Blood urea nitrogen to serum albumin ratio: a good predictor of in-hospital and 90-day all-cause mortality in patients with acute exacerbations of chronic obstructive pulmonary disease.

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.

Hypoxic Tumor-Derived Exosomes Induce M2 Macrophage Polarization via PKM2/AMPK to Promote Lung Cancer Progression.

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.

Leaf vein disease in Nelumbo nucifera caused by Nigrospora pyriformis infection in China.

Nelumbo nucifera (Nymphaeaceae) has both ornamental and nutritional uses in China. In July 2021, a novel disease was observed on plants in the White Lotus Science and Technology Expo Park in Guangchang county, Fuzhou city, Jiangxi province (26.79° N, 116.31° E). Infection was visible as nearly round black spots on the leaves in the early stages of infection. At later stages, the spots spread along the veins forming reticular necrosis until the entire leaf was infected, and the disease caused approximately 20% of leaves to die. To identify the pathogenic organism, 5×5 mm samples were taken from affected tissue adjoining healthy tissue, sterilized in 75% ethanol for 30 s, and immersed in 0.1% mercury chloride for a further 30 s, before washing in sterile water and transfer to potato glucose agar (PDA) plates. After culturing at 28℃±1℃ for five days, white regularly shaped round colonies were visible that after 10 days turned black with fluffy hyphae. The individual conidia produced by the conidiophore were initially a light-brown color which changed to black as the pigment accumulated; conidia were globose to subglobose, 17.10 (14.77-21.66) ×14.70 (12.08-16.93) µm in size (n=50), with glossy even surfaces lacking in septa, suggestive of Nigrospora. To verify this, PCR amplification was conducted using ITS1/ITS4 primers for the 5.8S rRNA gene. The primers EF1-728F and EF-2 were used for amplifying translation elongation factor 1α (O'Donnell et al. 1998, Carbone and Kohn 1999), and Bt-2a and Bt-2b (Glass and Donaldson 1995) for amplifying ß-tubulin. The sequences were found to be 99% to 100% identical to those of Nigrospora pyriformis in GenBank (accession numbers NR153469.1, KY019290.1, and KY019457.1, respectively). The sequences were uploaded to GenBank (accession numbers OK605048, OL362197, and OK662966), with lengths of 522 bp, 475 bp, and 410 bp, respectively. A maximum-likelihood phylogenetic tree was created in MEGA5. Pathogenicity was tested by four isolates hyphal inoculation and conducted in an experimental field of the White Lotus Science and Technology Expo Park. Five-millimeter discs were taken from infected and uninfected PDA plates and inoculated into five 1-month-old healthe lotus leaves using inoculations, three with the pathogen and an uninfected sample as the control every leaf. The discs were covered with moisturized sterile cotton and fixed with transparent tape. The wounds were moistened with sterile water and sealed with adhesive tape. After 14 days, spots were visible at the infected sites while the control sites showed no symptoms. The same pathogen was recovered from the infected leaves, fulfilling Koch's requirements. Leaf spot diseases resulting from N. pyriformis infection or infection with other Nigrospora species include infection of Chenopodium album by N. pyriformis (Chen et al. 2020), Eclipta prostrata by N. sphaerica (Qiu et al. 2022), Nicotiana tabacum by N. oryzae (Wang et al. 2022), and Oxalis corymbosa by N. hainanensis (Zheng et al. 2021). This investigation appears to be the first identification of Nelumbo nucifera vein disease resulting from Nigrospora pyriformis infection. The present results are useful for the management and avoidance of the disease caused by Nigrospora pyriformis.

Prognostic Role of Chronic Obstructive Pulmonary Disease and Asthma Physiology Score for in-Hospital and 1-year Mortality in Patients with Acute Exacerbations of COPD.

BACKGROUND AND OBJECTIVES: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often lead to high mortality. Chronic obstructive pulmonary disease and asthma physiology score (CAPS) is a simple clinical severity score. The aim of this study was to explore whether CAPS could be an effective predictor for in-hospital and 1-year mortality in AECOPD patients. Methods. We used CAPS to grade all patients and record their clinical characteristics. The receiver operator characteristic (ROC) curve was used to determine the cut-off of CAPS that discriminated survivors and non-survivors. Univariate and multivariate logistic regression analyses and Cox regression analyses were used to identify the risk factors for in-hospital and 1-year mortality, respectively. Results. 240 patients were enrolled in our study; 18 patients died during hospitalization and 29 patients died during the 1-year follow-up. Compared with in-hospital survivors, those who died were older (80.83 ± 6.06 vs. 76.94 ± 8.30 years old, P = 0.019) and had a higher percentage of congestive heart failure (61.1% vs. 14.4%, P < 0.001), higher CAPS levels (31.11 ± 10.05 vs. 16.49 ± 7.11 points, P < 0.001), and a lower BMI (19.48 ± 3.26 vs. 21.50 ± 3.86, P = 0.032). The area under the ROC curve of CAPS for in-hospital death was 0.91 (95% CI: 0.85-0.96) with a sensitivity of 0.889 and a specificity of 0.802 for a cut-off point of 21 points. CAPS ≥21 points was an independent risk factor for in-hospital mortality after adjustment for relative risk (RR) (RR = 13.28, 95% CI: 1.97-89.53, P = 0.008). Univariate Cox regression analysis showed that a CAPS ≥21 points (HR = 4.07, 95% CI: 1.97-8.44) was a risk factor for 1-year mortality. However, multivariate Cox regression analysis showed that CAPS (HR = 2.24, 95% CI: 0.90-5.53) was not associated with 1-year mortality. CONCLUSION: A CAPS ≥21 points was a strong and independent risk factor for in-hospital mortality in AECOPD patients and CAPS had no impact on the 1-year mortality in patients with acute exacerbations of COPD after discharge.

Association Between Extracellular Superoxide Dismutase Activity and 1-Year All-Cause Mortality in Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study.

Background and Objectives: Accumulating evidence suggests that oxidative stress is involved in the development of chronic obstructive pulmonary disease (COPD) and its progression. Activity of extracellular superoxide dismutase (ecSOD), the only extracellular enzyme eliminating superoxide radicals, has been reported to decline in acute exacerbations of COPD (AECOPD). However, the association between serum ecSOD activity and 1-year all-cause mortality in AECOPD patients remains unclear. The objective of our study was to explore the usefulness of ecSOD activity on admission in AECOPD as an objective predictor for 1-year all-cause mortality. Methods: We measured serum ecSOD activity in AECOPD patients on admission in a prospective cohort study. We also recorded their laboratory and clinical data. Multivariate Cox regression was used to analyze the association between ecSOD activity and the risk of 1-year all-cause mortality. Restricted cubic spline curves were used to visualize the relationship between ecSOD activity and the hazard ratio of 1-year all-cause mortality. Results: A total of 367 patients were followed up for 1 year, and 29 patients died during a 1-year follow-up period. Compared with survivors, the non-survivors were older (79.52 ± 8.39 vs. 74.38 ± 9.34 years old, p = 0.004) and had increased levels of tobacco consumption (47.07 ± 41.67 vs. 33.83 ± 31.79 pack-years, p = 0.037). Having an ecSOD activity ≤ 98.8 U/ml was an independent risk factor of 1-year all-cause mortality after adjustment for baseline differences, clinical variables and comorbidities [hazard ratio = 5.51, 95% confidence interval (CI): 2.35-12.95, p < 0.001]. Conclusion: Lower serum ecSOD activity was a strong and independent predictor of 1-year all-cause mortality in AECOPD patients.

Epigallocatechin gallate induces chemopreventive effects on rats with diethylnitrosamine­induced liver cancer via inhibition of cell division cycle 25A.

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 Sprague­Dawley 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 DEN­induced 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 EGCG­induced upregulation of p21waf1/Cip1 and downregulation of CDC25A.

Prognostic Role of NT-proBNP for in-Hospital and 1-Year Mortality in Patients with Acute Exacerbations of COPD.

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 in-hospital 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 in-hospital 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.

Prognostic role of D-dimer for in-hospital and 1-year mortality in exacerbations of COPD.

BACKGROUND AND OBJECTIVE: Serum 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). METHODS: Upon 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. RESULTS: In 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). CONCLUSION: D-dimer was a strong and independent risk factor for in-hospital and 1-year death for AECOPD patients.