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Automatic extraction of valuable, structured evidence from the exponentially growing clinical trial literature can help physicians practice evidence-based medicine quickly and accurately. However, current research on evidence extraction has been limited by the lack of generalization ability on various clinical topics and the high cost of manual annotation. In this work, we address these challenges by constructing a PICO-based evidence dataset PICO-DS, covering five clinical topics. This dataset was automatically labeled by a distant supervision based on our proposed textual similarity algorithm called ROUGE-Hybrid. We then present an Aceso-DSAL model, an extension of our previous supervised evidence extraction model - Aceso. In Aceso-DSAL, distantly-labelled and multi-topic PICO-DS was exploited as training corpus, which greatly enhances the generalization of the extraction model. To mitigate the influence of noise unavoidably-introduced in distant supervision, we employ TextCNN and MW-Net models and a paradigm of active learning to weigh the value of each sample. We evaluate the effectiveness of our model on the PICO-DS dataset and find that it outperforms state-of-the-art studies in identifying evidential sentences.
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In the present work the atomic, electronic and optical properties of two-dimensional graphene, borophene, and boron carbide heterojunction bilayer systems (Graphene-BC3, Graphene-Borophene and Graphene-B4C3) as well as their constituent monolayers are investigated on the basis of first-principles calculations using the HSE06 hybrid functional. Our calculations show that while borophene is metallic, both monolayer BC3 and B4C3 are indirect semiconductors, with band-gaps of 1.822 eV and 2.381 eV as obtained using HSE06. The Graphene-BC3 and Graphene-B4C3 bilayer heterojunction systems maintain the Dirac point-like character of graphene at the K-point with the opening of a very small gap (20-50 meV) and are essentially semi-metals, while Graphene-Borophene is metallic. All bilayer heterostructure systems possess absorbance in the visible region where the resonance frequency and resonance absorption peak intensity vary between structures. Remarkably, all heterojunctions support plasmons within the range 16.5-18.5 eV, while Graphene-B4C3 and Graphene-Borophene exhibit a π-type plasmon within the region 4-6 eV, with the latter possessing an additional plasmon at the lower energy of 1.5-3 eV. The dielectric tensor for Graphene-B4C3 exhibits complex off-diagonal elements due to the lower P3 space group symmetry indicating it has anisotropic dielectric properties and could exhibit optically active (chiral) effects. Our study shows that the two-dimensional heterostructures have desirable optical properties broadening the potential applications of the constituent monolayers.
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Introduction: Warning signs serve as proximal indicators of suicide risk, making early recognition imperative for effective prevention strategies. This study aimed to explore self-identified suicide warning signs among Chinese patients with mood disorders based on safety planning framework. Methods: Researchers collaborated with patients to develop a safety plan and compiled warning signs based on it. Word frequency and network analysis were conducted to identify key warning signs. Directed content analysis categorized these signs into cognitive, emotional, behavioral, or physiological themes according to the suicide mode theory. Additionally, we examined potential variations in reported warning signs among participants with different demographic characteristics, including age, gender, and history of suicide attempts. Results: "Low mood" and "crying" emerged as prominent warning signs, with "social withdrawal" closely following. Patients commonly reported emotional themes during suicidal crises, often experiencing two to three themes simultaneously, primarily focusing on emotional, behavioral, and physiological themes. Males exhibited a higher proportion of concurrently reporting three sign themes compared to females (P < 0.05), while no difference was observed in warning signs among patients with other demographic traits. Discussion: This study offers a nuanced understanding of warning signs among mood disorder patients in China. The findings underscore the necessity for comprehensive suicide risk management strategies, emphasizing interventions targeting emotional regulation and social support. These insights provide valuable information for enhancing suicide prevention and intervention efforts.
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Trastornos del Humor , Investigación Cualitativa , Humanos , Masculino , Femenino , Trastornos del Humor/psicología , Adulto , China , Persona de Mediana Edad , Prevención del Suicidio , Intento de Suicidio/estadística & datos numéricos , Intento de Suicidio/psicología , Ideación Suicida , Suicidio/psicología , Suicidio/estadística & datos numéricos , Adulto JovenRESUMEN
Suicidal thoughts and behaviors (STBs) are increasing among young people (aged 12-24 years) in China. Although Ecological Momentary Assessment (EMA) has been increasingly used to study STBs worldwide, no study has been conducted on young people with mood disorders (MD) in China. This mixed-method study aimed to evaluate the feasibility and acceptability of suicide risk monitoring in 75 young people with MD. Participants completed five to eight daily EMA surveys and wore smart bands for the EMA study. Semi-structured interviews were used to collect feedback. High adherence to EMA surveys (73.0 %) and smart bands (87.4 %) indicated feasibility. Participants reported an overall positive experience with the EMA study (helpful, friendly, and acceptable). Additionally, the reasons they were willing to comply with the EMA study were: (1) seeing the possibility of returning to "normal," and (2) experiencing the process of returning. However, a small proportion of participants had negative experiences (e.g., annoyance and missing prompts). The results of this mixed-methods study provide preliminary support for the feasibility and acceptability of using EMA (combined smartphones and wearable sensor devices) to assess suicidality among young people with MD in the Chinese cultural and social context.
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Evaluación Ecológica Momentánea , Estudios de Factibilidad , Trastornos del Humor , Ideación Suicida , Humanos , Femenino , Masculino , China , Adolescente , Adulto Joven , Trastornos del Humor/diagnóstico , Adulto , Medición de Riesgo , Teléfono Inteligente , Aceptación de la Atención de Salud , Niño , Suicidio/psicología , Dispositivos Electrónicos VestiblesRESUMEN
Objective: In recent years, there has been a significant increase in research using ecological momentary assessment (EMA) to explore suicidal thoughts and behaviors (STBs). Meanwhile, concerns have been raised regarding the potential impacts of frequent and intense STBs assessments on the study participants. Methods: From November 2021 to June 2023, a total of 83 adolescent and young adult outpatients (Mage = 21.0, SDage = 6.3, 71.1% female), who were diagnosed with mood disorders, were recruited from three psychiatric clinics in China. Smartphone-based EMA was used to measure suicidal thoughts three times per day at randomly selected times. We examined the change of suicidal thoughts in each measurement and within 1 day to evaluate potential adverse effects using Bayesian multilevel models. Results: The 3,105 effective surveys were nested in 83 participants (median follow-up days: 14 days). The results of two-level models indicated that suicidal thoughts decreased during the monitoring period. However, this effect varied among different individuals in the two-level model. Conclusion: Our findings did not support the notion that repeated assessment of suicidal thoughts is iatrogenic, but future research should continue to investigate the impact of frequent assessment on suicidal thoughts, taking into account individual differences and utilizing larger sample sizes.
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Evaluación Ecológica Momentánea , Ideación Suicida , Humanos , Femenino , Masculino , Adolescente , Adulto Joven , China , Adulto , Teorema de Bayes , Encuestas y Cuestionarios , Teléfono Inteligente , Trastornos del HumorRESUMEN
Air pollution levels tend to be higher in urban areas than in surrounding rural areas, and this air pollution has a negative effect on human health. However, the spatiotemporal patterns of urban-rural air pollution differences and the determinants of these differences remain unclear. Here, we calculate the Urban Air Pollution Island (UAPI) intensity for PM2.5 and PM10 on a monthly, seasonal, and annual scale for 2273 cities in China from 2000 to 2020. Subsequently, we analyze the influence of urban characteristics using a combined approach of a two-way fixed effects model and a spatial Durbin model. Results show a strong downward trend in the UAPI intensity since 2013, with reductions ranging from 42 % to 61 % until 2020, for both pollutants and in summer as well as winter. Consistently, the proportion of the cities experiencing the UAPI phenomenon decreased from 94.5 % to 77.3 % for both PM2.5 and PM10. We find a significant influence of urban morphology on UAPI. Specifically, urban sprawl, polycentric development, and an increase in urban green spaces are associated with a reduction in UAPI, while dense urban areas intensify it. Our study also reveals a robust inverted U-shaped relationship between stages of economic development and UAPI. Moreover, economic development and air pollution itself show spillover effects that oppose their direct impacts. These results suggest that urban and regional planning and more ambitious climate change mitigation policies could be more effective strategies for mitigating air pollution in cities than end-of-pipe control.
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Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Ciudades , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Contaminación del Aire/análisis , China , Monitoreo del Ambiente/métodosRESUMEN
This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.
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Vasculitis por IgA , Ratas , Animales , Vasculitis por IgA/tratamiento farmacológico , Monoterpenos , Administración Oral , Cromatografía Líquida con Espectrometría de MasasRESUMEN
Background: Health financing produce a broad range of healthy life expectancy (HLE) disparities. In West Africa, limited research exists on the association between health financing and HLE at ecological level during a consecutive period of time from the spatial perspectives. This study aimed to determine the existence, quantify the magnitude, and interpret the association between health financing and HLE. Methods: A Dynamic Spatial Durbin model was used to explain the association between HLE and health financing level and structure during 1995-2019 in West Africa. Spatial spillover effects were introduced to interpret the direct and indirect effects caused by health financing level and structure on HLE during the long and short terms. Results: Spatial dependence and clustering on HLE were observed in West Africa. Although the overall level of total health spending, government health spending, out-of-pocket health spending, and development assistance for health (DAH) increased from 1995 to 2019, government health spending per person experienced a declining trend. Out-of-pocket health spending per total health spending was the highest among other sources of health financing, decreasing from 57% during 1995-1999 to 42% during 2015-2019. Total health spending and out-of-pocket health spending affected HLE positively and negatively in the long term, respectively. Government health spending and prepaid private health spending per person had positive effects on local and adjacent country HLE in the short-term, while DAH had negative effects on the same. The short-term spatial spillover effects of government health spending, DAH, and prepaid private health spending per person were more pronounced than the long-term effects. Conclusions: Spatial variations of HLE existed at country-level in West Africa. Health financing regarding government, non-government, as well as external assistance not only affected HLE disparities at local scale but also among nearby countries. Policymakers should optimise supportive health financing transition policies and narrow the national gap to reduce health disparities and increase HLE. Externalities of policy of those health financing proxies should be took into consideration to promote health equity to improve global health governance.
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Financiación Gubernamental , Financiación de la Atención de la Salud , Humanos , Esperanza de Vida Saludable , Promoción de la Salud , Países en Desarrollo , Gastos en Salud , África OccidentalRESUMEN
Background: West African countries experienced the highest under-5 mortality rate (U5MR), the lowest life expectancy, and the poorest economic development. This study aimed to explore the spatiotemporal trend of U5MR and spatial spillover effects of health resources and services to provide a basis for establishing health policies and international cooperative mechanisms in West Africa. Methods: We retrieved data from the World Health Organization's Global Health Observatory, the United Nations Human Development Report, and the Global Burden of Disease Study 2019. Joinpoint regression analysis and Moran's I method were used to examine the temporal trend and spatial dependence of U5MR, respectively. Spatial regression analysis was used to examine the spatial spillover effects. Results: The long-term downward trends in U5MR were divided into multiple segments by two or three change points in 2013, 2014, or 2015, and the annual percentage change after 2015 was higher than before 2015. Global Moran's I was positive, significantly indicating positive spatial autocorrelation, which increased from 0.2850 (p = 0.0210) to 0.3597 (p = 0.0080). Based on spatial regression analysis, human development index (HDI), physicians density, nurses and midwives density, health center density, percentage of infants lacking immunization for diphtheria and measles, and coverage rate of at least one antenatal visit had negative spatial spillover effects on U5MR. HDI had the strongest negative correlation (ß = -0.0187 to -0.1054, p < 0.0001). Current health expenditure (CHE) per capita had positive spatial spillover effects on U5MR. Conclusion: This study revealed the spatiotemporal trend of U5MR in West African countries and spatial spillover effects of health resources and services. Promoting economic development, increasing health human resources, health expenditure, vaccination rate, antenatal care coverage, and the proportion of health professionals attending births not only reduced the local U5MR but also exerted spatial spillover effects on adjacent countries. The West African Health Organization may consider regional spillover mechanisms to develop regional health policy and intervention cooperation mechanisms, which will contribute to achieving the sustainable development goal on U5MR, Africa Agenda 2063, and universal health coverage.
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The conversion of ethanol into high-valuable chemicals and H2 by photocatalytic process provides a sustainable approach to produce carbon-chain-prolonged chemicals and hydrogen energy. In this article, Ni-MOF-74 was added to fabricate the hierarchical CdS/NiS-N composites with an elevated specific surface area during the hydrothermal synthesis of CdS microsphere, and the Ni-MOF-74 facilitate the self-assemble growth of CdS and provide a source of Ni for the formation of NiS. The as-prepared photocatalyst was subjected to photocatalytic ethanol conversion, and the hierarchical composite material CdS/NiS-N (100) formed by adding 100â mg of Ni-MOF-74 exhibits the highest photocatalytic activity and stability in an ethanol aqueous solution with a water content of 10 %. Under visible light irradiation, the conversion rate of ethanol reached 15.2 % at the photocatalytic reaction of 5â h. The selectivity of 2,3-butanediol(2,3-BDO) was 25 %, and the selectivity of acetaldehyde(AA) was 63 %. Through various characterizations, it has been proven that a large specific surface area and the coupling interface between CdS and NiS are key factors in improving photocatalytic performance. This work provides an effective strategy for constructing photocatalysts with coupled cocatalysts/semiconductors and large specific surface areas.
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PURPOSE OF REVIEW: Heart failure is a severe clinical syndrome with complex and unclarified mechanisms, and it poses a serious threat to human health. MicroRNA, a non-coding RNA, can directly bind to target genes and regulate their expression. The important role of microRNAs in the development of HF has become a hot topic of research in recent years. This paper summarizes and prospects the mechanisms of microRNAs in regulating cardiac remodeling during heart failure to provide reference ideas for further research and clinical treatment. RECENT FINDINGS: With extensive research, more target genes for microRNAs have been clarified. By modulating various molecules, microRNAs affect the contractile function of the myocardium and alter the process of myocardial hypertrophy, myocyte loss, and fibrosis, thereby interfering with the process of cardiac remodeling and exerting an important effect in the process of heart failure. Based on the above mechanism, microRNAs have promising applications in the diagnosis and treatment of heart failure. MicroRNAs form a complex post-transcriptional control mechanism of gene expression, and the increase or decrease of their content during heart failure largely alters the course of cardiac remodeling. By continuously identifying their target genes, it is expected to achieve more precise diagnosis and treatment of this important topic of heart failure.
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Insuficiencia Cardíaca , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Remodelación Ventricular/genética , Miocardio/metabolismo , Regulación de la Expresión GénicaRESUMEN
KEY MESSAGE: The salt-tolerance of transgenic soybean cleared for environmental release was improved by stable over-expression of AhBADH gene from Atriplex hortensis, which was demonstrated through molecular analysis and field experiments. An effective strategy for increasing the productivity of major crops under salt stress conditions is the development of transgenics that harbor genes responsible for salinity tolerance. Betaine aldehyde dehydrogenase (BADH) is a key enzyme involved in the biosynthesis of the osmoprotectant, glycine betaine (GB), and osmotic balance in plants, and several plants transformed with BADH gene have shown significant improvements in salt tolerance. However, very few field-tested transgenic cultivars have been reported, as most of the transgenic studies are limited to laboratory or green house experiments. In this study, we demonstrated through field experiments that AhBADH from Atriplex hortensis confers salt tolerance when transformed into soybean (Glycine max L.). AhBADH was successfully introduced into soybean by Agrobacterium mediated transformation. A total of 256 transgenic plants were obtained, out of which 47 lines showed significant enhancement of salt tolerance compared to non-transgenic control plants. Molecular analyses of the transgenic line TL2 and TL7 with the highest salt tolerance exhibited stable inheritance and expression of AhBADH in progenies with a single copy insertion. TL1, TL2 and TL7 exhibited stable enhanced salt tolerance and improved agronomic traits when subjected to 300mM NaCl treatment. Currently, the transgenic line TL2 and TL7 with stable enhanced salt tolerance, which have been cleared for environmental release, are under biosafety assessment. TL 2 and TL7 stably expressing AhBADH could then be applied in commercial breeding experiments to genetically improve salt tolerance in soybean.
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Atriplex , Tolerancia a la Sal , Tolerancia a la Sal/genética , Glycine max/metabolismo , Atriplex/genética , Atriplex/metabolismo , Fitomejoramiento , Betaína Aldehído Deshidrogenasa/genética , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Background: Cold exposure has been considered an essential risk factor for the global disease burden, while its role in cardiovascular diseases is still underappreciated. The increase in frequency and duration of extreme cold weather events like cold spells makes it an urgent task to evaluate the effects of ambient cold on different types of cardiovascular disease and to understand the factors contributing to the population's vulnerability. Methods: In the present systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane. We included original research that explored the association between cold exposure (low temperature and cold spell) and cardiovascular disease outcomes (mortality and morbidity). We did a random-effects meta-analysis to pool the relative risk (RR) of the association between a 1°C decrease in temperature or cold spells and cardiovascular disease outcomes. Results: In total, we included 159 studies in the meta-analysis. As a result, every 1°C decrease in temperature increased cardiovascular disease-related mortality by 1.6% (RR 1.016; [95% CI 1.015-1.018]) and morbidity by 1.2% (RR 1.012; [95% CI 1.010-1.014]). The most pronounced effects of low temperatures were observed in the mortality of coronary heart disease (RR 1.015; [95% CI 1.011-1.019]) and the morbidity of aortic aneurysm and dissection (RR 1.026; [95% CI 1.021-1.031]), while the effects were not significant in hypertensive disease outcomes. Notably, we identified climate zone, country income level and age as crucial influential factors in the impact of ambient cold exposure on cardiovascular disease. Moreover, the impact of cold spells on cardiovascular disease outcomes is significant, which increased mortality by 32.4% (RR 1.324; [95% CI 1.2341.421]) and morbidity by 13.8% (RR 1.138; [95% CI 1.015-1.276]). Conclusion: Cold exposure could be a critical risk factor for cardiovascular diseases, and the cold effect varies between disease types and climate zones. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022347247.
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Hierarchical micro/nanostructures assembled from nanorods and nanosheets have become promising candidates for photocatalysis. In this work, a series of hierarchical Cd-Ni-MOF micro/nanostructures, assembled from nanosheets and nanorods, were fabricated via a two-step solvothermal process involving the partial replacement of Ni2+ with Cd2+ in the Ni-MOF-74 structure. Different morphologies were obtained by considering different volume ratios of DMF and ethanol as the solvent during synthesis. Hierarchical Cd-Ni-MOF-T/CdS/NiS hybrid micro/nanostructures were synthesized by Ni2+ and Cd2+ exchange of Cd-Ni-MOFs with S2-. The as-prepared samples, which were composed of thin nanosheets alone, exhibited the best photocatalytic H2 evolution rate of about 40.08 mmol g-1 h-1. The p-n junction between CdS and NiS was found to be beneficial for the migration of photogenerated electrons from the conduction band (CB) of NiS to the CB of CdS. The heterojunction between CdS and Cd-Ni-MOF-T further promoted the transfer of an electron from the CB of CdS to the CB of Cd-Ni-MOF-T. Thus, this study demonstrated that hierarchical Cd-Ni-MOF-T/CdS/NiS architectures have a large specific surface area, leading to significantly improved photocatalytic activity.
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Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Tuberculosis/diagnóstico , Tuberculosis/metabolismo , Tuberculosis/microbiología , Mycobacterium tuberculosis/metabolismo , Empalme del ARN , Macrófagos/metabolismo , Biomarcadores , Enzimas Ubiquitina-Conjugadoras/metabolismo , Cinesinas/metabolismo , Factores de Empalme Serina-ArgininaRESUMEN
Objective: Promoting adolescent health is essential to achieving the goals of the Healthy China 2030 (HC 2030) initiative. As socioeconomic conditions improve and medical practices and disease patterns evolve, adolescent mortality rates and causes of death vary considerably. This study provides up-to-date data on adolescent mortality and causes of death in China, highlighting key areas of focus for investment in adolescent health. Methods: Data regarding mortality and causes of death in Chinese adolescents aged 10-19 years were extracted from the Global Burden of Disease study from 1990 to 2019. The data variables were examined according to year, sex, and age. The autoregressive integrated moving average model was used to predict non-communicable disease (NCD) mortality rates and rank changes in the leading causes of death until 2030. Results: The all-cause mortality rate (per 100,000 population) of Chinese adolescents aged 10-19 years steadily declined from 1990 (72.6/100,000) to 2019 (28.8). Male adolescents had a higher mortality (37.5/100,000 vs. 18.6 in 2019) and a slower decline rate (percent: -58.7 vs. -65.0) than female adolescents. Regarding age, compared with those aged 10-14 years, the mortality rate of adolescents aged 15-19 years had a higher mortality (35.9/100,000 vs. 21.2 in 2019) and a slower decrease rate (percent: -57.6 vs. -63.2). From 1990 to 2019, the rates of communicable, maternal, and nutritional diseases declined the most (percent: -80.0), while injury and NCDs mortality rates were relatively slow (percent: -50.0 and -60.0). In 2019, the five leading causes of death were road injuries (6.1/100,000), drowning (4.5), self-harm (1.9), leukemia (1.9), and congenital birth defects (1.3). Furthermore, NCDs' mortality rate decreased by -46.6% and -45.4% between 2015-2030 and 2016-2030, respectively. Conclusion: A notable decline was observed in all-cause mortality rates among Chinese adolescents aged 10-19 years. In addition, the mortality rates of NCDs are projected to meet the target from the Global Strategy for Women's, Children's, and Adolescents' Health (2016-2030) and HC2030 reduction indicators by 2030. However, it should be noted that injury is the leading cause of death, with sexual and age disparities remaining consistent.
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Causas de Muerte , Pueblos del Este de Asia , Enfermedades no Transmisibles , Adolescente , Niño , Femenino , Humanos , Masculino , Causas de Muerte/tendencias , Familia , Salud Global , Enfermedades no Transmisibles/epidemiologíaRESUMEN
TP53 is the most frequently mutated gene in muscle invasive bladder cancer (MIBC) and there are two gene signatures regarding TP53 developed for MIBC prognosis. However, they are limited to immune genes only and unable to be used individually across platforms due to their quantitative manners. We used 827 gene expression profiles from seven MIBC cohorts with varied platforms to build a pairwise TP53-derived transcriptome signature, 13 gene pairs (13-GPs). Since the 13-GPs model is a single sample prognostic predictor, it can be applied individually in practice and is applicable to any gene-expression platforms without specific normalization requirements. Survival difference between high-risk and low-risk patients stratified by the 13-GPs test was statistically significant (HR range: 2.26-2.76, all P < .0001). Discovery and validation sets showed that the 13-GPs was an independent prognostic factor after adjusting other clinical features (HR range: 2.21-2.82, all P < .05). Moreover, it was a potential supplement to the consensus molecular classification of MIBC to further stratify the LumP subtype (patients with better prognoses). High- and low-risk patients by the 13-GPs model presented distinct immune microenvironment and DDR mutation rates, suggesting that it might have the potential for immunotherapy. Being a general approach to other cancer types, this study demonstrated how we integrated gene variants with pairwise gene panels to build a single sample prognostic test in translational oncology.
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BACKGROUND: Although TRIpartite Motif containing 8 (TRIM8) gene plays an important role in a number of biological processes, such as inflammation, its function and mechanism in ulcerative colitis (UC) remain unknown. METHODS: The UC model was established by feeding mice with 3.5% dextran sulfate sodium (DSS). The animals were divided into the following four groups: control group, DSS group, DSS+short hairpin (sh)-NC group, and DSS+sh-TRIM8 group. Changes in body weight and disease activity index (DAI) score of mice in all the groups were recorded for 7 days. The animals were executed at the end of the experiment, and the expression of TRIM8 in colon tissue was detected by polymerase chain reaction and Western blot assays. The length of colon was measured, and the histopathological changes in mice colon were examined by hematoxylin and eosin staining. The expression of pro-inflammatory factors in mice serum and colonic tissue homogenate was detected by enzyme-linked-immunosorbent serologic assay. The expression of nuclear factor kappa B (NF-κB) pathway-related proteins in colonic tissues was detected by Western-blot analysis. RESULTS: TRIM8 was highly expressed in the colonic tissues of UC mice. Knockdown of TRIM8 improved DSS-induced weight loss, increased DAI score, shortened colon length, and alleviated colonic injury and inflammation in mice. Western-blot experiments showed that knockdown of TRIM8 inhibited DSS-induced phosphorylation of p65 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) protein but increased IκBα expression. CONCLUSION: Knockdown of TRIM8 inhibits UC injury and inflammatory response caused by DSS. This could be related to the regulation of NF-κB signaling pathway by TRIM8 protein.
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Colitis Ulcerosa , Proteínas del Tejido Nervioso , Ubiquitina-Proteína Ligasas , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/genética , Colitis Ulcerosa/metabolismo , Colon/patología , Sulfato de Dextran , Modelos Animales de Enfermedad , Inflamación/metabolismo , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Transducción de Señal , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: Exposure to tobacco imagery in films can result in tobacco use among adolescents and young adults. Efforts have been made to limit tobacco imagery in films in China. Our study investigates the level and trend of tobacco imagery in popular films in China from 2001 to 2020. METHODS: The running time of the 20 top-grossing films in China annually from 2001 to 2020 was divided into 5 min intervals, and those containing tobacco imagery were coded for the following aspects: country of origin, presence of warning, presence of minors and the presence of tobacco brands. RESULTS: We coded 9423 five-minute intervals across 400 films. Tobacco imagery occurred in 1344 intervals across 239 films. There was a declining trend in the proportion of films (r=-0.515, p=0.022) and the proportion of intervals (r=-0.004, p<0.001) with tobacco imagery over time. None of the films with tobacco imagery contained a warning for their audience against smoking. Chinese films contained more tobacco imagery than international films, and tobacco imagery related to minors and tobacco brands were present despite regulations. CONCLUSION: Tobacco imagery remains in films in China. The relevant authorities and film producers should ban films with tobacco imagery in China; for example, they should ban films with tobacco imagery from participating in awards, add warnings to films with tobacco imagery and give films containing tobacco imagery a default 'R' classification.