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1.
Stem Cells ; 35(4): 1053-1064, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28009085

RESUMO

The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors. While PRL2 deficiency resulted in moderate defects of thymopoiesis in the steady state, de novo generation of T cells from Prl2 null hematopoietic stem cells was significantly reduced following transplantation. Prl2 null HSPCs also showed impaired T cell differentiation in vitro. We found that Notch/RBPJ signaling upregulated PRL2 as well as c-Kit expression in T cell progenitors. Further, PRL2 sustains Notch-mediated c-Kit expression and enhances stem cell factor/c-Kit signaling in T cell progenitors, promoting effective DN1-DN2 transition. Thus, we have identified a critical role for PRL2 phosphatase in mediating Notch and c-Kit signals in early T cell progenitors. Stem Cells 2017;35:1053-1064.


Assuntos
Proteínas Imediatamente Precoces/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptores Notch/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Linfócitos T/citologia , Animais , Animais Recém-Nascidos , Diferenciação Celular , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Camundongos Endogâmicos C57BL , Modelos Biológicos , Transdução de Sinais , Timo/metabolismo , Regulação para Cima
2.
Alcohol Clin Exp Res ; 40(3): 457-66, 2016 03.
Artigo em Inglês | MEDLINE | ID: mdl-26934204

RESUMO

BACKGROUND: The aim of this study was to examine the effects of Cyanidin 3-O-ß-glucoside (C3G) on ethanol (EtOH)-induced acute liver injury in mice as well as in cultured hepatic cells exposed to EtOH, with a focus on the involvement of Silent Mating Type Information Regulation 2 Homolog 1 (SIRT1)/Forkhead fox-O-1 (FOXO1) signaling pathway, and to explore the underlying molecular mechanisms. METHODS: C57BL/6 adolescent male mice were given EtOH via intraperitoneal injection for 2 consecutive days, and the changes in the livers were detected via hematoxylin-eosin staining. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by biochemical methods. Protein expression of SIRT1, FOXO1, acetylated FOXO1 (ac-FOXO1), GRP78, p-eukaryotic initiation factor-2 (eIF2α), and apoptosis (p-JNK, p-c-Jun, and Bax) parameters was determined by Western blot. Reactive oxygen species (ROS) was detected by flow cytometry. Human hepatocytes Chang cell line was used to assay cell apoptosis by Annexin V and propidium iodide. In addition, mRNA levels of SIRT1, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemoattractant protein 1 in liver tissues were detected by real-time polymerase chain reaction. RESULTS: This study demonstrated that C3G (10 mg/kg) administration diminished EtOH-induced acute liver injury compared to control group, as evidenced by the significant decreases in ALT and AST levels. Pretreatment with C3G exerted anti-inflammatory effects as indicated by the decreased TNF-α and IL-6 levels, as well as decreased inflammatory foci and ballooning cells in liver tissue. The lessened hepatic injury was associated with enhanced SIRT1 protein expression and activity by C3G in vitro and in vivo. C3G treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, p-eIF2α), which was consistent with reduced levels of both p-c-Jun and Bax. Interestingly, EX527 inhibitor did not affect the protective function of C3G on alcohol-induced cell apoptosis. Moreover, alcohol exposure increased ROS level and decreased ac-FOXO1, while C3G intervention reversed this abnormality, and this may be related to SIRT1 activity by C3G. CONCLUSIONS: Anthocyanin C3G has significant potency in antioxidant, anti-inflammatory, and anti-apoptotic effects on hepatocytes exposed to EtOH by modulating the SIRT1/FOXO1 signaling pathway. Our findings illustrate a novel and definitive therapeutic action of C3G and represent an economically feasible therapeutic intervention to treat alcoholic liver disease.

3.
J Epidemiol ; 26(12): 654-660, 2016 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-27431649

RESUMO

BACKGROUND: Studies on the association between body mass index (BMI) and death risk among patients with hypertension are limited, and the results are inconsistent. We investigated the association between BMI and cardiovascular disease (CVD) and all-cause mortality among hypertensive patients in a population of Beijing, China. METHODS: We conducted a prospective cohort study of 2535 patients with hypertension aged 40 to 91 years from Beijing, China. Participants with a history of CVD at baseline were excluded from analysis. Cox proportional hazards regression models were used to estimate the association of different levels of BMI stratification with CVD and all-cause mortality. RESULTS: During a mean follow-up of 8.1 years, 486 deaths were identified, including 233 cases of CVD death. The multivariable-adjusted hazards ratios for all-cause mortality associated with BMI levels (<20, 20-22, 22-24, 24-26 [reference group], 26-28, 28-30, and ≥30 kg/m2) were 2.03 (95% confidence interval [CI], 1.48-2.78), 1.61 (95% CI, 1.18-2.20), 1.30 (95% CI, 0.95-1.78), 1.00 (reference), 1.12 (95% CI, 0.77-1.64), 1.33 (95% CI, 0.90-1.95), and 1.66 (95% CI, 1.10-2.49), respectively. When stratified by age, sex, or smoking status, the U-shaped association was still present in each subgroup (P > 0.05 for all interactions). Regarding the association of BMI with CVD mortality, a U-shaped trend was also observed. CONCLUSIONS: The present study showed a U-shaped association of BMI with CVD and all-cause mortality among patients with hypertension. A lowest risk of all-cause mortality was found among hypertensive patients with BMI between 24 and 26 kg/m2.


Assuntos
Índice de Massa Corporal , Doenças Cardiovasculares/mortalidade , Hipertensão/epidemiologia , Sobrepeso/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Pequim/epidemiologia , Causas de Morte , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estudos Prospectivos , Risco
4.
Water Sci Technol ; 69(10): 2052-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24845320

RESUMO

Optimal design of activated sludge process (ASP) using multi-objective optimization was studied, and a benchmark process in Benchmark Simulation Model 1 (BSM1) was taken as a target process. The objectives of the study were to achieve four indexes of percentage of effluent violation (PEV), overall cost index (OCI), total volume and total suspended solids, making up four cases for comparative analysis. Models were solved by the non-dominated sorting genetic algorithm in MATLAB. Results show that: ineffective solutions can be rejected by adding constraints, and newly added objectives can affect the relationship between the existing objectives; taking Pareto solutions as process parameters, the performance indexes of PEV and OCI can be improved more than with the default process parameters of BSM1, especially for N removal and resistance against dynamic NH4(+)-N in influent. The results indicate that multi-objective optimization is a useful method for optimal design ASP.


Assuntos
Benchmarking , Esgotos , Eliminação de Resíduos Líquidos/métodos , Reatores Biológicos , Conservação de Recursos Energéticos
5.
Mol Cancer Res ; 22(1): 94-103, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37756563

RESUMO

Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells. IMPLICATIONS: Our studies uncover a novel mechanism that fine-tunes oncogenic KIT signaling in leukemia cells and will likely identify PRL2 as a novel therapeutic target in AML with KIT mutations.


Assuntos
Leucemia Mieloide Aguda , Monoéster Fosfórico Hidrolases , Animais , Camundongos , Leucemia Mieloide Aguda/genética , Mutação , Monoéster Fosfórico Hidrolases/genética , Fosforilação , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de Sinais/genética
6.
Nicotine Tob Res ; 15(2): 320-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22614545

RESUMO

INTRODUCTION: Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a Chinese population. METHODS: We enrolled 248 smokers in a hospital-based, randomized, smoking cessation trial conducted at four outpatient centers in Beijing. A total of 123 participants received an 8-week course of sustained-release bupropion (Bup-SR) and 125 participants received 8 weeks of placebo. All participants received brief education and counseling on smoking cessation. We determined rates of abstinence and smoking reduction based on chemical verification and self-report at 8 and 12 weeks. RESULTS: At the end of the medication treatment (8 weeks) and at the end of the trial (12 weeks), the abstinence rates for Bup-SR were 29.3% and 39.8%, respectively, and 10.4% and 8.0% for placebo, respectively (both p < .001). Bup-SR was also superior to placebo in reducing cigarettes per day and urinary cotinine levels. CONCLUSION: Bup-SR is efficacious for smoking cessation in healthy Chinese patients treated in the outpatient setting. It is well tolerated with a few mild side effects.


Assuntos
Bupropiona/uso terapêutico , Abandono do Hábito de Fumar , Adulto , China , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento
7.
Stem Cell Rev Rep ; 18(4): 1478-1494, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35318613

RESUMO

Exposure to potentially lethal high-dose ionizing radiation results in bone marrow suppression, known as the hematopoietic acute radiation syndrome (H-ARS), which can lead to pancytopenia and possible death from hemorrhage or infection. Medical countermeasures to protect from or mitigate the effects of radiation exposure are an ongoing medical need. We recently reported that 16,16 dimethyl prostaglandin E2 (dmPGE2) given prior to lethal irradiation protects hematopoietic stem (HSCs) and progenitor (HPCs) cells and accelerates hematopoietic recovery by attenuating mitochondrial compromise, DNA damage, apoptosis, and senescence. However, molecular mechanisms responsible for the radioprotective effects of dmPGE2 on HSCs are not well understood. In this report, we identify a crucial role for the NAD+-dependent histone deacetylase Sirtuin 1 (Sirt1) downstream of PKA and CREB in dmPGE2-dependent radioprotection of hematopoietic cells. We found that dmPGE2 increases Sirt1 expression and activity in hematopoietic cells including HSCs and pharmacologic and genetic suppression of Sirt1 attenuates the radioprotective effects of dmPGE2 on HSC and HPC function and its ability to reduce DNA damage, apoptosis, and senescence and stimulate autophagy in HSCs. DmPGE2-mediated enhancement of Sirt1 activity in irradiated mice is accompanied by epigenetic downregulation of p53 activation and inhibition of H3K9 and H4K16 acetylation at the promoters of the genes involved in DNA repair, apoptosis, and autophagy, including p53, Ku70, Ku80, LC3b, ATG7, and NF-κB. These studies expand our understanding of intracellular events that are induced by IR but prevented/attenuated by dmPGE2 and suggest that modulation of Sirt1 activity may facilitate hematopoietic recovery following hematopoietic stress. Graphical Abstract.


Assuntos
Células-Tronco Hematopoéticas , Sirtuína 1 , Proteína Supressora de Tumor p53 , Animais , Apoptose/genética , Células-Tronco Hematopoéticas/efeitos da radiação , Camundongos , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
8.
Prev Chronic Dis ; 8(1): A13, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21159225

RESUMO

INTRODUCTION: As a result of rapid economic development in China, the lifestyles and dietary habits of its people have been changing, and the rates of obesity, diabetes, and other chronic conditions have increased substantially. We report the prevalence of type 2 diabetes and impaired fasting glucose (IFG) and the association between diabetes and overweight and obesity in Chinese adults. We also compare the results with those from the US National Health and Nutrition Examination Survey, 1999-2002. METHODS: Data were from adults aged 20 years or older who participated in the China National Nutrition and Health Survey, 2002 (n = 47,729). Diabetes and IFG were defined by the American Diabetes Association 2009 criteria. We assessed the prevalence of diabetes, IFG, and overweight and obesity by sex, age, region of residence, and ethnicity. RESULTS: The prevalence of diabetes and IFG in Chinese adults was 2.7% and 4.9%, respectively. The prevalence of diabetes increased with age and body mass index. Men and women had a similar prevalence of diabetes, but men had a significantly higher prevalence of IFG. The prevalence of diabetes among Chinese who lived in urban areas was 2 to 3 times higher than the prevalence among those who lived in rural areas (3.9% for urban areas and 6.1% for large cities vs 1.9% for rural areas), and the prevalence of IFG was 1.5 to 2 times higher (6.1% and 8.1% vs 4.2%, respectively). The prevalence of diabetes among Chinese women and young (20-39 y) and middle-aged (40-59 y) adults who lived in large cities was similar to the prevalence of diabetes in the US population. CONCLUSION: The prevalence of diabetes and IFG was much higher in urban than rural areas, particularly in the large cities of China. Prevention must be emphasized among adults to reduce the future social and economic burden of diabetes in China.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Inquéritos Epidemiológicos/estatística & dados numéricos , Adulto , Distribuição por Idade , Glicemia , China/epidemiologia , Jejum , Feminino , Humanos , Masculino , Prevalência , Caracteres Sexuais , Fatores Socioeconômicos , Adulto Jovem
9.
Zhonghua Yu Fang Yi Xue Za Zhi ; 44(10): 908-12, 2010 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-21176522

RESUMO

OBJECTIVE: To analyze the relationship between low to moderate physical activity and the prevalence of metabolic syndrome (MS). METHODS: A multi-stage stratified cluster sampling was conducted in 31 provinces, autonomous regions, and municipalities in the interior of China according to the program of the National Nutrition and Health Survey in 2002. Questionnaire survey, interview, physical examination, measurement of biochemical indices and dietary investigation were done. In total, the physical activity of 26 477 persons aged 18 or above were investigated. The duration of low to moderate physical activity was divided into five grades: 0-min/week, 90-min/week, 151-min/week, 301-min/week, over 420 min/week, and the MS prevalence were investigated respectively. The relationship between MS and age (including four age groups 18-, 35-, 45-, 60 or above) or the duration of physical time were investigated. RESULTS: The MS prevalence among persons aged 18 or above was 9.4% (2490/26 477). And the prevalence was 10.3% (1191/11 516) in man and 8.7%(1299/14 961) in women, respectively (χ(2) = 21.035, P = 0.000). The MS prevalence was 2.1% (127/6070) in 18-years old group and 15.0% (1012/6734) in over 60 years old group. The MS prevalence increased with increasing age (χ(2) = 776.768, P = 0.000). 81.2% (21 499/26 477) of subjects engaged in low to moderate intensity physical activity. The percentage of spending time on physical activity over 420 min/week was dominant and as high as 43.7% (11 561/26 477). The MS prevalence was 13.8% (166/1203) for 0-min grade, 13.2% (64/485) for 90-min grade, 11.8% (153/1298) for 151-min grade, 10.1% (124/1225) for 301-min grade and 12.5% (512/4090) for over 420 min grade (χ(2) = 9.58, P = 0.047). Logistic regression analysis results showed, the MS risk of subjects spending 301-min per week on low to moderate intensity physical activity was significantly low than the MS prevalence among subjects of 90-min grade, OR = 0.844 (95%CI: 0.675 - 0.968), and no statistical difference was found in people spending over 420 min per week OR = 0.936(95%CI: 0.769 - 1.136). CONCLUSION: Most of people aged 18 or above engaged in low to moderate intensity physical activity. MS prevalence may be decreased by low to moderate intensity physical activity for 301-min per week, but the decrease was not significant while the duration of time was longer than 420 min per week.


Assuntos
Exercício Físico , Síndrome Metabólica/epidemiologia , Adolescente , Adulto , Pressão Sanguínea , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Adulto Jovem
10.
Zhonghua Xin Xue Guan Bing Za Zhi ; 38(3): 230-8, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-20450565

RESUMO

OBJECTIVE: To investigate the blood pressure control rate and related influencing factors in hypertensive outpatients. METHODS: In this multicentre, cross-sectional registration survey, hypertensive outpatients were recruited from department of cardiology, nephrology and endocrinology of 92 tertiary hospitals in 22 cites across China. Each centre enrolled more than 50 hypertensive outpatients aged 18 years or older between 20 April 2009 and 31 May 2009. Outpatients were surveyed by clinical interview with BP measurement and questionnaire. RESULTS: A total of 5086 subjects were enrolled, 2032 in department of cardiology, 1510 in department of endocrinology and 1544 in department of nephrology, 27.1% and 25.3% patients were in Grade 2 or Grade 3 hypertension, 37.2% patients were complicated with diabetes, 22.4% with coronary artery disease, and 18.4% with renal-dysfunction. Overall, controlled BP was achieved in 30.6% patients. The control rate was 45.9% in uncomplicated hypertensive patients, 31.3% in hypertensive patients with coronary artery disease, 14.9% in patients with diabetes, and 13.2% in patients with renal-dysfunction. Calcium channel blocker (56.6%) and angiotensin-II receptor blockers (32.0%) were the most frequently used medications. The mean number of antihypertensive agents prescribed per patient was 1.73, over 54.1% patients were treated with more than 2 antihypertensive drugs. Combination therapy or single-pill combination with various anti-hypertensive components was prescribed to 8.3% and 12.7% hypertensive patients as initial therapy. Multiple logistic regression analysis showed that lower BMI, no alcohol intake, free medical care, no diabetes, no renal-dysfunction, lipid-lowering therapy, shorter interval of visiting physicians, regular taking antihypertensive medications, physical activity were the factors related to satisfactory blood pressure control rate in hypertensive outpatients. CONCLUSIONS: Blood pressure control rate among Chinese hypertensive outpatients was increased compared with epidemiological survey in 2002. BMI, co-morbidities, lower combination treatment rate, poor compliance were the key reasons for lower BP control rate. Increased use of combination therapy instead of monotherapy should be encouraged to hypertensive outpatients to improve BP control rate.


Assuntos
Hipertensão/epidemiologia , Hipertensão/terapia , Pacientes Ambulatoriais , Sistema de Registros , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
12.
Circulation ; 118(25): 2679-86, 2008 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-19106390

RESUMO

BACKGROUND: The present article aims to provide accurate estimates of the prevalence, awareness, treatment, and control of hypertension in adults in China. METHODS AND RESULTS: Data were obtained from sphygmomanometer measurements and an administered questionnaire from 141 892 Chinese adults >/=18 years of age who participated in the 2002 China National Nutrition and Health Survey. In 2002, approximately 153 million Chinese adults were hypertensive. The prevalence was higher among men than women (20% versus 17%; P<0.001) and was higher in successive age groups. Overall, the prevalence of hypertension was higher in urban compared with rural areas in men (23% versus 18%; P<0.01) and women (18% versus 16%; P<0.001). Of the 24% affected individuals who were aware of their condition, 78% were treated and 19% were adequately controlled. Despite evidence to suggest improved levels of treatment in individuals with hypertension over the past decade, compared with estimates from 1991, the ratio of controlled to treated hypertension has remained largely unchanged at 1:4. CONCLUSIONS: One in 6 Chinese adults is hypertensive, but only one quarter are aware of their condition. Despite increased rates of blood pressure-lowering treatment, few have their hypertension effectively controlled. National hypertension programs must focus on improving awareness in the wider community, as well as treatment and control, to prevent many tens of thousands of cardiovascular-related deaths.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hipertensão/epidemiologia , Hipertensão/terapia , Inquéritos Nutricionais , Adolescente , Adulto , Anti-Hipertensivos/uso terapêutico , China/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento , Adulto Jovem
13.
Zhonghua Nei Ke Za Zhi ; 48(5): 388-91, 2009 May.
Artigo em Chinês | MEDLINE | ID: mdl-19615156

RESUMO

OBJECTIVE: To investigate the impact of high plasma LDL-C level with or without metabolic syndrome (MS) on the incidence of stroke in Chinese adults. METHODS: Totally 42 626 subjects (25-75 years old) from Chinese National Health and Nutrition Survey in 2002 were stratified four groups based on plasma LDL-C level:<2.00 mmol/L group, 2.00-2.50 mmol/L group, 2.51-3.31 mmol/L group, and >or=3.32 mmol/L group. The prevalence of MS (with 2005 International Diabetes Federation criteria) and stroke and the risk factors of stroke were compared among the four groups. RESULTS: (1) The prevalence of MS and stroke increased with rising of LDL-C level. The prevalence of MS in LDL-C>or=3.32 mmol/L group increased 2.5 times (7.9% vs 20.1%) as compared with that in LDL-C<2.00 mmol/L group and the prevalence of stroke increased 4.2 times (0.5% vs 2.1%), all P<0.01. (2) In subjects with similar LDL-C level, the prevalence of stroke was significantly higher in a subgroup with MS than that without (P<0.01). (3) After adjustment for age, sex and smoking, logistic regression analysis showed that both LDL-C level and MS were positively associated with the development of stroke; the odds ratio (OR) was 2.35 and 3.15 (P<0.0001), respectively. (4) Compared with the subgroup of LDL-C<2.00 mmol/L without MS, OR for stroke in the subgroups of LDL-C 2.00-2.50 mmol/L, 2.51-3.31 mmol/L, and >or=3.32 mmol/L without MS was 1.03, 1.89, and 2.08, whereas the OR for stroke in the subgroups with MS and similar level of LDL-C was 4.38, 5.23 and 6.15; this indicated that the risk of stroke in subjects with MS increased by 3-4 times compared with subjects without (P<0.0001). CONCLUSION: Both high LDL-C level and MS are independent risk factors of stroke, but the risk of stroke will be further increased in the presence of high LDL-C level plus MS. It is suggested that combined intervention therapy of LDL-C and MS will play an important role in the prevention of stroke.


Assuntos
LDL-Colesterol/sangue , Síndrome Metabólica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Povo Asiático , Feminino , Humanos , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/sangue
14.
Zhonghua Yi Xue Za Zhi ; 89(6): 385-8, 2009 Feb 17.
Artigo em Chinês | MEDLINE | ID: mdl-19567115

RESUMO

OBJECTIVE: To investigate the impact of metabolic syndrome (MS) with or without hyperglycemia on stroke prevalence compared to that of diabetes alone. METHODS: 44 100 subjects, 20 570 males and 23 530 females, aged 25 - 75, who had participated in the Chinese Residents Nutrition and Health Examination Survey held in the mainland of China 2002, underwent anthropometry, measurement of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), high density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and 2 hour plasma glucose (2 h PG) after 75 g oral glucose tolerance test (OGTT). 22 570 subjects, 10 698 males and 11 872 females, were divided into 5 groups: control group without MS risk factors (n = 17 518), Group of diabetes mellitus (DM) without MS (n = 638), group of MS with normoglycemia (n = 2501), Group of MS with mild hyperglycemia (n = 1058), and group MS with DM (n = 855). The relationship between MS and stroke was studied by multiple logistic regression analysis. RESULTS: The prevalence of MS increased along with age. The MS prevalence rates of the subjects with FPG > or = 5.6 mmol/L in the age groups 25 - 34, 35 - 44, 45 - 54, and > or = 55 were 23.5%, 37.2%, 45.7%, and 53.0% respectively, all significantly higher than those of the subjects with the FPG < 5.6 mmol/L (2.2%, 4.7%, 7.8%, and 9.5% respectively, all P < 0.01). The prevalence rates of stroke of the groups of DM, normal blood sugar with MS, mild hyperglycemia with MS, and DM with MS were 2.94%, 2.27%, 2.89%, and 4.11%, respectively, all significantly higher than that of the control group (0.19%, all P < 0.01). After adjustment for age, sex, smoking status, and LDL-C, no significant difference was observed between the neighboring MS groups (all P > 0.05). Compared to the group of MS with normoglycemia, the OR value for stroke of the DM with MS was 1.84 (95% CI 1.20 - 2.83, P < 0.01), which was still significant after adjusting for LDL-C (P < 0.05). CONCLUSION: (1) People with glucose intolerance had very high prevalence of stroke than novmoglgcemic people. (2) Hyperglycemia in MS has an extremely important role in the impact of MS on stroke in Chinese. (3) Diabetes by itself has the same significance as the combination of MS components in the development of stroke.


Assuntos
Hiperglicemia/complicações , Síndrome Metabólica/complicações , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Glicemia/metabolismo , China/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hiperglicemia/epidemiologia , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia
15.
Nat Commun ; 10(1): 5649, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827082

RESUMO

Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. While TP53 mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. Here we discover that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Furthermore, genetic and pharmacological inhibition of EZH2 decreases the repopulating potential of p53 mutant HSPCs. Thus, we uncover an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies with TP53 mutations.


Assuntos
Epigênese Genética , Doenças Hematológicas/metabolismo , Hematopoese , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Doenças Hematológicas/genética , Doenças Hematológicas/fisiopatologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Masculino , Metilação , Camundongos Endogâmicos C57BL , Mutação , Ligação Proteica
16.
N Engl J Med ; 353(11): 1124-34, 2005 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16162883

RESUMO

BACKGROUND: With China's rapid economic development, the disease burden may have changed in the country. We studied the major causes of death and modifiable risk factors in a nationally representative cohort of 169,871 men and women 40 years of age and older in China. METHODS: Baseline data on the participants' demographic characteristics, medical history, lifestyle-related risk factors, blood pressure, and body weight were obtained in 1991 with the use of a standard protocol. The follow-up evaluation was conducted in 1999 and 2000, with a follow-up rate of 93.4 percent. RESULTS: We documented 20,033 deaths in 1,239,191 person-years of follow-up. The mortality from all causes was 1480.1 per 100,000 person-years among men and 1190.2 per 100,000 person-years among women. The five leading causes of death were malignant neoplasms (mortality, 374.1 per 100,000 person-years), diseases of the heart (319.1), cerebrovascular disease (310.5), accidents (54.0), and infectious diseases (50.5) among men and diseases of the heart (268.5), cerebrovascular disease (242.3), malignant neoplasms (214.1), pneumonia and influenza (45.9), and infectious diseases (35.3) among women. The multivariate-adjusted relative risk of death and the population attributable risk for preventable risk factors were as follows: hypertension, 1.48 (95 percent confidence interval, 1.44 to 1.53) and 11.7 percent, respectively; cigarette smoking, 1.23 (95 percent confidence interval, 1.18 to 1.27) and 7.9 percent; physical inactivity, 1.20 (95 percent confidence interval, 1.16 to 1.24) and 6.8 percent; and underweight (body-mass index [the weight in kilograms divided by the square of the height in meters] below 18.5), 1.47 (95 percent confidence interval, 1.42 to 1.53) and 5.2 percent. CONCLUSIONS: Vascular disease and cancer have become the leading causes of death among Chinese adults. Our findings suggest that control of hypertension, smoking cessation, increased physical activity, and improved nutrition should be important strategies for reducing the burden of premature death among adults in China.


Assuntos
Doenças Cardiovasculares/mortalidade , Causas de Morte , Neoplasias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte/tendências , China/epidemiologia , Estudos de Coortes , Exercício Físico , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar/efeitos adversos , Magreza/complicações
17.
Zhonghua Yi Xue Za Zhi ; 88(18): 1246-50, 2008 May 13.
Artigo em Chinês | MEDLINE | ID: mdl-18844096

RESUMO

OBJECTIVE: To analyze the association of stroke and metabolic syndrome as well as its component combinations in Chinese adults. METHODS: Logistic regression was used to analyze the data, including anthropometric measurement, fasting plasma glucose (FPG), blood lipids, and histories of smoking, drinking, and anamnesis, of 47,414 subjects, 22,305 males and 25,105 females, aged 20-75, obtained from Chinese National Health and Nutrition Survey in 2002. RESULTS: (1) Blood pressure and waist circumference were the most important factors associated with stroke. Along with the clustering of the risk factors, the subjects became more liable to suffer from stroke. Logistic regression showed that after adjustment for age, sex, smoking status, and LDL-C level, the odd ratio (OR) values of the individuals with one, two, three, and four or more factors were 3.01 (1.89-4.81) ,4.37 (2.72-7.01), 9.20 (5.75-14.73), and 13.09 (7.98-21.49) respectively. (2) The combinations of raised hypertension plus hyperglycemia and low LDL-C and central obesity were the most hazard groups, with the OR values of 16.58 (95% CI 8.78-31.32) for stroke. The OR value for the full metabolic syndrome was 10.79 (95% CI 6.81-17.10). Hypertriglyceridemia was not an independent risk factor of stroke. (3) The relationships of metabolic risk factors and stroke were various among different age groups. Stroke was not related with blood glucose, blood pressure, serum lipids, and obesity in the subjects under 35; in those aged 35-55, diastolic Bp and low HDL-C were most significantly related to stroke; as for those above 55, systolic Bp and waist circumference were most significantly related to stroke. CONCLUSION: Central obesity cored metabolic syndrome is an important risk factor of stroke. Different combinations of the components attribute variously to stroke. In people above middle age, stroke is related to metabolic risk factors.


Assuntos
Povo Asiático/estatística & dados numéricos , Doenças Metabólicas/complicações , Acidente Vascular Cerebral/diagnóstico , Adulto , Idoso , Glicemia/metabolismo , Distribuição da Gordura Corporal , China/epidemiologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Modelos Logísticos , Masculino , Doenças Metabólicas/sangue , Pessoa de Meia-Idade , Obesidade/complicações , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/etnologia , Síndrome , Adulto Jovem
18.
Zhonghua Yi Xue Za Zhi ; 88(38): 2679-82, 2008 Oct 21.
Artigo em Chinês | MEDLINE | ID: mdl-19260156

RESUMO

OBJECTIVE: To analyze whether isolated hypertension and metabolic syndrome ( Based on the 2005 IDF criteria) have equal risk on stroke in Chinese adults. METHODS: 25194 subjects (25-75 years old) from Chinese National Health and Nutrition Survey in 2002 were divided into control group, isolated hypertension ( i-HTN) group, metabolic syndrome (MS) without hypertension ( non-HTN/MS) group , MS with hypertension (HTN/MS) group. The clinical features and risk for stroke ( using multiple logistic stepwise regression analysis) were compared among 4 groups. RESULTS: (1) The clinic features in the i-HTN group was non-central obesity, and its plasma glucose, triglyceride 9TG), high density lipoprotein cholesterol ( HDL-C) levels were normal . (2) The prevalence of stroke in control group , i-HTN group, non-HTN/MS group and HTN/MS group was 0.14%, 1.27%, 1.19% and 2.14%, respectively. (3) After adjustment for age, sex, smoking, low density lipoprotein cholesterol level, logistic regression analysis showed that the i-HTN group, non-HTN/MS group and HTN/MS group had higher risk of stroke compared with the controls, the odd ratio (OR) were 4.18, 8.00, 8.69 (P < 0.01), respectively. Compared with i-HTN group, OR in HTN/MS group was 2.05, while no difference was found between i-HTN group and non-HTN/MS group ( P>0.05). (4) Among different components of the MS, hypertension (OR 2.33), central obesity (OR 2.09), low HDL-C (OR 1.69), hyperglycemia (OR 1.66) except hypertriglyceridemia were all significantly related to stroke (P < 0.01). CONCLUSION: (1) MS and hypertension were an independent risk factor for the development of stroke in Chinese adults. (2) Though there was no clinical features of insulin resistance in i-HTN group, it was observed that the i-HTN and non-HTN/MS had equal contribution to stroke. The risk of stroke will be further increased if hypertension included in the MS.


Assuntos
Hipertensão/epidemiologia , Síndrome Metabólica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Povo Asiático , China/epidemiologia , Humanos , Hipertensão/complicações , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etiologia
19.
Zhonghua Yi Xue Za Zhi ; 87(33): 2328-31, 2007 Sep 04.
Artigo em Chinês | MEDLINE | ID: mdl-18036295

RESUMO

OBJECTIVE: To assess the anticoagulation treatment in real-life practice for nonvalvular atrial fibrillation (AF) in Beijing. METHODS: A questionnaire survey was conducted among 583 patients with nonvalvular AFF, 327 males and 256 females, aged 40 - 93, selected randomly from 8 general hospitals (n = 375, 64.3%) and 7 community health service centers (n = 208, 35.7%) located in the 8 districts in Beijing city, mainly from the out-patient departments (n = 437, 75%). RESULTS: 110 of the 583 patients (18.9%) were prescribed warfarin in which the percentage of international normalized ratio (INR) range (2.0 - 3.0) was 39.1% (n = 43). 68.2% of them had taken warfarin for less than one year. Another 33 patients (5.7%) had ever taken warfarin. 346 patients (59.3%) took aspirin of which 85.7% were exposed to the dose of 76 - 150 mg/d, and no one was administered the dose of 325 mg/d. 18.9% of the 583 patients had not received any anticoagulation or antiplatelet drugs. 78.6% of patients had never got the advice about taking warfarin from their doctors, and over 75% of the patients lacked in knowledge about the necessity of anticoagulation treatment for AF patients. The prevalence of stroke in the total 583 patients was 22.8%, 22.0% in those receiving warfarin treatment, 24.3% in those receiving aspirin treatment, and 21.3% in those receiving neither anticoagulation treatment nor antiplatelet treatment, without significant differences among them (chi(2) = 1.09, P = 0.58). CONCLUSION: The percentage of taking anticoagulation treatment in real-life practice pf the AF patients in Beijing is lower than that of taking antiplatelet treatment. The period of anticoagulation treatment is short and the effect is not good. The percentage of taking aspirin is too high in the high risk patients of stroke, but the dose of aspirin is on the low side. Doctors' advice and knowledge related to anticoagulation treatment of the patients are important factors influencing the anticoagulation treatment.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Varfarina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , China/epidemiologia , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários
20.
Zhonghua Yu Fang Yi Xue Za Zhi ; 41(2): 122-5, 2007 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-17605239

RESUMO

OBJECTIVE: To study hypertension control, follow up and the factors associated with the rate of hypertension control. METHODS: Through a community-based study, the routine data were collected through a community hypertension managing software for one year. RESULTS: There were 3375 hypertension patients above 60 years old recruited in the information system. In the baseline, the rate of blood pressure control was 63.5%, and arranging intervals up to 6 months was 66.9%. Hypertension control rate for the baseline, the third month and the sixth month was 61.8%, 62.4% and 61.6%, respectively (chi2 = 0.16, P = 0.69). Among hypertensives whose blood pressure was stabilized in baseline, hypertension control rates for the third month and the sixth month was 72.9.8% and 72.1%, respectively (chi2 = 0.26, P = 0.61). Blood pressure stabilized over 6 months in comparing with others, and the proportion for regular taking medication was 96.2% and 97.7% (chi2 = 3.58, P = 0.06). The proportion for physical activity, less salt intake, weight control was significantly higher in the patients whose blood pressure control well over 6 month. CONCLUSION: Rate of blood pressure control among elderly patient with hypertension who frequently consults the doctor in the community is high. Ineffectiveness in systolic and diabetes control is the important factor, which decreases the rate of blood pressure. Physical activity, less salt intake, and weight control are of help to hypertension control. For those, the blood pressure are stabilized, a follow up with 3 to 6 months interval is appropriate.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Idoso , Pressão Sanguínea , Feminino , Seguimentos , Humanos , Hipertensão/fisiopatologia , Masculino
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