Introduction Liver cirrhosis generally occurs with the hemodynamic changes during the portal vein hypertension and finally leads to the atrophy of the right lobe of the liver and hepatic failure<sup>[1]</sup&...Introduction Liver cirrhosis generally occurs with the hemodynamic changes during the portal vein hypertension and finally leads to the atrophy of the right lobe of the liver and hepatic failure<sup>[1]</sup>.According to the hemodynamic changes,a hypothesis has been proposed that the liver volume is related to the istribution of blood from the splenic vein（SV）that involves nutrition from spleen and pancreas<sup>[2,3]</sup>.The objective of the present paper is to simulate the blood flow in real models of portal vein hypertension and validate the hypothesis using computational fluid dynamics（CFD）method.Methods This study includes 2 patients with liver cirrhosis and a set of 4 normal subjects.展开更多
Background Coronary artery stenting is commonly used for the treatment of coronary atherosclerosis,but it causes serious clinical complications,such as the in-stent restenosis(ISR).The main reason leading to ISR is th...Background Coronary artery stenting is commonly used for the treatment of coronary atherosclerosis,but it causes serious clinical complications,such as the in-stent restenosis(ISR).The main reason leading to ISR is the neointimal hyperplasia(NH),which is related to the stresses of plaque and artery,and to the altered local hemodynamic environment due to the presence of stents.Different stent structures indeed have various impacts on the stresses of plaque and artery,and the local hemodynamic environment,such as the wall shear stress(WSS),average WSS(AWSS),and WSS gradient(WSSG).Thus,it is important to evaluate the performance of stents with different structures by the mechanical factors after coronary stenting.Methods Six stents implanted into a stenotic curved coronary artery were treated separately,and they included three typical commercial stents(Palmaz-Schatz,Xience,and Cypher)and three author-developed stents,which were constructed by reducing the numbers of link(C-Rlink)and crown(C-Rcrown),and aligning the strut(C-Astrut)of the commercial Cypher Solid mechanical analyses of the balloon-stent-plaque-artery system in Abaqus were first performed to assess the performance of different stent structures and provide the deformed boundary of lumen for the subsequent hemodynamic analysis.With the deformed boundary,then hemodynamic analyses in Ansys were conducted to quanti-fy the hemodynamic parameters induced by different stent structures.Combining the solid mechanical and hemodynamic analyses,the performance of the six stents was evaluated.Results The results show that among the three commercial stents,the Palmaz-Schatz stent has the least stent dogboning and recoiling,which corresponds to the greatest maximum plastic strain as well as the largest diameter.However,it induces the greatest maximum stress of plaque,intima,and media.From the viewpoint of hemodynamics,the Palmaz-Schatz stent also performs better and it has smaller areas of adverse low WSS(<0.5 Pa),high WSS(>15 Pa),low AWSS(<0.5 Pa),and high WSSG(>5 000 Pa/m).Compared to the commercial Cypher stent,the author-developed Cypher-based C-Rcrown and C-Astrut stents have smaller recoiling,greater maximum plastic stain and larger diameter,which indicates the improved mechanical performance of the Cypher stent.Moreover,both C-Rcrown and C-Astrut have smaller areas of adverse low WSS,high WSS,and low AWSS,but only C-Rcrown has smaller area of adverse high WSSG.Nevertheless,the C-Rlink stent is inferior to the commercial Cypher stent.In both senses of the solid mechanical and local hemodynamic analyses,the C-Rcrown stent is superior to the commercial Cypher stent and other Cypher-based stents.Conclusions In this study,solid mechanical and hemodynamic analyses were carried out to study the effects of six stents with different structures on their performances after stenting.It was found that the Palmaz-Schatz stent performed better than other two commercial stents,and the performance of the Cypher stent could be improved by reducing the number of crowns of its strut.The present study comparatively evaluates the performance of different stents inside a curved artery,and could be used as a guide to select a suitable commercial stent for clinical application,and provide a way to improve the performance of the existing commercial stents.展开更多
Objective To observe value of 0D-1D coupling model and 3D fluid-structure interaction(FSI)model based on coronary CT angiography(CCTA)for displaying hemodynamic characteristics of coronary artery stenosis.Methods Base...Objective To observe value of 0D-1D coupling model and 3D fluid-structure interaction(FSI)model based on coronary CT angiography(CCTA)for displaying hemodynamic characteristics of coronary artery stenosis.Methods Based on CCTA data of the stenosed left anterior descending branch(LAD)in a patient with coronary heart disease,an 0D-1D coupling model and 3D FSI model were built,respectively.Then hemodynamic characteristic indexes,including the pressure,flow velocity and wall shear stress(WSS)were obtained in every 0.01 s during 1 s at 5 sampling points(i.e.sampling point 1—5)using these 2 models,respectively,and the consistencies of the results between models were evaluated with Spearman correlation coefficient r s.Results The time consuming for construction of 0D-1D coupling model and 3D FSI model was 0.033 min and 704 min,respectively.Both models showed basically distribution of the pressure,flow velocity and WSS of the stenosed LAD.For more details,the pressure at the stenosed segment of LAD and the proximal segment of stenosis were both higher,which gradually decreased at the distal segment of stenosis,and the flow velocity at the proximal segment of stenosis was in a relatively slow and uniform condition,with significantly increased flow velocity and WSS at the stenosed segment.Compared with 3D FSI model,0D-1D vascular coupling model was relatively unrefined and lack of distal flow lines when displaying blood flow velocity.For sampling point 2 at the stenosed segment of LAD,no significant consistency for pressure between 2 models was found(P=0.118),but strong consistency for the flow velocity and WSS(r s=0.730,0.807,both P<0.05).The consistencies of pressure,flow velocity and WSS between 2 models at the proximal and distal segment of stenosis,i.e.1,3—5 sampling points were week to moderate(r s=0.237—0.669,all P<0.05).Conclusion 0D-1D coupling model exhibited outstanding computational efficiency and might provide relatively reasonable results,while 3D FSI model showed higher accuracy for details and streamline when simulating LAD stenosis.展开更多
Introduction The endothelial cells(ECs)lining every blood vessel wall constantly expose to the mechanical forces generated by the blood flow.The EC responses to these hemodynamic forces play a critical role in the hom...Introduction The endothelial cells(ECs)lining every blood vessel wall constantly expose to the mechanical forces generated by the blood flow.The EC responses to these hemodynamic forces play a critical role in the homeostasis of the circulatory system.In addition to forming a transport barrier between the blood and vessel wall,vascular ECs play important roles in regulating circulation functions.Besides biochemical stimuli,blood flow induced(hemodynamic)mechanical stimuli,such as shear stress,pressure and circumferential stretch,modulate EC morphology and functions by activating mechanosensors,signaling pathways,and gene and protein expressions.The EC responses to the hemodynamic forces(mechano-sensing and transduction)展开更多
Nowadays,cardiovascular disease has gradually become the number one killer of human health.The Stanford type-A aortic dissection is a relatively common cardiovascular disease with potential hazards.The disease is caus...Nowadays,cardiovascular disease has gradually become the number one killer of human health.The Stanford type-A aortic dissection is a relatively common cardiovascular disease with potential hazards.The disease is caused by a partialtearing of the aortic intima.Thoracic endovascular aortic repair(TEVAR)is one of the most effective treatment for type A aortic dissection and has been widely used clinically to achieve thrombosis and reduce pressure by covering the incision tear in the FL.However,the effect of entry tear location on type-A aortic dissection and the prognosis of TEVAR intervention are unclear.In this work,the hemodynamic effects of the type-A aortic dissection in different entry and covering entry tear position were mainly studied.It can provide a new method or idea in the field of the aortic dissection hemodynamics,which is of great significance to provide a basic theoretical research on the development of aortic dissection in the aspect of clinical judgment.Two type-A aortic dissection models with different entry tear positions(Model 1:the entry tear was located at the entrance of the ascending aorta,Model 2:the entry tear was located at the starting position of the descending aorta)were reconstructed according to the computed tomography(CT)images of the patients.In our study,the thoracic aortic endovascular repair was simulated by covering the entry tear(Model 3).Then,the semi-automatic adaptive technology HyperMeshl0.0(Altair HyperWorks,Troy,Ml,USA)mesh generator was used to generate the high-quality tetrahedral 3D mesh.To clarify the hemodynamic effects of entry tear and coverage in aortic blood flow pattern,the comparative study on the true lumen(TL)and false lumen(FL)blood flow patterns of three models were carried out numerically(the time-dependent pulsatile waveform of pressure boundary conditions used at the aortic inlet were consistent with Rapezzis’s work,time-dependent pulsatile waveform of velocity at the descending aorta outlet and the time-dependent pulsatile waveform of pressure at the brachiocephalic artery,left common carotid artery,and left subclavian artery were obtained from the work of Olufsenet et al).The velocity vector,flow ratio,pressure,time-average wall shear stress(TAWSS)and relative residence time(RRT)were calculated to evaluate the hemodynamic changes.The results of this work indicated that(Ⅰ)the velocity was higher at the entry tear in aorta entrance;(Ⅱ)the helical development of the TL and FL might be related to the helical nature of aortic arch;(Ⅲ)the blood flow which passing the FL of Model 1,Model 2 and Model 3 in one cardiac cycle were approximately 26.63%,13.39%and 1%,respectively;(Ⅳ)the difference in intima wall pressure among the TL and FL was found varied a lot and shown a strong pulsation;(Ⅴ)the TAWSS distribution in TL and FL were quite different(the TAWSS in TL intima>8 Pa,the TAWSS in FL intima<4 Pa).In brief,the aortic morphology and location of the entry tear were found to have a significant effect on the hemodynamic of the aortic dissection.What’s more,we found that the risk of the aortic rupture could be higher if the position of entry tear is closer to the ascending aorta.By covering the entry tear to simulate TEVAR,the pressure of FL was reduced,which could provide some help for the treatment of early retrograde type-A dissection.展开更多
It is critical to combat tumor metastasis by eradicating disseminated tumor cells in any step during the metastasis process.After entering the blood circulation system,tumor cells are in suspension and experience cons...It is critical to combat tumor metastasis by eradicating disseminated tumor cells in any step during the metastasis process.After entering the blood circulation system,tumor cells are in suspension and experience considerable levels of fluid shear stress.However,the influence of hemodynamic shear stress on the survival of CTCs and the underlying mechanotransduction mechanisms remain unclear.This study shows that fluid shear stress can eliminate the majority of CTCs and the viability of suspended tumor cells depends on the stress magnitude,indicating that tumor cells can sense and respond to fluid shear stress.Mechanistically,the expression of Piezo1 but not Piezo2 is greatly upregulated in suspended tumor cells after shear stress treatment.Inhibiting/activating Piezo1 increases/decreases the viability of suspended tumor cells in shear flow,which depends on Piezo1-mediated calcium entry.These findings suggest that Piezo1 may be the major mechanosensor by which suspended tumor cells sense fluid shear stress.As the downstream effector of Piezo1,actomyosin in tumor cells is significantly activated under increasing shear stress.Its activity influences the survival of CTCs in shear flow and rescues the effects of Piezo1 on tumor cell survival,suggesting that hemodynamic shear stress regulates the survival of CTCs through Piezo1 mediated actomyosin activity.Importantly,fluid shear stress considerably up-regulates YAP/TAZ activity of suspended tumor cells and promotes their nuclear translocation in a magnitude-dependent manner.Inhibiting YAP/TAZ enhances the viability of suspended tumor cells in shear stress,while activating their activity decreases tumor cell survival,suggesting that YAP/TAZ activation promotes the apoptosis of suspended tumor cells,which is different from the findings that YAP/TAZ facilitates the survival of adherent cells to shear flow.Further,blocking the nuclear import of YAP/TAZ inactivates the sensation of suspended tumor cells to fluid shear flow and attenuates the dependence of tumor cell survival on different magnitudes of hemodynamic shear stress.The influence of Piezo1-actomyosin pathway on suspended tumor cells can be rescued by YAP/TAZ activity,suggesting that Piezo1-mediated signaling induces tumor cell apoptosis via nuclear translocation of YAP/TAZ.In addition,fluid shear stress can also activate the expressions of LATS1/2 and MST1/2 in Hippo pathway through Piezo1,which is known to inhibit YAP/TAZ activity.Silencing/activating LATS1/2 or MST1/2 inhibits/enhances the viability of CTCs under shear stress,the effects of which can be further rescued by YAP/TAZ.These findings suggest that the responses of suspended tumor cells to hemodynamic shear stress are partially mediated by Hippo signaling.After nuclear translocation,YAP/TAZ directly bind p73/PUMA,which further promotes the transcription of pro-apoptotic genes and induces the apoptosis of suspended tumor cells.In summary,these findings show that hemodynamic shear stress considerably influences the survival of CTCs in blood circulation.We have identified the calcium channel Piezo1 as a novel mechanosensor for the response of CTCs to fluid shear stress.Hemodynamic shear stress induces the apoptosis of suspended tumor cells through Piezo1-actomyosin-YAP/TAZ-p73/PUMA signaling,which is different from the mechanotranduction mechanisms for tumor cells in adherent.Therefore,this study has unveiled the novel mechanosensor of suspended CTCs in response to fluid shear stress and the subsequent mechanisms and identified Piezo1 and YAP/TAZ as the potential therapeutic targets,through which CTCs may be effectively eradicated in the vasculature to prohibit tumor metastasis.展开更多
Hemodynamic responses to hypoxic challenge on rats werechecked either in anesthetic state or in awake state. The rats in awake state wereunder taken hemodynamic study at 48 hours after Pentobarbital（PB） anesthesiaan...Hemodynamic responses to hypoxic challenge on rats werechecked either in anesthetic state or in awake state. The rats in awake state wereunder taken hemodynamic study at 48 hours after Pentobarbital（PB） anesthesiaand catheterization. Hemodynamic responses to hypoxic ventilation on dogs wasconducted either at 2 hours or at 4 hours after PB. During hypoxic ventilationflaxidel was used to maintain skeletal muscular relaxation, yet PB was not re-peated to diminish it’s influence on hypoxic responses. Blood gas assay was car-ried out in dogs during normoxia and hypoxic challenge. Hypoxic challengecaused significant increase of pulmonary artery pressure （Ppa） and almost nochange in systemic artery pressure （Psa） in awake rats. However in anestheticrats hypoxic challenge had little effect on Ppa, without influence on Psa. At 2and 4 hours after PB administration and catheterization hypoxic ventilationcaused similar change in blood gas （PaO<sub>2</sub> and PvO<sub>2</sub>）. However the second hy-poxic ventilation （4h） produced more significant pulmonary hemodynamic re-sponses （Ppa and TPVR greatly increased）. These results suggested thatpreferable acute hypoxic pulmonary hypertension developed either in awake ratsor in relatively shallow anesthetic state of dogs, indicating that PB anesthesiamay inhibit hypoxic pulmonary hemodynamic responses.展开更多
Objective To investigate the survival of different subgroups of pulmonary hypertension due to left heart disease(PH-LHD)in heart failure patients with reduced ejection fraction(HFrEF)and to detect possible hemodynamic...Objective To investigate the survival of different subgroups of pulmonary hypertension due to left heart disease(PH-LHD)in heart failure patients with reduced ejection fraction(HFrEF)and to detect possible hemodynamic variables associated with the prognosis of these patients.展开更多
In 1996 Li[1] proposed a novel left ventricular assist device-the dynamic aortic valve(DAV) which did not need the percutaneous drive-lines[2].An Intra-Aorta pump was produced by Biomedical Center of Beijing Universit...In 1996 Li[1] proposed a novel left ventricular assist device-the dynamic aortic valve(DAV) which did not need the percutaneous drive-lines[2].An Intra-Aorta pump was produced by Biomedical Center of Beijing University of Technology.It consisted of two parts:展开更多
基金supported by National Science Foundation of China(51176152)Specialized Research Fund for the Doctoral Program of Higher Education(20120201110070)the Fundamental Research Funds for the Central University(xjj2012115)
文摘Introduction Liver cirrhosis generally occurs with the hemodynamic changes during the portal vein hypertension and finally leads to the atrophy of the right lobe of the liver and hepatic failure<sup>[1]</sup>.According to the hemodynamic changes,a hypothesis has been proposed that the liver volume is related to the istribution of blood from the splenic vein（SV）that involves nutrition from spleen and pancreas<sup>[2,3]</sup>.The objective of the present paper is to simulate the blood flow in real models of portal vein hypertension and validate the hypothesis using computational fluid dynamics（CFD）method.Methods This study includes 2 patients with liver cirrhosis and a set of 4 normal subjects.
基金supported by the Natural Science Foundation of China ( NSFC) ( 31300780,11272091, 11422222,31470043)supported by the National 973 Basic Research Program of China ( 2013CB733800)China scholarship Council ( 201706090121) ,and ARC ( FT140101152)
文摘Background Coronary artery stenting is commonly used for the treatment of coronary atherosclerosis,but it causes serious clinical complications,such as the in-stent restenosis(ISR).The main reason leading to ISR is the neointimal hyperplasia(NH),which is related to the stresses of plaque and artery,and to the altered local hemodynamic environment due to the presence of stents.Different stent structures indeed have various impacts on the stresses of plaque and artery,and the local hemodynamic environment,such as the wall shear stress(WSS),average WSS(AWSS),and WSS gradient(WSSG).Thus,it is important to evaluate the performance of stents with different structures by the mechanical factors after coronary stenting.Methods Six stents implanted into a stenotic curved coronary artery were treated separately,and they included three typical commercial stents(Palmaz-Schatz,Xience,and Cypher)and three author-developed stents,which were constructed by reducing the numbers of link(C-Rlink)and crown(C-Rcrown),and aligning the strut(C-Astrut)of the commercial Cypher Solid mechanical analyses of the balloon-stent-plaque-artery system in Abaqus were first performed to assess the performance of different stent structures and provide the deformed boundary of lumen for the subsequent hemodynamic analysis.With the deformed boundary,then hemodynamic analyses in Ansys were conducted to quanti-fy the hemodynamic parameters induced by different stent structures.Combining the solid mechanical and hemodynamic analyses,the performance of the six stents was evaluated.Results The results show that among the three commercial stents,the Palmaz-Schatz stent has the least stent dogboning and recoiling,which corresponds to the greatest maximum plastic strain as well as the largest diameter.However,it induces the greatest maximum stress of plaque,intima,and media.From the viewpoint of hemodynamics,the Palmaz-Schatz stent also performs better and it has smaller areas of adverse low WSS(<0.5 Pa),high WSS(>15 Pa),low AWSS(<0.5 Pa),and high WSSG(>5 000 Pa/m).Compared to the commercial Cypher stent,the author-developed Cypher-based C-Rcrown and C-Astrut stents have smaller recoiling,greater maximum plastic stain and larger diameter,which indicates the improved mechanical performance of the Cypher stent.Moreover,both C-Rcrown and C-Astrut have smaller areas of adverse low WSS,high WSS,and low AWSS,but only C-Rcrown has smaller area of adverse high WSSG.Nevertheless,the C-Rlink stent is inferior to the commercial Cypher stent.In both senses of the solid mechanical and local hemodynamic analyses,the C-Rcrown stent is superior to the commercial Cypher stent and other Cypher-based stents.Conclusions In this study,solid mechanical and hemodynamic analyses were carried out to study the effects of six stents with different structures on their performances after stenting.It was found that the Palmaz-Schatz stent performed better than other two commercial stents,and the performance of the Cypher stent could be improved by reducing the number of crowns of its strut.The present study comparatively evaluates the performance of different stents inside a curved artery,and could be used as a guide to select a suitable commercial stent for clinical application,and provide a way to improve the performance of the existing commercial stents.
文摘Objective To observe value of 0D-1D coupling model and 3D fluid-structure interaction(FSI)model based on coronary CT angiography(CCTA)for displaying hemodynamic characteristics of coronary artery stenosis.Methods Based on CCTA data of the stenosed left anterior descending branch(LAD)in a patient with coronary heart disease,an 0D-1D coupling model and 3D FSI model were built,respectively.Then hemodynamic characteristic indexes,including the pressure,flow velocity and wall shear stress(WSS)were obtained in every 0.01 s during 1 s at 5 sampling points(i.e.sampling point 1—5)using these 2 models,respectively,and the consistencies of the results between models were evaluated with Spearman correlation coefficient r s.Results The time consuming for construction of 0D-1D coupling model and 3D FSI model was 0.033 min and 704 min,respectively.Both models showed basically distribution of the pressure,flow velocity and WSS of the stenosed LAD.For more details,the pressure at the stenosed segment of LAD and the proximal segment of stenosis were both higher,which gradually decreased at the distal segment of stenosis,and the flow velocity at the proximal segment of stenosis was in a relatively slow and uniform condition,with significantly increased flow velocity and WSS at the stenosed segment.Compared with 3D FSI model,0D-1D vascular coupling model was relatively unrefined and lack of distal flow lines when displaying blood flow velocity.For sampling point 2 at the stenosed segment of LAD,no significant consistency for pressure between 2 models was found(P=0.118),but strong consistency for the flow velocity and WSS(r s=0.730,0.807,both P<0.05).The consistencies of pressure,flow velocity and WSS between 2 models at the proximal and distal segment of stenosis,i.e.1,3—5 sampling points were week to moderate(r s=0.237—0.669,all P<0.05).Conclusion 0D-1D coupling model exhibited outstanding computational efficiency and might provide relatively reasonable results,while 3D FSI model showed higher accuracy for details and streamline when simulating LAD stenosis.
文摘Introduction The endothelial cells(ECs)lining every blood vessel wall constantly expose to the mechanical forces generated by the blood flow.The EC responses to these hemodynamic forces play a critical role in the homeostasis of the circulatory system.In addition to forming a transport barrier between the blood and vessel wall,vascular ECs play important roles in regulating circulation functions.Besides biochemical stimuli,blood flow induced(hemodynamic)mechanical stimuli,such as shear stress,pressure and circumferential stretch,modulate EC morphology and functions by activating mechanosensors,signaling pathways,and gene and protein expressions.The EC responses to the hemodynamic forces(mechano-sensing and transduction)
基金funded by the National Natural Science Foundation of China ( 11602007,11572014, 11832003)Key research and development program ( 2017YFC0111104)New Talent ( 015000514118002)
文摘Nowadays,cardiovascular disease has gradually become the number one killer of human health.The Stanford type-A aortic dissection is a relatively common cardiovascular disease with potential hazards.The disease is caused by a partialtearing of the aortic intima.Thoracic endovascular aortic repair(TEVAR)is one of the most effective treatment for type A aortic dissection and has been widely used clinically to achieve thrombosis and reduce pressure by covering the incision tear in the FL.However,the effect of entry tear location on type-A aortic dissection and the prognosis of TEVAR intervention are unclear.In this work,the hemodynamic effects of the type-A aortic dissection in different entry and covering entry tear position were mainly studied.It can provide a new method or idea in the field of the aortic dissection hemodynamics,which is of great significance to provide a basic theoretical research on the development of aortic dissection in the aspect of clinical judgment.Two type-A aortic dissection models with different entry tear positions(Model 1:the entry tear was located at the entrance of the ascending aorta,Model 2:the entry tear was located at the starting position of the descending aorta)were reconstructed according to the computed tomography(CT)images of the patients.In our study,the thoracic aortic endovascular repair was simulated by covering the entry tear(Model 3).Then,the semi-automatic adaptive technology HyperMeshl0.0(Altair HyperWorks,Troy,Ml,USA)mesh generator was used to generate the high-quality tetrahedral 3D mesh.To clarify the hemodynamic effects of entry tear and coverage in aortic blood flow pattern,the comparative study on the true lumen(TL)and false lumen(FL)blood flow patterns of three models were carried out numerically(the time-dependent pulsatile waveform of pressure boundary conditions used at the aortic inlet were consistent with Rapezzis’s work,time-dependent pulsatile waveform of velocity at the descending aorta outlet and the time-dependent pulsatile waveform of pressure at the brachiocephalic artery,left common carotid artery,and left subclavian artery were obtained from the work of Olufsenet et al).The velocity vector,flow ratio,pressure,time-average wall shear stress(TAWSS)and relative residence time(RRT)were calculated to evaluate the hemodynamic changes.The results of this work indicated that(Ⅰ)the velocity was higher at the entry tear in aorta entrance;(Ⅱ)the helical development of the TL and FL might be related to the helical nature of aortic arch;(Ⅲ)the blood flow which passing the FL of Model 1,Model 2 and Model 3 in one cardiac cycle were approximately 26.63%,13.39%and 1%,respectively;(Ⅳ)the difference in intima wall pressure among the TL and FL was found varied a lot and shown a strong pulsation;(Ⅴ)the TAWSS distribution in TL and FL were quite different(the TAWSS in TL intima>8 Pa,the TAWSS in FL intima<4 Pa).In brief,the aortic morphology and location of the entry tear were found to have a significant effect on the hemodynamic of the aortic dissection.What’s more,we found that the risk of the aortic rupture could be higher if the position of entry tear is closer to the ascending aorta.By covering the entry tear to simulate TEVAR,the pressure of FL was reduced,which could provide some help for the treatment of early retrograde type-A dissection.
文摘It is critical to combat tumor metastasis by eradicating disseminated tumor cells in any step during the metastasis process.After entering the blood circulation system,tumor cells are in suspension and experience considerable levels of fluid shear stress.However,the influence of hemodynamic shear stress on the survival of CTCs and the underlying mechanotransduction mechanisms remain unclear.This study shows that fluid shear stress can eliminate the majority of CTCs and the viability of suspended tumor cells depends on the stress magnitude,indicating that tumor cells can sense and respond to fluid shear stress.Mechanistically,the expression of Piezo1 but not Piezo2 is greatly upregulated in suspended tumor cells after shear stress treatment.Inhibiting/activating Piezo1 increases/decreases the viability of suspended tumor cells in shear flow,which depends on Piezo1-mediated calcium entry.These findings suggest that Piezo1 may be the major mechanosensor by which suspended tumor cells sense fluid shear stress.As the downstream effector of Piezo1,actomyosin in tumor cells is significantly activated under increasing shear stress.Its activity influences the survival of CTCs in shear flow and rescues the effects of Piezo1 on tumor cell survival,suggesting that hemodynamic shear stress regulates the survival of CTCs through Piezo1 mediated actomyosin activity.Importantly,fluid shear stress considerably up-regulates YAP/TAZ activity of suspended tumor cells and promotes their nuclear translocation in a magnitude-dependent manner.Inhibiting YAP/TAZ enhances the viability of suspended tumor cells in shear stress,while activating their activity decreases tumor cell survival,suggesting that YAP/TAZ activation promotes the apoptosis of suspended tumor cells,which is different from the findings that YAP/TAZ facilitates the survival of adherent cells to shear flow.Further,blocking the nuclear import of YAP/TAZ inactivates the sensation of suspended tumor cells to fluid shear flow and attenuates the dependence of tumor cell survival on different magnitudes of hemodynamic shear stress.The influence of Piezo1-actomyosin pathway on suspended tumor cells can be rescued by YAP/TAZ activity,suggesting that Piezo1-mediated signaling induces tumor cell apoptosis via nuclear translocation of YAP/TAZ.In addition,fluid shear stress can also activate the expressions of LATS1/2 and MST1/2 in Hippo pathway through Piezo1,which is known to inhibit YAP/TAZ activity.Silencing/activating LATS1/2 or MST1/2 inhibits/enhances the viability of CTCs under shear stress,the effects of which can be further rescued by YAP/TAZ.These findings suggest that the responses of suspended tumor cells to hemodynamic shear stress are partially mediated by Hippo signaling.After nuclear translocation,YAP/TAZ directly bind p73/PUMA,which further promotes the transcription of pro-apoptotic genes and induces the apoptosis of suspended tumor cells.In summary,these findings show that hemodynamic shear stress considerably influences the survival of CTCs in blood circulation.We have identified the calcium channel Piezo1 as a novel mechanosensor for the response of CTCs to fluid shear stress.Hemodynamic shear stress induces the apoptosis of suspended tumor cells through Piezo1-actomyosin-YAP/TAZ-p73/PUMA signaling,which is different from the mechanotranduction mechanisms for tumor cells in adherent.Therefore,this study has unveiled the novel mechanosensor of suspended CTCs in response to fluid shear stress and the subsequent mechanisms and identified Piezo1 and YAP/TAZ as the potential therapeutic targets,through which CTCs may be effectively eradicated in the vasculature to prohibit tumor metastasis.
文摘Hemodynamic responses to hypoxic challenge on rats werechecked either in anesthetic state or in awake state. The rats in awake state wereunder taken hemodynamic study at 48 hours after Pentobarbital（PB） anesthesiaand catheterization. Hemodynamic responses to hypoxic ventilation on dogs wasconducted either at 2 hours or at 4 hours after PB. During hypoxic ventilationflaxidel was used to maintain skeletal muscular relaxation, yet PB was not re-peated to diminish it’s influence on hypoxic responses. Blood gas assay was car-ried out in dogs during normoxia and hypoxic challenge. Hypoxic challengecaused significant increase of pulmonary artery pressure （Ppa） and almost nochange in systemic artery pressure （Psa） in awake rats. However in anestheticrats hypoxic challenge had little effect on Ppa, without influence on Psa. At 2and 4 hours after PB administration and catheterization hypoxic ventilationcaused similar change in blood gas （PaO<sub>2</sub> and PvO<sub>2</sub>）. However the second hy-poxic ventilation （4h） produced more significant pulmonary hemodynamic re-sponses （Ppa and TPVR greatly increased）. These results suggested thatpreferable acute hypoxic pulmonary hypertension developed either in awake ratsor in relatively shallow anesthetic state of dogs, indicating that PB anesthesiamay inhibit hypoxic pulmonary hemodynamic responses.
文摘Objective To investigate the survival of different subgroups of pulmonary hypertension due to left heart disease(PH-LHD)in heart failure patients with reduced ejection fraction(HFrEF)and to detect possible hemodynamic variables associated with the prognosis of these patients.
文摘In 1996 Li[1] proposed a novel left ventricular assist device-the dynamic aortic valve(DAV) which did not need the percutaneous drive-lines[2].An Intra-Aorta pump was produced by Biomedical Center of Beijing University of Technology.It consisted of two parts:
