Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI ...Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.展开更多
Huperzine A(Hup-A) is a poorly water-soluble drug with low oral bioavailability. A selfmicroemulsifying drug delivery system(SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of H...Huperzine A(Hup-A) is a poorly water-soluble drug with low oral bioavailability. A selfmicroemulsifying drug delivery system(SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion(SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve(AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension(P <0.01).The absorption rate constant(K_a) and the apparent permeability coefficient(P_(app)) for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of K_a and P_(app) of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration(C_(max)) of the blocking model were significantly lower than those of the control model(P<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%,respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.展开更多
The aim of this study was to develop a formulation to improve the oral absorption of baicalin(BA)by combining a phospholipid complex(PC)and self-emulsifying microemulsion drug delivery system(SMEDDS),termed BA–PC–SM...The aim of this study was to develop a formulation to improve the oral absorption of baicalin(BA)by combining a phospholipid complex(PC)and self-emulsifying microemulsion drug delivery system(SMEDDS),termed BA–PC–SMEDDS.BA–PC was prepared by a solvent evaporation method and evaluated by complexation percentage(CP).The physicochemical properties of BA–PC were determined.The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model.The improved bioavailability of BA in BA–PC–SMEDDS was confirmed in an in vivo rat model.The CP of BA–PC reached 100%when the molar ratio of drug to phospholipid(PP)was Z1:1.The solubility of BA–PC increased in both water and octanol,and the log P o/w of BA–PC was increased significantly.BA–PC–SMEDDS could be dispersed more evenly in water,compared to BA and BA–PC.Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA–PC was lower than that of free BA,while improved significantly in BA–PC–SMEDDS.The relative bioavailability of BA–PC(1:2)–SMEDDS was 220.37%.The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.展开更多
A three-dimensional finite element approach based on ABAQUS code was developed to investigate the effect of welding sequence on welding residual stress distribution in a thin-walled 6061 aluminum alloy structure. To o...A three-dimensional finite element approach based on ABAQUS code was developed to investigate the effect of welding sequence on welding residual stress distribution in a thin-walled 6061 aluminum alloy structure. To obtain sound numerical results, the therrno-mechanical behaviour was simulated using a direct-coupled formulation. Nine different simulation sequences were carried out by single-pass TIG welding of an octagonal pipe-plate joint, and the distributions of longitudinal and transverse residual stresses both on the outer and inner surfaces of the pipe were analyzed. The results suggest that the final residual stresses in the weld and its vicinity are not affected by the initial residual stresses of the structure. Selecting a suitable welding sequence can reduce the final residual stress in an octagonal pipe-plate joint.展开更多
AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior...AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion(SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds(jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids(borneol or camphor) was higher than by the monocyclic monoterpenes(menthol or menthone), and promotion by compounds with a hydroxyl group(borneol or menthol) was higher than those with a carbonyl group(camphor or menthone). The apparent permeability coefficient(Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant(Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein(P-gp) and organic cation transporters(OCT), rather than multidrug resistance protein(MRP) and breast cancer resistance protein(BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.展开更多
Understandings of the effect of hot deformation parameters close to the practical production line on grain refinement are crucial for enhancing both the strength and toughness of future rail steels.In this work,the au...Understandings of the effect of hot deformation parameters close to the practical production line on grain refinement are crucial for enhancing both the strength and toughness of future rail steels.In this work,the austenite dynamic recrystallization(DRX)behaviors of a eutectoid pearlite rail steel were studied using a thermo-mechanical simulator with hot deformation parameters frequently employed in rail production lines.The single-pass hot deformation results reveal that the prior austenite grain sizes(PAGSs)for samples with different deformation reductions decrease initially with an increase in deformation temperature.However,once the deformation temperature is beyond a certain threshold,the PAGSs start to increase.It can be attributed to the rise in DRX volume fraction and the increase of DRX grain with deformation temperature,respectively.Three-pass hot deformation results show that the accumulated strain generated in the first and second deformation passes can increase the extent of DRX.In the case of complete DRX,PAGS is predominantly determined by the deformation temperature of the final pass.It suggests a strategic approach during industrial production where part of the deformation reduction in low temperature range can be shifted to the medium temperature range to release rolling mill loads.展开更多
The present study was designed to investigate the effects of Laminaria japonica(Laminaria) on pharmacokinetics of glycyrrhetinic acid(GA) following oral administration of Liquorice extract in rats.Following oral admin...The present study was designed to investigate the effects of Laminaria japonica(Laminaria) on pharmacokinetics of glycyrrhetinic acid(GA) following oral administration of Liquorice extract in rats.Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract,respectively,plasma samples were obtained at various times and the concentrations of GA,liquiritigenin,and isoliquiritigenin were measured by LC-MS.The effects of Laminaria extract on pharmacokinetics of GA were also investigated,following single-dose and multidose of glycyrrhizic acid(GL).The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model.The metabolism of GL to GA in the contents of small and large intestines was also studied.The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA,accompanied by a shorter Tmax.Similar alteration was observed following multidose administration.However,pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria.Similarly,Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed.The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum,but did not affect the intestinal absorption of GA.It was found that Laminaria enhanced the metabolism of GL to GA in large intestine.In conclusion,Laminaria increased plasma exposures of GA following oral administration of liquorice or GL,which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.展开更多
This study investigates the single-pass absorption(SPA) of ion cyclotron range of frequency(ICRF) heating in hydrogen plasma of the EXL-50U spherical tokamak,which is an upgraded EXL-50 device with a central solenoid ...This study investigates the single-pass absorption(SPA) of ion cyclotron range of frequency(ICRF) heating in hydrogen plasma of the EXL-50U spherical tokamak,which is an upgraded EXL-50 device with a central solenoid and a stronger magnetic field.The reliability of the kinetic dispersion equation is confirmed by the one-dimensional full-wave code,and the applicability of Porkolab's simplified theoretical SPA model is discussed based on the kinetic dispersion equation.Simulations are conducted to investigate the heating effects of the fundamental and second harmonic frequencies.The results indicate that with the design parameters of the EXL-50U device,the SPA for second harmonic heating is 63%,while the SPA for fundamental heating is 13%.Additionally,the optimal injection frequencies are 23 MHz at 0.9 T and 31 MHz at 1.2 T.The wave vector of the antenna parallel to the magnetic field,with a value of k_‖=7.5 m^(-1),falls within the optimal heating region.Simulations reveal that the ICRF heating system can play an important role in the ion heating of the EXL-50U.展开更多
AIM： To characterize the intestinal transport and mechanism of metformin in rats and to investigate whether or not metformin is a substrate for P-glycoprotein （P-gp）. METHODS： The effective intestinal permeability...AIM： To characterize the intestinal transport and mechanism of metformin in rats and to investigate whether or not metformin is a substrate for P-glycoprotein （P-gp）. METHODS： The effective intestinal permeability of metformin was investigated using single-pass intestinal perfusion （SPIP） technique in male Waster rats. SPIP was performed in three isolated intestinal segments （duodenum, jejunum and ileum） at the same concentration of metformin （50 μg/mL） to test if the intestinal transport of metformin exhibited site- dependent changes, and in a same isolated intestinal segment （duodenal segment） at three different concentrations of metformin （10, 50, 200 μg/mL） to test if the intestinal transport of metformin exhibited concentration-dependent changes. Besides, P-gp inhibitor verapamil （400 μg/mL） was co-perfused with metformin （50 μg/mL） in the duodenum segment to find out if the intestinal absorption of metformin was affected by P-gp exiting along the gastrointestinal track. Stability studies were conducted to ensure that the loss of metformin could be attributed to intestinal absorption. RESULTS： The effective permeability values （Peff） of metformin in the jejunum and ileum at 50μg/mL were significantly lower than those in the duodenum at the same concentration. Besides, Peff values in the duodenum at high concentration （200 μg/mL） were found to be significantly lower than those at low and medium concentrations （10 and 50 μg/mL）. Moreover the coperfusion with verapamil did not increase the Peff value of metformin at 50 μg/mL in the duodenum.CONCLUSION： Metformin could be absorbed from the whole intestine, with the main absorption site at duodenum. This concentration-dependent permeability behavior in the duodenum indicates that metformin is transported by both passive and active carrier-mediated saturable mechanism. The Peff value can not be increased by co-perfusion with verapamil, indicating that absorption of metformin is not efficiently transported展开更多
文摘Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.
基金supported by the National Natural Science Foundation of China(Grant Nos.8127410081573615)+2 种基金Natural Science Foundation of Anhui Province of China(Grant No.1408085QH189)Key Project for the Excellent Higher Education of Anhui Province of China(Grant No.2013SQRL019ZD)Research Project for the Science and Technology of Bozhou city of China(Grant No.BK2015005)
文摘Huperzine A(Hup-A) is a poorly water-soluble drug with low oral bioavailability. A selfmicroemulsifying drug delivery system(SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion(SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve(AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension(P <0.01).The absorption rate constant(K_a) and the apparent permeability coefficient(P_(app)) for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of K_a and P_(app) of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration(C_(max)) of the blocking model were significantly lower than those of the control model(P<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%,respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.
基金This work was supported by grants from the National Natural Science Foundation of China(No.30973953C1909)。
文摘The aim of this study was to develop a formulation to improve the oral absorption of baicalin(BA)by combining a phospholipid complex(PC)and self-emulsifying microemulsion drug delivery system(SMEDDS),termed BA–PC–SMEDDS.BA–PC was prepared by a solvent evaporation method and evaluated by complexation percentage(CP).The physicochemical properties of BA–PC were determined.The synergistic effect of PC and SMEDDS on permeation of BA was studied in vitro with Caco-2 cells and in situ with a single pass intestinal perfusion model.The improved bioavailability of BA in BA–PC–SMEDDS was confirmed in an in vivo rat model.The CP of BA–PC reached 100%when the molar ratio of drug to phospholipid(PP)was Z1:1.The solubility of BA–PC increased in both water and octanol,and the log P o/w of BA–PC was increased significantly.BA–PC–SMEDDS could be dispersed more evenly in water,compared to BA and BA–PC.Both the Caco-2 cell uptake and single-pass intestinal perfusion models illustrated that transport of BA in BA–PC was lower than that of free BA,while improved significantly in BA–PC–SMEDDS.The relative bioavailability of BA–PC(1:2)–SMEDDS was 220.37%.The combination system of PC and SMEDDS had a synergistic effect on improving the oral absorption of BA.
基金Project(61075005)supported by the Fund of State Key Laboratory of Advanced Design and Manufacture for Vehicle Body in Hunan University,ChinaProject(09JJ1007)supported by Preeminent Youth Fund of Hunan Province,ChinaProject(51075132)supported by the National Natural Science Foundation of China
文摘A three-dimensional finite element approach based on ABAQUS code was developed to investigate the effect of welding sequence on welding residual stress distribution in a thin-walled 6061 aluminum alloy structure. To obtain sound numerical results, the therrno-mechanical behaviour was simulated using a direct-coupled formulation. Nine different simulation sequences were carried out by single-pass TIG welding of an octagonal pipe-plate joint, and the distributions of longitudinal and transverse residual stresses both on the outer and inner surfaces of the pipe were analyzed. The results suggest that the final residual stresses in the weld and its vicinity are not affected by the initial residual stresses of the structure. Selecting a suitable welding sequence can reduce the final residual stress in an octagonal pipe-plate joint.
基金supported by China Pharmaceutical University Training Programs of Innovation for Undergraduates(No.02640390)
文摘AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis(TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion(SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds(jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids(borneol or camphor) was higher than by the monocyclic monoterpenes(menthol or menthone), and promotion by compounds with a hydroxyl group(borneol or menthol) was higher than those with a carbonyl group(camphor or menthone). The apparent permeability coefficient(Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant(Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein(P-gp) and organic cation transporters(OCT), rather than multidrug resistance protein(MRP) and breast cancer resistance protein(BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.
基金financially supported by the National Natural Science Foundation of China(Nos.52293395 and 52293393)the Xiongan Science and Technology Innovation Talent Project of MOST,China(No.2022XACX0500)。
文摘Understandings of the effect of hot deformation parameters close to the practical production line on grain refinement are crucial for enhancing both the strength and toughness of future rail steels.In this work,the austenite dynamic recrystallization(DRX)behaviors of a eutectoid pearlite rail steel were studied using a thermo-mechanical simulator with hot deformation parameters frequently employed in rail production lines.The single-pass hot deformation results reveal that the prior austenite grain sizes(PAGSs)for samples with different deformation reductions decrease initially with an increase in deformation temperature.However,once the deformation temperature is beyond a certain threshold,the PAGSs start to increase.It can be attributed to the rise in DRX volume fraction and the increase of DRX grain with deformation temperature,respectively.Three-pass hot deformation results show that the accumulated strain generated in the first and second deformation passes can increase the extent of DRX.In the case of complete DRX,PAGS is predominantly determined by the deformation temperature of the final pass.It suggests a strategic approach during industrial production where part of the deformation reduction in low temperature range can be shifted to the medium temperature range to release rolling mill loads.
基金supported by funding from the National Basic Research Program of China(973 Program)(Nos.2011CB505300,2011CB505303)
文摘The present study was designed to investigate the effects of Laminaria japonica(Laminaria) on pharmacokinetics of glycyrrhetinic acid(GA) following oral administration of Liquorice extract in rats.Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract,respectively,plasma samples were obtained at various times and the concentrations of GA,liquiritigenin,and isoliquiritigenin were measured by LC-MS.The effects of Laminaria extract on pharmacokinetics of GA were also investigated,following single-dose and multidose of glycyrrhizic acid(GL).The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model.The metabolism of GL to GA in the contents of small and large intestines was also studied.The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA,accompanied by a shorter Tmax.Similar alteration was observed following multidose administration.However,pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria.Similarly,Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed.The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum,but did not affect the intestinal absorption of GA.It was found that Laminaria enhanced the metabolism of GL to GA in large intestine.In conclusion,Laminaria increased plasma exposures of GA following oral administration of liquorice or GL,which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.
基金supported by the National Magnetic Confinement Fusion Energy Program of China (No.2018 YFE0311300)the High-End Talents Program of Hebei Province, Innovative Approaches Towards Development of Carbon-Free Clean Fusion Energy (No.2021HBQZYCSB 006)the Compact Fusion Project of the ENN Group。
文摘This study investigates the single-pass absorption(SPA) of ion cyclotron range of frequency(ICRF) heating in hydrogen plasma of the EXL-50U spherical tokamak,which is an upgraded EXL-50 device with a central solenoid and a stronger magnetic field.The reliability of the kinetic dispersion equation is confirmed by the one-dimensional full-wave code,and the applicability of Porkolab's simplified theoretical SPA model is discussed based on the kinetic dispersion equation.Simulations are conducted to investigate the heating effects of the fundamental and second harmonic frequencies.The results indicate that with the design parameters of the EXL-50U device,the SPA for second harmonic heating is 63%,while the SPA for fundamental heating is 13%.Additionally,the optimal injection frequencies are 23 MHz at 0.9 T and 31 MHz at 1.2 T.The wave vector of the antenna parallel to the magnetic field,with a value of k_‖=7.5 m^(-1),falls within the optimal heating region.Simulations reveal that the ICRF heating system can play an important role in the ion heating of the EXL-50U.
基金Supported by the National "863" Program of China, No.2003AA2Z347Dthe National "973" Program of China, No.2004CB518902
文摘AIM： To characterize the intestinal transport and mechanism of metformin in rats and to investigate whether or not metformin is a substrate for P-glycoprotein （P-gp）. METHODS： The effective intestinal permeability of metformin was investigated using single-pass intestinal perfusion （SPIP） technique in male Waster rats. SPIP was performed in three isolated intestinal segments （duodenum, jejunum and ileum） at the same concentration of metformin （50 μg/mL） to test if the intestinal transport of metformin exhibited site- dependent changes, and in a same isolated intestinal segment （duodenal segment） at three different concentrations of metformin （10, 50, 200 μg/mL） to test if the intestinal transport of metformin exhibited concentration-dependent changes. Besides, P-gp inhibitor verapamil （400 μg/mL） was co-perfused with metformin （50 μg/mL） in the duodenum segment to find out if the intestinal absorption of metformin was affected by P-gp exiting along the gastrointestinal track. Stability studies were conducted to ensure that the loss of metformin could be attributed to intestinal absorption. RESULTS： The effective permeability values （Peff） of metformin in the jejunum and ileum at 50μg/mL were significantly lower than those in the duodenum at the same concentration. Besides, Peff values in the duodenum at high concentration （200 μg/mL） were found to be significantly lower than those at low and medium concentrations （10 and 50 μg/mL）. Moreover the coperfusion with verapamil did not increase the Peff value of metformin at 50 μg/mL in the duodenum.CONCLUSION： Metformin could be absorbed from the whole intestine, with the main absorption site at duodenum. This concentration-dependent permeability behavior in the duodenum indicates that metformin is transported by both passive and active carrier-mediated saturable mechanism. The Peff value can not be increased by co-perfusion with verapamil, indicating that absorption of metformin is not efficiently transported
