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One of the major mediators of multidrug resistance (MDR) in non-small cell lung cancer (NSCLC) is the overexpression of ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we conducted in vitro and in vivo experiments to determine whether PD153035, an inhibitor of EGFR, could reverse ABCG2-mediated MDR in human NSCLC and transfected cells overexpressing ABCG2. The efficacy of SN-38, topotecan, and mitoxantrone (MX) were significantly increased by PD153035, PD153035 significantly reversed ABCG2-mediated MDR by attenuating the efflux activity of this transporter. In addition, PD153035 significantly down-regulated the expression of the ABCG2 transporter protein. Furthermore, a combination of PD153035 and topotecan, exhibited significant synergistic anticancer activity against mice xenografted with human H460/MX20â¯cells. These results, provided that they can be extrapolated to humans, suggest that the combination of topotecan and PD153035 could be a promising therapeutic strategy to attenuate the resistance to topotecan, as well as other anticancer drugs, mediated by the overexpression of ABCG2.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas de Neoplasias/genética , Quinazolinas/administración & dosificación , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Masculino , Ratones , Quinazolinas/farmacología , Topotecan/administración & dosificación , Topotecan/farmacología , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIM: To assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29) in Chinese patients with colorectal cancer (CRC). METHODS: From March 2014 to January 2015, 356 patients with CRC from four different hospitals in China were enrolled in the study, and all patients self-administered the EORTC QLQ-CR29 and the quality of life core questionnaire (EORTC QLQ-C30). Evaluation of the scores was based on the Karnofsky Performance Scale (KPS). The reliability and validity of the questionnaires were assessed by Cronbach's α coefficient, the Spearman correlation test and Wilcoxon rank sum test. RESULTS: The EORTC QLQ-CR29 showed satisfactory reliability (α > 0.7), although the urinary frequency and blood and mucus in stool dimensions had only moderate reliability (α = 0.608). The multitrait scaling analyses showed good convergent (r > 0.4) and discriminant validity. Significant differences were obtained for each item in the different KPS subgroups (KPS ≤ 80; KPS > 80). Body image and most single-item dimensions showed statistically significant differences in patients with a stoma compared with the rest of the patients. CONCLUSION: The EORTC QLQ-CR29 exhibits high validity and reliability in Chinese patients with CRC, and can therefore be recommended as a valuable tool for the assessment of quality of life in these patients.
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Imagen Corporal/psicología , Neoplasias Colorrectales/psicología , Psicometría/métodos , Calidad de Vida , Estomas Quirúrgicos/efectos adversos , Adulto , Anciano , Pueblo Asiatico/psicología , China/epidemiología , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
OBJECTIVES: The aims of this study were to explore the Pittsburgh Sleep Quality Index (PSQI) and health service utilization in Chinese general population, to investigate the association between PSQI and health service utilization and to identify the independent contributions of social demographic variables, health related factors and PSQI to health service utilization. METHODS: In a cross-sectional community-based health survey using a multi-instrument questionnaire, 4067 subjects (≥15 years old) were studied. The Chinese version of the PSQI was used to assess sleep quality. Health service utilization was measured by recent two-week physician visit and annual hospitalization rates. RESULTS: Higher PSQI scores were associated with more frequent health service utilization. Higher scores in subjective sleep quality were associated with higher rate of recent two-week physician visit (adjusted OR = 1.24 per SD increase, P = 0.015). Higher scores in habitual sleep efficiency (adjusted OR = 1.24 per SD increase, P = 0.038) and sleep disturbances (adjusted OR = 2.09 per SD increase, P < 0.001) were associated with more frequent annual hospitalization. The independent influence of PSQI on the risk of recent two-week physician visit was 0.7%, and that of annual hospitalization 31.4%. CONCLUSIONS: Poorer sleep quality predicted more frequent health service utilization. The independent contribution of PSQI on health service utilization was smaller than social demographic variables.
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Aceptación de la Atención de Salud , Sueño , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China , Análisis por Conglomerados , Estudios Transversales , Femenino , Hospitalización , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Previous studies have confirmed that low serum albumin levels in acute ischemic stroke patients increased the risk for poor outcome and death, demonstrating the neuroprotective role of albumin. However, there are few studies investigating the relationship between albumin levels and recurrence of stroke. The aim of this study was to evaluate the effect of serum albumin level on the risk of recurrence in patients with acute ischemic stroke. METHODS: Seven hundred fifty-three consecutive patients with acute first-ever ischemic stroke were recruited in this study. Recurrent outcome was measured 1 year after stroke through home interviews (n = 692). RESULTS: Patients with recurrence had significantly lower serum albumin level than those without recurrence (37.07 ± 4.21 vs 38.91 ± 3.25). The multiple logistic regression adjustment for confounding factors showed that the association remained significant for patients in the second albumin quartile, the third quartile, and the fourth quartile compared with patients in the first quartile (adjusted odds ratio [aOR] = 0.543, 95% confidence interval [CI]: 0.307-0.959, P= .036; aOR = 0.449, 95% CI: 0.249-0.812, P= .008; and aOR = 0.290, 95% CI: 0.148-0.570, P < .001). CONCLUSION: Lower serum albumin level increases the risk of recurrence in patients with acute ischemic stroke, suggesting that serum albumin level might be used as an indicator for stroke recurrence.
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Isquemia Encefálica/metabolismo , Hipoalbuminemia/metabolismo , Obesidad/metabolismo , Sobrepeso/metabolismo , Albúmina Sérica/metabolismo , Accidente Cerebrovascular/metabolismo , Delgadez/metabolismo , Anciano , Isquemia Encefálica/complicaciones , Isquemia Encefálica/epidemiología , China/epidemiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Hipoalbuminemia/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/epidemiología , Oportunidad Relativa , Sobrepeso/epidemiología , Pronóstico , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Delgadez/epidemiologíaRESUMEN
The 14-item Chalder Fatigue Scale (CFS) is widely used, while the 11-item version is seldom to be found in current research in mainland China. The objectives of the present study is to compare the reliability and construct validity between these two versions and to confirm which may be better for the mainland Chinese setting. Based on a cross-sectional health survey with a constructive questionnaire, 1887 individuals aged 18 years or above were selected. Socio-demographic, health-related, gynecological data were collected, and 11-item and 14-item Chalder Fatigue Scale (CFS) were used to assess fatigue. Confirmatory factor analysis and exploratory structural equation modeling (ESEM) were performed to test the fit of models of the two versions. Confirmatory factor analysis of the two versions of CFS did not support the two-factor theorized models. In addition, a three-factor ESEM model of the 11-item version, but not the 14-item version, showed better factor structure and fitness than the other models examined. Both the versions had good internal consistency reliability and a satisfactory internal consistency (Ω = 0.78-0.96, omega coefficient indicates the internal consistency reliability) was obtained from the optimal model. This study provided evidence for satisfactory reliability and structural validity for the three-factor model of the 11-item version, which was proven to be superior to the 14-item version for this data.
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Pueblo Asiatico/psicología , Pueblo Asiatico/estadística & datos numéricos , Pruebas Diagnósticas de Rutina/normas , Fatiga/diagnóstico , Fatiga/psicología , Psicometría , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China , Estudios Transversales , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Adulto JovenRESUMEN
It is well known that excess iodide can lead to thyroid colloid retention, a classic characteristic of iodide-induced goiter. However, the mechanism has not been fully unrevealed. Iodide plays an important role in thyroid function at multiple steps of thyroid colloid synthesis and transport among which sodium/iodide symporter (NIS) and pendrin are essential. In our study, we fed female BALB/c mice with different concentrations of high-iodine water including group A (control group, 0 µg/L), group B (1500 µg/L), group C (3000 µg/L), group D (6000 µg/L), and group E (12,000 µg/L). After 7 months of feeding, we found that excess iodide could lead to different degrees of thyroid colloid retention. Besides, NIS and pendrin expression were downregulated in the highest dose group. The thyroid iodide intake function detected by urine iodine assay and thyroidal (125)I experiments showed that the urine level of iodine increased, while the iodine intake rate decreased when the concentration of iodide used in feeding water increased (all p < 0.05 vs. control group). In addition, transmission electron microscopy (TEM) indicated a reduction in the number of intracellular mitochondria of thyroid cells. Based on these findings, we concluded that the occurrence of thyroid colloid retention exacerbated by excess iodide was associated with the suppression of NIS and pendrin expression, providing an additional insight of the potential mechanism of action of excess iodide on thyroid gland.
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Proteínas de Transporte de Anión/antagonistas & inhibidores , Yoduros/farmacología , Simportadores/antagonistas & inhibidores , Glándula Tiroides/efectos de los fármacos , Animales , Proteínas de Transporte de Anión/genética , Proteínas de Transporte de Anión/metabolismo , Coloides/química , Coloides/metabolismo , Femenino , Yoduros/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Transportadores de Sulfato , Simportadores/genética , Simportadores/metabolismo , Glándula Tiroides/metabolismo , Glándula Tiroides/patologíaRESUMEN
OBJECTIVE: To explore the impact of workplace violence on job performance and quality of life of community healthcare workers in China, especially the relationship of these three variables. METHODS: From December 2013 to April 2014, a total of 1404 healthcare workers were recruited by using the random cluster sampling method from Community Health Centers in Guangzhou and Shenzhen. The workplace violence scale, the job performance scale and the quality of life scale (SF-36) were self-administered. The structural equation model constructed by Amos 17.0 was employed to assess the relationship among these variables. RESULTS: Our study found that 51.64% of the respondents had an experience of workplace violence. It was found that both job performance and quality of life had a negative correlation with workplace violence. A positive association was identified between job performance and quality of life. The path analysis showed the total effect (ß = -0.243) of workplace violence on job performance consisted of a direct effect (ß = -0.113) and an indirect effect (ß = -0.130), which was mediated by quality of life. CONCLUSIONS: Workplace violence among community healthcare workers is prevalent in China. The workplace violence had negative effects on the job performance and quality of life of CHCs' workers. The study suggests that improvement in the quality of life may lead to an effective reduction of the damages in job performance caused by workplace violence.
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Servicios de Salud Comunitaria , Personal de Salud/estadística & datos numéricos , Calidad de Vida , Rendimiento Laboral/estadística & datos numéricos , Violencia Laboral/estadística & datos numéricos , Adulto , China , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Recursos Humanos , Lugar de Trabajo , Adulto JovenRESUMEN
BACKGROUND: Fatigue has been widely studied in the general population; however, limited studies have investigated it in the female population. The objectives of this community-based study were to (1) investigate the prevalence of fatigue, (2) explore the relationship between gynecological history and experiences of fatigue, and (3) identify risk factors for fatigue in middle-aged and elderly women. METHODS: Based on a cross-sectional health study that employed a multi-instrument questionnaire, 1272 women aged 45years or older dwelling in the community were included. The Chinese version of Chalder Fatigue Scale (CFS) was used to assess fatigue, and socio-demographic, health-related, and gynecological data were also collected. Fatigue was defined as a total CFS score≥4. RESULTS: The prevalence of fatigue among women aged over 45years was 33.9%. Multivariate logistic regression analysis identified that older age, single marital status, lower education level, the presence of chronic diseases, underweight, hospitalization in the last year, postmenopause, and a higher number of live births were associated with an increased risk of fatigue (P<0.05). CONCLUSIONS: Our results indicated that fatigue was common in middle-aged and elderly females. Being postmenopausal and having more than three live births were the particular gynecological factors contributing to fatigue in the general population.
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Fatiga/epidemiología , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Prevalencia , Características de la Residencia , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The aim of this study was to investigate the prevalence of posttraumatic stress disorder (PTSD) and its risk factors among survivors in a heavily-hit area five years after the Wenchuan earthquake in 2008, China. METHODS: 684 survivors from Beichuan county, the center of the Wenchuan Earthquake in 2008, were evaluated using the PTSD Checklist-Civilian Version (PCL-C) questionnaire in 2013. RESULTS: The prevalence of PTSD among survivors was 9.2% in 2013. Significant risk factors of PTSD included gender (females 12.1%, males 5.2%), age (18-35 y 0.8%, 36-59 y 9.7%, ≥60 y 12.9%), occupation (farmers 12.2%, non-farmers 1.6%), education (less than high school 11.0%; > = high school 0.8%) and family member loss (yes: 12.4%, no: 7.3%). Multivariate logistic regression showed that females, older people, farmers and those with family member loss were significantly more likely to develop PTSD. CONCLUSIONS: Posttraumatic stress symptoms remained relatively common among survivors five years after the "5.12" Earthquake in Beichuan county, China. It is important to provide psychological aid and social support for survivors to decease health burden from PTSD, especially for females, farmers, old age survivors and those with family member loss.
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Desastres , Terremotos , Trastornos por Estrés Postraumático/epidemiología , Sobrevivientes/estadística & datos numéricos , Adulto , Anciano , China/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Prevalencia , Calidad de Vida/psicología , Factores de Riesgo , Distribución por Sexo , Apoyo Social , Trastornos por Estrés Postraumático/psicología , Encuestas y Cuestionarios , Sobrevivientes/psicología , Adulto JovenRESUMEN
To investigate the roles and mechanism(s) of epigallocatechin gallate (EGCG) in carcinogenesis in malignant transformed cell line, cadmium-induced malignant transformed cells were treated with different doses of EGCG. Then cell proliferation, cell apoptosis, hTERT mRNA and protein level, and c-Myc protein levels were measured at different time points. EGCG was found to inhibit cell proliferation in a dose-dependent manner. Cell cycle was changed in the transformed cells after EGCG treatment with significantly increased cell numbers in G0/G1 phase and decreased cell numbers in S phase compared to control group, P < 0.001. EGCG was also found to promote cell apoptosis with a time-dependent manner. Both mRNA and protein levels of hTERT gene were significantly decreased in cells after treated with EGCG, P < 0.001. c-Myc protein level was significantly decreased after EGCG treatment, especially in the highest dose group (i.e. 200 µg/ml). The decrease in c-Myc protein level was accompanied by the reduction of hTERT protein levels. EGCG can inhibit cell proliferation and promote apoptosis in malignant cadmium-transformed cell line. The mechanism may be its ability to reduce c-Myc gene expression and consequently inhibits hTERT gene expression, which in turn decrease the telomerase activity.
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BACKGROUND: Community-based health education programs may be helpful in improving health outcomes in patients with chronic illnesses. This study aimed to evaluate community-based health education strategies in the management of hypertensive patients with low socioeconomic status in Dongguan City, China. METHODS: This was a randomized, non-blinded trial involving 360 hypertensive patients enrolled in the community health service centre of Liaobu Town, Dongguan City, China. Participants were randomized to receive one of the three community-based health education programs over 2 years: self-learning reading (Group 1), monthly regular didactic lecture (Group 2), monthly interactive education workshop (Group 3). Outcomes included the changes in the proportion of subjects with normalized blood pressure (BP), hypertension-related knowledge score, adherence to antihypertensive treatment, lifestyle, body mass index and serum lipids. RESULTS: After the 2-y intervention, the proportion of subjects with normalized BP increased significantly in Group 2 (from 41.2% to 63.2%, p<0.001), and increased more substantially in Group 3 (from 40.2% to 86.3%, p<0.001), but did not change significantly in Group 1. Improvements in hypertension-related knowledge score, adherence to regular use of medications, appropriate salt intake and regular physical activity were progressively greater from group 1 to group 2 to group 3. Group 3 had the largest reductions in body mass index and serum LDL cholesterol levels. CONCLUSION: Interactive education workshops may be the most effective strategy in community-based health promotion education programs for hypertensive patients in improving patients' knowledge on hypertension and alleviating clinical risk factors for preventing hypertension-related complications.
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Centros Comunitarios de Salud/organización & administración , Conductas Relacionadas con la Salud , Educación en Salud/métodos , Hipertensión/terapia , Educación del Paciente como Asunto/métodos , Participación del Paciente/estadística & datos numéricos , Adulto , Antihipertensivos/uso terapéutico , China , Femenino , Humanos , Hipertensión/prevención & control , Masculino , Persona de Mediana Edad , Evaluación de Programas y Proyectos de SaludRESUMEN
BACKGROUND: Rural-to-urban migrant workers have been increasing rapidly in China over recent decades. Health related quality of life (HRQOL) may affect health service utilization. There is a lack of data on HRQOL in relation to health service utilization in Chinese rural-to-urban migrant workers. This study was aimed to explore the influence of HRQOL on health service utilization in Chinese rural-to-urban female migrant workers. METHODS: This was a cross-sectional survey of 1,438 female rural-to-urban migrant workers in Shenzhen-Dongguan economic zone, China in 2013. HRQOL was assessed by the 36-items Health Survey Short Form (SF-36). Health service utilization was measured by any physician visit over the recent two weeks and any hospitalization over the last 1-year (annual hospitalization). Clustered logistic regression was used to analyze the influence of HRQOL on health service utilization. RESULTS: Lower scores in three HRQOL domains (bodily pain, general health, role physical) were associated with more frequent health service utilization in female rural-to-urban migrant workers. Bodily pain and general health were associated with an independent influence of 15.6% on the risk of recent two-week physician visit, while role physical and general health were associated with an independent influence of 21.2% on the risk of annual hospitalization. The independent influence of HRQOL on health service utilization was smaller than that of socio-demographic and health-related variables. CONCLUSIONS: HRQOL may have a modest influence on health service utilization in Chinese rural-to-urban female migrant workers - an underprivileged population in urban China.
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Calidad de Vida , Migrantes , Servicios Urbanos de Salud/estadística & datos numéricos , Adolescente , Adulto , China , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Hospitalización/estadística & datos numéricos , Humanos , Modelos Logísticos , Persona de Mediana Edad , Salud Rural , Salud Urbana , Salud de la Mujer , Adulto JovenRESUMEN
Translation elongation factor-1d (TEF-1δ) has been identified as a novel cadmium-responsive proto-oncogene. However, it is still unclear whether TEF-1δ could be a potential biomarker of cadmium exposure. Rats were treated with CdCl2 at different concentrations (high dose 1.225, mid-dose 0.612 and low dose 0.306 mg/kg body weight, respectively) for 14 weeks, and the cadmium levels, weight coefficients, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCR), 24-h urine protein (24hPro), urinary creatinine (Cr) and pathological features were determined. The TEF-1δ expression in white blood cells and multiple organs were examined by reverse transcription polymerase chain reaction (PCR) and were also confirmed with fluorescence quantitative PCR. A cadmium dose-dependent increase (p < 0.05) of cadmium levels in blood, urine, liver, kidney, heart and lung, and the weight coefficients was observed. The liver and renal function indictors including AST, ALT, SCR, BUN and 24hPro, were elevated in a cadmium dose-dependent manner (p < 0.05). Significant pathological changes in liver, kidney, heart and lung were indicated. The TEF-1δ expression was up-regulated in both blood and organs (p < 0.05). Moreover, the expression level of blood TEF-1δ was positively correlated to TEF-1δ expression level, cadmium level and toxicity in the organs (p < 0.01). This study indicates that blood TEF-1δ is a novel valuable biomarker for cadmium exposure and its organ toxicity.
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BACKGROUND: Famine provides quasi-experimental conditions for testing the hypothesis of "programming" health effects by poor nutrition in early life. It remains uncertain whether early life exposure to famine increases the risk of hypertension in adulthood. There is a lack of data on the relative impact of exposure to famine during fetal development versus infancy (<2 years postnatal). We sought to assess the impact of exposure to the 1959-1961 Chinese Great Famine (the largest in human history) during fetal development and infancy on the risks of hypertension, short stature and obesity in adulthood. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective cohort study of 12,065 adults (46-53 years of age) born 1957-1964 in the Zhongshan and Nanhai municipalities of Guangdong province, China. Adjusting for socio-demographic and lifestyle characteristics, as compared to subjects who were unexposed to famine, the risk of hypertension was not significantly elevated in subjects exposed to famine during fetal development only overall, but was 1.36-fold higher in those exposed during the first trimester of pregnancy only [adjusted odds ratio (OR) 1.36 (95% confidence intervals 1.03-1.79)], 1.83-fold higher in those exposed during infancy only [adjusted OR 1.83 (1.61-2.08)], and 1.31-fold higher in those exposed during both fetal development and infancy [adjusted OR 1.31 (1.14-1.51)]. Exposure to famine during infancy increased the risk of short stature. Early life exposure to famine did not increase the risk of obesity. CONCLUSIONS/SIGNIFICANCE: Exposure to the Chinese Great Famine during the first trimester of pregnancy only, or during infancy only, or during both fetal development and infancy increased the risk of hypertension in adulthood, suggesting an important role of changes in exposure to famine during fetal development and from prenatal to early postnatal life in developmental "programming" cardiovascular disease risk.
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Hipertensión/diagnóstico , Efectos Tardíos de la Exposición Prenatal , Presión Sanguínea , Estatura , Índice de Masa Corporal , Peso Corporal , China , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Hipertensión/etiología , Recién Nacido , Masculino , Persona de Mediana Edad , Obesidad , Oportunidad Relativa , Embarazo , Estudios Retrospectivos , Riesgo , Inanición , Factores de TiempoRESUMEN
BACKGROUND: This study was the first of its kind to analyze the finance protection in New Rural Cooperative Medical Scheme in China using a claim database analysis. METHODS: A claim database analysis of all hospitalizations reimbursed from the New Rural Cooperative Medical Scheme between January 2005 and December 2008 in Panyu district of Guangzhou covering 108,414 discharges was conducted to identify the difference in real reimbursement rate among 5 hospitalization cost categories by sex, age, and hospital type and to investigate the distributions of hospital-type choices among age and hospitalization cost categories. RESULTS: The share of total cost reimbursed was only 34% on average, and increased with age but decreased with higher hospitalization cost, undermining catastrophic coverage. Older people were more likely to be hospitalized at lower level hospitals with higher reimbursement rate. The mean cost per hospitalization and average length of stay increased whereas the real reimbursement rate decreased with hospital level among the top 4 diseases with the same ICD-10 diagnostic code (3-digit level) for each age group. CONCLUSIONS: Providing better protection against costly medical needs will require shifting the balance of objectives somewhat away from cost control toward more generous reimbursement, expanding the list of treatments that the insurance will cover, or some other policy to provide adequate care at lower cost facilities where more of the cost is now covered.
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Costos de Hospital/estadística & datos numéricos , Hospitalización/economía , Reembolso de Seguro de Salud/economía , Servicios de Salud Rural/economía , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , China , Femenino , Humanos , Lactante , Recién Nacido , Revisión de Utilización de Seguros/estadística & datos numéricos , Clasificación Internacional de Enfermedades , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/economía , Factores Sexuales , Factores Socioeconómicos , Adulto JovenRESUMEN
Eukaryotic translation initiation factor 3 (eIF3) and elongation factor 1δ (eEF-1δ) are novel cadmium (Cd) responsive proto-oncogenes. This research investigated the expression of these genes in Cd-exposed workers (n = 58), and to evaluate their usefulness as biomarkers of Cd exposure. According to urinary Cd concentration, the subjects were divided into four groups (urinary Cd concentration ≥0.1 µg/g.Cr, ≥1.0 µg/g.Cr, ≥5.0 µg/g.Cr and ≥50.0 µg/g.Cr). Subjects exhibited increased severe health problems with higher urinary Cd concentrations. The eIF3 and eEF-1δ expression in the blood were investigated with real-time PCR. PCR data showed a strong positive correlation between blood eEF-1δ and urinary Cd concentrations (r = 0.788, p < 0.01), and a weak positive correlation between blood eIF3 expression and urinary Cd concentrations (r = 0.569, p < 0.05). These findings, for the first time, demonstrate that the blood eEF-1δ overexpression can be used as a molecular biomarker of Cd-exposed population.
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Cadmio/toxicidad , Cadmio/orina , Enfermedades Profesionales/inducido químicamente , Exposición Profesional , Factor 1 de Elongación Peptídica/sangre , Faringitis/inducido químicamente , Adulto , Biomarcadores/sangre , Biomarcadores/orina , China , Factor 3 de Iniciación Eucariótica/sangre , Femenino , Humanos , Masculino , Enfermedades Profesionales/sangre , Enfermedades Profesionales/orina , Faringitis/sangre , Faringitis/orinaRESUMEN
Cadmium (Cd) and its compounds are well-known human carcinogens, but the mechanisms underlying the carcinogenesis are not entirely understood yet. Aberrant methylation was investigated in order to obtain insight into the DNA repair-related epigenetic mechanisms underlying CdCl(2)-induced malignant transformation of human bronchial epithelial cells (16HBE). Gene expression and DNA methylation were assessed in untreated control cells; 5th, 15th, and 35th passage of CdCl2-treated cells and tumorigenic cells (TCs) from nude mice by using high-performance liquid chromatography, real-time PCR, Western blot analysis, and methylation-specific PCR assay. During Cd-induced malignant transformation, global DNA methylation progressively increased and was associated with the overexpression of the DNA methyltransferase genes DNMT1 and DNMT3a but not DNMT3b. Expression of both the messenger RNA and proteins of the DNA repair genes (hMSH2, ERCC1, XRCC1, and hOGG1) progressively reduced and DNA damage increased with Cd-induced transformation. The promoter regions of hMSH2, ERCC1, XRCC1, and hOGG1 were heavily methylated in the 35th passage transformed cells and the TCs. The DNA demethylating agent 5-aza-2'-deoxycytidine could reverse the Cd-induced global DNA hypermethylation, DNMT hyperactivity, and the silencing of hMSH2, ERCC1, XRCC1, and hOGG1 in a time-dependent manner. The results indicate that DNMT1 and DNMT3a overexpression can result in global DNA hypermethylation and silencing of the hMSH2, ERCC1, XRCC1, and hOGG1 genes. They may partly explain the epigenetic mechanisms underlying the carcinogenesis due to Cd.
Asunto(s)
Bronquios/efectos de los fármacos , Cloruro de Cadmio/toxicidad , Carcinógenos/toxicidad , Transformación Celular Neoplásica/inducido químicamente , Metilación de ADN , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/genética , Células Epiteliales/efectos de los fármacos , Animales , Azacitidina/análogos & derivados , Azacitidina/farmacología , Western Blotting , Bronquios/enzimología , Bronquios/patología , Línea Celular Transformada , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Cromatografía Líquida de Alta Presión , Metilasas de Modificación del ADN/antagonistas & inhibidores , Enzimas Reparadoras del ADN/metabolismo , Decitabina , Inhibidores Enzimáticos/farmacología , Células Epiteliales/enzimología , Células Epiteliales/patología , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Desnudos , Regiones Promotoras Genéticas , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de TiempoRESUMEN
OBJECTIVE: To study the alternative expression and sequence of human elongation factor-1 delta (human EF-1 delta p31) during malignant transformation of human bronchial epithelial cells induced by cadmium chloride (CdC12) and its possible mechanism. METHODS: Total RNA was isolated at different stages of transformed human bronchial epithelial cells (16HBE) induced by CdCl2 at a concentration of 5.0 microM. Special primers and probe for human EF-1 delta p31 were designed and expression of human EF-1 delta mRNA from different cell lines was detected with fluorescent quantitative PCR technique. EF-18 cDNA from different cell lines was purified and cloned into pMD 18-T vector followed by confirming and sequencing analysis. RESULTS: The expressions of human EF-1 beta p31 at different stages of 16HBE cells transformed by CdCl2 was elevated (P < 0.01 or P < 0.05). Compared with their corresponding non-transformed cells, the overexpression level of EF-1 delta p31 was averagely increased 2.9 folds in Cd-pretransformed cells, 4.3 folds in Cd-transformed cells and 7.2 folds in Cd-tumorigenic cells. No change was found n the sequence of overexpressed EF-1beta p31 at different stages of 16HBE cells transformed by CdCl2. CONCLUSION: Overexpression of human EF-1beta p31 is positively correlated with malignant transformation of 16HBE cells induced by CdC12, but is not correlated with DNA mutations.
Asunto(s)
Transformación Celular Neoplásica/metabolismo , Células Epiteliales/patología , Regulación Neoplásica de la Expresión Génica , Factor 1 de Elongación Peptídica/metabolismo , Mucosa Respiratoria/patología , Cloruro de Cadmio , Línea Celular , Transformación Celular Neoplásica/inducido químicamente , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Humanos , Factor 1 de Elongación Peptídica/genética , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismo , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To analyze the relationship between malignant transformation and abnormal expression of eukaryotic initiation factor 3 (eIF3 p36) in human bronchial epithelial (16HBE) cells induced by cadmium chloride (CdCl2). METHODS: 16HBE cells were treated several times with different concentrations of CdCl2. Tumorigenic potential of transformed cells was identified by assays for anchorage-independent growth in soft agar and for tumorigenicity in nude mice after the 35th passage. Total RNA was isolated from 16HBE cells induced by CdCl2, including non-transformed, Cd-transformed, and Cd-tumorigenic cell lines. Special primers for eIF3 p36 were designed and the expression of eIF3 mRNA in different cell lines was detected with fluorescent quantitative-polymerase chain reaction technique (FQ-PCR). RESULTS: The 35th passage of 16HBE cells transformed by CdCl2 exhibited overlapping growth. Compared with the non-transformed cells, colonies of transformed cell lines in soft agar showed statistically significant increases and dose-dependent effects (P<0.01). All Cd-induced transformed cell lines formed tumors in nude mice within 2 weeks of inoculation, but none of the mice injected with non-transformed cells showed tumors even after 3 weeks. All tumors were pathologically identified as poorly differentiated squamous cell carcinoma. The eIF3 p36 genes in different stages of 16HBE cells transformed by CdCl2 were elevated as compared with the non-transformed control (P<0.01), and the eIF3 expression increased with the degree of cell malignancy. CONCLUSION: CdCl2 is capable of inducing morphological transformation in 16HBE cells and transformed cells are potentially tumorigenic. Over-expression of eIF3 p36 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2 and may be one of the molecular mechanisms potentially responsible for carcinogenesis due to Cd.
Asunto(s)
Bronquios/efectos de los fármacos , Cloruro de Cadmio/farmacología , Transformación Celular Neoplásica , Factores Eucarióticos de Iniciación/metabolismo , Animales , Secuencia de Bases , Bronquios/citología , Bronquios/metabolismo , Cartilla de ADN , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Humanos , Ratones , Ratones Desnudos , Reacción en Cadena de la PolimerasaRESUMEN
OBJECTIVE: This study was undertaken to evaluate the ecological association between terrestrial natural radionuclide, indoor radon concentration, natural radioactivity and leukemia incidence among children under 18 years of age. METHODS: Data were gathered from the disease surveillance program and literature reading while software SPSS 13.0 was used to calculate the Spearman's correlation. RESULTS: The incidence rates of childhood (0-18 year) leukemia showed significant differences in different places with the highest as 3.13/10(5) in Jiangmen area and the lowest as 0.42/10(5) in Maoming area. The incidence in Jiangmen was 7.45 times higher than that in Maoming. There was a rank correlation between the incidence of childhood leukemia and the mean concentrations of natural radio-nuclides in soil (226Ra and 232Th), with a positive correlation observed for overall leukemia (r(s) = 0.70, P = 0.011; r(s) = 0.66, P= 0.02 for 226 Ra and 232Th respectively) and acute lymphoblastic leukemia (ALL) (r(s) = 0.66, P = 0.019; r(s) = 0.64, P = 0.025 for 226 Ra and 232Th respectively). Associations between the incidence of childhood leukemia and the indoor gamma radiation dose rate, the total annual average effective dose equivalent from natural background radiationwere also analyzed (both r(s) = 0.59, P = 0.042). CONCLUSION: The natural radioactivity was likely to be a causative factor for childhood leukemia in Guangdong.