Objective To study ischemic effects on reentrant activities and cardiac arrhythmias using a computational approach. Method The Noble 98 mathematical model of ventricular cell was used in the study. The operator splitting and adaptive time step methods were utilized to integrate the partial differential equations in cardiac conduction models. The ischemic cells were simulated by decreasing the intracellular ATP concentration, reducing the Na+ conductance, and increasing the extracellular K+ concentration in a two-dimensional tissue. Spiral waves were initiated by the cross field technique. Result The results showed that spiral waves in local severe ischemia displayed three different morphologies,whereas in moderate ischemia only two kinds of wave forms exhibited. When the degree of ischemia reached a critical value, the reentrant wave could break. But for larger areas of ischemia spiral wave formed a typical functional reentry around the obstacle. Conclusion The study demonstrates that size and level of ischemia have effects on VTs and VFs. Large ischemic area is beneficial for maintenance of spiral wave and can provide a high probability in the genesis of VTs. Spiral waves can easily break up and degenerate into VFs under critical area or level of ischemia.

Hepatitis B surface antigen (HBsAg) carrying preS sequences could be an ideal candidate for a new hepatitis B virus (HBV) vaccine with higher efficacy. Here we report the success in achieving efficient and stable expression of hepatitis B virus S antigen and preS1 epitope fusion protein (S/preS1) in CHO cells. The HMRCHEF53u/Neo-S/preS1 expression vector carrying S/preS1 gene was constructed and transfected into CHO-S cells. A stable and high-expression CHO cell line, named 10G6, was selected by ELISA and limiting dilution analysis. Western blotting analysis showed S/preS1 expressed from 10G6 cells possessed both S and preS1 antigenicity. 10G6 cells displayed characters of favorable growth and stable S/preS1 expression in repeated batch cultures as evaluated by viable cell density, viability and S/preS1 concentration. And cultivation of 10G6 cells in fed-batch mode resulted in S/preS1 production at 17-20 mg/L with viable cell density at 7 x 10(6)-10 x 10(6) cells/mL.
Animals ; CHO Cells ; Cricetulus ; Epitopes ; biosynthesis ; genetics ; Hepatitis B Surface Antigens ; biosynthesis ; genetics ; immunology ; Hepatitis B Vaccines ; biosynthesis ; genetics ; Hepatitis B virus ; Protein Precursors ; biosynthesis ; genetics ; immunology ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Transfection

Electrical instability easily induces a unidirectional conduction block, resulting in ventricular tachycardia (VT) or even fibrillation (VF). Cardiac memory affects dynamic electrical characteristics through previous pacing so that it makes the memory important in arrhythmia study. This paper investigates the impact of the rapid pacing duration on cellular excitability and its mechanism. Based on the canine endocardial single cell, a one-dimensional tissue model was developed. Simulations were realized with OpenMP parallel programming method. The results showed that with repetitive pacing, the cellular excitability became low while the conduction velocity decreased. Accumulation of intracellular [Ca2+]i and [Na+]i and depletion of [K+]i led to the shift of membrane current-voltage curves, changing the membrane resistance. Excitability determined by the resistance at the large width of stimulus pulse, therefore, it suggested that [Ca2+]i and [K+]i-induced memory formed the ionic substrates for the alteration of excitability.
Action Potentials ; Animals ; Computer Simulation ; Dogs ; Electric Stimulation ; Electrocardiography ; Heart Conduction System ; physiopathology ; Myocardial Contraction ; physiology ; Myocytes, Cardiac ; physiology ; Refractory Period, Electrophysiological ; physiology ; Tachycardia, Ventricular ; etiology ; physiopathology ; Ventricular Fibrillation ; etiology ; physiopathology

Objective To study the expression of eukaryotic translation initiation factor 4E(eIF4E)in the pathological scars and its probable role in the pathogenesis of pathological scars.Methods Immunohistochemiscal technique was performed to detect the expression and distribution of eIF4E protein in hypertrophic scars(14 cases),keloids(25 cases),mature scars(20 cases)and normal skins(20 cases).Reverse transcription polymerase chain reaction(RT-PCR)was used to detect the eIF4E mRNA level in hypertrophic scars(7 cases),keloids(8 cases),mature scars(8 cases)and normal skins(8 cases).Results Thepositive rate of eIF4E protein expression was remarkably significant difference between normal scars and pathological scars(P＜0.05).The level of eIF4E mRNA in pathological scars 1.73±0.31was higher than that in control group 0.99±0.28.There was significant difference between two groups (P＜O.05).Conclusions The expression of eIF4E is increased in pathological scar.eIF4 E expression is closely associated with the development of pathological scar.Therefore,eIF4E overexpression may play an important role in the proliferation of fibroblasts and in the pathogenesis of pathological scar.

Cardiac reentry is one of the important factors to induce arrhythmias. It could lead to ventricular tachycardia (VT) or even fibrillation (VF), resulting in sudden cardiac death. With the wide use of computer in the quantitative study of electrophysiology, the three-dimensional virtual heart for simulations needs to be developed imminently in computer. In this paper, numerical algorithm of the model was studied. The three-dimensional model was constructed by integrating Luo-Rudy 1991 ventricular cell model and diffusion equation. The operator splitting method was employed to solve the model. The alternate direction iterative (ADI) format and seven-point centered difference method were used for the partial differential equation. And the discrete format with second-order accuracy was taken for the boundary conditions. The results showed that the ADI format and seven-point centered difference method both could successfully figure out the membrane potential and electrical activities with good numerical stability. However, computing consumption could be greatly reduced with the ADI format, implying that the ADI method with large time step was more powerful in numerical simulations.
Action Potentials ; Algorithms ; Heart ; physiology ; Heart Ventricles ; Humans ; Imaging, Three-Dimensional ; Models, Cardiovascular ; Myocardium

Malignant arrhythmias and ventricular fibrillation are generally accepted as one of the major causes of death in cardiovascular diseases. Based on the H-H equations, the mathematical model of the cardiac cell action potential consists of the ion channels, pumps, exchangers and transporters that are closely connected with intra- and extra-cellular ion concentrations, the channel's conditions, nerve transductors and drugs. It can build the link between cell electrophysiology and clinical pathophysiology. By altering the cellular environments the computer simulating study on this kind of model can help us look into the electrophysiological changes of the cardiac tissue and even the whole heart and investigate the mechanisms of the cardiac arrhythmias as well. The components of the model and its computer simulating study are introduced in the paper.
Action Potentials ; Arrhythmias, Cardiac ; physiopathology ; Computer Simulation ; Heart ; physiopathology ; Humans ; Models, Cardiovascular ; Ventricular Fibrillation ; physiopathology

Objective To analyze the prognostic factors in patients with initially diagnosed bone-only metastatic nasopharyngeal carcinoma (NPC). Methods We collected the data of 68 patients with initially diagnosed bone-only metastatic NPC admitted to The Affiliated Tumor Hospital of Shantou University Medical College from 1997 to 2015. Forty-nine patients received chemoradiotherapy. The Kaplan-Meier method was used to calculate the overall survival rate;the log-rank test was used for univariate prognostic analysis;the Cox model was used for multivariate prognostic analysis. Results The median follow-up was 953 months. The 1-, 2-, 3-, and 5-year overall survival ( OS) rates were 53%, 38%, 21%, and 15%, respectively. The median OS time was 134 months. The univariate prognostic analysis showed that spinal metastases, the number of bone metastases, lactic dehydrogenase level before treatment, the radiotherapy technology and dose for primary tumor, and the short-term outcome of primary tumor were associated with OS ( P=002, 001, 000, 002, 002, 001 ) . The multivariate prognostic analysis showed that ≤3 bone metastases, dose to primary tumor>65 Gy, and intensity-modulated radiotherapy ( IMRT) were favorable prognostic factors for OS ( P=003,002,004) . Conclusions For patients with initially diagnosed bone-only metastatic NPC, active treatment ( IMRT, dose to primary tumor>65 Gy) should be considered for those with ≤3 bone metastases to achieve a complete response of primary tumor.

Purpose: SOX12 is overexpressed in many cancers, and we aimed to explore the biological function and mechanism of SOX12 in thyroid cancer. Materials and Methods: We first analyzed the expression of SOX12 in thyroid cancer using data in The Cancer Genome Atlas. Immunohistochemistry and qRT-PCR were performed to identify SOX12 expression in thyroid cancer tissue and cells. Thyroid cancer cells were transfected with small interfering RNA targeting SOX12, and cellular functional experiments, including CCK8, wound healing, and Transwell assays, were performed. Protein expression was examined by Western blot analysis. A xenograft model was developed to evaluate the effect of SOX12 on tumor growth in vivo. Results: SOX12 expression was increased in thyroid cancer tissue and cells. SOX12 promoted cell proliferation, migration, and invasion and accelerated tumor growth in vivo. The expression of PCNA, Cyclin D1, E-cadherin, Snail, MMP-2, and MMP-9 was affected by SOX12 knockdown. Bioinformatic analysis showed that SOX12 could interact with the POU family. SOX12 knockdown inhibited the expression of POU2F1, POU2F2, POU3F1 and POU3F2, and SOX12 expression showed a positive correlation with POU2F1, POU3F1, and POU3F2 expression in clinical data. POU2F1 and POU3F1 were able to reverse the effect of SOX12 knockdown on thyroid cancer cells. Conclusion SOX12 affects the progression of thyroid cancer by regulating epithelial-mesenchymal transition and interacting with POU2F1 and POU3F1, which may be novel targets for thyroid cancer molecular therapy.

Torsades de Pointes is a kind of severe ventricular arrhythmia. Myocardial ischaemia is one of the major causes leading to TdP. In this paper the mechanisms of the TdP were quantitatively studied under the condition of ischaemia based on the Noble98 dynamic model of the ventricular action potential. The study was conducted on one-dimensional homogeneous myocardium with the method of computer simulation. The models were firstly developed to simulate the lower excitability, extracellular accumulation of the K+ concentration or the decreased gap junctions in ischaemic myocardium. By separately reducing the Na+ conductance, increasing the extracellular K+ concentration or decreasing the conductance of the gap junctions enabled us to study the effect of each change in isolation. Then different degrees of ischaemic models were established to study their physiological features. The study showed that the conduction velocity became slower with the ischaemia aggravation, the action potential duration became shorter and the width of the vulnerable window obviously became larger than the normal conditions. The results illustrated that ischaemia was easily leading to unidirectional conduction block and resulted in re-entry and arrhythmias.
Computer Simulation ; Models, Cardiovascular ; Myocardial Ischemia ; physiopathology

On the basis of mammalian ventricular action potential model Noble98, and with the use of Runge-Kutta for solution, the Wenckebach periodicity phenomenon, the transmural heterogeneity of the ventricular myocardium and its rate dependence are studied. The results indicate that these inherent properties may, lead to temporal-space disorganized in the normal heart,and may become the underlying factors for arrhythmias. At the same time, in this study are established the basic methods for quantitative cellular electrophysiology which is essential for future studies on the mechanism of arrhythmia.
Action Potentials ; physiology ; Arrhythmias, Cardiac ; physiopathology ; Computer Simulation ; Electrophysiology ; Heart Conduction System ; physiology ; Heart Ventricles ; Humans ; Ion Channels ; metabolism ; Models, Cardiovascular ; Myocytes, Cardiac ; physiology