RESUMO
PURPOSE: The interplay between sleep quality, anxiety, and depression among breast cancer patients remains poorly understood. This study aimed to investigate and compare the symptoms relationships among these three factors in Chinese breast cancer patients, utilizing two sleep assessments. METHODS: Our study encompassed 288 participants diagnosed with breast cancer, from whom we collected demographic information through questionnaires. Sleep quality symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist actigraphy, while anxiety and depression symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). Network analyses were conducted using R to calculate the centrality (strength) and further identify central symptoms and bridge symptoms in two networks that differed by sleep assessments. Central symptoms are closely related to other symptoms, whereas bridge symptoms indicate that symptoms may increase spread risk between different conditions. RESULTS: In the network using PSQI data, "I have lost interest in my appearance" had the highest strength centrality (rs = 2.417), followed by "sleep duration" (rs = 1.068) and "sleep efficiency" (rs = 0.955). In the network using wrist actigraphy data, "wake after sleep onset" had the highest strength value (rs = 2.437), followed by "sleep efficiency" (rs = 2.397) and "sleep latency" (rs = 1.506). Two bridge symptoms were identified: "I feel cheerful" and "I look forward with enjoyment to things" in both networks. CONCLUSIONS: Depressive symptoms played a leading role in the sleep-anxiety-depression network, underscoring the need for targeted intervention tailored to survivors' specific needs. IMPLICATIONS FOR CANCER SURVIVORS: Health workers can give priority to symptom-specific screening and therapies, incorporating psychological support into standard cancer care.
RESUMO
PURPOSE: Osteosarcoma, a highly malignant primary bone tumor primarily affecting adolescents, frequently develops resistance to initial chemotherapy, leading to metastasis and limited treatment options. Our study aims to uncover novel therapeutic targets for metastatic and recurrent osteosarcoma. METHODS: In this study, we proved the potential of modulating the YAP1-regulated glutamine metabolic pathway to augment the response of OS to DFMO. We initially employed single-cell transcriptomic data to gauge the activation level of polyamine metabolism in MTAP-deleted OS patients. This was further substantiated by transcriptome sequencing data from recurrent and non-recurrent patient tissues, confirming the activation of polyamine metabolism in progressive OS. Through high-throughput drug screening, we pinpointed CIL56, a YAP1 inhibitor, as a promising candidate for a combined therapeutic strategy with DFMO. In vivo, we utilized PDX and CDX models to validate the therapeutic efficacy of this drug combination. In vitro, we conducted western blot analysis, qPCR analysis, immunofluorescence staining, and PuMA experiments to monitor alterations in molecular expression, distribution, and tumor metastasis capability. We employed CCK-8 and colony formation assays to assess the proliferative capacity of cells in the experimental group. We used flow cytometry and reactive oxygen probes to observe changes in ROS and glutamine metabolism within the cells. Finally, we applied RNA-seq in tandem with metabolomics to identify metabolic alterations in OS cells treated with a DFMO and CIL56 combination. This enabled us to intervene and validate the role of the YAP1-mediated glutamine metabolic pathway in DFMO resistance. RESULTS: Through single-cell RNA-seq data analysis, we pinpointed a subset of late-stage OS cells with significantly upregulated polyamine metabolism. This upregulation was further substantiated by transcriptomic profiling of recurrent and non-recurrent OS tissues. High-throughput drug screening revealed a promising combination strategy involving DFMO and CIL56. DFMO treatment curbs the phosphorylation of YAP1 protein in OS cells, promoting nuclear entry and initiating the YAP1-mediated glutamine metabolic pathway. This reduces intracellular ROS levels, countering DFMO's anticancer effect. The therapeutic efficacy of DFMO can be amplified both in vivo and in vitro by combining it with the YAP1 inhibitor CIL56 or the glutaminase inhibitor CB-839. This underscores the significant potential of targeting the YAP1-mediated glutamine metabolic pathway to enhance efficacy of DFMO. CONCLUSION: Our findings elucidate YAP1-mediated glutamine metabolism as a crucial bypass mechanism against DFMO, following the inhibition of polyamine metabolism. Our study provides valuable insights into the potential role of DFMO in an "One-two Punch" therapy of metastatic and recurrent osteosarcoma.
RESUMO
Background: Physical activity can alleviate negative emotions in college students by enhancing mood and cognitive functions. Yet, the mechanisms underlying these benefits remain unclear. Purpose: This study examines the association between physical activity and negative emotions-specifically, depression, anxiety, and stress-in college students. Additionally, we explore the mediating effects of psychological resilience and coping styles to offer theoretical and practical insights for mitigating students' negative emotions. Methods: Using a stratified random sampling approach, a total of 1,380 college students, from five universities in Hangzhou, Nanjing, and Wenzhou, were included in the analysis. The survey instruments included the Physical Activity Rating Scale, Connor-Davidson Resilience Scale, Simple Coping Style Scale, and Depression-Anxiety Stress Scale. The data were statistically analyzed using multivariate methods with IBM SPSS 25.0 and the PROCESS V3.3 plug-in. Results: (1) College students engage in a low level of physical activity, with male students participating significantly more than female students (p < 0.001). (2) Physical activity was significantly positively correlated with psychological resilience and positive coping styles (t = 9.126, p < 0.001; t = 23.087, p < 0.001) and overall negative correlated with negative emotions in college students (t = -3.601, p < 0.001). (3) Psychological resilience and positive coping styles were found to play a chain mediating role between physical activity and negative emotions. The mediation effect consists of two paths: physical activity â psychological resilience â negative emotions (effect value: -0.0324), and physical activity â psychological resilience â positive coping â negative emotions (effect value: -0.0099). (4) Female students demonstrated higher levels of positive coping (p < 0.001), while male students exhibited more negative emotions (p < 0.001). Conclusion: Our study identifies a significant indirect link, mediated by psychological resilience and positive coping styles, between physical activity and the reduction of negative emotions. Targeted interventions addressing gender differences, such as offering special courses and providing specialized exercise programs and emotional management strategies, can enhance psychological resilience and positive coping mechanisms. Consequently, these measures can alleviate the adverse effects of negative emotions. Our findings have broader implications for both research and practical interventions in promoting mental health among college students.
RESUMO
Osteosarcoma (OS) is a "cold" tumor enriched in noninflammatory M2 phenotype tumor-associated macrophages (TAMs), which limits the efficacy of immunotherapy. The acidic tumor microenvironment (TME), generated by factors such as excess hydrogen (H+) ions and high lactate levels, activates immunosuppressive cells, further promoting a suppressive tumor immune microenvironment (TIME). Therefore, a multitarget synergistic combination strategy that neutralizes the acidic TME and reprograms TAMs can be beneficial for OS therapy. Here, a calcium carbonate (CaCO3)/polydopamine (PDA)-based nanosystem (A-NPs@(SHK+Ce6)) is developed. CaCO3 nanoparticles are used to neutralize H+ ions and alleviate the suppressive TIME, and the loaded SHK not only synergizes with photodynamic therapy (PDT) but also inhibits lactate production, further reversing the acidic TME and repolarizing TAMs to consequently lead to enhanced PDT-induced tumor suppression and comprehensive beneficial effects on antitumor immune responses. Importantly, A-NPs@(SHK+Ce6), in combination with programmed cell death protein 1 (PD-1) checkpoint blockade, shows a remarkable ability to eliminate distant tumors and promote long-term immune memory function to protect against rechallenged tumors. This work presents a novel multiple-component combination strategy that coregulates the acidic TME and TAM polarization to reprogram the TIME.
RESUMO
The advancements in the field of micro-robots for drug delivery systems have garnered considerable attention. In contrast to traditional drug delivery systems, which are dependent on blood circulation to reach their target, these engineered micro/nano robots possess the unique ability to navigate autonomously, thereby enabling the delivery of drugs to otherwise inaccessible regions. Precise drug delivery systems can improve the effectiveness and safety of synthetic lethality strategies, which are used for targeted therapy of solid tumors. MYC-overexpressing tumors show sensitivity to CDK1 inhibition. This study delves into the potential of Ro-3306 loaded magnetic-driven hydrogel micro-robots in the treatment of MYC-dependent osteosarcoma. Ro-3306, a specific inhibitor of CDK1, has been demonstrated to suppress tumor growth across various types of cancer. We have designed and fabricated this micro-robot, capable of delivering Ro-3306 precisely to tumor cells under the influence of a magnetic field, and evaluated its chemosensitizing effects, thereby augmenting the therapeutic efficacy and introducing a novel possibility for osteosarcoma treatment. The clinical translation of this method necessitates further investigation and validation. In summary, the Ro-3306-loaded magnetic-driven hydrogel micro-robots present a novel strategy for enhancing the chemosensitivity of MYC-dependent osteosarcoma, paving the way for new possibilities in future clinical applications.
RESUMO
Alternative splicing (AS) serves as a pivotal mechanism in transcriptional regulation, engendering transcript diversity, and modifications in protein structure and functionality. Across varying tissues, developmental stages, or under specific conditions, AS gives rise to distinct splice isoforms. This implies that these isoforms possess unique temporal and spatial roles, thereby associating AS with standard biological activities and diseases. Among these, AS-related RNA-binding proteins (RBPs) play an instrumental role in regulating alternative splicing events. Under physiological conditions, the diversity of proteins mediated by AS influences the structure, function, interaction, and localization of proteins, thereby participating in the differentiation and development of an array of tissues and organs. Under pathological conditions, alterations in AS are linked with various diseases, particularly cancer. These changes can lead to modifications in gene splicing patterns, culminating in changes or loss of protein functionality. For instance, in cancer, abnormalities in AS and RBPs may result in aberrant expression of cancer-associated genes, thereby promoting the onset and progression of tumors. AS and RBPs are also associated with numerous neurodegenerative diseases and autoimmune diseases. Consequently, the study of AS across different tissues holds significant value. This review provides a detailed account of the recent advancements in the study of alternative splicing and AS-related RNA-binding proteins in tissue development and diseases, which aids in deepening the understanding of gene expression complexity and offers new insights and methodologies for precision medicine.
Assuntos
Processamento Alternativo , Neoplasias , Humanos , Processamento Alternativo/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Neoplasias/genéticaRESUMO
Background: Osteoporotic vertebral compression fractures (OVCFs) are the most common type of fragility fracture. Distinguishing between OVCFs and other types of vertebra diseases, such as old fractures (OFs), Schmorl's node (SN), Kummell's disease (KD), and previous surgery (PS), is critical for subsequent surgery and treatment. Combining with advanced deep learning (DL) technologies, this study plans to develop a DL-driven diagnostic system for diagnosing multi-type vertebra diseases. Methods: We established a large-scale dataset based on the computed tomography (CT) images of 1,051 patients with OVCFs from Luhe Hospital and used data of 46 patients from Xuanwu Hospital as alternative hospital validation dataset. Each patient underwent one examination. The dataset contained 11,417 CT slices and 19,718 manually annotated vertebrae with diseases. A two-stage DL-based system was developed to diagnose five vertebra diseases. The proposed system consisted of a vertebra detection module (VDModule) and a vertebra classification module (VCModule). Results: The training and testing dataset for the VDModule consisted of 9,135 and 3,212 vertebrae, respectively. The VDModule using the ResNet18-based Faster region-based convolutional neural network (R-CNN) model achieved an area under the curve (AUC), false-positive (FP) rate, and false-negative (FN) rate of 0.982, 1.52%, and 1.33%, respectively, in the testing dataset. The training dataset for VCModule consisted of 14,584 and 47,604 diseased and normal vertebrae, respectively. The testing dataset consisted of 4,489 and 15,122 diseased and normal vertebrae, respectively. The ResNet50-based VCModule achieved an average sensitivity and specificity of 0.919 and 0.995, respectively, in diagnosing four kinds of vertebra diseases except for SN in the testing dataset. In the alternative hospital validation dataset, the ResNet50-based VCModule achieved an average sensitivity and specificity of 0.891 and 0.989, respectively, in diagnosing four kinds of vertebra diseases except for SN. Conclusions: Our proposed DL system can accurately diagnose four vertebra diseases and has strong potential to facilitate the accurate and rapid diagnosis of vertebral diseases.
RESUMO
BACKGROUND: Frailty is an age-related health condition affecting an estimated 18% of older adults in Europe and past evidence has shown a relationship between socioeconomic factors and frailty. We examined population frailty trends and the association between frailty and 5-year mortality by education tertiles and income quartiles at ages 75, 85 and 95 in Swedish registry data. METHODS: All Swedish residents born in 1895-1945 and in the Total Population Register from 1990 to 2020 were included. Frailty was assessed with the Hospital Frailty Risk Score (HFRS), which sums 109 weighted International Classification of Diseases (ICD codes), collected from the National Patient Register. RESULTS: Regardless of education and income, frailty increased over time, though the association between frailty and 5-year mortality remained stable. Particularly in earlier birth cohorts, although the highest education and income levels had the highest mean HFRS scores, the lowest education and income levels accounted for greater proportions among the frail. These trends varied slightly by sex and age. Men and women had similar levels of frailty, but frailty was more strongly associated with mortality among men. CONCLUSION: Over time, education and income levels were more equally represented among the frail population in more recent years. More equitable distribution over time may suggest improvement in health disparities, though more work is needed. The overall increase in frailty and unchanged association with mortality indicates that additional research is needed to better understand how to best support the growing ageing population. This would then support the long-term viability of the healthcare system.
RESUMO
Objective: This study investigated factors influencing the knowledge, attitudes, practice profiles, and vaccination intentions among Chinese nursing students and nursing interns toward the coronavirus disease (COVID-19) vaccination. Materials and Methods: The multicenter cross-sectional study was based on a self-reported questionnaire collecting information among nursing students and nursing interns from three major geographic regions of China, and the sample was selected by consecutive sampling. The questionnaire was developed by knowledge, attitudes, and practice (KAP) theory. Univariate and multivariate logistic regression were used for statistical analysis. Results: A total of 3180 nursing students and interns (effective rate: 99.8%) from six Chinese provinces were polled. The vaccine hesitation rate was 9.65% (307/3180), 2230 participants (70.1%) had gotten at least one dose of the vaccine, and 643 participants (67.7%) had indicated a readiness to be vaccinated. The results showed that older age, higher academic background, perfect vaccine management, others' recommendations, influenza vaccination history, epidemic under control, knowledge of vaccines or intervals, and vaccine knowledge training were associated with higher vaccination rates. Conversely, vaccine hesitancy was caused by a perceived lack of physical need, uncertainty about vaccination requirements, and fear of vaccination. Conclusion: This study provided population-based estimates of COVID-19 vaccine uptake intention among mainland Chinese nursing students and interns. Factors such as age, education, vaccine knowledge, and attitudes influence COVID-19 vaccine behaviour. Relevant authorities should understand the barriers to COVID-19 vaccination from knowledge, attitude and practice, which is significant for formulating effective response strategies in future global public health crises.
RESUMO
Herein, we design a novel "crossbreeding" dye (BC-OH) within the second near-infrared (NIR-II) window based on BODIPY and chromene chromophores. BC-OH can serve as a platform to construct activatable NIR-II probes with small spectral crosstalk, thereby making a breakthrough in imaging in vivo H2O2 fluctuation in an APAP-induced liver injury model with high signal-to-background ratio.
Assuntos
Corantes Fluorescentes , Peróxido de Hidrogênio , Compostos de Boro , Fígado/diagnóstico por imagem , Imagem Óptica/métodosRESUMO
Targeted drug delivery using micro-nano robots (MNRs) is a rapidly advancing and promising field in biomedical research. MNRs enable precise delivery of drugs, addressing a wide range of healthcare needs. However, the application of MNRs in vivo is limited by power issues and specificity in different scenarios. Additionally, the controllability and biological safety of MNRs must be considered. To overcome these challenges, researchers have developed bio-hybrid micro-nano motors that offer improved accuracy, effectiveness, and safety for targeted therapies. These bio-hybrid micro-nano motors/robots (BMNRs) use a variety of biological carriers, blending the benefits of artificial materials with the unique features of different biological carriers to create tailored functions for specific needs. This review aims to give an overview of the current progress and application of MNRs with various biocarriers, while exploring the characteristics, advantages, and potential hurdles for future development of these bio-carrier MNRs.
RESUMO
Uniting photothermal therapy (PTT) with magnetic resonance imaging (MRI) holds great potential in nanotheranostics. However, the extensively utilized hydrophobicity-driven assembling strategy not only restricts the intramolecular motion-induced PTT, but also blocks the interactions between MR agents and water. Herein, we report an aggregation-induced emission luminogen (AIEgen)-mediated polyelectrolyte nanoassemblies (APN) strategy, which bestows a unique "soft" inner microenvironment with good water permeability. Femtosecond transient spectra verify that APN well activates intramolecular motion from the twisted intramolecular charge transfer process. This de novo APN strategy uniting synergistically three factors (rotational motion, local motion, and hydration number) brings out high MR relaxivity. For the first time, APN strategy has successfully modulated both intramolecular motion and magnetic relaxivity, achieving fluorescence lifetime imaging of tumor spheroids and spatio-temporal MRI-guided high-efficient PTT.
Assuntos
Corantes Fluorescentes , Imageamento por Ressonância Magnética , Polieletrólitos , ÁguaRESUMO
Pancreatic ductal adenocarcinoma (PDAC), as one of the most malignant tumors with dense desmoplastic stroma, forms a specific matrix barrier to hinder effective diagnosis and therapy. To date, a paramount challenge is in the search for intelligent nanotheranostics for such hypopermeable tumors, especially in breaking the PDAC-specific physical barrier. The unpredictable in vivo behaviors of nanotheranostics, that is, real-time tracking where, when, and how they cross the physical barriers and are taken up by tumor cells, are the major bottleneck. Herein, we elaborately design sequence-activated nanotheranostic TCM-U11&Cy@P with dual-channel near-infrared fluorescence outputs for monitoring in vivo behaviors in a sequential fashion. This nanotheranostic with a programmable targeting capability effectively breaks through the PDAC barriers. Ultimately, the released aggregation-induced emission (AIE) particle TCM-U11 directly interacts with PDAC cells and penetrates into the deep tissue. Impressively, this fluorescent nanotheranostic intraoperatively can map human clinical PDAC specimens with high resolution. We believe that this unique sequence-activated fluorescent strategy expands the repertoire of nanotheranostics in the treatment of hypopermeable tumors.
RESUMO
BACKGROUND: Recently, a novel 4-tiered classification of left ventricular hypertrophy (LVH) based on ventricular dilatation (indexed LV end-diastolic volume [EDV]) and concentricity (mass/EDV0.67) has improved all-cause and cardiovascular mortality risk stratification. However, their possible association with ischemic stroke has not been extensively evaluated in the general population. METHODS: We evaluated a cross-sectional study of 11,037 subjects from the general population of China in whom echocardiographic and ischemic stroke data were available to subdivide patients with LVH into four geometric patterns: indeterminate, dilated, thick and both thick and dilated hypertrophy. RESULTS: Compared with normal LV geometry, indeterminate and thick hypertrophy showed a higher prevalence of ischemic stroke (p < .05). Ischemic stroke was significantly greater in participants with indeterminate (adjusted odd ratio [OR]:1.635, 95% confidence interval [CI]: 1.115-2.398) and thick (2.143 [1.329-3.456]) hypertrophy but not significantly in those with dilated (1.251 [0.803-1.950]) and both thick and dilated hypertrophy (0.926 [0.435-1.971]) compared with normal geometry in multivariable analysis. CONCLUSIONS: Indeterminate and thick hypertrophy were significantly associated with the presence of ischemic stroke in the general Chinese population. The new 4-tiered categorization of LVH can permit a better understanding of which subjects are at high enough risk for ischemic stroke to warrant early targeted therapy. Key messages This was the first study to investigate whether a 4-tiered classification of LVH defines subgroups in the general population that are at variable risks of ischemic stroke. We identified that thick hypertrophy carried the greatest odd for ischemic stroke, independently of traditional risk factors, followed by indeterminate hypertrophy. The new 4-tiered categorization of LVH emerged as a valuable operational approach, a potential alternative to LVM, to refine ischemic stroke stratification in general population.