Bo Song

Zhengzhou University, Cheng, Henan Sheng, China

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Publications (47)104.57 Total impact

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    ABSTRACT: Purpose: Cerebral cavernous malformations (CCMs) are vascular anomalies predominantly in the central nervous system but may include lesions in other tissues, such as the retina, skin and liver. The main clinical manifestations include seizures, hemorrhage, recurrent headaches and focal neurological deficits. Previous studies of familial CCMs (FCCMs) have mainly reported in Hispanic and Caucasian cases. Here, we report on FCCMs in a Chinese family further characterized by a novel CCM1 gene mutation. Materials and methods: We investigated clinical and neuroradiological features of a Chinese family of 30 members. Furthermore, we used exome capture sequencing to identify the causing gene. The CCM1 mRNA expression level in three patients of the family and 10 wild-type healthy individuals were detected by real-time quantitative polymerase chain reaction (real-time RT-PCR). Results: Brain magnetic resonance imaging demonstrated multiple intracranial lesions in seven members. The clinical manifestation of CCM was found in five of these cases, including recurrent headaches, weakness, hemorrhage and seizures. Moreover, we identified a novel nonsense mutation c.1159G>T (p. E387*) in the CCM1 gene in the pedigree. Based on real-time RT-PCR results, we have found that the CCM1 mRNA expression level in three patients was reduced by 35% than that in wild-type healthy individuals. Conclusions: Our finding suggests that the novel nonsense mutation c.1159G>T in CCM1 gene is associated with FCCM, and that CCM1 haploinsufficiency may be the underlying mechanism of CCMs. Furthermore, it also demonstrates that exome capture sequencing is an efficient and direct diagnostic tool to identify causes of genetically heterogeneous diseases.
    No preview · Article · Dec 2015 · The International journal of neuroscience
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    ABSTRACT: Background and purpose: The relationship between plasma level of total homocysteine (tHcy) and white matter hyperintensities (WMHs), especially in patients with acute ischemic stroke (AIS), is controversial. The present study investigated the association between these two as well as WMH locations in a large cohort of patients with AIS. Methods: Consecutive patients were reviewed from a prospective ischemic stroke database. Clinical data, including tHcy level and WMHs, were assessed. WMHs were assessed using the Fazekas scale and Age-Related White Matter Changes (ARWMC) visual grading scale. The association between tHcy and WMH locations was investigated by using multivariate logistic regression analyses. Results: A total of 923 out of 1,205 patients were examined. The average age was 58.9 ± 11.9 years; 31.6% were female. Elevated tHcy level was significantly associated with WMHs. For the highest tHcy quartile, the odds ratio (OR) (95% confidence interval; CI) was 1.891 (1.257; 2.843) according to the Fazekas scale and 1.781 (1.185; 2.767) according to the ARWMC scale when compared to the lowest quartile. However, in a subgroup analysis, only WMHs in the periventricular area and left or right frontal areas were found to be independently associated with tHcy level. For the highest tHcy quartile, the OR (95% CI) was 1.761 (1.172; 2.648) for the periventricular WMHs, 1.768 (1.134; 2.756)for the left frontal WMHs, and 1.890 (1.206; 2.960)for the right frontal WMHs. Conclusions: In patients with AIS, plasma tHcy level is related to WMHs, especially WMHs distributed within the periventricular and frontal areas.
    Preview · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: Mutations in CHCHD2 gene have been reported in autosomal dominant Parkinson's disease (ADPD). However, there is still lack of evidence supported CHCHD2 mutations lead to ADPD in other populations. We performed whole exome sequencing, positron emission tomography (PET), and haplotype analyses in an ADPD pedigree and then comprehensively screened for CHCHD2 gene mutations in additional 18 familial parkinsonism pedigrees, 364 sporadic PD patients, and 384 healthy controls to assess the frequencies of known and novel rare nonsynonymous CHCHD2 mutations. We identified a heterozygous variant (c.182C>T; p.Thr61Ile) in the CHCHD2 gene in the ADPD pedigree. PET revealed a significant reduction in dopamine transporter binding in the putamen and caudate nucleus of the proband, similar to idiopathic PD. The single nucleotide variant 5C>T (Pro2Leu) in CHCHD2 was confirmed to have a significantly higher frequency among sporadic PD patients than controls. Our results confirm that ADPD can be caused by CHCHD2 mutations and show that the Pro2Leu variant in CHCHD2 may be a risk factor for sporadic PD in Chinese populations.
    No preview · Article · Nov 2015 · Neurobiology of aging
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    ABSTRACT: Background and purpose: The risk of stroke after a transient ischemic attack (TIA) for patients with a positive diffusion-weighted image (DWI), i.e., transient symptoms with infarction (TSI), is much higher than for those with a negative DWI. The aim of this study was to validate the predictive value of a web-based recurrence risk estimator (RRE; http://www.nmr.mgh.harvard.edu/RRE/) of TSI. Methods: Data from the prospective hospital-based TIA database of the First Affiliated Hospital of Zhengzhou University were analyzed. The RRE and ABCD2 scores were calculated within 7 days of symptom onset. The predictive outcome was ischemic stroke occurrence at 90 days. The receiver-operating characteristics curves were plotted, and the predictive value of the two models was assessed by computing the C statistics. Results: A total of 221 eligible patients were prospectively enrolled, of whom 46 (20.81%) experienced a stroke within 90 days. The 90-day stroke risk in high-risk TSI patients (RRE ≥4) was 3.406-fold greater than in those at low risk (P <0.001). The C statistic of RRE (0.681; 95% confidence interval [CI], 0.592-0.771) was statistically higher than that of ABCD2 score (0.546; 95% CI, 0.454-0.638; Z = 2.115; P = 0.0344) at 90 days. Conclusion: The RRE score had a higher predictive value than the ABCD2 score for assessing the 90-day risk of stroke after TSI.
    Preview · Article · Sep 2015 · PLoS ONE
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    ABSTRACT: Background: Single small subcortical infarctions (SSSIs) in the lenticulostriate artery territory can be classified as proximal single small subcortical infarction (pSSSI) or distal single small subcortical infarction (dSSSI) lesions depending on the involvement of the lowest part of the basal ganglia. It was reported that pSSSI lesions have more characteristics of large artery atherosclerosis, whereas dSSSI lesions are more characteristic of small vessel disease. Because infarction of small vessels is more likely to be distal and may result in small lesions, we hypothesized that the clinical features of dSSSI lesions might be heterogeneous and classified based on lesion size. Methods: Lenticulostriate SSSI patients admitted within 72 hours of stroke onset were included from a prospectively registered hospital-based stroke database. We determined the location (lowest slice [LS] involved) and size (total number of slices [TNS] involved) of SSSIs on magnetic resonance imagings. Based on lesion location, SSSIs were divided into pSSSI (LS ≤ 2) and dSSSI (LS > 2); the latter were further subdivided into distal and small SSSI (ds-SSSI, TNS ≤ 2) or distal and large SSSI (dl-SSSI, TNS > 2). The clinical characteristics were compared between different groups. Results: A total of 204 patients were included out of 1158 patients registered in the database. We found that ds-SSSI was most often associated with severe white matter hyperintensities. However, patients with dl-SSSI most often had a higher rate of additional concurrent atherosclerotic disease as coronary heart disease, compared to patients with ds-SSSI. Conclusions: The pathogenesis of dSSSI may be heterogeneous depending on lesion size.
    No preview · Article · Sep 2015 · Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association
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    ABSTRACT: Multiple system atrophy (MSA) is a neurodegenerative disease, and its pathological hallmark is the accumulation of α-synuclein proteins. Homocysteine (Hcy) is an intermediate amino acid generated during the metabolism of methionine. Hcy may contribute to the pathogenesis of neurodegenerative disorders. Vitamin B12 and folate are cofactors necessary for the methylation of homocysteine. This study compared the levels of serum Hcy, vitamin B12 and folate in patients with MSA with those in healthy people to reveal the possible association between MSA and plasma levels of Hcy, vitamin B12 and folate. We enrolled 161 patients with MSA and 161 healthy people in this study. The association between MSA and the levels of Hcy, vitamin B12 and folate were analyzed using binary logistic regression. The mean level of Hcy in patients with MSA was significantly higher than that in healthy controls (16.23 ± 8.09 umol/l vs 14.04 ± 4.25 umol/l, p < 0.05). After adjusting for age, sex and medical history, the odds ratio for Hcy was 1.07 (95% CI = 1.01-1.13, p < 0.05) for patients with MSA. Vitamin B12 and folate levels were not significantly different between patients with MSA and controls. Our data suggest that higher levels of Hcy may be associated with an increased risk for MSA.
    Preview · Article · Aug 2015 · PLoS ONE
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    ABSTRACT: To investigate the potential benefits of inpatient statin therapy on mortality of acute stroke patients with very low admission low-density lipoprotein cholesterol (LDL-C) level (<1.81 mmol/L). The acute stroke patients with admission LDL-C level less than 1.81 mmol/L were enrolled from the China National Stroke Registry. The patients were divided into statin group and non-statin group during hospitalization. The association between statin therapy and mortality of participants in 1 year was analyzed by multivariable binary logistic regression models. A total of 1018 patients were enrolled, and the cumulative mortality rate was 10.1% at 3 months, 13.1% at 6 months, and 15.9 % at 1 year. The all-cause mortality rate in statin group was significantly lower than that in non-statin group (3.6% versus 13.7% at 3 months, P < .001; 6.2% versus 16.9% at 6 months, P < .001; 8.4% versus 20% at 1 year, P < .001). The logistic analyses showed that statin therapy during hospitalization was independently associated with decreased mortality at 3 months (odds ratio [OR], .35; 95% confidence interval [CI], .18-.67), at 6 months (OR, .42; 95% CI, .25-.73) and at 1 year (OR, .47; 95% CI, .29-.76). Statin use during hospitalization could decrease mortality of acute ischemic stroke patients with very low admission LDL-C. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Aug 2015 · Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association
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    ABSTRACT: Recent studies have convincingly documented that hypogonadism is a component of various hereditary disorders and is often recognized as an important clinical feature in combination with various neurological symptoms, yet, the causative genes in a few related families are still unknown. High-throughput sequencing has become an efficient method to identify causative genes in related complex hereditary disorders. In this study, we performed exome sequencing in a family presenting hypergonadotropic hypogonadism with neurological presentations of mental retardation, epilepsy, ataxia, and leukodystrophy. After bioinformatic analysis and Sanger sequencing validation, we identified compound heterozygous mutations: c.482G>A (p.R161Q) and c.609G>A (p.W203X) in MMACHC gene in this pedigree. MMACHC was previously confirmed to be responsible for methylmalonic aciduria (MMA) combined with homocystinuria, cblC type (cblC disease), a hereditary vitamin B12 metabolic disorder. Biochemical and gas chromatography-mass spectrometry (GC-MS) examinations in this pedigree further supported the cblC disease diagnosis. These results indicated that hypergonadotropic hypogonadism may be a novel clinical manifestation of cblC disease, but more reports on additional patients are needed to support this hypothesis. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Aug 2015 · Gene
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    ABSTRACT: Associations between hyperhomocysteinemia and prognosis of stroke were seldom explored and always indefinite. We therefore performed a study to elucidate the relationship between homocysteine levels and stroke prognosis. Between 2008 and 2013, baseline data and blood samples of acute ischemic stroke patients were collected from the Henan Province Stroke Registry. Using a prospective cohort, scheduled follow-up, and multivariable logistic regression analysis, associations among the blood homocysteine level and acute neurological impairment and outcomes, stroke recurrence, and all-cause death were investigated. Relevant cutoff homocysteine levels were determined using the area under the receiver operating characteristics curve. Of 1,460 patients, 1,342 completed the 12-month follow-up. We observed higher homocysteine levels in males, those with an advanced age, concomitant hyperlipidemia, a smoking habit, and excessive alcohol consumption. The homocysteine level was an independent risk factor for severe neurological impairment (adjusted relative risk [RR]: 1.021, 95% confidence interval [CI]: 1.004-1.037), a poor functional outcome (adjusted RR with 95% CI: 3-month, 1.029, 1.018-1.039; 6-month, 1.029, 1.018-1.039; and 12-month, 1.038, 1.027-1.049), and stroke recurrence in the large artery atherosclerosis subtype (adjusted RR: 1.025, 1.006-1.045). The optimal cutoff for severe neurological impairment was 17.64 µmol/L, and the cutoffs for poor functional outcomes were 17.28 µmol/L, 17.28 µmol/L, and 14.78 µmol/L at 3, 6, and 12 months, respectively. We found an elevated homocysteine level independently predicted severe neurological impairment, a poor functional outcome, and stroke recurrence in the large artery atherosclerosis stroke subtype. The relevant cutoff homocysteine levels also provide a reference for future clinical work.
    No preview · Article · Aug 2015 · Current neurovascular research
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    Full-text · Dataset · Jul 2015

  • No preview · Article · Jul 2015 · Brain
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    ABSTRACT: Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease (CMT), is a genetically heterogeneous disorder that affects both sensory and motor peripheral nerves. HMSN is characterized by distal and symmetric muscle atrophy in the lower limbs and hands, foot abnormalities, and distal sensory loss. It is associated with more than 50 causative genes or loci; however, the genetic cause remains undetermined in almost 50% of HMSN cases.
    No preview · Article · Jul 2015 · Neurology
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    ABSTRACT: Little is known about the effects of induced pluripotent stem cell (iPSC) treatment on acute cerebral inflammation and injuries after intracerebral hemorrhage (ICH), though they have shown promising therapeutic potentials in ischemic stoke. An ICH model was established by stereotactic injection of collagenase VII into the left striatum of male Sprague-Dawley (SD) rats. Six hours later, ICH rats were randomly divided into two groups and received intracerebrally 10 μl of PBS with or without 1×106 of iPSCs. Subsequently, neural function of all ICH rats was assessed at days 1, 3, 7, 14, 28 and 42 after ICH. Inflammatory cells, cytokines and neural apoptosis in the rats' perihematomal regions, and brain water content were determined on day 2 or 3 post ICH. iPSC differentiation was determined on day 28 post ICH. Nissl+ cells and glial fibrillary acidic protein (GFAP)+ cells in the perihematoma and the survival rates of rats in two groups were determined on post-ICH day 42. Compared with control animals, iPSCs treatment not only improved neurological function and survival rate, but also resulted in fewer intracephalic infiltrations of neutrophils and microglia, along with decreased interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α), and increased IL-10 in the perihematomal tissues of ICH rats. Furthermore, brain oedema formation, apoptosis, injured neurons and glial scar formation were decreased in iPSCs-transplanted rats. Our findings indicate that iPSCs transplantation attenuate cerebral inflammatory reactions and neural injuries after ICH, and suggests that multiple mechanisms including inflammation modulation, neuroprotection and functional recovery might be involved simultaneously in the therapeutic benefit of iPSC treatment against hemorrhagic stroke.
    Preview · Article · Jun 2015 · PLoS ONE
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    ABSTRACT: Calcium intake has been associated with stroke risk in a prior meta-analysis, however, newly published results are inconsistent. Dairy food benefits on stroke incidence may involve a calciumrelated mechanism. We have therefore updated this meta-analysis with particular references to any possibility of a calcium-mediated dairy food risk reduction of stroke risk. We searched multiple databases and bibliographies for prospective cohort studies. Reports with multivariate-adjusted relative risk (RR) and corresponding 95% confidence intervals (CI) for the association of calcium intake with stroke incidence were considered. Ten studies with 371,495 participants and 10,408 stroke events were analyzed. The pooled analysis showed no statistically significant association of the risk of total stroke (RR=0.96; 95% CI: 0.89-1.04) and stroke subtypes with the highest and lowest calcium intake quantiles. Nevertheless, high dairy calcium intake was significantly associated with an approximately 24% reduction of stroke risk. (RR=0.76; 95% CI: 0.66-0.86). Furthermore, a long-term follow-up (>=14 years) was helpful to reduce the risk of stroke (RR=0.67; 95% CI: 0.51-0.88). Additionally, a non-linear dose-response relationship was predicted between calcium intake and stroke risk. Dairy calcium intake is inversely associated with stroke incidence. There is a non-linear dose-response relationship between calcium intake and stroke risk. However, when the follow-up time is long enough, the inverse relationship is independent of dose. Additional large cohort studies are required to illustrate this relationship in detail.
    Full-text · Article · Jun 2015 · Asia Pacific Journal of Clinical Nutrition
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    ABSTRACT: We used a combined approach of whole-exome sequencing and candidate mutation validation to identify the disease-causing gene in a hereditary spastic paraplegia (HSP) patient with lower motor neuron involvement, mild cerebellar signs and dysgenesis of the corpus callosum. HSP is a clinically and genetically heterogeneous neurodegenerative disorder characterized by degeneration of the corticospinal tract motor neurons and resulting in progressive lower limb spasticity, often with a complicated phenotype. We identified novel compound heterozygous mutations in the SPG11 gene in this patient as follows: a mutation in exon 32, c.6194C>G transition (p.S2056X) and a novel c.5121+1C>T splicing mutation. Our finding suggests that these novel compound heterozygous mutations in SPG11 are associated with HSP and lower motor neuron involvement, mild cerebellar signs and dysgenesis of the corpus callosum. This study also demonstrates that exome sequencing is an efficient and rapid diagnostic tool for identifying the causes of some complex and genetically heterogeneous neurodegenerative diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · May 2015 · Journal of Clinical Neuroscience
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    ABSTRACT: Stem cell to be a new intervention for treating intracerebral hemorrhage (ICH) might benefit humans. Therefore, we collected animal studies to find the effect of this innovative treatment. In July 2014, we searched Medline (from 1950), Embase (from 1980), China Biology Medicine disk (from 1978) for studies on stem cells used for treating experimental ICH in animal models that reported neurobehavioral and structural outcome. We evaluated the quality of these studies and used a weighted mean difference random affects model for the meta-analysis. We have collected 30 studies from 650 publications identified through systematic review describing the effects of 5 different type of stem cells on 12 different neurobehavioral scales with 1101 rodents or monkeys. Although there is lack of uniformity of the evaluation methods, these researches showed consistent improvements both in neurobehavioral function and structural outcomes. Besides, the quality of these studies needs to be raised. In conclusion, stem cells hold extensive potential in treating ICH, which should be further evaluated with more evidence-based, high-quality animal studies.
    No preview · Article · May 2015 · Neurological Sciences
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    ABSTRACT: Background The association between atherogenic dyslipidemia and stroke recurrence remains unclear, and may be influenced by different subtypes of ischemic stroke.AimsWe aimed to investigate whether atherogenic dyslipidemia contributed to stroke recurrence in ischemic stroke patients and in those with certain subtypes of ischemic stroke.Methods We conducted a prospective hospital-based study enrolling patients with acute ischemic stroke. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol <40 mg/dl and triglycerides ≥200 mg/dl. Ischemic stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The patients were followed up at 3, 6, 12 and 24 months after stroke onset. The association between atherogenic dyslipidemia and stroke recurrence was analyzed by using multivariable Cox regression model.ResultsIn the 510 ischemic stroke patients, 64 patients (12·5%) had atherogenic dyslipidemia, and 66 patients (12·9%) experienced stroke recurrence events within 24 months. Kaplan–Meier analysis revealed that stroke recurrence rate was significantly higher in patients with atherogenic dyslipidemia than those without in all the stroke patients (20·3% vs. 11·9%; P = 0·048), and more evident in those of large-artery atherosclerosis subtype (31·0% vs. 14·1%; P = 0·014), but not in the other subtypes. Multivariable Cox regression analysis revealed that atherogenic dyslipidemia was associated with higher stroke recurrence risk among stroke patients of large-artery atherosclerosis subtype (hazard ratio, 2·79; 95% confidence interval, 1·24–6·28), but not significant in all the stroke patients (hazard ratio, 1·69; 95% confidence interval, 0·85–3·37).Conclusions Atherogenic dyslipidemia is associated with higher risk of stroke recurrence in ischemic stroke patients. Such association might be more pronounced in large-artery atherosclerosis subtype and needs further investigation to establish such relationship.
    Full-text · Article · Apr 2015 · International Journal of Stroke
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    ABSTRACT: Progressive pseudorheumatoid dysplasia (PPD) is an extremely rare autosomal recessive genetic disease caused by mutation of the Wnt1-inducible signaling pathway protein 3 (WISP3) gene. Here, we characterize the clinical manifestations and features of PPD and screen for WISP3 mutations. We performed genetic testing for PPD in a Chinese family, after investigating the clinical particulars and family history, in addition to 200 healthy individuals, who served as the controls for this study. All 5 exons and the exon-intron boundaries of the WISP3 gene were amplified by polymerase chain reaction (PCR) and sequenced directly. We identified a missense mutation (c.667T>G, p.C223G) in the maternal allele and a nonsense mutation (c.756C>A, p.C252X) in the paternal allele in the two affected individuals. To our knowledge, the mutation c.756C>A has not been reported previously. In these patients, there was a specific period when their condition markedly improved after having been very serious. Moreover, severe compression of lumbar spinal cord led to conspicuous spinal disorders in the proband. Our study suggests that novel C223G and C252X mutations in exon 4 of the WISP3 gene are responsible for PPD in Chinese patients. Furthermore, we report certain unique phenotypic characteristics in our patients. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Mar 2015 · Gene
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    ABSTRACT: Cerebral hemorrhage (ICH) is a serious stroke subtype, currently lacking effective treatment. Recent research has shown that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) play a key role in the immune response of ischemic stroke. However, Tregs in human hemorrhagic stroke are poorly investigated. In this study, a total of 90 ICH patients and 60 healthy controls were recruited. The frequency of circulating Tregs, plasma levels of TGF-β and IL-10, and the severity of neural dysfunction in ICH patients were investigated at different time points post ICH. We found that the peripheral frequency of Tregs in ICH patients was significantly increased, accompanied by boosted activated T cells. Importantly, the elevation of circulating Tregs in patients with severe dysfunction was much higher than that in less-severe patients, suggesting that disease severity affects circulating Tregs to exert regulatory function. Furthermore, both TGF-β and IL-10 that are related to the function of Tregs, were also increased in the peripheral blood of ICH patients. Our results demonstrate that Tregs-mediated immune imbalance might affect the development and severity of ICH, and suggest that Tregs may be used as tools and targets of cellular immunotherapy to effectively treat acute hemorrhagic stroke. Copyright © 2015. Published by Elsevier Ireland Ltd.
    No preview · Article · Feb 2015 · Neuroscience Letters

  • No preview · Article · Feb 2015 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics