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Abstract:Objective To investigate the detailed molecular mechanism of matrix stiffness regulating cell drug resistance. Methods Polyacrylamide hydrogels of soft substrate (10 kPa), hard substrate (38 kPa) and rigid substrate (57 kPa) with different matrix stiffness were configured to simulate the physical matrix stiffness at different stages of breast cancer in vivo. Results The cell proliferation rate of the hard substrate was significantly higher than that of the soft and rigid substrates. The intracellular endocytosis was significantly lower on the hard substrate. The YAP nucleus translocation increased significantly on the hard substrate, compared with the soft and the rigid substrates, indicating that YAP was a key molecule involved in drug resistance of tumor cells. Conclusions Matrix stiffness could regulate the drug resistance of breast cancer cells through YAP activation. This study not only provides a new direction for elucidating the mechanism of drug resistance, but also lays a new foundation for the drug delivery system of breast cancer treatment.

Abstract:Objective To find the key factors that have great influences on the bistable properties between let7 and LIN28 by exploring the effects of different parameters on the negative feedback bistable system, and provide insights for regulating the drug resistance generated during treatment. Methods The bistability of two-dimensional system was studied by dynamics modeling, and the influence of the parameters on stability behavior of the system was investigated from the portrait of nullclines. Results The parameters showed heterogeneous effects on bistability behavior of the system. A shift in parameter values could regulate the characteristics of bistability and might even make a switch back and forth between bistability and monostability. Conclusions Targeted regulation of sensitive parameters can potentially achieve the goal of controlling drug resistance.

Abstract:Objective To investigate the influences of different matrix stiffness on proliferation ability and glucose metabolism of hepatocellular carcinoma (HCC) cells and to explore the correlation between metabolism and biological behavior changes of HCC cells resulted from the stiffness of extracellular matrix (ECM)．Methods The proliferation changes of HepG2 cells cultured on matrix with different stiffness were detected by CCK-8 assay and cell count assay. 2-NBDG and flow cytometry were used to detect the effect of matrix stiffness on glucose uptake. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of Glut1. Then, 2-DG was used to inhibit glycolysis, and the influences of matrix stiffness on proliferation of HepG2 cells were detected. Results The proliferation ability, glucose uptake and the expression of Glut1 of HepG2 cells increased with the matrix stiffness increasing. When glycolysis was inhibited, the proliferation ability of HepG2 cells grown on matrix with different stiffness was similar. Conclusions The mechanical microenvironment had an important effect on proliferation of HCC cells; matrix with a larger stiffness might promote proliferation of HCC cells through regulating glycolysis. The research findings provide a corresponding experimental basis for the clinical treatment of HCC cells and drug development targeting glucose metabolism.

Abstract:Objective To establish a new method to measure the elastic modulus of living circulating tumor cells (CTCs) by micropipette aspiration. Methods Living CTCs were enriched by commercial microfluidic chips and identified individually using EpCAM antibody under fluorescence microscope. The elastic modulus of CTCs was measured using micropipette aspiration and compared with cancer cell lines. Results For the elastic modulus of different cancer cell lines, heterogeneity was found not only between the different types of cancer cell lines but also inside the same cell line. The CTCs in breast cancer had a smaller elasticity modulus compared with MCF-7 cancer cell line. Conclusions This method can measure the elastic modulus of living CTCs, which provides cell mechanics data for studying the relationship between physical properties of CTCs and diagnosis of cancers, as well as developing the physical biomarkers of tumor cells.

Abstract:Objective To study the effect of intercellular adhesion of tumor cells on immune response of human body. Methods A tumor growth-cellular immune feedback model was developed based on cellular Potts model (CPM) to simulate the progression of tumor cells and the cellular immune feedback system, and the influence of adhesion between tumor cells on the immune system was analyzed. Results Under the condition of tumor intercellular adhesion with normal intensity, tumor cells could escape when the immune system was weak and be eliminated when the immune system was strong. Under the condition of tumor intercellular adhesion with low intensity, tumor cells could escape when the immune system was weak, while exhibited behavior of oscillation and could not be eliminated when the immune system was strong. Conclusions Higher adhesion between tumor cells inhibited escape of tumor cells from the immune system, while lower adhesion between tumor cells could effectively help the tumor escape killing from the immune system. When the tumor was extremely spread, the immune system could not completely eliminate tumor cells.

Abstract:Objective To make quantitative analysis on collected cell images combined with machine learning integrated clustering algorithm, so as to explore a method for fast recognition and classification of cells in mixed cultures based on morphology. Methods The morphometric properties of A549 and 3T3 cells in vitro were characterized by immunostaining, the fluorescent images were then analyzed with CellProfiler to extract the parameters of cell morphology. The parameters were loaded into CellProfiler Analyst to be trained with machine learning algorithm, and a rule was developed to form a generalization capability for cell classification in mixed cultures. Results The accuracy of the training classifier was 81-24%, and the binary classifications of A549 and 3T3 cells could be realized. Conclusions The method of machine learning is very effective in parameter clustering. The application of machine learning into cell image recognition can provide pre-judgment for rapid pathological examination of tissue sections, thereby reducing the workload of doctors and improving the accuracy of diagnosis.

Abstract:Objective To compare and analyze the mechanical performance of a new biodegradable stent and a common stent and their effects on treating the stenotic vessels. Methods Using finite numerical simulation, the new stent and the common stent were implanted into vessels with a diameter stenosis of 30%, and their support performance and influences on reshaping the stenotic vessels were investigated. Results The radial recoiling ratio and dog-boning ratio of the new stent were decreased by 26.6% and 34.7%, respectively, compared with the common stent. Besides, the stenotic vessel deployed with the new stent recoiled less and had a flatter and larger lumen. Conclusions Compared with the common stent, the new stent has stronger scaffold performance and a better therapeutic effect on stenotic vessels. The new stent with stronger scaffold performance is highly expected to be an alternative choice in interventional surgeries.

Abstract:Objective To compare the hemodynamic characteristics in internal carotid artery models, which were obtained by multi-scale unidirectional and bidirectional coupling models, so as to provide references for selecting models in further studies. Methods Based on the nuclear magnetic resonance image of one patient with mild stenosis of internal carotid artery, the lumped parameter model of the circle of Willis and the three-dimensional model of internal carotid artery were constructed. Those two different multi-scale models were constructed by unidirectional and bidirectional coupling. Results With the increase of stenosis degree, the inlet and outlet blood pressure and the outlet blood flow of internal carotid artery all decreased under two kinds of coupling method. The distribution of low time average wall shear stress (TAWSS) and high oscillatory shear index (OSI) of the internal carotid artery both increased with the increase of stenosis degree under two kinds of coupling method in general. The anterior cerebral artery segment showed lower shear stress and higher OSI with bidirectional coupling in 70% stenosis, and the blood flow direction of posterior communicating artery was changed, which was significantly different from unidirectional coupling results. Conclusions At a low degree of stenosis, the result of those two kinds of coupling method were consistent in general, but there was a significant difference in 70% stenosis, and the result of bidirectional coupling was closer to physiological parameters. The research findings can be better applied to the hemodynamic study of cerebrovascular diseases.

Abstract:Objective To explore the power output and blood compatibility of a novel electromagnetic pulsatile blood pump. Methods First, a theoretical model was established to analyze the driving force of the blood pump, and the experimental driving voltage satisfying the conditions was calculated based on this model. Then, the output flow rate, output pressure characteristics and hemolysis performance of the new blood pump in vitro were preliminarily analyzed by simulated circulation experiments. Results The experimental result showed that when the pump load was 73-5 mmHg (9-78 kPa, 1 mmHg=0-133 kPa), the driving voltage was 35 V and the pulsation frequency was 75 beats/min, the flow rate of the pump was 3-18 L/min, producing high, low and average pressure of 132, 66, 98 mmHg (17-56, 8-78, 13-03 kPa), and the normalized index of haematolysis (NIH) in vitro was (0-049 15+0-003 75) mg/dL. Conclusions The new pulsatile blood pump can satisfy the clinical requirements for perfusion of isolated organs and short-term assistance of cardiopulmonary bypass, which is of great significance to the development of cardiopulmonary bypass blood pump.

Abstract:Objective To analyze the influence regularities of different sizes on thermal stress field of bipolar high-frequency electric knife. Methods Based on the ANSYS software, the electric-thermal coupling simulation analysis was performed for thermal stress field of bipolar high-frequency electric knife during working. The effects of 3 different insulation layer thicknesses (0-5, 1-0, 1-5 mm), electrode thicknesses (0-5, 1-0, 1-5 mm) and coating thicknesses (3, 6, 9 μm) on thermal stress field of bipolar high-frequency electric knife were studied. Results If thickness of the insulation layer was larger, deformation of the myocardial tissues would be smaller due to thermal stress, that is, the thickness of the insulation layer was inversely proportional to thermal deformation of the myocardial tissue during working process of the high-frequency electric knife. For the 3 electrode thicknesses, 1-0 mm was a better choice. And for the 3 coating thicknesses, 6 μm was a better choice. Conclusions The component sizes for the high-frequency electric knife have an important influence on thermal stress field, and the result can provide guidance for design of the high-frequency electric knife.

Abstract:Objective Aiming at solving the problems of pain on the anteromedial tibia, tibial component loosening and osteoarthritis progression after unicompartmental knee arthroplasty (UKA), the influence of different geometric shapes of tibial component pegs on stress distributions in tibia was analyzed by finite element method. Methods The finite element models with UKA were established and validated. Geometric shapes of tibial component were designed. Under the same loading condition, the tibial components with double-peg, single-keel, double-keel and cross-star were studied for finite element analysis and compared with intact model, so as to evaluate the influence of tibial component with different shapes on stresses of cortical bone in anteromedial tibia, cancellous bone under tibial component and cartilage in contralateral tibia. Results Compared with the intact model, the peak stress of cortical bone in anteromedial tibia with double-peg, single-keel, double-keel and cross-star tibial components increased by 56.1%, 55.9%, 54.5% and 68-4%, respectively. The peak stress of cancellous bone under tibial component with single-keel and double-keels decreased by 8.1% and 15.6% respectively, while the peak stress of cancellous bone under tibial component with double-peg and cross-star increased by 67-9% and 121-5%, which were higher than the fatigue yield stress of cancellous bone. The peak stress of cartilage in contralateral tibia with double-peg, single-keel, double-keel and cross-star tibial components decreased by 42.1%, 26.6%, 24.2% and 28.5%, respectively. ConclusionsThe load distribution of the medial and lateral tibia changed after UKA operation, and a greater load was observed on the replacement side. Single-keel and double-keel tibial components were more effective in reducing stresses on cortical bone in anteromedial tibia and cancellous bone, while the stress distribution in tibia with single-keel tibial component was closer to that of the intact tibia. The research findings can provide theoretical references for designing single-keel tibial component of unicompartmental knee prosthesis which conforms to better mechanical properties of the knee joint.

Abstract:Objective To study the stress distributions of mandible defect by reconstruction with polyetheretherketone (PEEK) and its composite reconstruction plate through three-dimensional finite element analysis. Methods The finite element models of reconstruction plate of titanium alloy, PEEK, carbon-fiber-reinforced polyetheretherketone (CFR)-PEEK with 30% endless carbon fibers and CFR-PEEK with 68% endless carbon fibers were established by CBCT scanning，Mimics software，SolidWorks, Geomagic Studio and ANSYS Workbench software, and titanium alloy served as control. Two occlusal situations were simulated in the mandible model. Loading I: anterior region loading with 300 N; loading II: left posterior region with 300 N. Results The ratio of the maximum Von Mises stress of the reconstructed plate to its yield strength under two load situations: PEEK system ＞ 30%CFR-PEEK system ＞ titanium alloy system ＞ 68% CFR-PEEK system; the maximum stress of the mandible: PEEK system ＞ 30% CFR-PEEK system ＞ titanium alloy system ＞ 68% CFR-PEEK system. In the PEEK system, the maximum Von Mises stress of reconstructed plate and mandibular exceeded its yield strength under loading I; in the other systems, the maximum Von Mises stresses of mandible and reconstruction plate were below the yield strength. Conclusions The reconstruction plate of CFR-PEEK with 68% endless carbon fibers distributed the stresses in a similar manner as the titanium reconstruction plate, which could meet the mechanical strength requirements of mandible defect reconstruction. The fracture risk of the reconstructed plate was lower than that of titanium alloy, but the incidence of stress shielding was slightly higher. The result can provide references for the selection of materials and clinical application of reconstruction plate for mandibular defects.

Abstract:Objective To investigate the effect of calcitriol on osteogenic differentiation of mesenchymal stem cells (MSCs) induced by bone morphogenetic protein 9 (BMP9). Methods The experiment was divided into four groups: control group, calcitriol group, BMP9 group and BMP9+calcitriol group. Quantitative PNPP method was used to detect alkaline phosphatase (ALP) activity. RT-PCR and Western blotting method analyzed expression of osteocalcin（OCN）and osteopontin (OPN). Alizarin red staining assessed the formation of mineralized nodules. In addition, the changes of cell morphology and elastic modulus during osteogenic differentiation were studied by atomic force microscope. ResultsCompared with control group, calcitriol alone had no significant effect on the osteogenic differentiation of MSCs, but calcitriol could enhanced expression of osteogenic markers and formation of mineralized nodules induced by BMP9. However, neither calcitriol nor BMP9 could affect elastic modulus of cells. The combined treatment of BMP9 and calcitol could enhance phosphorylation of AKT and β-catenin which were both important for osteogenesis. The pretreated PI3K inhibitor could inhibit phosphorylation of AKT and β-catenin as well as ALP activity in BMP9+calcitriol group. In addition, calcitriol did not affect the BMP/Smad signaling pathway induced by BMP9. Conclusions Calcitriol synergies with BMP9 could promote MSCs osteogenesis by activating the PI3K/AKT signaling pathway. The study about effects and mechanisms of different regulatory factors on osteogenic differentiation of MSCs is of great significance for the treatment of osteoporosis and the development of bone tissue engineering.

Abstract:Objective To study the influence of foot progression angle on tibial shock during running. Methods The normal, toe-in and toe-out gait of fifteen healthy adults was tested during running trials on a treadmill. The differences in tibial shock (impact peak, average loading rate, instantaneous loading rate and maximum tibia acceleration) for runners at different foot progression angles were analyzed to explore the influence of foot progression angle on tibial shock. The changes in sagittal plane trunk angle, strike pattern, stride frequency and step width of runners under three gaits were also compared to explore its possible causes. Results Compared with normal gait, the maximum tibial acceleration of toe-in and toe-out gait was increased by 19.3% and 24.5%, impact peak was increased by 7.6%, average loading rate was increased by 7.9% and 9.5%, instantaneous loading rate was increased by 3.9% and 10-.9%, with significant statistic differences. No significant changes were found in sagittal plane trunk angle, strike pattern, stride frequency and step width. Conclusions Foot progression angle might be an another gait parameter which affected tibial shock during running in addition to other related known gait parameters such as sagittal plane trunk angle, strike pattern, stride frequency and step width，which would provide an important reference for prevention of tibial stress fracture.

Abstract:Due to the three-dimensional spiral-shaped geometry of aorta, the flow pattern within the human aorta is helical in late systole. Helical flow widely exists in the human arterial system as one typical flow pattern. Studies demonstrate that the helical flow plays a positive physiological role in facilitating blood flow transport, suppressing disturbed blood flow, preventing the accumulation of atherogenic low density lipoproteins on the luminal surfaces of arteries, enhancing oxygen transport from the blood to the arterial wall and reducing the adhesion of blood cells on the arterial surface. Therefore, the potential clinical applications of helical flow were summarized, so as to provide references for the optimal design of cardiovascular interventional therapies and devices.

Abstract:Understanding the biomechanical properties of periodontal ligament is of great significance for orthodontic treatment. Due to the complexity of periodontal ligament structures, previous studies mainly used in vitro experiments, which had limitations. In order to obtain accurate and actual data, in vivo experiments on biomechanical properties of periodontal ligaments will become a trend of development in the future. In this article, the method, types, progress, advantages and disadvantages of in vivo experiments on biomechanical properties of periodontal ligaments were reviewed and prospected.