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1.
Int J Cancer ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33285002

RESUMO

Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV-score, sex, and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008-2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95%CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95%CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men ages 55-59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV-score in a high-risk population. Adding non-viral risk factors did not improve NPC prediction.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33220929

RESUMO

Dysfunction of long noncoding RNA (lncRNA) is associated with tumorigenesis of various malignancies, including glioma. Previously, lncRNA ARRDC1 antisense RNA 1(ARRDC1-AS1) has been reported to be dysregulated in several tumors. However, the roles of ARRDC1-AS1 in glioma have not been investigated. In this study, we firstly reported that ARRDC1-AS1 expression was distinctly increased in both glioma specimens and cell lines, and high ARRDC1-AS1 expression was associated with advanced clinical progression and poor prognosis of glioma patients. Additionally, STAT1 could activate the transcription of ARRDC1-AS1. Functional studies revealed that knockdown of ARRDC1-AS1 suppressed the proliferation, migration and invasion of glioma cells. Mechanisms exploration indicated ARRDC1-AS1 served as a sponge of miR-432-5p to upregulate PRMT5 expressions. Rescue experiments indicated that knockdown of miR-432-5p reversed the inhibiting effects of ARRDC1-AS1 knockdown on glioma cells. Overall, our findings highlighted the importance of STAT1/ARRDC1-AS1/miR-432-5p/PRMT5 axis in glioma progression and offered novel strategies for glioma treatments.

3.
Parkinsons Dis ; 2020: 1216568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062247

RESUMO

Introduction: This study investigated the influence of lockdown during the 2019 coronavirus disease (COVID-19) pandemic on the quality of life of patients with Parkinson's disease (PD). Methods: We conducted a questionnaire survey involving 113 patients with PD from Xihu District, Hangzhou, Zhejiang. During the epidemic prevention and control period (February 1 to March 31, 2020), patients enrolled were asked to fill out questionnaires, including the "COVID-19 Questionnaire for PD Patients during the Period of Epidemic Prevention and Control" and "39-item Parkinson's Disease Questionnaire (PDQ-39)." During the phase of gradual release of epidemic prevention and control (April 1 to April 30, 2020), all patients were followed up again, and PDQ-39 questionnaires were completed. Results: The quality of life for patients during the period of epidemic prevention and control was worse than that after epidemic prevention and control (P < 0.001). The biggest problem that they faced was that they could not receive their doctor's advice or guidance regularly. The quality of life of patients who had difficulty getting doctors' guidance or those who changed their routine medication due to lockdown was even worse. Telemedicine was quite effective and efficient for patients to get doctors' guidance during lockdown. Conclusions: The inconvenient treatment during the pandemic directly caused the aggravation of patients' symptoms and the decline in their quality of life. It is suggested that social media (such as WeChat or Tencent QQ) are used for regular interactions and follow-up appointments for patients with inconvenient medical treatment.

4.
Cancer Med ; 8(5): 2561-2571, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30843658

RESUMO

BACKGROUND: The association between smoking and nasopharyngeal carcinoma (NPC) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by persistently reactivating EBV in long-term based on a prospective cohort design. METHODS: A NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies (VCA-IgA, EBNA1-IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios (aHRs) of smoking on NPC incidence. In the non-NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations (GEE). RESULTS: With a median of 7.54 years, 71 NPCs were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHRs of developing NPC among ever smokers were 3.00 (95%CI: 1.46-6.16). Stratified by sex, the HRs of ever smoking were 2.59 (95%CI: 1.07-6.23) for male and 3.75 (95%CI: 1.25-11.20) for female, respectively. Among the non-NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3-5 years of follow up, with adjusted odds ratios (aORs) of 1.68 (95%CI: 1.29-2.18) for VCA-IgA and 1.92 (95%CI: 1.42-2.59) for EBNA1-IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE. CONCLUSION: Smoking could significantly increase the long-term risk of NPC in southern China, partly by persistently reactivating EBV.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/fisiologia , Carcinoma Nasofaríngeo/epidemiologia , Carcinoma Nasofaríngeo/etiologia , Fumar/efeitos adversos , Adulto , Idoso , China/epidemiologia , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco
5.
Cancer Commun (Lond) ; 38(1): 7, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29764502

RESUMO

BACKGROUND: The association of circulating inflammation markers with nasopharyngeal carcinoma (NPC) is still largely unclear. This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China. METHODS: The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study (150 NPC patients and 150 controls) using multiplex assay platforms. Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection. Odds ratios (ORs) and 95% confidence intervals (CIs) relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models. The associations were validated in 60 patients with NPC and 120 controls in a subsequent nested case-control study within a NPC screening trial. Potential interactions between serum cytokines and Epstein-Barr virus (EBV) relating to the risk of NPC were assessed using a likelihood ratio test. RESULTS: The levels of serum macrophage inflammatory protein (MIP)-1α and MIP-1ß in the highest categories were associated with a decreased risk of NPC in both the case-control study (MIP-1α: OR = 0.49, 95% CI = 0.26-0.95; MIP-1ß: OR = 0.47, 95% CI = 0.22-1.00) and the nested case-control study (MIP-1α: OR = 0.13, 95% CI = 0.03-0.62; MIP-1ß: OR = 0.20, 95% CI = 0.04-0.94), compared with those in the lowest categories. Furthermore, individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study (MIP-1α: OR = 16.28, 95% CI = 7.11-37.23; MIP-1ß: OR = 12.86, 95% CI = 5.9-28.05) and the nested case-control study (MIP-1α: OR = 86.12, 95% CI = 10.58-701.03; MIP-1ß: OR = 115.44, 95% CI = 13.92-957.73). CONCLUSIONS: Decreased preclinical MIP-1α and MIP-1ß levels might be associated with a subsequently increased risk of NPC. More mechanistic studies are required to fully understand this finding.


Assuntos
Quimiocina CCL3/sangue , Quimiocina CCL4/sangue , Carcinoma Nasofaríngeo/sangue , Neoplasias Nasofaríngeas/sangue , Adulto , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China , Citocinas/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/etnologia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/etnologia , Razão de Chances , Fatores de Risco
6.
Brain Res ; 1678: 106-115, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29056525

RESUMO

Autophagy alterations have been observed in a variety of neurological disorders, however, very few studies have focused on autophagy alterations in epilepsy. The ketogenic diet (KD) likely ameliorates neuronal loss in several seizure models. However, whether this neuroprotective function occurs via starvation-induced autophagy and its prevalence in chronic kindled seizures remains unknown. The aim of this study was to determine the role of autophagy following seizure under KD, and the potential mechanism involved. Pentylenetetrazol (PTZ)-kindled rats, which were fed a Normal diet (ND) or KD, were pretreated with intraventricular infusions of saline, autophagy inducer rapamycin (RAP), or inhibitor 3-methyladenine (3-MA). KD alleviated seizure severity, decreased the number of Fluoro-jade B (FJB)-positive cells in the hippocampus of kindled rats. These effects were abolished by 3-MA pretreatment. RAP pretreatment did not affect seizure severity, but decreased the number of FJB-positive cells in ND group. KD decreased the percentage of damaged mitochondria in kindled group. Hippocampal Beclin-1 was increased by KD in vehicle group. The autophagy proteins Atg5, Beclin-1 and the ratio of microtubule-associated protein 1 light chain 3 (LC3) II to LC3-I in kindled KD-fed rats were higher, and the autophagy substrate P62 was lower than those in the kindled ND-fed rats, indicating an increase in autophagy following KD. Pretreatment with RAP increased the level of LC3-II/LC3-I, and pretreatment with 3-MA increased the level of P62 in KD-fed rats. To further clarify the mechanism of autophagy protection, the levels of key mitochondria related molecules were examed. The results showed that mitochondrial cytochrome c was up-regulated, cytosolic cytochrome c and the downstream cleaved caspase-3 was down-regulated in KD-fed rats, indicating a decrease in mitochondrial apoptosis. Taken together, our results indicated that KD activates autophagic pathways and reduces brain injury during PTZ-kindled seizures. The neuroprotective effect of KD is likely exerted via a reduction of mitochondrial cytochrome c release.


Assuntos
Autofagia/fisiologia , Dieta Cetogênica/métodos , Convulsões/fisiopatologia , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Caspase 3/metabolismo , Citocromos c/metabolismo , Epilepsia/metabolismo , Hipocampo/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Pentilenotetrazol/farmacocinética , Ratos , Ratos Sprague-Dawley , Convulsões/tratamento farmacológico , Sirolimo/farmacologia
7.
BMC Cancer ; 16(1): 796, 2016 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-27733148

RESUMO

BACKGROUND: Southern China is an endemic area for primary liver cancer (PLC), but it is unclear if rates have changed in recent decades. We evaluated PLC incidence and estimated the effects of age, period of diagnosis, and birth cohort in Sihui City, Guangdong Province, China. METHODS: Age-standardized rates (ASRs) of PLC were examined for both males and females from 1987 to 2011. Joinpoint regression analysis was conducted to estimate the annual percent changes in PLC incidence. The age-period-cohort (APC) model was used to investigate the effects of age, diagnosis period, and birth cohort on the relative risk (RR) of PLC. RESULTS: A total of 2988 PLC cases were identified in this period, with average ASRs of 51.1/100,000 for males and 11.7/100,000 for females. Joinpoint regression analysis revealed increasing PLC incidence throughout the entire period in both males (average annual change of 1.65 %) and females (0.20 %). RRs increased gradually in both sexes from the youngest age group (30-34 years) to the oldest (80-84 years). In males, the RR decreased during diagnosis period from 1987-1991 to 1997-2001 and remained stable thereafter. In females, RRs fluctuated with diagnosis period throughout the entire period. Incidence tended to increase with birth cohort from 1905-1909 to 1975-1979 in both males and females; however, female incidence plateaued in the youngest cohorts born between 1955 and 1974, while incidence in males increased sharply in the cohorts born between 1965 and 1974. According to APC analysis, the full age-period-cohort (APC) model fit the data best, and the period-cohort (PC) model would be enough to explain variability of rates in females. CONCLUSION: The PLC incidence rate in males of Sihui City has increased more significantly than female over the last 25 years. Despite the age effect in male, this trend mainly reflects the effects of risk factors that are present in early life (birth cohort) and period change in both genders.


Assuntos
Neoplasias Hepáticas/epidemiologia , Vigilância da População , China/epidemiologia , Feminino , História do Século XX , História do Século XXI , Humanos , Incidência , Neoplasias Hepáticas/história , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Risco
8.
Brain Res ; 1646: 451-458, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27343950

RESUMO

The ketogenic diet (KD) controls seizure and improves cognition in patients with drug refractory epilepsy. However, few experimental models have shown this neuroprotective effect on cognition. In this study, we investigated the cognitive protective effects of KD in pentylenetetrazol (PTZ)-kindled rats. We used two relatively low-stress behavioral assessment methods, the novel object recognition (NOR) task and the novel placement recognition (NPR) task, to reveal impairment in item and spatial memory, respectively. We used the Morris water maze (MWM) test for comparisons amongst memory assessment methods. The KD group had a slower body weight gain and shorter bregma-lambda length than the control normal diet (ND) group. KD did not increase anxiety or decrease motor activities in an open-field test. KD attenuated the decrease in exploration ratio both in NOR and NPR tasks in kindled rats. Compared to the kindled ND rats, kindled KD rats stayed longer in target quarter during the probe trial testing of MWM. However, there were no differences in memory acquisition based on the MWM test results. In conclusion, KD attenuated the spatial and item memory impairment in PTZ-induced seizures.


Assuntos
Dieta Cetogênica , Excitação Neurológica , Transtornos da Memória/dietoterapia , Convulsões/complicações , Memória Espacial/fisiologia , Animais , Peso Corporal , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/etiologia , Pentilenotetrazol , Ratos , Ratos Sprague-Dawley , Reconhecimento Psicológico/fisiologia , Convulsões/induzido quimicamente
9.
Int J Comput Assist Radiol Surg ; 6(2): 187-99, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20589441

RESUMO

PURPOSE: To accelerate the simultaneous algebraic reconstruction technique (SART) with motion compensation for speedy and quality computed tomography reconstruction by exploiting CUDA-enabled GPU. METHODS: Two core techniques are proposed to fit SART into the CUDA architecture: (1) a ray-driven projection along with hardware trilinear interpolation, and (2) a voxel-driven back-projection that can avoid redundant computation by combining CUDA shared memory. We utilize the independence of each ray and voxel on both techniques to design CUDA kernel to represent a ray in the projection and a voxel in the back-projection respectively. Thus, significant parallelization and performance boost can be achieved. For motion compensation, we rectify each ray's direction during the projection and back-projection stages based on a known motion vector field. RESULTS: Extensive experiments demonstrate the proposed techniques can provide faster reconstruction without compromising image quality. The process rate is nearly 100 projections s (-1), and it is about 150 times faster than a CPU-based SART. The reconstructed image is compared against ground truth visually and quantitatively by peak signal-to-noise ratio (PSNR) and line profiles. We further evaluate the reconstruction quality using quantitative metrics such as signal-to-noise ratio (SNR) and mean-square-error (MSE). All these reveal that satisfactory results are achieved. The effects of major parameters such as ray sampling interval and relaxation parameter are also investigated by a series of experiments. A simulated dataset is used for testing the effectiveness of our motion compensation technique. The results demonstrate our reconstructed volume can eliminate undesirable artifacts like blurring. CONCLUSION: Our proposed method has potential to realize instantaneous presentation of 3D CT volume to physicians once the projection data are acquired.


Assuntos
Gráficos por Computador , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Algoritmos , Artefatos , Humanos , Aumento da Imagem/métodos , Imageamento Tridimensional , Matemática , Movimento (Física) , Software , Fatores de Tempo
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