Fractal Geometry Illustrated Left Atrial Appendage Morphology That Predicted Thrombosis and Stroke in Patients With Atrial Fibrillation.

Background: This study aims to correlate the morphological complexity of left atrial appendage (LAA) with thrombosis and stroke in patients with atrial fibrillation (AF). Methods: The training cohort consisted of 46 patients with AF (age 55.8 ± 7.2 years, 73.9% men) who were referred for radiofrequency catheter ablation. An independent validation cohort consisting of 443 patients with AF was enrolled for further verification. All patients in the training cohort underwent both transesophageal echocardiography (TEE) and enhanced computed tomography (CT). Fractal dimension (FD) analysis was performed to evaluate the morphological complexity of LAAs quantitatively. Clinical and imaging manifestations, FD of LAAs, and diagnostic accuracy were investigated and compared between patients with AF in both training and validation cohorts. Results: In the training cohort, LAAs (n = 22) with thrombi had significantly higher FD than those without thrombi (n = 24) h 0.44 ± 0.07 vs. 2.35 ± 0.11, p = 0.003). Receiver-operating characteristic (ROC) analysis suggested that the diagnostic accuracy of FD combined with a CHA2DS2-VaSc score was significantly higher than that of the CHA2DS2-VaSc score alone in low- to moderate-risk patients with AF (area under the curve 0.8479 vs. 0.6958, p = 0.009). The results were also validated in an independent external validation cohort and demonstrated that increased FD was associated with stroke. Hemodynamic analysis revealed that LAAs with thrombi and high FD were prone to blood stasis and lower blood flow rate. Conclusion: LAA morphological complexity is closely associated with thrombosis and stroke in patients with paroxysmal AF. A new risk assessment system combining CHA2DS2-VaSc score and FD has a higher diagnostic accuracy in predicting LAA thrombosis.

Optimization of 4D flow MRI velocity field in the aorta with divergence-free smoothing.

Divergence-free smoothing with wall treatment (DFSwt) method is proposed for processing with four-dimensional (4D) flow magnetic resonance imaging (MRI) data of blood flows to enhance the quality of flow field with physical constraints. The new method satisfies the no-slip wall boundary condition and applies wall function of velocity profile for better estimating the velocity gradient in the near-wall region, and consequently improved wall shear stress (WSS) calculation against the issue of coarse resolution of 4D flow MRI. In the first testing case, blood flow field obtained from 4D flow MRI is well smoothed by DFSwt method. A great consistency is observed between the post-processed 4D flow MRI data and the computational fluid dynamics (CFD) data in the interested velocity field. WSS has an apparent improvement due to the proposed near-wall treatment with special wall function comparing to the result from original 4D flow MRI data or the DFS-processed data with no wall function. The other five cases also show the same performance that smoothed velocity field and improved WSS estimation are achieved on 4D flow MRI data optimized by DFSwt. The improvements will benefit the study of hemodynamics regarding the determination of location or the potential possibility of lesions.

Experimental investigation of the influence of the hydraulic performance of an axial blood pump on intraventricular blood flow.

Blood flow inside the left ventricle (LV) is a concern for blood pump use and contributes to ventricle suction and thromboembolic events. However, few studies have examined blood flow inside the LV after a blood pump was implanted. In this study, in vitro experiments were conducted to emulate the intraventricular blood flow, such as blood flow velocity, the distribution of streamlines, vorticity and the standard deviation of velocity inside the LV during axial blood pump support. A silicone LV reconstructed from computerized tomography (CT) data of a heart failure patient was incorporated into a mock circulatory loop (MCL) to simulate human systemic circulation. Then, the blood flow inside the ventricle was examined by particle image velocimetry (PIV) equipment. The results showed that the operating conditions of the axial blood pump influenced flow patterns within the LV and areas of potential blood stasis, and the intraventricular swirling flow was altered with blood pump support. The presence of vorticity in the LV from the thoracic aorta to the heart apex can provide thorough washing of the LV cavity. The gradually extending stasis region in the central LV with increasing blood pump support is necessary to reduce the thrombosis potential in the LV.

A 3-dimensional-printed left ventricle model incorporated into a mock circulatory loop to investigate hemodynamics inside a severely failing ventricle supported by a blood pump.

Intraventricular blood stasis is a design consideration for continuous flow blood pumps and might contribute to adverse events such as thrombosis and ventricular suction. However, the blood flow inside left ventricles (LVs) supported by blood pumps is still unclear. In vitro experiments were conducted to imitate how the hydraulic performance of an axial blood pump affects the intraventricular blood flow of a severe heart failure patient, such as velocity distribution, vorticity, and standard deviation of velocity. In this study, a silicone model of the LV was constructed from the computed tomography data of one patient with heart failure and was 3D printed. Then, intraventricular flow was visualized by particle image velocimetry equipment within a mock circulation loop. The results showed that the axial blood pump suctions most of the blood in a severely failing LV, there was an altered flow status within the LV, and blood stasis appeared in the central region of the LV. Some blood may be suctioned from the aortic valve to the blood pump because the patient's native heart was severely failing. Blood stasis at the LV center may cause thrombosis in the LV. The vortex flow near the inner wall of the LV can thoroughly wash the left ventricular cavity.

Matrine has pro-apoptotic effects on liver cancer by triggering mitochondrial fission and activating Mst1-JNK signalling pathways.

Mitochondrial homeostasis is closely associated with liver cancer progression via multiple mechanisms and is also a potential tumour-suppressive target in clinical practice. However, the role of mitochondrial fission in liver cancer cell viability has not been adequately investigated. Matrine, a type of alkaloid isolated from Sophoraflavescens, has been widely used to treat various types of cancer. However, the molecular effect of matrine on mitochondrial homeostasis is unclear. Therefore, the aim of the current study was to determine the role of mitochondrial fission in cell apoptosis, viability, migration and proliferation of HepG2 cells in vitro. The effect of matrine on mitochondrial fission and its mechanism were also explored. The results of our study showed that HepG2 cells treated with matrine had reduced viability, an increased apoptotic rate, a blunted migratory response, and impaired proliferation capacity. At the molecular level, matrine treatment activated mitochondrial fission, which promoted mitochondrial dysfunction, caused cellular oxidative stress, disrupted cellular energy metabolism and initiated cell apoptotic pathways. However, blockade of mitochondrial fission abolished the deleterious effects of matrine on HepG2 cells. Further, we demonstrated that the Mst1-JNK signalling axis was required for matrine-modulated mitochondrial fission. Matrine-mediated mitochondrial dysfunction was reversed by inhibiting Mst1-JNK pathways. Together, our results demonstrated that mitochondrial fission could be a potential upstream tumour-suppressive signal for liver cancer by modifying mitochondrial function and cell death. By contrast, matrine exerted an anticancer function in liver cancer by activating mitochondrial fission mediated by Mst1-JNK pathways.

Matrine promotes liver cancer cell apoptosis by inhibiting mitophagy and PINK1/Parkin pathways.

Matrine is a natural alkaloid isolated from the root and stem of the legume plant Sophora. Its anti-proliferative and pro-apoptotic effects on several types of cancer have been well-documented. However, the role of matrine in regulating mitochondrial homeostasis, particularly mitophagy in liver cancer apoptosis, remains uncertain. The aim of our study was to explore whether matrine promotes liver cancer cell apoptosis by modifying mitophagy. HepG2 cells were used in the study and treated with different doses of matrine. Cell viability and apoptosis were determined by MTT assay, TUNEL staining, western blotting, and LDH release assay. Mitophagy was monitored by immunofluorescence assay and western blotting. Mitochondrial function was assessed by immunofluorescence assay, ELISA, and western blotting. The results of our study indicated that matrine treatment dose-dependently reduced cell viability and increased the apoptotic rate of HepG2 cells. Functional studies demonstrated that matrine treatment induced mitochondrial dysfunction and activated mitochondrial apoptosis by inhibiting protective mitophagy. Re-activation of mitophagy abolished the pro-apoptotic effects of matrine on HepG2 cells. Molecular investigations further confirmed that matrine regulated mitophagy via the PINK1/Parkin pathways. Matrine blocked the PINK1/Parkin pathways and repressed mitophagy, whereas activation of the PINK1/Parkin pathways increased mitophagy activity and promoted HepG2 cell survival in the presence of matrine. Together, our data indicated that matrine promoted HepG2 cell apoptosis through a novel mechanism that acted via inhibiting mitophagy and the PINK1/Parkin pathways. This finding provides new insight into the molecular mechanism of matrine for treating liver cancer and offers a potential target to repress liver cancer progression by modulating mitophagy and the PINK1/Parkin pathways.