The relationship between medical staff burnout and subjective wellbeing: the chain mediating role of psychological capital and perceived social support.

Background: Medical staff play a crucial role in delivering healthcare services, especially during epidemics of infectious diseases such as coronavirus disease 2019 (COVID-19). However, there is a growing issue of burnout and low wellbeing among this group. While it is widely recognized that burnout has a negative impact on subjective wellbeing, the exact relationship between the two is not yet completely understood. The purpose of this study is to explore the chain mediating role of psychological capital and perceived social support between burnout and subjective wellbeing among medical staff. Methods: Using the convenient sampling method, 604 medical staff were selected for a cross-sectional study. All participants completed a self-report questionnaire that collected demographic information, as well as data from the Maslach Burnout Inventory-Human Services Survey, General Wellbeing Schedule, Psychological Capital Questionnaire, and Perceived Social Support Scale. SPSS 27.0 and SPSS PROCESS macro were used for data analysis. Results: There was a significant correlation between burnout, psychological capital, perceived social support, and subjective wellbeing (p < 0.01). Burnout not only has a direct negative impact on the subjective wellbeing of medical staff (effect: -0.2045; Bootstrap 95%CI: -0.2506, -0.1583), but also exerts an indirect influence on subjective wellbeing through three pathways: the independent mediating effect of psychological capital (effect: -0.0481; Bootstrap 95%CI: -0.0876, -0.0109), the independent mediating effect of perceived social support (effect: -0.0092; Bootstrap 95%CI: -0.0203, -0.0003), and the chained mediating effect of psychological capital and perceived social support (effect: -0.0092; Bootstrap 95%CI: -0.0183, -0.0019). Conclusion: High burnout in medical staff can impair the level of psychological capital, leading to diminished perceived social support and ultimately reduced subjective wellbeing. The findings of this study contribute to understanding the potential pathways between burnout and subjective wellbeing and provide preliminary data support for developing strategies to improve the mental health of medical staff.

Effect of breathing exercises on patients with interstitial lung disease: A systematic review and meta-analysis.

PURPOSE: This study was designed to synthesize the efficacy and safety of breathing exercises in interstitial lung disease (ILD) patients by reviewing the literature and comparing the impact of different control group types, ILD subtypes, breathing exercise action modes or methods, and intervention durations on clinical efficacy. METHODS: Systematic searches were conducted across 9 electronic databases, including PubMed, to retrieve English and Chinese studies reporting on ILD patients from inception to February 12, 2024. Study selection and data extraction were independently conducted by two researchers. The quality of the included studies was assessed using the Cochrane risk of bias tool. The data were analysed using RevMan 5.4 and STATA 17.0 software. RESULTS: The search identified 25 studies. Compared to the control group, the breathing exercise group exhibited significantly improved lung function (FVC%pred: MD = 3.46, 95%CI = 1.04 to 5.88; DLCO%pred: MD = 3.20, 95% CI = 2.91 to 3.48), dyspnoea (MRC or mMRC scale: MD = - 0.50, 95%CI = - 0.77 to - 0.22), exercise capacity (6MWD: MD = 32.65, 95% CI = 14.77 to 50.53), and HRQoL (SGRQ: MD = - 6.53, 95% CI = - 8.72 to - 4.34) in ILD patients. According to the subgroup analysis, significant improvements consistent with the overall results were observed in the control group with usual treatment. Compared with the control group, breathing exercises had varying degrees of improvement in the mixed diagnostic group, known-cause group, and fibrotic group of ILD patients; breathing exercises alone significantly improved DLCO%pred, MRC (or mMRC), and SGRQ; and the improvement in breathing exercises as part of pulmonary rehabilitation (PR) was more notable. Different durations of breathing exercise could promote the efficacy of different aspects of treatment for ILD patients. CONCLUSIONS: Compared with usual treatment, breathing exercises can improve lung function, exercise capacity, and HRQoL in ILD patients, particularly without high requirements for intervention duration. The efficacy of breathing exercises varies for different ILD subtypes, and incorporating breathing exercises as part of PR can be more beneficial for ILD patients. No studies have shown significant risks for ILD patients engaging in breathing exercises.

Oncogenic lncRNA MALAT-1 recruits E2F1 to upregulate RAD51 expression and thus promotes cell autophagy and tumor growth in non-small cell lung cancer.

INTRODUCTION: LncRNA MALAT-1 expression is involved in regulating activities of non-small-cell lung cancer (NSCLC) cells. This study aimed to investigate the effects of lncRNA MALAT-1 on chemosensitivity of NSCLC cells by regulating autophagy. METHODS: We first validated the expression of lncRNA MALAT-1 in NSCLC cell lines. NSCLC cell lines with high lncRNA MALAT-1 expression were exposed to doxorubicin (DOX) to assess chemosensitivity. Further LncMAP database retrieval and ChIP, RIP and luciferase activity assays were conducted to explore interplay between lncRNA MALAT-1, RAD51, and E2F1. Immunofluorescence staining was performed to evaluate formation of autophagosomes in NSCLC cells. Ectopic expression and knockdown methods were used for in vitro mechanism experiments and in vivo substantiation. RESULTS: LncRNA MALAT-1 was overexpressed in NSCLC cells, and could promote NSCLC cell autophagy and inhibit its chemosensitivity. In vitro cell mechanism verification experiments showed that lncRNA MALAT-1 could recruit transcription factor E2F1 to bind to the promoter of RAD51, so as to promote the transcriptional expression of RAD51. In addition, cell function experiments in vitro showed that ectopically expressed lncRNA MALAT-1 promoted NSCLC cell autophagy and inhibited its chemosensitivity, while RAD51 knockdown negated its effect. Finally, in vivo animal experiments confirmed that lncRNA MALAT-1 silencing could impede the tumor growth. CONCLUSIONS: Taken together, this study revealed that silencing lncRNA MALAT-1 enhanced chemosensitivity of NSCLC cells by promoting autophagy, highlighting a feasible approach to prevent chemoresistance in NSCLC treatment.

Downregulation of miR-23b by transcription factor c-Myc alleviates ischemic brain injury by upregulating Nrf2.

Ischemic brain injury (IBI) is a common acute cerebral vessel disease that occurs secondary to blockage in arteries, mainly characterized by insufficient blood supply to the brain. The transcription factor c-Myc in IBI continues to be implicated in numerous studies. This study was conducted with emphasis placed on the underlying mechanism of c-Myc in IBI. Clinical samples were collected from IBI patients. Middle cerebral artery occlusion (MCAO) was induced in mice by inserting a suture from the external carotid artery to the anterior cerebral artery through the internal carotid artery to mechanically block the blood supply at the origin of the middle cerebral artery, and cortical neurons from mice were exposed to oxygen glucose deprivation (OGD) conditions for IBI model in vitro construction. RT-qPCR was performed to determine microRNA-23b (miR-23b) expression. TUNEL staining and Western blot analysis was conducted to detect apoptosis. The regulatory relationship was analyzed by dual-luciferase reporter gene assay. After loss- and gain-of-function assays, triphenyltetrazolium chloride staining was carried out to detect the area of cerebral infarction, after which the spatial memory in mice was evaluated with Morris water maze test. As per our findings, miR-23b was upregulated in the serum of IBI patients and OGD-treated murine primary neurons. Silencing of miR-23b resulted in reduced OGD-induced neuronal apoptosis. miR-23b inversely targeted nuclear factor erythroid 2-related factor 2 (Nrf2) and c-Myc negatively regulated miR-23b expression. Overexpression of c-Myc and inhibition of miR-23b led to reduced neurological scores of infarction area, neuronal apoptosis, shortened platform arrival time and significantly increased the time spent on the platform quadrant and the times of crossing the platform in vivo. Collectively, downregulated miR-23b by c-Myc might alleviate IBI by upregulating Nrf2.

Role of HDAC6 inhibition in sepsis-induced acute respiratory distress syndrome (Review).

Acute respiratory distress syndrome (ARDS) induced by sepsis contributes remarkably to the high mortality rate observed in intensive care units, largely due to a lack of effective drug therapies. Histone deacetylase 6 (HDAC6) is a class-IIb deacetylase that modulates non-nuclear protein functions via deacetylation and ubiquitination. Importantly, HDAC6 has been shown to exert anti-cancer, anti-neurodegeneration, and immunological effects, and several HDAC6 inhibitors have now entered clinical trials. It has also been recently shown to modulate inflammation, and HDAC6 inhibition has been demonstrated to markedly suppress experimental sepsis. The present review summarizes the role of HDAC6 in sepsis-induced inflammation and endothelial barrier dysfunction in recent years. It is proposed that HDAC6 inhibition predominantly ameliorates sepsis-induced ARDS by directly attenuating inflammation, which modulates the innate and adaptive immunity, transcription of pro-inflammatory genes, and protects endothelial barrier function. HDAC6 inhibition protects against sepsis-induced ARDS, thereby making HDAC6 a promising therapeutic target. However, HDAC inhibition may be associated with adverse effects on the embryo sac and oocyte, necessitating further studies.

circ_001504 promotes the development of renal cell carcinoma by sponging microRNA-149 to increase NUCB2.

Renal cell carcinoma (RCC) accounts for over 90% of primary renal tumors in adults. Although treatment approaches have steadily improved over the years, the prognosis outcome remains poor. With the aim of developing novel targets for RCC treatment, we explored the role of the circular RNA (circRNA) circ_001504 in the progression of RCC. We initially detected the expression of circ_001504 and microRNA (miRNA)-149 in RCC tissues and cells. RT-qPCR results showed that circ_001504 was highly expressed in RCC tissues, whereas miR-149 was poorly expressed. Interestingly, downregulation of circ_001504 suppressed malignant phenotypes in RCC cells, and upregulation of miR-149 exerted a similar effect. Bioinformatics analysis suggested potential binding sites between circ_001504 and miR-149, verified by a dual-luciferase reporter gene assay. Next, we identified nucleobindin 2 (NUCB2), a calcium-binding protein, as a target gene of miR-149. Furthermore, our data suggested that circ_001504 might serve as a competing endogenous RNA of miR-149, serving to elevate the expression of NUCB2. The silencing of circ_001504 resulted in decreased NUCB2 expression, which could be reversed by miR-149 inhibition. In addition, in vivo experiments demonstrated that circ_001504 depletion could suppress tumor growth in an established mouse RCC model. Collectively, reduced expression of circ_001504 lowered NUCB2 expression by sponging miR-149, thereby attenuating RCC progression, providing insight into circ_001504/miR-149/NUCB2 feedback loop into RCC treatment.

Heavy shackles: The experience of symptom distress and coping behaviors of Chinese patients with chronic obstructive pulmonary disease.

People with chronic obstructive pulmonary disease exhibit various symptoms, some of which can negatively affect their daily lives. Thus, they may adopt coping behaviors to improve their condition. This qualitative descriptive study investigated symptom distress and coping behaviors among 19 Chinese patients with chronic obstructive pulmonary disease using individual, semi-structured, face-to-face interviews. We identified the following three themes for the patients' symptom distress: distressing symptoms, inescapable imprisonment, and no choice other than being a burden to the family. The various coping behaviors of the patients were categorized into the following three themes: struggle during the medical treatment process, careful maintenance of daily life, and coping with negative emotions. Although all patients experienced physical and psychological distress, they displayed a strong desire to improve their lives and health. By recognizing the patients' symptom distress and coping behaviors, tailored interventions could be developed to improve the quality of their lives.

miR-21 regulates immunosuppression mediated by myeloid-derived suppressor cells by impairing RUNX1-YAP interaction in lung cancer.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity and contribute to immunosuppressive microenvironment during tumor development including lung cancer. Accumulating evidence shows microRNAs (miRNAs) affect tumor-expanded MDSC accumulation and function in tumor microenvironment and favor solid tumor growth. Herein, we aim to characterize the role of miR-21 in regulating the accumulation and activity of MDSCs in lung cancer. METHODS: The proportions of MDSCs, T helper cells (Th), and cytotoxic T lymphocytes (CTL) were evaluated by flow cytometric analyses of peripheral blood and tumor tissues collected from Lewis lung-cancer-bearing mice. T cell proliferation assay was performed in CD4+ or CD8+ T cells cocultured with MDSCs. MDSC apoptosis was examined by flow cytometric analysis. The levels of IL-10, TGF-ß, and GM-CSF in mouse serum were determined by ELISA. miR-21 targeting RUNX1 and RUNX1 interaction with YAP were evaluated by RIP, dual-luciferase reporter gene, and ChIP assays. RESULTS: MiR-21 inhibition by its antagomir reduced the proportion of MDSCs, increased the proportion of Th and CTL in peripheral blood and tumor tissues of Lewis lung-cancer-bearing mice, protected Th and CTL from the suppression of MDSCs, increased apoptosis of MDSCs, but reduced IL-10, TGF-ß and GM-CSF levels in mouse serum. RUNX1 could transcriptionally inhibit the YAP expression, whereas miR-21 targeting RUNX1 led to elevated YAP expression levels. Mechanistic investigation showed that miR-21 maintained MDSC accumulation in tumor microenvironment and promoted immunosuppressive ability of MDSCs in Lewis lung-cancer-bearing mice by down-regulating RUNX1and up-regulating YAP. CONCLUSIONS: Taken together, the study provides evidence that targeting miR-21 in MDSCs may be developed as an immunotherapeutic approach to combat lung cancer development.

Mechanism of deep eutectic solvents enhancing catalytic function of cytochrome P450 enzymes in biosynthesis and organic synthesis.

Indigo is an insoluble blue dye, which generates serious pollution in its production process. Increasing focus has come to the biosynthesis of indigo that are more environment-preserved and high-efficient. Hence, this study was designed to explore the specific role of various deep eutectic solvents (DESs) on cytochromeP45-BM-3 catalyzing indole to produce indigo. DESs were synthesized by heating and stirring. The structure of the solvent was analyzed by nuclear magnetic resonance (NMR) and fourier transform infrared spectrum (FT-IR), and the relationship between the viscosity, density and refractive index of the solvent, and the water content of the solvent was examined. Circular dichroism spectrometer was used to detect the tertiary structure of the enzyme protein. The effect of solvent type, concentration, pH, temperature, and water content on the catalytic activity and stability of P450 BM-3 was measured using an ultraviolet spectrophotometer. A new solvent biphasic system was established using DESs and buffers, and indigo was prepared using recombinant E. coli-biocatalyzed indole. DESs were low-melting eutectics formed by molecules interaction of components through hydrogen bonding. The physical properties of DESs such as density, viscosity, and refractive index varied with water content and temperature of the solvent. The pH, water content, and temperature of DESs were positively correlated with the catalytic activity of P450 BM-3. To sum up, DESs can improve the catalytic activity and thermal stability of P450 BM-3. Indigo can be efficiently prepared using the DESs-buffer biphasic system.

The Possible Pathogenesis of Idiopathic Pulmonary Fibrosis considering MUC5B.

BACKGROUND: Overexpression of the MUC5B protein is associated with idiopathic pulmonary fibrosis (IPF), but little information is available regarding the pathogenic effects and regulatory mechanisms of overexpressed MUC5B in IPF. MAIN BODY: The overexpression of MUC5B in terminal bronchi and honeycomb cysts produces mucosal host defensive dysfunction in the distal airway which may play an important role in the development of IPF. This review addresses the possible association of overexpression of MUC5B, with MUC5B promoter polymorphism, MUC5B gene epigenetic changes, effects of some transcriptional factors, and inflammatory mediators in IPF. In addition, the associated signaling pathways which may influence the expression of MUC5B are also discussed. CONCLUSION: This work has important implications for further exploration of the mechanisms of overexpression of MUC5B in IPF, and future personalized treatment.

A novel circular RNA hsa_circ_0020123 exerts oncogenic properties through suppression of miR-144 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide, while circulatory. Circular RNAs (circRNAs) are found to play important roles in cancer initiation and development. Herein, a novel functional circRNA hsa_circ_0020123 had been identified in NSCLC progression in this study, and elevated hsa_circ_0020123 expression could be observed in cancer tissues compared with that in matched normal lung tissues. Moreover, up-regulation of hsa_circ_0020123 was recognized to be closely associated with a poor differentiation degree, lymph node metastasis, a high TNM stage and dismal prognosis for NSCLC patients. Typically, knockdown of hsa_circ_0020123 could inhibit the NSCLC growth and metastasis both in vitro and in vivo, which could be reversed by the hsa_circ_0020123 overexpression. Importantly, miR-144 was identified as the hsa_circ_0020123-associated miRNA through performing RNA in vivo precipitation (RIP) in NSCLC cells using a biotin-labeled hsa_circ_0020123 probe. Besides, our results suggested that, miR-144 suppression had determined the oncogenic properties mediated by hsa_circ_0020123. In addition, hsa_circ_0020123 could upregulate ZEB1 and EZH2 through competitively binding with miR-144. Finally, the administration of hsa_circ_0020123 siRNA could suppress the growth and metastasis in NSCLC-bearing mice in vivo. In conclusion, the hsa_circ_0020123-miR-144-ZEB1/EZH2 axis is critical for NSCLC progression, which indicates that hsa_circ_0020123 is a potential target for NSCLC treatment.

Fatal pulmonary infection with respiratory syncytial virus in an immunocompromised adult patient: A case report.

RATIONALE: Respiratory syncytial virus (RSV) is a single-stranded negative-sense RNA virus that belongs to the family of paramyxoviruses. RSV is the most common pathogen that causes acute lower respiratory tract infection in infants and young children. However, its incidence in immunocompromised adults remains unclear. In the present study, we report an adult patient with chronic nephropathy, who received long-term immunosuppressants and died of rapid respiratory failure due to RSV infection. PATIENT CONCERNS: A 54-year-old male patient with chronic nephropathy, who received long-term immunosuppressants, was admitted to the Department of Respiratory Medicine due to the symptoms of fever, cough, expectoration, and dyspnea. DIAGNOSES: Pulmonary radiology revealed multiple bilateral ground-glass opacity. Laboratory tests revealed elevated inflammation indicators, implying infection with bacteria, viruses, and/or fungi. Furthermore, the patient was positive for RSV antibodies, without positive results for other pathogens. Moreover, the patient was immunocompromised due to the long-term use of corticosteroids and immunosuppressants, as evidenced by decreased total IgG levels and reduced CD4 and CD8 T-lymphocyte counts. INTERVENTIONS AND OUTCOME: Despite the intensive anti-infection treatment and respiratory support, the patient developed rapid progression, and subsequently died of respiratory failure. LESSONS: RSV infection should be fully considered in adults who are immunocompromised or have underlying diseases, such as nephropathy patients receiving long-term immunosuppressants, especially in the presence of respiratory symptoms and computed tomography (CT) chest findings of diffuse ground-glass opacities.

Effect of SLC34A2 gene mutation on extracellular phosphorus transport in PAM alveolar epithelial cells.

A mutation in the IIb sodium phosphate transporter SLC34A2 gene has recently been described in pulmonary alveolar microlithiasis (PAM) patients. Experiments in this study were aimed at confirming the role of the gene product in PAM by comparing phosphorylated products in extracellular fluid of alveolar epithelial cells overexpressing the SLC34A2 gene or its mutated version. Eukaryotic expression vectors were constructed and transfected into A549 human alveolar epithelial cells. There were three groups of cells including those transfected with empty vector plasmid pcDNA3.1(+) (plasmid control group), those transfected with normal SLC34A2 gene expressed from pcDNA3.1 (normal control group), and those transfected with a version of the PAM SLC34A2 gene linked to the pcDNA3.1(+) (PAM group). Transfection efficiencies were detected by reverse transcription-polymerase chain reaction (RT-PCR). At 48 h after transfection, the concentration of inorganic phosphorus in the culture medium was detected using an automatic biochemical analyzer. Our results showed the concentration of inorganic phosphorus in the supernatant of the normal control group was significantly lower than that in the plasmid control and PAM groups (P<0.01), and the concentration in the PAM group was significantly lower than that in the plasmid control group (P<0.01). Based on our findings it is possible that the SLC34A2 gene mutation is the cause of the pathogenic changes observed in PAM patients, given that the function of the phosphate transporter seems to be affected and it is conceivable that it would lead to extracellular fluid alterations in vivo.