Zhi Song

The Third Xiangya Hospital of the Central South University, Ch’ang-sha-shih, Hunan, China

Are you Zhi Song?

Claim your profile

Publications (44)87.17 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson’s disease (PD) is a common neurodegenerative disorder of complex etiology. Mounting evidence indicates that genetic abnormalities play an important role in the pathogenesis of PD. To date, at least 20 genetic loci and 15 disease-causing genes for parkinsonism have been identified, as well as some susceptibility genes conferring risk to PD. More recently, mutations in the RAB39B gene (RAB39B, member RAS oncogene family) have been reported to cause X-linked intellectual disability and early-onset PD with α-synuclein pathology. To evaluate whether variants in the RAB39B gene are related to PD in Chinese Han population, we conducted genetic analysis of the RAB39B gene in 502 patients with PD from Mainland China. No pathogenic mutation or variant was identified in the coding region or exon/intron boundaries of the gene. Our results suggest that mutation(s) in the coding region of the RAB39B gene plays little or no role in the development of PD in Chinese population.
  • Ru Chen, Zelin Deng, Zhi Song
    [Show abstract] [Hide abstract]
    ABSTRACT: Malignant middle cerebral artery infarction (MMI) is always associated with high mortality rates. Early decompressive craniectomy is crucial to its treatment. The purpose of this study was to establish a reliable model for an early prediction of MMI. Using a retrospective survey, we have collected the data of 132 patients with middle cerebral artery infarction. According to a prognosis, the patients are divided into the MMI group (n = 36) and the non-MMI group (n = 96). All the patients are represented by their clinical, biochemical, and imaging features. Then a random forest (RF) prediction model is established on the clinical data. Meanwhile, 3 traditional prediction models, including univariate linear discriminant analysis (LDA) model, multivariate LDA model, and binary logistic regression analysis (BLRA), are built to compare with the RF model. The prediction performance of different models is assessed by the area under the receiver operating characteristic curves (AUCs). Four parameters, Glasgow Coma Scale, midline shifting, area, and volume of focus, selected as predictors in all models. As independent predictors, their AUCs are .72-.80, and when the sensitivities are high (.91-.95), the specificities are low (.32-.53). The AUC of RF model is .96, 95% confidence interval (CI) is (.93-.99), sensitivity is 1, and specificity is .85. The AUC of the multivariate LDA model is .87 and 95% CI is (.80-.93). The AUC of the BLRA model is .86 and 95% CI is (.80-.93). The RF performs very well in the given clinical data set, which indicates that the RF is applicable to the early prediction of the MMI. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 03/2015; 24(5). DOI:10.1016/j.jstrokecerebrovasdis.2014.12.016 · 1.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Febrile seizures (FS), the most frequent type of seizures in children, occur in neurologically normal infants and children between the ages of 3 months and 5 years with genetic predisposition. The aim of this study was to identify the responsible gene in a four-generation Chinese Han pedigree with autosomal dominant FS. Seven family members (three affected and four unaffected) were enrolled in this study. Exome sequencing was conducted and a duplication mutation c.649dupC (p.R217Pfs*8) in the proline-rich transmembrane protein 2 gene (PRRT2) was identified. The mutation co-segregated with the disorder and was absent in normal controls. To our knowledge, this is the first report of a pedigree with complete penetrance of FS, which is caused by mutation in the PRRT2 gene. FS is a novel phenotype of the c.649dupC (p.R217Pfs*8) mutation. Our discovery broadens the spectrum of genetic causes of FS and the spectrum of phenotypes linked to mutation in the PRRT2 gene.
    Molecular Neurobiology 12/2014; DOI:10.1007/s12035-014-9047-4 · 5.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Copper is an essential trace element that serves as an important catalytic cofactor for cuproenzymes, carrying out major biological functions in growth and development. Although Wilson's disease (WD) is unquestionably caused by mutations in the ATP7B gene and subsequent copper overload, the precise role of copper in inducing pathological changes remains poorly understood. Our study aimed to explore, in HepG2 cells exposed to copper, the cell viability and apoptotic cells was tested by MTT and Hoechst 33342 stainning respectively, and the signaling pathways involved in oxidative stress response, apoptosis and lipid metabolism were determined by real time RT-PCR and Western blot analysis. The results demonstrate dose- and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10μM , 200μM and 500μM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited. These findings provide new insights into possible mechanisms accounting for the development of liver apoptosis and steatosis in the early stages of Wilson's disease.
    The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 12/2014; 25(Suppl 1):S116-S121. DOI:10.5152/tjg.2014.5064 · 0.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have demonstrated the protective effect of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases. Increased levels of the potential ALDH2 substrate 4-hydroxynonenal (4-HNE) are involved in myocardial/cerebral ischemia accompanied by a high level of oxidative stress. In this investigation, we first performed a case-control study to explore the potential association of ALDH2 rs671 polymorphism and post-stroke epilepsy (PSE). Then, we performed an in vitro study to determine whether the overexpression of ALDH2 could decrease the level of oxidative stress and the apoptosis ratio induced by 4-HNE. There was a significant difference in the distribution of the allele and genotype frequencies of the rs671 polymorphism between PSE patients and ischemic stroke (IS) patients. Individuals with the rs671 A allele showed significantly higher levels of plasma 4-HNE. The overexpression of ALDH2 partially blocked the increased levels of malondialdehyde (MDA), reactive oxygen species (ROS) and apoptosis ratio induced by 4-HNE and also partially restored the ALDH2 activity in PC12 cells; these effects were reversed in the presence of εV1-2. Our results suggest that the ALDH2 rs671 polymorphism is associated with PSE susceptibility and affects the 4-HNE levels. Targeting ALDH2 might be a useful strategy for the treatment or prevention of PSE.
    PLoS ONE 10/2014; 9(10):e109634. DOI:10.1371/journal.pone.0109634 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Stroke is one of the main causes of death and adult chronic disability. Recently, 2 independent genome-wide association studies reported that the genetic variants (rs556621 and rs11984041) are significantly associated with large artery atherosclerosis (LAA). Methods: To determine whether these 2 variants are associated with the pathogenesis of LAA in stroke patients from the Xinjiang Uyghur autonomous region of China, both variants were evaluated in a series of 733 LAA stroke patients (434 Han and 299 Uyghur) and 725 age-, gender-, smoking-, alcohol habits-and ethnicity-matched controls (401 Han and 324 Uyghur). Results: For rs556621, significant differences in genotypic and allelic distributions were observed between Uyghur patients and controls (P = .045 for genotypic distribution, P = .042 for allelic distribution) but not in the Chinese Han cohort (P > .05). No significant differences were found in genotypic and allele distributions between patients and controls for rs11984041 in either the Chinese Han or Uyghur cohort (P > .05). Conclusions: The variant rs556621 but not rs11984041 may increase susceptibility of LAA stroke in the Xinjiang Uyghur population.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 10/2014; 23(10). DOI:10.1016/j.jstrokecerebrovasdis.2014.06.015 · 1.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson disease (PD) is the second most common progressive neurodegenerative disorder. It is characterized by selective loss of dopamine-producing neurons and aggregation of alpha-synuclein (SNCA) in neurons of particular brain regions. At least 20 loci and 15 disease-causing genes have been identified. Rare missense or multiplication mutations in the SNCA gene have been reported to be involved in some familial and sporadic cases of PD. More recently, two novel pathogenic missense mutations (p.H50Q and p.G51D) were identified in the SNCA gene. To evaluate whether mutation(s) in the coding region of SNCA gene is related to PD in Chinese population, we investigated the SNCA gene in 502 PD patients of Chinese Han ethnicity from Mainland China. No pathogenic mutation was identified in the coding region of the gene. A known G to A transition (c.306 + 66G>A, rs10005233) in the intron 4, which does not potentially change splicing, was identified. Our data indicate that mutations in the coding region of the SNCA gene are not likely to be a common cause of PD in Chinese population.
    Acta neurologica Belgica 08/2014; DOI:10.1007/s13760-014-0347-2 · 0.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Infantile nystagmus (IN) is characterized by bilateral involuntary, periodic, and predominantly ocular oscillations. In this article, we describe a mutation screen conducted on a 4-generation family in which 4 patients were affected with X-linked IN (XLIN). Experimental study. A 4-generation Chinese Han family including 4 symptomatic members with IN and 200 normal male controls. DNA was extracted from peripheral blood, and the FERM domain-containing 7 gene (FRMD7) was amplified on DNA samples of all the available family members. The mutation screen was conducted by performing direct DNA sequencing. A nonsense mutation (R335X) in the FRMD7 gene was identified in 4 male patients and an asymptomatic female member. Although the R335X mutation in the FRMD7 gene has been previously described, the clinical features, including both disease penetrance and severity, among individuals with FRMD7 mutation in our family vary greatly. One female member with the heterozygous R335X mutation had no clinical manifestation of the disease. This incomplete penetrance suggests that random X-chromosome inactivation may play a role in the pathogenesis of IN, and that loss of functional FRMD7 may account for the development of this disorder. Our findings may be helpful in the genetic counseling of patients with nystagmus.
    Canadian Journal of Ophthalmology 02/2014; 49(1):50-3. DOI:10.1016/j.jcjo.2013.09.001 · 1.30 Impact Factor
  • Hao Deng, Wen Zheng, Zhi Song
    [Show abstract] [Hide abstract]
    ABSTRACT: Epilepsy is a common and diverse set of chronic neurological disorders characterized by spontaneous, unprovoked, and recurrent epileptic seizures. Environmental factors and acquired disposition are proposed to play a role to the pathogenesis of epilepsy. Genetic factors are important contributors as well. Comparing to the phenotype of epilepsy caused by mutation of single gene on an autosome, the phenotype of X-linked epilepsy is more complex. X-linked epilepsy usually manifests as part of a syndrome or epileptic encephalopathy, and the variability of clinical manifestations of X-linked epilepsy may be attributed to several factors including the type of genetic mutation, methylation, X chromosome random inactivation, and mosaic distribution. As a result, it is difficult to establish the genotype-phenotype correlation, diagnostic tests, and genetic counseling. In this review, we provide an overview of the X-linked epilepsy including responsible loci and genes, the molecular biology, the associated complex phenotypes, and the interference factors. This information may provide us a better understanding of the pathogenesis of X-linked epilepsy and may contribute to clinical diagnosis and therapy of epilepsy.
    Molecular Neurobiology 11/2013; DOI:10.1007/s12035-013-8589-1 · 5.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To determine the effect of Parkinson's disease-weight bearing exercise for better balance (PD-WEBB) exercise on balance impairment and falls in people with Parkinson's disease (PD). Methods: A single-blind, randomized controlled clinical trial was conducted. The falls efficacy scale score, unified Parkinson disease rating scale (UPDRS) score and Mini-BESTest score were measured and compared between a PD-WEBB group and a control group. Results: The falls efficacy scale score, UPDRS-2 score, UPDRS-3 score and Mini-BESTest score were improved in the PD-WEBB group compared with the control group (P<0.05), with no significant change in UPDRS-1 score between the two groups. Conclusion: PD-WEBB training can significantly improve the balance impairment and quality of life to prevent falls. PD-WEBB training is suitable for PD patients in China, and is a reasonable, effective and sustainable training of family and community assessment model.
    Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 11/2013; 38(11):1172-1176. DOI:10.3969/j.issn.1672-7347.2013.11.015
  • Source
    Neuroscience Letters 10/2013; 555:134-136. DOI:10.1016/j.neulet.2013.09.037 · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Exome sequencing in a large essential tremor (ET) family identified a novel nonsense mutation (p.Q290X) in the fused in sarcoma gene (FUS) as the cause of this family. Because of the clinical overlap between ET and Parkinson's disease (PD), the role of FUS in an independent cohort of PD patients from China mainland was evaluated. The entire coding region of FUS in 508 Chinese Han patients with PD and the identified variants in 633 normal controls were evaluated. A variant was further screened in an additional 382 controls for the frequency in our population. A novel variant c.696C > T (p.Y232Y) in 2 sporadic patients with PD and six variants (c.52C > A, p.P18T; c.52C > T, p.P18S; c.147C > A, p.G49G; c.291C > T, p.Y97Y; c.684C > T, p.G228G; c.1176G > A, p.M392I) without significant difference in genotypic and allelic distributions in our PD cohort were identified. The FUS gene is not a genetic risk factor for PD in the population of Chinese Han ethnicity.
    Parkinsonism & Related Disorders 09/2013; 20(1). DOI:10.1016/j.parkreldis.2013.09.010 · 4.13 Impact Factor
  • Hao Deng, Xiaofei Xiu, Zhi Song
    [Show abstract] [Hide abstract]
    ABSTRACT: Epilepsy is one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system. The clinical features of this disorder are recurrent seizures, difference in age onset, type, and frequency, leading to motor, sensory, cognitive, psychic, or autonomic disturbances. Since the discovery of the first monogenic gene mutation in 1995, it is proposed that genetic factor plays an important role in the mechanism of epilepsy. Genes discovered in idiopathic epilepsies encode for ion channel or neurotransmitter receptor proteins, whereas syndromes with epilepsy as a main feature are caused by genes that are involved in functions such as cortical development, mitochondrial function, and cell metabolism. The identification of these monogenic epilepsy-causing genes provides new insight into the pathogenesis of epilepsies. Although most of the identified gene mutations present a monogenic inheritance, most of idiopathic epilepsies are complex genetic diseases exhibiting a polygenic or oligogenic inheritance. This article reviews recent genetic and molecular progresses in exploring the pathogenesis of epilepsy, with special emphasis on monogenic epilepsy-causing genes, including voltage-gated channels (Na(+), K(+), Ca(2+), Cl(-), and HCN), ligand-gated channels (nicotinic acetylcholine and GABAA receptors), non-ion channel genes as well as the mitochondrial DNA genes. These progresses have improved our understanding of the complex neurological disorder.
    Molecular Neurobiology 08/2013; 49(1). DOI:10.1007/s12035-013-8523-6 · 5.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Wilson's disease (WD) is an autosomal recessive inherited disorder caused by mutations in the ATPase Cu(2+) transporting beta polypeptide gene (ATP7B). The detailed metabolism of copper-induced pathology in WD is still unknown. Gene mutations as well as the possible pathways involved in the ATP7B deficiency were documented. The ATP7B gene was analyzed for mutations in 18 Chinese Han families with WD by direct sequencing. Cell viability and apoptosis analysis of ATP7B small interfering RNA (siRNA)-treated human liver carcinoma (HepG2) cells were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst 33342 staining. Finally, the expression of B-cell CLL/lymphoma 2 (BCL2), BCL2-associated X protein (BAX), sterol regulatory element binding protein 1 (SREBP1), and minichromosome maintenance protein 7 (MCM7) of ATP7B siRNA-treated cells were tested by real-time polymerase chain reaction (real-time PCR) and Western blot analysis. Twenty different mutations including four novel mutations (p.Val145Phe, p.Glu388X, p.Thr498Ser and p.Gly837X) in the ATP7B gene were identified in our families. Haplotype analysis revealed that founder effects for four mutations (p.Arg778Leu, p.Pro992Leu, p.Ile1148Thr and p.Ala1295Val) existed in these families. Transfection of HepG2 cells with ATP7B siRNA resulted in decreased mRNA expression by 86.3%, 93.1% and 90.8%, and decreased protein levels by 58.5%, 85.5% and 82.1% at 24, 48 and 72 hours, respectively (All P<0.01). In vitro study revealed that the apoptotic, cell cycle and lipid metabolism pathway may be involved in the mechanism of WD. Our results revealed that the genetic cause of 18 Chinese families with WD and ATP7B deficiency-induce apoptosis may result from imbalance in cell cycle and lipid metabolism pathway.
    PLoS ONE 07/2013; 8(7):e66526. DOI:10.1371/journal.pone.0066526 · 3.53 Impact Factor
  • Parkinsonism & Related Disorders 06/2013; 19(10). DOI:10.1016/j.parkreldis.2013.05.018 · 4.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Variants in the leucine-rich repeat and lg domain containing nogo receptor-interacting protein 1 gene (LINGO1) have been identified to be associated with the increased risk of essential tremor (ET), especially among Caucasians. To explore whether the LINGO1 gene plays a role in ET susceptibility, we performed a systematic genetic analysis of the coding region in the LINGO1 gene. Four nucleotide variants have been genotyped, including three known variants (rs2271398, rs2271397, and rs3743481), and a novel G→C transition (ss491228439). Extended analysis showed no significant difference in genotypic and allelic distributions between 151 patients and 301 control subjects for these four variants (all P > 0.05). However, further sex-stratified analysis revealed that the C allele of rs2271397 and ss491228439 contributed the risk of ET in female (P = 0.017, OR = 2.139, 95 % CI 1.135 ~ 4.030 for rs2271397 and P = 0.038, OR = 1.812, 95 % CI 1.027 ~ 3.194 for ss491228439). Haplotype analysis indicated that A465-C474-C714 haplotype was significantly associated with increased risk of ET in female (P = 0.041, OR = 1.800, 95 % CI 1.020 ~ 3.178). Our results indicate that the LINGO1 variants are associated with ET in Chinese Han female patients.
    Journal of Molecular Neuroscience 06/2013; 51(2). DOI:10.1007/s12031-013-0029-1 · 2.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-minobutyric acid, and changes in the intra- and extracellular environment.
    Neural Regeneration Research 05/2013; 8(14):1316-26. DOI:10.3969/j.issn.1673-5374.2013.14.008 · 0.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We conducted genetic analysis of the fused in sarcoma gene (FUS) in Chinese Han patients with essential tremor (ET) in a case-control association study. One hundred eighty unrelated patients with ET were screened for mutations in the coding region and exon-intron boundaries of FUS. Reverse transcriptase polymerase chain reaction analysis was performed to evaluate if the c.1176G>A variant results in change of splice site. Two hundred seventy-three normal control subjects were also analyzed when DNA variants were identified in ET cohort. A novel missense mutation, c.1176G>A (p.M392I), in FUS was identified in a 62-year-old patient. Four known variants (c.52C>A, p.P18T; c.147C>A, p.G49G; c.291T>C, p.Y97Y; c.684C>T, p.G228G) were observed in the case-control study without statistically significant differences in genotype and allele distributions. Mutation(s) in FUS might be associated with a small subset of ET cases in the Chinese population.
    Neurobiology of aging 04/2013; 34(8). DOI:10.1016/j.neurobiolaging.2013.03.001 · 4.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Growing evidences show that genetic abnormalities play an important role in the etiopathogenesis of Parkinson disease (PD). At least 18 genetic loci and 13 disease-related genes for parkinsonism have been identified. Recently, the p.Ala502Val and p.Arg1205His variants in the eukaryotic translation initiation factor 4-gamma 1 gene (EIF4G1) were found to be associated with PD. To evaluate whether the EIF4G1 p.Ala502Val and p.Arg1205His variants are related to PD in Chinese Han population, we conducted genetic examination of these two variants in 425 PD patients from Mainland China and none was found in our patients. We did identify a known non-pathogenic polymorphism c.3660C>T (p.Ala1220Ala, rs143852330) in a 73-year-old male patient. Our results, consistent with other recent reports, suggest that the EIF4G1 p.Ala502Val and p.Arg1205His variants are a rare cause of PD, at least in Chinese population.
    Neuroscience Letters 04/2013; 543. DOI:10.1016/j.neulet.2013.02.056 · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: (1) Neuronal synchronization underlies brain functioning, and it seems possible that blocking excessive synchronization in an epileptic neural network could reduce or even control seizures. (2) Local field potential coupling is a very common phenomenon during synchronization in networks. Removal of neurons or neuronal networks that are coupled can significantly alter the extracellular field potential. Interventions of coupling mediated by local field potentials could result in desynchronization of epileptic seizures. (3) The synchronized electrical activity generated by neurons is sensitive to changes in the size of the extracellular space, which affects the efficiency of field potential transmission and the threshold of cell excitability. (4) Manipulations of the field potential fluctuations could help block synchronization at seizure onset.
    Neural Regeneration Research 03/2013; 8(8):745-53. DOI:10.3969/j.issn.1673-5374.2013.08.009 · 0.23 Impact Factor

Publication Stats

136 Citations
87.17 Total Impact Points


  • 2009–2015
    • The Third Xiangya Hospital of the Central South University
      Ch’ang-sha-shih, Hunan, China
  • 2013–2014
    • South Central College
      Central, Louisiana, United States
  • 2010–2013
    • Central South University
      • • Department of Neurology
      • • Center of Experimental Medicine
      Ch’ang-sha-shih, Hunan, China
  • 2012
    • Xiangya Hospital of Central South University
      Ch’ang-sha-shih, Hunan, China