Potential Value of Expiratory CT in Quantitative Assessment of Pulmonary Vessels in COPD.

Objective: To investigate the associations between intrapulmonary vascular volume (IPVV) depicted on inspiratory and expiratory CT scans and disease severity in COPD patients, and to determine which CT parameters can be used to predict IPVV. Methods: We retrospectively collected 89 CT examinations acquired on COPD patients from an available database. All subjects underwent both inspiratory and expiratory CT scans. We quantified the IPVV, airway wall thickness (WT), the percentage of the airway wall area (WA%), and the extent of emphysema (LAA%-950) using an available pulmonary image analysis tool. The underlying relationship between IPVV and COPD severity, which was defined as mild COPD (GOLD stage I and II) and severe COPD (GOLD stage III and IV), was analyzed using the Student's t-test (or Mann-Whitney U-test). The correlations of IPVV with pulmonary function tests (PFTs), LAA%-950, and airway parameters for the third to sixth generation bronchus were analyzed using the Pearson or Spearman's rank correlation coefficients and multiple stepwise regression. Results: In the subgroup with only inspiratory examinations, the correlation coefficients between IPVV and PFT measures were -0.215 ~ -0.292 (p < 0.05), the correlation coefficients between IPVV and WT3-6 were 0.233 ~ 0.557 (p < 0.05), and the correlation coefficient between IPVV and LAA%-950 were 0.238 ~ 0.409 (p < 0.05). In the subgroup with only expiratory scan, the correlation coefficients between IPVV and PFT measures were -0.238 ~ -0.360 (p < 0.05), the correlation coefficients between IPVV and WT3-6 were 0.260 ~ 0.566 (p < 0.05), and the correlation coefficient between IPVV and LAA%-950 were 0.241 ~ 0.362 (p < 0.05). The multiple stepwise regression analyses demonstrated that WT were independently associated with IPVV (P < 0.05). Conclusion: The expiratory CT scans can provide a more accurate assessment of COPD than the inspiratory CT scans, and the airway wall thickness maybe an independent predictor of pulmonary vascular alteration in patients with COPD.

Optimal threshold in low-dose CT quantification of emphysema.

OBJECTIVE: Low-dose CT is now widely used in the screening of lung cancer and the detection of pulmonary nodules. There has also been increasing interest in using Low-dose CT for evaluating emphysema. In conventional dose CT, the threshold of -950HU is a common threshold for density-based emphysema quantification for worldwide population. However, the optimal threshold for assessing emphysema at low-dose CT has not been determined. The purpose of this study is to determine the optimal threshold for low-dose CT quantification of emphysema for Chinese population. MATERIALS AND METHODS: In this study, 548 low-dose chest CT examinations acquired from different subjects (119 none, 49 mild, 163 moderate, 152 severe, and 65 very severe obstruction) are collected. At the level of the entire lung and individual lobes, the extent of emphysema was quantified by the percentage of the low attenuation area (LAA%) at a wide range of thresholds from -850HU to -1000HU. Both Pearson and Spearman's rank correlation coefficients were used to assess the correlations between 1) LAA% and pulmonary functions and 2) LAA% and the five-category classification. The statistical significance of the difference between correlation coefficients were evaluated using Steiger'Z test. RESULTS: LAA% had a good correlation with both pulmonary function (|r| = 0.1-0.600, p < 0.001) and the five-category classification (r = 0.163-0.602, p < 0.001) in both the entire lung and individual lobes under different thresholds. The highest correlation coefficient is obtained at -940HU instead of -950HU. CONCLUSION: Low-dose CT can be used for quantitative assessment of emphysema, and the threshold of -940HU is a suitable threshold for quantifying emphysema in low-dose CT images for Chinese population.

Soluble receptor for advanced glycation end-products promotes angiogenesis through activation of STAT3 in myocardial ischemia/reperfusion injury.

Soluble receptor for advanced glycation end-products (sRAGE), which exerts cardioprotective effect through inhibiting cardiomyocyte apoptosis and autophagy during ischemia/reperfusion (I/R) injury, is also known to enhance angiogenesis in post-ischemic reperfusion injury-critical limb ischemia (PIRI-CLI) mice. However, whether sRAGE protects the heart from myocardial I/R injury via promoting angiogenesis remains unclear. Myocardial model of I/R injury was conducted by left anterior descending (LAD) ligation for 30 min and reperfusion for 2 weeks in C57BL/6 mice. And I/R injury in cardiac microvascular endothelial cells (CMECs) was duplicated by oxygen and glucose deprivation. The results showed that I/R-induced cardiac dysfunction, inflammation and myocardial fibrosis were all reversed by sRAGE. CD31 immunohistochemistry staining showed that sRAGE increased the density of vessels after I/R injury. The results from cultured CMECs showed that sRAGE inhibited apoptosis and increased proliferation, migration, angiogenesis after exposure to I/R. These effects were dependent on signal transducer and activator of transcription 3 (STAT3) pathway. Together, the present study demonstrated that activation of STAT3 contributed to the protective effects of sRAGE on myocardial I/R injury via promoting angiogenesis.

Soluble receptor for advanced glycation end-products enhanced the production of IFN-γ through the NF-κB pathway in macrophages recruited by ischemia/reperfusion.

The current study investigated the role of sRAGE in the production of IFN­Î³ in macrophages with I/R treatment. The number of macrophages in myocardial tissues treated with I/R with or without sRAGE was determined via immunohistochemical staining. Proliferative activity of macrophages was analyzed by a 5­BrdU incorporation assay. Differentiation of macrophages was detected via immunofluorescence staining of iNOS (M1 macrophage marker). IFN­Î³ production, due to sRAGE stimulation, in Raw 264.7 macrophages and the NF­κB signaling pathway were measured using western blotting. A ChIP assay was used to examine the interactions between NF­κB and the promoter of IFN­Î³. The results showed that the number of macrophages in I/R­treated myocardial tissues was increased following sRAGE infusion. Proliferation of macrophages was increased significantly in the presence of sRAGE; after I/R treatment, the cells preferred to differentiate into M1 macrophages. IFN­Î³ expression in Raw 264.7 macrophages was suppressed by an NF­κB inhibitor (Bay117082) but enhanced by sRAGE, with or without I/R treatment. Furthermore, sRAGE increased the phosphorylation of IκB, IKK and NF­κB, as well as the translocation of NF­κB into the nucleus of Raw 264.7 macrophages, with or without I/R treatment. ChIP results showed that sRAGE promoted NF­κB binding to the promoter of IFN­Î³ in Raw 264.7 macrophages. Therefore, the findings of the present study indicated that sRAGE protected the heart from I/R injuries, which might be mediated by promoting infiltration and the differentiation of macrophages into M1, which would then synthesize and secrete IFN­Î³ through activating the NF­κB signaling pathway.

Soluble receptor for advance glycation end-products inhibits ischemia/reperfusion-induced myocardial autophagy via the STAT3 pathway.

The pathogenesis of myocardial ischemia/reperfusion (I/R) is poorly understood, but recent evidence suggests that autophagy plays crucial roles in I/R injuries. Soluble receptor for advanced glycation end-products (sRAGE) exerts protective effects during I/R by decreasing cardiac apoptosis, which is mediated via increasing the ubiquitin proteasome system (UPS) and signal transducer and activator of transcription 3 (STAT3). The present study examined the effects and mechanisms of sRAGE on I/R-triggered cardiac autophagy. I/R was performed in mice or primary neonatal cardiomyocytes with or without sRAGE administration or overexpression. Cardiac function and infarct size were detected in mouse hearts. Apoptosis, autophagy and autophagy-related signaling pathways were detected in mouse hearts and cardiomyocytes. The results demonstrated that sRAGE significantly improved cardiac function and reduced infarct size during I/R in mice. sRAGE inhibited I/R-induced apoptosis, which correlated with a reduction in autophagy-associated proteins, including ATG7, Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3). sRAGE reduced autophagosome formation during I/R in vivo and in vitro. sRAGE significantly activated STAT3, but not mammalian target of rapamycin (mTOR), during I/R in vivo and in vitro, and suppression of STAT3 abolished the sRAGE inhibition of autophagy during I/R in vitro. Activation of autophagy using ATG7 overexpression with an adenovirus significantly abolished the sRAGE-induced reduction of cardiac apoptosis during I/R. These results suggest that sRAGE inhibits I/R injuries in the heart via a decrease in autophagy, a process that is dependent on STAT3 activation.

Study on detecting leachate leakage of municipal solid waste landfill site.

The article studies the detection of the leakage passage of leachate in a waste landfill dam. The leachate of waste landfill has its own features, like high conductivity, high chroma and an increasing temperature, also, the horizontal flow velocity of groundwater on the leakage site increases. This article proposes a comprehensive tracing method to identify the leakage site of an impermeable membrane by using these features. This method has been applied to determine two leakage sites of the Yahu municipal solid waste landfill site in Pingshan District, Shenzhen, China, which shows that there are two leachate leakage passages in the waste landfill dam A between NZK-2 and NZK-3, and between NZK-6 and NZK-7.