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Purpose: Breast cancer is the leading cause of cancer mortality among women. Radiotherapy can reduce recurrence and prolong survival of patients accepting breast-conserving surgery (BCS). This study aims to compare acute skin reactions in patients receiving hypofractionated versus conventional radiotherapy at a single institution and to summarize the relevant influencing factors. Methods: This study analyzed 152 patients who underwent either hypofractionated or conventional whole-breast irradiation (WBI) after BCS. Acute skin toxicity was assessed according to the Radiation Therapy Oncology Group (RTOG) criteria. Predictive factors for acute skin toxicity were identified using multivariate analysis and visualized using a forest spot. Results: Grade 0 reactions occurred in 75.34% vs 70.89%, grade 1 in 16.44% vs 15.19%, grade 2 in 8.22% vs 12.66%, and grade 3 in 0% vs 1.27% of patients receiving hypofractionated and conventional WBI, respectively. There was no statistically significant difference in acute skin reaction in patients treated with hypofractionated radiation compared with conventional radiation (P = 0.62). Multivariate analysis revealed that metastatic lymph nodes (P = 0.021), whole-breast planning target volume (PTV-WB) (P < 0.001), and tumor bed planning target volume (PTV-TB) (P = 0.002) were significantly correlated with higher rates of acute skin toxicity. Conclusion: Hypofractionated WBI demonstrated similar acute skin adverse reactions compared to conventional WBI. These findings indicate that hypofractionated radiotherapy offers comparable tolerance, equivalent curative effect, convenience, and economic benefits, supporting its clinical promotion.
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Sepsis, a systemic inflammation that occurs in response to a bacterial infection, is a significant medical challenge. Research conducted over the past decade has indicated strong associations among a patient's nutritional status, the composition of their gut microbiome, and the risk, severity, and prognosis of sepsis. Octanoic acid (OA) plays a vital role in combating sepsis and has a protective effect on both animal models and human patients. In this discussion, the potential protective mechanisms of OA in sepsis, focusing on its regulation of the inflammatory response, immune system, oxidative stress, gastrointestinal microbiome and barrier function, metabolic disorders and malnutrition, as well as organ dysfunction are explored. A comprehensive understanding of the mechanisms by which OA act may pave the way for new preventive and therapeutic approaches to sepsis.
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OBJECTIVE: This study aims to determine the association of gestational diabetes mellitus (GDM) and the results of newborn hearing screening(NHS). METHODS: A nested case-control study was conducted in a cohort of newborns who were born between June 2021 to December 2021 and underwent neonatal hearing screening.GDM was diagnosed according to the 75 g 2 h oral glucose tolerance test (OGTT) at 24-28 gestational weeks.A total of 369 pregnant women at the same hospital were individually matched in a 1:2 ratio by maternal age (±2 years), gestational age (±3 days) and sex of newborn.Chi-square test was utilized to evaluate associations between GDM and the results of NHS. RESULTS: Abnormal NHS results in the GDM group was more frequent than non-GDM group.When comparing the two groups (GDM case and contol), we found significant differences (p < 0.05) between them.Whereas the difference was not statistically significant (p > 0.05) by delivery modes in both case and control groups. CONCLUSION: Maternal history of GDM could lead to significantly higher failling rate of NHS.
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Purpose: This study was performed to investigate influencing factors of preoperative muscle mass-to-fat ratio (MMFR) and its impact on overall survival and postoperative complications of colon cancer. Methods: Patients who underwent colectomy for stage I-III colon cancer at the Second Affiliated Hospital of Soochow University between January 2016 and December 2022 were included. The skeletal muscle and fat area at the third lumbar vertebra were measured with preoperative CT measurement. MMFR was defined as the ratio of skeletal muscle area to total fat area, and low MMFR was defined as the 2 lowest tertiles (≤0.585). Univariate and multivariable analyses were conducted to assess the impact of MMFR on overall complications and survival outcomes. Kaplan-Meier survival curves and log-rank test were used to compare the overall survival between high MMFR and low MMFR groups. Results: A total of 885 patients were analyzed. Female sex, older age, high body mass index, sarcopenia, and high cancer stage were more likely to result in low MMFR. Complications, including intestinal fistula, chylous fistula and organ space surgical site infection were significantly higher in the low MMFR group. Low MMFR was an independent factor associated with overall complications (odds ratio, 1.940; 95% confidence interval [CI], 1.252-3.007; P < 0.01) and long-term survival (hazard ratio, 2.222; 95% CI, 1.443-3.425; P < 0.01). Furthermore, patients with high MMFR had a higher survival rate than patients with low MMFR (P < 0.01). Conclusion: Low MMFR is an independent factor that predicts worse overall survival and complications in patients with colon cancer.
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BACKGROUND: Accurate condition assessment is critical for improving the prognosis of neonatal respiratory distress syndrome (RDS), but current assessment methods for RDS pose a cumulative risk of harm to neonates. Thus, a less harmful method for assessing the health of neonates with RDS is needed. AIM: To analyze the relationships between pulmonary ultrasonography and respiratory distress scores, oxygenation index, and chest X-ray grade of neonatal RDS to identify predictors of neonatal RDS severity. METHODS: This retrospective study analyzed the medical information of 73 neonates with RDS admitted to the neonatal intensive care unit of Liupanshui Maternal and Child Care Service Center between April and December 2022. The pulmonary ultrasonography score, respiratory distress score, oxygenation index, and chest X-ray grade of each newborn before and after treatment were collected. Spearman correlation analysis was performed to determine the relationships among these values and neonatal RDS severity. RESULTS: The pulmonary ultrasonography score, respiratory distress score, oxygenation index, and chest X-ray RDS grade of the neonates were significantly lower after treatment than before treatment (P < 0.05). Spearman correlation analysis showed that before and after treatment, the pulmonary ultrasonography score of neonates with RDS was positively correlated with the respiratory distress score, oxygenation index, and chest X-ray grade (ρ = 0.429-0.859, P < 0.05). Receiver operating characteristic curve analysis indicated that pulmonary ultrasonography screening effectively predicted the severity of neonatal RDS (area under the curve = 0.805-1.000, P < 0.05). CONCLUSION: The pulmonary ultrasonography score was significantly associated with the neonatal RDS score, oxygenation index, and chest X-ray grade. The pulmonary ultrasonography score was an effective predictor of neonatal RDS severity.
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OBJECTIVES: This study was designed to determine the incidence, contributing factors, and prognostic implications of acute kidney injury (AKI) recovery patterns in patients who experienced AKI after valve replacement surgery (VRS). DESIGN: A retrospective cohort study was conducted. SETTING: The work took place in a postoperative care center in a single large-volume cardiovascular center. PARTICIPANTS: Patients undergoing VRS between January 2010 and December 2019 were enrolled. INTERVENTION: Patients were categorized into three groups based on their postoperative AKI status: non-AKI, AKI with early recovery (less than 48 hours), and persistent AKI. MEASUREMENT AND MAIN RESULTS: The primary outcome was in-hospital major adverse clinical events. The secondary outcomes included in-hospital and 1-year mortality. A total of 4,161 patients who developed AKI following VRS were included. Of these, 1,513 (36.4%) did not develop postoperative AKI, 1,875 (45.1%) experienced AKI with early recovery, and 773 (18.6%) had persistent AKI. Advanced age, diabetes, New York Heart Association III-IV heart failure, moderate-to-severe renal dysfunction, anemia, and AKI stages 2 and 3 were identified as independent risk factors for persistent AKI. In-hospital major adverse clinical events occurred in 59 (3.9%) patients without AKI, 88 (4.7%) with early AKI recovery, and 159 (20.6%) with persistent AKI (p < 0.001). Persistent AKI was independently associated with an increased risk of in-hospital adverse events and 1-year mortality. In contrast, AKI with early recovery did not pose additional risk compared with non-AKI patients. CONCLUSIONS: In patients who develop AKI following VRS, early AKI recovery does not pose additional risk compared with non-AKI. However, AKI lasting more than 48 hours is associated with an increased risk of in-hospital and long-term adverse outcomes.
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Stacking of van der Waals (vdW) heterostructures and chemical element doping have emerged as crucial methods for enhancing the performance of semiconductors. This study proposes a novel strategy for modifying heterostructures by codoping MoS2 with two elements, Re and W, resulting in the construction of a RexWyMo1-x-yS2/WSe2 heterostructure for the preparation of photodetectors. This approach incorporates multiple strategies to enhance the performance, including hybrid stacking of materials, type-II band alignment, and regulation of element doping. As a result, the RexWyMo1-x-yS2/WSe2 devices demonstrate exceptional performance, including high photoresponsivity (1550.22 A/W), high detectivity (8.17 × 1013 Jones), and fast response speed (rise/fall time, 190 ms/1.42 s). Moreover, the ability to tune the band gap through element doping enables spectral response in the ultraviolet (UV), visible light, and near-infrared (NIR) regions. This heterostructure fabrication scheme highlights the high sensitivity and potential applications of vdW heterostructure (vdWH) in optoelectronic devices.
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To investigate the influence of water content on the rockburst phenomena in tunnels with horizontal joints, experiments were conducted on simulated rock specimens exhibiting five distinct levels of water absorption. Real-time monitoring of the entire blasting process was facilitated through a high-speed camera system, while the microscopic structure of the rockburst debris was analyzed using scanning electron microscopy (SEM) and a particle size analyzer. The experimental findings revealed that under varying degrees of water absorption, the specimens experienced three stages: debris ejection; rockburst; and debris spalling. As water content increased gradually, the intensity of rockburst in the specimens was mitigated. This was substantiated by a decline in peak stress intensity, a decrease in elastic modulus, delayed manifestation of pre-peak stress drop, enhanced amplitude, diminished elastic potential energy, and augmented dissipation energy, resulting in an expanded angle of rockburst debris ejection. With increasing water content, the bond strength between micro-particles was attenuated, resulting in the disintegration of the bonding material. Deformation failure was defined by the expansion of minuscule pores, gradual propagation of micro-cracks, augmentation of fluffy fine particles, exacerbation of structural surface damage akin to a honeycomb structure, diminishment of particle diameter, and a notable increase in quantity. Furthermore, the augmentation of secondary cracks and shear cracks, coupled with the enlargement of spalling areas, signified the escalation of deformation failure. Simultaneously, the total mass of rockburst debris gradually diminished, accompanied by a corresponding decrease in the proportion of micro and fine particles within the debris.
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Cases of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the urinary system are rare, and reports of primary MiNENs in the ureter are lacking. Herein, we present the case of a 71-year-old man who presented with painless gross hematuria and weight loss. Contrast-enhanced abdominal computed tomography (CT) revealed a tumor, comprising small cell neuroendocrine carcinoma (SCNEC) and adenocarcinomatous components, attached to the ureter. The SCNEC components were strongly positive for synaptophysin, CD56 and INSM1 and adenocarcinomatous components were strongly positive for CDX2 and cytokeratin 20, respectively. Four weeks post-surgery, the patient received four cycles of cisplatin-based chemotherapy; the 7-month follow-up CT confirmed that he was healthy without disease recurrence. The occurrence of MiNEN in the ureter with SCNEC and adenocarcinomatous components is extremely rare, wherein histopathological and immunohistochemical features aid in the diagnosis MiNEN. With its aggressive nature, MiNEN can only be effectively treated by early diagnosis and radical surgery.
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INTRODUCTION: Recent advancements in androgenetic alopecia (AGA) treatment have highlighted the efficacy of botulinum toxin (BoNT). However, inconsistencies in injection sites and depths warrant attention. It remains unclear which injection strategy is most beneficial for patients. METHODS: This split-scalp randomized controlled trial divided each enrolled participant's scalp along the midline: one side was randomized to receive intramuscular BoNT injections in the surrounding muscles, while the other side received intradermal BoNT injections directly into the balding areas. This study evaluated the impact of treatment on hair density and diameter through trichoscopic examinations conducted at baseline and 12 weeks post treatment. Additionally, assessments of pain and overall safety were integrated into the study protocol. RESULTS: Twenty-nine patients completed the study, with significant improvements in hair density observed in the intramuscular injection group compared to the intradermal group (p < 0.001). Both groups exhibited increases in hair diameter, but no significant difference was found between the two methods (p = 0.433). Pain evaluation revealed that intradermal injections in balding areas were more painful than intramuscular injections (p = 0.036), with no severe adverse reactions reported except for a single case of alopecia areata following injection. CONCLUSION: Our research revealed that both BoNT injection strategies enhanced hair diameter 12 weeks post-treatment, with intramuscular injections significantly improving hair density more effectively. Despite the promising outcomes, the variability in patient responses underscores the necessity for personalized approaches and further research to refine injection protocols for optimized efficacy and safety. TRIAL REGISTRATION NUMBER: ChiCTR2400080190.
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8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) base is the predominant form of commonly observed DNA oxidative damage. DNA impairment profoundly impacts gene expression and serves as a pivotal factor in stimulating neurodegenerative disorders, cancer, and aging. Therefore, precise quantification of 8-oxoG has clinical significance in the investigation of DNA damage detection methodologies. However, at present, the existing approaches for 8-oxoG detection pose challenges in terms of convenience, expediency, affordability, and heightened sensitivity. We employed the sandwich enzyme-linked immunosorbent assay (ELISA) technique, a highly efficient and swift colorimetric method, to detect variations in 8-oxo-dG content in MCF-7 cell samples stimulated with different concentrations of hydrogen peroxide (H2O2). We determined the concentration of H2O2 that induced oxidative damage in MCF-7 cells by detecting its IC50 value in MCF-7 cells. Subsequently, we treated MCF-7 cells with 0, 0.25, and 0.75 mM H2O2 for 12 h and extracted 8-oxo-dG from the cells. Finally, the samples were subjected to ELISA. Following a series of steps, including plate spreading, washing, incubation, color development, termination of the reaction, and data collection, we successfully detected changes in the 8-oxo-dG content in MCF-7 cells induced by H2O2. Through such endeavors, we aim to establish a method to evaluate the degree of DNA oxidative damage within cell samples and, in doing so, advance the development of more expedient and convenient approaches for DNA damage detection. This endeavor is poised to make a meaningful contribution to the exploration of associative analyses between DNA oxidative damage and various domains, including clinical research on diseases and the detection of toxic substances.
Subject(s)
8-Hydroxy-2'-Deoxyguanosine , DNA Damage , Enzyme-Linked Immunosorbent Assay , Hydrogen Peroxide , Oxidative Stress , Humans , DNA Damage/drug effects , MCF-7 Cells , Enzyme-Linked Immunosorbent Assay/methods , Hydrogen Peroxide/pharmacology , Oxidative Stress/drug effects , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/analysisABSTRACT
Natural products play a pivotal role in drug discovery, and the richness of natural products, albeit significantly influenced by various environmental factors, is predominantly determined by intrinsic genetics of a series of enzymatic reactions and produced as secondary metabolites of organisms. Heretofore, few natural product-related databases take the chemical content into consideration as a prominent property. To gain unique insights into the quantitative diversity of natural products, we have developed the first TerPenoids database embedded with Content information (TPCN) with features such as compound browsing, structural search, scaffold analysis, similarity analysis and data download. This database can be accessed through a web-based computational toolkit available at http://www.tpcn.pro/. By conducting meticulous manual searches and analyzing over 10 000 reference papers, the TPCN database has successfully integrated 6383 terpenoids obtained from 1254 distinct plant species. The database encompasses exhaustive details including isolation parts, comprehensive molecule structures, chemical abstracts service registry number (CAS number) and 7508 content descriptions. The TPCN database accentuates both the qualitative and quantitative dimensions as invaluable phenotypic characteristics of natural products that have undergone genetic evolution. By acting as an indispensable criterion, the TPCN database facilitates the discovery of drug alternatives with high content and the selection of high-yield medicinal plant species or phylogenetic alternatives, thereby fostering sustainable, cost-effective and environmentally friendly drug discovery in pharmaceutical farming. Database URL: http://www.tpcn.pro/.
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Terpenes , Terpenes/metabolism , Terpenes/chemistry , Databases, Chemical , Databases, FactualABSTRACT
Drug therapy is vital in cancer treatment. Accurate analysis of drug sensitivity for specific cancers can guide healthcare professionals in prescribing drugs, leading to improved patient survival and quality of life. However, there is a lack of web-based tools that offer comprehensive visualization and analysis of pancancer drug sensitivity. We gathered cancer drug sensitivity data from publicly available databases (GEO, TCGA and GDSC) and developed a web tool called Comprehensive Pancancer Analysis of Drug Sensitivity (CPADS) using Shiny. CPADS currently includes transcriptomic data from over 29 000 samples, encompassing 44 types of cancer, 288 drugs and more than 9000 gene perturbations. It allows easy execution of various analyses related to cancer drug sensitivity. With its large sample size and diverse drug range, CPADS offers a range of analysis methods, such as differential gene expression, gene correlation, pathway analysis, drug analysis and gene perturbation analysis. Additionally, it provides several visualization approaches. CPADS significantly aids physicians and researchers in exploring primary and secondary drug resistance at both gene and pathway levels. The integration of drug resistance and gene perturbation data also presents novel perspectives for identifying pivotal genes influencing drug resistance. Access CPADS at https://smuonco.shinyapps.io/CPADS/ or https://robinl-lab.com/CPADS.
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Drug Resistance, Neoplasm , Internet , Neoplasms , Software , Humans , Neoplasms/drug therapy , Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Computational Biology/methods , Databases, Genetic , Transcriptome , Gene Expression Profiling/methodsABSTRACT
Addressing the challenge of understanding how cellular interfaces dictate the mechanical resilience and adhesion of archaeal cells, this study demonstrates the role of the surface layer (S-layer) in methanogenic archaea. Using a combination of atomic force microscopy and single-cell force spectroscopy, we quantified the impact of S-layer disruption on cell morphology, mechanical properties, and adhesion capabilities. We demonstrate that the S-layer is crucial for maintaining cell morphology, where its removal induces significant cellular enlargement and deformation. Mechanical stability of the cell surface is substantially compromised upon S-layer disruption, as evidenced by decreased Young's modulus values. Adhesion experiments revealed that the S-layer primarily facilitates hydrophobic interactions, which are significantly reduced after its removal, affecting both cell-cell and cell-bubble interactions. Our findings illuminate the S-layer's fundamental role in methanogen architecture and provide a chemical understanding of archaeal cell surfaces, with implications for enhancing methane production in biotechnological applications.
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Microscopy, Atomic Force , Single-Cell Analysis , Surface Properties , Archaea/chemistry , Archaea/metabolism , Cell Adhesion , Hydrophobic and Hydrophilic InteractionsABSTRACT
Programmed cell death (PCD) is a basic process of life that is closely related to the growth, development, aging and disease of organisms and is one of the hotspots of life science research today. PCD is a kind of genetic control, autonomous and orderly important cell death that involves the activation, expression, and regulation of a series of genes. In recent years, with the deepening of research in this field, new mechanisms of multiple PCD pathways have been revealed. This article reviews and summarizes the multiple PCD pathways that have been discovered, analyses and compares the morphological characteristics and biomarkers of different types of PCD, and briefly discusses the role of various types of PCD in the diagnosis and treatment of different diseases, especially malignant tumors.
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Apoptosis , Humans , Apoptosis/genetics , Animals , Neoplasms/pathology , Neoplasms/genetics , Neoplasms/metabolism , Signal TransductionABSTRACT
OBJECTIVE: To retrospectively analyze the risk factors for postoperative delirium (POD) after orthopedic surgery in elderly patients and establish an individualized nomogram to predict the risk of POD. METHODS: The data of 1011 patients who underwent orthopedic surgery from January 2019 to January 2022 were retrospectively analyzed. Univariate and multivariate logistic analyses were used to screen for independent risk factors. Stepwise regression was conducted to screen risk factors to construct a nomogram to predict the risk of POD after orthopedic surgery in elderly individuals, and nomogram validation analyses were performed. RESULTS: The logistic regression results showed that age (≥ 75 years old vs. < 75 years old; odds ratio (OR) = 2.889; 95% confidence interval (CI), 1.149, 7.264), sex (male vs. female, OR = 2.368; 95% CI, 1.066, 5.261), and preoperative cognitive impairment (yes vs. no, OR = 13.587; 95% CI, 4.360, 42.338) were independent risk factors for POD in elderly patients who underwent orthopedic surgery (P < 0.05). A nomogram was constructed using 7 risk factors, i.e., age, American Society of Anesthesiologists (ASA) classification, sex, preoperative hemoglobin (Hb), preoperative pulmonary disease, cognitive impairment, and intraoperative infusion volume. The area under the curve (AUC) showed good discrimination (0.867), the slope of the calibration curve was 1.0, and the optimal net benefit of the nomogram from the decision curve analysis (DCA) was 0.01-0.58. CONCLUSION: This study used 7 risk factors to construct a nomogram to predict the risk of POD after major orthopedic surgery in elderly individuals, and the nomogram had good discrimination ability, accuracy, and clinical practicability.
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Purpose: Investigate the efficacy of blood microRNAs (miRNAs) as diagnostic biomarkers for Chronic Obstructive Pulmonary Disease (COPD). Patients and Methods: We conducted a comprehensive search in English and Chinese databases, selecting studies based on predetermined criteria. Diagnostic parameters like summarized sensitivity (SSEN), summarized specificity (SSPE), summarized positive likelihood ratio (SPLR), summarized negative likelihood ratio (SNLR), and diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curves were analyzed using a bivariate model. Each parameter was accompanied by a 95% confidence interval (CI). Results: Eighteen high-quality studies were included. For diagnosing COPD with blood miRNAs, the SSEN was 0.83 (95% CI 0.76-0.89), SSPE 0.76 (95% CI 0.70-0.82), SPLR 3.50 (95% CI 2.66-4.60), SNLR 0.22 (95% CI 0.15-0.33), DOR 15.72 (95% CI 8.58-28.77), and AUC 0.86 (95% CI 0.82-0.88). In acute exacerbations, SSEN was 0.85 (95% CI 0.76-0.91), SSPE 0.80 (95% CI 0.73-0.86), SPLR 4.26 (95% CI 3.05-5.95), SNLR 0.19 (95% CI 0.12-0.30), DOR 22.29 (95% CI 11.47-43.33), and AUC 0.89 (95% CI 0.86-0.91). Conclusion: Blood miRNAs demonstrate significant accuracy in diagnosing COPD, both in general and during acute exacerbations, suggesting their potential as reliable biomarkers.
Subject(s)
Area Under Curve , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive , ROC Curve , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/genetics , Humans , Odds Ratio , MicroRNAs/blood , Biomarkers/blood , Middle Aged , Aged , Genetic Markers , Male , Circulating MicroRNA/blood , Circulating MicroRNA/genetics , Female , Prognosis , Lung/physiopathologyABSTRACT
BACKGROUND: Nurses with a strong professional self-concept tend to exhibit a positive mindset and strong work engagement, delivering high-quality patient care. Although numerous quantitative studies have examined the factors impacting professional self-concept, there remains a limited exploration of these factors from the perspective of nurses themselves. METHODS: This qualitative descriptive study uses the PERMA theory and Social Cognitive Theory as the theoretical framework. Semi-structured interviews were conducted with 15 nurses from six public hospitals in China. The data were analyzed thematically using a combination of inductive and deductive approaches. RESULTS: Nurses' understanding of professional self-concept could be divided into four categories: professional identity, competence, care, and knowledge. Factors influencing nurses' professional self-concept were categorized into eight subthemes in three domains: (1) personal factors, including psychological qualities and attitude towards the nursing profession; (2) occupational-related behavioral factors, including role-oriented behavior and knowledge-oriented behavior; and (3) work environment and external factors, including external evaluation and perceptions of nurses, time allocation, nursing work tasks, work atmosphere, school education, and perceived supports. CONCLUSIONS: This study found that, although nurses had different personal experiences, their perceptions of professional self-concept were similar. Nurses' professional self-concept is a multidimensional concept and involves various factors, such as personality, work-related characteristics, environment, and family. To thrive in a nursing career, nurses must discern the factors that can enhance or hinder their professional self-concept. By identifying and adjusting these factors, personalized support and positive interventions can be tailored to meet nurses' specific needs, which ultimately nurtures their professional development. TRIAL REGISTRATION: This study was registered on December 14, 2022, in the Chinese Clinical Trial Registry (ChiCTR2200066699) as part of our ongoing study.
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Confocal fluorescence imaging of fine structures of the cell membrane is important for understanding their biofunctions but is often neglected due to the lack of an effective method. Herein, we develop new amphiphilic rhodamine fluorescent probe RMGs in combination with basal imaging for this purpose. The probes show high signal-to-noise ratio and brightness and low internalization rate, making them suitable for imaging the fine substructures of the cell membrane. Using the representative probe RMG3, we not only observed the cell pseudopodia and intercellular nanotubes but also monitored the formation of migrasomes in real time. More importantly, in-depth imaging studies on more cell lines revealed for the first time that hepatocellular carcinoma cells secreted much more adherent extracellular vesicles than other cell lines, which might serve as a potential indicator of liver cells. We believe that RMGs may be useful for investigating the fine structures of the cell membrane.
Subject(s)
Cell Membrane , Fluorescent Dyes , Rhodamines , Fluorescent Dyes/chemistry , Rhodamines/chemistry , Humans , Cell Membrane/chemistry , Optical Imaging , Microscopy, Confocal/methods , Surface-Active Agents/chemistryABSTRACT
BACKGROUND/AIM: Cancer-induced bone pain (CIBP) is one of the most common symptoms of bone metastasis of tumor cells. The hypothalamus may play a pivotal role in the regulation of CIBP. However, little is known about the exact mechanisms. MATERIALS AND METHODS: First, we established a CIBP model to explore the relationship among hypothalamic ghrelin, NPY and CIBP. Then, we exogenously administered NPY and NPY receptor antagonists to investigate whether hypothalamic NPY exerted an antinociceptive effect through binding to NPY receptors. Finally, we exogenously administered ghrelin to investigate whether ghrelin alleviated CIBP by inducing the production of hypothalamic NPY through the AMPK-mTOR pathway. Body weight, food intake and behavioral indicators of CIBP were measured every 3 days. Hypothalamic ghrelin, NPY and the AMPK-mTOR pathway were also measured. RESULTS: The expression of hypothalamic ghrelin and NPY was simultaneously decreased in cancer-bearing rats, which was accompanied by CIBP. Intracerebroventricular (i.c.v.) administration of NPY significantly alleviated CIBP in the short term. The antinociceptive effect of NPY was reversed with the i.c.v. administration of the Y1R and Y2R antagonists. The administration of ghrelin activated the AMPK-mTOR pathway and induced hypothalamic NPY production to alleviate CIBP. This effect of ghrelin on NPY and antinociception was reversed with the administration of a GHS-R1α antagonist. CONCLUSION: Ghrelin could induce the production of hypothalamic NPY through the AMPK-mTOR pathway to alleviate CIBP, which can provide a novel therapeutic mechanism for CIBP.