Rationale For the high prevalence of frail in patients with chronic obstructive pulmonary disease (COPD), further study should explore an in-depth understanding of the relationship between frailty and prognosis of COPD. Objective To determine the correlation between frailty and risk of acute exacerbation, hospitalizations, and mortality in older patients with stable COPD. Participants and Methods Consecutive older adults (≥65) diagnosed with stable COPD from January 2018 to July 2019, with an average follow-up of 546 days (N = 309). Frailty was defined by the Fried frailty phenotype. Poisson regression was performed to assess the influence of frailty on the incidence of acute exacerbations of COPD (AECOPD) and all-cause hospitalizations in a year. Cox regression was performed to evaluate the effect of frailty on all-cause mortality in patients with stable COPD. Results The prevalence of frailty was 49.8%. The most common phenotypic characteristics were weakness (99.4%) followed by slowness (92.9%). After adjustment, frailty increased the incidence of AECOPD (IRR = 1.75, 95% CI: 1.09–2.82) and all-cause hospitalizations (IRR = 1.39, 95% CI 1.04–1.87) within a year. Slowness was associated with AECOPD (IRR = 1.77, 95% CI: 1.03–3.03), and weakness was associated with increased all-cause hospitalizations (IRR = 1.53, 95% CI: 1.04–2.25). The all-cause mortality risk was more than twofold higher in frail patients (HR = 2.54, 95% CI: 1.01–6.36) than non-frail patients. Low physical activity (HR = 2.66, 95% CI: 1.17–6.05) and weight loss (HR = 2.15, 95% CI: 1.02–4.51) were significantly associated with increased all-cause mortality in patients with COPD. Conclusion Frailty increased the incidence of acute exacerbation and hospitalization, as well as increased mortality in older patients with stable COPD. This knowledge will help physicians identify high-risk groups with COPD and frailty who may benefit from targeted interventions to prevent disease progression.

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Background Frail patients with chronic obstructive pulmonary disease (COPD) face a higher risk of adverse outcomes, but there is no clear consensus on which frailty measures are most suitable for COPD patients. Herein we evaluated the ability of frailty measurements in predicting 1-year acute exacerbation, hospitalization, and mortality in older patients with COPD. Methods A total of 302 patients [median age: 86 years (IQR: 80–90), 22.2% female] were admitted to the Department of Geriatric Medicine were prospectively enrolled in this study. Frailty status was assessed using the Fried Frailty Phenotype (FFP), Clinical Frailty Scale (CFS), Frailty Index of Accumulative Deficits (FI-CD), and Short Physical Performance Battery (SPPB). Cox proportional hazard regression and Poisson regression were used to evaluating the association of the adverse outcomes with frailty as assessed using the four instruments. The discrimination accuracy of these tools in predicting the 1-year all-cause mortality was also compared. Results Prevalence of frailty ranged from 51% (using FFP) to 64.2% (using CFS). The four frail instruments were associated with 1-year mortality. After an average follow-up time of 2.18 years (IQR: 1.56–2.62 years), frailty as defined by four instruments (except for FI-CD), was associated with death [FFP: Hazard ratio (HR) = 3.11, 95% confidence interval (CI) 1.30–7.44; CFS: HR = 3.68, 95% CI 1.03–13.16; SPPB: HR = 3.74, 95% CI 1.39–10.06). Frailty was also associated with acute exacerbation (using FFP) and hospitalization (using FFP, CFS, and FI-CD). Frail showed a moderate predictive ability [area under the curve ranging (AUC) 0.70–0.80] and a high negative predictive value (0.98–0.99) for 1-year mortality. Conclusions With the four different frailty assessment tools, frailty was associated with poor prognosis in older patients with stable COPD. The FFP, CFS, FI-CD, and SPPB instruments showed similar performance in predicting 1-year mortality.

ABSTRACT. The role of estrogen in inducing chemoresistanceis not yet fully understood. The objective of this study was to observe the relationship between estrogen levels and cellular response to chemotherapeutic drugs in non-small cell lung cancer (NSCLC) and to reveal the potential mechanisms involved. Cell viability was analyzed after pre-treating NSCLC cells with different levels of estrogen (E2), followed by treatment with an anti-tumor drug for 48 h. The roles of various estrogen receptors (ERs) were examined in vitro by blocking the activity of each ER individually. The ER pathway was further confirmed in NSCLC tissues. It was found that 10-1000 nM E2 resulted in a decreased cellular response to DDP in H1650 cells compared to the use of cisplatin alone (P < 0.05). However, this result was not demonstrated in H1299 cells, which lack p53. Both ERa and ERb were associated with E2-induced cisplatin chemoresistance, though they had opposite functions. p53 expression did not correlate with the expression of ERa or ERb individually. However, a statistically significant correlation between p53 expression and ERa to ERb mRNA ratio was observed (P < 0.001, R = -0.676). These findings suggest that E2-induced DDP chemoresistance depends on the balance between ERa and ERb expression and the p53 pathway.

Background: With the large-scale production and application of amorphous silica nanoparticles (aSiNPs), it’s the adverse health effects that are more worthy of our attention. Our previous research has demonstrated for the first time that aSiNPs induced cytokinesis failure, which resulted in abnormally high incidences of multinucleation in vitro, but the underlying mechanisms remain unknown. Therefore, the purpose of this study was firstly to explore whether aSiNPs induced multinucleation in vivo, and secondly to investigate the underlying mechanism of how aSiNPs caused abnormal cytokinesis and multinucleation.Methods: Male ICR mice with intratracheal instillation of aSiNPs were used as an experimental model in vivo. Human hepatic cell line (L-02) was introduced for further mechanism study. Results: In vivo, histopathological results showed that the rate of multinucleation was significantly increased in liver and lung tissue after aSiNPs treatment. In vitro, immunofluorescence results manifested that aSiNPs directly caused microfilaments agglomeration. Following mechanistic studies indicated that aSiNPs not only induced excessive ROS and down-regulation of the PI3k 110β/Aurora B pathway, but also inhibited the expression of centralspindlin subunits MKLP1 and CYK4 as well as downstream cytokines regulation related proteins Ect2, Cep55, CHMP2A and RhoA. Meanwhile, the particles caused abnormal co-localization of the key mitotic regulatory kinase Aurora B and the centralspindlin complex, which resulted in incomplete cytokinesis. To further clarify the role of PI3K inhibition and excessive ROS in cytokinesis failure induced by aSiNPs, PI3K activator IGF and ROS inhibitors NAC were selected. In the aSiNPs treated group, IGF increased the phosphorylation level of Aurora B and improved the relative ratio of the centralspindlin cluster; and NAC reduced the ratio of multinucleation, alleviated the PI3k 110β/Aurora B pathway inhibition, and then increased the expression of MKLP1, CYK4 and cytokinesis-related proteins, whilst it simultaneously directly restored the clustering of the centralspindlin.Conclusion: This study demonstrated that aSiNPs led to multinucleation formation both in vivo and in vitro. aSiNPs exposure caused microfilaments agglomeration and inhibited the PI3k 110β / Aurora B pathway through excessive ROS, which then hindered the centralspindlin cluster as well as restrained the expression of centralspindlin subunits and cytokinesis-related proteins, which ultimately created cytokinesis failure and the formation of multinucleation.