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The increasing elderly population is driving higher utilization rates of long-term care facilities, where residents often have multiple chronic diseases, making them potential candidates for palliative care. Timely palliative care interventions can improve their quality of life and medical autonomy. This study systematically reviews the effectiveness of palliative care programs in long-term care facilities. Databases such as PubMed, EMBASE, Cochrane Library, and Airiti Library were searched up to 31 December 2023, using PICO criteria and the following keywords: 'care home', 'nursing home', 'residential aged care facility', and 'long-term care facility' for patients; and 'Gold Standard Framework in Care Homes', 'integrated care pathway', 'care home project', and 'palliative care program' for interventions. Seven articles were included. The results indicate that the Program of All-Inclusive Care for the Elderly (PACE) intervention did not significantly influence overall quality of life but did improve the quality of death. There were no statistical differences in comfort or quality of death between the dementia and non-dementia groups. However, PACE significantly reduced healthcare costs. The implementation of the Liverpool Care Pathway (LCP) notably enhanced the control of terminal symptoms, while the Gold Standard Framework in Care Homes (GSFCH) effectively improved end-of-life care rates, do-not-resuscitate (DNR) signing rates, advance care planning (ACP) completion rates, and reduced inappropriate readmission rates. While palliative care interventions are shown to improve the quality of end-of-life care, their practical application should be adapted to fit the implementation conditions and capabilities of domestic long-term care facilities.
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Emerging evidence indicates that transfer RNA (tRNA)-derived small RNAs (tsRNAs), originated from tRNA with high abundance RNA modifications, play an important role in many complex physiological and pathological processes. However, the biological functions and regulatory mechanisms of modified tsRNAs in cancer remain poorly understood. Here, it is screened for and confirmed the presence of a novel m7G-modified tsRNA, m7G-3'-tiRNA LysTTT (mtiRL), in a variety of chemical carcinogenesis models by combining small RNA sequencing with an m7G small RNA-modified chip. Moreover, it is found that mtiRL, catalyzed by the tRNA m7G-modifying enzyme mettl1, promotes bladder cancer (BC) malignancy in vitro and in vivo. Mechanistically, mtiRL is found to specifically bind the oncoprotein Annexin A2 (ANXA2) to promote its Tyr24 phosphorylation by enhancing the interactions between ANXA2 and Yes proto-oncogene 1 (Yes1), leading to ANXA2 activation and increased p-ANXA2-Y24 nuclear localization in BC cells. Together, these findings define a critical role for mtiRL and suggest that targeting this novel m7G-modified tsRNA can be an efficient way for to treat BC.
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Anexina A2 , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Humanos , Fosforilación/genética , Anexina A2/metabolismo , Anexina A2/genética , Ratones , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Proto-Oncogenes Mas , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Regulación Neoplásica de la Expresión Génica/genéticaRESUMEN
BACKGROUND: To date, most existing models for predicting neuromyelitis optica spectrum disorder (NMOSD) are based primarily on clinical characteristics. Blood-based NMOSD severity and prognostic predictive immune- and inflammation-related biomarkers are needed. We aimed to investigate the associations between plasma inflammatory biomarkers and relapse and attack severity in NMOSD. METHODS: This two-step, single-center prospective cohort study included discovery and validation cohorts. We quantified 92 plasma inflammatory proteins by using Olink's proximity extension assay and identified differentially expressed proteins in the relapse group (relapse within 1 year of follow-up) and severe attack group. To define a new molecular prognostic model, we calculated the risk score of each patient based on the key protein signatures and validated the results in the validation cohort. RESULTS: The relapse prediction model, including FGF-23, DNER, GDNF, and SLAMF1, predicted the 1-year relapse risk. The severe attack prediction model, including PD-L1 and MCP-2, predicted the severe clinical attack risk. Both the relapse and severe attack prediction models demonstrated good discriminative ability and high accuracy in the validation cohort. CONCLUSIONS: Our discovered biomarker signature and prediction models may complement current clinical risk stratification approaches. These inflammatory biomarkers could contribute to the discovery of therapeutic interventions and prevent NMOSD progression.
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Biomarcadores , Neuromielitis Óptica , Recurrencia , Humanos , Neuromielitis Óptica/sangre , Neuromielitis Óptica/diagnóstico , Femenino , Biomarcadores/sangre , Masculino , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Estudios de Cohortes , Índice de Severidad de la Enfermedad , Inflamación/sangre , Inflamación/diagnóstico , PronósticoRESUMEN
(1) Background: Evidence suggested inconsistent results in anxiety and depression scores among female and male cancer patients. The present systematic review and meta-analysis aimed to assess how anxiety and depression conditions among cancer patients vary according to sex. (2) Methods: This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The protocol was registered in PROSPERO with id no. CRD42024512553. The search strategy involved combining keywords using Boolean operators, including "Anxiety", "Cancer", and "Depression", across several databases: Embase, PubMed, Scopus, and Web of Science. The outcomes were evaluated using the Hospital Anxiety and Depression Scale (HADS). (3) Results: Data were collected from five studies, enrolling a total of 6317 cancer patients, of whom 2961 were females and 3356 males. For each study, HADS-A and HADS-D scores were considered, also differentiating HADS scores according to cancer typology, and then three different meta-analyses were performed. Generally, females reported significantly higher levels of depression scores than males and, conversely, males reported significantly greater levels of anxiety than females. (4) Conclusions: Previous studies suggested higher rates of depression and anxiety conditions in females than in males, but the present data highlighted controversial findings, since males reported significantly higher levels of anxiety than females. In this scenario, the theoretical approach justified females being more open than males to expressing anxiety or depression conditions. It would be necessary for healthcare professionals to improve effective measures purposed at assessing and mitigating depressive symptoms in cases of advanced cancer, thereby improving their mental health, given the high rates of depression in advanced cancer patients, due to the difficulty level of performing their daily living activities, which deteriorate further over time.
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The COVID-19 pandemic led to significant burnout among nurses, resulting in a shortage of nursing staff. Issues related to nursing work have received significant attention recently, and only healthy nurses are capable of providing good quality patient care. The authors employed Bronfenbrenner's Ecological System Theory to analyze the impact of the COVID-19 pandemic on nurses and proposed specific strategies and recommendations to enhance the nursing workplace. Under the Ecological System Theory, several factors, including inadequate preparedness, dangerous working environment, work-family conflicts, discrimination due to public panic, and health damage, contribute to nurse burnout. Whether during or after the COVID-19 pandemic, it is necessary to provide education programs to enhance the professional abilities of nurses, foster policies that promote a positive practice work environment, implement a triage system based on the severity of patients, elevate the image of the nursing profession, monitor the health of nurses, and advocate for transformational leadership. The nursing workplace should help nurses gain greater confidence and improve their ability to handle various workplace challenges. In the future, medical institutions should provide a better work environment for nurses and expect the public to pay more attention to the development of the nursing profession.
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Agotamiento Profesional , COVID-19 , Pandemias , Lugar de Trabajo , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Agotamiento Profesional/epidemiología , Agotamiento Profesional/prevención & control , Enfermeras y Enfermeros/psicología , SARS-CoV-2RESUMEN
Objective: Bladder cancer is one of the most prominent malignancies affecting the urinary tract, characterized by a poor prognosis. Our previous research has underscored the pivotal role of m6A methylation in the progression of bladder cancer. Nevertheless, the precise relationship between N6-methyladenosine (m6A) regulation of long non-coding RNA (lncRNA) and bladder cancer remains elusive. Methods: This study harnessed sequencing data and clinical records from 408 bladder cancer patients in the TCGA database. Employing R software, we conducted bioinformatics analysis to establish an m6A-lncRNA co-expression network. Analyzing the differences between high and low-risk groups, particularly at the immunological level, and subsequently investigating the primary regulatory factors of these lncRNA, validating the findings through experiments, and exploring their specific cellular functions. Results: We identified 50 m6A-related lncRNA with prognostic significance through univariate Cox regression analysis. In parallel, we employed a LASSO-Cox regression model to pinpoint 11 lncRNA and calculate risk scores for bladder cancer patients. Based on the median risk score, patients were categorized into low-risk and high-risk groups. The high-risk cohort exhibited notably lower survival rates than their low-risk counterparts. Further analysis pointed to RBM15 and METTL3 as potential master regulators of these m6A-lncRNA. Experimental findings also shed light on the upregulated expression of METTlL3 and RBM15 in bladder cancer, where they contributed to the malignant progression of tumors. The experimental findings demonstrated a significant upregulation of METTL3 and RBM15 in bladder cancer specimens, implicating their contributory role in the oncogenic progression. Knockdown of METTL3 and RBM15 resulted in a marked attenuation of tumor cell proliferation, invasion, and migration, which was concomitant with a downregulation in the cellular m6A methylation status. Moreover, these results revealed that RBM15 and METTL3 function in a synergistic capacity, positing their involvement in cancer promotion via the upregulation of m6A modifications in long non-coding RNAs. Additionally, this study successfully developed an N-methyl-N-nitrosourea (MNU)-induced rat model of in situ bladder carcinoma, confirming the elevated expression of RBM15 and METTL3, which paralleled the overexpression of m6A-related- lncRNAs observed in bladder cancer cell lines. This congruence underscores the potential utility of these molecular markers in in vivo models that mirror human malignancies. Conclusion: This study not only offers novel molecular targets,but also enriches the research on m6A modification in bladder cancer, thereby facilitating its clinical translation.
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The interaction between oxygen species and metal sites of various orbitals exhibits intimate correlation with the oxygen reduction reaction (ORR) kinetics. Herein, a new approach for boosting the inherent ORR activity of atomically dispersed Fe-N-C matrix is represented by implanting Fe atomic clusters nearby. The as-prepared catalyst delivers excellent ORR activity with half-wave potentials of 0.78 and 0.90 V in acidic and alkaline solutions, respectively. The decent ORR activity can also be validated from the high-performance rechargeable Zn-air battery. The experiments and density functional theory calculations reveal that the electron spin-state of monodispersed Fe active sites is transferred from the low spin (LS, t2g 6 eg 0) to the medium spin (MS, t2g 5 eg 1) due to the involvement of Fe atomic clusters, leading to the spin electron filling in σ∗ orbit, by which it favors OH- desorption and in turn boosts the reaction kinetics of the rate-determining step. This work paves a solid way for rational design of high-performance Fe-based single atom catalysts through spin manipulation.
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BACKGROUND: Enhanced communication in end-of-life care (EOL) improves preparation and treatment decisions for patients with advanced cancer, affecting their quality of life at the end of life. Question prompt list (QPL) has been shown to enhance physician-patient communication in patients with cancer, but there is a lack of systematic review and meta-analysis for those with advanced cancer. Enhanced communication in end-of-life care improves preparation and treatment decisions for patients with advanced cancer, affecting their quality of life at the end of life. OBJECTIVE: To review the effectiveness of QPL intervention on physician-patient communication and health outcomes during consultation in patients with advanced cancer. METHODS: CINAHL, Embase, Scopus, and PsycINFO databases were undertaken using inclusion criteria for relevant articles up to August 2021. Pooled standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated using random-effects models. We used the Cochrane risk-of-bias assessment tool and modified Jadad scale to assess the quality of the studies. RESULTS: Seven RCTs with 1059 participants were included, of which six studies were eligible for the meta-analysis. The pooled meta-analysis results indicated that QPL in patients with advanced cancer had a significant positive effect on the total number of questions asked (SMD, 0.73; 95% CI, 0.28 to 1.18; I2 = 83%) and on the patients' expectations for the future (SMD, 0.67; 95% CI, 0.08 to 1.25; I2 = 88%). There were no significant improvements in health-related outcomes such as end of life, anxiety, and quality of life. CONCLUSIONS: Using QPL in advanced cancer consultations boosts patient questions which helps communication but not health-related indicators. Optimal results depend on full reading, but timing varies. Future research should examine the relationship between communication and health outcomes, including patient/physician behavior and social context.
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Comunicación , Neoplasias , Relaciones Médico-Paciente , Calidad de Vida , Cuidado Terminal , Humanos , Neoplasias/psicología , Neoplasias/terapia , Cuidado Terminal/métodos , Cuidado Terminal/psicología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: In Taiwan, the Patients' Right to Autonomy Act was enacted in 2019. However, advance care planning (ACP) implementation rates remain low in long-term care facilities. AIM: This study explored the barriers to initiate a discussion about ACP among older Taiwanese residents of nursing homes and their families. METHODS: A descriptive qualitative design was used. Face-to-face interviews were individually conducted with 38 participants (residents: 18; family members: 20), and data were analyzed through content analysis. RESULTS: Five themes were identified: (1) having cultural or spiritual concerns (both groups), (2) prioritizing the bigger picture (family) (both groups), (3) waiting for the right time (both groups), (4) feeling unsure (residents), and (5) following the pace of the residents (family members). CONCLUSION: The results indicate that discussing ACP with Chinese people and their families clashes with traditional Chinese culture. To implement ACP in long-term care facilities based in regions with ethnically Chinese populations, medical professionals must ensure that the residents and their family members understand advance directives and their role in ensuring a good death and must act as a bridge between residents and their family members to assist them in making consensual end-of-life-care decisions with residents.
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Planificación Anticipada de Atención , Pueblos del Este de Asia , Cuidado Terminal , Humanos , Directivas Anticipadas , Casas de SaludRESUMEN
3-Methylcholanthracene (3-MC) is one of the most carcinogenic polycyclic aromatic hydrocarbons (PAHs). Long-term exposure to PAHs has been thought of as an important factor in urothelial tumorigenesis. N6-methyladenosine (m6A) exists widely in eukaryotic organisms and regulates the expression level of specific genes by regulating mRNA stability, translation efficiency, and nuclear export efficiency. Currently, the potential molecular mechanisms that regulate m6A modification for 3-MC carcinogenesis remain unclear. Here, we profiled mRNA, m6A, translation and protein level using "-omics" methodologies, including transcriptomes, m6A profile, translatomes, and proteomics in 3-MC-transformed urothelial cells and control cells. The key molecules SLC3A2/SLC7A5 were screened and identified in 3-MC-induced uroepithelial transformation. Moreover, SLC7A5/SLC3A2 promoted uroepithelial cells malignant phenotype in vitro and in vivo. Mechanically, METTL3 and ALKBH5 mediated m6A modification of SLC3A2/SLC7A5 mRNA in 3-MC-induced uroepithelial transformation by upregulating the translation of SLC3A2/SLC7A5. Furthermore, programmable m6A modification of SLC3A2/SLC7A5 mRNA affected the expression of its proteins. Taken together, our results revealed that the m6A modification-mediated SLC3A2/SLC7A5 translation promoted 3-MC-induced uroepithelial transformation, suggesting that targeting m6A modification of SLC3A2/SLC7A5 may be a potential therapeutic strategy for bladder cancer related to PAHs.
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Transportador de Aminoácidos Neutros Grandes 1 , Hidrocarburos Policíclicos Aromáticos , Humanos , Metilcolantreno/toxicidad , Carcinogénesis , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/genética , ARN Mensajero/genética , Metiltransferasas/genética , Cadena Pesada de la Proteína-1 Reguladora de FusiónRESUMEN
Analyzing the vast amount of omics data generated comprehensively by high-throughput sequencing technology is of utmost importance for scientists. In this context, we propose HiOmics, a cloud-based platform equipped with nearly 300 plugins designed for the comprehensive analysis and visualization of omics data. HiOmics utilizes the Element Plus framework to craft a user-friendly interface and harnesses Docker container technology to ensure the reliability and reproducibility of data analysis results. Furthermore, HiOmics employs the Workflow Description Language and Cromwell engine to construct workflows, ensuring the portability of data analysis and simplifying the examination of intricate data. Additionally, HiOmics has developed DataCheck, a tool based on Golang, which verifies and converts data formats. Finally, by leveraging the object storage technology and batch computing capabilities of public cloud platforms, HiOmics enables the storage and processing of large-scale data while maintaining resource independence among users.
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INTRODUCTION: N6-methyladenosine (m6A) modification contributes to the pathogenesis and development of various cancers, including bladder cancer (BCa). In particular, integrin α6 (ITGA6) promotes BCa progression by cooperatively regulating multisite m6A modification. However, the therapeutic effect of targeting ITGA6 multisite m6A modifications in BCa remains unknown. OBJECTIVES: We aim to develop a multisite dCasRx- m6A editor for assessing the effects of the multisite dCasRx-m6A editor targeted m6A demethylation of ITGA6 mRNA in BC growth and progression. METHODS: The multisite dCasRx- m6A editor was generated by cloning. m6A-methylated RNA immunoprecipitation (meRIP), luciferase reporter, a single-base T3 ligase-based qPCR-amplification, Polysome profiling and meRIP-seq experiments were performed to determine the targeting specificity of the multisite dCasRx-m6A editor. We performed cell phenotype analysis and used in vivo mouse xenograft models to assess the effects of the multisite dCasRx-m6A editor in BC growth and progression. RESULTS: We designed a targeted ITGA6 multi-locus guide (g)RNA and established a bidirectional deactivated RfxCas13d (dCasRx)-based m6A-editing platform, comprising a nucleus-localized dCasRx fused with the catalytic domains of methyltransferase-like 3 (METTL3-CD) or α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5-CD), to simultaneously manipulate the methylation of ITGA6 mRNA at four m6A sites. The results confirmed the dCasRx-m6A editor modified m6A at multiple sites in ITGA6 mRNA, with low off-target effects. Moreover, targeted m6A demethylation of ITGA6 mRNA by the multisite dCasRx-m6A editor significantly reduced BCa cell proliferation and migration in vitro and in vivo. Furthermore, the dCasRx-ALKBH5-CD and ITGA6 multi-site gRNA delivered to 5-week-old BALB/cJNju-Foxn1nu/Nju nude mice via adeno-associated viral vectors significantly inhibited BCa cell growth. CONCLUSION: Our study proposes a novel therapeutic tool for the treatment of BC by applying the multisite dCasRx-m6A editor while highlighting its potential efficacy for treating other diseases associated with abnormal m6A modifications.
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ARN Guía de Sistemas CRISPR-Cas , Neoplasias de la Vejiga Urinaria , Humanos , Ratones , Animales , Integrina alfa6/genética , Integrina alfa6/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratones Desnudos , Línea Celular Tumoral , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Desmetilación , Metiltransferasas/genética , Metiltransferasas/metabolismoRESUMEN
BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP). PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR). RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107). CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Terapia Neoadyuvante/efectos adversos , Receptor ErbB-2/uso terapéutico , Mastectomía , Resultado del Tratamiento , Paclitaxel , Ciclofosfamida/uso terapéutico , Trastuzumab/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
A photoredox-catalyzed intermolecular tandem sulfonamination/cyclization of enaminones was realized by using N-aminopyridinium salts as the sulfonaminated reagents without transition-metal catalysts or bases. The reaction exhibits a broad scope and good functional group tolerance, good yields, and regioselectivity. Preliminary mechanistic studies support the radical property of the reaction and the involvement of N-centered radical intermediates.
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Gallium ion (Ga+ ) beam damage induced indium (In) precipitation in indium gallium arsenide (InGaAs)/indium aluminium arsenide (InAlAs) multiple quantum wells and its corresponding evolution under electron beam irradiation was investigated by valence electron energy loss spectroscopy (VEELS) and high-angle annular dark-field imaging (HAADF) in scanning transmission electron microscopy (STEM). Compared with argon ion milling for sample preparation, the heavier projectiles of Ga+ ions pose a risk to trigger In formation in the form of tiny metallic In clusters. These are shown to be sensitive to electron irradiation and can increase in number and size under the electron beam, deteriorating the structure. Our finding reveals the potential risk of formation of In clusters during focused ion beam (FIB) preparation of InGaAs/InAlAs quantum well samples and their subsequent growth under STEM-HAADF imaging, where initially invisible In clusters of a few atoms can move and swell during electron beam exposure.
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Purpose: Inhibition of the cyclin-dependent kinase (CDK) 4/6-retinoblastoma (RB) pathway exerts a considerable inhibitory effect, preventing the spread and metastasis of breast cancer cells and promoting tumor regression. In this study, we examined the antitumor activity of TQB3616, a novel inhibitor of CDK4/6 activity, which showed a greater efficacy improvement in antitumor effects. Methods: TQB3616 group, abemaciclib group and endocrine or HER-2 targeted combination therapy group were set up respectively. The effects of drugs on cell proliferation activity, cell cycle, apoptosis, downstream protein expression and gene expression of HR positive (T47D, MCF-7) and HER-2 positive (BT474, MDA-MB-361) breast cancer cell lines were studied. The antiproliferative effect of TQB3616 was also measured in vivo. Results: TQB3616 showed a remarkable inhibitory effect on the proliferation of hormone receptor-positive breast cancer cells in vitro. In addition, TQB3616 combined with endocrine therapy or Human Epidermal Growth Factor Receptor 2 (HER2) targeted therapy showed significant synergistic antitumor activity in estrogen receptor (ER)-positive/HER2-negative or HER2-positive breast cancer. In contrast to abemaciclib, which targets the CDK4/6 pathway with proven efficacy, the oral agent TQB3616 not only induced G1 stalling, leading to a profound reduction in the level of RB protein phosphorylated at Ser807/811, but also showed enhanced tumor killing effects by promoting cell apoptosis. Oral administration of TQB3616 showed more potent antitumor activity than abemaciclib in an in vitro breast cancer xenograft model, causing significant tumor regression associated with sustained target inhibition in tumor tissue and manageable in vivo toxicity. Conclusion: The results of this study indicate that TQB3616 is a novel CDK4/6 inhibitor, and its highly effective antitumor activity against breast cancer is expected to yield promising therapeutic effects in clinical studies.
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Breast cancer has surpassed lung cancer as the most common cause of cancer deaths, worldwide. Early breast cancers are treatment sensitive and patients under standardized treatment have prolonged. Breast cancer treatment has significantly evolved from the conventional surgical approach and radiotherapy to local and systemic adjuvant therapies. Though localized breast cancers are clinically manageable, distant recurrence is a cause of morbid concern. Adjuvant systemic therapy is effective in both distant and local recurrences and hence gained significant attention. Early breast cancer prognosis has greatly improved in the past 3 decades with reduced mortality rates due to the widespread use of adjuvant therapy. It can markedly increase the cure rate of breast cancers, and postoperative adjuvant therapy became a part of comprehensive breast cancer treatment. Further research to understand the early breast cancer characteristics could expand the treatment modalities that can improve the outcomes and survival benefits of breast cancer patients.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/cirugía , Terapia Combinada , Pronóstico , Quimioterapia Adyuvante , Recurrencia Local de NeoplasiaRESUMEN
Objective: The participation of patients with advanced cancer(s) in clinical trials is vital for new drug development. We aimed to investigate patients' decision-making processes and satisfaction with their decision (SWD) to participate; the study's purpose was to provide results that can help support high-quality research in clinical trials. In addition, we explored how shared decision-making (SDM) mediates the relationship between understanding informed consent forms and SWD to participate in a clinical trial. Methods: A cross-sectional study was conducted. A purposive sample of 111 cancer patients was recruited, and they completed a questionnaire on demographic characteristics, SDM, and decision-making satisfaction to participate in a clinical trial. Correlation and mediation analyses were used. Results: Participants aged under 65 years and with higher education reported high SWDs, and SDM significantly mediated the relationship between self-assessed understanding of informed consent forms and SWDs related to clinical trials. Conclusions: SDM in patients with lung or liver cancer was a significant mediator between understanding the informed consent form and the patient's SWD. The higher the SWD level of participating in clinical trials, the better study team members' SDM involvement and the better the comprehension of informed consent forms. In addition, patients' age and education level should also be considered as influencing factors in SWD. This survey is the first in Taiwan to examine SDM in drug-related clinical trials. The study results provide evidence to support SDM in a clinical trial model and develop informed consent process policies in research facilities.
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High altitude exposure leads to various cognitive impairments. The cerebral vasculature system plays an integral role in hypoxia-induced cognitive defects by reducing oxygen and nutrition supply to the brain. RNA N6-methyladenosine (m6A) is susceptible to modification and regulates gene expression in response to environmental changes, including hypoxia. However, the biological significance of m6A in endothelial cell performance under hypoxic conditions is unknown. Using m6A-seq, RNA immunoprcipitation-seq, and transcriptomic co-analysis, the molecular mechanism of vascular system remodeling under acute hypoxia is investigated. A novel m6A reader protein, proline-rich coiled-coil 2B (PRRC2B), exists in endothelial cells. PRRC2B knockdown promoted hypoxia-induced endothelial cell migration by regulating alternative splicing of the alpha 1 chain of collagen type XII in an m6A-dependent manner and the decay of matrix metallopeptidase domain 14 and ADAM metallopeptidase domain 19 mRNA in an m6A-independent manner. In addition, conditional knockout of PRRC2B in endothelial cells promotes hypoxia-induced vascular remodeling and cerebral blood flow redistribution, thus alleviating hypoxia-induced cognitive decline. Therefore, PRRC2B is integral in the hypoxia-induced vascular remodeling process as a novel RNA-binding protein. These findings provide a new potential therapeutic target for hypoxia-induced cognitive decline.
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Células Endoteliales , Remodelación Vascular , Ratones , Animales , ARN , Hipoxia , MetaloproteasasRESUMEN
BACKGROUND: Mindfulness-based cognitive therapy (MBCT) may have positive physiological and psychological benefits for breast cancer survivors. However, few studies involved a combination of the relevant literatures to confirm the effects. METHODS: Our study included randomized controlled trials (RCTs) and non-RCTs comparing interventions of MBCT and control protocols for alleviation of symptoms among breast cancer survivors. We calculated pooled mean differences (MDs), standardized mean differences (SMDs), and 95% confidence intervals (CIs) by using random effects models to estimate summary effect sizes. RESULTS: Thirteen trials with 20-245 participants were considered in our studies; for the meta-analysis, 11 of these studies were eligible for assessment. The pooled meta-analysis results revealed that at the end of the MBCT intervention, participants' anxiety (SMD, - 0.70; 95% CI, - 1.26 to - 0.13; I2 = 69%), pain (SMD, - 0.64; 95% CI, - 0.92 to - 0.37; I2 = 0%), and depression (SMD, - 0.65; 95% CI, - 1.14 to - 0.17; I2 = 75%) levels significantly decreased, and their mindfulness (MD, 8.83; 95% CI, 3.88 to 13.78; I2 = 68%) levels significantly increased. CONCLUSION: The MBCT may be associated with improved pain, anxiety, depression, and mindfulness. However, the quantitative analysis pointed to an inconclusive result due to moderate to high levels of heterogeneity among indicator of anxiety, depression, and mindfulness. Future work requires more studies to better elucidate the clinical significance of this possible association. The results suggest that MBCT is highly beneficial as an intervention for patients who have received treatment for breast cancer.