RESUMO
BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION: Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Estudos de Coortes , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Colesterol , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
PURPOSE: Pellino3, an ubiquitin E3 ligase, prevents the formation of the death-induced signaling complex in response to TNF-α by targeting receptor-interacting protein kinase 1 (RIPK1), and bioinformatics analysis predicted an interaction between Pellino3 and caspofungin, a common antifungal drug used in clinics. This study aimed to explore the effect of caspofungin on brain injury in ischemic stroke and the underlying mechanisms. METHODS: Ischemic stroke injury was induced in Sprague Dawley rats by occlusion of the middle cerebral artery (MCA) for 2 h, followed by 24 h reperfusion. PC12 cells were deprived of both oxygen and glucose for 8 h and then were cultured for 24 h with oxygen and glucose to mimic an ischemic stroke in vitro. RESULTS: Animal experiments showed brain injury (increase in neurological deficit score and infarct volume) concomitant with a downregulation of Pellino3, a decreased ubiquitination of RIPK1, and an up-regulation of necroptosis-associated proteins [RIPK1, RIPK3, mixed lineage kinase domain-like protein (MLKL), p-RIPK1, p-RIPK3, and p-MLKL]. Administration of caspofungin (6 mg/kg, i.m.) at 1 h and 6 h after ischemia significantly improved neurological function, reduced infarct volume, up-regulated Pellino3 levels, increased RIPK1 ubiquitination, and down-regulated protein levels of RIPK1, p-RIPK1, p-RIPK3, and p-MLKL. PC12 cells deprived of oxygen/glucose developed signs of cellular injury (LDH release and necroptosis) concomitant with downregulation of Pellino3, decreased ubiquitination of RIPK1, and elevated necroptosis-associated proteins. These changes were reversed by overexpression of Pellino3. CONCLUSION: We conclude that Pellino3 has an important role in counteracting necroptosis via ubiquitination of RIPK1 and caspofungin can suppress the brain cell necroptosis in ischemic stroke through upregulation of Pellino3.
Assuntos
Lesões Encefálicas , AVC Isquêmico , Ratos , Animais , Regulação para Cima , Caspofungina/farmacologia , AVC Isquêmico/tratamento farmacológico , Ratos Sprague-Dawley , Necroptose , Encéfalo , Infarto , Oxigênio , Glucose/farmacologia , ApoptoseRESUMO
OBJECTIVE: To explore the correlation between cerebrovascular hemodynamic index (CVHI)accumulative score and subclinical arteriosclerosis indicators.â© Methods: A total of 27 184 cases were collected from the Health Management Center, the Third Xiangya Hospital, Central South University. Linear regression analysis was carried out to confirm the correlations between CVHI accumulative score and the modified Framingham stroke profile (FSP), as well as between CVHI accumulative score and cerebrovascular diseases (ICVD) scale. The correlation between CVHI accumulative score and brachial-ankle pulse wave velocity (baPWV), carotid plaque orcarotid intima-media thickness (CIMT) was analyzed by multifactor logistic regression model in 11 580 cases. Moreover, the correlation between CVHI accumulative score and microalbuminuria or serum cystatin C was performed by multifactor logistic regression model in 9 860 cases.â© Results: In this study, the people whose CVHI accumulative score was less than 75 accounted for 12.98%. The CVHI accumulative score was negatively related with the modified FSP score (r=-0.484, P<0.01) or ICVD score (r=-0.455, P<0.01). The multifactor logistic regression model found that the baPWV, carotid plaque, microalbuminuria and serum cystatin C were independent predictors for CVHI accumulative score.â© Conclusion: The CVHI accumulative score is correlated with the modified FSP score, ICVD score and indexes of subclinical arteriosclerosis (baPWV, carotid plaque, microalbuminuria and serum cystatin C). The CVHI accumulative score could be used as a tool for zero-level and primary prevention of cerebral stroke.
Assuntos
Índice Tornozelo-Braço , Doenças das Artérias Carótidas/fisiopatologia , Espessura Intima-Media Carotídea , Circulação Cerebrovascular , Análise de Onda de Pulso , Albuminúria , Transtornos Cerebrovasculares/fisiopatologia , Cistatina C/sangue , Hemodinâmica , Humanos , Análise de Regressão , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND/AIMS: To investigate the roles of the oxidative stress related-genes ALOX5, ALOX5AP and MPO in ischemic stroke susceptibility in the Han Chinese population. METHODS: A total of 351 ischemic stroke patients and 417 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 gene polymorphisms were genotyped. RESULTS: We identified that rs2107545 of MPO gene was significantly associated with ischemic stroke susceptibility after adjusting for covariates. Furthermore, we also considered the likely complexity of oxidative stress and inflammatory process in stroke by assessing the combined effects of multiple genes. Generalized multifactor dimensionality reduction (GMDR) analysis revealed that the combination of ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 was significantly associated with increased risk of ischemic stroke (P=0.0040, OR (95% CI) =1.991 (1.241 to 3.195)). Additionally, the MPO rs2107545 genotype was significantly associated with clinical outcomes at 6 months after discharge from the hospital. CONCLUSION: Our study revealed that epistatic interaction among the ALOX5, ALOX5AP and MPO genes played a significant role in vulnerability to ischemic stroke. Furthermore, these results also suggest that the rs2107545 of MPO gene can be used as a biomarker for the susceptibility and prognosis of ischemic stroke patients.
Assuntos
Proteínas Ativadoras de 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/genética , Isquemia Encefálica/genética , Peroxidase/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Idoso , Povo Asiático/genética , Isquemia Encefálica/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Acidente Vascular Cerebral/epidemiologiaRESUMO
OBJECTIVE: To analyze the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and ischemic stroke.â© Methods: Corresponding data, with case-control studies or cohorts regarding Lp-PLA2 and ischemic stroke, were retrieved from PubMed, Web of Science, Embase, the Cochrane Library, Chinese Biomedical Literature (CMB), VIP, China National Knowledge Infrastructure (CNKI), and Wanfang Database. Meta-analysis was performed by using Stata12.0.â© Results: Eight studies including 46 034 participants met the inclusion criteria. Meta-analysis showed that the combined effect of relative risk (RR) between Lp-PLA2 mass and ischemic stroke was [1.04 (0.98 to 1.11)] and that the combined effect of RR between Lp-PLA2 activity and ischemic stroke was [1.03 (0.96 to 1.10)], suggesting that Lp-PLA2 mass and activity were not associated with ischemic stroke.â© Conclusion: It cannot be considered that Lp-PLA2 mass and Lp-PLA2 activity was the risk factor for ischemic stroke.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/fisiologia , Isquemia Encefálica/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Ischemic stroke (IS) is a multifactorial disease that displays a strong genetic predisposition. However, the genetic architecture of IS has yet to be fully elucidated. It was hypothesized that epistasis between genes in multiple atherothrombotic pathways may play a vital role in determining the susceptibility to IS. The aim of the present study was to investigate the contributions of the hypothesized genetic factors to IS and the interactions between these genetic factors in a Chinese population. METHODS: In this study, 351 cases with IS and 417 control subjects from a Chinese population were genotyped for single-nucleotide polymorphisms (SNPs) in 12 genes hypothesized to be involved in atherosclerosis, coagulation, and related pathways. We examined SNP main effects and epistatic interactions between these polymorphic loci. RESULTS: rs710446 of the KNG1 gene was associated with IS susceptibility based on an additive genetic model (rs710446: P = .012; odds ratio [OR], 1.247; 95% confidence interval [CI], 1.050-1.481) after adjusting for covariates. Furthermore, an epistatic interaction between the ALOX5AP, THBD, and KNG1 gene was also identified in association with stroke susceptibility (P < .001 after 1000 permutations). Based on the chi-squared test, the OR of the high-risk combination of the three-locus model increased the risk of IS by 2.53-fold (95% CI, 1.60-4.01; P < .0001). CONCLUSIONS: Our findings support the association of the epistatic interactions of ALOX5AP, THBD, and KNG1 and present novel evidence for the main effect of KNG1 gene on IS susceptibility, suggesting a modulation of stroke risk by a genetic main effect and gene-gene interactions.
Assuntos
Proteínas Ativadoras de 5-Lipoxigenase/genética , Epistasia Genética/genética , Predisposição Genética para Doença/genética , Cininogênios/genética , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Trombomodulina/genética , Idoso , Povo Asiático/genética , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/genética , China/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
Remodeling of extracellular matrix (ECM) and breakdown of blood-brain barrier (BBB) are crucial events in the pathogenesis of intracerebral hemorrhage (ICH). Matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-2, are the most important degrading enzymes in the ECM and BBB. These proteolytic effects are controlled predominantly by tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is the main endogenous inhibitor of MMP-9. Two polymorphisms in the TIMP-1 gene (rs4898 and rs2070584) were selected through a literature review and successfully genotyped in a study sample of 410 ICH patients and 305 controls. Differences in genotype and allele frequencies of identified polymorphisms were determined. Furthermore, the serum levels of TIMP-1 were measured in a subgroup of 96 ICH patients on days 1 after ICH onset and 76 controls. Analyses showed that C allele of rs2070584 was significantly associated with the development of ICH in male subjects (p = 0.037, OR = 1.535, 95%CI 1.025-2.300). Multiple logistic regression analysis under three genetic models demonstrated both rs4898 and rs2070584 were not risk factors for ICH in female subjects. Furthermore, serum levels of TIMP-1 were significantly higher in ICH patients than those in normal controls. However, the serum levels of TIMP-1 showed a nonsignificant decrease, depending on the alleles and genotypes of rs2070584 both in male and female cases. In conclusion, this is the first association study of the TIMP-1 gene variants with ICH. Our data suggest that C allele of rs2070584 is a risk factor for ICH development in the Chinese male population. However, the precise function of this variant needs further investigation.
Assuntos
Hemorragia Cerebral/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Adulto , Idoso , Povo Asiático/etnologia , Povo Asiático/genética , Pressão Sanguínea , Hemorragia Cerebral/sangue , Hemorragia Cerebral/etnologia , Hemorragia Cerebral/fisiopatologia , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Fatores Sexuais , Inibidor Tecidual de Metaloproteinase-1/sangueRESUMO
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.
Assuntos
Aterosclerose/complicações , Predisposição Genética para Doença/genética , Variação Genética , Polimorfismo Genético , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias/patologia , Estudos de Casos e Controles , China/etnologia , Etnicidade , Feminino , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The hygroscopicity and optical properties of alkylaminium sulfates (AASs) were investigated using a hygroscopicity tandem differential mobility analyzer coupled to a cavity ring-down spectrometer and a nephelometer. AAS particles do not exhibit a deliquescence phenomenon and show a monotonic increase in diameter as the relative humidity (RH) ascends. Hygroscopic growth factors (GFs) for 40, 100 and 150 nm alkylaminium sulfate particles do not show an apparent Kelvin effect when RH is less than 45%, whereas GFs of the salt aerosols increase with initial particle size when RH is higher than 45%. Calculation using the Zdanovskii-Stokes-Robinson mixing rule suggests that hygroscopic growth of triethylaminium sulfate-ammonium sulfate mixtures is non-deliquescent, occurring at very low RH, implying that the displacement of ammonia by amine will significantly enhance the hygroscopicity of (NH4)2SO4 aerosols. In addition, light extinction of AAS particles is a combined effect of both scattering and absorption under dry conditions, but is dominated by scattering under wet conditions.
Assuntos
Material Particulado/química , Ésteres do Ácido Sulfúrico/química , Aerossóis , MolhabilidadeRESUMO
OBJECTIVE: To explore the association between apolipoprotein AI (ApoAI) gene rs12721026 polymorphism and cerebral hemorrhage (CH) in Changsha Han population, and to evaluate the effect of rs12721026 polymorphism on plasma lipid levels. METHODS: A total of 273 patients with CH and 140 healthy controls were collected. The rs12721026 polymorphism of ApoAI was analyzed by SNaPshot genotyping analysis and DNA sequencing. The total cholesterol (TG), triglyceride (TC), HDL-C and LDL-C were examined by oxidase method. RESULTS: There was no significant difference in the genotype and allele frequencies of rs12721026 polymorphism between the CH group and the control group (P>0.05). Both in the CH group and in the control group, the level of HDL-C of the TT gene type of rs12721026 was significantly higher than that of the GT/GG gene type (P<0.05). There was no significant difference in the levels of TG, TC and LDL-C among different subgroups of gene types. CONCLUSION: There may be no association between apoAI gene rs12721026 polymorphism with CH in Changsha Han population, which may still influence the HDL-C levels.
Assuntos
Apolipoproteína A-I/genética , Hemorragia Cerebral/genética , Colesterol/sangue , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangue , Povo Asiático , Estudos de Casos e Controles , Hemorragia Cerebral/sangue , Frequência do Gene , Genótipo , Humanos , Lipídeos , Análise de Sequência de DNARESUMO
Monitoring hypochlorite levels in water is of great importance because of its high toxicity and wide applications as water disinfectants. In this manuscript, carbon dot (CD) was electrochemically prepared by using dopamine and epigallocatechin gallate (molar ratio 1:1) as the carbon source for efficient hypochlorite determination. By electrolyzing the solution at 10 V for 12 min with PBS as an electrolyte, dopamine would react with epigallocatechin at the anode, and through polymerization, dehydration, and carbonization, strong blue-fluorescent CDs were obtained. CDs were characterized by UV-Vis spectroscopy, fluorescence spectroscopy, high-resolution transmission electron microscopy, FT-IR, etc. These CDs have an excitation wavelength at 372 nm and an emission wavelength at 462 nm, owing an average particle size of 5.5 nm. The presence of hypochlorites can quench the fluorescence of CDs, and its reduction in intensity is linear with hypochlorite concentration over the range of 0.5-50 µM, ΔF/F0 = 0.0056 + 0.0194CClO-, R2=0.997. The detection limit achieved 0.23 µM (S/N = 3). The mechanism for fluorescence quenching is via a dynamic process. Different from many other fluorescence methods based on the strong oxidizing ability of hypochlorites, our method shows strong selectivity toward hypochlorites over other oxidizing agents such as H2O2. The assay was validated by the detection of hypochlorites in water samples, with recoveries between 98.2% and 104.3%.
Assuntos
Pontos Quânticos , Pontos Quânticos/química , Ácido Hipocloroso , Dopamina , Carbono/química , Peróxido de Hidrogênio , Espectroscopia de Infravermelho com Transformada de Fourier , Água , Corantes Fluorescentes/químicaRESUMO
BACKGROUND: Recent studies have uncovered that vitexin compound B-1 (VB-1) can protect neurons against hypoxia/reoxygenation (H/R)-induced oxidative injury through suppressing NOX4 expression. OBJECTIVE: The aims of this study are to investigate whether VB-1 can protect the rat brain against ischemia/ reperfusion (I/R) injury and whether its effect on NOX4 expression is related to modulation of certain miRNAs expression. METHODS: Rats were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score and infarct volume concomitant with an upregulation of NOX4 expression, increase in NOX activity, and downregulation of miR-92b. RESULTS: Administration of VB-1 reduced I/R cerebral injury accompanied by a reverse in NOX4 and miR-92b expression. Similar results were achieved in a neuron H/R injury model. Next, we evaluated the association of miR-92b with NOX4 by its mimics in the H/R model. H/R treatment increased neurons apoptosis concomitant with an upregulation of NOX4 and NOX activity while downregulation of miR-92b. All these effects were reversed in the presence of miR-92b mimics, confirming the function of miR-92b in suppressing NOX4 expression. CONCLUSION: We conclude the protective effect of VB-1 against rat cerebral I/R injury through a mechanism involving modulation of miR-92b/NOX4 pathway.
Assuntos
NADPH Oxidase 4 , Traumatismo por Reperfusão , Animais , Ratos , EncefalopatiasRESUMO
BACKGROUND: Upregulation of mitochondrial E3 ubiquitin ligase 1 (Mul1) contributes to brain injury in ischemic stroke due to disturbance of mitochondrial dynamics, and bioinformatics analysis predicts that Mul1 is a potential target of Dipsacoside B. OBJECTIVE: The aim of the study was to explore whether Dipsacoside B can exert a beneficial effect on brain injury in the ischemic stroke rat via targeting Mul1. METHODS: The SD rat brains or PC12 cells were subjected to 2 h-ischemia or 8 h-hypoxia plus 24 h-reperfusion or 24 h-reoxygenation to establish the ischemic stroke rat model in vivo or in vitro, which were treated with Dipsacoside B at different dosages. The brain or PC12 cell injury, relevant protein levels and mitochondrial functions were measured by methods of biochemistry, flow cytometry or Western blot. RESULTS: The neurological dysfunction and brain injury (such as infarction and apoptosis) observed in the ischemic stroke rats were accompanied by increases in Mul1 and Dynamin-related protein 1 (Drp1) levels along with decreases in mitofusin 2 (Mfn2) level and ATP production. These effects were attenuated by Dipsacoside B. Consistently, cell injury (necroptosis and apoptosis) occurred in the PC12 cells exposed to hypoxia concomitant with the upregulation of Mul1 and Drp1 along with downregulation of Mfn2 and mitochondrial functions (such as increases in reactive oxygen species production and mitochondrial fission and decreases in mitochondrial membrane potential and ATP production).These phenomena were reversed in the presence of Dipsacoside B. CONCLUSION: Dipsacoside B can protect the rat brain against ischemic injury via inhibition of Mul1 due to the improvement of mitochondrial function.
Assuntos
Lesões Encefálicas , AVC Isquêmico , Trifosfato de Adenosina/metabolismo , Animais , Apoptose , Hipóxia , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Ácido Oleanólico/análogos & derivados , Células PC12 , Ratos , Ratos Sprague-Dawley , Saponinas , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Endosomal sorting complex required for transport III (ESCRT-III) machinery is a key component to counteract the mixed lineage kinase domain-like pseudokinase (MLKL)-induced plasma membrane broken in cells undergoing necroptosis. Based on the bioinformatics analysis, polymyxin B, a polypeptide antibiotic, is predicted to simultaneously interact with ESCRT-III subunits and necroptosis-relevant proteins. This study aims to explore whether polymyxin B could reduce necroptosis in the stroke rat brain via enhancing the ESCRT-III machinery and/or suppressing the RIPK1/RIPK3/MLKL pathway. The stroke rats showed evident brain injury, concomitant with the downregulation of ESCRT-III subunits and the upregulation of necroptosis-relevant proteins. Post-ischemic administration of polymyxin B could alleviate the brain injury, accompanied by restoration of the levels of ESCRT-III subunits and suppression of necroptosis-relevant proteins. And, polymyxin B exerted similar effects in hypoxia-treated HT22 cells. We conclude that polymyxin B can reduce necroptosis in the stroke rat brain via enhancing the ESCRT-III machinery and suppressing the RIPK1/RIPK3/MLKL pathway simultaneously.
Assuntos
Lesões Encefálicas , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Ratos , Complexos Endossomais de Distribuição Requeridos para Transporte , Polimixina B , Proteínas Quinases/metabolismoRESUMO
We developed and validated a new diagnostic scoring system by simultaneously comparing 28 factors (including clinical, laboratory, and imaging) of HIV uninfected adult tuberculous meningitis (TBM) with viral meningitis (VM), bacterial meningitis (BM), and cryptococcal meningitis (CM). Predictors of TBM diagnosis obtained by logistic regression. A total of 382 patients with intracranial infection participated, and eight factors were independently associated with TBM diagnosis: symptom duration, evidence of extracranial tuberculosis, cerebrospinal fluid (CSF) leukocyte, CSF neutrophil, CSF protein, low serum sodium, meningeal enhancement, and tuberculomas. Factors are assigned according to weight, a score of ≥ 5 was suggestive of TBM with a sensitivity of 85.8% and a specificity of 87.7%, and the area under the receiver operating characteristic curve was 0.923. When applied to a prospective validation cohort, this scoring model showed robust performance. Our study suggests that the application of this score can help diagnose TBM more efficiently.
Assuntos
Meningites Bacterianas/diagnóstico , Meningite Criptocócica/diagnóstico , Meningite Viral/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Meníngea/diagnóstico , Adolescente , Adulto , Idoso , Estudos de Coortes , Diagnóstico Precoce , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/microbiologia , Adulto JovemRESUMO
OBJECTIVE: To explore the association between single nucleotide polymorphisms (SNPs) of KLK1 gene and cerebral hemorrhage in Changsha Han Chinese. METHODS: Two hundred and seventy-three cerebral hemorrhage (CH) patients and 140 healthy controls were collected. The SNPs of rs5516 and rs5517 loci of KLK1 gene were analyzed by SNaPshot methods and direct sequencing. RESULTS: (1)Genotype and allele frequencies in rs5516 locus had no difference between the CH patients and controls (P> 0.05). However, the A allele frequency of the rs5517 locus in CH patients was higher than that in the control group (0.419, 0.321 respectively, P< 0.05). (2)In the control group,the levels of diastolic blood pressure (DBP) of the GA and AA genotype carriers of the rs5517 locus were significantly higher than those of the GG genotype (P< 0.05), while the levels of blood pressure were not significantly different among different genotypes of the rs5516 polymorphism in both CH patients and the control group(P> 0.05). CONCLUSION: Author's preliminary results suggested that the rs5517 polymorphism was associated with cerebral hemorrhage, while the rs5516 polymorphism was not in Changsha Han Chinese.
Assuntos
Hemorragia Cerebral/genética , Polimorfismo de Nucleotídeo Único/genética , Calicreínas Teciduais/genética , Adulto , Idoso , Povo Asiático/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: To investigate the relationship between T704C polymorphism of angiotensinogen (AGT) gene and cerebral hemorrhage and its impact on the levels of blood pressure in Han people in Changsha. METHODS: A total of 273 cerebral hemorrhage patients (the cerebral hemorrhage group) and 140 normal controls (the control group) were collected from Jan. 2005 to Jan. 2009. DNA was extracted from their peripheral blood samples. The polymorphism of AGT-T704C was analyzed by SNaPshot and direct DNA sequencing. The possible risk factors of cerebral hemorrhage were investigated at the same time. Each group was divided into 2 subgroups (a high blood pressure subgroup and a normal blood pressure subgroup) according to whether they had essential hypertension. Logistic regression analysis was used to detect the relationship between cerebral hemorrhage and all its possible risk factors and AGT-T704C polymorphism. RESULTS: The drinking history, coronary heart disease history, essential hypertension history, and blood levels of lipids were shown significant difference between the cerebral hemorrhage group and the control group (P<0.05). Logistic regression analysis showed that hypertension history, systolic blood pressure level, and high density lipoprotein cholesterol level were independent risk factors for cerebral hemorrhage in Han people in Changsha. The genotype C/C, C/T, and T/T frequencies of AGT-T704C polymorphism in the cerebral hemorrhage group and the control group were 0.692, 0.279, 0.029 and 0.629, 0.350, 0.021, respectively. The allele C and T frequencies of AGT-T704C polymorphism in the 2 groups were 0.832, 0.168 and 0.804, 0.196, respectively. The frequencies of all the genotypes and alleles had no significant difference between the 2 groups and their subgroups (P>0.05). CONCLUSION: The polymorphism of AGT-T704C may not be associated with cerebral hemorrhage and not related to the levels of lipids and blood pressure in Han people in Changsha. Hypertension history, systolic blood pressure level, and high density lipoprotein cholesterol level are the main risk factors of cerebral hemorrhage in Han people in Changsha.
Assuntos
Angiotensinogênio/genética , Hemorragia Cerebral/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Sequência de Bases , China/etnologia , Feminino , Genótipo , Humanos , Hipertensão/complicações , Lipoproteínas HDL/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: To explore the association between single nucleotide polymorphism (SNPs) of KLK1 gene and cerebral hemorrhage in Changsha Han population. METHODS: We enrolled 273 patients with cerebral hemorrhage and 140 normal people. The SNPs (including rs3212855 and rs5515) of KLK1 gene were analyzed by Snapshot method and direct sequencing. RESULTS: We found rs5515 was not a polymorphic site in Changsha Han population. Genotype and allele frequency in rs3212855 were not different between patients with cerebral hemorrhage and the controls (P>0.05). The blood pressure level was not different between the genotype subgroups. CONCLUSION: Neither rs5515 nor rs3212855 is associated with cerebral hemorrhage.
Assuntos
Hemorragia Cerebral/genética , Calicreínas/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/etnologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: We investigated whether early worsening of cerebrospinal fluid (CSF) predicts the later paradoxical tuberculomas and is a potential predictive biomarker. METHODS: Patients of HIV-negative tuberculous meningitis fulfilling the inclusion criteria(n = 98) underwent clinical and CSF evaluation, together with repeated neuroimaging. We compared the baseline clinical data and continuous CSF of patients who did (n = 36) and did not (n = 62) develop paradoxical tuberculomas, and reported the changes associated with symptomatic tuberculomas. A logistic regression analysis was developed to reveal predictors for paradoxical tuberculomas. RESULTS: The proportion of worsening CSF parameters (WBC count and percent neutrophils) in the paradoxical tuberculomas group (27/36, 75.0%) was significantly higher than the non-paradoxical tuberculomas group (15/62, 24.2%). The logistic regression analysis revealed that worsening CSF parameters was the highest risk predictor for paradoxical tuberculomas. Most worsening CSF parameters (81.0%) occurred within two weeks after treatment (2-24 days, median 7 days), and paradoxical tuberculomas commonly happened two weeks later (12 days to 13 months, median 22 days). The period between worsening CSF parameters and paradoxical tuberculomas ranged from 6 to 383 days (median 21days). There were no significant differences in mortality and prognosis between the two groups. CONCLUSIONS: Early worsening of CSF parameters predicts subsequent development or progression of tuberculomas.
Assuntos
Antituberculosos/uso terapêutico , Tuberculoma/etiologia , Tuberculose Meníngea/complicações , Tuberculose Meníngea/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido Cefalorraquidiano/química , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculoma/líquido cefalorraquidiano , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/microbiologia , Adulto JovemRESUMO
BACKGROUND: Apolipoprotein B (ApoB) levels have been shown to be associate with risk of ischemic stroke. The apolipoprotein B gene (APOB) polymorphisms may influence levels of ApoB and risk of ischemic stroke, but whether they are associated with risk of ischemic cerebral infarction (CI) with family history (CIFH) or not is unknown. AIMS: To investigate the possible association of the polymorphism of APOB C7673T with CIFH in Han Chinese from Changsha. SETTINGS AND DESIGN: The study population included 47 patients with CIFH and 83 patients with cerebral infarction with no family history (CINFH). Control population included 100 healthy subjects with no history of ischemic stroke matched for age, sex, and ethnic background. MATERIALS AND METHODS: The APOB C7673T polymorphism was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma lipids levels were also examined by standard enzymatic methods and enzyme-linked immunosorbent assay (ELISA). STATISTICS: The statistical analysis was done using SPSS 14.0 software package. A P value < 0.05 was taken as significant. RESULTS: This study showed an association between the APOB C7673T polymorphism and CI, especially CIFH in Han Chinese from Changsha. The T alleles frequency of the C7673T polymorphism was significantly higher in both the CIFH and CINFH groups when compared with the control group (P < 0.01; P < 0.05; respectively). And the T allele frequency in CIFH group (0.17) was higher than CINFH (0.09) group (P = 0.056). In both the CIFH and CINFH groups the serum levels of TC and LDL cholesterol were significantly high in the TT and TC genotypes than that in the CC genotype (P < 0.01), while the serum level of HDL cholesterol in the TT and TC genotypes was significantly lower than that in the CC genotype (P < 0.05). CONCLUSIONS: The APOB C7673T polymorphism is related to CI, especially CIFH through changing serum lipid levels in a Chinese population.