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Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.
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Background: Fatigue poses risks to occupational health and safety, affecting individuals' work efficiency, physical health, and social security, as well as human wellbeing and quality of life. Olfactory interventions, due to their low interference, are considered promising strategies for mitigating fatigue and reducing occupational health hazards. Objective: The objective of this review is to bridge the current gaps in the literature by conducting a scoping review of olfactory interventions on human alertness. It aims to explore their application in various occupational settings and to provide comprehensive and practical guidance for the practical application of olfactory interventions in mitigating fatigue and reducing occupational risks. Methods: The literature research was conducted in English using electronic databases such as Web of Science. Keywords related to scent and fatigue and the review followed PRISMA Extension for Scoping Reviews and PICO framework. Results: 28 studies were included in this work. Participant characteristics, fatigue measurement methods, and scent intervention methods, such as types of scents, intervention strategies, and scent presentation systems, are thoroughly investigated and discussed. Additionally, the study places a specific emphasis on the applications and research within the field of scent interventions for fatigue driving. Olfactory interventions have been applied to populations in various occupational fields, demonstrating beneficial effects on both physiological and psychological fatigue. Conclusions: Olfactory intervention is effective and promising for enhancing alertness and improving the occupational environment. To provide detailed and practical guidance for the actual application of olfactory intervention in fatigue relief and reducing occupational health and safety hazards, further research into the potential mechanisms, applications, and efficacy assessment systems of fatigue-related olfactory interventions is necessary.
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Fatiga , Salud Laboral , Humanos , Fatiga/prevención & control , Calidad de Vida , OdorantesRESUMEN
Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitinâproteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.
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Fatigued driving threatens the safety of people's lives and property. Scent countermeasures offer minimal disruption and high efficacy, making them a promising approach. The aim of this study was to explore the application of scent countermeasures in alleviating fatigued driving. This study explored changes in EEG frequency bands (alpha, beta, theta, and gamma) and the activity of EEG metrics (R(α/ß), Rθ/(α+ß) and R(α+θ)/(α+ß)) in the temporal lobe during driving tasks, selected fatigued driving identifiers, and aided validation by investigating subjective fatigue with the Karolinska Sleepiness Scale (KSS). The EEG indicators all increased, with a significant increase in R(α/ß). R(α/ß) was combined with the KSS to explore the effects of three scents, peppermint, grapefruit, and lavender, on driving fatigue. The subjective questionnaire results indicated that all three scents significantly improved driving fatigue, with significantly lower levels of driving fatigue compared to the control group. The analysis of EEG signals revealed a significant decrease in R(α/ß) after the implementation of scent countermeasures. Moreover, R(α/ß) was found to be lower in all three odor intervention groups compared to the control group. All three scents were found to significantly alleviate driving fatigue. The grapefruit scent had a better timely effect in relieving driving fatigue and the lavender scent had a longer effectiveness. This study provides further exploration for the application of odor interventions to alleviate driving fatigue. This study provides a practical reference for drivers to use odors to avoid fatigue in order to improve road safety.
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Conducción de Automóvil , Electroencefalografía , Fatiga , Odorantes , Humanos , Fatiga/prevención & control , Fatiga/fisiopatología , Masculino , Odorantes/análisis , Adulto , Femenino , Adulto JovenRESUMEN
Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.
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Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , Docetaxel/uso terapéutico , Neoplasias Nasofaríngeas/patología , Factores de Transcripción/uso terapéutico , Resistencia a Antineoplásicos , Fluorouracilo/uso terapéutico , Quimioradioterapia/métodos , Cisplatino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ubiquitina TiolesterasaRESUMEN
In light of the adverse environmental impact of the R134a refrigerant, replacing it with a more environmentally friendly refrigerant has become imperative than ever. This study presents an experimental investigation into the utilization of R152a and R134a refrigerants in a vapor compression refrigeration system employing a variable displacement oil-free linear compressor. The potential for the replacement of R134a with R152a was examined based on energy, environmental, and economic performance analyses. The outcomes indicated that R152a exhibited a higher coefficient of performance (COP) in comparison to R134a under identical operating conditions. Specifically, when the pressure ratio was 2.0 and the piston stroke was 11 mm, R152a's COP was 13.0% higher than R134a. It was also discovered that reducing the operating stroke and increasing the pressure ratio could effectively lower CO2 emissions and total costs. Under the 2.0 pressure ratio and 9-mm piston stroke, R134a produced 1082.4 kg more CO2 emissions than R152a, representing a 209% increase. In addition, the R152a and R134a total cost was reduced by 8.3% with the 2.5 pressure ratio and 11-mm piston stroke. Notably, the results of the current study demonstrated that R152a outperformed R134a in energy consumption, environmental friendliness, and economy in oil-free linear compressor refrigeration systems. R152a used less electric power, generated fewer CO2 emissions, and naturally reduced predicted running costs in order to maintain the same COP.
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BACKGROUND: To summarize the impact of radiotherapy (RT) and chemotherapy delays on patients with nasopharyngeal carcinoma (NPC) during the COVID-19 pandemic. METHODS: We retrospectively included 233 patients with stage II-IVa NPC treated with RT and chemotherapy between December 11, 2019 and March 11, 2020. The outcomes were elevation in the EBV DNA load between two adjacent cycles of chemotherapy or during RT, and 1-year disease-free survival (DFS). RESULTS: RT delay occurred in 117 (50%) patients, and chemotherapy delay occurred in 220 (94%) patients. RT delay of ≥ 6 days was associated with a higher EBV DNA elevation rate (20.4% vs. 3.6%, odds ratio [OR] = 6.93 [95% CI = 2.49-19.32], P < 0.001), and worse 1-year DFS (91.2% vs. 97.8%, HR = 3.61 [95% CI = 1.37-9.50], P = 0.006), compared with on-schedule RT or delay of < 6 days. Chemotherapy delay of ≥ 10 days was not associated with a higher EBV DNA elevation rate (12.5% vs. 6.8%, OR = 1.94 [95% CI = 0.70-5.40], P = 0.20), or worse 1-year DFS (93.8% vs. 97.1%, HR = 3.73 [95% CI = 0.86-16.14], P = 0.059), compared with delay of < 10 days. Multivariable analyses showed RT delay of ≥ 6 days remained an independent adverse factor for both EBV DNA elevation and DFS. CONCLUSION: To ensure treatment efficacy for patients with nonmetastatic NPC, initiation of RT should not be delayed by more than 6 days; the effect of chemotherapy delay requires further investigation.
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OBJECTIVES: To develop and validate a joint model for dynamic prediction of overall survival (OS) in nasopharyngeal carcinoma (NPC) based on longitudinal post-treatment plasma cell-free Epstein-Barr virus (cfEBV) DNA load. PATIENTS AND METHODS: We analyzed 695 patients with non-metastatic NPC and detectable post-treatment cfEBV DNA load who did not receive adjuvant therapy. We fitted the trajectories of post-treatment cfEBV DNA load as a function of time into a linear mixed-effect model and fitted a Cox regression model with covariates including age, T and N stages, and lactate dehydrogenase level. Finally, we combined both via joint modeling to develop and validate our dynamic model. RESULTS: A strong positive correlation was found between the individual longitudinal post-treatment cfEBV DNA load and the risk of death from any cause (P < 0.001). We developed a joint model capable of providing subject-specific dynamic prediction of conditional OS based on the evolution of the individual plasma cfEBV DNA load trajectory. The joint model showed reliable performance in both training and validation cohorts, with a large area under the curve (interquartile range [IQR]: training cohort, 0.775-0.850; validation cohort, 0.826-0.900) and low prediction errors (IQR: training cohort, 0.017-0.078; validation cohort, 0.034 -0.071). An increasing amount of data on cfEBV DNA load was associated with better model performance. CONCLUSION: Our model provided reliable subject-specific dynamic prediction of conditional OS, which could help guide individualized post-treatment surveillance, risk stratification, and management of NPC in the future.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , ADN Viral/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , Humanos , Lactato Deshidrogenasas , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , PronósticoRESUMEN
Chemoresistance is the leading cause of poor prognosis in head and neck squamous cell carcinoma (HNSC); however, promising biomarkers to identify patients for stratified chemotherapy are lacking. Sideroflexin 3 (SFXN3) is an important mitochondrial serine transporter during one-carbon metabolism, which is involved in the proliferation of cancer cells. However, the specific role of SFXN3 in HNSC remains unknown. In this study, we performed expression and survival analysis for SFXN3 in pan-cancer using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) and found that SFXN3 served as a potential oncogene in HNSC. Notably, SFXN3 expression was found to be positively associated with enriched tumor-infiltrating macrophages, other immune suppressive cells, and immune checkpoint expression and resistance to paclitaxel. Gene, clinical, and immune variables included in the univariate and multivariate analyses showed that SFXN3 expression was an independent risk factor. Moreover, the LINC01270/hsa-miR-29c-3p/SFXN3 axis was identified as the most likely upstream non-coding RNA-related pathway of SFXN3 in HNSC using bioinformatic analysis, expression analysis, correlation analysis, and survival analysis. Taken together, our findings demonstrated that a non-coding RNA-mediated high expression of SFXN3 is a prognostic biomarker and is associated with the immunosuppressive microenvironment in HNSC.
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Neoplasias de Cabeza y Cuello , MicroARNs , Carbono , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Humanos , Proteínas de la Membrana , MicroARNs/genética , Paclitaxel/uso terapéutico , Pronóstico , ARN no Traducido , Serina , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Microambiente Tumoral/genéticaRESUMEN
Photoperiod and thermo-sensitive genic male sterile (PTGMS) rice is an important resource for two line hybrid rice production. The SQUAMOSA-promoter binding, such as the (SPL) gene family, encode the plant specific transcription factors that regulate development and defense responses in plants. However, the reports about SPLs participating in male fertility regulation are limited. Here, we identified 19 OsSPL family members and investigated their involvement in the fertility regulation of the PTGMS rice lines, PA2364S and PA2864S, with different fertility transition temperatures. The results demonstrated that OsSPL2, OsSPL4, OsSPL16 and OsSPL17 affect male fertility in response to temperature changes through the MiR156-SPL module. WGCNA (weighted gene co-expression network analysis) revealed that CHI and APX1 were co-expressed with OsSPL17. Targeted metabolite and flavonoid biosynthetic gene expression analysis revealed that OsSPL17 regulates the expression of flavonoid biosynthesis genes CHI, and the up regulation of flavanones (eriodictvol and naringenin) and flavones (apigenin and luteolin) content contributed to plant fertility. Meanwhile, OsSPL17 negatively regulates APX1 to affect APX (ascorbate peroxidase) activity, thereby regulating ROS (reactive oxygen species) content in the tapetum, controlling the PCD (programmed cell death) process and regulating male fertility in rice. Overall, this report highlights the potential role of OsSPL for the regulation of male fertility in rice and provides a new insight for the further understanding of fertility molecular mechanisms in PTGMS rice.
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Oryza , Fertilidad/genética , Flavonoides/metabolismo , Regulación de la Expresión Génica de las Plantas , Oryza/metabolismo , Fotoperiodo , TemperaturaRESUMEN
Background: Inhibitory checkpoints are promising antitumor targets and predictive biomarkers in a variety of cancers. We aimed to identify the expression levels and prognostic value of multiple inhibitory checkpoints supported by preclinical and clinical evidence in head and neck lymphoepithelioma-like carcinoma (HNLELC). Methods: The expression of seven inhibitory checkpoints were evaluated in the tumor nest (TN) and tumor stroma (TS) of 102 HNLELC specimens using immunohistochemistry and digital pathology, and an inhibitory checkpoint-based signature (ICS) was subsequently constructed using the LASSO Cox regression model. Results: PD-L1, B7H3, and IDO-1 were mostly expressed in the TN, with median H-score of TN vs TS: 63.6 vs 14.6; 8.1 vs 1.0; 61.5 vs 34.7 (all P < 0.001), whereas PD-1, TIM-3, LAG-3, and VISTA were mainly observed in the TS, with median H-score of TN vs TS: 0.2 vs 12.4, 3.4 vs 7.1, 6.2 vs 11.9, 16.4 vs 47.2 (all P < 0.001), respectively. The most common simultaneously expressed combinations consisted of PD-L1 + B7H3 + IDO-1 + TIM-3 + LAG-3 + VISTA and B7H3 + IDO-1 + TIM-3 + LAG-3 in the TN (both occurring in 8.8% of patients) and PD-L1 + B7H3 + IDO-1 in the TS (4.9%). In addition, high-ICS patients had shorter 5-year disease-free (40.6% vs 81.7%; P < 0.001), regional recurrence-free (63.5% vs 88.2%; P = 0.003), and overall survival (73.5% vs 92.9%; P = 0.006) than low-ICS patients. Multivariate analysis revealed that ICS represented an independent predictor, which could significantly complement the predictive performance of TNM stage for 3-year (AUC 0.724 vs 0.619, P = 0.014), 5-year (AUC 0.727 vs 0.640, P = 0.056), and 10-year disease-free survival (AUC 0.815 vs 0.709, P = 0.023). Conclusions: The expression of inhibitory checkpoints and ICS classifier may increase the prognostic value of the TNM staging system and guide the rational design of personalized inhibitory checkpoint blockade therapy in HNLELC.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Antígenos B7/metabolismo , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/mortalidad , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
Radiotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC), and approximately 20% of patients experience treatment failure due to tumour radioresistance. However, the exact regulatory mechanism remains poorly understood. Here, we show that the deubiquitinase USP44 is hypermethylated in NPC, which results in its downregulation. USP44 enhances the sensitivity of NPC cells to radiotherapy in vitro and in vivo. USP44 recruits and stabilizes the E3 ubiquitin ligase TRIM25 by removing its K48-linked polyubiquitin chains at Lys439, which further facilitates the degradation of Ku80 and inhibits its recruitment to DNA double-strand breaks (DSBs), thus enhancing DNA damage and inhibiting DNA repair via non-homologous end joining (NHEJ). Knockout of TRIM25 reverses the radiotherapy sensitization effect of USP44. Clinically, low expression of USP44 indicates a poor prognosis and facilitates tumour relapse in NPC patients. This study suggests the USP44-TRIM25-Ku80 axis provides potential therapeutic targets for NPC patients.
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Carcinogénesis/genética , Roturas del ADN de Doble Cadena/efectos de la radiación , Reparación del ADN/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Ubiquitina Tiolesterasa/genética , Apoptosis/genética , Apoptosis/efectos de la radiación , Carcinogénesis/metabolismo , Línea Celular , Línea Celular Tumoral , Metilación de ADN , Puntos de Control de la Fase G2 del Ciclo Celular/genética , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de la radiación , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Autoantígeno Ku/genética , Autoantígeno Ku/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Regiones Promotoras Genéticas/genética , Tolerancia a Radiación/genética , Análisis de Supervivencia , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
BACKGROUND: Induction chemotherapy (ICT) plus concurrent chemoradiotherapy (CCRT) and CCRT alone were the optional treatment regimens in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. Currently, the choice of them remains equivocal in clinical practice. We aimed to develop a deep learning-based model for treatment decision in NPC. METHODS: A total of 1872 patients with stage T3N1M0 NPC were enrolled from four Chinese centres and received either ICT+CCRT or CCRT. A nomogram was constructed for predicting the prognosis of patients with different treatment regimens using multi-task deep learning radiomics and pre-treatment MR images, based on which an optimal treatment regimen was recommended. Model performance was assessed by the concordance index (C-index) and the Kaplan-Meier estimator. FINDINGS: The nomogram showed excellent prognostic ability for disease-free survival in both the CCRT (C-index range: 0.888-0.921) and ICT+CCRT (C-index range: 0.784-0.830) groups. According to the prognostic difference between treatments using the nomogram, patients were divided into the ICT-preferred and CCRT-preferred groups. In the ICT-preferred group, patients receiving ICT+CCRT exhibited prolonged survival over those receiving CCRT in the internal and external test cohorts (hazard ratio [HR]: 0.17, p<0.001 and 0.24, p=0.02); while the trend was opposite in the CCRT-preferred group (HR: 6.24, p<0.001 and 12.08, p<0.001). Similar results for treatment decision using the nomogram were obtained in different subgroups stratified by clinical factors and MR acquisition parameters. INTERPRETATION: Our nomogram could predict the prognosis of T3N1M0 NPC patients with different treatment regimens and accordingly recommend an optimal treatment regimen, which may serve as a potential tool for promoting personalized treatment of NPC. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, Beijing Natural Science Foundation, Strategic Priority Research Program of CAS, Project of High-Level Talents Team Introduction in Zhuhai City, Beijing Natural Science Foundation, Beijing Nova Program, Youth Innovation Promotion Association CAS.
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Aprendizaje Profundo , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Nomogramas , Planificación de la Radioterapia Asistida por Computador/métodos , Adolescente , Adulto , Anciano , Toma de Decisiones Clínicas/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/radioterapiaRESUMEN
This cross-sectional and longitudinal descriptive analysis aimed to track the evolving landscape of global immuno-oncology (IO) trials and provide insight into the resolution of IO-related controversies. Clinical trials (n = 4510) registered on ClinicalTrials.gov in 2007 to 2019 studying immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), cancer vaccines and immune modulators were included. Most of IO trials are Phase 2 and focus on ICIs and multiple IO therapies. The United States leads global IO research, with stable growth and the best methodological quality. Mainland China ranks first in the number of ACT trials but has the lowest article publication rate (6.2%). A multiple-arm comparative design is often adopted in multiple IO therapies trials (44.0%). Trials studying ICIs and multiple IO therapies are likely to use early registration (80.0% and 86.6%) and stringent corticosteroid-/infection-related criteria. Hospitals have provided the most extensive and strongest support for all IO categories. Big pharma prefers to fund Phase 3-4 ICI trials (6.98%), while small pharma has a wider sponsorship favoring Phase 1-2 trials. The "partial-use-of-corticosteroids" strategy is generally well accepted in ICI trials with a definitive trend (32.5%; P < .001) but is associated with the poor dissemination of results (P ≤ .020), while the complete disclosure and standardization of dose/timing limits are still lacking. Disparities in design features and dissemination of results are widespread in IO trials and are modulated by IO category, cancer type and sponsor. We propose policy reforms to redefine the timely publication of IO trials and standardize the resolution of corticosteroid-/infection-related issues.
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Actitud del Personal de Salud , Ensayos Clínicos como Asunto/normas , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/tendencias , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Pautas de la Práctica en Medicina/normas , Academias e Institutos , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Estudios Longitudinales , PronósticoRESUMEN
OBJECTIVE: This study focused on developing an effective nomogram for improving prognostication for patients with primary nasopharyngeal carcinoma (NPC) restaged according to the eighth edition of the AJCC/UICC TNM staging system. METHODS: Based on data of 5,903 patients with non-metastatic NPC (primary cohort), we used Cox regression analysis to identify survival risk factors and created a nomogram. We used the nomogram to predict overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the primary and independent validation (3,437 patients) cohorts. Moreover, we compared the prognostic accuracy between the 8th TNM system and the nomogram. RESULTS: The nomogram included gender, age, T stage, N stage, Epstein-Barr virus DNA, hemoglobin, C-reactive protein, lactate dehydrogenase, and radiotherapy with/without induction or concurrent chemotherapy. In the prediction of OS, DMFS and DFS, the nomogram had significantly higher concordance index (C-index) and area under ROC curve (AUC) than the TNM system alone. Calibration curves demonstrated satisfactory agreements between nomogram-predicted and observed survival. The stratification in different groups permitted remarkable differentiation among Kaplan-Meier curves for OS, DMFS, and DFS. CONCLUSION: The nomogram led to a more precise prognostic prediction for NPC patients in comparison with the 8th TNM system. Therefore, it could facilitate individualized and personalized patients' counseling and care.
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PURPOSE: To estimate the prognostic value of deep learning (DL) magnetic resonance (MR)-based radiomics for stage T3N1M0 nasopharyngeal carcinoma (NPC) patients receiving induction chemotherapy (ICT) prior to concurrent chemoradiotherapy (CCRT). METHODS: A total of 638 stage T3N1M0 NPC patients (training cohort: n = 447; test cohort: n = 191) were enrolled and underwent MRI scans before receiving ICT + CCRT. From the pretreatment MR images, DL-based radiomic signatures were developed to predict disease-free survival (DFS) in an end-to-end way. Incorporating independent clinical prognostic parameters and radiomic signatures, a radiomic nomogram was built through multivariable Cox proportional hazards method. The discriminative performance of the radiomic nomogram was assessed using the concordance index (C-index) and the Kaplan-Meier estimator. RESULTS: Three DL-based radiomic signatures were significantly correlated with DFS in the training (C-index: 0.695-0.731, all p < 0.001) and test (C-index: 0.706-0.755, all p < 0.001) cohorts. Integrating radiomic signatures with clinical factors significantly improved the predictive value compared to the clinical model in the training (C-index: 0.771 vs. 0.640, p < 0.001) and test (C-index: 0.788 vs. 0.625, p = 0.001) cohorts. Furthermore, risk stratification using the radiomic nomogram demonstrated that the high-risk group exhibited short-lived DFS compared to the low-risk group in the training cohort (hazard ratio [HR]: 6.12, p < 0.001), which was validated in the test cohort (HR: 6.90, p < 0.001). CONCLUSIONS: Our DL-based radiomic nomogram may serve as a noninvasive and useful tool for pretreatment prognostic prediction and risk stratification in stage T3N1M0 NPC.
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Aprendizaje Profundo , Neoplasias Nasofaríngeas , Humanos , Espectroscopía de Resonancia Magnética , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/radioterapia , Nomogramas , PronósticoRESUMEN
In the present study, Bipolaris maydis was used to synthesise silver nanoparticles (AgNPs). Several parameters that influence the synthesis of AgNPs such as fungus age, the concentration of Ag nitrate (AgNO3), and incubation time were explored to find the optimum synthesis condition. Furthermore, the antifungal activity of AgNPs against Exserohilum turcicum was determined by measuring inhibition zone diameter, colony formation, and conidia germination. The optimal biosynthesis system included fungus age of 7 days, 8â mM AgNO3, and an incubation time of 120â h. Under these conditions, synthesised NPs were near round, and the average particle size was about 21â nm. At the experiment, the diameter of the inhibition zone reached a maximum of 8â mM AgNO3 and 72â h. In addition, the inhibition rate of colony and conidia reached 83.39 and 100%, respectively, with 200â µg/ml AgNPs. The results offer a novel pathway for phytopathogen control and make it likely to develop new eco-friendly antimicrobial.
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Antifúngicos/metabolismo , Ascomicetos/efectos de los fármacos , Ascomicetos/metabolismo , Nanopartículas del Metal/química , Plata/química , Antifúngicos/química , Antifúngicos/farmacología , Ascomicetos/química , Pruebas de Sensibilidad MicrobianaRESUMEN
Employing a structure-based strategy, we have designed a new class of potent small-molecule inhibitors of the anti-apoptotic proteins Bcl-2 and Bcl-xL. An initial lead compound with a new scaffold was designed based upon the crystal structure of Bcl-xL and U.S. Food and Drug Administration (FDA) approved drugs and was found to have an affinity of 100 µM for both Bcl-2 and Bcl-xL. Linking this weak lead to another weak-affinity fragment derived from Abbott's ABT-737 led to an improvement of the binding affinity by a factor of >10 000. Further optimization ultimately yielded compounds with subnanomolar binding affinities for both Bcl-2 and Bcl-xL and potent cellular activity. The best compound (21) binds to Bcl-xL and Bcl-2 with K(i) < 1 nM, inhibits cell growth in the H146 and H1417 small-cell lung cancer cell lines with IC(50) values of 60-90 nM, and induces robust cell death in the H146 cancer cell line at 30-100 nM.
Asunto(s)
Antineoplásicos/síntesis química , Piperazinas/síntesis química , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Sulfonamidas/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Polarización de Fluorescencia , Humanos , Modelos Moleculares , Estructura Molecular , Piperazinas/química , Piperazinas/farmacología , Unión Proteica , Estereoisomerismo , Relación Estructura-Actividad , Sulfonamidas/química , Sulfonamidas/farmacología , Proteína bcl-X/antagonistas & inhibidoresRESUMEN
AKT is a promising target for anticancer drug development. In this work, a bioinformatics approach was applied to search for AKT inhibitors based on the correlation analysis between phospho-Ser473 AKT expression level and the antiproliferative data of NCI small molecule compounds against NCI 60 cancer cell lines, the candidate compounds were then subject to AKT kinase assay. The possible effects of potent compound on PI3K/AKT, PDK1, and MAPK, its antiproliferative and apoptosis-inducing effects on breast cancer cells which have high-levels of AKT activation were assessed by Western blot analysis, cell viability assay, and apoptosis assay. One compound, CMEP (NSC632855, 9-chloro-2-methylellipticinium acetate) was identified with all three correlation algorithm, Pearson's, Sperman's, and Kendall's, showing a high-ranked correlation coefficient. CMEP inhibits only AKT, but does not inhibit PI3K, PDK1, or MAPK. CMEP also inhibits heregulin-induced AKT activation, does not inhibit heregulin-induced MAPK activation in MCF-7 breast cancer cells. Increased concentrations of ATP reverse the AKT inhibitory effect of CMEP. CMEP inhibits growth and induces apoptosis in breast cancer cells which have high-levels of AKT activation and lack functional PTEN; however, CMEP only shows a minimal activity in NIH3T3 cells which do not have AKT activation. In conclusion, a lead compound CMEP, as an AKT selective inhibitor has been identified started with a bioinformatics-based approach. CMEP inhibits growth and induces apoptosis in cancer cells which have high-levels of AKT activation and lack PTEN or harbor PTEN mutation.