012). Here we will mainly discuss most recent progress on using converted functional neural cells to treat neurological diseases and highlight potential clinical challenges and future perspectives.
Amyotrophic Lateral Sclerosis ; therapy ; Animals ; Cell Transdifferentiation ; Cell- and Tissue-Based Therapy ; Induced Pluripotent Stem Cells ; cytology ; Neurons ; cytology ; transplantation ; Parkinson Disease ; therapy ; Stroke ; therapy

Objective To investigate the effectiveness and safety of intravenous immunoglobulin combined with oral glucocorticoid in the treatment of myasthenia gravis in elderly patients.Methods A total of 235 elderly patients diagnosed as myasthenia gravis in our hospital were enrolled in our study from January 2012 to December 2016,and randomly divided into observation group (intravenous immunoglobulin combined with oral glucocorticoid n =118) and control group (oral glucocorticoid only,n =117).The clinical curative effect,immune function index,QMG scale,symptom remission time,length of hospitalization,and adverse reactions in both groups were recorded and analyzed after two-week treatment.Results The total effective rate was significantly higher in observation group (106/117,90.6％) than in control group (84/118,71.2％) (x2=5.621,P=0.000).The levels of serum IgG1,IgG3,and complement C3 were significantly higher in observation group than in control group (P ＜0.05).The QMG scale,symptom remission time,and length of hospitalization were lower in observation group [(9.2 ± 4.0) score,(6.2 ± 1.6) d,(14.4 ± 3.3) d]than in the control group [(13.4 ± 6.1) score,(11.6 ± 2.4) d,(25.1 ± 4.8) d] (t =6.158,19.797,and 20.078,P=0.000,0.002 and 0.009).No serious adverse reaction was observed in both groups.Conclusions The combined therapies of intravenous immunoglobulin and oral glucocorticoid for myasthenia gravis in the elderly have remarkable effectiveness.It is close to an ideal treatment because it effectively inhibits a disease progression in time,regulates an immune function,and shortens a hospitalization time.

Objective To observe the expression of neuropilin-1 (NRP-1) in glioma cells of different grades,and evaluate the application value of a novel molecular probe(USPIO-PEG-tLyP-1)in the grading diagnosis of heterotopic glioma in nude mice by magnetic resonance imaging (MRI).Methods Expression levels of NRP-1 in glioma cell lines of different grades were detected by Western-Blot.USPIO-PEG-tLyP-1 was synthesized by carbon diimine method.The U87-MG tumor-bearing mice model (U87-MG group) and CHG-5 tumor-bearing mice model(CHG-5 group) were established with 10 mice in each group.Six tumorbearing mice with a tumor volume about 0.6 cm3 were selected from each group,and they were given with 2mg/kg molecular probes via tail vein respectively and was detected by MRI at 0 h,6 h,12 h and 24 h,then R2 values were calculated.After the imaging,tumor-bearing mice were sacrificed,and tumor tissue sections were made.The iron particles in the sections was detected by Prussian blue staining.The binding ability of molecular probes and tumor tissues in the two groups was compared.Results The expression of NRP-1 in U87-MG and CHG-5 cell lines was significantly higher than that in HA.In addition,the expression of NRP-1 in U87-MG was higher than that in CHG-5 cell(P＜0.01).MRI results showed that R2 values of tumor tissues in the two groups were compared,and the difference was not statistically significant before the injection of molecular probe(U87-MG group(10.35±0.52)vs CHG-5 group(9.86±0.43),t=1.779,P=0.106).The R2 value of tumor tissue in the U87-MG group was higher than that in the CHG-5 group after the injection of molecular probe (6 h:U87-MG group (11.63±0.85)vs CHG-5 group (10.51 ±0.49),t=2.796,P=0.019;12h:U87-MG group(14.23±0.68)vs CHG-5 group(12.29±0.28),t=6.462,P=0.000;24 h:U87-MG group (13.36±0.92) vs CHG-5 group(11.32±0.64),t=4.459,P=0.001).The results of Prussian blue staining showed that there were significantly more blue staining particles in tumor tissues of the U87-MG group than that of the CHG-5 group,and the difference was statistically significant(P＜0.01).Conclusion The NRP-1 targeted molecular probe can be used for grading diagnosis of high and low grade heterotopic brain glioma in nude mice.

Objective To investigate the clinical manifestations,imaging features,molecular genetic characteristics and possible pathogenic mechanisms of hereditary cerebral small vessel disease (CSVD) caused by heterozygous mutation of HtrA serine protease-1 (HTRA1) gene.Methods The clinical data of a Chinese Han family with CSVD carrying a heterozygous mutation of HTRA 1 gene,which came from the Department of Neurology,Henan Provincial People's Hospital in March 2018,were analyzed retrospectively.The clinical and radiographic features were summarized.Several high-throughput whole exon high-throughput sequencing was used to capture the mutation sites and the Sanger sequencing was used to validate the results.The family diagram was drawn and the 3D model construction and mutation function prediction were performed using silico tools.The relevant literature was reviewed and the pathogenesis was explored.Results The pedigree map showed that the family had an autosomal dominant inheritance pattern.Three generations of the family were investigated,and three family members in the same generation suffered from the disease.The first symptom of the proband was diplopia at the age of 39,accompanied by recurrent stroke,cognitive impairment and mood disorders,without alopecia.Head magnetic resonance imaging revealed bilateral diffuse,symmetric lesions,multiple lacunar infarcts,perivascular space,and microbleeds.The elder sister of the proband developed symptoms of left limb weakness at the age of 46,whose other clinical and imaging features were similar to those of the proband.The proband's mother died at the age of 59 due to repeated strokes.Whole exon sequencing indicated heterozygous missense mutation at c.821G＞A locus of HTRA1 gene in the proband and her 4th elder sibling,which was a new pathogenic mutation after consulting several mutation sites of databases.Function prediction suggested pathogenicity.Conclusions The heterozygous mutation of c.821G＞A in HTRA1 gene may lead to autosomal dominant CVSD.This genetic type should be given clinical attention.