The aim of this study was to investigate the relationship between lymphocyte to monocyte ratio (LMR) and the severity of coronary artery disease (CAD) by using Gensini score.A total of 199 patients, who had undergone coronary angiography, were included in the study and retrospectively analyzed. Among them, 49 patients who had normal coronary arteries were selected as the control group. Patients with CAD were divided into 2 groups, those with low Gensini score (≤40) and those with high Gensini score (≥40).Our results showed that LMR in the severe atherosclerosis group was significantly lower than those of the mild atherosclerosis group and the control group. There was a closely significant correlation between the Gensini score and LMR (r = −0.362, P < .001). Furthermore, multivariate logistic regression analysis demonstrated that LMR (odds ratio, 0.715; 95% confidence interval [CI], 0.551–0.927; P = .012) was independent predictors of severe atherosclerosis. Using an optimal LMR cut-off value of 5.06, LMR predicted severe atherosclerosis with a sensitivity of 57.1% and specificity of 69.7% (area under curve = 0.634; 95% CI, 0.545–0.724; P = .005). Then patients with CAD group was divided into 2 groups according to the LMR value of 5.06. Patients with LMR ≤ 5.06 had worse prognosis, with a higher rate of cardiovascular events during up to 1 year follow-up.Our study demonstrated that LMR was independently and positively associated with the severity of coronary atherosclerosis, providing a new insight in the application of inflammation index evaluating the severity of CAD. And LMR may be a useful predictor of future cardiovascular events in patients with CAD.
Esophageal cancer related gene-4 (Ecrg4) has been shown to be a tumor suppressor in many organs. Exosomes are naturally secreted nanosized particles that carry signal molecules including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) among others. Upon internalization, exosomes unload their cargos that in turn modulate the biology of the recipient cells. Mounting evidence has shown that exosomal miRNAs are functional. However, reports that exosomes carry functional mRNAs remain scarce. We found that serum exosomes contain ECRG4 open reading frame. To simulate serum exosomal ECRG4, stable cell line expressing ECRG4 was created, from which exosomes were isolated and characterized, and the internalization and the resulting biological effects of exosomal ECRG4 were evaluated. Results showed that serum exosomes contain higher levels of ECRG4 mRNA in healthy individuals than their cancer counterparts. Exosomal ECRG4 can be internalized and unload the encapsulated ECRG4 into recipient cells, which subsequently suppressed cell proliferation in vitro, and inhibited tumor growth in a xenograft mouse model. Mechanistically, ECRG4-containing exosomes, when internalized, suppressed the expression of genes commonly implicated in inflammation, cell proliferation, and angiogenesis. Given that exosome is an ideal vehicle for therapeutics delivery and that ECRG4 is a tumor suppressor gene, the exosomal ECRG4 can be exploited as a formulation for cancer gene therapy.
Aim The aim of this work was to examine the mediating role of transition shock on the relationships between resilience, social support, work environment, and turnover intention in newly graduated nurses. Background Reports assessing the associations between nurses' resilience, social support, work environment, and turnover intention, both directly and through the mediating effect of transition shock, are scarce. Methods This was a cross‐sectional study, which recruited 361 Chinese newly graduated nurses with <1 year of work experience. Results Resilience, social support, and work environment directly and significantly predicted transition shock (direct effect −0.158 to −0.350, p < .01). Resilience, work environment, and transition shock directly and significantly affected turnover intention (direct effect −0.118 to −0.257, p < .05). Transition shock mediated the relationships between resilience, social support, work environment, and turnover intention indirectly and significantly (indirect effect −0.019 to −0.041, p < .05). Conclusions The results suggest that nurse managers could enhance resilience and social support and establish a positive work environment to reduce transition shock and turnover intention. Implications for Nursing Management Nurse managers could continuously provide resilience training and develop a supportive workplace climate for newly graduated nurses to facilitate smooth transition into clinical practice, could alleviate their transition shock and turnover intention.
Background/Aims: Mutations in the Ras/Raf/MEK/ERK pathway are detected in 50% of colorectal cancer cases and play a crucial role in cancer development and progression. Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma and inhibits the cell viability of other types of cancer cells. Methods: HCT116 colorectal cancer cells were treated with cobimetinib, and MTT assay, colony formation assay, and flow cytometry were used to evaluate cell viability, cell cycle, and apoptosis, respectively. The expression of genes associated with the cell cycle and apoptosis were evaluated by quantitative real-time PCR and western blotting. To explore use of cobimetinib in colorectal cancer treatment and further understand its mechanisms, RNA-seq technology was used to identify differentially expressed genes (DEGs) between cobimetinib-treated and untreated HCT116 cells. Furthermore, we compared these DEGs with Gene Expression Omnibus data from colorectal cancer tissues and normal colonic epithelial tissues. Results: We found that cobimetinib not only inhibited cell proliferation but also induced G1 phase arrest and apoptosis in HCT116 colorectal cancer cells, suggesting that cobimetinib may useful in colorectal cancer therapy. After cobimetinib treatment, 3,495 DEGs were obtained, including 2,089 upregulated genes and 1,406 downregulated genes, and most of these DEGs were enriched in the cell cycle, DNA replication, and DNA damage repair pathways. Our results revealed that some genes with high expression in colorectal cancer tissues were downregulated by cobimetinib in HCT116 cells, including CCND1, E2F1, CDC25C, CCNE2, MYC, and PCNA. These genes have vital roles in DNA replication and the cell cycle. Furthermore, genes with low expression in colorectal cancer tissues were upregulated by cobimetinib, including PRKCA, PI3K, RTK, and PKC. Based on our results, the PKC and PI3K pathways were activated after cobimetinib treatment, and inhibition of these two pathways can increase the cytotoxicity of cobimetinib in HCT116 cells. Notably, cobimetinib appeared to enhance the efficacy of 5-fluorouracil (5-FU) by decreasing TYMS expression, high expression of which is responsible for 5-FU resistance in colorectal cancer. Conclusions: Our results suggest the potential use of cobimetinib in colorectal cancer therapy.
Background Data on professional quality of life in newly graduated nurses are scarce. This study aimed to describe the levels of professional quality of life, and to explore the relationships of transition shock, empathy, resilience and coping strategies with professional quality of life in newly graduated nurses. Methods This was a cross-sectional study, which used a two-stage sampling method to recruit 393 newly graduated nurses in Sichuan province of China. Multiple regression analysis was used to explore the effects of transition shock, empathy, resilience and coping strategies on professional quality of life. Data were collected using standardized scales. Results The prevalence of average levels of compassion satisfaction, burnout and secondary traumatic stress in newly graduated nurses were 80.2, 38.2 and 57.5%, respectively. Transition shock was a significant negative predictor, and empathy, resilience and adaptive coping were significant positive predictors for compassion satisfaction. Transition shock and passive coping were significant positive predictors, and empathy was a significant negative predictor for burnout and secondary traumatic stress. Resilience and adaptive coping contributed to burnout significantly and negatively. Conclusion Higher transition shock and lower empathy cause lower compassion satisfaction and higher compassion fatigue. More resilience and adaptive coping cause more compassion satisfaction and less burnout. More passive coping contributes to higher compassion fatigue. Strategies such as transition or preceptorship programmes, and empathy, resilience and coping training are effective methods to reduce transition shock, facilitate empathy, resilience and coping, and consequently, enhance professional quality of life in newly graduated nurses.
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