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BACKGROUND: Due to the unique working environment and nature of work in emergency departments, nurses are prone to experiencing compassion fatigue (CF), leading to job burnout and attrition. As more Generation Z (Gen Z) nurses enter the emergency department with distinct personality traits compared to previous generations, studying their experiences with CF will inform future management strategies. METHODS: The qualitative phenomenological research method was utilised to investigate CF among Gen Z emergency nurses at a hospital in Shanghai, China. Data were collected through face-to-face semi-structured interviews and analyzed using Colaizzi's seven-step phenomenological analysis method. Study participants were purposively selected. RESULTS: Three main themes and nine sub-themes emerged from the study: secondary traumatic stress, including physiological symptoms, psychological symptoms, and behavioral changes; cumulative effects, including impaired empathy, interference with family life, and post-traumatic growth (PTG); coping strategies, including cognitive reconstruction, seeking support, and facilitating action. CONCLUSIONS: The aim of this study is to investigate the experience of CF among Gen Z emergency nurses, providing managers with a reference for future management strategies. The significance of multi-dimensional support for Gen Z emergency nurses is underscored by our findings. Additionally, interventions that enhance resilience and competency can facilitate their psychological transformation after experiencing CF and promote accelerated personal growth.
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BACKGROUND: The period of standardized training is a transitional stage when Generation Z newly graduated registered nurses (Gen Z NGRNs) change their role from student to nurse. Affected by the COVID-19, they lack clinical practice and practicum experience in emergency departments in their university studies. At the beginning of career, they are under great pressure. Resilience is one of the factors that reduce their stress level and increases endurance. It is of interest to understand how this representative group of nurses gained and played the experience of resilience early in their careers. OBJECTIVE: To explore Gen Z NGRNs' experience and process of resilience, to provide a new perspective and theoretical basis for psychological rehabilitation or intervention of medical staff who experienced transition shock. METHODS: This study employed a qualitative design based on the phenomenological approach. 18 nurses from a third-level class-A hospital in Shanghai who participated in standardized training in emergency department were enrolled using purposive sampling. Data collection was through in-depth and semi-structured interviews and continued until reaching data saturation. RESULTS: The investigation uncovered three themes and ten subthemes. Pressure and challenge contained high workload and high risk coexist, death's stress response, more emergencies and high professional requirements. Coping and adaptation contained team help, psychological restructuring, peer support, transformational leadership. Reflection and planning contained enhance learning, appreciate life. CONCLUSIONS: Our study described the embodiment and coping experience of the physical and mental stress faced by Gen Z NGRNs during their standardized training in the emergency department. It is emphasized that nurse educators should pay attention to the character and actual needs of Gen Z NGRNs, explore and formulate strategies, so as to guide NGRNs to quickly adapt and grow in the new role. The ultimate goal is to increase nurse retention and improve the quality of nursing.
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BACKGROUND: Patient safety is a top priority for the global healthcare system and a prerequisite for high-quality nursing care. In China, newly graduated registered nurses are required to receive two years of standardized training to ensure patient safety. The pre-service safety training program aims to provide safe, high-quality, and effective nursing care. However, perceptions and experiences of newly graduated registered nurses on pre-service safety training programs have not yet been explored. OBJECTIVES: To investigate newly graduated registered nurses' perceptions and experiences of the pre-service safety training program in a tertiary hospital in China. DESIGN: A phenomenological approach was used for this qualitative study. SETTINGS: Tertiary hospital in Shanghai, China. PARTICIPANTS: A total of 19 newly graduated registered nurses who participated in the pre-service safety training program. METHODS: Data were collected using semi-structured, face-to-face, in-depth interviews and analyzed using the Colaizzi seven-step framework. RESULTS: Three themes and nine sub-themes emerged: (1) satisfaction with the approaches and content of the training, (2) gaining benefits and growth, and (3) suggestions for the training. CONCLUSION: It is meaningful for newly graduated registered nurses to receive safety training before entering clinical practice and was praised by participants for helping them improve safety competence and change safety behaviors. Continuing safety training and optimizing the training modules and evaluation methods will maximize the effectiveness of safety training.
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Enfermeiras e Enfermeiros , Cuidados de Enfermagem , Humanos , China , Pesquisa Qualitativa , Atenção à SaúdeRESUMO
OBJECTIVE: To qualitatively explore the factors that enhance resilience among emergency nurses (ENs). DESIGN: This study is an exploratory qualitative investigation. Semistructured in-depth interviews were used for data collection, while qualitative content analysis was applied for data analysis. SETTING: A grade A tertiary hospital in Shanghai, China. PARTICIPANTS: The study subjects comprised 17 ENs, who were selected using a purposive sampling method. RESULTS: Three main themes and the nine subthemes emerged from the study, that is, individual resources, including competency, personality traits and occupational benefits; family resources, including close parent-child attachment and supportive family dynamics; social resources, including peer support, organisational support, resilient leadership and popular support. CONCLUSION: This qualitative study explored the factors promoting resilience among ENs and provided a reference for managers to formulate future management strategies. From the perspective of positive psychology, nurses should receive comprehensive support, focusing on improving their professional accomplishment and role ability while prioritising the development of resilient leadership. These efforts are expected to drive progress and growth across the emergency care team.
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Serviços Médicos de Emergência , Enfermeiras e Enfermeiros , Resiliência Psicológica , Humanos , China , Pesquisa Qualitativa , LiderançaRESUMO
The effects of immunotherapeutics on interactions between immune and cancer cells are modulated by multiple components in the tumour microenvironment (TME), including endothelium and tumour stroma, which provide both a physical barrier and immunosuppressive stimuli. Herein, we report a recirculating chip to enable continuous immune cell recirculation through a microfluidic cell array to include these crucial players. This system consists of a three-layered cell array (µFCA) spatially emulating the TME, with tailored fluidic circuits establishing T cell recirculation. This platform enables the study of dynamics among the TME, immune cells in a circulatory system and cancer cell responses thereof. Through this system, we found that tumour endothelium hindered T cell infiltration into the reconstructed breast cancer tumour compartment. This negative effect was alleviated when treated with anti-human PD-L1 (programmed cell death ligand 1) antibody. Another key stromal component - cancer associated fibroblasts - attenuated T cell infiltration, compared against normal fibroblasts, and led to reduced apoptotic activity in cancer cells. These results confirm the capability of our tumour-on-a-chip system in identifying some key axes to target in overcoming barriers to immunotherapy by recapitulating immune cell interactions with the reconstructed TME. Our results also attest to the feasibility of scaling up this system for high-throughput cancer immunotherapeutic screening.
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Neoplasias , Microambiente Tumoral , Humanos , Microfluídica , Imunoterapia , Linfócitos TRESUMO
Gene editing in the brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches mainly rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain. We demonstrate a safe and effective gene editing technique by using focused ultrasound (FUS) to transiently open the BBB for the transport of intravenously delivered CRISPR/Cas9 machinery to the brain.
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Encéfalo , Edição de Genes , Encéfalo/diagnóstico por imagem , Barreira Hematoencefálica , Transporte Biológico , MicrobolhasRESUMO
Gene editing in the mammalian brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain. We demonstrate a safe and effective gene editing technique by using focused ultrasound (FUS) to transiently open the BBB for the transport of intravenously delivered CRISPR/Cas9 machinery to the brain.
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Drug screening in oncology, especially for triple-negative breast cancer (TNBC), has high demand but remains unsatisfactory. Currently available models are either nonrepresentative of the complex tumor microenvironment or only suitable for low throughput screening, resulting in a low-yield success for drug development. To tackle these issues, the L-TumorChip system is developed in this study. It is a three-layered microfluidic tumor-on-a-chip platform integrating tumor microvasculature and tumor-stromal microenvironment with high throughput screening capability. Its layered and modular design is readily scalable through simple integration of multiple units. Here, L-TumorChip is validated with a TNBC model. The L-TumorChip system emulates certain tumor-stroma complexities and tumor-endothelium interactions, including TNBC invasion through the leaky microvasculature and angiogenesis. Additionally, with this L-TumorChip, the influence of different stromal cells, including normal fibroblasts, mesenchymal stem cells, and cancer-associated fibroblasts (CAF), on cancer cell growth as well as the stromal effects on drug responses to doxorubicin treatment is investigated. The presence of CAF delays drug pharmacokinetics, while apoptotic responses indicated by caspase-3 activities are higher in coculture with normal fibroblasts. Collectively, the L-TumorChip system represents a translational high-throughput screening toolkit that enables drug screening with a scenario closer to the in vivo conditions. This potential use may therefore facilitate development of new cancer drugs.
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Fibroblastos Associados a Câncer , Preparações Farmacêuticas , Linhagem Celular Tumoral , Humanos , Dispositivos Lab-On-A-Chip , Microambiente TumoralRESUMO
Severe sepsis represents a common, expensive, and deadly health care issue with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis would help develop new therapeutic strategies against severe sepsis. In this study, we identified the crucial role of cell-free DNA (cfDNA) in the regulation of the Toll-like receptor 9-mediated proinflammatory pathway in severe sepsis progression. Hypothesizing that removing cfDNA would be beneficial for sepsis treatment, we used polyethylenimine (PEI) and synthesized PEI-functionalized, biodegradable mesoporous silica nanoparticles with different charge densities as cfDNA scavengers. These nucleic acid-binding nanoparticles (NABNs) showed superior performance compared with their nucleic acid-binding polymer counterparts on inhibition of cfDNA-induced inflammation and subsequent multiple organ injury caused by severe sepsis. Furthermore, NABNs exhibited enhanced accumulation and retention in the inflamed cecum, along with a more desirable in vivo safety profile. Together, our results revealed a key contribution of cfDNA in severe sepsis and shed a light on the development of NABN-based therapeutics for sepsis therapy, which currently remains intractable.
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Ácidos Nucleicos Livres , Nanopartículas , Sepse , DNA/uso terapêutico , Humanos , Polietilenoimina/uso terapêutico , Sepse/etiologia , Sepse/genéticaRESUMO
For patients carrying BRCA1 mutations, at least one-third develop triple negative breast cancer (TNBC). Not only is TNBC difficult to treat due to the lack of molecular target receptors, but BRCA1 mutations (BRCA1m) also result in chemotherapeutic resistance, making disease recurrence more likely. Although BRCA1m are highly heterogeneous and therefore difficult to target, BRCA1 gene's synthetic lethal pair, PARP1, is conserved in BRCA1m cancer cells. Therefore, we hypothesize that targeting PARP1 might be a fruitful direction to sensitize BRCA1m cancer cells to chemotherapy. We used CRISPR/Cas9 technology to generate PARP1 deficiency in two TNBC cell lines, MDA-MB-231 (BRCA1 wild-type) and MDA-MB-436 (BRCA1m). We explored whether this PARP1 disruption (PARP1m) could significantly lower the chemotherapeutic dose necessary to achieve therapeutic efficacy in both a 2D and 3D tumor-on-a-chip model. With both BRCA1m and PARP1m, the TNBC cells were more sensitive to three representative chemotherapeutic breast cancer drugs, doxorubicin, gemcitabine and docetaxel, compared with the PARP1 wild-type counterpart in the 2D culture environment. However, PARP1m did not result in this synergy in the 3D tumor-on-a-chip model, suggesting that drug dosing in the tumor microenvironment may influence the synergy. Taken together, our results highlight a discrepancy in the efficacy of the combination of PARP1 inhibition and chemotherapy for TNBC treatment, which should be clarified to justify further clinical testing.
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CRISPR/Cas9 technology enables targeted gene editing; yet, the efficiency and specificity remain unsatisfactory, particularly for the nonvirally delivered, plasmid-based CRISPR/Cas9 system. To tackle this, a self-assembled micelle is developed and evaluated for human papillomavirus (HPV) E7 oncogene disruption. The optimized micelle enables effective delivery of Cas9 plasmid with a transient transgene expression profile, benefiting the specificity of Cas9 recognition. Furthermore, the feasibility of using the micelle is explored for another nucleic acid-guided nuclease system, Natronobacterium gregoryi Argonaute (NgAgo). Both systems are tested in vitro and in vivo to evaluate their therapeutic potential. Cas9-mediated E7 knockout leads to significant inhibition of HPV-induced cancerous activity both in vitro and in vivo, while NgAgo does not show significant E7 inhibition on the xenograft mouse model. Collectively, this micelle represents an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine-based therapeutics.
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A unique interaction between the cyanine dye and negatively charged quantum dot is used to construct a signal-on biaptameric quantum dot (QD) Förster resonance energy transfer (FRET) beacon for protein detection and distinct aptamer characterization. The beacon comprises a pair of aptamers, one intercalated with the cyanine dye (YOYO-3) and the other conjugated to a negatively charged, carboxyl-QD. When the target protein is present, structural folding and sandwich association of the two aptamers take place. As a consequence, YOYO-3 is displaced from the folded aptamer and transferred to the unblocked QD surface to yield a target concentration-dependent FRET signal. As a proof-of-principle, we demonstrate the detection of thrombin ranging from nanomolar to submicromolar concentrations and confirm the dye translocation using cylindrical illumination confocal spectroscopy (CICS). The proposed beacon provides a simple, rapid, signal-on FRET detection for protein as well as a potential platform for distinct aptamer screening.
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Aptâmeros de Peptídeos/química , Corantes Fluorescentes/química , Oxazóis/química , Pontos Quânticos/química , Trombina/análise , HumanosRESUMO
The current state of screening methods for drug discovery is still riddled with several inefficiencies. Although some widely used high-throughput screening platforms may enhance the drug screening process, their cost and oversimplification of cell-drug interactions pose a translational difficulty. Microfluidic cell-chips resolve many issues found in conventional HTS technology, providing benefits such as reduced sample quantity and integration of 3D cell culture physically more representative of the physiological/pathological microenvironment. In this review, we introduce the advantages of microfluidic devices in drug screening, and outline the critical factors which influence device design, highlighting recent innovations and advances in the field including a summary of commercialization efforts on microfluidic cell chips. Future perspectives of microfluidic cell devices are also provided based on considerations of present technological limitations and translational barriers.
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Técnicas de Cultura de Células/instrumentação , Avaliação Pré-Clínica de Medicamentos/instrumentação , Ensaios de Triagem em Larga Escala/instrumentação , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/instrumentação , Animais , Técnicas de Cultura de Células/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Desenho de Equipamento , Ensaios de Triagem em Larga Escala/métodos , Humanos , Técnicas Analíticas Microfluídicas/métodosRESUMO
A new quantum dot (QD)-aptamer (apt) beacon that acts by folding-induced dissociation of a DNA intercalating dye, BOBO-3(B), is demonstrated with label-free thrombin detection. The beacon, denoted as QD-apt:B, is constructed by (1) coupling of a single-stranded thrombin aptamer to Qdot 565 via EDC/Sulfo-NHS chemistry and (2) staining the duplex regions of the aptamer on QD with excess BOBO-3 before thrombin binding. When mixing a thrombin sample with QD-apt:B, BOBO-3 is competed away from the beacon due to target-induced aptamer folding, which then causes a decrease in QD fluorescence resonance energy transfer (FRET)-mediated BOBO-3 emission and achieves thrombin quantitation. In this work, the effects of Mg(2+), coupling time, and aptamer type on the beacon's performances are investigated and discussed thoroughly with various methods, including transmission electron microscopy (TEM), dynamic light scattering (DLS), and two-color differential gel electrophoresis. Using the best aptamer beacon (HTQ37), we attain highly specific and wide-range detection (from nM to µM) of thrombin in buffer, and the beacon can sense nM-range thrombin in 15% diluted serum. Compared to the reported QD aptamer assays, our method is advantageous from the aspect of using a simple sensory unit design without losing the detection sensitivity. Therefore, we consider the QD-apt:B beacon a potential alternative to immuno-reagents and an effective tool to study nucleic acid folding on QD as well.