Explore the vast range of titles available.

Epithelial–mesenchymal transition (EMT) mediated by fluid shear stress (FSS) in the tumor microenvironment plays an important role in driving metastasis of the malignant tumor. As a mechanotransducer, Yes‐associated protein (YAP) is known to translocate into the nucleus to initiate transcription of genes involved in cell proliferation upon extracellular biophysical stimuli. Here, we showed that FSS facilitated cytoskeleton rearrangement in hepatocellular carcinoma cells, which led to the release of YAP from its binding partner, integrin β subunit, in the cytomembrane. Moreover, we found that upregulation of guanine nucleotide exchange factor (GEF)‐H1, a microtubule‐associated Rho GEF, is a critical step in the FSS‐induced translocation of YAP. Nuclear YAP activated the expression of the EMT‐regulating transcription factor SNAI1, but suppressed the expression of N6‐methyladenosine (m6A) modulators; together, this promoted the expression of EMT‐related genes. We also observed that FSS‐treated HepG2 cells showed markedly increased tumorigenesis and metastasis in vivo. Collectively, our findings unravel the underlying molecular processes by which FSS induces translocation of YAP from the cytomembrane to the nucleus, contributes to EMT and enhances metastasis in hepatocellular carcinoma. Here, we describe the underlying mechanism by which fluid shear stress (FSS) induces epithelial–mesenchymal transition (EMT) and enhances metastasis in hepatocellular carcinoma. Upon FSS, Yes‐associated protein (YAP) was released from its membrane binding partner integrin β subunits. Upregulation of GEF‐H1 promoted FSS‐induced nuclear translocation of YAP, which in turn regulated EMT‐related gene expression through SNAI1 and m6A modulators.

ObjectiveTo develop a model using patient-specific computational fluid dynamics (CFD) to predict the required anastomotic size for total anomalous pulmonary venous connection (TAPVC) surgery and to forecast surgical outcomes.MethodsBased on clinical data from patients, a CFD model was used to simulate the anastomosis between pulmonary venous confluence and the left atrium. Blood flow velocity, wall shear stress, power loss, and pressure were calculated using numerical algorithms within the model. Various sizes of anastomosis were applied during the simulation. The energy dissipation at the anastomosis was computed from the results and compared with real-world data.ResultsAs the simulated anastomotic size increased, blood flow velocity, pulmonary venous pressure, and energy loss decreased. However, when the anastomotic size exceeded 18 mm, the efficiency of energy conversion no longer improved. The realistic and simulated velocities matched well for anastomosis sizes ranging from 15 to 20 mm.ConclusionThe model can assist surgeons in preoperative planning for determining the anastomotic size in TAPVC surgical treatment.

The pulsatile properties of arterial flow and pressure have been thought to be important. Nevertheless, a gap still exists in the hemodynamic effect of pulsatile flow in improving blood flow distribution of veno-arterial extracorporeal membrane oxygenation (VA ECMO) supported by the circulatory system. The finite-element models, consisting of the aorta, VA ECMO, and intra-aortic balloon pump (IABP) are proposed for fluid-structure interaction calculation of the mechanical response. Group A is cardiogenic shock with 1.5 L/min of cardiac output. Group B is cardiogenic shock with VA ECMO. Group C is added to IABP based on Group B. The sum of the blood flow of cardiac output and VA ECMO remains constant at 4.5 L/min in Group B and Group C. With the recovery of the left ventricular, the flow of VA ECMO declines, and the effective blood of IABP increases. IABP plays the function of balancing blood flow between left arteria femoralis and right arteria femoralis compared with VA ECMO only. The difference of the equivalent energy pressure (dEEP) is crossed at 2.0 L/min to 1.5 L/min of VA ECMO. PPI’ (the revised pulse pressure index) with IABP is twice as much as without IABP. The intersection with two opposing blood generates the region of the aortic arch for the VA ECMO (Group B). In contrast to the VA ECMO, the blood intersection appears from the descending aorta to the renal artery with VA ECMO and IABP. The maximum time-averaged wall shear stress (TAWSS) of the renal artery is a significant difference with or not IABP (VA ECMO: 2.02 vs. 1.98 vs. 2.37 vs. 2.61 vs. 2.86 Pa; VA ECMO and IABP: 8.02 vs. 6.99 vs. 6.62 vs. 6.30 vs. 5.83 Pa). In conclusion, with the recovery of the left ventricle, the flow of VA ECMO declines and the effective blood of IABP increases. The difference between the equivalent energy pressure (EEP) and the surplus hemodynamic energy (SHE) indicates the loss of pulsation from the left ventricular to VA ECMO. 2.0 L/min to 1.5 L/min of VA ECMO showing a similar hemodynamic energy loss with the weak influence of IABP.

Background Peripheral ECMO is an effective cardiopulmonary support in clinical. The perfusion level could directly influence the performances and complications. However, there are few studies on the effects of the perfusion level on hemodynamics of peripheral ECMO. Methods The geometric model of cardiovascular system with peripheral ECMO was established. The blood assist index was used to classify the perfusion level of the ECMO. The flow pattern from the aorta to the femoral artery and their branches, blood flow rate from aorta to brain and limbs, flow interface, harmonic index of blood flow, wall shear stress and oscillatory shear index were chosen to evaluate the hemodynamic effects of peripheral ECMO. Results The results demonstrated that the flow rate of aorta outlets increased and perfusion condition had been improved. And the average flow to the upper limbs and brain has a positive correlation with BAI (r = 0.037, p < 0.05), while there is a negative correlation with lower limbs (r = − 0.054, p < 0.05). The HI has negative correlation with BAI (p < 0.05, r < 0). The blood interface is further from the heart with the BAI decrease. And the average WSS has negative correlation with BAI (p < 0.05, r = − 0.983) at the bifurcation of femoral aorta and has positive correlation with BAI (p < 0.05, r = 0.99) at the inner aorta. The OSI under different BAI is higher (reaching 0.4) at the inner wall of the aortic arch, the descending aorta and the femoral access. Conclusions The pathogenesis of peripheral ECMO with different perfusion levels varies; its further research will be thorough and extensive.

Objectives Does the manipulation of the off-pump CABG (OPCAB) in patient with depressed left ventricular function is better than on-pump CABG (ONCAB) approach in in-hospital mortality and morbidities? Here we undertook a meta-analysis of the best evidence available on the comparison of primary and second clinical outcomes of the off-pump and on-pump CABG. Design Systematic literature reviewer and meta-analysis. Data sources PubMed, EMBASE, Web of science and Cochrane Center Registry of Controlled Trials were searched the studies which comparing the use of the off-pump CABG(OPCAB) and on-pump CABG (ONCAB) for patients with LVD during January 1990.1 to January 2018. Eligibility criteria All observation studies and randomized controlled trials comparing on-pump and off-pump as main technique for multi-vessel coronary artery disease (defined as severe stenosis (>70%) in at least 2 major diseased coronary arteries) with left ventricular dysfunction(defined as ejection fraction (EF) 40% or less) were included. Data extraction and synthesis Authors will screen and select the studies extract the following data, first author, year of publication, trial characters, study design, inclusion and exclusion criteria, graft type, clinical outcome, assess the risk of bias and heterogeneity. Study-specific estimates will pool through the modification of the Newcastle-Ottawa scale for the quality of study and while leave-one-out analysis will be used to detect the impact of individual studies on the robustness of outcomes. Results Among the 987 screened articles, a total of 16 studies (32,354 patients) were included. A significant relationship between patient risk profile and benefits from OPCAB was found in terms of the 30-day mortality (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.73–0.97; P  = 0.02), stroke (OR, 0.69; 95% CI, 0.55–0.86; P  = 0.00) , myocardial infarction (MI) (OR, 0.71; 95% CI, 0.53–0.96; P  = 0.02), renal failure (OR, 0.71; 95% CI, 0.55–0.93; P  = 0.01), pulmonary complication (OR, 0.68; 95% CI, 0.52–0.90; P  = 0.01), infection (OR, 0.67; 95% CI, 0.49–0.91; P  = 0.00),postoperative transfusion (OR, 0.25; 95% CI, 0.08–0.84; P  = 0.02) and reoperation for bleeding (OR, 0.56; 95% CI, 0.41–0.75; P  = 0.00). There was no significant difference in atrial fibrillation (AF) (OR, 0.96;95%; CI, 0.78–1.41; P  = 0.56) and neurological dysfunction (OR, 0.88; 95% CI, 0.49–1.57; P  = 0.65). Conclusions Compared with the on-pump CABG with LVD, using the off-pump CABG is a better choice for patients with lower mortality, stroke, MI, RF, pulmonary complication, infection, postoperative transfusion and reoperation for bleeding. Further randomized studies are warranted to corroborate these observational data.

Background Hemodynamic characteristics of the interaction influence among support level and model of LVAD, and coupling β-blocker has not been reported. Methods In this study, the effect of support level and model of LVAD on cardiovascular hemodynamic characteristics is investigated. In addition, the effect of β-blocker on unloading with LVAD is analyzed to elucidate the mechanism of LVAD coupling β-blocker. A multi-scale model from cell level to system level is proposed. Moreover, LVAD coupling β-blocker has been researching to explain the hemodynamics of cardiovascular system. Results Myocardial force was decreased along with the increase of support level of LVAD, and co-pulse mode was the lowest among the three support modes. Additionally, the β-blocker combined with LVAD significantly reduced the left ventricular volume compared with LVAD support without β-blocker. However, the left ventricular pressure under both cases has no significant difference. External work of right ventricular was increased along with the growth of support level of only LVAD. The LVAD under co-pulse mode achieved the lowest right-ventricular EW among the three support modes. Conclusions Co-pulse mode with β-blocker could be an optimal strategy for promoting cardiac structure and function recovery.

Centrifugal pump is a key core component of spacecraft thermal control system, and its operational stability directly determines the life of the spacecraft. In microgravity environment, buoyancy effect disappears, and the influence of surface tension effect on cavitation flow cannot be ignored. The centrifugal pump used in the thermal control system of spacecraft is taken as the research object. The critical cavitation coefficient of a centrifugal pump under microgravity and ground gravity, as well as the cavitation flow field at different flow rates, were studied through numerical simulation. The existence of surface tension can to some extent increase the dimensionless head of centrifugal pumps during cavitation, and the degree of increase in head by surface tension is positively correlated with the inlet flow rate. The existence of surface tension will delay the development process of cavitation in the entire impeller basin. The effect of surface tension on the cavitation of micro pumps is specifically manifested as delaying the initiation and development of bubbles, while accelerating the contraction of bubbles. The research results can provide a basis for the design optimization of centrifugal pumps in microgravity environments.

Lumped parameter model (LPM) is a common numerical model for hemodynamic simulation of human’s blood circulatory system. The numerical simulation of enhanced external counterpulsation (EECP) is a typical biomechanical simulation process based on the LPM of blood circulatory system. In order to simulate patient-specific hemodynamic effects of EECP and develop best treatment strategy for each individual, this study developed an optimization algorithm to individualize LPM elements. Physiological data from 30 volunteers including approximate aortic pressure, cardiac output, ankle pressure and carotid artery flow were clinically collected as optimization objectives. A closed-loop LPM was established for the simulation of blood circulatory system. Aiming at clinical data, a sensitivity analysis for each element was conducted to identify the significant ones. We improved the traditional simulated annealing algorithm to iteratively optimize the sensitive elements. To verify the accuracy of the patient-specific model, 30 samples of simulated data were compared with clinical measurements. In addition, an EECP experiment was conducted on a volunteer to verify the applicability of the optimized model for the simulation of EECP. For these 30 samples, the optimization results show a slight difference between clinical data and simulated data. The average relative root mean square error is lower than 5%. For the subject of EECP experiment, the relative error of hemodynamic responses during EECP is lower than 10%. This slight error demonstrated a good state of optimization. The optimized modeling algorithm can effectively individualize the LPM for blood circulatory system, which is significant to the numerical simulation of patient-specific hemodynamics.

Background. Type 2 diabetes is a major health concern worldwide. The present study is aimed at discovering effective biomarkers for an efficient diagnosis of type 2 diabetes. Methods. Differentially expressed genes (DEGs) between type 2 diabetes patients and normal controls were identified by analyses of integrated microarray data obtained from the Gene Expression Omnibus database using the Limma package. Functional analysis of genes was performed using the R software package clusterProfiler. Analyses of protein-protein interaction (PPI) performed using Cytoscape with the CytoHubba plugin were used to determine the most sensitive diagnostic gene biomarkers for type 2 diabetes in our study. The support vector machine (SVM) classification model was used to validate the gene biomarkers used for the diagnosis of type 2 diabetes. Results. GSE164416 dataset analysis revealed 499 genes that were differentially expressed between type 2 diabetes patients and normal controls, and these DEGs were found to be enriched in the regulation of the immune effector pathway, type 1 diabetes mellitus, and fatty acid degradation. PPI analysis data showed that five MCODE clusters could be considered as clinically significant modules and that 10 genes (IL1B, ITGB2, ITGAX, COL1A1, CSF1, CXCL12, SPP1, FN1, C3, and MMP2) were identified as “real” hub genes in the PPI network using algorithms such as Degree, MNC, and Closeness. The sensitivity and specificity of the SVM model for identifying patients with type 2 diabetes were 100%, with an area under the curve of 1 in the training as well as the validation dataset. Conclusion. Our results indicate that the SVM-based model developed by us can facilitate accurate diagnosis of type 2 diabetes.

The role of pulsatile unloading in hemodynamic changes in intraventricular flow and ventricular wall stress remains unknown. In this study, a finite element model of the left ventricle (LV) is proposed to calculate the mechanical response. The constitutive model of the LV is composed of a quasi-incompressible transversely isotropic model and an active contraction of the myocardium model. Pulsatile unloading is provided by the left ventricular assist device (LVAD), which is implanted between the aortic root and aortic arch. Support models (constant speed and co-pulse) were utilized to study the effect of pulsatile unloading on intraventricular flow and ventricular stress. The result indicates that the formation time of the vortex increases under pulsatile unloading. The area rate of high time-averaged wall shear stress (TAWSS) increased after pulsatile unloading. The area of the high oscillatory shear index (OSI) region (OSI > 0.375) was calculated for heart failure, constant speed, and co-pulse (9.9 cm2, 9.6 cm2, and 9.2 cm2, respectively). The maximum value of the stress that reflects the level of stretch declined after pulsatile unloading (66.4 kPa, 30.9 kPa, and 21.3 kPa, respectively). Besides, pulsatile unloading impacts the maximum value of thickness at the ventricular wall (−0.75 mm, −1 mm, and −1.25 mm, respectively). The change ratios of the thickness are 10%, 14%, and 17%, respectively. In conclusion, pulsatile unloading contributes to the distribution of intraventricular flow and the formation time of the vortex. Co-pulse support significantly reduces the maximum value of the ventricular wall stress and the area of high stress on the ventricular wall.