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In contemporary literature, little attention has been paid to the association between coronavirus disease-2019 (COVID-19) and cancer risk. We performed the Mendelian randomization (MR) to investigate the causal associations between the three types of COVID-19 exposures (critically ill COVID-19, hospitalized COVID-19, and respiratory syndrome coronavirus 2 (SARS-CoV-2) infection) and 33 different types of cancers of the European population. The results of the inverse-variance-weighted model indicated that genetic liabilities to critically ill COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (odds ratio [OR] = 1.0924; p-value = 0.0116), esophageal cancer (OR = 1.0004; p-value = 0.0226), colorectal cancer (OR = 1.0010; p-value = 0.0242), stomach cancer (OR = 1.2394; p-value = 0.0331), and colon cancer (OR = 1.0006; p-value = 0.0453). The genetic liabilities to hospitalized COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (OR = 1.1096; p-value = 0.0458), esophageal cancer (OR = 1.0005; p-value = 0.0440) as well as stomach cancer (OR = 1.3043; p-value = 0.0476). The genetic liabilities to SARS-CoV-2 infection had suggestive causal associations with the increased risk for stomach cancer (OR = 2.8563; p-value = 0.0019) but with the decreasing risk for head and neck cancer (OR = 0.9986, p-value = 0.0426). The causal associations of the above combinations were robust through the test of heterogeneity and pleiotropy. Together, our study indicated that COVID-19 had causal effects on cancer risk.
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Neoplasias da Mama , COVID-19 , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Feminino , SARS-CoV-2 , Estado Terminal , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Circular RNAs (circRNAs) are implicated with the progression of multiple cancers, including breast cancer. Besides, circRNA dysregulation is involved in the chemoresistance of cancer development. This study aimed to investigate the role of circRNA-cyclin dependent kinase 1 (circCDK1) in breast cancer. Quantitative real-time PCR (qPCR) and western blot were applied for expression analysis. Cell viability was determined by the cell counting kit-8 (CCK-8). Cell proliferation was evaluated by CCK-8, colony formation and 5-ethynyl-2'-deoxyuridine assays. Cell apoptosis was assessed by flow cytometry and the activities of caspase3 and caspase9. The potential binding between miR-489-3p and circCDK1 or CDK1 was verified by RNA immunoprecipitation assay, dual-luciferase reporter assay and pull-down assay. Animal models were constructed to explore the role of circCDK1 in vivo. CircCDK1 was overexpressed in Tamoxifen-resistant breast cancer cells, LCC2 and LCC9. The expression of circCDK1 in tumor tissues with Tamoxifen resistance was higher than that in tissues without Tamoxifen resistance. CircCDK1 knockdown strengthened the sensitivity of Tamoxifen in LCC2 and LCC9 cells and reduced Tamoxifen IC50. The downregulation of circCDK1 inhibited LCC2 andLCC9 cell proliferation and promoted cell apoptosis. CDK1 was the parent gene of circCDK1 and circCDK1 positively regulated CDK1 expression by targeting miR- 489-3p. CDK1 overexpression reversed the effects of circCDK1 knockdown. MiR-489-3p inhibition also reversed the effects of circCDK1 knockdown. CircCDK1 knockdown was verified to enhance Tamoxifen sensitivity in animal models. CircCDK1 knockdown enhanced the sensitivity of Tamoxifen in breast cancer cells and suppressed cell growth and survival by depleting CDK1 expression via releasing miR- 489-3p.
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Neoplasias da Mama , MicroRNAs , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proteína Quinase CDC2/genética , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular , Tamoxifeno/farmacologiaRESUMO
BACKGROUND: Peptic ulcer disease (PUD) is a common digestive disorder, of which the prevalence decreased in the past few decades. However, the decreasing tendency has plateaued in recent years due to changes in risk factors associated with the etiology of PUD, such as non-steroidal anti-inflammatory drug use. In this study, we investigated the epidemiological and the sociodemographic characteristics of PUD in 204 countries and territories from 1990 to 2019 based on data from the Global Burden of Disease, Injuries and Risk Factors (GBD) Study. METHODS: Demographic characteristics and annual prevalence, incidence, mortality, disability-adjusted life years (DALYs) and age-standardized death rate (ASR) data associated with PUD were obtained and analyzed. According to the sociodemographic index (SDI), the numbers of patients, ASRs, estimated annual percentage changes and geographical distributions were assessed with a generalized linear model and presented in world maps. All evaluations of numbers and rates were calculated per 100,000 population with 95% uncertainty intervals (UIs). RESULTS: In 2019, the global prevalence of PUD was approximately 8.09 [95% UI 6.79-9.58] million, representing a 25.82% increase from 1990. The age-standardized prevalence rate was 99.40 (83.86-117.55) per 100,000 population in 2019, representing a decrease of 143.37 (120.54-170.25) per 100,000 population from 1990. The age-standardized DALY rate in 2019 was decreased by 60.64% [74.40 (68.96-81.95) per 100,000 population] compared to that in 1990. In both sexes, the numbers and ASRs of the prevalence, incidence, deaths and DALYs were higher in males than in females over 29 years. Regionally, South Asia had the highest age-standardized prevalence rate [156.62 (130.58-187.05) per 100,000 population] in 2019. A low age-standardized death rate was found in the high-income super-region. Among nations, Kiribati had the highest age-standardized prevalence rate [330.32 (286.98-379.81) per 100,000 population]. Regarding socioeconomic status, positive associations between the age-standardized prevalence, incidence, death rate, DALYs and SDI were observed globally in 2019. CONCLUSIONS: Morbidity and mortality due to PUD decreased significantly from 1990 to 2019, while a gradual upward inclination has been observed in recent 15 years, which might be associated with changes in risk factors for PUD. Attention and efforts by healthcare administrators and society are needed for PUD prevention and control.
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Carga Global da Doença , Úlcera Péptica , Feminino , Humanos , Incidência , Masculino , Úlcera Péptica/epidemiologia , Prevalência , Anos de Vida Ajustados por Qualidade de Vida , Fatores de RiscoRESUMO
BACKGROUND: Relevant studies focusing on epidemiological of profiles hypertensive disorders of pregnancy from global data that report the cause-specific prevalence and trends of hypertensive disorders of pregnancy at global, regional and national levels from 1990 to 2019 by age and sociodemographic index are still limited. METHODS: For hypertensive disorders of pregnancy, point prevalence, annual incidence, and years lived with disability numbers and age standardized rates per 100,000 population were compared at regional and national levels by age and sociodemographic index using data from the global Burden of Disease 2019 Study, covering populations from 204 countries and territories. Estimates are reported with uncertainty intervals to exhibit the changing trends during a specific period. RESULTS: The incidence of hypertensive disorders of pregnancy increased from 16.30 million to 18.08 million globally, with a total increase of 10.92 % from 1990 to 2019. The age-standardized incidence rate decreased, with an estimated annual percent change of -0.68 (95 % confidence interval [CI] -0.49 to -0.86). The number of deaths due to hypertensive disorders of pregnancy was approximately 27.83 thousand in 2019, representing a 30.05 % decrease from 1990. Based on the incidence and prevalence, the number of deaths and years lived with disability were highest in the group aged 25-29 years, followed by the groups aged 30-34 and 20-24 years, while the lowest estimated incidence rate was observed in the group aged 25-29 years and higher incidence rates were observed in the youngest and oldest groups. Positive associations between incidence rates and the sociodemographic index and human development index were found for all countries and regions in 2019. Age-standardized incidence rates were higher in countries/regions with lower sociodemographic indices and human development indices. CONCLUSIONS: Our study provides a comprehensive overview of the global burden of hypertensive disorders of pregnancy. The death and incidence rates are decreasing in most countries and all regions except for those with low sociodemographic and human development indexes. This difference is mainly due to the increasing attention to prenatal examinations and health education. Further investigations should focus on forecasting the global disease burden of specific hypertensive disorders of pregnancy and modifiable risk factors.
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Hipertensão Induzida pela Gravidez/epidemiologia , Feminino , Saúde Global/tendências , Humanos , Hipertensão Induzida pela Gravidez/mortalidade , Incidência , Gravidez , Fatores SocioeconômicosRESUMO
BACKGROUND: Gastric cancer (GC) commonly relates to dismal prognosis and lacks efficient biomarkers. This study aimed to establish an antioxidant-related gene signature and a comprehensive nomogram to explore novel biomarkers and predict GC prognosis. METHODS: Clinical and expression data of GC patients were extracted from The Cancer Genome Atlas database. Univariate and multivariate Cox analyses were utilized to construct a score-based gene signature and survival analyses were conducted between high- and low-risk groups. Furthermore, we established a prognostic nomogram integrating clinical variables and antioxidant-related gene signature. Its predictive ability was validated by Harrell' concordance index and calibration curves and an independent internal cohort verified the consistency of the antioxidant gene signature-based nomogram. RESULTS: Four antioxidant-related genes (CHAC1, GGT5, GPX8, and PXDN) were significantly associated with overall survival of GC patients but only two genes, CHAC1 (HR = 0.803, P < 0.05) and GPX8 (HR = 1.358, P < 0.05), were confirmed as independent factors. A score-based signature was constructed and could act as an independent prognosis predictor (P < 0.05). Patients with lower scores showed significantly better prognosis (P < 0.05). Comprehensive nomogram combining the antioxidant-related gene signature and clinical parameters (age, gender, grade, and stage) was established and effectively predicted overall survival of GC patients [3-year survival AUC = 0.680, C index = 0.665 (95% CI 0.614-0.716)]. The independent internal validation cohort verified the reliability and good consistency of the model [3-year survival AUC = 0.703, C index = 0.706 (95% CI 0.612-0.800)]. CONCLUSIONS: Innovative antioxidant-related gene signature and nomogram performed well in assessing GC prognoses. This study enlightened further investigation of antioxidant system and provided novel tools for GC patient management.
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Neoplasias Gástricas , Antioxidantes , Humanos , Nomogramas , Peroxidases , Prognóstico , Reprodutibilidade dos Testes , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: The risk of lymph node positivity in early-stage colon cancer is a parameter that impacts therapeutic recommendations. However, little is known about the effect of age on lymph node positivity in colon cancer with mucosal invasion. In this study, we aimed to quantify the effect of younger age on lymph node positivity in colon cancer with mucosal invasion. METHODS: All patients were identified between 2004 and 2014 in the Surveillance, Epidemiology, and End Results database. Patients were stage T1-T2, did not undergo preoperative radiotherapy, had at least one lymph node examined, and underwent a standard colon cancer operation. Demographics and pathological data were compared between different age ranges. A nomogram model was built to estimate the probability of nodal involvement according to different characteristics. Decision curve analysis was performed by calculating the net benefits for a range of threshold probabilities. RESULTS: This study identified 41,490 patients who met the eligibility criteria for our study. 1.4% (n = 620) of patients were under 40 years old; 5.9% (n = 2571) were between 40 and 49 years old. Within each T stage, positive lymph node rates decreased with increasing age. In univariate analyses, the positive lymph node rates for patients 20 to 39 years of age were significantly higher than in patients in the reference group for stages T1 and T2. After dividing the colon into the left and right parts, these trends remained. The lymph node metastatic rate was higher in the right colon than in the left colon in terms of different age ranges. The nomogram prediction system represents a novel model with which to estimate lymph node metastasis in early T stage colon adenocarcinomas based on four risk factors with a C-index of 0.657 (95% CI: 0.658-0666). CONCLUSIONS: Our study demonstrates that the risk of lymph node metastasis was higher in young (< 40 years) patients with early-stage colon adenocarcinomas. Therefore, more aggressive screening and therapeutic strategies should be considered for young patients with colon adenocarcinoma.
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Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Linfonodos/patologia , Adenocarcinoma/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Colo/patologia , Neoplasias do Colo/cirurgia , Técnicas de Apoio para a Decisão , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nomogramas , Estudos Retrospectivos , Adulto JovemRESUMO
Spastic paraplegia 20 methylation was characterized in gastric cancer in our previous study. However, its mechanism remains unknown. Cell proliferation, colony formation, flow cytometry, wound healing, in vitro Transwell assays and in vivo xenografts were performed. A nomogram model was established to make a more accurate prognostic prediction for gastric cancer patients. Knockout of Spastic paraplegia 20 promoted gastric cancer cell proliferation, G2/M arrest in vitro and tumor growth in vivo. The EGFR/MAPK pathway was activated as a consequence of Spastic paraplegia 20 deletion. EGFR kinase or ERK1/2 inhibitors impaired Spastic paraplegia 20 knockout-induced cancer cell growth. Gastric cancer patients with poor spartin expression (72/161, 44.7%) exhibited a worse prognosis compared with the high expression group with median survival times of 16 and 54 months, respectively. The nomogram model stratified gastric cancer patients into 3 distinct prognostic groups with 3-year survival rates of 100%, 77%, and 35%. Furthermore, it had a better discrimination than the TNM staging system (C index: 0.785, AIC: 752.8708 VS. C index: 0.712; AIC: 775.1223). Methylation-induced Spastic paraplegia 20 silencing facilitates gastric cancer cell proliferation by activating the EGFR/MAPK signaling pathway. The nomogram based on spartin expression provided significantly better discrimination compared with the traditional AJCC TNM staging system and provided an individualized prediction of the survival for gastric cancer patient survival.
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Receptores ErbB/metabolismo , Inativação Gênica , Sistema de Sinalização das MAP Quinases , Proteínas/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Animais , Azacitidina/farmacologia , Sequência de Bases , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Masculino , Metilação , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Análise Multivariada , Nomogramas , Prognóstico , Neoplasias Gástricas/enzimologia , Análise de Sobrevida , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Fibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development. We hypothesize it's stable final product, plasma D-dimer, may be associated with CTCs appearance and can reflect the metastatic phenotype in cancer patients. METHODS: We first verified our hypothesis in different murine gastric cancer metastasis models in vivo, plasma D-dimer and fibrinogen as well as its degradation products were directly examined in three metastasis immune-deficient mouse models and in controls. Next, we gathered and analyzed the result of plasma D-dimer levels and CTCs numbers in 41 advanced primary gastric cancer (GC) patients. A follow-up study was conducted in these patients. RESULTS: In three in vivo murine metastasis models, plasma D-dimer levels were extremely elevated in a hematogenous and intraperitoneal murine model of metastasis compared with a subcutaneous tumor model and the control group, supporting our previous hypothesis. While in 41 GC patients, the result displayed that plasma D-dimer levels were remarkably increased in patients with distant metastases, especially in visceral metastases patients. Additionally, linear association was shown between D-dimer level and CTCs numbers (R 2 = 0.688, p < 0.001), additionally, plasma D-dimer represent a better survival predictor than CTCs. CONCLUSIONS: Plasma D-dimer is an essential accompaniment of CTCs in GC that is easy to measure and lower in cost, and can be used in the detection of hematogenous metastasis.
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Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Células Neoplásicas Circulantes/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Fibrinogênio/metabolismo , Seguimentos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica/patologiaRESUMO
BACKGROUND: The aim of this study is to develop a prognostic nomogram for patients with adenocarcinoma of esophagogastric junction and compare its predictive accuracy with the traditional tumor-node-metastasis (TNM) malignant staging system. METHODS: Patients from the Surveillance, Epidemiology, and End Results Program (from 1988 to 2011) and the First Affiliated Hospital of Xi'an Jiaotong University (from 2005 to 2010) were collected retrospectively. Preselected multiple potential interactions were tested irrespective of significance as nomogram parameters. And the Harrell's C-index was used to estimate the accuracy of the nomogram system. Model validation was performed using bootstrap to quantify our modeling strategy. RESULTS: In our study, six clinical associated factors (age, sex, depth of invasion, metastasized lymph nodes, examined lymph nodes, histological grade) were evaluated in the nomogram. In the training set, the nomogram exhibited superior discrimination power compared with the American Joint Committee on Cancer (AJCC) TNM classification (Harrell's C-index, 0.69 and 0.63, respectively). Calibration of the nomogram predicted survival was similar to the actual overall survival. In the validation set, the discrimination of nomogram was also better than the AJCC TNM staging system (C-index, 0.75 and 0.65, respectively), and the calibration of nomogram predicted survival was within a 10 % margin of actual overall survival. CONCLUSIONS: Based on the patients with adenocarcinoma of esophagogastric junction from a Western and an Eastern database, the nomogram provided significantly improved discrimination than the traditional AJCC TNM classification and also provided an accurate individualized prediction of the survival.
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Adenocarcinoma/mortalidade , Neoplasias Esofágicas/mortalidade , Junção Esofagogástrica/patologia , Nomogramas , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Adulto JovemRESUMO
Y2O3 dispersion-strengthened Molybdenum (Mo) composites were prepared by the mechanical alloying of Mo and Y powders then consolidation by spark plasma sintering. The effects of Chromium (Cr) addition (0 wt. %, 5 wt. %, 10 wt. % and 15 wt. %, respectively) on the mechanical performance and high-temperature oxidation resistance of Mo-Y2O3 were investigated. The introduction of Cr had a significant influence on the mechanical property and oxidation resistance of the Mo-Y2O3 composite. The highest bending strength reached 932 MPa when the addition of Cr content was 5 wt. % (Mo-5Cr-1Y sample). This improvement is likely attributable to the dual mechanism of grain refinement and solid solution strengthening. Moreover, the Mo-5Cr-1Y sample showed the thinnest oxide layer thickness after high-temperature oxidation tests, and exhibited the best oxidation resistance performance compared with the other samples. First principle calculation reveals that Cr could improve the Mo-MoO3 interface bonding to prevent rapid spalling of the oxide layer. Meanwhile, Cr also facilitates the formation of the dense Cr2(MoO4)3 layer on the surface, which can inhibit further oxidation.
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The evolution of the microstructure and the mechanical properties of a 15-6 martensite precipitated hardened (15-6 PH) stainless steel after thermal treatment and long-term aging at 480 °C were investigated. Compared with 17-4 PH steel, the content of Cr decreased and Ni increased in the newly developed 15-6 PH steel; therefore, reversed austenite formed after thermal treatment at 620 °C of the solution-treated 15-6 PH steel. Although the reversed austenite may reduce the strength of the steel, it is very beneficial for the inhibition of the aging brittleness of the steel. During the accelerated thermal aging at 480 °C, the Cu-rich phase gradually coarsened, and its crystal structure changed, while the reversed austenite phase sightly increased and the Charpy impact energy maintained a rather high value. The increase of the reversed austenite content can offset the reduction of the strengthening effect of the Cu-rich phase and therefore maintain an excellent impact property of the material after thermal aging.
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PURPOSE: To assess the efficacy of neoadjuvant endocrine therapy in female HR-positive/HER2-negative breast cancer patients. DATA AND METHODS: We identified female patients aged ≥18 years with cT1-4N0-XM0, HR(+), and HER2(-) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as "surgery-first," while those who received NET before surgery were classified as "NET." Propensity score-matching, Cox proportional-hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. RESULTS: Among 432,387 cases, 2914 NET patients and 2914 surgery-first patients were matched. Compared with the surgery-first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery-first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery-first vs. NET: HR 2.17, 95% CI: 1.93-2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(-), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05). CONCLUSION: NET may be a more effective treatment procedure than surgery-first in female HR-positive/HER2-negative, non-metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher-level evidence-based data.
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Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Receptor ErbB-2/metabolismo , Idoso , Adulto , Resultado do Tratamento , Antineoplásicos Hormonais/uso terapêutico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Mastectomia , Quimioterapia Adjuvante/métodosRESUMO
PURPOSES: To identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma-CpGs island methylator phenotype (G-CIMP) but have an unmethylated promoter of O-6-methylguanine-DNA methyltransferase (unMGMT). METHODS: The discovery-validation approach was planned incorporating a series of G-CIMP-/unMGMT GBM cohorts with DNA methylation microarray data and clinical information, to construct multi-CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration. RESULTS: By analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy-related CpGs, from which a 10-CpG risk signature was further constructed. Both the 64-CpG panel and the 10-CpG risk signature were validated showing significant correlations with overall survival of G-CIMP-/unMGMT GBMs when treated with RT/TMZ, rather than RT alone. The 10-CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on GPR81, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of MGMT expression. CONCLUSIONS: The 64 TMZ efficacy-related CpGs and in particular the 10-CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G-CIMP-/unMGMT GBMs.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Metilação de DNA , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Glioma/genética , Metilases de Modificação do DNA/genética , Fenótipo , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Proteínas Supressoras de Tumor/genética , Enzimas Reparadoras do DNA/genéticaRESUMO
Al2O3-forming austenitic steel (AFA steel) is an important candidate material for advanced reactor core components due to its excellent corrosion resistance and high temperature strength. Al is a strong ferrite-forming element. Therefore, it is necessary to increase the Ni content to stabilize austenite. Ni is expensive and highly active, and so increasing the Ni content not only increases the costs but also damages the radiation resistance. Mn is a low-cost austenitic stable element. Its substitution for Ni will not only help to improve the irradiation resistance of austenitic steel, but also reduce the cost. In order to explore the feasibility of Mn-substituted Ni-stabilized austenite in AFA steel, this paper summarized the research progress of Mn-added AFA steels, whilst the research status of traditional Mn-added austenitic steels are also referred to and compared herein. The effect of the addition of Mn on the microstructure and properties of AFA steel was analyzed. The results show that Mn can promote the precipitation of the M23C6 phase and inhibit the precipitation of the B2-NiAl phase and secondary NbC phase. With the increase in Mn content, the strength of AFA steel at room temperature and high temperature decreased slightly, the room temperature elongation increased slightly, while the high temperature elongation and creep resistance decreased obviously. In addition, for austenitic steel free of Al, the addition of Mn will destroy the oxide layer of Cr2O3, which will decrease the oxidation resistance of the steel. But the preliminary study shows that Mn has little effect on the Al2O3 oxide layer. It is worth studying the effect of Mn-substituted Ni on the oxidation resistance of AFA steel. In summary, more efforts are necessary to investigate the optimal Mn content to balance the advantages and disadvantages of introducing Mn instead of Ni.
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Fe/Al composite coatings with compositions of Fe-25 wt.% Al, Fe-50 wt.% Al and Fe-75 wt.% Al were deposited on pure Al and P91 steel plates by a cold spray, respectively. The microstructure of the cross-section of the fabricated coatings was characterized by SEM and EDX. The bonding strength between the coatings and substrates was measured and analyzed. The effects of the Fe/Al ratios and substrate hardness on the deposition behavior were investigated. It was interesting to find fragmented zones in all fabricated coatings, which were composed of large integrated Al particles and small fragmented Al particles. Meanwhile, the fraction of fragmented zones varied with the fraction of the actual Fe/Al ratio. An Fe/Al ratio of 50/50 appeared to be an optimized ratio for the higher bonding strength of coatings. The in situ hammer effect caused by larger and harder Fe particles played an important role in the cold spray process. The substrate with the higher hardness strengthened the in situ hammer effect and further improved the bonding strength.
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Fiber-reinforced silica aerogel blankets (FRABs) are an important high-temperature thermal insulation material for industry applications that have emerged in recent years. In order to better understand the performance evolution of FRABs at high temperatures, the effect of heat treatment at different temperatures on the performance of FRABs as well as their base material, hydrophobic silica aerogel powder and glass wool, was investigated. The property evolution of the hydrophobic silica aerogel powder showed two stages with an increase in thermal treatment temperatures. The skeleton structure of the aerogel remained unchanged, but the residual organic chemicals, such as hydrophobic groups, were decomposed when the heat treatment temperature was lower than 400 °C. Above 400 °C, the skeleton began to shrink with the increase in temperature, which led to an increase in thermal conductivity. The structure and room-temperature thermal conductivity of the glass wool blanket were less affected by a heat treatment temperature under 600 °C. Therefore, the performance degradation of FRABs at high temperatures is mainly due to the change in the aerogel powder. The insulation performance of the glass wool and FRAB at high temperatures was studied using a heating table which was designed to simulate working conditions. The energy savings of using FRABs instead of glass fiber were calculated and are discussed here.
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In order to meet the growing energy demand, more environmentally friendly and efficient GEN-IV reactors have emerged. Additionally, nuclear structural materials need larger more safety margins for accident scenarios as a result of the Fukushima accident. In order to extend the failure time and lessen the effect of accidents, this design method for accident-tolerant fuel materials calls for cladding materials to maintain good corrosion resistance and mechanical properties during a beyond design basis accident (BDBA). Accidents involving nuclear reactors would undoubtedly result in higher temperatures, which would make it much harder for materials to withstand corrosion. Oxide dispersion strengthened (ODS) FeCrAl alloys have shown promise as candidate materials because of their extraordinarily slow reaction rates under high-temperature steam. However, the addition of the Al element renders the alloy's high-temperature mechanical properties insufficient. In particular, studies on the alloy's creep properties are extremely rare, despite the fact that the creep properties are crucial in the real service environment. Therefore, this paper focuses on the creep properties of ODS FeCrAl alloy, summarizes and analyzes the research results of this material, and provides a reference for future research and applications.
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It is important to improve the liquid lead corrosion resistance of fuel cladding alloy for promoting the development of lead-based reactors. The corrosion behaviors of traditional T91 steel and similar oxide dispersion strengthen ODS-type steels with or without the addition of Al, and were examined and compared at 600 °C in static oxygen-controlled liquid Pb in this research. High-temperature liquid lead corrosion tests were carried out for 120 h, 240 h, 500 h, 1000 h, and 2000 h, respectively, for three prepared samples. After the experiment, the corrosion behavior was evaluated and compared mainly based on the aspects of appearance, corrosion depth, microstructure, and composition difference. It was found that just the ODS design did not show a positive effect on corrosion resistance, while the addition of Al is beneficial to improving the corrosion resistance of ODS steel. The maximum corrosion depth of 9CrAl ODS is only 51.8 µm after corrosion for 2000 h, which is much lower than that of 9Cr-ODS steel. A thin film containing Al/Cr formed in the corrosion area after adding Al in 9Cr ODS steel, which played a positive role in corrosion resistance.
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INTRODUCTION: Immediate postmastectomy reconstruction for breast cancer has been widely used due to its unique esthetic and psychological effects. However, no other population-based study has investigated the effects of different reconstruction types on the survival in patients with triple negative breast cancer (TNBC). METHODS: We selected patients who met the eligibility criteria from the Surveillance, Epidemiology, and End Results cancer registry (N = 9760). We then assessed the effect of different reconstructive surgical approaches (implant, autologous, implant and autologous combined reconstruction) on the overall survival (OS) and breast cancer-specific survival (BCSS) by using the Kaplan-Meier survival curve and Cox proportional hazard regression analyses. The nomograms were used to predict OS and BCSS. And the competitive risk model was used to assess breast cancer-specific death (BCSD) and non-breast cancer-specific death (NBCSD). RESULTS: Statistical analysis suggested that the three reconstruction methods had better OS and BCSS with lower hazard than mastectomy alone (log-rank test, p < 0.05). Multivariate stratified analysis showed that patients aged 40-60 years had the greatest improvement in OS (Adjusted hazard ratio [AHR], 0.646; 95% Confidence Interval [CI], 0.439-0.950; p = 0.026) with combined reconstruction. BCSS could be improved only by implant reconstruction (AHR, 0.672; 95% CI, 0.514-0.878; p = 0.004). In addition, autologous reconstruction (AHR, 0.570; 95% CI, 0.350-0.929; p = 0.024) and implant reconstruction (AHR, 0.538; 95% CI, 0.339-0.853; p = 0.008) improved OS in patients >60 years of age. The survival prediction model quantified the survival benefits of TNBC patients undergoing different surgeries. Moreover, the C-indexes showed the good predictive ability of the nomograms. CONCLUSIONS: Our results suggest that for TNBC patients, there is a survival benefit of immediate postmastectomy reconstruction compared with mastectomy alone. Among them, implant reconstruction has the most obvious advantage.
Assuntos
Neoplasias da Mama , Mamoplastia , Neoplasias de Mama Triplo Negativas , Humanos , Pessoa de Meia-Idade , Feminino , Mastectomia , Programa de SEER , Mama/cirurgiaRESUMO
Second primary breast cancer (SPBC) was potentially related to other cancers, which may impact its incidence, prognosis and therapeutic approaches. Nevertheless, few studies have characterized this relationship and analyzed the subtypes of SPBC. Our study intended to investigate the occurrence and prognosis of SPBC. We analyzed the patterns, clinical characteristics, standardized incidence ratio (SIR) and standardized mortality ratio (SMR) of patients with SPBC. The propensity score matching (PSM) approach was further used to balance the differences in clinical features between patients with primary breast cancer (PBC) and SPBC, then Kaplan-Meier (KM) survival analysis was used to compare their overall survival and breast cancer-specific survival. Finally, a predictive model was constructed to estimate the 3- and 5-year survival rates of SPBC patients. We found that the SIR of individuals with SPBC was significantly higher in cancer survivors than in the general population (SIR=1.16, 95% CI=1.15-1.17, P<0.05). SPBC patients with first primary lung/bronchus cancer had a much higher SMR (SMR=1.71, 95% CI=1.58-1.85, P<0.05) compared with survivors of other malignancies. Individuals with SPBC had a larger proportion of the HR-/HER2- subtype than those with PBC. Particularly among survivors of estrogen-dependent ovarian and breast cancer, the proportion of the HR-/HER2- subtype of SPBC considerably rose. After propensity score matching, we discovered that SPBC patients' overall survival remained poorer than that of PBC patients (HR=1.43, 95% CI=1.39-1.47, P<0.001). However, the prognosis of SPBC in first primary thyroid cancer survivors was better than PBC patients (HR=0.64, 95% CI=0.55-0.75, P<0.001). Also, an extreme gradient boosting (XGBoost) model was developed to evaluate the 3-year (AUC=0.817) and 5-year survival (AUC=0.825) of SPBC patients. Our data demonstrated the distinct biological performance of SPBC with various first primary cancers. Furthermore, our findings revealed an indispensable role of first primary cancer (FPC) in the development of SPBC and provided an additional theoretical basis for the clinical follow-up and identification of SPBC.