Gabexate mesilate(GM) is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis(TP),edematous pancreatitis,and acute necrotizing pancreatitis. However,due ...Gabexate mesilate(GM) is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis(TP),edematous pancreatitis,and acute necrotizing pancreatitis. However,due to the characteristics of pharmacokinetics,the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration,which is difficult to manage. Specially,when the blood supply of pancreas is directly damaged,intravenous administration is difficult to exert the optimum therapy effect. To address it,a novel thermosensitive in-situ gel of gabexate mesilate(GMTI) was developed,and the optimum formulation of GMTI containing 20.6%(w/w) P-407 and 5.79%(w/w) P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro,and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin(HE) staining,and its curative effect on grade Ⅱ pancreas injury was also evaluated by testing amylase(AMS),C-reactive protein(CRP) and trypsinogen activation peptide(TAP),and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/m L in GM group and GMTI group,respectively(P〈0.05 vs. P-407),and completely inhibited at 10.0 and 20.0 mg/m L(P〈0.01 vs. P-407). After local injection of 10 mg/m L GMTI to rat leg muscular tissue,muscle fiber texture was normal,and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore,the expression of AMS,CRP and TAP was significantly increased in TP group as compared with control group(P〈0.01),and significantly decreased in GM group as compared with TP group(P〈0.01),and also slightly inhibited after 1.0 and 5.0 mg/m L GMTI treatment as compared with TP group(P〈0.05),and significantly inhibited after 10.0 and 20.0 mg/m L GMTI treatment as compared with TP group(P〈0.01). HE staining results demonstrated that pancreas cells were uniformly distributed in control group,and they were loosely arranged,partially dissolved,with deeply stained nuclei in TP group. Expectedly,after gradient GMTI treatment,pancreas cells were gradually restored to tight distribution,with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes,and alleviate the severity of trauma-induced pancreatitis,and had a potential drug developing and clinic application value.展开更多
Ancient books that record the history of different periods are precious for human civilization.But the protection of them is facing serious problems such as aging.It is significant to repair the damaged characters in ...Ancient books that record the history of different periods are precious for human civilization.But the protection of them is facing serious problems such as aging.It is significant to repair the damaged characters in ancient books and restore their original textures.The requirement of the restoration of the damaged character is keeping the stroke shape correct and the font style consistent.In order to solve these problems,this paper proposes a new restoration method based on generative adversarial networks.We use the shape restoration network to complete the stroke shape recovery and the font style recovery.The texture repair network is responsible for reconstructing texture details.In order to improve the accuracy of the generator in the shape restoration network,we use the adversarial feature loss(AFL),which can update the generator and discriminator synchronously to replace the traditional perceptual loss.Meanwhile,the font style loss is proposed to maintain the stylistic consistency for the whole character.Our model is evaluated on the datasets Yi and Qing,and shows that it outperforms current state-of-the-art techniques quantitatively and qualitatively.In particular,the Structural Similarity has increased by 8.0%and 6.7%respectively on the two datasets.展开更多
基金supported by National Natural Science Foundation of China(No.81471682 and 81327003)
文摘Gabexate mesilate(GM) is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis(TP),edematous pancreatitis,and acute necrotizing pancreatitis. However,due to the characteristics of pharmacokinetics,the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration,which is difficult to manage. Specially,when the blood supply of pancreas is directly damaged,intravenous administration is difficult to exert the optimum therapy effect. To address it,a novel thermosensitive in-situ gel of gabexate mesilate(GMTI) was developed,and the optimum formulation of GMTI containing 20.6%(w/w) P-407 and 5.79%(w/w) P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro,and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin(HE) staining,and its curative effect on grade Ⅱ pancreas injury was also evaluated by testing amylase(AMS),C-reactive protein(CRP) and trypsinogen activation peptide(TAP),and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/m L in GM group and GMTI group,respectively(P〈0.05 vs. P-407),and completely inhibited at 10.0 and 20.0 mg/m L(P〈0.01 vs. P-407). After local injection of 10 mg/m L GMTI to rat leg muscular tissue,muscle fiber texture was normal,and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore,the expression of AMS,CRP and TAP was significantly increased in TP group as compared with control group(P〈0.01),and significantly decreased in GM group as compared with TP group(P〈0.01),and also slightly inhibited after 1.0 and 5.0 mg/m L GMTI treatment as compared with TP group(P〈0.05),and significantly inhibited after 10.0 and 20.0 mg/m L GMTI treatment as compared with TP group(P〈0.01). HE staining results demonstrated that pancreas cells were uniformly distributed in control group,and they were loosely arranged,partially dissolved,with deeply stained nuclei in TP group. Expectedly,after gradient GMTI treatment,pancreas cells were gradually restored to tight distribution,with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes,and alleviate the severity of trauma-induced pancreatitis,and had a potential drug developing and clinic application value.
基金the National Social Science Foundation of China under Grant 19BYY171the Fundamental Research Funds for the Central Universities under Grant XDJK2013C117+4 种基金Ph.D.Fund of Southwest University No.20130553China Postdoctoral Science Foundation under Grant 2015M580765Chongqing Postdoctoral Science Foundation under Grant Xm2016041Chongqing Natural Science Foundation(cstc2019jcyj-msxmX0130)Chongqing City science and technology education research projects(KJQN201801901).
文摘Ancient books that record the history of different periods are precious for human civilization.But the protection of them is facing serious problems such as aging.It is significant to repair the damaged characters in ancient books and restore their original textures.The requirement of the restoration of the damaged character is keeping the stroke shape correct and the font style consistent.In order to solve these problems,this paper proposes a new restoration method based on generative adversarial networks.We use the shape restoration network to complete the stroke shape recovery and the font style recovery.The texture repair network is responsible for reconstructing texture details.In order to improve the accuracy of the generator in the shape restoration network,we use the adversarial feature loss(AFL),which can update the generator and discriminator synchronously to replace the traditional perceptual loss.Meanwhile,the font style loss is proposed to maintain the stylistic consistency for the whole character.Our model is evaluated on the datasets Yi and Qing,and shows that it outperforms current state-of-the-art techniques quantitatively and qualitatively.In particular,the Structural Similarity has increased by 8.0%and 6.7%respectively on the two datasets.