RESUMO
Precise selection of patients who could benefit from immune checkpoint inhibitors (ICIs) is an important challenge for immunotherapy in lung cancer. POTEE (POTE Ankyrin Domain Family Member E) is a member of one primate-specific gene family which have been identified as cancer-related antigens and potential target for immunotherapy of cancer. Here, we investigated the correlation between POTEE mutation and the clinical outcome of ICIs treatment in non-small cell lung cancer (NSCLC). We merged three NSCLC cohorts (n = 165) to assess predictive value of POTEE mutation of immunotherapy efficacy in NSCLC. The prognostic analysis and the potential molecular mechanism exploration were conducted based on the data from The Cancer Genome Atlas (TCGA) database. In the merged cohort, patients with POTEE-mutation (POTEE-Mut) had a significantly higher objective response rate (ORR) (100% vs 27.7%; P < 0.001) and longer progression-free survival (PFS) (P = 0.001; HR 0.08; 95% CI 0.01 - 0.54) compared to patients with POTEE wild-type (POTEE-WT) in NSCLC. Also, patients with POTEE-Mut showed higher ORR (100% vs 27.2%; P < 0.001) and longer PFS (P = 0.001; HR 0.07; 95% CI 0.01 - 0.52) in lung adenocarcinoma (LUAD). POTEE mutation was significantly associated with higher tumor mutational burden (TMB) and higher neoantigen load (NAL), but not with PD-L1 expression in LUAD. Gene set enrichment analyses (GSEA) analysis revealed prominent enrichment of signatures related to DNA repair in POTEE-Mut group (P < 0.001) in LUAD. Our results indicate that POTEE mutation could serve as a potential predictive biomarker for ICIs in LUAD. However, prospective cohort studies are still needed for further validation.
Assuntos
Adenocarcinoma de Pulmão , Antígenos de Neoplasias , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Biomarcadores , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Estudos Prospectivos , Humanos , Antígenos de Neoplasias/genéticaRESUMO
Hepatocellular carcinoma ranks fourth in cancer-related causes of death worldwide and second in China. Patients with hepatocellular carcinoma (HCC) at the early stage have a better prognosis compared to HCC patients at the late stage. Therefore, early screening for HCC is critical for clinical treatment decisions and improving the prognosis of patients. Ultrasound (US), computed tomography (CT), and serum alpha fetoprotein (AFP) have been used to screen HCC, but HCC is still difficult to be diagnosed in the early stage due to the low sensitivity of the above methods. It is urgent to find a method with high sensitivity and specificity for the early diagnosis of HCC. Liquid biopsy is a noninvasive detection method using blood or other bodily fluids. Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) are important biomarkers for liquid biopsy. Recently, HCC screening methods using the application of cfDNA and ctDNA have become the hot spot of early HCC diagnostics. In this mini review, we summarize the latest research progress of liquid biopsy based on blood cfDNA in early screening of HCC.
Assuntos
Carcinoma Hepatocelular , Ácidos Nucleicos Livres , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Ácidos Nucleicos Livres/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , Biópsia Líquida/métodosRESUMO
Metastatic urothelial carcinoma (mUC) is associated with poor prognosis. Cisplatin-based combination chemotherapy is the preferred initial regimen for patients with mUC. However, a substantial proportion of patients cannot receive cisplatin-based chemotherapy due to renal impairment or other comorbidities. Currently, immune checkpoint inhibitors (ICI) showed to be effective in cisplatin-ineligible mUC patients on first-line treatment. Tislelizumab is an anti-human programmed death receptor-1 monoclonal IgG4 antibody, which was specifically engineered to minimize binding to FcɣR on macrophages to abrogate antibody-dependent phagocytosis. But there is no report of tislelizumab as a first-line treatment for cisplatin-ineligible patients with mUC currently. Here, we report a cisplatin-ineligible mUC patient with PD-L1-negative, microsatellite stable (MSS), high tumor mutational burden (TMB-H) obtained complete response receiving tislelizumab therapy after laparoscopic debulking surgery. Progression-free survival has exceeded 16 months since treatment with tislelizumab. To our knowledge, this is the first reported case of cisplatin-ineligible mUC patient with PD-L1-negative, MSS and TMB-H who responded well to tislelizumab as a first-line treatment. However, we still need more studies to assess the efficacy of tislelizumab as a first-line treatment in cisplatin-ineligible mUC patients and to confirm predictive values of TMB for efficacy of tislelizumab.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/cirurgia , Cisplatino/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/genética , Neoplasias Urológicas/cirurgia , Antígeno B7-H1/metabolismo , Anticorpos Monoclonais/uso terapêuticoRESUMO
Genomic fusions of anaplastic lymphoma kinase (ALK) are a well-established therapeutic target in non-small-cell lung cancer (NSCLC). Although various ALK fusion variants have been identified in NSCLC, their responses to ALK tyrosine-kinase inhibitors (TKIs) are heterogeneous. We report the case of a 71-year-old female patient diagnosed with lung adenocarcinoma with liver metastases. A novel CTNND1 (exon 14)-ALK (exon 20) fusion was identified from the biopsy sample by next-generation sequencing (NGS) and validated by immunohistochemistry (IHC) staining. Alectinib was administered, and the patient soon achieved partial response (PR). The progression-free survival (PFS) exceeded 15 months as of January 25, 2022. Our findings expand the spectrum of ALK rearrangements and provide a potential treatment option for lung adenocarcinoma patients with CTNND1-ALK fusions.
Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Idoso , Quinase do Linfoma Anaplásico/genética , Carbazóis , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Piperidinas , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
As one of the most important industrial cities in Northwest China, Lanzhou currently suffers from serious air pollution. This study analyzed the formation mechanism and potential source areas of persistent air pollution in Lanzhou during the heating period from November 1, 2016 to March 31, 2017 based on the air pollutant concentrations and relevant meteorological data. Our findings indicate that particulate pollution was extremely severe during the study period. The daily PM2.5 and PM10 concentrations had significantly negative correlations with daily temperature, wind speed, maximum daily boundary layer height, while the daily PM2.5 and PM10 concentrations showed significantly positive correlations with daily relative humidity. Five persistent pollution episodes were identified and classified as either stagnant accumulation or explosive growth types according to the mechanism of pollution formation and evolution. The PM2.5 and PM10 concentrations and PM2.5/PM10 ratio followed a growing "saw-tooth cycle" pattern during the stagnant accumulation type event. Dust storms caused abrupt peaks in PM10 and a sharp decrease in the PM2.5/PM10 ratio in explosive growth type events. The potential sources of PM10 were mainly distributed in the Kumtag Desert in Xinjiang Uygur Autonomous Region, the Qaidam Basin and Hehuang Valley in Qinghai Province, and the western and eastern Hexi Corridor in Gansu Province. The contributions to PM10 were more than 120 µg/m3. The important potential sources of PM2.5 were located in Hehuang Valley in Qinghai and Linxia Hui Autonomous Prefecture in Gansu; the concentrations of PM2.5 were more than 60 µg/m3.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Cidades , Monitoramento Ambiental , Calefação , Material Particulado/análise , Estações do AnoRESUMO
BACKGROUND: It is uncertain that the effect of free triiodothyronine (FT3) within normal ranges on initial severity and early functional outcomes in acute ischemic stroke (AIS) patients with Intracranial Atherosclerotic Stenosis (ICAS). The predictive values of white blood cell (WBC) and FT3 are also unclear in symptomatic ICAS (sICAS) patients. METHODS: We consecutively reviewed 848 ischemic stroke patients admitted into Xiangya Hospital within 72 h after symptom onset. sICAS was defined as AIS patient with degree of ICAS ≥50% proved by magnetic resonance angiography, computed tomography angiography or digital subtraction angiography. WBC and FT3 were assessed within 24 h after admission. Neurological severity was evaluated on admission using the National Institutes of Health Stroke Scale (NIHSS). Stroke outcomes were defined by the modified Rankin Scale (mRS) on the 14th day after admission. RESULTS: Logistic regression analysis showed that hypertension, lower FT3 and higher WBC concentrations independently associated with severe stroke [FT3 (odds ratio(OR) = 0.543, 95% confidence interval(95% CI): 0.383-0.769); hypertension (OR = 0.436, 95% CI: 0.238-0.800); WBC (OR = 1.17; 95% CI:1.041-1.316]. Besides, lower FT3, higher FT4, higher WBC and higher plasma glucose concentrations independently associated with unfavorable outcomes [FT3 (OR = 0.460; 95% CI: 0.306-0.690); FT4 (OR = 1.151; 95% CI: 1.055-1.255); WBC (OR = 1.178; 95% CI: 1.039-1.334); Plasma glucose (OR = 1.160; 95% CI: 1.002-1.342)]. CONCLUSIONS: Lower FT3 levels within normal ranges and higher WBC count are independently associated with the severity and early poor prognosis of sICAS simultaneously, FT3 and WBC count might be important biomarkers for sICAS patients.
Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Arteriosclerose Intracraniana/complicações , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Tri-Iodotironina/sangue , Isquemia Encefálica/complicações , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Symptomatic intracranial atherosclerotic stenosis (ICAS) and extracranial atherosclerotic stenosis (ECAS) are different in many aspects. Here, we explored the association between the location or severity of atherosclerotic stenosis and pro- or antiangiogenic factors, specifically vascular endothelial growth factor (VEGF) and endostatin (ES). METHODS: We evaluated 198 consecutive patients with acute ischemia stroke: 132 with large-artery atherosclerosis (LAA) and 66 with small-artery occlusion (small-vessel occlusion). The LAA group was subclassified into 102 patients with ICAS and 30 with ECAS. Independent associations of VEGF, ES levels, and VEGF/ES ratio with the location of cerebral stenosis and the severity or short-term prognosis (14th day modified Rankin Scale) of ICAS were evaluated. RESULTS: Plasma concentrations of VEGF and ES were lower (P < .05) in ICAS (38.07, 32.76-46.28 pg/mL and 58.95, 55.04-59.77 ng/mL) than those in ECAS (45.00, 34.30-83.34 pg/mL and 140.74, 85.63-231.21 ng/mL). Logistic regression analysis showed that VEGF concentrations and dyslipidemia were independently associated with ICAS, with odds ratios of .987 [95% CI = (.976, .998)] and .265 [95% CI = (.103, .792)], respectively. Moreover, plasmatic VEGF levels increased gradually along with the severity of ICAS (P = .003), and lower levels of ES (P = .040) or a higher VEGF/ES ratio (P = .048) were related to unfavorable short-term prognosis of ICAS. CONCLUSION: Lower VEGF levels are associated with the presence of symptomatic ICAS, but not with ECAS. Furthermore, the severity of ICAS is positively correlated with the levels of VEGF, and lower ES levels or a predominance of VEGF over ES are predictors of poor short-term prognosis of ICAS.
Assuntos
Isquemia Encefálica/sangue , Estenose das Carótidas/sangue , Doenças de Pequenos Vasos Cerebrais/sangue , Endostatinas/sangue , Arteriosclerose Intracraniana/sangue , Acidente Vascular Cerebral/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Povo Asiático , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etnologia , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/etnologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico , Doenças de Pequenos Vasos Cerebrais/etnologia , Distribuição de Qui-Quadrado , China , Avaliação da Deficiência , Feminino , Humanos , Arteriosclerose Intracraniana/diagnóstico , Arteriosclerose Intracraniana/etnologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etnologia , Fatores de TempoRESUMO
Platelet glycoprotein (GP) mediated the role of platelet in coagulation. Platelet GP Ia 807C/T is the only GP polymorphism associated with the expression levels of GP Ia/IIa (the platelet collagen receptor). Recently, the GP Ia 807C/T polymorphism has been reported to have no association with cerebral hemorrhage (CH) in two studies pertained to Caucasian populations. The purpose of this study is to evaluate the association between platelet GP Ia 807C/T polymorphism and CH in a Han Chinese population. We performed genotype analysis for platelet GP Ia 807C/T polymorphism in a case-control study involving 195 patients with CH and 116 age- and sex-matched controls. In contrast to previous reports, we found that the frequencies of GP Ia 807C/T T allele, CT and TT genotype were much higher in CH patients than in controls (33.9% vs. 22.8%, p = 0.004; 45.5% and 11.1% vs. 40.4% and 2.6%, p = 0.022). Logistic regression analysis revealed that the presence of GP Ia 807C/T C allele and CC genotype were both associated with a decreased risk of CH compared with T allele, CT and TT genotypes, respectively (adjusted odds ratio [OR] = 0.565, 95% CI: 0.384-0.887, p = 0.005; adjusted OR = 0.172, 95% CI: 0.043-0.639, p = 0.009; adjusted OR = 0.254, 95% CI: 0.085-0.961, p = 0.041, respectively). These findings indicated that platelet GP Ia 807C/T polymorphism could be a protective factor of CH in the Chinese population.
Assuntos
Hemorragia Cerebral/genética , Integrina alfa2/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de ProteçãoRESUMO
OBJECTIVE: Little attention has been paid to the epidemiological characteristics of lacunar infarction (LAC) in China before. This study aimed to examine the incidence and survival of LAC in a southern Chinese population. METHODS: From 2004-2010 in Changsha, two communities with a registered population of â¼100 000 were selected and data from first-ever ischaemic stroke (IS) cases were prospectively collected. Then the epidemiological characteristics of LAC and non-LAC were evaluated. RESULTS: During the study period, the age-standardized incidence increased at an annual rate of 0.7% (p < 0.001) for LAC and 2.0% (p < 0.001) for non-LAC. The mean annual age-standardized incidence of LAC and non-LAC was 28.2/100 000 and 45.0/100 000, respectively. Compared with non-LAC patients, the prevalence of hypertension, diabetes and hyperlipidemia was significantly higher in patients with LAC (p < 0.05). Although the 30-day fatality rate was significantly lower in patients with LAC than non-LAC (0.5% vs. 14.9%, p < 0.001), there was no significant difference in survival between the two groups (96.7% vs. 95.2%, p = 0.203) after excluding the patients who died within 1 year of stroke onset. CONCLUSION: LAC is a common stroke sub-type in southern China and the long-term prognosis is not benign.
Assuntos
Acidente Vascular Cerebral Lacunar/epidemiologia , Adulto , Idoso , Infarto Encefálico/epidemiologia , Infarto Encefálico/mortalidade , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral Lacunar/mortalidadeRESUMO
The Basigin (BSG, also known as CD147/extracellular matrix metalloproteinase inducer) belongs to the immunoglobulin superfamily (IgSF). It is a cellular receptor for cyclophilin A (CypA), and is originally known as tumor cell collagenase stimulatory factor (TCSF), which could abundantly expressed on the surface of tumor cells, haematopoietic, monocytes, epithelial endothelial cells and smooth muscle cells. Accumulating evidence showed that BSG played an important role in stimulating the secretion of matrix metalloproteinases (MMPs), which has been reported to be involved in the development of atherosclerosis. Since atherosclerosis is an important risk factor for atherosclerotic cerebral infarction (ACI), we speculate that BSG genetic polymorphisms may influence formation of atherosclerosis and then development of ACI. This study aimed to detect the potential association of the single nucleotide polymorphisms (SNP, -631 G > T, -318 G > C, 10141 G > A and 10826 G > A) of BSG gene in Hunan Han Chinese population with ACI. We genotyped 199 ACI patients and 188 matched healthy controls for the four BSG SNP by method of matrix-assisted laser desorption/ionization-time-offlight mass spectrometry (MALDI-TOF MS). Our results suggested that all the polymorphisms were observed in the subjects from Changsha area of Hunan Province. However, no significant difference was observed between the distribution of these SNP in cases and controls. Therefore, we speculate that BSG genetic polymorphisms might not be an important factor in the development of ACI in our Chinese Han population.
Assuntos
Povo Asiático/genética , Basigina/genética , Infarto Cerebral/etiologia , Infarto Cerebral/genética , Predisposição Genética para Doença/genética , Arteriosclerose Intracraniana/complicações , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Arteriosclerose Intracraniana/genética , Masculino , Pessoa de Meia-IdadeRESUMO
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
OBJECTIVE: To explore the expression profile of Ephrin-B2 in the ischemic penumbra after transient focal cerebral ischemia in rats, and to clarify the mechanism of Ephrin-B2 triggering angiogenesis. METHODS: Sprague-Dawley rats were randomly divided into a normal group, a sham operation group and ischemic-reperfusion 1, 3, 7, 14, and 28 d groups. Suture-occluded method was used to establish the focal middle cerebral artery occlusion model and the ischemic brain was reperfused 2 h after the occlusion. Western blot and quantitative real-time reverse-transcription polymerase chain reaction were used to detect the dynamic expression profile of Ephrin-B2 in the penumbra cortex. Double immunofluorescence was used to speculate the location and the co-expression of Ephrin-B2 in blood vessels, neurons and astrocytes. Microvessel density was quantified by the number of CD31+ cells. Rats were subjected to neurologic functional tests by modified neurological severity scores (mNSS) before sacrifice. RESULTS: Compared with the sham group, Ephrin-B2 protein and mRNA level of the penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 7 and 14 (P<0.01), and declined at day 28. Double immunofluorescence indicated that Ehprin-b2 was expressed in the neurons, blood vessels and astrocytes; mNSS peaked at day 7, and gradually declined at day 14. The microvessel density of penumbra cortex in the ischemic group increased 3 days (P<0.05) after the reperfusion, peaked at day 14 (P<0.01), and gradually declined at 48 h. CONCLUSION: Cerebral ischemia reperfusion induces the over-expression of Ephrin-B2, with a dynamic trend, suggesting that Ehprin-b2 may improve post-stroke functional recovery by enhancing angiogenesis and neurogenesis.
Assuntos
Isquemia Encefálica/metabolismo , Córtex Cerebral/metabolismo , Efrina-B2/metabolismo , Animais , Astrócitos/metabolismo , Encéfalo/patologia , Infarto da Artéria Cerebral Média , Ataque Isquêmico Transitório , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismoRESUMO
Sugars are renewable resources essential to human life, but they are rarely used as raw materials for the industrial production of carbon-based materials, especially for the preparation of carbon fiber-reinforced carbon-matrix (C/C) composites, which are extremely useful for the semiconductor and aerospace sectors. Herein, a method utilizing sugar-derived carbon to replace petrochemicals as dense matrix to preparing C/C composites is reported. The matrix from sugar-derived C/C (S-C/C) composites has a nanocrystalline graphite structure that is highly thermally stable and effectively bonded to the carbon fibers. The mechanical properties of the S-C/C composite are comparable to those prepared from petrochemical sources; significantly, it exhibits a linear ablation rate of 0.03 mm s-1 after 200 s of ablation at 3000 °C in 10 MW m-2 heat flux. This new class of S-C/C is promising for use in a broad range of fields, ranging from semiconductor to aerospace.
RESUMO
Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both myocardial and cerebral infarctions. Recent studies indicate that the single nucleotide polymorphism (SNP) rs3850641 in TNFSF4 is associated with higher risk of myocardial infarction, but little is known about the association between TNFSF4 variation and cerebral infarction (CI). A case-control study involving 385 CI patients and 385 age-matched, sex-matched non-CI controls was conducted in a Chinese population, only the most common subtype, atherosclerosis CI, was recruited. Two SNPs of TNFSF4, rs3850641 and rs3861950, were genotyped by the TaqMan SNP genotyping method, and verified partly by genomic DNA sequencing. The results revealed a significant allelic association between rs3861950 and CI (Odds ration = 1.733, 95 % confidence interval = 1.333-2.254, P = 0.000). Genotypic association analysis demonstrated that the CC genotype of rs3861950 confers susceptibility to CI (Odds ration = 2.896, 95 % confidence interval = 1.368-6.132), and it was associated with a significantly higher risk of ischemic stroke (Odds ration = 3.520, 95 % confidence interval = 1.546-8.015, P = 0.003) after adjusting for the other confirmed risk factors such as the history of hypertension, diabetes, CAD, smoking and alcohol drinking. While the odds ratio of the T allele to the C allele was 1.733 (95 % confidence interval: 1.333-2.254). However, there was no significant association between rs3850641 and CI (Odds ration = 1.288, 95 % confidence interval = 0.993-1.670, P = 0.056). TNFSF4 gene polymorphism rs3861950, but not rs3850641, is associated with the risk of atherosclerosis CI in a Chinese population.
Assuntos
Alelos , Povo Asiático , Infarto Cerebral/genética , Genótipo , Ligante OX40/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/epidemiologia , Aterosclerose/genética , Estudos de Casos e Controles , Infarto Cerebral/epidemiologia , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Excessive delay of presentation for stroke in China is reported. In this study, an intervention trial was conducted to promote urgent therapy for acute ischemic stroke. Two communities in Changsha were selected as either intervention or control community from November 2007 to December 2011. Public and professional education was regularly implemented in the intervention community. Publics' knowledge about early identification and urgent therapy of ischemic stroke was surveyed before and after intervention in the two communities. During the intervention period, first-ever ischemic stroke cases occurring in the intervention community (intervention group) and that in the control community (control group) were collected and followed for 90 days. After intervention, the publics' knowledge levels in the intervention community improved significantly. Intervention group' average presentation time was shorter than control group (8.3 ± 5.8 vs. 10.5 ± 6.5 h, P = 0.018). Percentage of presentation time within 3 h (48.0 %), the rate of ambulance use (59.0 %), and thrombolytic therapy (9.3 %) in the intervention group was all obviously higher than that in the control group (21.5, 41.3, and 4.5, respectively). When admitted, the intervention group had lower mean systolic blood pressure (160.8 ± 26.7 vs. 164.7 ± 26.8 mmHg, P = 0.000) than control group. Survivors in the intervention group were more likely to be in higher Barthel index scoring groups than that in the control group at day 90 [(75, 50-100) vs. (65, 35-90), P = 0.035]. Public and professional education may promote prompt presentation and urgent therapy for ischemic stroke, which may be helpful for patients' prognosis.
Assuntos
Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Acidente Vascular Cerebral/terapia , Doença Aguda , China , Feminino , Humanos , MasculinoRESUMO
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
The mechanical properties of laser powder bed fused (LPBFed) Invar 36 alloy have been limited by the presence of manufacturing defects. It is imperative to investigate the influence of these defects on the mechanical behavior of LPBFed Invar 36 alloy. In this study, in-situ X-ray computed tomography (XCT) tests were conducted on LPBFed Invar 36 alloy fabricated at different scanning speeds to examine the relationship between manufacturing defects and mechanical behavior. For LPBFed Invar 36 alloy fabricated at a scanning speed of 400 mm/s, the manufacturing defects were randomly distributed and tended to be elliptical in shape. Plastic deformation behavior was observed, and failure initiated from defects inside the material resulting in ductile failure. Conversely, for LPBFed Invar 36 alloy fabricated at a scanning speed of 1000 mm/s, numerous lamellar defects were observed mainly located between deposition layers, and their quantity was significantly increased. Little plastic deformation behavior was observed, and failure initiated from defects on the shallow surface of the material resulting in brittle failure. The differences in manufacturing defects and mechanical behavior are attributed to changes in input energy during the laser powder bed fusion process.
RESUMO
BACKGROUND AND PURPOSE: Low rates of thrombolysis for ischemic stroke in China have mainly been attributed to delays in presentation to the hospital. This study aimed to evaluate factors associated with these delays. METHODS: Data were from a prospective, multicenter, hospital-based registry of patients with acute stroke (ChinaQUEST [Quality Evaluation of Stroke Care and Treatment]), which involved 62 hospitals across a variety of economic and geographic regions in China during 2006. Univariate and multivariate analyses were undertaken to determine associations between variables of interest and delays to hospital presentation. RESULTS: Median time to hospital presentation was 15.0 hours for 6102 cases (interquartile range, 2.8-51.0 hours). A total of 1546 (25%) patients arrived within 3 hours and 2244 (37%) patients arrived within 6 hours after symptom onset. Factors that prolonged time to presentation were: visiting a local doctor before presenting at emergency (OR, 0.48; P<0.001), symptom onset at home (OR, 0.62; P<0.001), transfer to a large (Level III) hospital for management (OR, 0.70; P=0.04), and history of diabetes (OR, 0.78; P=0.01). In contrast, factors that accelerated presentation to the hospital were hemorrhagic stroke (OR, 2.25; P<0.001), history of atrial fibrillation (OR, 1.94; P<0.001), unconsciousness at presentation (OR, 1.91; P<0.001), transfer by ambulance (OR, 1.91; P<0.001), and history of coronary artery disease (OR, 1.20; P=0.04). CONCLUSIONS: Health promotion strategies to improve community awareness of early symptoms of stroke, establishment of an alert system to cater for patients likely to experience stroke at home, and wider availability and use of ambulance services are promising methods to help expedite presentation to hospital poststroke and thereby improve the management of stroke in China.
Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Acidente Vascular Cerebral/terapia , Fatores Etários , Idoso , China/epidemiologia , Etnicidade , Feminino , Hong Kong/epidemiologia , Hospitais/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Fatores Socioeconômicos , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica/estatística & dados numéricos , Fatores de Tempo , Transporte de Pacientes/estatística & dados numéricos , Resultado do Tratamento , População UrbanaRESUMO
The aim of this study was to evaluate the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG), an active component extracted from Polygonum multiflorum, on learning/memory deficits in Alzheimer's disease (AD). We randomly divided 24 male Sprague-Dawley rats among 4 groups: (i) the sham-operated group (control); (ii) sham-operated group also treated with TSG (sham+TSG); (iii) beta amyloid treated group (Aß); and (iv) Aß treatment group also treated with TSG (Aß+TSG). Rats in the Aß and Aß+TSG groups were treated with Aß1â42 intracerebroventricularly, whereas the control and sham+TSG groups were given phosphate-buffered saline. Rats in the sham+TSG and Aß+TSG groups were then treated intragastrically with TSG (50 mg·(kg body mass)⻹·day⻹) for 4 weeks, and rats in the Aß and control groups were treated with saline. The results from Morris water maze tests, electron microscopy, real-time polymerase chain reaction, and Western blotting demonstrated that Aß1â42 induced impairment in learning and memory, degeneration in synaptic structures, and downregulation of Src and NR2B at the gene and protein level, respectively. These alterations were reversed by the administration of TSG, suggesting that TSG exerts anti-AD properties by protecting synaptic structure and function. TSG-induced upregulation of Src and NR2B may be responsible for this process.
Assuntos
Doença de Alzheimer/prevenção & controle , Modelos Animais de Doenças , Glucosídeos/uso terapêutico , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Nootrópicos/uso terapêutico , Estilbenos/uso terapêutico , Membranas Sinápticas/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides , Animais , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/prevenção & controle , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/prevenção & controle , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Neurônios/ultraestrutura , Fármacos Neuroprotetores/uso terapêutico , Fragmentos de Peptídeos , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Membranas Sinápticas/metabolismo , Membranas Sinápticas/ultraestrutura , Regulação para Cima/efeitos dos fármacosRESUMO
Intracerebral hemorrhage (ICH) is a heterogeneous disease with genetic factors playing an important role. Association studies on a wide range of candidate pathways suggest a weak but significant effect for several alleles with ICH risk. Among the most widely investigated genes are those involved in the renin-angiotensin-aldosterone system (e.g., angiotensin-converting enzyme), coagulation pathway (e.g., Factor XIII, Factor VII, platelet-activating factor acetylhydrolase, Factor V Leiden, and beta1-tubulin), lipid metabolism (e.g., apolipoproteins (Apo)E, Apo(a), ApoH), homocysteine metabolism (e.g., methylenetetrahydrofolate reductase), inflammation (e.g., interleukin-6 and tumor necrosis-alpha) and other candidate pathways. To identify the robustness of the above associations with ICH, a search of Pubmed (1988 through December 2011) was performed, with searches limited to English-language studies conducted among adult human subjects. This article presents a review of the examined literature on the genetics of ICH.