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BACKGROUNDS: The study aimed to estimate bladder cancer burden and its attributable risk factors in China, Japan, South Korea, North Korea and Mongolia from 1990 to 2019, to discuss the potential causes of the disparities. METHODS: Data were obtained from the Global Burden of Disease Study 2019. The annual percent change (APC) and average annual percent change (AAPC) were calculated by Joinpoint analysis, and the independent age, period and cohort effects were estimated by age-period-cohort analysis. RESULTS: In 2019, the highest incidence (7.70 per 100,000) and prevalence (51.09 per 100,000) rates of bladder cancer were in Japan, while the highest mortality (2.31 per 100,000) and DALY rates (41.88 per 100,000) were in South Korea and China, respectively. From 1990 to 2019, the age-standardized incidence and prevalence rates increased in China, Japan and South Korea (AAPC > 0) and decreased in Mongolia (AAPC < 0), while mortality and DALY rates decreased in all five countries (AAPC < 0). Age effects showed increasing trends for incidence, mortality and DALY rates, while the prevalence rates increased first and then decreased in older groups. The cohort effects showed downward trends from 1914-1918 to 2004-2008. Smoking was the greatest contributor and males had the higher burden than females. CONCLUSION: Bladder cancer was still a major public health problem in East Asia. Male and older population suffered from higher risk, and smoking played an important role. It is recommended that more efficient preventions and interventions should be operated among high-risk populations, thereby reduce bladder cancer burden in East Asia.
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Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Anciano , Adulto , Incidencia , Prevalencia , Asia Oriental/epidemiología , Anciano de 80 o más Años , Costo de Enfermedad , Carga Global de Enfermedades , Adulto Joven , Pueblos del Este de AsiaRESUMEN
In the digital era, increasingly more Chinese older adults have become Internet users, but the digital divide deeply affects their health. Based on the China Longitudinal Aging Social Survey, the influence of Internet use on older adults' physical and mental health are examined. It is found that digital access, online socializing and information/knowledge acquisition improve older adults' physical and mental health, while Internet skills can hardly influence their health. Social connection and adaptation are two important channels through which Internet use improves older adults' health. Younger and better-educated older adults gain more health benefits from Internet access, but online socializing and economic activities show stronger positive health effects in less-educated older adults. Narrowing the digital divide and promoting digital cohesion are important for the health of older population, so the health and pensions sector and geriatric nursing providers should help this group integrate into digital life to improve their health.
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BACKGROUND: This study aims to analyze breast cancer burden attributable to high body mass index (BMI) and high fasting plasma glucose (FPG) in China from 1990 to 2019. METHODS: Data were obtained from the Global Burden of Disease (GBD) study 2019. Deaths and disability-adjusted life years (DALYs) were used for attributable burden, and age-period-cohort (APC) model was used to evaluate the independent effects of age, period and birth cohort. RESULTS: In 2019, the age-standardized mortality and DALY rates of breast cancer attributable to high BMI were 1.107 (95% UI: 0.311, 2.327) and 29.990 (8.384, 60.713) per 100 000, and mortality and DALY rates attributable to high FPG were 0.519 (0.095, 1.226) and 13.662 (2.482, 32.425) per 100 000. From 1990 to 2019, the age-standardized mortality and DALY rates of breast cancer attributable to high BMI increased by 1.192% and 1.180%, and the trends of high FPG were not statistically significant. The APC results showed that the age effects of high BMI and high FPG-mortality and DALY rates increased, with the highest rates in the age group over 80 years. The birth cohort effects of high BMI showed "inverted V" shapes, while high FPG showed downward trends. CONCLUSIONS: Age was the main reason for the increase of attributable burden, and postmenopausal women were the high-risk groups. Therefore, targeted prevention measures should be developed to improve postmenopausal women's awareness and effectively reduce the prevalence of obesity and diabetes, thereby reducing the breast cancer burden caused by metabolic factors in China.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/mortalidad , China/epidemiología , Persona de Mediana Edad , Adulto , Anciano , Índice de Masa Corporal , Factores de Riesgo , Estudios Epidemiológicos , Glucemia/metabolismo , Carga Global de Enfermedades , Pueblos del Este de AsiaRESUMEN
BACKGROUNDS: The study aimed to analyze epidemiology burden of male prostate cancer across the BRICS-plus, and identify potential risk factors by assessing the associations with age, period, birth cohorts and sociodemographic index (SDI). METHODS: Data were extracted from the Global Burden of Disease Study 2019. The average annual percent change (AAPC) was calculated to assess long-term trends, and age-period-cohort analysis was used to analyze these three effects on prostate cancer burden. Quantile regression was used to investigate the association between SDI and health outcomes. RESULTS: The higher incidence and mortality were observed in Mercosur and SACU regions, increasing trends were observed in prostate cancer incidence in almost all BRICS-plus countries (AAPC > 0), and EEU's grew by 24.31% (%AAPC range: -0.13-3.03). Mortality had increased in more than half of countries (AAPC > 0), and SACU grew by 1.82% (%AAPC range: 0.62-1.75). Incidence and mortality risk sharply increased with age across all BRICS-plus countries and globally, and the peak was reached in the age group 80-84 years. Rate ratio (RR) of incidence increased with birth cohorts in all BRICS-plus countries except for Kazakhstan where slightly decrease, while mortality RR decreased with birth cohort in most of BRICS-plus countries. SDI presented significantly positive associations with incidence in 50 percentiles. The deaths attributable to smoking declined in most of BRICS-plus nations, and many countries in China-ASEAN-FTA and EEU had higher values. CONCLUSION: Prostate cancer posed a serious public health challenge with an increasing burden among most of BRICS-plus countries. Age had significant effects on prostate cancer burden, and recent birth cohorts suffered from higher incidence risk. SDI presented a positive relationship with incidence, and the smoking-attributable burden was tremendous in China-ASEAN-FTA and EEU region. Secondary prevention should be prioritized in BRICS-plus nations, and health policies targeting important populations should be strengthened based on their characteristics and adaptability.
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Carga Global de Enfermedades , Neoplasias de la Próstata , Humanos , Masculino , Anciano de 80 o más Años , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiología , China/epidemiología , Neoplasias de la Próstata/epidemiologíaRESUMEN
BACKGROUND: The inhibitory effect of γδT17 cells on the formation of murine malignant pleural effusions (MPE) has been established. However, there is limited understanding regarding the phenotypic characterization of γδ T cells in MPE patients and their recruitment to the pleural cavity. METHODS: We quantified γδ T cell prevalence in pleural effusions and corresponding peripheral blood from malignant and benign patients using immunohistochemistry and flow cytometry. The expression of effector memory phenotype, stimulatory/inhibitory/chemokine receptors and cytokines on γδ T cells in MPE was analyzed using multicolor flow cytometry. The infiltration of γδ T cells in MPE was assessed through immunofluorescence, ELISA, flow cytometry and transwell migration assay. RESULTS: We observed a significant infiltration of γδ T cells in MPE, surpassing the levels found in blood and benign pleural effusion. γδ T cells in MPE exhibited heightened expression of CD56 and an effector memory phenotype, while displaying lower levels of PD-1. Furthermore, γδ T cells in MPE showed higher levels of cytokines (IFN-γ, IL-17A and IL-22) and chemokine receptors (CCR2, CCR5 and CCR6). CCR2 expression was notably higher in the Vδ2 subtype compared to Vδ1 cells. Moreover, the complement C5a enhanced cytokine release by γδ T cells, upregulated CCR2 expression in Vδ2 subsets, and stimulated the production of chemokines (CCL2, CCL7 and CCL20) in MPE. In vitro utilizing CCR2 neutralising and C5aR antagonist significantly reduced the recruitment of γδ T cells. CONCLUSIONS: γδ T cells infiltrate MPE by overexpressing CCR2 and exhibit hightened inflammation, which is further augmented by C5a.
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Derrame Pleural Maligno , Derrame Pleural , Animales , Humanos , Ratones , Quimiotaxis , Citocinas , Inflamación , Derrame Pleural Maligno/patología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Receptores de Quimiocina , Complemento C5a/metabolismoRESUMEN
Cadmium (Cd) exposure increases the risk of chronic kidney disease (CKD). But the contribution of dietary Cd intake, the primary exposure route of Cd in humans, to the CKD burden remains to be evaluated in China. Concentrations of Cd in foods and population glomerular filtration rate (GFR) were retrieved from studies published between January 2000 and February 2023 in China. Daily food consumption in adults aged ≥35 years old was obtained from two nationwide Chinese surveys. Dietary Cd intake and its contribution rate among total Cd exposure from diet, inhalation, smoking and water were evaluated. Urinary Cd (UCd) was estimated using the toxicokinetic (TK) model based on dietary Cd intake. The effect of Cd on kidney function has been quantified with the previously published dose-response relationship between UCd and GFR. The incidence and disability-adjusted life years (DALYs) of CKD attributable to dietary Cd intake were derived considering the contribution rate of dietary Cd intake at the national and provincial levels. The national average dietary Cd intake was 0.6891 µg/kg bw/day, contributing 63.69% of total Cd exposure. The Cd exposure through foods resulted in 2.34 (95% uncertainty interval, UI: 1.54-3.40) stage 4 CKD and 0.37 (95% UI: 0.20-0.59) stage 5 CKD cases per 100,000 persons/year in mainland China, 2020. The corresponding DALYs loss associated with stage 4 and stage 5 CKD due to dietary Cd intake were 5.14 (95% UI: 3.24-7.67) and 4.78 (95% UI: 2.32-8.30) per 100,000 persons/year, together accounting for 2% of total DALYs of CKD. Greater dietary Cd intake and corresponding burden of late-stage CKD were observed in Southern areas than in Northern areas. Diet remains the primary exposure to Cd in Chinese adults. Efforts to reduce dietary Cd exposure would positively impact public health, especially in Southern provinces with high Cd exposure.
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Improving citizen epidemic prevention information literacy is one of the most cost-efficient and important measures to improve people's epidemic prevention abilities to effectively deal with future public health crises. Epidemic prevention information literacy is beneficial to improve individuals' ability to deal with public health crises in the future. By summarizing related domestic and international research, and utilizing an empirical methodology, we constructed an epidemic prevention information literacy assessment model with good reliability, validity, and model fit. The model is composed of four indicators: (1) "epidemic prevention information awareness"; (2) "epidemic prevention information knowledge"; (3) "epidemic prevention information ability"; (4) "epidemic prevention information morality". We used the model to assess the epidemic prevention information literacy of Chinese citizens. The results showed the following: (1) the overall level of the epidemic prevention information literacy of Chinese citizens was comparatively high, however, its development was unbalanced, and the capability and moral levels of the epidemic prevention information were comparatively low; (2) the four dimensions of the epidemic prevention information literacy were different in terms of the citizens' education levels and locations. We analyzed the probable causes of these problems, and we propose specific corresponding countermeasures. The research provides a set of methods and norms for the evaluation of citizen epidemic prevention information literacy in the post-epidemic era.
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Alfabetización en Salud , Humanos , Reproducibilidad de los Resultados , Alfabetización en Salud/métodos , Alfabetización Informacional , Escolaridad , China/epidemiologíaRESUMEN
Background: Precise breast cancer-related mortality forecasts are required for public health program and healthcare service planning. A number of stochastic model-based approaches for predicting mortality have been developed. The trends shown by mortality data from various diseases and countries are critical to the effectiveness of these models. This study illustrates the unconventional statistical method for estimating and predicting the mortality risk between the early-onset and screen-age/late-onset breast cancer population in China and Pakistan using the Lee-Carter model. Methods: Longitudinal death data for female breast cancer from 1990 to 2019 obtained from the Global Burden of Disease study database were used to compare statistical approach between early-onset (age group, 25-49 years) and screen-age/late-onset (age group, 50-84 years) population. We evaluated the model performance both within (training period, 1990-2010) and outside (test period, 2011-2019) data forecast accuracy using the different error measures and graphical analysis. Finally, using the Lee-Carter model, we predicted the general index for the time period (2011 to 2030) and derived corresponding life expectancy at birth for the female breast cancer population using life tables. Results: Study findings revealed that the Lee-Carter approach to predict breast cancer mortality rate outperformed in the screen-age/late-onset compared with that in the early-onset population in terms of goodness of fit and within and outside forecast accuracy check. Moreover, the trend in forecast error was decreasing gradually in the screen-age/late-onset compared with that in the early-onset breast cancer population in China and Pakistan. Furthermore, we observed that this approach had provided almost comparable results between the early-onset and screen-age/late-onset population in forecast accuracy for more varying mortality behavior over time like in Pakistan. Both the early-onset and screen-age/late-onset populations in Pakistan were expected to have an increase in breast cancer mortality by 2030. whereas, for China, it was expected to decrease in the early-onset population. Conclusion: The Lee-Carter model can be used to estimate breast cancer mortality and so to project future life expectancy at birth, especially in the screen-age/late-onset population. As a result, it is suggested that this approach may be useful and convenient for predicting cancer-related mortality even when epidemiological and demographic disease data sets are limited. According to model predictions for breast cancer mortality, improved health facilities for disease diagnosis, control, and prevention are required to reduce the disease's future burden, particularly in less developed countries.
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Background and aims: Complement activation is essential for tuberculosis pleural effusion. However, little is known about the value of complement regulatory protein (CD46, CD55, and CD59) in the differential diagnosis of tuberculosis. Materials and methods: Ninety-nine patients with exudative pleural effusion admitted to Xiangya Hospital of Central South University from June 1, 2021to November 14, 2022 were enrolled. The expression levels of soluble CD46 (sCD46), soluble CD55 (sCD55), and soluble CD59 (sCD59) in pleural effusion were quantified by enzyme-linked immunosorbent assay, and the receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic and co-diagnostic values. Results: The ADA level is higher in TPE patients than non-TPE patients. It is well-found that TPE patients had lower levels of sCD46, sCD55, and sCD59 compared with non-TPE patients. Moreover, the expression of sCD46, sCD55, and sCD59 in pleural effusion was negatively correlated with ADA. In addition, the diagnostic efficacy of sCD46, sCD55 and sCD59 was comparable to that of ADA, with 0.896, 0.857, 0.858 and 0.893, respectively. Furthermore, combine detection of sCD46, sCD55, sCD59 and ADA could improve the diagnostic accuracy. Conclusions: Complement regulatory factors (CD46, CD55, and CD59) were validated by this project to be promising candidate biomarkers for the diagnosis of TPE with high accuracy. The combination of the CD46, CD55, and CD59 and ADA assay exist a better diagnostic value in TPE.
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Derrame Pleural , Tuberculosis Pleural , Humanos , Tuberculosis Pleural/diagnóstico , Adenosina Desaminasa/metabolismo , Biomarcadores/metabolismo , Derrame Pleural/diagnóstico , Curva ROC , Proteínas del Sistema ComplementoRESUMEN
Background: Interleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects between them. Methods: We conducted a bi-directional two-sample Mendelian randomization (MR) study to assess the causal associations between ILs and prostate cancer. Genetic instruments and summary-level data for 10 ILs were obtained from three genome-wide association meta-analyses. Prostate cancer related data were obtained from the PRACTICAL (79,148 cases and 61,106 controls), UK Biobank (7,691 cases and 169,762 controls) and FinnGen consortium (10,414 cases and 124,994 controls), respectively. Results: The odds ratio of prostate cancer was 0.92 (95% confidence interval (CI), 0.89, 0.96; P=1.58×10-05) and 1.12 (95% CI, 1.07, 1.17; P=6.61×10-07) for one standard deviation increase in genetically predicted IL-1ra and IL-6 levels, respectively. Genetically predicted levels of IL-1ß, IL-2a, IL-6ra, IL-8, IL-16, IL-17, IL-18, and IL-27 were not associated with the risk of prostate cancer. Reverse MR analysis did not find the associations between genetic liability to prostate cancer and higher levels of IL-1ra (ß, -0.005; 95% CI, -0.010, 0.001; P=0.111) and IL-6 (ß, 0.002; 95% CI, -0.011, 0.014; P=0.755). Conclusion: This MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it.
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Background: Brazil, Russia, India, China, South Africa, and 30 other Asian nations make up the BRICS-Plus, a group of developing countries that account for about half of the world's population and contribute significantly to the global illness burden. This study aimed to analyzed the epidemiological burden of female breast cancer (BC) across the BRICS-Plus from 1990 to 2019 and studied the associations with age, period, birth cohort and countries' sociodemographic index (SDI). Methods: The BC mortality and incidence estimates came from the 2019 Global Burden of Disease Study. We estimated cohort and period effects in BC outcomes between 1990 and 2019 using age-period-cohort (APC) modeling. The maximum likelihood (ML) of the APC-model Poisson with log (Y) based on the natural-spline function was used to estimate the rate ratio (RR). We used annualized rate of change (AROC) to quantify change over the previous 30 years in BC across BRICS-Plus and compare it to the global. Results: In 2019, there were about 1.98 million female BC cases (age-standardized rate of 45.86 [95% UI: 41.91, 49.76]) and 0.69 million deaths (age-standardized rate of 15.88 [95% UI: 14.66, 17.07]) around the globe. Among them, 45.4% of incident cases and 51.3% of deaths were attributed to the BRICS-Plus. China (41.1% cases and 26.5% deaths) and India (16.1% cases and 23.1% deaths) had the largest proportion of incident cases and deaths among the BRICS-Plus nations in 2019. Pakistan came in third with 5.6% cases and 8.8% deaths. Over the past three decades, from 1990 to 2019, the BRICS-Plus region's greatest AROC was seen in Lesotho (2.61%; 95%UI: 1.99-2.99). The birth cohort impacts on BC vary significantly among the BRICS-Plus nations. Overall, the risk of case-fatality rate tended to decline in all BRICS-Plus nations, notably in South Asian Association for Regional Cooperation (SAARC) and China-ASEAN Free Trade Area (China-ASEAN FTA) countries, and the drop in risk in the most recent cohort was lowest in China and the Maldives. Additionally, there was a substantial negative link between SDI and case fatality rate (r1990= -0.91, p<0.001; r2019= -0.89, p<0.001) in the BRICS-Plus in both 1990 and 2019, with the Eurasian Economic Union (EEU) nations having the highest case fatality rate. Conclusions: The BC burden varies remarkably between different BRICS-Plus regions. Although the BRICS' efforts to regulate BC succeeded, the overall improvements lagged behind those in high-income Asia-Pacific nations. Every BRICS-Plus country should strengthen specific public health approaches and policies directed at different priority groups, according to BRIC-Plus and other high-burden nations.
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A low-cost natural silicate ore supported Fe2O3 (FeSO) was synthesized for catalytic ozonation of sulfamethoxazole (SMX). XRD, SEM-EDS, BET, FTIR and XPS results of the FeSO catalyst confirmed that the natural silicate ore was successfully modified with iron oxide. The effects of key factors, such as catalyst dosage, initial solution pH, reaction temperature, inorganic anions and initial concentration, on ozonation degradation were systemically investigated. The degradation rate of SMX (20 mg L-1) was 88.1% after 30 min, compared with only 35.1% SMX degradation rate in the absence of the catalyst, and the total organic carbon (TOC) removal reached 49.1% after 60 min. Reaction mechanisms revealed that surface hydroxyl groups of FeSO were a critical factor for hydroxyl radical (ËOH) production leading to fast SMX degradation in the ozone decomposition process. The degradation products were detected, and the possible pathways of SMX were then proposed. This study provides guidance for preparing a low-cost catalyst and analyzing the degradation products and pathways of SMX in the ozonation process, which is of significance in practical industrial applications.
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BACKGROUND: Prostate, bladder and kidney cancers are common age-related genitourinary cancers. China's population is aging at an increasing rate, so predicting the morbidity and mortality of prostate, bladder, and kidney cancer in China is of great significance to provide epidemiological evidence for forward planning and implementation of national health policies. METHODS: Numbers of incidences and deaths by cancer (prostate, bladder and kidney), sex (male and female) and age groups from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study. We applied Bayesian age-period-cohort models to predict incidences and deaths to 2030. We also calculated Age-standardized incidence rate (ASIR) and mortality rate (ASMR), their trends were quantified by estimated average percentage change (EAPC) and 95% confidence interval (CI). RESULTS: Predictions suggest that by 2030, there will be 315,310 prostate cancer cases, 192,390 bladder cancer cases and 126,980 kidney cancer cases. The ASIRs will increase to 25.54/100,000 for prostate cancer (EAPC: 2.88, 95% CI, 2.84, 2.93), 7.54/100,000 for bladder cancer (EAPC: 2.58, 95% CI, 2.54, 2.61) and 5.63/100,000 for kidney cancer (EAPC: 4.78, 95% CI, 4.54, 5.02). Number of deaths in 2030 will be 81,540, 61,220, and 41,940, respectively. Different ASMR changes are observed, the ASMR for prostate cancer will drop to 7.69/100,000 (EAPC: -0.29, 95% CI, -0.31, -0.27), the ASMR for bladder cancer will stabilize at 2.49/100,000 (EAPC: 0.00, 95% CI, -0.02, 0.03), the ASMR of kidney cancer will increase to 1.84/100,000 (EAPC: 3.45, 95% CI, 3.22, 3.67). From 1990 to 2030, higher numbers of cases and rates are reported among males and in the 60 plus age group, both ASIR and ASMR of bladder and kidney cancers presents progressively widening differences between both males and females and between the < 60 and the ≥ 60 age groups. CONCLUSION: Morbidity and mortality of the three genitourinary cancers are predicted to increase further over the next decade. It highlights the need for timely development and implementation of optimal health policies to curb the epidemic trends.
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Neoplasias Renales , Neoplasias de la Próstata , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Próstata , Neoplasias de la Vejiga Urinaria/epidemiología , Vejiga Urinaria , Teorema de Bayes , Incidencia , China/epidemiología , Neoplasias Renales/epidemiología , Neoplasias de la Próstata/epidemiologíaRESUMEN
BACKGROUND: Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. METHODS: We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis. RESULTS: The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07-1.43, P = 0.0045), 1.08 (95% CI 1.01-1.17, P = 0.0175), 0.94 (95% CI 0.67-1.30, P = 0.6891), 1.29 (95% CI 0.88-1.89, P = 0.1922), 1.23 (95% CI 0.85-1.78, P = 0.2623), and 1.04 (95% CI 0.76-1.42, P = 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92-1.20, P = 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96-1.26, P = 0.1725) and 0.84 (95% CI 0.69-1.02, P = 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08-1.58, P = 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11-1.43, P = 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05-1.23, P = 0.0021) were associated with BPH after the adjustment of BMI. CONCLUSION: This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.
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Análisis de la Aleatorización Mendeliana , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/etiología , Hiperplasia Prostática/genética , Polimorfismo de Nucleótido Simple , Obesidad/epidemiología , Obesidad/genética , Obesidad/complicaciones , Índice de Masa Corporal , Estilo de Vida , Estudio de Asociación del Genoma Completo , Factores de RiesgoRESUMEN
Background: The association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association. Materials and methods: In this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10-8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources. Results: The genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512-1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10-8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676-1.125, p = 0.292). Conclusion: Our MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.
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BACKGROUND: Lyme disease is a zoonotic disease caused by infection with Borrelia burgdorferi (Bb), the involvement of the nervous system in Lyme disease is usually referred to as Lyme neuroborreliosis (LNB). LNB has diverse clinical manifestations, most commonly including meningitis, Bell's palsy, and encephalitis. However, the molecular pathogenesis of neuroborreliosis is still poorly understood. Comprehensive transcriptomic analysis following Bb infection could provide new insights into the pathogenesis of LNB and may identify novel biomarkers or therapeutic targets for LNB diagnosis and treatment. METHODS: In the present study, we pooled transcriptomic dataset of Macaca mulatta (rhesus) from our laboratory and the human astrocyte dataset GSE85143 from the Gene Expression Omnibus database to screen common differentially expressed genes (DEGs) in the Bb infection group and the control group. Functional and enrichment analyses were applied for the DEGs. Protein-Protein Interaction network, and hub genes were identified using the Search Tool for the Retrieval of Interaction Genes database and the CytoHubba plugin. Finally, mRNA expression of hub genes was validated in vitro and ex vivo from Bb infected models and normal controls by quantitative reverse transcription PCR (qRT-PCR). RESULTS: A total of 80 upregulated DEGs and 32 downregulated DEGs were identified. Among them, 11 hub genes were selected. The pathway enrichment analyses on 11 hub genes revealed that the PI3K-Akt signaling pathway was significantly enriched. The mRNA levels of ANGPT1, TLR6, SREBF1, LDLR, TNC, and ITGA2 in U251 cells and/or rhesus brain explants by exposure to Bb were validated by qRT-PCR. CONCLUSION: Our study suggested that TLR6, ANGPT1, LDLR, SREBF1, TNC, and ITGA may be candidate mammal biomarkers for LNB, and the TLR6/PI3K-Akt signaling pathway may play an important role in LNB pathogenesis.
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Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Neuroborreliosis de Lyme , Animales , Biomarcadores , Borrelia burgdorferi/genética , Grupo Borrelia Burgdorferi/genética , Sistema Nervioso Central , Humanos , Macaca mulatta/genética , Mamíferos , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero , Receptor Toll-Like 6/genética , TranscriptomaRESUMEN
OBJECTIVES: We hope to identify key molecules that can be used as markers of asthma severity and investigate their correlation with immune cell infiltration in severe asthma. METHODS: An asthma dataset was downloaded from the Gene Expression Omnibus database and then processed by R software to obtain differentially expressed genes (DEGs). First, multiple enrichment platforms were applied to analyze crucial biological processes and pathways and protein-protein interaction networks related to the DEGs. We next combined least absolute shrinkage and selection operator logistic regression and the support vector machine-recursive feature elimination algorithms to screen diagnostic markers of severe asthma. Then, a local cohort consisting of 40 asthmatic subjects (24 with moderate asthma and 16 with severe asthma) was used for biomarker validation. Finally, infiltration of immune cells in asthma bronchoalveolar lavage fluid and their correlation with the screened markers was evaluated by CIBERSORT. RESULTS: A total of 97 DEGs were identified in this study. Most of these genes are enriched in T cell activation and immune response in the asthma biological process. CC-chemokine receptor 7 (CCR7) and natural killer cell protein 7(NKG7) were identified as markers of severe asthma. The highest area under the ROC curve (AUC) was from a new indicator combining CCR7 and NKG7 (AUC = 0.851, adj. p < 0.05). Resting and activated memory CD4 T cells, activated NK cells, and CD8 T cells were found to be significantly higher in the severe asthma group (adj. p < 0.01). CCR7 and NKG7 were significantly correlated with these infiltrated cells that showed differences between the two groups. In addition, CCR7 was found to be significantly positively correlated with eosinophils (r = 0.38, adj. p < 0.05) infiltrated in bronchoalveolar lavage fluid. CONCLUSION: CCR7 and NKG7 might be used as potential markers for asthma severity, and their expression may be associated with differences in immune cell infiltration in the moderate and severe asthma groups.
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Asma , Asma/diagnóstico , Asma/genética , Biomarcadores/metabolismo , Líquido del Lavado Bronquioalveolar , Humanos , Activación de Linfocitos , Receptores CCR7/genéticaRESUMEN
BACKGROUND: Pleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remain challenging. Although monocytes have been confirmed as an important immune cell in tuberculosis and malignancy, little is known about the role of monocytes subpopulations in the diagnosis of pleural effusion. METHODS: Pleural effusion samples and peripheral blood samples were collected from 40 TPE patients, 40 MPE patients, and 24 transudate pleural effusion patients, respectively. Chemokines (CCL2, CCL7, and CX3CL1) and cytokines (IL-1ß, IL-17, IL-27, and IFN-γ) were measured by ELISA. The monocytes phenotypes were analyzed by flow cytometry. The chemokines receptors (CCR2 and CX3CR1) and cytokines above in different monocytes subsets were analyzed by real-time PCR. Receiver operating characteristic curve analysis was performed for displaying differentiating power of intermediate and nonclassical subsets between tuberculous and malignant pleural effusions. RESULTS: CCL7 and CX3CL1 levels in TPE were significantly elevated in TPE compared with MPE and transudate pleural effusion. Cytokines, such as IL-1ß, IL-17, IL-27, and IFN-γ, in TPE were much higher than in other pleural effusions. Moreover, CD14+ CD16++ nonclassical subset frequency in TPE was remarkably higher than that in MPE, while CD14++ CD16+ intermediate subset proportion in MPE was found elevated. Furthermore, CX3CL1-CX3CR1 axis-mediated infiltration of nonclassical monocytes in TPE was related to CX3CL1 and IFN-γ expression in TPE. Higher expression of cytokines (IL-1ß, IL-17, IL-27, and IFN-γ) were found in nonclassical monocytes compared with other subsets. Additionally, the proportions of intermediate and nonclassical monocytes in pleural effusion have the power in discriminating tuberculosis from malignant pleural effusion. CONCLUSIONS: CD14 and CD16 markers on monocytes could be potentially used as novel diagnostic markers for diagnosing TPE and MPE.
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Interleucina-27 , Derrame Pleural Maligno , Derrame Pleural , Tuberculosis , Biomarcadores , Exudados y Transudados/metabolismo , Humanos , Interleucina-17 , Monocitos/metabolismo , Derrame Pleural/diagnóstico , Derrame Pleural/metabolismo , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/metabolismo , Tuberculosis/diagnósticoRESUMEN
BACKGROUND: Clinical research has frequently not been taught in a practical way, often resulting in a very didactic approach rendering it not very accessible for medical undergraduates. Simulation can provide an immersive, interactive, and reflective experience and may be applied to the clinical research curriculum. METHODS: A 7-step model, modified from Kern's six-step approach and Khamis's stepwise model, was used to develop the curriculum. A questionnaire survey on undergraduates' attitude towards, knowledge and practice of clinical research and simulation education was conducted to generate a targeted needs assessment. The simulation framework was integrated into the development of educational strategies. Experts were consulted to assess the curriculum prior to implementation. RESULTS: Talent construction in China needs an innovative capability-enhanced clinical research curriculum. Sixty-six clinical undergraduates in our school completed the survey. 89.39% (59/66) of them hadn't participated in clinical research, while 93.94% (62/66) would like to conduct clinical trials if possible. 75.76% of respondents didn't have knowledge of or practical abilities in clinical trials. The mean score for practical ability (2.02 ± 0.92) was lower than that of knowledge (2.20 ± 0.93) (P < 0.01). The dimension of case report form got the lowest score among the five dimensions. Participating in clinical research (P = 0.04) and learning for themselves (P < 0.01) by a few students may have increased the total score. The curriculum was designed to simulate the whole process from protocol writing, registration, ethical approval, implementation, and data analysis to reporting based on one case study, and was divided into two parts to simulate different types of research: randomized controlled trials and observational studies. It was conducted in semesters 5 and 7 respectively, both including 16 sessions. After expert consultation, one session having a 29.01% coefficient of variation was adjusted and replaced. The final simulation class design scenario scripts are provided for reference. CONCLUSIONS: The targeted needs assessment exposed medical undergraduates' poor knowledge of and abilities in clinical research. This is the first report of a simulation-based clinical research curriculum developed in China, and adds curriculum development and design details to the limited related published studies.