Search

Abstract Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.

The occurrence of bone metastasis is a grave medical concern that substantially impacts the quality of life in patients with cancer. The precise mechanisms underlying bone metastasis remain unclear despite extensive research efforts, and efficacious therapeutic interventions are currently lacking. The ability of osteoclasts to degrade the bone matrix makes them a crucial factor in the development of bone metastasis. Osteoclasts are implicated in several aspects of bone metastasis, encompassing the formation of premetastatic microenvironment, suppression of the immune system, and reactivation of quiescent tumor cells. Contemporary clinical interventions targeting osteoclasts have proven effective in mitigating bone-related symptoms in patients with cancer. This review comprehensively analyzes the mechanistic involvement of osteoclasts in bone metastasis, delineates potential therapeutic targets associated with osteoclasts, and explores clinical evidence regarding interventions targeting osteoclasts.

Mineralized collagen scaffold is one of the best choices for bone defects treatment, but weak mechanical strength is the main factor restricting its development. Recent studies demonstrated that despite being a fundamental form of mechanical stimulation in human activities, the impact of cyclic compressive stress on collagen mineralization remains unclear, with even less known about the dynamic mechanical mechanism. This study employed cyclic compressive stress to investigate its effect on collagen mineralization. The findings revealed that cyclic compressive strain promotes collagen mineralization by facilitating increased mineral penetration into the collagen and altering mineral morphology on the collagen surface. As the mineral volume fraction of mineralized collagen rises, its elastic modulus also increases. Additionally, the finite element simulation results proved that cyclic compressive stress can impact mineral distribution by affecting their transport and deposition, consequently influencing the stress distribution and regulating mechanical properties of mineralized collagen. Alterations in mechanical properties provide feedback on internal stress distribution, subsequently impacting mineral mineralization. This study achieves a closed-loop study on the mechanical regulated collagen mineralization, offers insight into the mechanism of collagen mineralization, paving the way for further exploration of biomineralization mechanisms and potentially inspiring novel approaches for the fabrication of mineralized collagen scaffolds.

This study aimed to investigate the effect of the transverse sinus (TS) stenosis (TSS) position caused by arachnoid granulation on patients with venous pulsatile tinnitus (VPT) and to further identify the types of TSS that are of therapeutic significance for patients. Multiphysics interaction models of six patients with moderate TSS caused by arachnoid granulation and virtual stent placement in TSS were reconstructed, including three patients with TSS located in the middle segment of the TS (group 1) and three patients with TTS in the middle and proximal involvement segment of the TS (group 2). The transient multiphysics interaction simulation method was applied to elucidate the differences in biomechanical and acoustic parameters between the two groups. The results revealed that the blood flow pattern at the TS and sigmoid sinus junction was significantly changed depending on the stenosis position. Preoperative patients had increased blood flow in the TSS region and TSS downstream where the blood flow impacted the vessel wall. In group 1, the postoperative blood flow pattern, average wall pressure, vessel wall vibration, and sound pressure level of the three patients were comparable to the preoperative state. However, the postoperative blood flow velocity decreased in group 2. The postoperative average wall pressure, vessel wall vibration, and sound pressure level of the three patients were significantly improved compared with the preoperative state. Intravascular intervention therapy should be considered for patients with moderate TSS caused by arachnoid granulations in the middle and proximal involvement segment of the TS. TSS might not be considered the cause of VPT symptoms in patients with moderate TSS caused by arachnoid granulation in the middle segment of the TS.

Craniotomy is an invasive operation with great trauma and many complications, and patients undergoing craniotomy should enter the ICU for monitoring and treatment. Based on electronic medical records (EMR), the discovery of high-risk multi-biomarkers rather than a single biomarker that may affect the length of ICU stay (LoICUS) can provide better decision-making or intervention suggestions for clinicians in ICU to reduce the high medical expenses of these patients and the medical burden as much as possible. The multi-biomarkers or medical decision rules can be discovered according to some interpretable predictive models, such as tree-based methods. Our study aimed to develop an interpretable framework based on real-world EMRs to predict the LoICUS and discover some high-risk medical rules of patients undergoing craniotomy. The EMR datasets of patients undergoing craniotomy in ICU were separated into preoperative and postoperative features. The paper proposes a framework called Rules-TabNet (RTN) based on the datasets. RTN is a rule-based classification model. High-risk medical rules can be discovered from RTN, and a risk analysis process is implemented to validate the rules discovered by RTN. The performance of the postoperative model was considerably better than that of the preoperative model. The postoperative RTN model had a better performance compared with the baseline model and achieved an accuracy of 0.76 and an AUC of 0.85 for the task. Twenty-four key decision rules that may have impact on the LoICUS of patients undergoing craniotomy are discovered and validated by our framework. The proposed postoperative RTN model in our framework can precisely predict whether the patients undergoing craniotomy are hospitalized for too long (more than 15 days) in the ICU. We also discovered and validated some key medical decision rules from our framework.

Modified macroporous structures and active osteogenic substances are necessary to overcome the limited bone regeneration capacity and low degradability of self-curing calcium phosphate cement (CPC). Curcumin (CUR), which possesses strong osteogenic activity and poor aqueous solubility/bioavailability, esterifies the side chains in hyaluronic acid (HA) to form a water-soluble CUR-HA macromolecule. In this study, we incorporated the CUR-HA and glucose microparticles (GMPs) into the CPC powder to fabricate the CUR-HA/GMP/CPC composite, which not only retained the good injectability and mechanical strength of bone cements, but also significantly increased the cement porosity and sustained release property of CUR-HA in vitro. CUR-HA incorporation greatly improved the differentiation ability of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts by activating the RUNX family transcription factor 2/fibroblast growth factor 18 (RUNX2/FGF18) signaling pathway, increasing the expression of osteocalcin and enhancing the alkaline phosphatase activity. In addition, in vivo implantation of CUR-HA/GMP/CPC into femoral condyle defects dramatically accelerated the degradation rate of cement and boosted local vascularization and osteopontin protein expression, and consequently promoted rapid bone regeneration. Therefore, macroporous CPC based composite cement with CUR-HA shows a remarkable ability to repair bone defects and is a promising translational application of modified CPC in clinical practice.

Changes in the frequency composition of the human electroencephalogram are associated with the transitions to epileptic seizures. Cross-frequency coupling (CFC) is a measure of neural oscillations in different frequency bands and brain areas, and specifically phase–amplitude coupling (PAC), a form of CFC, can be used to characterize these dynamic transitions. In this study, we propose a method for seizure detection and prediction based on frequency domain analysis and PAC combined with machine learning. We analyzed two databases, the Siena Scalp EEG database and the CHB-MIT database, and used the frequency features and modulation index (MI) for time-dependent quantification. The extracted features were fed to a random forest classifier for classification and prediction. The seizure prediction horizon (SPH) was also analyzed based on the highest-performing band to maximize the time for intervention and treatment while ensuring the accuracy of the prediction. Under comprehensive consideration, the results demonstrate that better performance could be achieved at an interval length of 5 min with an average accuracy of 85.71% and 95.87% for the Siena Scalp EEG database and the CHB-MIT database, respectively. As for the adult database, the combination of PAC analysis and classification can be of significant help for seizure detection and prediction. It suggests that the rarely used SPH also has a major impact on seizure detection and prediction and further explorations for the application of PAC are needed.

Objective: To explore the influence of the blood flow-diameter scaling laws of QαD3, QαD2.7 and QαD7╱3 on the numerical simulation of fraction flow reserve based on CTA images and to find the optimal exponents. Methods: 1) 26 patients with coronary artery disease were screened according to the inclusion criteria; 2) Microcirculation resistance (Rm) was calculated under the 3, 2.7 and 7/3 power of the flow-diameter scaling law, which were recorded as 3Rm, 2.7Rm and 7/3Rm, respectively; 3) 3Rm, 2.7Rm and 7/3Rm were used as exit boundary conditions to simulate FFRCT, quoted as 3FFRCT, 2.7FFRCT and 7/3FFRCT, respectively; 4) The correlation and diagnostic performance between three kinds of FFRCT and FFR were analyzed. Results: The p-values of comparing 3Rm, 2.7Rm and 7/3Rm with FFR were 0.004, 0.005 and 0.010, respectively; the r value between 7/3FFRCT and FFR (0.96) was better than that of 3FFRCT (0.95) and 2.7FFRCT (0.95); the 95% LoA between 7/3FFRCT and FFR (-0.08~0.11) was smaller than that of 3FFRCT (-0.10~0.12) and 2.7FFRCT (-0.09~0.11); the AUC and accuracy of 7/3FFRCT [0.962 (0.805-0.999), 96.15%] were the same as those of 2.7FFRCT [0.962 (0.805-0.999), 96.15%] and better than those of 3FFRCT [0.944 (0.777-0.996), 92.3%]. The prediction threshold of 7/3FFRCT (0.791) was closer to 0.8 than that of 3FFRCT (0.816) and 2.7FFRCT (0.787). Conclusion: The blood flow-diameter scaling law affects the FFRCT simulation by influencing the exit boundary condition Rm of the calculation. With QαD7╱3, FFRCT had the highest diagnostic performance. The blood flow-diameter scaling law provides theoretical support for the blood flow distribution in the bifurcated vessel and improves the FFRCT model.

Aortic valve disease (AVD) often coexists with coronary artery disease (CAD), but whether and how the two diseases are correlated remains poorly understood. In this study, a zero–three dimensional (0-3D) multi-scale modeling method was developed to integrate coronary artery hemodynamics, aortic valve dynamics, coronary flow autoregulation mechanism, and systemic hemodynamics into a unique model system, thereby yielding a mathematical tool for quantifying the influences of aortic valve stenosis (AS) and aortic valve regurgitation (AR) on hemodynamics in large coronary arteries. The model was applied to simulate blood flows in six patient-specific left anterior descending coronary arteries (LADs) under various aortic valve conditions (i.e., control (free of AVD), AS, and AR). Obtained results showed that the space-averaged oscillatory shear index (SA-OSI) was significantly higher under the AS condition but lower under the AR condition in comparison with the control condition. Relatively, the overall magnitude of wall shear stress was less affected by AVD. Further data analysis revealed that AS induced the increase in OSI in LADs mainly through its role in augmenting the low-frequency components of coronary flow waveform. These findings imply that AS might increase the risk or progression of CAD by deteriorating the hemodynamic environment in coronary arteries.

Sigmoid sinus wall dehiscence (SSWD) is an important etiology of venous pulsatile tinnitus (VPT) and is treated by sigmoid sinus wall reconstruction (SSWR). This study aimed to investigate the therapeutic effects of the different degrees of SSWR and the prognostic effect in patients with VPT. Personalized models of three patients with SSWD (control), 3/4SSWD, 1/2SSWD, 1/4SSWD, and 0SSWD were reconstructed. A multiphysics interaction approach was applied to elucidate the biomechanical and acoustic changes. Results revealed that after SSWR, the average pressure of venous vessel on the SSWD region reduced by 33.70 ± 12.53%, 35.86 ± 12.39%, and 39.70 ± 12.45% (mean ± SD) in three patients with 3/4SSWD, 1/2SSWD, and 1/4SSWD. The maximum displacement of the SSWR region reduced by 25.91 ± 30.20%, 37.20 ± 31.47%, 52.60 ± 34.66%, and 79.35 ± 18.13% (mean ± SD) in three patients with 3/4SSWD, 1/2SSWD, 1/4SSWD, and 0SSWD, with a magnitude approximately 10−3 times that of the venous vessel in the SSWD region. The sound pressure level at the tympanum reduced by 23.72 ± 1.91%, 31.03 ± 14.40%, 45.62 ± 19.11%, and 128.46 ± 15.46% (mean ± SD). The SSWR region was still loaded with high stress in comparison to the surrounding region. The SSWR region of the temporal bone effectively shielded the high wall pressure and blocked the transmission of venous vessel vibration to the inner ear. Patients with inadequate SSWR still had residual VPT symptoms despite the remission of VPT symptoms. Complete SSWR could completely solve VPT issues. High-stress distribution of the SSWR region may be the cause of the recurrence of VPT symptoms.

Objective: After coronary artery bypass grafting (CABG) surgery, the main causes of poor instant patency of left internal mammary arteries (LIMAs) are competitive flow and anastomotic stenosis, but how to determine the cause of LIMA non-patency without interfering with the native coronary artery is still a difficult problem to be solved urgently.Methods: In this study, a 0D-3D coupled multiscaled CABG model of anastomotic stenosis and competitive flow was constructed. After calculation, the flow waveform of the LIMA was extracted, and the waveform shape, common clinical parameters (average flow, PI, and DF), and graft flow FFT ratio results (F0/H1 and F0/H2) were analyzed.Results: For LIMA, these three common clinical parameters did not differ significantly between the anastomotic stenosis group and competitive flow group. However, the waveform shape and FFT ratio (especially F0/H2) of the competitive flow group were significantly different from those of the anastomotic stenosis group. When the cause was competitive flow, there was systolic backflow, and F0/H2 was too high (>14.89). When the cause was anastomotic stenosis, the waveform maintained a bimodal state and F0/H2 was in a normal state (about 1.17).Conclusion: When poor instant patency of the LIMA is found after CABG, the causes can be determined by graft flow waveform shape and F0/H2.

Objective Renal sympathetic denervation (RDN) is an alternative treatment for resistant hypertension (RH). This study aims to compare ablation effects using three radiofrequency applicators (i.e., balloon-based four electrodes, spiral and monopolar devices). Methods An idealized three-dimensional model of the renal artery was established using COMSOL Multiphysics to mimic radiofrequency ablation (RFA). Radiofrequency (RF) energy was delivered to the tissue at the same simulation settings, i.e., 4, 6, and 8 W for 60 s, using the three abovementioned RF applicators. The temperature distribution in the tissue was calculated using the coupled electrical–thermal–fluid finite element method. Lesion borders were defined using 50 °C isotherms. The maximum lesion depth, width, area, and circumferential coverage rate were compared among the three applicators at a blood flow of 0.4 m/s. Monopolar RF ablations in a renal artery phantom model were performed to validate the reliability of the simulation method. Results The balloon-based system yields greater lesion depths and widths compared with spiral and monopolar denervation under the same power. The range of maximum lesion depth is 1.58–3.11 mm for balloon-based RDN, 0.90–1.81 mm for spiral RDN and 1.12–2.38 mm for monopolar RDN, at a power of 4–8 W. The corresponding ranges of maximum lesion width are 2.22–5.73, 1.48–3.54, and 1.93–5.31 mm, respectively, and the circumferential coverage rates of the renal artery are 41.43%–91.99%, 31.71%–66.23%, and 9.55%–23.06%, respectively. The average velocity after balloon-based, spiral, and monopolar RDN increases by 3, 5, and 1 cm/s, respectively. The validation of the computer model offered prediction errors are

Anzai et al. propose a deep learning approach to estimate the 3D hemodynamics of complex aorta-coronary artery geometry in the context of coronary artery bypass surgery. Their method reduces the calculation time 600-fold, while allowing high resolution and similar accuracy as traditional computational fluid dynamics (CFD) method.

Background: The underuse of invasive fraction flow reserve (FFR) in clinical practice has motivated research towards its non-invasive prediction. The early attempts relied on solving the incompressible three-dimensional Navier–Stokes equations in segmented coronary arteries. However, transient boundary condition has a high resource intensity in terms of computational time. Herein, a method for calculating FFR based on steady-state geometric multiscale (FFRSS) is proposed.Methods: A total of 154 moderately stenotic vessels (40–80% diameter stenosis) from 136 patients with stable angina were included in this study to validate the clinical diagnostic performance of FFRSS. The method was based on the coronary artery model segmented from the patient’s coronary CTA image. The average pressure was used as the boundary condition for the inlet, and the microcirculation resistance calculated by the coronary flow was used as the boundary condition for the outlet to calculate the patient-specific coronary hyperemia. Then, the flow velocity and pressure distribution and the FFRss of each coronary artery branch were calculated to evaluate the degree of myocardial ischemia caused by coronary stenosis. Also, the FFRSS and FFRCT of all patients were calculated, and the clinically measured FFR was used as the “gold standard” to verify the diagnostic performance of FFRSS and to compare the correlation between FFRSS and FFRCT.Results: According to the FFRSS calculation results of all patients, FFRSS and FFR have a good correlation (r = 0.68, p < 0.001). Similarly, the correlation of FFRSS and FFRCT demonstrated an r of 0.75 (95%CI: 0.67–0.72) (p < 0.001). On receiver-operating characteristic analysis, the optimal FFRSS cut point for FFR≤0.80 was 0.80 (AUC:0.85 [95% confidence interval: 0.79 to 0.90]; overall accuracy:88.3%). The overall sensitivity, specificity, PPV, and NPV for FFRSS ≤0.80 versus FFR ≤0.80 was 68.18% (95% CI: 52.4–81.4), 93.64% (95% CI: 87.3–97.4), 82.9%, and 91.1%, respectively.Conclusion: FFRSS is a reliable diagnostic index for myocardial ischemia. This method was similar to the closed-loop geometric multiscale calculation of FFR accuracy but improved the calculation efficiency. It also improved the clinical applicability of the non-invasive computational FFR model, helped the clinicians diagnose myocardial ischemia, and guided percutaneous coronary intervention.

Bone has a special structure that is both stiff and elastic, and the composition of bone confers it with an exceptional mechanical property. However, bone substitute materials that are made of the same hydroxyapatite (HA) and collagen do not offer the same mechanical properties. It is important for bionic bone preparation to understand the structure of bone and the mineralization process and factors. In this paper, the research on the mineralization of collagen is reviewed in terms of the mechanical properties in recent years. Firstly, the structure and mechanical properties of bone are analyzed, and the differences of bone in different parts are described. Then, different scaffolds for bone repair are suggested considering bone repair sites. Mineralized collagen seems to be a better option for new composite scaffolds. Last, the paper introduces the most common method to prepare mineralized collagen and summarizes the factors influencing collagen mineralization and methods to analyze its mechanical properties. In conclusion, mineralized collagen is thought to be an ideal bone substitute material because it promotes faster development. Among the factors that promote collagen mineralization, more attention should be given to the mechanical loading factors of bone.

In this paper, we study the dynamic behavior of a stochastic tungiasis model for public health education. First, the existence and uniqueness of global positive solution of stochastic models are proved. Secondly, by constructing Lyapunov function and using Ito^ formula, sufficient conditions for disease extinction and persistence in the stochastic model are proved. Thirdly, under the condition of disease persistence, the existence and uniqueness of an ergodic stationary distribution of the model is obtained. Finally, the importance of public health education in preventing the spread of tungiasis is illustrated through the combination of theoretical results and numerical simulation.

Background: Extracorporeal membrane oxygenation (ECMO) provides cardiopulmonary support for critically ill patients. Portable ECMO devices can be applied in both in-hospital and out-of-hospital emergency conditions. We evaluated the safety and biocompatibility of a novel centrifugal pump and ECMO device of the OASSIST ECMO System (Jiangsu STMed Technologies Co., Suzhou, China) in a 168-h ovine ECMO model.Methods: The portable OASSIST ECMO system consists of the control console, the pump drive, and the disposable centrifugal pump. Ten healthy sheep were used to evaluate the OASSIST ECMO system. Five were supported on veno-venous ECMO and five on veno-arterial ECMO, each for 168 h. The systemic anticoagulation was achieved by continuous heparin infusion to maintain the activated clotting time (ACT) between 220 and 250 s. The rotary speed was set at 3,200–3,500 rpm. The ECMO configurations and ACT were recorded every 6 hours (h). The free hemoglobin (fHb), complete blood count, and coagulation action test were monitored, at the 6th h and every 24 h after the initiation of the ECMO. The dissection of the pump head and oxygenator were conducted to explore thrombosis.Results: Ten sheep successfully completed the study duration without device-related accidents. The pumps ran stably, and the ECMO flow ranged from 1.6 ± 0.1 to 2.0 ± 0.11 L/min in the V-V group, and from 1.8 ± 0.1 to 2.4 ± 0.14 L/min in the V-A group. The anticoagulation was well-performed. The ACT was maintained at 239.78 ± 36.31 s, no major bleeding or thrombosis was observed during the ECMO run or in the autopsy. 3/5 in the V-A group and 4/5 in the V-V group developed small thrombus in the bearing pedestal. No obvious thrombus formed in the oxygenator was observed. The hemolytic blood damage was not significant. The average fHb was 0.17 ± 0.12 g/L. Considering hemodilution, the hemoglobin, white blood cell, and platelets didn't reduce during the ECMO runs.Conclusions: The OASSIST ECMO system shows satisfactory safety and biocompatibility for the 168-h preclinical evaluation in the ovine model. The OASSIST ECMO system is promising to be applied in clinical conditions in the future.

Distraction osteogenesis (DO) is a mechanobiological process of regenerating bone tissue by tension stress. DO is used clinically to lengthen bones or to treat critical size bone defects. Although DO provides satisfactory results in many cases, the prolonged period of treatment remains a major challenge that needs to be overcome. Various attempts have been devoted to accelerating bone regeneration during DO. One common approach is manipulation of the applied mechanical loading by altering distraction strategies. In this article, we reviewed relevant in vivo animal studies exploring the effects of changing mechanical environments, by varying distraction parameters (e.g., rate and frequency) or adding compression loading, on bone regeneration in DO. We further presented how the mechanically-regulated bone regeneration process during DO could be simulated by in silico models incorporating mechano-regulatory tissue differentiation rules. A comprehensive review of those in vivo and in silico studies may not solely provide important references for development of improved DO protocols in clinic, but also promote a deeper understanding of the mechanobiological mechanism of bone regeneration.

Trabecular bone is natural material with heterogeneous tissue properties. The effect of tissue heterogeneity on the micromechanical behavior of trabecular bone is commonly evaluated by microCT-based finite element (microFE) analysis. Results from prior work remain inconclusive and lack of experimental validation. To address these issues, we combined microFE analysis with mechanical testing and microCT-based digital volume correlation (DVC), as a validation for the microFE approach. Porcine trabecular specimens were tested in compression as sequential microCT scans were taken. DVC was performed to extract “realistic” boundary conditions that were applied to microFE models, and to measure microstructural deformation and strain of the trabecular specimens. Heterogeneous and homogeneous microFE models of each trabecular specimen were created and compared with the experimentally measured microstructural displacement and strains. Results showed strong correlations between DVC-measured and microFE-predicted trabecular displacement and strain fields (R2 ​> ​0.9, p ​

The interventional treatment of cerebral aneurysm requires hemodynamics to provide proper guidance. Computational fluid dynamics (CFD) is gradually used in calculating cerebral aneurysm hemodynamics before and after flow-diverting (FD) stent placement. However, the complex operation (such as the construction and placement simulation of fully resolved or porous-medium FD stent) and high computational cost of CFD hinder its application. To solve these problems, we applied aneurysm hemodynamics point cloud data sets and a deep learning network with double input and sampling channels. The flexible point cloud format can represent the geometry and flow distribution of different aneurysms before and after FD stent (represented by porous medium layer) placement with high resolution. The proposed network can directly analyze the relationship between aneurysm geometry and internal hemodynamics, to further realize the flow field prediction and avoid the complex operation of CFD. Statistical analysis shows that the prediction results of hemodynamics by our deep learning method are consistent with the CFD method (error function

A computational hemodynamics method was employed to investigate how the morphotype and functional state of aortic valve would affect the characteristics of blood flow in aortas with pathological dilation, especially the intensity and distribution of flow turbulence. Two patient-specific aortas diagnosed to have pathological dilation of the ascending segment while differential aortic valve conditions (i.e., one with a stenotic and regurgitant RL bicuspid aortic valve (RL-BAV), whereas the other with a quasi-normal tricuspid aortic valve (TAV)) were studied. When building the computational models, in addition to in vivo data-based reconstruction of geometrical model and boundary condition setting, the large eddy simulation method was adopted to quantify potential flow turbulence in the aortas. Obtained results revealed the presence of complex flow patterns (denoted by time-varying changes in vortex structure), flow turbulence (indicated by high turbulent eddy viscosity (TEV)), and regional high wall shear stress (WSS) in the ascending segment of both aortas. Such hemodynamic characteristics were significantly augmented in the aorta with RL-BAV. For instance, the space-averaged TEV in late systole and the wall area exposed to high time-averaged WSS (judged by WSS> two times of the mean WSS in the entire aorta) in the ascending aortic segment were increased by 176% and 465%, respectively. Relatively, flow patterns in the descending aortic segment were less influenced by the aortic valve disease. These results indicate that aortic valve disease has profound impacts on flow characteristics in the ascending aorta, especially the distribution and degree of high WSS and flow turbulence.

Abstract Background Enhanced external counterpulsation (EECP) is an effective method for treating patients with cerebral ischemic stroke, while hemodynamics is the major contributing factor in the treatment of EECP. Different counterpulsation modes have the potential to lead to different acute and long-term hemodynamic changes, resulting in different treatment effects. However, various questions about appropriate counterpulsation modes for optimizing hemodynamic effects remain unanswered in clinical treatment. Methods A zero-dimensional/three-dimensional (0D/3D) geometric multiscale model of the cerebral artery was established to obtain acute hemodynamic indicators, including mean arterial pressure (MAP) and cerebral blood flow (CBF), as well as localized hemodynamic details for the cerebral artery, which includes wall shear stress (WSS) and oscillatory shear index (OSI). Counterpulsation was achieved by applying pressure on calf, thigh and buttock modules in the 0D model. Different counterpulsation modes including various pressure amplitudes and pressurization durations were applied to investigate hemodynamic responses, which impact acute and long-term treatment effects. Both vascular collapse and cerebral autoregulation were considered during counterpulsation. Results Variations of pressure amplitude and pressurization duration have different impacts on hemodynamic effects during EECP treatment. There were small differences in the hemodynamics when similar or different pressure amplitudes were applied to calves, thighs and buttocks. When increasing pressure amplitude was applied to the three body parts, MAP and CBF improved slightly. When pressure amplitude exceeded 200 mmHg, hemodynamic indicators almost never changed, demonstrating consistency with clinical data. However, hemodynamic indicators improved significantly with increasing pressurization duration. For pressurization durations of 0.5, 0.6 and 0.7 s, percentage increases for MAP during counterpulsation were 1.5%, 23.5% and 39.0%, for CBF were 1.2%, 23.4% and 41.6% and for time-averaged WSS were 0.2%, 43.5% and 85.0%, respectively. Conclusions When EECP was applied to patients with cerebral ischemic stroke, pressure amplitude applied to the three parts may remain the same. Patients may not gain much more benefit from EECP treatment by excessively increasing pressure amplitude above 200 mmHg. However, during clinical procedures, pressurization duration could be increased to 0.7 s during the cardiac circle to optimize the hemodynamics for possible superior treatment outcomes.

Traditional enhanced external counterpulsation (EECP) used for the clinical treatment of patients with coronary heart disease only assesses diastolic/systolic blood pressure (Q = D/S > 1.2). However, improvement of the hemodynamic environment surrounding vascular endothelial cells of coronary arteries after long-term application of EECP is the basis of the treatment. Currently, the quantitative hemodynamic mechanism is not well understood. In this study, a standard 0D/3D geometric multi-scale model of the coronary artery was established to simulate the hemodynamic effects of different counterpulsation modes on the vascular endothelium. In this model, the neural regulation caused by counterpulsation was thoroughly considered. Two clinical trials were carried out to verify the numerical calculation model. The results demonstrated that the increase in counterpulsation pressure amplitude and pressurization duration increased coronary blood perfusion and wall shear stress (WSS) and reduced the oscillatory shear index (OSI) of the vascular wall. However, the impact of pressurization duration was the predominant factor. The results of the standard model and the two real individual models indicated that a long pressurization duration would cause more hemodynamic risk areas by resulting in excessive WSS, which could not be reflected by the change in the Q value. Therefore, long-term pressurization during each cardiac cycle therapy is not recommended for patients with coronary heart disease and clinical treatment should not just pay attention to the change in the Q value. Additional physiological indicators can be used to evaluate the effects of counterpulsation treatment.

Clinically, fractional flow reserve (FFR)-guided coronary artery bypass grafting (CABG) is more effective than CABG guided by coronary angiography alone. However, no scholars have explained the mechanism from the perspective of hemodynamics. Two patients were clinically selected; their angiography showed 70% coronary stenosis, and the FFRs were 0.7 (patient 1) and 0.95 (patient 2). The FFR non-invasive computational model of the two patients was constructed by a 0–3D coupled multiscaled model, in order to verify that the model can accurately calculate the FFR results. Virtual bypass surgery was performed on these two stenoses, and a CABG multiscaled model was constructed. The flow rate of the graft and the stenosis coronary artery, as well as the wall shear stress (WSS) and the oscillatory shear index (OSI) in the graft were calculated. The non-invasive calculation results of FFR are 0.67 and 0.91, which are close to the clinical results, which proves that our model is accurate. According to the CABG model, the flow ratios of the stenosis coronary artery to the graft of patient 1 and patient 2 were 0.12 and 0.42, respectively. The time-average wall shear stress (TAWSS) results of patient 1 and patient 2 grafts were 2.09 and 2.16 Pa, respectively, and WSS showed uniform distribution on the grafts. The OSI results of patients 1 and 2 grafts were 0.0375 and 0.1264, respectively, and a significantly high OSI region appeared at the anastomosis of patient 2. The FFR value of the stenosis should be considered when performing bypass surgery. When the stenosis of high FFR values is grafted, a high OSI region is created at the graft, especially at the anastomosis. In the long term, this can cause anastomotic blockage and graft failure.

Mineralized collagen is the basic unit in hierarchically organized natural bone with different structures. Polyacrylic acid (PAA) and periodic fluid shear stress (FSS) are the most common chemical and physical means to induce intrafibrillar mineralization. In the present study, non-mineralized collagen, extrafibrillar mineralized (EM) collagen, intrafibrillar mineralized (IM) collagen, and hierarchical intrafibrillar mineralized (HIM) collagen induced by PAA and FSS were prepared, respectively. The physical and chemical properties of these mineralized collagens with different microstructures were systematically investigated afterwards. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed that mineralized collagen with different microstructures was prepared successfully. The pore density of the mineralized collagen scaffold is higher under the action of periodic FSS. Fourier transform infrared spectroscopy (FTIR) analysis showed the formation of the hydroxyapatite (HA) crystal. A significant improvement in the pore density, hydrophilicity, enzymatic stability, and thermal stability of the mineralized collagen indicated that the IM collagen under the action of periodic FSS was beneficial for maintaining collagen activity. HIM collagen fibers, which are prepared under the co-action of periodic FSS and sodium tripolyphosphate (TPP), may pave the way for new bone substitute material applications.

The abnormal diameter of the coronary artery is twice or more than the normal diameter, which is a coronary artery aneurysm (CAA). According to the clinical statistics, CAA shows high occurrence on right coronary artery (RCA). The most common cause of CAA in adults is atherosclerosis, which destroys the elastic fibers in the middle layer of the blood vessel. Under the intravascular pressure, the weak wall bulges outward and form CAA. This article aims to explain the hemodynamic mechanism of coronary artery aneurysm shows high occurrence on RCA. Occurrence of CAA was simulated by the volume growth of coronary artery. Firstly, a 0–3D multi-scale model of normal coronary artery was constructed to obtain the hemodynamic environments of coronary artery. Then, fluid-structure interaction of normal and atherosclerotic blood vessel was performed to obtain volume growth rate of the coronary artery. Atherosclerosis was simulated by modifying Young’s modulus in middle layer of the blood vessel. Finally, creep simulation was performed to compare the deformation of the blood vessels under the accumulation of time. Under normal condition, the volume growth rate of the RCA is 2.28 times and 1.55 times of the LAD and the LCX. After atherosclerosis, the volume growth rate of the RCA was 2.69 times and 2.12 times of the LAD and the LCX. And the volume growth rate of the RCA was 3.85 times and 3.45 times of the LAD and the LCX after further deepening of atherosclerosis. The expansion time above the average volume growth rate of the RCA, the LAD and the LCX respectively were 0.194, 0.168 and 0.179 s. The RCA is 2.06 times the original, the LAD and LCX are 1.53 times and 1.56 times after 10 years in creep simulation. It can be concluded that the RCA is more prone to aneurysms originated from the larger expansion of the RCA under normal physiological condition, and the larger expansion is magnified under atherosclerosis condition with destroyed vessel elasticity, and further magnified during the time accumulated viscoelastic creep to develop to aneurysm eventually.

(1) Background: Arrhythmia, which is an umbrella term for various types of abnormal rhythms of heartbeat, has a high prevalence in both the general population and patients with coronary artery disease. So far, it remains unclear how different types of arrhythmia would affect myocardial perfusion and the risk/severity of myocardial ischemia. (2) Methods: A computational model of the coronary circulation coupled to the global cardiovascular system was employed to quantify the impacts of arrhythmia and its combination with coronary artery disease on myocardial perfusion. Furthermore, a myocardial supply–demand balance index (MSDBx) was proposed to quantitatively evaluate the severity of myocardial ischemia under various arrhythmic conditions. (3) Results: Tachycardia and severe irregularity of heart rates (HRs) depressed myocardial perfusion and increased the risk of subendocardial ischemia (evaluated by MSDBx), whereas lowering HR improved myocardial perfusion. The presence of a moderate to severe coronary artery stenosis considerably augmented the sensitivity of MSDBx to arrhythmia. Further data analyses revealed that arrhythmia induced myocardial ischemia mainly via reducing the amount of coronary artery blood flow in each individual cardiac cycle rather than increasing the metabolic demand of the myocardium (measured by the left ventricular pressure-volume area). (4) Conclusions: Both tachycardia and irregular heartbeat tend to increase the risk of myocardial ischemia, especially in the subendocardium, and the effects can be further enhanced by concomitant existence of coronary artery disease. In contrast, properly lowering HR using drugs like β-blockers may improve myocardial perfusion, thereby preventing or relieving myocardial ischemia in patients with coronary artery disease.

While coronary revascularization strategies guided by instantaneous wave-free ratio (iFR) are, in general, noninferior to those guided by fractional flow reserve (FFR) with respect to the rate of major adverse cardiac events at one-year follow-up in patients with stable angina or an acute coronary syndrome, the overall accuracy of diagnosis with iFR in large patient cohorts is about 80% compared with the diagnosis with FFR. So far, it remains incompletely understood what factors contribute to the discordant diagnosis between iFR and FFR. In this study, a computational method was used to systemically investigate the respective effects of various cardiovascular factors on FFR and iFR. The results showed that deterioration in aortic valve disease (e.g., regurgitation or stenosis) led to a marked decrease in iFR and a mild increase in FFR given fixed severity of coronary artery stenosis and that increasing coronary microvascular resistance caused a considerable increase in both iFR and FFR, but the degree of increase in iFR was lower than that in FFR. These findings suggest that there is a high probability of discordant diagnosis between iFR and FFR in patients with severe aortic valve disease or coronary microcirculation dysfunction.

Coronary artery aneurysms (CAAs) have been reported to associate with an increased risk for thrombosis. Distinct to the brain aneurysm, which can cause a rupture, CAA’s threat is more about its potential to induce thrombosis, leading to myocardial infarction. Case reports suggest that thrombosis risk varied with the different CAA diameters and hemodynamics effects (usually wall shear stress (WSS), oscillatory shear index (OSI), and relative residence time (RRT)) may relate to the thrombosis risk. However, currently, due to the rareness of the disease, there is limited knowledge of the hemodynamics effects of CAA. The aim of the study was to estimate the relationship between hemodynamic effects and different diameters of CAAs. Computational fluid dynamics (CFD) provides a noninvasive means of hemodynamic research. Four three-dimensional models were constructed, representing coronary arteries with a normal diameter (1x) and CAAs with diameters two (2x), three (3x), and five times (5x) that of the normal diameter. A lumped parameter model (LPM) which can capture the feature of coronary blood flow supplied the boundary conditions. WSS in the aneurysm decreased 97.7% apparently from 3.51 Pa (1x) to 0.08 Pa (5x). OSI and RRT in the aneurysm were increased apparently by two orders of magnitude from 0.01 (1x) to 0.30 (5x), and from 0.38 Pa−1 (1x) to 51.59 Pa−1 (5x), separately. Changes in the local volume of the CAA resulted in dramatic changes in local hemodynamic parameters. The findings demonstrated that thrombosis risk increased with increasing diameter and was strongly exacerbated at larger diameters of CAA. The 2x model exhibited the lowest thrombosis risk among the models, suggesting the low-damage (medication) treatment may work. High-damage (surgery) treatment may need to be considered when CAA diameter is 3 times or higher. This diameter classification method may be a good example for constructing a more complex hemodynamic-based risk stratification method and could support clinical decision-making in the assessment of CAA.

Coronary artery bypass grafts (CABGs), including saphenous vein grafts (SVGs) or left internal mammary artery (LIMA) grafts, are recently applied to treat coronary artery aneurysm (CAA). Surgical outcomes are considered to be related to surgical strategies (types of the bypass graft and whether CAA ligated or not) and the size of the CAA (usually characterized by diameter). However, the understanding of the relationship between the surgical outcomes and the abovementioned factors is limited. Previous studies related to CABG treatments have shown hemodynamic studies could help evaluate surgical outcomes through graft mass flow rate, wall shear stress (WSS), and oscillatory shear index (OSI). It is believed that the hemodynamic study of applying CABGs to CAA, which is not studied yet, could help us understand the different CABG surgeries. The aim of the study was to evaluate the hemodynamic differences among different surgical methods. To do this, eight three-dimensional models were constructed, representing application of SVGs and LIMA grafts to CAAs (whether ligated or not) with diameters two, three, and five times the normal diameter, to perform computational fluid dynamics (CFD) simulation. The lumped-parameter model (LPM) was coupled to the boundary of the 3D models which increase the complexity of the simulation, but it can ensure the stability of the simulation boundary conditions. The results show that SVG (no matter whether ligated or not) hemodynamic characteristics are positive, with an average high graft mass flow rate of 70 ml/min, an average WSS of 0.479 Pa, and a low OSI of 0.001. LIMA with CAA ligation has the same characteristics with higher WSS (average 1.701 Pa). The hemodynamic characteristics of LIMA without CAA ligation are negative, including high reverse mass flow rate and high OSI (0.367). The results indicate that the surgical outcomes of LIMA with CAA ligation are likely to be the best among these models. The surgical outcomes of LIMA without CAA ligation seem to be undesirable due to the high reverse mass flow and high OSI. The CAA diameter may not have a significant effect on surgical outcomes.

The current 3D CABG model is time consuming, a lumped parameter CABG model may solve this problem. A coronary lumped parameter model without stenosis and graft was constructed. The stenosis resistance was calculated and graft model was constructed. After calculation, the graft flow results of CABG lumped parameter model fit well with 3D CABG model results.

Abstract In this paper we consider the existence of nonoscillatory solutions of higher-order neutral differential equations with distributed coefficients and delays. We use the B a n a c h $Banach$ contraction principle to obtain new sufficient condition for the existence of nonoscillatory solutions.

The objective of this paper is to provide a new method for estimating crash rate and severity simultaneously.This study explores a Heckman selection model of the crash rate and severity simultaneously at different levels and a two-step procedure is used to investigate the crash rate and severity levels. The first step uses a probit regression model to determine the sample selection process, and the second step develops a multiple regression model to simultaneously evaluate the crash rate and severity for slight injury/kill or serious injury (KSI), respectively. The model uses 555 observations from 262 signalized intersections in the Hong Kong metropolitan area, integrated with information on the traffic flow, geometric road design, road environment, traffic control and any crashes that occurred during two years.The results of the proposed two-step Heckman selection model illustrate the necessity of different crash rates for different crash severity levels.A comparison with the existing approaches suggests that the Heckman selection model offers an efficient and convenient alternative method for evaluating the safety performance at signalized intersections.

We consider the existence of nonoscillatory solutions of higher-order neutral differential equations with distributed coefficients. We use the Banach contraction principle to obtain new sufficient condition for the existence of nonoscillatory solutions.

New sufficient conditions are obtained for oscillation for the solutions of systems of a class of higher-order quasilinear partial functional differential equations with distributed deviating arguments. The obtained results are illustrated by example.

Background . Single ventricle disease is treated by Glenn surgery. It is generally accompanied by stenosis on a pulmonary artery or its branches, which has great effect on hemodynamics. This study investigated the hemodynamic influence of different pulmonary stenosis degree in Glenn procedure. Materials . Four three-dimensional Glenn models with different left pulmonary artery stenosis rates as, respectively, 0% (model 1), 25% (model 2), 50% (model 3), and 75% (model 4) by the diameter were generated. Method . Geometric multiscale analysis method was used in the numerical simulations by coupling the lumped parameter model (LPM) and three-dimensional model. Results . During one cardiac cycle, the flow ratio between left pulmonary artery and superior vena cava was about 0.49 for models 1, 2, and 3, while the ratio decreased to 0.34 for model 4. On the other hand, hemodynamics parameters like power loss and oscillation shear index show complications of the stenosis to the postoperative development. Conclusion . When the stenosis rate is above 75%, it is suggested to treat stenosis before Glenn procedure, while when the stenosis rate is below 50%, there is no necessity to pay attention to it due to the little effect it makes.

In this paper we consider the existence, multiplicity, and nonexistence of positive periodic solutions for n-dimensional nonautonomous functional differential system x'(t)=H(t,x(t))-λB(t)F(x(t-τ(t))), where hi are ω-periodic in t and there exist ω-periodic functions αi,βi∈C(R,R+) such that αi(t)≤(hi(t,x)/xi)≤βi(t),∫0ω‍αi(t)dt>0, for x∈R+n all with xi>0, and t∈R, limxi→0+(hi(t,x)/xi) exist for t∈R; bi∈C(R,R+) are ω-periodic functions and ∫0ω‍bi(t)dt>0;fi∈C(R+n,R+), fi(x)>0 for x >0; τ∈(R,R) is an ω-periodic function. We show that the system has multiple or no positive ω-periodic solutions for sufficiently large or small λ>0, respectively.

In this paper, we consider the existence of nonoscillatory solutions for system of variable coefficients higher-order neutral differential equations with distributed deviating arguments. We use the Banach contraction principle to obtain new sufficient conditions for the existence of nonoscillatory solutions.

We consider the existence for eventually positive solutions of high-order nonlinear neutral differential equations with distributed delay. We use Lebesgue's dominated convergence theorem to obtain new necessary and sufficient condition for the existence of eventually positive solutions.