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1.
Neuroradiology ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31482191

RESUMO

PURPOSE: This study aimed to evaluate prognostic parameters associated with favorable clinical prognosis and assess the feasibility and safety of three different treatment strategies in patients with acute intracranial vertebrobasilar artery occlusion (VBAO). METHODS: A total of 159 patients with acute VBAO at 3 stroke centers between September 2015 and October 2018 were retrospectively analyzed. Eighty-nine patients underwent mechanical thrombectomy (MT) alone, 43 underwent MT with additional rescue angioplasty, and 27 underwent primary balloon angioplasty (without or with stenting). In patients treated with primary or rescue balloon angioplasty (without or with stenting), a low-dose intra-arterial tirofiban injection was used. The reperfusion status was assessed after the procedure, and the functional outcome was assessed at 90-day follow-up. The baseline characteristics and 90-day prognosis of three different treatment subgroups were comparatively analyzed. RESULTS: Overall, successful reperfusion and a favorable outcome were achieved in 96.86% (154/159) and 46.54% (74/159) patients, respectively. The onset to puncture time (461.96 min vs 603.59 min, P = 0.000), procedure time (64.12 min vs 70.47 min, P = 0.007), and onset to reperfusion time (526.08 min vs 674.47 min, P = 0.000) were significantly shorter in patients with favorable outcomes than in those with poor outcomes. Among different endovascular treatment subgroups, no significant differences were found in successful reperfusion and 90-day outcome. Low-dose tirofiban did not increase the risk of symptomatic intracranial hemorrhage and the 90-day mortality in patients with acute VBAO. CONCLUSION: Individualized endovascular treatment strategy for selected patients with acute VBAO could achieve satisfactory reperfusion rate and favorable prognosis.

3.
Stroke ; : STROKEAHA119025732, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31409268

RESUMO

Background and Purpose- In patients with symptomatic intracranial atherosclerotic stenosis, identifying the underlying stroke mechanisms may inform secondary prevention. We aimed to propose reproducible classification criteria for stroke mechanisms based on routine neuroimaging in symptomatic intracranial atherosclerotic stenosis and explore their clinical implications. Methods- We recruited patients with acute ischemic stroke attributed to 50% to 99% intracranial atherosclerotic stenosis in anterior circulation from 2 centers. Two investigators independently classified probable stroke mechanisms as parent artery atherosclerosis occluding penetrating artery, artery-to-artery embolism, hypoperfusion, and mixed mechanisms, with prespecified criteria based on infarct topography and magnetic resonance/computed tomography angiography. These stroke mechanisms were correlated with features of the patients at baseline and recurrent ischemic stroke in the same territory or relevant transient ischemic attack within 1 year. Results- Among 153 patients recruited, the most common stroke mechanisms were isolated hypoperfusion (35.3%) and mixed mechanism of artery-to-artery embolism and hypoperfusion (37.3%) that was associated with higher incidence of dyslipidemia (P=0.045) and hypertension (P=0.033) than patients with other stroke mechanisms. The proposed criteria showed substantial to excellent intrarater and interrater reproducibilities (κ, 0.791-0.908). Overall, 31 patients received interventional treatment of the diseased intracranial artery; 122 received medical treatment, among whom a mixed mechanism of artery-to-artery embolism and hypoperfusion at baseline was associated with higher risk of ischemic stroke in the same territory within 1 year (24.4% versus 7.8%; hazard ratio, 3.40; 95% CI, 1.25-9.20; log-rank P=0.010) than other mechanisms combined. Conclusions- Artery-to-artery embolism and hypoperfusion commonly coexist in ischemic stroke attributed to intracranial atherosclerotic stenosis, which may be associated with higher risk of stroke relapse.

5.
Neuromuscul Disord ; 29(7): 549-553, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31255525

RESUMO

Limb-girdle myasthenia with tubular aggregates, a subtype of congenital myasthenic syndrome, is an extremely rare autosomal recessive genetic disease characterized by prominent limb-girdle weakness and good response to acetylcholinesterase inhibitor therapy. Herein, we reported two novel mutations of GFPT1 gene in a Chinese pedigree. Two siblings presented with fatigue, weakness of limb-girdle and decrement of the muscle action potential with repetitive nerve stimulation. Thus, myasthenia gravis was initially suspected, but anti-AChR antibodies were negative. Two novel missense mutations (p.Lys154Asn and p.Asn363Ser) in GFPT1 were identified through genetic testing conducted on 167 well-established genes associated with muscular diseases by targeted high throughput sequencing. Both mutations have not been recorded in the dsSNP database, Exome Aggregation Consortium database and 1000 Genomes Project database. The mutation sites were co-segregated with the phenotype and conserved between the different species. The mutations were not found in the 200 unrelated normal controls. Muscle biopsies revealed tubular aggregates, in accordance with previous reports with GFPT1 mutations. Subsequently, dramatic improvement in strength occurred following anti-cholinesterase therapy. Our study will be helpful for the diagnosis and treatment for Limb-girdle myasthenia with tubular aggregates.

6.
Transl Stroke Res ; 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31325153

RESUMO

Cell death is a hallmark of secondary brain injury following intracerebral hemorrhage (ICH). The E3 ligase CHIP has been reported to play a key role in mediating necroptosis-an important mechanism of cell death after ICH. However, there is currently no evidence supporting a function of CHIP in ICH. In the present study, we aimed to determine whether CHIP plays an essential role in brain injury after ICH. Our findings indicated that CHIP expression was increased in the peri-hematomal area in rat models of ICH. The AAV/BBB viral platform enables non-invasive, widespread, and long-lasting global neural expression of target genes. Treatment with AAV/BBB-CHIP ameliorated brain injury and inhibited neuronal necroptosis and inflammation in wild type (WT) rats following ICH. Furthermore, rats with CHIP deficiency experienced severe brain injury and increased levels of neuronal necroptosis and inflammation relative to their WT counterparts. However, treatment with AAV/BBB-CHIP attenuated the effects of CHIP deficiency after ICH. Collectively, our results demonstrate that CHIP inhibits necroptosis and pathological inflammation following ICH, and that overexpression of CHIP may represent a therapeutic intervention for ICH. Moreover, the AAV/BBB viral platform may provide a novel avenue for the treatment of brain injury.

7.
BMJ ; 365: l2211, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171523

RESUMO

OBJECTIVE: To test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis. DESIGN: Open label, blinded endpoint, randomised controlled phase II trial. SETTING: Prospective studies conducted at 26 centres in China, August 2015 to March 2017. PARTICIPANTS: 675 patients with acute minor stroke or transient ischaemic attack. INTERVENTION: Ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset. MAIN OUTCOME MEASURES: Primary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year. RESULTS: At 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P<0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42). CONCLUSION: Patients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations. TRIAL REGISTRATION: Clinicaltrials.gov NCT02506140.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ticagrelor/uso terapêutico , Adulto , Idoso , Plaquetas/efeitos dos fármacos , China , Quimioterapia Combinada , Feminino , Humanos , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/fisiologia , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-31196701

RESUMO

INTRODUCTION: This study reports a novel mutation site of the phospholipase A2 group VI (PLA2G6) gene, and analyzes the information of 67 previously published cases to elucidate PLA2G6 phenotype-genotype variations. METHODS: We collected clinical data and examined gene mutation sites from one Chinese patient with adult-onset ataxia and her family. Next-generation sequencing (NGS) and Sanger sequencing were used to verify possible mutations. PolyPhen-2, SIFT, and MutationTaster were used to predict their pathogenicity. For analyzing the distribution frequency of the mutation, 597 healthy controls were recruited. We also analyzed the clinical and genetic information of 67 cases from 23 studies in Pubmed database. RESULTS: A novel compound heterozygous mutation of the PLA2G6 gene, c.1648delC and c.991G > T, was found in the Chinese patient, and classified as pathogenic. The c.1648delC variation was absent in ExAC, 1000G, dbSNP databases and the 597 healthy controls. Of the 67 cases, 29 presented ataxia. The signs of cerebellar atrophy appeared in the MRIs of most patients, while signs of iron accumulation were absent in older-aged patients with a compound heterozygous mutation. Thirty-eight patients showed no ataxia. A negative or mild extrapyramidal symptom accompanied by a low age, a homogenous mutation, while moderate or severe extrapyramidal symptoms were associated with an old age and a compound heterozygous mutation. CONCLUSION: A novel compound heterozygous mutation of the PLA2G6 gene, c.1648delC and c.991G > T, is associated with adult onset ataxia. Phenotype-genotype variations of PLA2G6 are predicted to be caused by the loss of protein or enzyme activity of phospholipase-2.

9.
J Neurol ; 266(7): 1796-1800, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31041581

RESUMO

BACKGROUND: Recently, rs2421947 in DNM3 (dynamin 3) was reported as a genetic modifier of age at onset (AAO) of LRRK2 G2019S-related Parkinson's disease (PD) in a genome-wide association study in Arab-Berber population. Rs356219 in SNCA (α-synuclein) was also reported to regulate the AAO of LRRK2-related PD in European populations, and GAK (Cyclin G-associated kinase) rs1524282 was reported to be associated with an increased PD risk with an interaction with SNCA rs356219. G2019S variant is rare in Asian populations, whereas two other Asian-specific LRRK2 variants, G2385R and R1628P, are more frequent with a twofold increased risk of PD. METHODS: In this study, we investigated whether rs2421947, rs356219 and rs1524282 modified AAO in LRRK2-related PD patients in Han Chinese population. We screened LRRK2 G2385R and R1628P variants in 732 PD patients and 1992 healthy controls, and genotyped DNM3 rs2421947, SNCA rs356219 and GAK rs1524282 among the LRRK2 carriers. RESULTS: The SNCA rs356219-G allele was found to increase the risk of PD in LRRK2 carriers (OR 1.50, 95%CI 1.08-2.01, P = 0.016), and the AAO of AG + GG genotypes was 4 years earlier than AA genotype (P = 0.006). Nonetheless, no similar association was found in DNM3 rs2421947 and GAK rs1524282. CONCLUSIONS: Our results show that SNCA but not DNM3 or GAK is associated with AAO of LRRK2-PD patients in Chinese population.

10.
J Stroke Cerebrovasc Dis ; 28(7): 1860-1865, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31064695

RESUMO

BACKGROUND AND PURPOSE: Previous studies have shown that common variants within CYP3A4 and CYP3A5 are associated with statin pharmacokinetics and the risk of cardiovascular disease. However, the association of variants in CYP3A4 and CYP3A5 with the prognosis of ischemic stroke remains undetermined. Therefore, we investigated this herein. METHODS: Four hundred thirty-three consecutive patients with acute ischemic stroke were recruited. The outcome at the 1-year follow-up was assessed using the modified Rankin Scale (mRS). Two variants, CYP3A4*1G and CYP3A5*3, were genotyped by the improved Multiple Ligase Detection Reaction platform. RESULTS: Binary logistic regression analysis showed that the CYP3A4*1G/*1G homozygote was associated with poor outcome at 1 year (mRS score ≥2) after adjustment for conventional factors in the additive model (odds ratio [OR] = 2.92; 95% confidence interval, 1.07-7.98; P = .037) and recessive model (OR = 3.37; 95% confidence interval, 1.26-9.04; P = .016). Subgroup analysis indicated that the CYP3A4*1G/*1G homozygote was associated with poor prognosis at 1 year among patients with stable high-intensity atorvastatin therapy (40-80 mg/d) after adjustment for conventional factors in the additive model (OR = 8.16; 95% confidence interval, 1.50-44.44; P = .015) and recessive model (OR = 9.06; 95% confidence interval, 1.72-47.64; P = .009). No significant association was identified between CYP3A5*3 and the 1-year outcome of patients with ischemic stroke. CONCLUSIONS: Our study findings suggest that the CYP3A4*1G/CYP3A4*1G genotype may be associated with poor prognosis at 1 year after acute ischemic stroke in the Han Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Isquemia Encefálica/genética , Citocromo P-450 CYP3A/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Idoso , Atorvastatina/administração & dosagem , Atorvastatina/farmacocinética , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/enzimologia , Isquemia Encefálica/etnologia , China/epidemiologia , Citocromo P-450 CYP3A/metabolismo , Avaliação da Deficiência , Feminino , Frequência do Gene , Homozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Prevenção Secundária/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/enzimologia , Acidente Vascular Cerebral/etnologia , Fatores de Tempo , Resultado do Tratamento
11.
Exp Cell Res ; 380(1): 90-99, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981669

RESUMO

Simple and pure synthetic coating substrates are needed to overcome the disadvantages of traditional coating products like animal derived Matrigel in stem cell research. Since integrins are of great importance in cell adhesion and cell-ECM communication, in this study, a commercially available integrin array established by synthetic integrin binding peptides is used to screen coating substrates for iPSCs and NEPs. The results showed that binding peptides of integrin α5ß1, αVß1, αMß2 and αIIbß3 supported cell adhesion of iPSCs, while α5ß1, αVß1 and αIIbß3 binding peptides supported NEPs adhesion. Additionally, integrin α5ß1 binding peptide was revealed to support rapid expansion of iPSCs and iPSC-derived NEPs, as well as the process of NEPs generation, with equal efficiency as Matrigel. In this work, we demonstrated that by supporting stem cell growth in an integrin dependent manner, the integrin array and coating system has the potential to develop more precise and efficient systems in neurological disease modeling.

12.
Ann Neurol ; 85(5): 752-764, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30840312

RESUMO

OBJECTIVE: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model. METHODS: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressurepoststenotic /pressureprestenotic ) and translesional wall shear stress ratio (WSSR = WSSstenotic - throat /WSSprestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year. RESULTS: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004). INTERPRETATION: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764.

13.
Naunyn Schmiedebergs Arch Pharmacol ; 392(7): 879-886, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30879099

RESUMO

10ß,17ß-dihydroxyestra-1,4-dien-3-one (DHED) which is a brain-selective prodrug of 17ß-estradiol has been reported to improve the cognitive function in Alzheimer's disease (AD) mice model. However, little is known about the potential mechanism for cognitive improvement. In the present study, we used AD mice to investigate the effects and mechanisms of DHED treatment. Female Tg2576 transgenic AD mice were ovariectomized and then treated by implanting Alzet osmotic minipumps containing DHED or vehicle subcutaneously for 8 weeks. Consistent with previous report, DHED treatment ameliorated cognitive function of AD mice with decreasing Aß levels in the hippocampus. Besides, we also found DHED treatment could reduce oxidative and inflammatory stress and the level of p-tau. The mechanisms underlying the cognitive function improvement may be linked with estrogen receptor (ER)-klf5-NF-κB pathway, demonstrated by decreased expression of klf5 and the secretion of inflammatory cytokines. However, the effects of DHED treatment could be reversed when ERα was inhibited by ICI182780. Taken together, our findings uncovered a new mechanism for DHED to improve the cognitive function of AD mice and may provide a viable therapy to treat AD.

14.
Neurol Sci ; 40(6): 1255-1265, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30891637

RESUMO

Myotonic dystrophy type 1 (DM1) is caused by CTG nucleotide repeat expansions in the 3'-untranslated region (3'-UTR) of the dystrophia myotonica protein kinase (DMPK) gene. The expanded CTG repeats encode toxic CUG RNAs that cause disease, largely through RNA gain-of-function. DM1 is a fatal disease characterized by progressive muscle wasting, which has no cure. Regenerative medicine has emerged as a promising therapeutic modality for DM1, especially with the advancement of induced pluripotent stem (iPS) cell technology and therapeutic genome editing. However, there is an unmet need to identify in vitro outcome measures to demonstrate the therapeutic effects prior to in vivo clinical trials. In this study, we examined the muscle regeneration (myotube formation) in normal and DM1 myoblasts in vitro to establish outcome measures for therapeutic monitoring. We found normal proliferation of DM1 myoblasts, but abnormal nuclear aggregation during the early stage myotube formation, as well as myotube degeneration during the late stage of myotube formation. We concluded that early abnormal nuclear aggregation and late myotube degeneration offer easy and sensitive outcome measures to monitor therapeutic effects in vitro.

15.
Kaohsiung J Med Sci ; 35(2): 111-115, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30848025

RESUMO

Remifentanil was a µ-agonist, with a rapid onset, a powerful narcotic analgesic activity and a fast nonspecific esterases hydrolyzation and theoretically an ideal opioid for percutaneous dilatational tracheostomy (PDT). The present study discussed use of remifentanil in critically ill patients undergoing PDT. Ninety-nine patients were randomly assigned to the propofol/remifentanil group (PR group, n = 49) or the propofol group (P group, n = 50). Two patients (one in P group and one in PR group) were excluded and transferred to surgical way of tracheostomy because of uncontrolled bleeding. The primary outcomes were critical care pain observation (CPOT) scores during PDT; hemodynamic response and side effects, such as bleeding and muscle rigidity (MR). CPOT scores in P group were significantly higher than in PR group during incision and dilation stages (P < 0.05 and P < 0.01). Systolic blood pressure had a significant drop after a bolus of remifentanil in PR group compared with patients in P group (P < 0.056). The incidence of MR was significantly higher in PR group than in P group (P < 0.05). Recovery time in PR group was significantly shorter than in P group (P < 0.05). The occurrence of tachycardia, bleeding, vomiting, and nausea had no statistically differences in both groups. Patients in PR group were undergoing shorter recovery time and better experience of pain in PDT compared with patients in P group, but MR seemed to be higher in PR group. Remifentanil seemed to be a safe and effective opioid used in critically ill patients undergoing PDT.


Assuntos
Estado Terminal , Remifentanil/uso terapêutico , Traqueostomia , Adulto , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Dor/etiologia , Dor/fisiopatologia , Propofol/administração & dosagem , Propofol/efeitos adversos , Propofol/uso terapêutico , Estudos Prospectivos , Remifentanil/administração & dosagem , Remifentanil/efeitos adversos , Traqueostomia/efeitos adversos , Escala Visual Analógica
16.
Sci Rep ; 9(1): 1173, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718523

RESUMO

To determine whether positive or negative DWI TIA patients could get benefits from HST we conducted a cohort study which data from the prospective, hospital-based, TIA database of the First Affiliated Hospital of Zhengzhou University. The end-point was 7-day and 90-day incidence of stroke. Cox proportional hazard regression models were used to analyze the association between end-points and high-intensity statin treatment in TIA patients with positive and negative DWI. A total of 987 eligible TIA patients were analyzed. The stroke risk of patients with positive DWI was about a four-fold increase compared to that with negative DWI (7 d, 10.9 versus 1.8, p < 0.001 and 90 d, 18.3 versus 4.2, p < 0.001). After adjusting confounding factors, HST significantly improved both 7-day (HR 0.331, 95% CI 0.165-0.663; p = 0.002) and 90-day (HR 0.480, 95% CI 0.288-0.799; p = 0.005) outcomes in positive DWI patients. As a conclusion, high-intensity statin use reduces the 90 days' recurrent stroke risk in DWI-positive TIA patients but not in DWI-negative patients.

17.
PLoS One ; 14(2): e0211833, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30730945

RESUMO

The aim of this study was to evaluate the association of dynamic neutrophil-to-lymphocyte ratio (NLR) with 3-month functional outcomes in patients with sICH. We retrospectively identified 213 consecutive patients with sICH hospitalized in The First Affiliated Hospital of Zhengzhou University from January 2017 to May 2018. Patients were divided into functional independence (FI) or unfavorable prognosis (UP) groups based on 3-month outcomes. Admission leukocyte counts within 24 hours of symptom onset were obtained, and the recorded fraction, of which the numerator is neutrophil and the denominator is lymphocyte, as NLR0. Determined NLR1, NLR3, NLR7, and NLR14 were recorded on day 1 (n = 77), day 3 (n = 126), day 7 (n = 123), and day 14 (n = 105), respectively. The relationships between dynamic NLR or leukocyte counts and clinical features were evaluated using Spearman's or Kendall's correlation analysis. Logistic regression analyses were used to identify the risk factors for unfavorable 3-month prognosis. The patients' dynamic NLR was positively associated with the National Institutes of Health Stroke Scale, ICH score, and hematoma volume at admission, while inversely correlated to the onset GCS score and FI at 3-month follow-up. Furthermore, higher NLR or lower absolute lymphocyte count obtained at admission was independently risk factor for UP at 3 months (adjusted odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.003, 1.12; OR: 0.41, 95% CI: 0.18, 0.94, respectively). In conclusion, higher NLR and lower lymphocyte counts at early stages were predictive of 3-month unfavorable outcomes in sICH patients.

18.
Stem Cell Res ; 35: 101395, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30776674

RESUMO

Several SLC20A2 mutations have been implicated as potential causes of Fahr's disease, a subtype of primary familial brain calcification (PFBC), but very few patient-derived induced pluripotent stem cell (iPSC) models have been established. We have identified a novel SLC20A2 mutation in a family with Fahr's disease. We subsequently obtained dermal fibroblasts from a patient in this family. These fibroblasts were successfully transformed into iPSCs by employing episomal plasmids expressing OCT3/4, SOX2, KLF4, LIN28, and L-MYC. Our approach offers a resource and a platform for further research into the mechanism of Fahr's disease and could facilitate development and screening of pharmaceutical and gene therapies.


Assuntos
Doenças dos Gânglios da Base , Calcinose , Técnicas de Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Mutação , Doenças Neurodegenerativas , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III , Adolescente , Doenças dos Gânglios da Base/genética , Doenças dos Gânglios da Base/metabolismo , Doenças dos Gânglios da Base/patologia , Calcinose/genética , Calcinose/metabolismo , Calcinose/patologia , Linhagem Celular , Derme/metabolismo , Derme/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Masculino , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/metabolismo
19.
Stem Cell Res ; 34: 101366, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616143

RESUMO

MEOX2 mutation has been reported as a potential cause of familial Alzheimer's disease. Recently, a novel MEOX2 mutation was identified in a family with Alzheimer's disease. The dermal fibroblasts of the patient were obtained and successfully transformed into induced pluripotent stem cells (iPSCs), employing episomal plasmids expressing OCT3/4, SOX2, KLF4, LIN28, and L-MYC. Our model may offer a good platform for further research on the pathomechanism, drug testing, and gene therapy of this disease.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Técnicas de Cultura de Células/métodos , Proteínas de Homeodomínio/genética , Células-Tronco Pluripotentes Induzidas/patologia , Mutação/genética , Idoso , Animais , Sequência de Bases , Linhagem Celular , Humanos , Masculino , Camundongos SCID
20.
Neurobiol Aging ; 75: 38-41, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30530185

RESUMO

Previously we identified the p.Thr61Ile mutation in coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) in a Chinese family with autosomal dominant Parkinson's disease. But the mechanism is still unclear. In this study, we explored the effects of CHCHD2 p.Thr61Ile mutation in cells and its association with coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10). We found that overexpression of Parkinson's disease-associated T61I mutant CHCHD2 did not produce mitochondrial dysfunction. Rather, its protective effect from stress was abrogated. And, the level of the CHCHD2 protein and mRNA in patient fibroblasts was not significantly different from control. In addition, CHCHD2 T61I mutation caused increased interaction with CHCHD10 and reduced CHCHD10 level. The mitochondrial ultrastructural alterations in CHCHD2 T61I mutant patient fibroblasts are similar to that of CHCHD10 mutations. We therefore propose that CHCHD10 is involved in the development of Parkinson's disease caused by CHCHD2 loss-of-function mutation p.T61I.


Assuntos
Proteínas Mitocondriais/genética , Mutação/genética , Doença de Parkinson/genética , Fatores de Transcrição/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Associação Genética , Humanos , Mitocôndrias/metabolismo
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