Background and objectiveSerum D-dimer is elevated in respiratory disease. The objective of our study was to investigate the effect of D-dimer on in-hospital and 1-year mortality after acute exacerbations of chronic obstructive pulmonary disease (AECOPD).MethodsUpon admission, we measured 343 AECOPD patients’ serum D-dimer levels and arterial blood gas analysis, and recorded their clinical characteristics. The level of D-dimer that discriminated survivors and non-survivors was determined using a receiver operator curve (ROC). The risk factors for in-hospital mortality were identified through univariate analysis and multiple logistic regression analyses. To evaluate the predictive role of D-dimer for 1-year mortality, univariate and multivariate Cox regression analyses were performed.ResultsIn all, 28 patients died, and 315 patients survived in the in-hospital period. The group of dead patients had lower pH levels (7.35±0.11 vs 7.39±0.05, P<0.0001), higher D-dimer, arterial carbon dioxide tension (PaCO2), C-reactive protein (CRP), and blood urea nitrogen (BUN) levels (D-dimer 2,244.9±2,310.7 vs 768.2±1,078.4 µg/L, P<0.0001; PaCO2: 58.8±29.7 vs 46.1±27.0 mmHg, P=0.018; CRP: 81.5±66, P=0.001; BUN: 10.20±6.87 vs 6.15±3.15 mmol/L, P<0.0001), and lower hemoglobin levels (118.6±29.4 vs 128.3±18.2 g/L, P=0.001). The areas under the ROC curves of D-dimer for in-hospital death were 0.748 (95% confidence interval (CI): 0.641–0.854). D-dimer ≥985 ng/L was a risk factor for in-hospital mortality (relative risk =6.51; 95% CI 3.06–13.83). Multivariate logistic regression analysis also showed that D-dimer ≥985 ng/L and heart failure were independent risk factors for in-hospital mortality. Both univariate and multivariate Cox regression analyses showed that D-dimer ≥985 ng/L was an independent risk factor for 1-year death (hazard ratio (HR) 3.48, 95% CI 2.07–5.85 for the univariate analysis; and HR 1.96, 95% CI 1.05–3.65 for the multivariate analysis).ConclusionD-dimer was a strong and independent risk factor for in-hospital and 1-year death for AECOPD patients.

Background and objective: The association between N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations and in-hospital and 1-year mortality in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients is largely unknown. Our objective was to explore the usefulness of NT-proBNP concentrations in AECOPD patients as a prognostic marker for in-hospital and 1-year mortality. Methods: NT-proBNP levels were measured in patients upon admission and laboratory and clinical data were also recorded. The cut-point for the NT-proBNP concentration level for inhospital death was obtained using the receiver operating characteristic (ROC) curve. Univariate and multivariate logistic regression and Cox regression were used in the analyses of factors of inhospital and 1-year mortality. Results: A total of 429 patients were enrolled. Twenty-nine patients died during hospitalization and 59 patients died during the 1-year follow-up. Patients who died in-hospital compared with those in-hospital survivors were older (80.14±6.56 vs 75.93±9.45 years, p=0.003), had a higher percentage of congestive heart failure (65.52% vs 33.75%, p<0.001), had higher NT-proBNP levels (5767.00 (1372.50-12,887.00) vs 236.25 (80.03-1074.75) ng/L, p<0.001), higher neutrophil counts (10.52±5.82 vs 7.70±4.31, p=0.016), higher D-dimer levels (1231.62±1921.29 vs 490.11±830.19, p=0.048), higher blood urea nitrogen levels (9.91±6.33 vs 6.51±4.01 mmol/L, p=0.001), a lower body mass index (19.49±3.57 vs 22.19±4.76, p=0.003), and higher hemoglobin levels (122.34 ±25.36 vs 130.57±19.63, p=0.034). The area under the ROC curve (AUC) for NT-proBNP concentration was 0.88 (95% confidence interval [CI], 0.84-0.93). NT-proBNP concentrations ≥551.35 ng/L were an independent prognostic factor for both in-hospital and 1-year mortality after adjustment for relative risk (RR) (RR=29.54, 95% CI 3.04-286.63, p=0.004 for the multivariate logistic regression analysis) and hazard ratio (HR) (HR=4.47, 95% CI, 2.38-8.41, p <0.001 for the multivariate cox regression analysis). Conclusion: NT-proBNP was a strong and independent predictor of in-hospital and 1-year mortality in AECOPD patients.

Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes (exos) play an important role in the communication between lung cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined. Exos were isolated from A549 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exos. CCK-8 assay, flow cytometry, Western blot, wound healing, and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of A549 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis. In vivo nude mice model was established to determine the regulatory effect of hypoxia/exos on the progression of lung cancer. Hypoxic A549 cell-derived exos (hypoxia/exos) promoted the proliferation and migration, and inhibited the apoptosis in A549 cells. The expression of PKM2 was significantly upregulated in hypoxia/exos. Hypoxic exosomal PKM2 induced M2 polarization of macrophages by activating AMPK pathway. Co-culture with hypoxia/exos-treated macrophages enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and lung metastasis of A549 cells. Our findings reveal that hypoxic exosomal PKM2 induces M2 macrophage polarization via AMPK pathway, and thus exerts a simulative effect on the growth and metastasis of lung carcinoma.

epigallocatechin gallate (eGcG), the most active monomer in green tea (GT), has demonstrated potential therapeutic and preventive effects on various tumors, including liver cancer. However, the anticancer mechanisms of eGcG in liver cancer remain to be elucidated. The abnormal expression of cell division cycle 25A (CDC25A) has been identified in liver cancer and is closely associated with malignancy and poor prognosis in patients with hepatocellular carcinoma (Hcc). The present study used human hepatoma cell lines and rats with diethylnitrosamine (den)-induced Hcc as models to investigate the association between the effect of eGcG on liver cancer and regulation of the p21waf1/cip1/cdc25a axis. The results demonstrated that eGcG can inhibit the proliferation of HepG2 and Huh7 cells, reduce the expression of cdc25a and increase the expression of p21waf1/cip1 in HepG2. In vivo, Hcc was induced by den in Sprague-dawley rats. EGCG significantly reduced tumor volume and improved the survival rates of rats with Hcc. The expression levels of cdc25a mrna and protein in liver tissues and the level of serum γ glutamyl transpeptidase in rats treated with eGcG were significantly decreased, while p21waf1/cip1 mrna and protein expression levels were increased compared with the Hcc group, in the process of den-induced Hcc. no significant difference in the chemopreventive effects on liver cancer was observed between GT extract and eGcG under an eGcG equivalence condition. Thus, eGcG can suppress human hepatoma cell proliferation and prolong the survival of rats with Hcc, and the potential mechanism may be involved in eGcG-induced upregulation of p21waf1/cip1 and downregulation of cdc25a.

Background Previous studies on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have found that those who died in hospital had higher blood urea nitrogen levels and a worse nutritional status compared to survivors. However, the association between the blood urea nitrogen to serum albumin ratio (BUN/ALB ratio) and in-hospital and short-term prognosis in patients with AECOPD remains unclear. The aim of this study was to explore the usefulness of BUN/ALB ratio in AECOPD as an objective predictor for in-hospital and 90-day all-cause mortality. Methods We recorded the laboratory and clinical data in patients with AECOPD on admission. By drawing the ROC curve for the patients, we obtained the cut-off point for the BUN/ALB ratio for in-hospital death. Multivariate logistic regression was used for analyses of the factors of in-hospital mortality and multivariate Cox regression was used to analyze the factors of 90-day all-cause mortality. Results A total of 362 patients were recruited and 319 patients were finally analyzed. Twenty-three patients died during hospitalization and the fatality rate was 7.2%. Furthermore, 14 patients died by the 90-day follow-up. Compared with in-hospital survivors, patients who died in hospital were older (80.78 ± 6.58 vs. 75.09 ± 9.73 years old, P = 0.001), had a higher prevalence of congestive heart failure(69.6% vs. 27.4%, P < 0.001), had a higher BUN/ALB ratio [0.329 (0.250–0.399) vs. 0.145 (0.111–0.210), P < 0.001], had higher neutrophil counts [10.27 (7.21–14.04) vs. 6.58 (4.58–9.04), P < 0.001], higher blood urea nitrogen levels [10.86 (7.10–12.25) vs. 5.35 (4.14–7.40), P < 0.001], a lower albumin level (32.58 ± 3.72 vs. 36.26 ± 4.53, P < 0.001) and a lower lymphocyte count [0.85 (0.58–1.21) vs. 1.22 (0.86–1.72), P = 0.001]. The ROC curve showed that the area under the curve (AUC) of BUN/ALB ratio for in-hospital death was 0.87, (95%CI 0.81–0.93, P < 0.001), the best cut-off point value to discriminate survivors from non-survivors in hospital was 0.249, the sensitivity was 78.3%, the specificity was 86.5%, and Youden’s index was 0.648. Having a BUN/ALB ratio ≥ 0.249 was an independent risk factor for both in-hospital and 90-day all-cause mortality after adjustment for relative risk (RR; RR = 15.08, 95% CI 3.80–59.78, P < 0.001 for a multivariate logistic regression analysis) and hazard ratio (HR; HR = 5.34, 95% CI 1.62–17.57, P = 0.006 for a multivariate Cox regression analysis). Conclusion An elevated BUN/ALB ratio was a strong and independent predictor of in-hospital and 90-day all-cause mortality in patients with AECOPD.