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Abstract:Objective To study the regular pattern of inhalational particulate matter deposition in respiratory tract and its influencing factors during breathing by numerical simulation method. Methods Three-dimensional finite element model of normal human respiratory tract was established to simulate the airflow distributions in respiratory tract during inspiration. The particles were released at the entrance of nose or mouth to simulate the deposition process of suspended particles by inhaled airflow in respiratory tract. Different parameters such as particle diameter, particle density and flow rate of air volume were used for comparative analysis to investigate their functions as influencing factors when particle deposition happened in respiratory tract. Results The particles were mainly deposited in nasal threshold, nasal middle airway, nasopharynx, and bronchial inner wall of respiratory tract. The particle deposition rate increased with the parameters of particle diameter, particle density and air volume flow rate increasing. The influence of different parameters on the deposition rate was not the same. Conclusions The particle is mainly deposited at the site with complex geometry or at the position where path direction changes violently. Particle diameter, density and breathing airflow rate will affect the deposition rate in respiratory tract. These research findings will provide numerical references for the clinical assessment on risk of respiratory diseases caused by air pollution.

Abstract:Objective To clarify the influence from left ventricular assist device （LVAD） cannula anastomosis on micro-emboli movement by numerical simulation methods. Methods Firstly, a patient-specific aorta geometric model was reconstructed based on CT scan images of a patient with heart failure. Three geometric models of LVAD support were established according to clinical practice, and the outflow cannula of LVAD was anastomosed at the three different locations of ascending aorta (the anterior wall, between anterior wall and lateral wall, the lateral wall of ascending aorta). Secondly, the computational fluid dynamic (CFD) approach combined with the discrete phase theory was used to calculate the hemodynamic states, and Fluent finite element software was used for numerical simulation of the fluid. Finally, the micro-emboli distribution flow pattern, wall shear stress (WSS) and velocity vector were extracted to evaluate the hemodynamic state. Results The probability of micro-emboli entering the brain vessel at the three different anastomosis locations were 23.6%, 33.8% and 36.7%, respectively. Besides, vortex was observed around the anastomosis locations. Conclusions The different anastomosis locations of LVAD cannula can significantly change the hemodynamic environment, which will influence micro-emboli movement in the aorta. The research findings provide some insights and theoretical support for optimizing the anastomosis to decrease occurrence risk of stroke in clinic.

Abstract:Objective To analyze and compare the effects of structure parameters on synchronous motor ability between the blood vessel and stent after stent implantation by using finite element method and grey correlation theory. Methods The magnesium alloy stent of S closed-loop type was selected, and 9 models of such stents with different materials, numbers of support in circumferential direction, support lengths and initial diameters were established by using SolidWorks, and these stent models were meshed by using HyperMesh. The synchronous motor ability between the blood vessel and stent after stent implantation was simulated by using ABAQUS, and the influencing factors of different structure parameters on bending stiffness were investigated and compared by using grey correlation theory. Results The effect of materials on stent flexibility was obvious. The flexibility of magnesium alloy stent was the best, and the bending stiffness was 0.958 N?(rad?mm)-1; the best flexibility of stents were those with 5-support in circumferential direction, 1.0 mm-support length, and 1.4 mm-initial diameter, and their bending stiffness was 0.853,0.829 and 1.024 N?(rad?mm)-1, respectively. Conclusions The flexibility of magnesium alloy stent is the best, followed by stainless steel stent, and cobalt-chromium stent ranks last. With the increase of support numbers in circumferential direction, support length and initial diameter, the stent flexibility shows the decreasing tendency; the grey correlation analysis shows that the effect of materials on stent flexibility is the most significant, followed by support numbers in circumferential direction and support length, while initial diameter exerts the smallest influence. The analysis of structure parameter effects on stent flexibility will provide more scientific guidance for stent design and development as well as its intervention treatment in clinic.

Abstract:Objective To predict signal transduction pathways of the integrin adhesome via bioinformatics method, so as to provide references for experimental study on the mechanism of integrin-related signal transduction pathways. Methods First, the interaction network between the interactive integrin adhesome was constructed, and the confidence probability of each interaction was used as its link weight, respectively. Secondly, the pathways of the minimum weight were identified via a standard dynamic programming algorithm. Finally, all pathways calculated by the algorithm were aggregated into some probable networks. Results Seven signal transduction pathways were obtained from the integrin adhesome interaction network that contained 147 components with 736 interactions. In every predicted signal transduction pathway, the coverage rate of the proteins with Gene Ontology annotation was calculated. Conclusions By research on signal transduction pathways the pathogenesis of some diseases can be explored at the molecular level. Several possible signal transduction pathways obtained in this study have some reference value for exploring disease mechanism in basic medical sciences, and also provide some useful information for such exploration under the stimulation of external signals including mechanical or chemical signals.

Abstract:Objective To investigate the synergic effects of substrate stiffness and topography on the morphology, proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs). Methods rBMSCs were cultured on polydimethylsiloxane (PDMS) substrates with different stiffness (3.5, 0.27 MPa) and ordered ridges and grooves (width 0.3 or 1.8 μm, depth 0.5 μm) or planar substrate. Inverted fluorescence microscope was used to observe the morphology of rBMSCs. CCK-8 reagent was used to detect the proliferation of rBMSCs. Alkaline phosphatase (ALP) kit was used to detect the ALP activity of rBMSCs. Immunofluorescence technique was used to detect the expression of osteocalcin (OCN) and collagen I (COL Ⅰ). QRT-PCR technique was used to detect the expression of Runx2 mRNA. Results rBMSCs cultured on substrate with 3.5 MPa stiffness, 0.3 μm ridge width, 0.3 μm groove width showed greater proliferation, spreading, cytoskeleton arrangement, and OCN and COL Ⅰ secretion, ALP activity, Runx2 mRNA expression were significantly increased as compared to cells cultured on other groups. Conclusions Substrate stiffness has an obvious influence on rBMSCs proliferation, while substrate stiffness and topography can synergistically promote the proliferation and osteogenic differentiation of rBMSCs. The research findings not only help to understand the biophysical factors in the pathogenesis of certain diseases (such as osteoporosis), but also provide a theoretical basis for developing new materials for bone tissue engineering.

Abstract:Objective To explore the effects of mechano-growth factor (MGF) E peptide on cell viability, migration and invasion of anterior cruciate ligament (ACL) fibroblasts. Methods ACL fibroblasts were used in this study and (1) were treated with MGF E peptide (0, 10 and 100 μg/L) for 24 h. Then, the medium was changed by 1% fetal bovine serum (FBS)-low glucose DMEM medium. Cell activity, DNA content, cell apoptosis, matrix metalloproteinases-2 (MMP-2) and MMP-9 activity, type I collagen (COL I) and type III collagen (COL III) mRNA expression were measured after continued culture for 6 and 30 h; (2) were treated with MGF E peptide (0, 5, 10, 20, 50 and 100 μg/L) for 48 h. Then, cell activity and MMP-2 activity were verified. Cell migration and invasion of ACL fibroblasts were further tested by cell scratch test and transwell assay, respectively. Results (1) At 6 h, 10 μg/L MGF E peptide significantly promoted MMP-2 and MMP-9 activities, but had no effect on cell viability, proliferation, apoptosis and mRNA expression of COL I and COL III. 100 μg/L MGF E peptide also significantly promoted MMP-2 and MMP-9 activities, as well as mRNA expression of COL I and COL III. However, it had no effect on the cell viability, proliferation and apoptosis. At 30 h, 10 μg/L MGF E peptide significantly promoted MMP-9 activity and mRNA expression of COL I and COL II, but had no effect on cell viability, proliferation, MMP-2 activity and apoptosis. 100 μg/L MGF E peptide also significantly promoted MMP-9 activity and mRNA expression of COL III, but had no effect on the cell viability, proliferation, MMP-2 activity, cell apoptosis and mRNA expression of type I collagen. (2) MGF E peptide significantly promoted migration and invasion of ACL fibroblasts with dose-dependent manner in a certain degree, which might depend on the increase of MMP-2 activity. Conclusions MGF E peptide can actively accelerate synthesis and degradation of the extracellular matrix, further promote migration and invasion of ACL fibroblasts, help ACL fibroblasts to move to the injurious site during repair process, which plays an important role in ACL tissue repair, regeneration and recovery after surgery.

Abstract:Objective By studying biomechanical responses of the femur-prosthesis-tibia complex under normal standing condition after tumor-type hinged knee arthroplasty, to investigate the cause of femoral perforation in patients after knee arthroplasty, so as to provide a theoretical basis for optimal design and manufacturing of tumor-type hinged artificial knee prosthesis. Methods By coupling CT and 3D optical scanning, the finite element model of the subject-specific femur-prosthesis-tibia complex was established and was validated regarding its availability, so as to analyze stress distribution and stress shielding phenomenon of the complex in standing position. Results (1) Under the loading state of standing, the stress on the femur was significantly larger than that on the tibia, and presented an evident concentration phenomenon. The proximal 1/3 of femoral shaft presented a larger stress, with a stress shielding effect. (2) As the model was based on geometry and bone characteristics of the patient in clinic, the location of femur stress concentration was close to that of femur perforation in the patient, which indicated that femur injury behavior might occur when its own gravity was applied such as the patient condition. Conclusions After implantation of the tumor-type hinged artificial knee prosthesis, the prosthesis marrow needle goes deep into marrow cavities, which brings certain pressure to the marrow cavities even under normal standing condition. The produced stress shielding effect and the match of the prosthesis marrow needle to the marrow cavity are all likely to cause stress concentration on the femur, even make femur crack or perforation, and eventually affect the surgery quality. Thus, the prosthesis design should be carefully optimized before surgery in order to reduce or avoid such phenomenon that is related to the postoperative complication rate.

Abstract:Objective To investigate the validity of screw-rod system for fixing pelvic fractures by comparing the biomechanical behaviors from using screw-rod system or steel plate for fixing Tile B2 type pelvic fractures. Methods The finite element models of normal pelvis including ligaments, and Tile B2 fractured pelvis fixed by different screw-rod fixations (2 screws at fractured side, 3 screws at fractured side and at healthy side), and steel plate fixation were established. The vertical load (500 N) was applied on the upper terminal plate of the first body of the sacrum to simulate pelvis load during double-leg standing, single-leg standing and sitting. The displacement and stress distributions on normal pelvis and fractured pelvis with screw-rod fixation or with steel plate fixation were compared and analyzed. Results Both the screw-rod system and steel plate could effectively fix the fractured pelvis, and the fixation models showed similar displacement and stress distribution as normal pelvis. The largest displacement of fractured pelvis with 3-screw fixation on the diseased side was smallest under each working condition, and its stress level was also obviously lower than that of the other internal fixation models. During double-leg standing, compared with 2 screws fixation, 3 screws at healthy side fixation, and steel plate fixation, the Von Mises stress for 3 screws at fractured side fixation was reduced by 30.4%, 20.8%, 20.3%; during single-leg standing, the Von Mises stress for 3 screws at fractured side fixation was reduced by 31.8%,25.4%,18.5%; during sitting, the Von Mises stress for 3 screws at fractured side fixation is reduced by -6.5%,28.0%,61.1%,respectively. Conclusions The screw-rod system can fix Tile B2 pelvic fracture effectively, especially for 3-screw fixation on the fractured side. The results can provide the theory basis for clinical treatment of pelvic fracture.

Abstract:Objective To study biomechanical properties such as range of motion (ROM), intervertebral disc stress, ligament tension of inferior cervical spinal segment after the treatment of Discover, Prodisc-C artificial intervertebral disc replacement, and anterior cervical discectomy and fusion (ACDF), as well as mechanical property changes of the prosthesis after implantation. Methods Three kinds of operation plan on C5-6 cervical disc degeneration were established: Discover model, Prodisc-C model and ACDF model, as well as C4-7 segment original model of cervical vertebra. Biomechanical property changes after operation in cervical spine C4-7 segment in sagittal, coronal and transverse section were analyzed. Results ROM changes of cervical segment C5-C6 were as following: in Discover model it increased by 12.7%-73.1%, Prodisc-C model increased by 74%-98%, ACDF decreased by 55.8%-71.8%. The stress of C4-5 intervertebral disc after Discover artificial disc replacement showed no obvious increase, while the stress of C6-7 intervertebral disc decreased by 33.2%-54.2% under flexion, extension and axial rotation conditions. The amplification of ligament tension in Discover model decreased by 30%-40% as compared to that in Prodisc-C model. The maximum stress of Discover model (36.72 MPa) appeared under flexion condition, which was smaller than that in Prodisc-C model. Conclusions Artificial disc replacement can help to keep movement performance for segment after surgery. As a newly developed artificial intervertebral disc prosthesis, Discover makes some progress in the aspect of decreasing ligament stress and maintaining spinal stability. The research findings will provide theoretical basis for the clinical study on ACDF and artificial cervical intervertebral disc replacement surgeries.

Abstract:Objective In view of the uncertainties of material parameters for child craniocerebral tissues, the effects of such parameters on responses of child head under direct impact loads were investigated. Methods The impact simulation experiments were conducted under direct impact loads by using a validated finite element model of 3-year-old child head. Taguchi orthogonal method and variance analysis were performed to analyze the material properties of craniocerebral tissues in child head. Results Elastic modulus of the skull had statistically significant effects on impact responses of child head. With the skull elastic modulus increasing, the coup pressure decreased significantly (P=0.000), whereas the contrecoup pressure (P=0.000) and maximum Von Mises stress of the skull increased significantly (P=0.000). The linear viscoelastic material parameters of brain tissues also had statistically significant effects on impact responses of child head. With the increase of the short-time shear modulus of brain tissues, the maximum shear stress of brain tissues increased significantly (P=0.000) whereas the maximum principal strain decreased significantly (P=0.000). Conclusions These statistical analysis results can provide references for selecting material parameter of craniocerebral tissues in finite element model of child head, which will be helpful to improve diagnosis accuracy of brain injuries such as concussion difficult to be definitely diagnosed when using brain CT images in clinic.

Abstract:Objective To investigate the effect of asymmetric lumbar discectomy on facet joint force and stability of lumbar spine. Methods Seven human cadaver specimens (L2-3 segment) were selected to make intact, 1/4 discectomy and 1/2 discectomy status and applied with pure moment of 7.5 N?m. The range of motion (ROM) and facet joint force of L2-3 segment during flexion/extension, lateral bending and axial rotation were recorded, respectively. Results During extension, a significant increase in facet joint force was found under 1/4 discectomy status at the remained side. During lateral bending, the facet joint force at both sides under 1/2 discectomy status increased significantly than that under intact status. During axial rotation, facet joint force increased significantly only at the side without discectomy under 1/2 discectomy status. Except flexion, ROM under 1/4 discectomy and 1/2 discectomy status were larger than that under intact status in all the other motion directions (P<0.05). There was no significant difference in ROM between both sides during lateral bending and axial rotation direction. Conclusions The asymmetric lumbar discectomy can increase the ROM in all motion directions except flexion, and can enlarge the facet joint force asymmetrically, which indicate that instability of lumbar spine and facet joint force increasing resulted from asymmetric degeneration of the disc might lead to backache.

Abstract:Objective To collect the kinematics and kinetics functional parameters of healthy human lower limbs during stair ascent and descent, so as to provide data for designing the gait trajectory and selecting the driving components of the exoskeleton walker to achieve the motion of stair climbing. Methods Common staircase as an experimental setup was designed, and the three-dimensional (3D) motion capture system and 3D force plate were used to simultaneously measure the ankle, knee, hip motion information during stair ascent and descent. The movement characteristics of the lower limb during stair climbing was analyzed by SPSS statistical software and Origin graphics software, and the functional parameters during stair ascent and decent were also compared and analyzed. Results The joint angle at the sagittal plane, joint moment variation with gait and activity limits in lower limbs of healthy youth during stair ascent and descent were obtained by the experiment. The ranges of motion in ankle，knee and hip joints during stair ascent were -10.66°-13.26°, 6.85°-88.92°, 1.31°-50.18°,while those during stair descent were -37.42°-27.18°,9.83°-95.53°,8.01°-31.62°.The maximum ankle, knee and hip joint moment during stair ascent and descent were 1.788, 1.121, 0.946 N?m/kg, respectively. Conclusions The gait parameters variation with gait and the joint range of motion in human lower limb were significantly different during stair ascent and descent. Separate design targeting at stair ascent or stair descent is required for gait planning of walking aids, and the selection of driving element should consider the maximum moment in each joint during stair ascent and descent.

Abstract:Objective To study the effect of mechanical stretch on expression of inflammasome related factors in human periodontal ligament cells (HPDLCs). Methods HPDLCs were subjected to mechanical stretch with a 20% elongation magnitude for 6 h or 24 h, respectively. The mRNA and protein expression levels of IL-1β, Caspase-1 and NLRP3 were detected by real-time quantitative PCR and Western blot. The levels of IL-1β in the cell-culture medium of HPLCs in response to mechanical stretch for 1, 2, 4, 6 h were detected by ELISA, respectively. In control group, HPDLCs were cultured in similar conditions but not subjected with stretch. Results The mRNA and protein expression levels of IL-1β, Caspase-1 and NLRP3 were up-regulated with mechanical stretch for 6 h (P<0.05). The protein expression level of NLRP3 was up-regulated with mechanical stretch for 24 h (P<0.05). Compared with control group, the content of IL-1β in the cell-culture medium of HPLCs was increased significantly in response to mechanical stretch for 4 h and 6 h(P<0.05). Conclusions The expression of NLRP3/Caspase-1/IL-1β related factors in HPDLCs can be induced by 20% mechanical stretch for 6 h.

Abstract:In the environment of adaptive mechanics, osteoblasts, which are the main functional cells of bone formation, are one of the main cells in response to the mechanical loading. With the development of technology, more and more astronauts, pilots and other are exposed to the hypergravity environment. In order to better understand the mechanobiology response of osteoblasts under hypergravity, this paper reviews the mechanobiological research progress in morphology, gene expression, cytokine secretion and signal transduction pathways of ostoblasts, so as to thoughts and preparations for mechanobiology research of bone tissues in hypergravity environment.

Abstract:Notch-1 signaling pathway is responsible for cell differentiation, development, proliferation and apoptosis. Recent studies show that Notch-1 signaling pathway is also involved in cancer progression, including cell invasion, motility and cancer metastasis. Activation of Notch-1 signaling pathway can directly or indirectly induce cell proliferation and migration. In tumor cells, activation of Notch-1 facilitates epithelial-mesenchymal transition (EMT), keeps its mesenchyme characteristics and induces cell adhesion. Notch-1 signaling pathway also cross-talks with other pathways to regulate cell fate, such as PI3K/Akt, NF-κB pathways. The evidence shows that aberrant Notch-1 activation has been found in different solid tumors, which participates in regulating tumor metastasis. In this review, the Notch structure and function, Notch-1 signal and tumorigenesis, tumor metastasis via Notch-1 signaling, and Notch-1 signaling targeted-therapy were comprehensively summarized. To clarify the roles of Notch-1 signal pathway in tumor metastasis and its regulatory mechanisms as well as the current treatment strategies for Notch-1 signal pathway will provide references for studies on pathomechanism and clinical treatment of cancers.