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1.
Front Med (Lausanne) ; 9: 831260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530042

RESUMO

Background: Aging, as a multi-dimensional process, can be measured at different hierarchical levels including biological, phenotypic, and functional levels. The aims of this study were to: (1) compare the predictive utility of mortality by three aging measures at three hierarchical levels; (2) develop a composite aging measure that integrated aging measures at different hierarchical levels; and (3) evaluate the response of these aging measures to modifiable life style factors. Methods: Data from National Health and Nutrition Examination Survey 1999-2002 were used. Three aging measures included telomere length (TL, biological level), Phenotypic Age (PA, phenotypic level), and frailty index (FI, functional level). Mortality information was collected until December 2015. Cox proportional hazards regression and multiple linear regression models were performed. Results: A total of 3,249 participants (20-84 years) were included. Both accelerations (accounting for chronological age) of PA and FI were significantly associated with mortality, with HRs of 1.67 [95% confidence interval (CI) = 1.41-1.98] and 1.59 (95% CI = 1.35-1.87), respectively, while that of TL showed non-significant associations. We thus developed a new composite aging measure (named PC1) integrating the accelerations of PA and FI, and demonstrated its better predictive utility relative to each single aging measure. PC1, as well as the accelerations of PA and FI, were responsive to several life style factors including smoking status, body mass index, alcohol consumption, and leisure-time physical activity. Conclusion: This study demonstrates that both phenotypic (i.e., PA) and functional (i.e., FI) aging measures can capture mortality risk and respond to modifiable life style factors, despite their inherent differences. Furthermore, the PC1 that integrated phenotypic and functional aging measures outperforms in predicting mortality risk in comparison with each single aging measure, and strongly responds to modifiable life style factors. The findings suggest the complementary of aging measures at different hierarchical levels and highlight the potential of life style-targeted interventions as geroprotective programs.

2.
Front Oncol ; 12: 835901, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463371

RESUMO

Although the link between sugar-sweetened beverages (SSB) and pancreatic cancer has been suggested for its insulin-stimulating connection, most epidemiological studies showed inconclusive relationship. Whether the result was limited by sample size is explored. This prospective study followed 491,929 adults, consisting of 235,427 men and 256,502 women (mean age: 39.9, standard deviation: 13.2), from a health surveillance program and there were 523 pancreatic cancer deaths between 1994 and 2017. The individual identification numbers of the cohort were matched with the National Death file for mortality, and Cox models were used to assess the risk. The amount of SSB intake was recorded based on the average consumption in the month before interview by a structured questionnaire. We classified the amount of SSB intake into 4 categories: 0-<0.5 serving/day, ≥0.5-<1 serving per day, ≥1-<2 servings per day, and ≥2 servings per day. One serving was defined as equivalent to 12 oz and contained 35 g added sugar. We used the age and the variables at cohort enrolment as the reported risks of pancreatic cancers. The cohort was divided into 3 age groups, 20-39, 40-59, and ≥60. We found young people (age <40) had higher prevalence and frequency of sugar-sweetened beverages than the elderly. Those consuming 2 servings/day had a 50% increase in pancreatic cancer mortality (HR = 1.55, 95% CI: 1.08-2.24) for the total cohort, but a 3-fold increase (HR: 3.09, 95% CI: 1.44-6.62) for the young. The risk started at 1 serving every other day, with a dose-response relationship. The association of SSB intake of ≥2 servings/day with pancreatic cancer mortality among the total cohort remained significant after excluding those who smoke or have diabetes (HR: 2.12, 97% CI: 1.26-3.57), are obese (HR: 1.57, 95% CI: 1.08-2.30), have hypertension (HR: 1.90, 95% CI: 1.20-3.00), or excluding who died within 3 years after enrollment (HR: 1.67, 95% CI: 1.15-2.45). Risks remained in the sensitivity analyses, implying its independent nature. We concluded that frequent drinking of SSB increased pancreatic cancer in adults, with highest risk among young people.

3.
Nutrients ; 14(2)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35057488

RESUMO

We aimed to investigate the effects of a low-glycemic index (GI) diet on the body mass and blood glucose of patients with four common metabolic diseases by conducting a systematic review and meta-analysis of studies comparing a low-GI diet (LGID) and other types of diet. Search terms relating to population, intervention, comparator, outcomes, and study design were used to search three databases: PubMed, Embase, and the Cochrane Library. We identified 24 studies involving 2002 participants. Random-effects models were used for 16 studies in the meta-analysis and stratified analyses were performed according to the duration of the intervention. The systematic review showed that LGIDs slightly reduced body mass and body mass index (BMI) (p < 0.05). BMI improved more substantially after interventions of >24 weeks and there was no inter-study heterogeneity (I2 = 0%, p = 0.48; mean difference (MD) = -2.02, 95% confidence interval (CI): -3.05, -0.98). Overall, an LGID had superior effects to a control diet on fasting blood glucose (FBG) and glycosylated hemoglobin. When the intervention exceeded 30 days, an LGID reduced FBG more substantially (MD = -0.34, 95% CI: -0.55, -0.12). Thus, for patients with metabolic diseases, an LGID is more effective at controlling body mass and blood glucose than a high-GI or other diet.


Assuntos
Dieta para Diabéticos/métodos , Dieta/métodos , Índice Glicêmico , Doenças Metabólicas/dietoterapia , Adolescente , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Doenças Metabólicas/sangue , Pessoa de Meia-Idade , Adulto Jovem
4.
HGG Adv ; 3(1): 100078, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35047863

RESUMO

Pancreatic cancer is a deadly disease that accounts for approximately 5% of cancer deaths worldwide, with a dismal 5-year survival rate of 10%. Known genetic risk factors explain only a modest proportion of the heritable risk of pancreatic cancer. We conducted a whole-exome case-control sequencing study in 1,591 pancreatic cancer cases and 2,134 cancer-free controls of European ancestry. In our gene-based analysis, ATM ranked first, with a genome-wide significant p value of 1 × 10-8. The odds ratio for protein-truncating variants in ATM was 24, which is substantially higher than prior estimates, although ours includes a broad 95% confidence interval (4.0-1000). SIK3 was the second highest ranking gene (p = 3.84 × 10-6, false discovery rate or FDR = 0.032). We observed nominally significant association signals in several genes of a priori interest, including BRCA2 (p = 4.3 × 10-4), STK11 (p = 0.003), PALB2 (p = 0.019), and TP53 (p = 0.037), and reported risk estimates for known pathogenic variants and variants of uncertain significance (VUS) in these genes. The rare variants in established susceptibility genes explain approximately 24% of log familial relative risk, which is comparable to the contribution from established common susceptibility variants (17%). In conclusion, this study provides new insights into the genetic susceptibility of pancreatic cancer, refining rare variant risk estimates in known pancreatic cancer susceptibility genes and identifying SIK3 as a novel candidate susceptibility gene. This study highlights the prominent importance of ATM truncating variants and the underappreciated role of VUS in pancreatic cancer etiology.

5.
BMJ Open ; 11(12): e051397, 2021 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-34903541

RESUMO

PURPOSE: The National Colorectal Cancer Cohort (NCRCC) study aims to specifically assess risk factors and biomarkers related to endpoints across the colorectal cancer continuum from the aetiology through survivorship. PARTICIPANTS: The NCRCC study includes the Colorectal Cancer Screening Cohort (CRCSC), which recruited individuals who were at high risk of CRC between 2016 and 2020 and Colorectal Cancer Patients Cohort (CRCPC), which recruited newly diagnosed patients with CRC between 2015 and 2020. Data collection was based on questionnaires and abstraction from electronic medical record. Items included demographic and lifestyle factors, clinical information, survivorship endpoints and other information. Multiple biospecimens including blood, tissue and urine samples were collected. Participants in CRCSC were followed by a combination of periodic survey every 5 years and annual linkage with regional or national cancer and death registries for at least 10 years. In CRCPC, follow-up was conducted with both active and passive approaches at 6, 12, 18, 24, 36, 48 and 60 months after surgery. FINDINGS TO DATE: A total of 19 377 participants and 15 551 patients with CRC were recruited in CRCSC and in CRCPC, respectively. In CRCSC, 48.0% were men, and the average age of participants at enrolment was 58.7±8.3 years. In CRCPC, 61.4% were men, and the average age was 60.3±12.3 years with 18.9% of participants under 50 years of age. FUTURE PLANS: Longitudinal data and biospecimens will continue to be collected. Based on the cohorts, several studies to assess risk factors and biomarkers for CRC or its survivorship will be conducted, ultimately providing research evidence from Chinese population and optimising evidence-based guidelines across the CRC continuum.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco
6.
Glob Health Res Policy ; 6(1): 37, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593054

RESUMO

BACKGROUND: COVID-19 has seriously affected people's mental health and changed their behaviors. Previous studies for mental state and behavior promotion only targeted limited people or were not suitable for daily activity restrictions. Therefore, we decided to explore the effect of health education videos on people's mental state and health-related behaviors. METHODS: Based on WeChat, QQ, and other social media, we conducted an online survey by snowball sampling. Spearman's non-parametric method was used to analyze the correlation related to mental health problems and health-related behaviors. Besides, we used binary logistic regression analyses to examine mental health problems and health-related behaviors' predictors. We performed SPSS macro PROCESS (model 4 and model 6) to analyze mediation relationships between exposure to health education videos and depression/anxiety/health-related behaviors. These models were regarded as exploratory. RESULTS: Binary logistic regression analyses indicated that people who watched the health education videos were more likely to wear masks (OR 1.15, p < 0.001), disinfect (OR 1.26, p < 0.001), and take temperature (OR 1.37, p < 0.001). With higher level of posttraumatic growth (PTG) or perceived social support (PSS), people had lower percentage of depression (For PSS, OR 0.98, p < 0.001; For PTG, OR 0.98, p < 0.01) and anxiety (For PSS, OR 0.98, p < 0.001; For PTG, OR 0.98, p = 0.01) and better health behaviors. The serial multiple-mediation model supported the positive indirect effects of exposure to health education videos on the depression and three health-related behaviors through PSS and PTG (Depression: B[SE] = - 0.0046 [0.0021], 95% CI - 0.0098, - 0.0012; Mask-wearing: B[SE] = 0.0051 [0.0023], 95% CI 0.0015, 0.0010; Disinfection: B[SE] = 0.0059 [0.0024], 95% CI 0.0024, 0.0012; Temperature-taking: B[SE] = 0.0067 [0.0026], 95% CI 0.0023, 0.0013). CONCLUSION: Exposure to health education videos can improve people's self-perceived social support and inner growth and help them cope with the adverse impact of public health emergencies with better mental health and health-related behaviors.


Assuntos
COVID-19/psicologia , Comportamentos Relacionados com a Saúde , Educação em Saúde/estatística & dados numéricos , Saúde Mental/estatística & dados numéricos , Saúde Pública/estatística & dados numéricos , Adulto , Idoso , China , Feminino , Educação em Saúde/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Apoio Social , Adulto Jovem
8.
Aging (Albany NY) ; 13(20): 23757-23768, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34695805

RESUMO

Circular RNAs (circRNAs) have demonstrated critical roles in the development of cancers. This study aimed to explore the function of circular RNA circPRKCI/miR-20a-5p/SOX4 axis in acute lymphoblastic leukemia (ALL). Our data showed that the expression of circPRKCI and SOX4 was enhanced while the expression of miR-20a-5p was reduced in the clinical T-ALL samples. The expression of miR-20a-5p was negatively associated with circPRKCI and SOX4 in the T-ALL patients and the expression of circPRKCI was positive correlated with SOX4 in the T-ALL patients. Functionally, the silencing of circPRKCI suppressed the viability of T-ALL cells. Conversely, the knockdown of circPRKCI promoted the apoptosis of T-ALL cells. The levels of cleaved PARP and cleaved caspase3 were induced by the depletion of circPRKCI in T-ALL cells. Mechanically, the luciferase activity of circPRKCI was significantly decreased in T-ALL cells after the treatment of miR-20a-5p mimic. Meanwhile, the silencing of circPRKCI promoted the expression of miR-20a-5p in T-ALL cells, implying that circPRKCI serves as a competitive endogenous RNAs (ceRNA) of miR-20a-5p. We validated that the treatment of miR-20a-5p mimic inhibited the viability of T-ALL cells. MiR-20a-5p mimic enhanced the apoptosis of T-ALL cells. The expression of cleaved PARP and cleaved caspase3 was increased by miR-20a-5p mimic in the cells. In summarization, we concluded that circular RNA circPRKCI contributed to malignant progression of T-cell acute lymphoblastic leukemia by modulating miR-20a-5p/SOX4 axis. Targeting circPRKCI may serve as a promising therapeutic strategy of T-ALL.


Assuntos
MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras , RNA Circular/genética , Fatores de Transcrição SOXC/genética , Adulto , Medula Óssea/metabolismo , Medula Óssea/patologia , Feminino , Humanos , Masculino , MicroRNAs/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , RNA Circular/metabolismo , Fatores de Transcrição SOXC/metabolismo
9.
Sci Rep ; 11(1): 19742, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611226

RESUMO

It has been well-known that built environment features influence the risk of chronic diseases. However, the existing data of its relationship with telomere length, a biomarker of biological aging, is still limited, with no study available for Mexican Americans. This study investigates the relationship between several factors of the built environment with leukocyte telomere length among 5508 Mexican American adults enrolled in Mano-A-Mano, the Mexican American Cohort Study (MACS). Based on the quartile levels of telomere length, the study population was categorized into four groups, from the lowest (1st quartile) to the highest telomere length group (4th quartile). For individual built environment factors, their levels did not differ significantly across four groups. However, in the multinominal logistic regression analysis, increased Rundle's land use mixture (LUM) and Frank's LUM were found statistically significantly associated with increased odds of having high levels of telomere length (Rundle's LUM: 2nd quartile: Odds ratio (OR) 1.26, 95% Confidence interval (CI) 1.07, 1.48; 3rd quartile: OR 1.25, 95% CI 1.06, 1.46; 4th quartile: OR 1.19, 95% CI 1.01, 1.41; Frank's LUM: 2nd quartile: OR 1.34, 95% CI 1.02, 2.63; 3rd quartile: OR 1.55, 95% CI 1.04, 2.91; 4th quartile: OR 1.36, 95% CI 1.05, 2.72, respectively). The associations for Rundle's LUM remained significant after further adjusting other non-redundant built environment factors. Finally, in stratified analysis, we found the association between Rundle's LUM and telomere length was more evident among younger individuals (< 38 years old), women, and those with obesity, born in Mexico, having low levels of physical activity, and having low levels of acculturation than their relative counterparts. In summary, our results indicate that land use mixture may impact telomere length in leukocytes in Mexican Americans.


Assuntos
Ambiente Construído , Leucócitos , Americanos Mexicanos/genética , Modelos Teóricos , Telômero/genética , Adulto , Envelhecimento , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Homeostase do Telômero , Adulto Jovem
10.
Ann Med ; 53(1): 1621-1631, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34498502

RESUMO

PURPOSES: There is increasing concern regarding cardiovascular risk in non-alcoholic fatty liver disease (NAFLD) patients with liver fibrosis. This study aims: (1) to assess the association between NAFLD and liver fibrosis status and the development of carotid plaque (CP), and (2) to identify CP risk factors among general population with different baseline NAFLD and liver fibrosis status. METHODS: This retrospective cohort study included 14,288 adult participants who went for regular health check-ups between 2014 and 2019, in one hospital in Zhejiang, China. NAFLD was diagnosed by abdominal ultrasound and the NAFLD fibrosis score (NFS) was calculated to reflect the extent of liver fibrosis. Cox proportional hazards analyses were applied to assess the risk of CP development across groups with different baseline NAFLD and NFS status. RESULTS: NAFLD participants with high NFS had higher risk of CP compared to non-NAFLD participants (adjusted hazard ratio 1.68, 95% confidence interval [CI] 1.43-1.96, p < .001). Progression from NAFLD free and NAFLD with low NFS to NAFLD with high NFS are associated with 1.56-fold (95% CI 1.21-2.01, p = .001) and 1.43-fold (95% CI 1.11-1.84, p = .006) increased risk of CP, respectively. Risk factors associated with CP vary based on baseline NAFLD and NFS status. Among NAFLD participants with high NFS, hypertension is the only significant risk factor after adjustment for other potential influencing factors. CONCLUSIONS: NAFLD and liver fibrosis status can be an independent predictor for CP development regardless of metabolic abnormalities. Hypertension is a major risk factor for CP development among NAFLD patients with high NFS.KEY MESSAGESNon-alcoholic fatty liver disease (NAFLD) and liver fibrosis status can be an independent predictor for development of carotid plaque.Progression from NAFLD free and NAFLD with low NAFLD fibrosis score (NFS) to NAFLD with high NFS are associated with increased risk of carotid plaque.Risk factors associated with carotid plaque vary based on baseline NAFLD and NFS status, and hypertension plays the most important role among patients with NAFLD and high NFS.


Assuntos
Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Placa Aterosclerótica , Adulto , China/epidemiologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/mortalidade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
11.
Aging (Albany NY) ; 13(17): 21513-21525, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491905

RESUMO

For facilitating risk communication in clinical management, such a ratio-based measure becomes easier to understand if expressed as a loss of life expectancy. The cohort, consisting of 543,410 adults in Taiwan, was recruited between 1994 and 2008. Health risks included lifestyle, biomarkers, and chronic diseases. A total of 18,747 deaths were identified. The Chiang's life table method was used to estimate a loss of life expectancy. We used Cox regression to calculate hazard ratios (HRs) for health risks. The increased mortality from cardio-metabolic risks such as high cholesterol (HR=1.10), hypertension (HR=1.48) or diabetes (HR=2.02) can be converted into a loss of 1.0, 4.4, and 8.9 years in life expectancy, respectively. The top 20 of the 30 risks were associated with a loss of 4 to 10 years of life expectancy, with 70% of the cohort having at least two such risk factors. Smoking, drinking, and physical inactivity each had 5-7 years loss. Individuals with diabetes or an elevated white count had a loss of 7-10 years, while prolonged sitting, the most prevalent risk factor, had a loss of 2-4 years. Those with diabetes (8.9 years) and proteinuria (9.1 years) present at the same time showed a loss of 16.2 years, a number close to the sum of each risk. Health risks, expressed as life expectancy loss, could facilitate risk communication. The paradigm shift in expressing risk intensity can help set public health priorities scientifically to promote a focus on the most important ones in primary care.


Assuntos
Causas de Morte , Doença Crônica , Expectativa de Vida , Estilo de Vida , Educação de Pacientes como Assunto/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Doenças Cardiovasculares , Estudos de Coortes , Comunicação , Diabetes Mellitus , Exercício Físico , Feminino , Humanos , Longevidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar , Taiwan , Adulto Jovem
12.
Int J Adv Manuf Technol ; : 1-36, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34465936

RESUMO

Cutting fluid has cooling and lubricating properties and is an important part of the field of metal machining. Owing to harmful additives, base oils with poor biodegradability, defects in processing methods, and unreasonable emissions of waste cutting fluids, cutting fluids have serious pollution problems, which pose challenges to global carbon emissions laws and regulations. However, the current research on cutting fluid and its circulating purification technique lacks systematic review papers to provide scientific technical guidance for actual production. In this study, the key scientific issues in the research achievements of eco-friendly cutting fluid and waste fluid treatment are clarified. First, the preparation and mechanism of organic additives are summarized, and the influence of the physical and chemical properties of vegetable base oils on lubricating properties is analyzed. Then, the process characteristics of cutting fluid reduction supply methods are systematically evaluated. Second, the treatment of oil mist and miscellaneous oil, the removal mechanism and approach of microorganisms, and the design principles of integrated recycling equipment are outlined. The conclusion is concluded that the synergistic effect of organic additives, biodegradable vegetable base oils and recycling purification effectively reduces the environmental pollution of cutting fluids. Finally, in view of the limitations of the cutting fluid and its circulating purification technique, the prospects of amino acid additive development, self-adapting jet parameter supply system, matching mechanism between processing conditions and cutting fluid are put forward, which provides the basis and support for the engineering application and development of cutting fluid and its circulating purification.

13.
Cancer Epidemiol ; 73: 101972, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34216957

RESUMO

BACKGROUND: Aberrant Wnt/beta-catenin pathway activation is implicated in Multiple Myeloma (MM) development, but little is known if genetic variants within this pathway contribute to MM susceptibility. METHODS: We performed a discovery candidate pathway analysis in 269 non-Hispanic white MM cases and 272 controls focusing on 171 variants selected from 26 core genes within the Wnt/beta-catenin pathway. Significant candidate variants (P < 0.05) were selected for validation in internal and external non-Hispanic white populations totaling 818 cases and 1209 controls. We also examined significant variants in non-Hispanic black and Hispanic case/control study populations to identify potential differences by race/ethnicity. Possible biological functions of candidate variants were predicted in silico. RESULTS: Seven variants were significantly associated with MM risk in non-Hispanic whites in the discovery population, of which LRP6:rs7966410 (OR: 0.57; 95 % CI: 0.38-0.88; P = 9.90 × 10-3) and LRP6:rs7956971 (OR: 0.64; 95 % CI: 0.44-0.95; P = 0.027) remained significant in the internal and external populations. CSNK1D:rs9901910 replicated among all three racial/ethnic groups, with 2-6 fold increased risk of MM (OR: 2.40; 95 % CI: 1.67-3.45; P = 2.43 × 10-6 - non-Hispanic white; OR: 6.42; 95 % CI: 2.47-16.7; P = 3.14 × 10-4 - non-Hispanic black; OR: 4.31; 95 % CI: 1.83-10.1; P = 8.10 × 10-4 - Hispanic). BTRC:rs7916830 was associated with a significant 37 % and 24 % reduced risk of MM in the non-Hispanic white (95 % CI: 0.49-0.82; P = 5.60 × 10-4) and non-Hispanic Black (95 % CI: 0.60-0.97; P = 0.028) population, respectively. In silico tools predicted that these loci altered function through via gene regulation. CONCLUSION: We identified several variants within the Wnt/beta-catenin pathway associated with MM susceptibility. Findings of this study highlight the potential genetic role of Wnt/beta-catenin signaling in MM etiology among a diverse patient population.


Assuntos
Mieloma Múltiplo , Via de Sinalização Wnt , beta Catenina , Afro-Americanos/genética , Afro-Americanos/estatística & dados numéricos , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/etnologia , /estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/etnologia , Mieloma Múltiplo/genética , /estatística & dados numéricos , Via de Sinalização Wnt/genética , beta Catenina/genética
14.
Nat Commun ; 12(1): 4487, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301922

RESUMO

Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Neoplasias Embrionárias de Células Germinativas/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Testiculares/genética , Linhagem Celular Tumoral , Mapeamento Cromossômico , Redes Reguladoras de Genes/genética , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Metanálise como Assunto , Neoplasias Embrionárias de Células Germinativas/metabolismo , Mapas de Interação de Proteínas/genética , Neoplasias Testiculares/metabolismo
15.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(1): 61-67, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-34117846

RESUMO

This study aimed to quantitatively assess the effectiveness of the Wuhan lockdown measure on controlling the spread of coronavirus diesase 2019 (COVID-19). : Firstly,estimate the daily new infection rate in Wuhan before January 23,2020 when the city went into lockdown by consulting the data of Wuhan population mobility and the number of cases imported from Wuhan in 217 cities of Mainland China. Then estimate what the daily new infection rate would have been in Wuhan from January 24 to January 30th if the lockdown measure had been delayed for 7 days,assuming that the daily new infection in Wuhan after January 23 increased in a high,moderate and low trend respectively (using exponential, linear and logarithm growth models). Based on that,calculate the number of infection cases imported from Wuhan during this period. Finally,predict the possible impact of 7-day delayed lockdown in Wuhan on the epidemic situation in China using the susceptible-exposed-infectious-removed (SEIR) model. : The daily new infection rate in Wuhan was estimated to be 0.021%,0.026%,0.029%,0.033% and 0.070% respectively from January 19 to January 23. And there were at least 20 066 infection cases in Wuhan by January 23,2020. If Wuhan lockdown measure had been delayed for 7 days,the daily new infection rate on January 30 would have been 0.335% in the exponential growth model,0.129% in the linear growth model,and 0.070% in the logarithm growth model. Correspondingly,there would have been 32 075,24 819 and 20 334 infection cases travelling from Wuhan to other areas of Mainland China,and the number of cumulative confirmed cases as of March 19 in Mainland China would have been 3.3-3.9 times of the officially reported number. Conclusions: Timely taking city-level lockdown measure in Wuhan in the early stage of COVID-19 outbreak is essential in containing the spread of the disease in China.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis , China/epidemiologia , Cidades , Humanos , SARS-CoV-2
16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(1): 52-60, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-34117851

RESUMO

:To evaluate the impact of socioeconomic status,population mobility,prevention and control measures on the early-stage coronavirus disease 2019 (COVID-19) development in major cities of China. : The rate of daily new confirmed COVID-19 cases in the 51 cities with the largest number of cumulative confirmed cases as of February 19,2020 (except those in Hubei province) were collected and analyzed using the time series cluster analysis. It was then assessed according to three aspects,that is, socioeconomic status,population mobility,and control measures for the pandemic. : According to the analysis on the 51 cities,4 development patterns of COVID-19 were obtained,including a high-incidence pattern (in Xinyu),a late high-incidence pattern (in Ganzi),a moderate incidence pattern (in Wenzhou and other 12 cities),and a low and stable incidence pattern (in Hangzhou and other 35 cities). Cities with different types and within the same type both had different scores on the three aspects. : There were relatively large difference on the COVID-19 development among different cities in China,possibly affected by socioeconomic status,population mobility and prevention and control measures that were taken. Therefore,a timely public health emergency response and travel restriction measures inside the city can interfere the development of the pandemic. Population flow from high risk area can largely affect the number of cumulative confirmed cases.


Assuntos
COVID-19 , China/epidemiologia , Cidades , Humanos , SARS-CoV-2 , Classe Social
17.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(1): 68-73, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-34117853

RESUMO

:To predict the epidemiological trend of coronavirus disease 2019 (COVID-19) by mathematical modeling based on the population mobility and the epidemic prevention and control measures. : As of February 8,2020,the information of 151 confirmed cases in Yueqing,Zhejiang province were obtained,including patients' infection process,population mobility between Yueqing and Wuhan,etc. To simulate and predict the development trend of COVID-19 in Yueqing, the study established two-stage mathematical models,integrating the population mobility data with the date of symptom appearance of confirmed cases and the transmission dynamics of imported and local cases. : It was found that in the early stage of the pandemic,the number of daily imported cases from Wuhan (using the date of symptom appearance) was positively associated with the number of population travelling from Wuhan to Yueqing on the same day and 6 and 9 days before that. The study predicted that the final outbreak size in Yueqing would be 170 according to the number of imported cases estimated by consulting the population number travelling from Wuhan to Yueqing and the susceptible-exposed-infectious-recovered (SEIR) model; while the number would be 165 if using the reported daily number of imported cases. These estimates were close to the 170,the actual monitoring number of cases in Yueqing as of April 27,2020. : The two-stage modeling approach used in this study can accurately predict COVID-19 epidemiological trend.


Assuntos
COVID-19 , China/epidemiologia , Surtos de Doenças , Humanos , Modelos Teóricos , Pandemias , SARS-CoV-2
18.
Nat Commun ; 12(1): 2788, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986289

RESUMO

Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.


Assuntos
Neoplasias da Mama/patologia , Carcinogênese/patologia , Efrina-A4/metabolismo , Células-Tronco Neoplásicas/patologia , Ribonuclease Pancreático/metabolismo , Antígeno AC133/metabolismo , Animais , Neoplasias da Mama/genética , Carcinogênese/genética , Linhagem Celular , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Ligação Proteica/genética , Ribonuclease Pancreático/sangue , Ribonuclease Pancreático/genética , Resultado do Tratamento
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 508-514, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812422

RESUMO

OBJECTIVE: To investigate the clinicopathological features of intestinal diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical features, pathological morphology, immunophenotype, and EBER in situ hybridization of 136 DLBCL patients diagnosed in Jinan People's Hospital Affiliated to Shandong First Medical University from January 2007 to October 2014 were analyzed retrospectively. A total of 136 DLBCL samples were obtained, the DLBCL sites were categorized as: duodenum (n=23), ileocecal region (n=63), other small intestine (n=29), rectum (n=7), and other large intestine (n=14). Survival curves for the DLBCL patients were plotted using the Kaplan-Meier method and judged by the Log-rank test. RESULTS: Patients with DLBCL of the ileocecal region and other small intestine except duodenum were mainly male (P=0.042), and had a higher proportion of limited-stage tumors(P=0.015), and lower International Prognostic Index (IPI) (P=0.001). Patients with DLBCL of ileocecal region had higher incidence of lactate dehydrogenase elevation (P=0.007), and higher incidence of intestinal obstruction or perforation (P<0.001) than those with DLBCL of other regions. The 5-year overall survival and 5-year progression-free survival of patients with DLBCL in ileocecal and other small intestine sites were higher than those in other sites, but the differences were not statistically significant (P=0.135, 0.459). Fifty percent of intestinal DLBCL were germinal center B cell-like (GCB) subtypes. A low-grade B-cell lymphoma was found in 21% of 136 tumor samples. In ileocecal and other small intestinal specimens, the proportion of low-grade B-cell lymphoma was 29%, and the difference was statistically significant(P=0.025). About 16% of 136 DLBCL samples expressed follicular lymphoma while no mucosa-associated lymphoid tissue lymphoma . The Epstein-Barr virus-encoded RNA-1 (EBER1) positive rate of duodenal DLBCL was significantly higher than that of other sites (5/23, 22% vs 2/63, 3%, P=0.001). CONCLUSION: The intestinal DLBCL is commonly observed in male, and ileocecal is the most primary site. Patients with DLBCL of the ileocecal region and small intestine except duodenum have low IPI, high proportion of limited-stage tumors, low level of lactate dehydrogenase, high incidence of intestinal obstruction or perforation, and low incidence of inert lymphoma. The EBER1 positive rate of DLBCL in duodenal is higher.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Herpesvirus Humano 4 , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
20.
Int J Epidemiol ; 50(3): 975-986, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-33787881

RESUMO

BACKGROUND: The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC. METHODS: We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status. RESULTS: During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26). CONCLUSIONS: This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12-16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.


Assuntos
Neoplasias Nasofaríngeas , Hong Kong/epidemiologia , Humanos , Masculino , Carcinoma Nasofaríngeo/epidemiologia , Neoplasias Nasofaríngeas/epidemiologia , Estudos Observacionais como Assunto , Estudos Prospectivos , Fatores de Risco , Singapura , Fumar/epidemiologia , Taiwan
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