The pulmonary biopharmaceutics and anti-inflammatory effects after intratracheal and intravenous administration of Re-Du-Ning injection.

BACKGROUND: Re-Du-Ning injection (RDN) is a renowned heat-clearing traditional Chinese medicine for the treatment of respiratory diseases owing to its anti-inflammatory effects. However, very little is known about the pulmonary distribution and lung exposure-efficacy relationships. This study aimed to investigate the pulmonary distribution and biopharmaceutics concerning lung penetrability and affinity and the local anti-inflammatory effects after intravenous and pulmonary administration of RDN. METHODS: Two iridoids and seven phenolic acid components were selected as the chemical markers in RDN. The in vitro pulmonary distribution and biopharmaceutics were conducted by evaluating the binding and disassociation kinetics of chemical markers in lung tissue explants whereas the in vivo evaluation was performed by determining the time-dependent concentrations of chemical markers in plasma, lung epithelial lining fluid (ELF), lung tissues and immune cells in the ELF after intratracheal and intravenous administrations of RDN. The inhibitory effects on tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production were used to evaluate the anti-inflammatory effect of RDN on lung tissues in vitro and on mice with LPS-induced lung inflammation. RESULTS: The chemical markers of RDN exhibited excellent lung penetrability but poor lung affinity in vitro and in vivo. After intravenous administration, the chemical markers appeared to rapidly penetrate through the lung tissue to reach the ELF, leading to markedly higher drug exposure to ELF and immune cells in the ELF than to lung tissues. Compared to intravenous injection, the intratracheal instillation of RDN increased drug exposure to lung tissue and immune cells in the ELF by up to > 80-fold, leading to improved anti-inflammatory potency and prolonged duration of action. CONCLUSION: The drug exposure to immune cells in the ELF was correlated with the lung-targeted anti-inflammatory effects of RDN and pulmonary delivery has the potential to replace intravenous injection of RDN for the treatment of respiratory diseases.

PI3K inhibitor ZSTK474 enhancing the antitumor of vesicular stomatitis virus A51 against osteosarcoma / 解剖学报

Objective To explore whether PI3K inhibitor combined with oncolytic virus can play an effective oncolytic effect on osteosarcoma. Methods The cytotoxicity to tumor cells was detected by MTT method, and the mechanism of enhancing the anti-tumor activity was explored by observation of the swelling of endoplasmic reticulum using electron microscope and the expression of apoptosis-related proteins using Western blotting. The tumor clearance ability of the combination of the PI3k inhibitor ZSTK474 and vesicular stomatitis virus A51 (VSVA51) was verified by anti-tumor experiment in vivo. The apoptosis of tumor cells was verified by immunohistochemistry. Results PI3K inhibitor could be used as sensitizers of oncolytic VSVA51, and confirmed that the)' promoted the strong apoptosis of osteosarcoma cells by aggravating the stress of endoplasmic reticulum in tumor cells (P < 0 . 01). In vivo experiments also showed that PI3K inhibitors combined with VSVA51 could significantly promote the oncolytic effect of osteosarcoma (P<0.001), and this combination therapy enhanced the infiltration of immune cells in the tumor (P<0.001). Conclusion PI3K inhibitors combined with oncolytic virus is a potential therapy for osteosarcoma.

Boundary detection using double-opponency and spatial sparseness constraint.

Brightness and color are two basic visual features integrated by the human visual system (HVS) to gain a better understanding of color natural scenes. Aiming to combine these two cues to maximize the reliability of boundary detection in natural scenes, we propose a new framework based on the color-opponent mechanisms of a certain type of color-sensitive double-opponent (DO) cells in the primary visual cortex (V1) of HVS. This type of DO cells has oriented receptive field with both chromatically and spatially opponent structure. The proposed framework is a feedforward hierarchical model, which has direct counterpart to the color-opponent mechanisms involved in from the retina to V1. In addition, we employ the spatial sparseness constraint (SSC) of neural responses to further suppress the unwanted edges of texture elements. Experimental results show that the DO cells we modeled can flexibly capture both the structured chromatic and achromatic boundaries of salient objects in complex scenes when the cone inputs to DO cells are unbalanced. Meanwhile, the SSC operator further improves the performance by suppressing redundant texture edges. With competitive contour detection accuracy, the proposed model has the additional advantage of quite simple implementation with low computational cost.

Relationship of c-kit and platelet-derived growth factor receptor alpha gene mutation features with prognosis of patients with gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the relationship between c-kit and platelet-derived growth factor receptor alpha(PDGFRA) gene mutation features and the prognosis of gastrointestinal stromal tumor(GIST).</p><p><b>METHODS</b>Clinicopathological, genetic testing and follow-up informations of patients admitted to the Shanxi Tumor Hospital from June 2000 to January 2009 were collected. The survival was calculated and univariate analysis was conducted using the Kaplan-Meier method. Multivariate analysis was conducted by the Cox regression method.</p><p><b>RESULTS</b>The 5-year disease-free survival rate was 61.5% and the 5-year overall survival rate was 67.4%. The 5-year disease-free survival rates of patients without disease among those with c-kit exon 11 mutation (n=77), c-kit exon 9 mutation(n=4), and PDGFRA exon 18 mutation (n=2) were 63.4%, 14.3% and 100%, and the 5-year overall survival rates were 70.8%, 50.0% and 100%, respectively. In the patients with c-kit exon 11 mutation, the 5-year disease-free survival rates among those with point mutations(n=26), deletion mutations(n=44), and duplication mutations(n=7) were 87.1%, 44.9% and 80.0%, and the 5-year overall survival rates were 88.1%, 57.0% and 100%, respectively. There were significant differences in overall survival among different factors. Multivariate analysis showed that gene mutation was not the independent factor of prognosis(P=0.492).</p><p><b>CONCLUSIONS</b>In GIST patients undergoing surgery without imatinib treatment, mutated genotype is better than wild type in terms of prognosis. Gene mutation is not the independent factor of prognosis in GIST patients.</p>