CN106777934B - A simulation system for analyzing CaMKII-induced ventricular arrhythmias - Google Patents
A simulation system for analyzing CaMKII-induced ventricular arrhythmias Download PDFInfo
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Abstract
A kind of analogue system causing ventricular arrhythmia for analyzing CaMKII is related to a kind of assistant analysis tool for carrying out arrhythmia cordis research.The present invention includes: the electro photoluminescence setup module of the region setting and stimulation parameter setting for electro photoluminescence；The simulation object of information for the parameter of simulation object to be arranged and the electro photoluminescence information of electro photoluminescence setup module is combined to export simulation object is arranged and output module, it include: checking for CaMKII modulin information, the subcellular simulation unit of modification and editor's typing, for recording the cell simulation unit of the information of cell membrane action potential, fiber simulation unit for the information that operation of recording current potential conducts in the fibre, tissue simulation unit for the information that operation of recording current potential conducts in the tissue, whole-heartedly room simulation unit for the information that operation of recording current potential conducts in ventricle.The present invention is used for the assistant analysis of arrhythmia cordis research.
Description
Technical field
The present invention relates to a kind of assistant analysis tools for carrying out arrhythmia cordis research.
Background technique
Cardiovascular disease can cause sudden cardiac death.According to statistics, there are about 3,500,000 people to die of cardiovascular disease every year in China, often
Just there is 1 people to die of cardiovascular disease within 10 seconds, wherein 90% or more by the malignant ventriculars rhythm of the heart such as Ventricular Tachycardia, ventricular fibrillation
Caused by not normal.The lethality of cardiovascular disease alreadys exceed cancer, becomes the first killer of human health.
Most of arrhythmia cordis is not only limited to the change of single channel function, and with age, anoxic, ischemic, inflammation
Disease, tissue damage and overall disease are closely related, these factors cause the electricity and structural remodeling of heart, promote the mortality rhythm of the heart
Not normal generation.In recent years, more and more researches show that, multi-functional CaMKII (Ca/CaM kinase II, calcium/calcium tune
The protein kinase ii that albumen relies on) increase with Cellular Oxidation, the high level activation of ion channel, intracellular Ca2+ and sodium disorder, group
It is closely related to knit the pathogenic factors such as damage, and the CaMKII of high level activation is promoted by adjusting ion channel and transcription factor
Reform organization caused by the reconstruct of electricity caused by ion channel dysfunction and Apoptosis fibrosis, CaMKII are almost participated in
Form the whole process of arrhythmia cordis.
Currently, for CaMKII cause ventricular arrhythmia research, heart physiological virologist mostly from cell, gene,
Heart mechanism is studied on the microcosmic level such as albumen, molecule, obtained result is usually tested and also tends to only reflect subcellular
Or single celled local characteristics, it can not further elucidate from microscopic lesions and develop into macroscopical whole cardiopathic process；The clinical heart
The focus of work is then placed on macro-level by splanchnology man, they are often concerned with the performance of whole cardiac conditions, and ignore disease
The microscopic origin of disease is also built upon greatly in the analysis of surface electrocardiogram and the resolution of experience the diagnosis of heart disease.At present
There are no a kind of assistant analysis tools of relationship between reaction CaMKII micro-variations and ventricular arrhythmia macro manifestations, currently
This macroscopic view and microcosmic two poles development exact can not understand heart so that having differences and contradiction for cardiopathic understanding
The process of lesion causes cardiopathic treatment and diagnosis still pessimistic, has seriously affected the efficiency of antiarrhythmic drug exploitation,
Considerably increase the funds expenditure of pathomechanism research and new treatment exploitation.
Summary of the invention
There is presently no a kind of reaction CaMKII micro-variations and ventricular arrhythmia macro manifestations in order to solve by the present invention
Between relationship assistant analysis tool the problem of, and then propose it is a kind of for analyze CaMKII cause ventricular arrhythmia emulation
System, to help people to analyze relationship between CaMKII micro-variations and ventricular arrhythmia macro manifestations.
A kind of analogue system causing ventricular arrhythmia for analyzing CaMKII, comprising: electro photoluminescence setup module and emulation
Object setting and output module；
(Regions) and stimulation ginseng is arranged in the electro photoluminescence setup module (CaseParams), the region for electro photoluminescence
Number setting (StimulateParams), specific stimulation parameter include: simulation time (time), iuntercellular conductance (DD), emulation
Cell type (voxel) that step-length (dt), stimulus type title (name), electro photoluminescence are directed to, intensity of electric stimulus (strength),
Electro photoluminescence initial time (startTime) and deadline (endTime)；
The simulation object setting and output module (VolumeControl), for the parameter of simulation object to be arranged, and are tied
Close the information of the electro photoluminescence information output simulation object of electro photoluminescence setup module；Include:
Typing, including cell membrane are checked, modify and edited to subcellular simulation unit for CaMKII modulin information
The modification and typing of ionophorous protein information and intracellular Ca2+ GAP-associated protein GAP information；
Cell simulation unit, for recording the information of cell membrane action potential, including resting potential, maximum depolarising speed
Rate, maximum depolarising current potential and Action Potential Duration；
Fiber simulation unit, for the information that operation of recording current potential conducts in the fibre, including when conduction of velocity, multipole
Between, repolarization dispersion and pseudo- electrocardiogram；
Simulation unit is organized, for the information that operation of recording current potential conducts in the tissue, including tissue surface current potential, wave crest
Track, the frequency of wave crest action potential and wave crest action potential；
Whole-heartedly room simulation unit, for the information that operation of recording current potential conducts in ventricle, including ventricle surfaces current potential, wave
The frequency of peak action potential and wave crest action potential.
Preferably, the subcellular simulation unit regulates and controls parameter, the activation amount of CaMKII by input CaMKII
(CaMKa) and typing is checked, modifies and edited to gating parameter, realization CaMKII modulin information；Subcellular emulation simultaneously
Unit exports ion channel current.
Preferably, the cell simulation unit, by all on input cell type, extracellular electro photoluminescence, cell membrane
Ion channel current realizes the information of record cell membrane action potential；Cell simulation unit exports cell membrane potential simultaneously.
Preferably, the fiber simulation unit, by inputting fiber electro photoluminescence size and location, cell type, cell number
Mesh, iuntercellular conductance, cell membrane potential realize the information that operation of recording current potential conducts in the fibre；Fiber simulation unit simultaneously
Output fiber surface potential.
Preferably, the tissue simulation unit, by input tissue electro photoluminescence size and location, tissue geometry,
Type, the iuntercellular conductance, cell membrane potential of cell；Realize the information that operation of recording current potential conducts in the tissue；It organizes simultaneously
Simulation unit output organization surface potential.
Preferably, the whole-heartedly room simulation unit, by the geometry for inputting whole-heartedly room electro photoluminescence size and location, whole-heartedly room
Structure, the type of cell, iuntercellular conductance, cell membrane potential；Realize the information that operation of recording current potential conducts in ventricle；Simultaneously
Whole-heartedly room simulation unit exports whole-heartedly chamber surface current potential.
Preferably, a kind of analogue system causing ventricular arrhythmia for analyzing CaMKII further includes simulation video control
Molding block (MovieControl), the input and output control of the simulation video for analogue system dynamic process；Including inputting mesh
Record (inputDir), output directory (outputDir), start file index (startindex), ends file index
(endindex), the broadcasting and printing of video.
The invention has the following advantages:
A kind of analogue system causing ventricular arrhythmia for analyzing CaMKII of the present invention, provides a kind of reaction
The assistant analysis tool of relationship between CaMKII micro-variations and ventricular arrhythmia macro manifestations recognizes from multiple dimensioned angle
The means of CaMKII (protein kinase ii that calcium/calmodulin relies on) control mechanism have been constructed from microcosmic CaMKII molecule to macro
The bridge for seeing heart organ provides the research microcosmic electrophysiological change of CaMKII for entire complicated cardiac system function
Analysis tool.It can promote the effective communication between cardiac molecular biologist and clinician by the present invention, can promote
The understanding of CaMKII proarrhythmia mechanism, can effectively promote antiarrhythmic drug development efficiency and saving funds are opened
Branch.
Detailed description of the invention
Fig. 1 electro photoluminescence setup module Simulation Interface；
Fig. 2 is the kinetic curve of the activation amount (CaMKa) of CaMKII；Abscissa is time (Time), and ordinate is
The activation amount representative fraction (fraction) of CaMKa；
Fig. 3 is the kinetic curve of the ion channel in cell membrane INa electric current under being adjusted by CaMKII；Abscissa is the time
(Time), ordinate is INa electric current, and μ A/PF is microampere/pico farad；
Fig. 4 is the kinetic curve of the ion channel in cell membrane INaL electric current under being adjusted by CaMKII；Abscissa is the time
(Time), ordinate is INaL electric current；
Fig. 5 is the kinetic curve of the ion channel in cell membrane ICaL electric current under being adjusted by CaMKII；Abscissa is the time
(Time), ordinate is ICaL electric current；
Fig. 6 is the kinetic curve of the ion channel in cell membrane Ito electric current under being adjusted by CaMKII；Abscissa is the time
(Time), ordinate is Ito electric current；
Fig. 7 is the kinetic curve of the intracellular Ca2+ GAP-associated protein GAP Irel electric current under being adjusted by CaMKII；When abscissa is
Between (Time), ordinate be the corresponding ion stream of Irel, mM/ms be mmoles/millisecond；
Fig. 8 is the kinetic curve of the intracellular Ca2+ GAP-associated protein GAP Iup electric current under being adjusted by CaMKII；Abscissa is the time
(Time), ordinate is the corresponding ion stream of Iup, and mM/ms is mmoles/millisecond；
Fig. 9 is the cell membrane potential curve under being adjusted by CaMKII；Abscissa is time (Time), and ordinate is movement electricity
Position (AP)；
Figure 10 is the Simulation Interface of fiber simulation unit；
Figure 11 is fiber surface Repolarization time curve；Abscissa is cell quantity (Cell number), and ordinate is movement
Current potential duration (APD90)；
Figure 12 is fiber surface electrocardiogram；Abscissa is time (Time), and ordinate is electrocardiogram (ECG)；
Figure 13 is tissue simulation unit Simulation Interface；
Figure 14 is the wave crest track of tissue surface current potential；
Figure 15 is the action potential of wave crest；Abscissa is time (Time), and ordinate is action potential (AP)；
Figure 16 is the frequency of wave crest action potential (by taking square tissue as an example)；Abscissa is frequency, and ordinate is frequency
Corresponding amplitude (P)；
Figure 17 is whole-heartedly room simulation unit Simulation Interface；
Figure 18 is the action potential of whole-heartedly chamber surface；Abscissa is time (Time), and ordinate is action potential (AP)；
Figure 19 is the frequency of whole-heartedly chamber surface action potential；Abscissa is frequency, and ordinate is the corresponding amplitude of frequency
(P)。
Specific embodiment
Specific embodiment 1:
A kind of analogue system causing ventricular arrhythmia for analyzing CaMKII, comprising: electro photoluminescence setup module and emulation
Object setting and output module；
As shown in Figure 1, the electro photoluminescence setup module (CaseParams), the region for electro photoluminescence is arranged
(Regions) and stimulation parameter setting (StimulateParams), specific stimulation parameter include: simulation time (time), it is thin
Cell type (voxel) that intercellular conductance (DD), simulation step length (dt), stimulus type title (name), electro photoluminescence are directed to, electricity thorn
Swash intensity (strength), electro photoluminescence initial time (startTime) and deadline (endTime)；
The simulation object setting and output module (VolumeControl), for the parameter of simulation object to be arranged, and are tied
Close the information of the electro photoluminescence information output simulation object of electro photoluminescence setup module；Include:
Typing, including cell membrane are checked, modify and edited to subcellular simulation unit for CaMKII modulin information
The modification and typing of ionophorous protein information and intracellular Ca2+ GAP-associated protein GAP information；
Cell simulation unit, for recording the information of cell membrane action potential, including resting potential, maximum depolarising speed
Rate, maximum depolarising current potential and Action Potential Duration；
Fiber simulation unit, for the information that operation of recording current potential conducts in the fibre, including when conduction of velocity, multipole
Between, repolarization dispersion and pseudo- electrocardiogram；
Simulation unit is organized, for the information that operation of recording current potential conducts in the tissue, including tissue surface current potential, wave crest
Track, the frequency of wave crest action potential and wave crest action potential；
Whole-heartedly room simulation unit, for the information that operation of recording current potential conducts in ventricle, including ventricle surfaces current potential, wave
The frequency of peak action potential and wave crest action potential.
Specific embodiment 2:
Subcellular simulation unit described in present embodiment regulates and controls parameter, the activation amount of CaMKII by input CaMKII
(CaMKa) and typing is checked, modifies and edited to gating parameter, realization CaMKII modulin information；Subcellular emulation simultaneously
Unit exports ion channel current.
In subcellular simulation unit, the expression process of CaMKII modulin:
Input: CaMKII regulates and controls parameter, and (CaMKo indicates the activation ratio of CaMKII under equilibrium state；BCaMK indicates CaMKII
Dephosphorylized rate；The rate of aCaMK expression CaMKII phosphorylation；The Michaelis constant of KmCaM expression calmodulin；KmCaMK
Indicate the Michaelis constant of CaMKII)
Output: the activation amount (CaMKa) of CaMKII
Programming code is as follows:
In subcellular simulation unit, adjustment effect process of the CaMKII for ion channel: (said by taking INaL as an example
It is bright)
Input: the activation amount (CaMKa) and gating parameter of CaMKII
Output: ionic current (by taking INaL as an example)
Programming code is as follows:
It is included INa, INaL, ICaL and Ito by the CaMKII ion channel in cell membrane electric current adjusted, Fig. 2-6 is to pass through
This system emulation obtains the figure that data are drawn.
Fig. 2 is the kinetic curve of the activation amount (CaMKa) of CaMKII；
Fig. 3 is the kinetic curve of the ion channel in cell membrane INa electric current under being adjusted by CaMKII；
Fig. 4 is the kinetic curve of the ion channel in cell membrane INaL electric current under being adjusted by CaMKII；
Fig. 5 is the kinetic curve of the ion channel in cell membrane ICaL electric current under being adjusted by CaMKII；
Fig. 6 is the kinetic curve of the ion channel in cell membrane Ito electric current under being adjusted by CaMKII.
In subcellular simulation unit, CaMKII modulin is expressed as follows the information of intracellular Ca2+ GAP-associated protein GAP:
It is included Irel and Iup by the CaMKII intracellular Ca2+ GAP-associated protein GAP adjusted, Fig. 7-8 is obtained by this system emulation
Obtain the figure that data are drawn.
Fig. 7 is the kinetic curve of the intracellular Ca2+ GAP-associated protein GAP Irel electric current under being adjusted by CaMKII；
Fig. 8 is the kinetic curve of the intracellular Ca2+ GAP-associated protein GAP Iup electric current under being adjusted by CaMKII.
Other modules, unit and parameter are same as the specific embodiment one.
Specific embodiment 3:
Cell simulation unit described in present embodiment, by owning on input cell type, extracellular electro photoluminescence, cell membrane
Ion channel current, realize record cell membrane action potential information；Cell simulation unit exports cell membrane potential simultaneously.
Cell simulation unit, records the information of cell membrane action potential, including resting potential, maximum Depolarization rate, most
Big depolarising current potential and Action Potential Duration；The specific implementation process is as follows:
Input: cell type, extracellular electro photoluminescence, ion channel current all on cell membrane (by taking INaL as an example)
Output: cell membrane changes current potential (itot)
Programming code is as follows:
CaMKII adjusts cell membrane movement electricity by adjusting ion channel in cell membrane electric current and intracellular Ca2+ GAP-associated protein GAP
Position, Fig. 9 are that the figure for obtaining data and being drawn is emulated by this system.
Fig. 9 is the cell membrane potential curve under being adjusted by CaMKII.
Other modules, unit and parameter are the same as one or two specific embodiments.
Specific embodiment 4:
Fiber simulation unit described in present embodiment, by inputting fiber electro photoluminescence size and location, cell type, cell
Number, iuntercellular conductance, cell membrane potential realize the information that operation of recording current potential conducts in the fibre；Fiber emulation simultaneously is single
First output fiber surface potential.The Simulation Interface of fiber simulation unit is as shown in Figure 10.
Fiber simulation unit, the information that operation of recording current potential conducts in the fibre, including it is conduction of velocity, Repolarization time, multiple
Pole dispersion and pseudo- electrocardiogram；The specific implementation process is as follows:
Input: fiber electro photoluminescence size and location, cell type, cell number, iuntercellular conductance, cell membrane change current potential
(itot)
Output: fiber surface current potential
Program code is as follows:
On fiber level, the neurological susceptibility of arrhythmia cordis is measured by calculating Repolarization time and electrocardiogram two indices,
Figure 11-12 is that the figure for obtaining data and being drawn is emulated by this system.
Figure 11 is fiber surface Repolarization time curve；
Figure 12 is fiber surface electrocardiogram.
Other modules, unit and parameter are identical as one of specific embodiment one to three.
Specific embodiment 5:
Simulation unit is organized described in present embodiment, passes through input tissue electro photoluminescence size and location, the geometry knot of tissue
Structure, the type of cell, iuntercellular conductance, cell membrane potential；Realize the information that operation of recording current potential conducts in the tissue；Group simultaneously
Knit simulation unit output organization surface potential.Organize simulation unit Simulation Interface as shown in figure 13.
Simulation unit is organized, for the information that operation of recording current potential conducts in the tissue, including tissue surface current potential, wave crest
Track, the frequency of wave crest action potential and wave crest action potential；The specific implementation process is as follows:
Input: tissue electro photoluminescence size and location, the geometry of tissue, the type of cell, iuntercellular conductance, cell membrane
Change current potential (itot)
Output: tissue surface current potential
Program code is as follows:
In organisational level, the frequency of wave crest action potential is calculated by obtaining the wave crest track of tissue surface current potential,
The neurological susceptibility of arrhythmia cordis is measured with this, Figure 14-16 is that the figure for obtaining data and being drawn is emulated by this system.
Figure 14 is the wave crest track of tissue surface current potential；
Figure 15 is the action potential of wave crest；
Figure 16 is the frequency of wave crest action potential (by taking square tissue as an example).
Other modules, unit and parameter are identical as one of specific embodiment one to four.
Specific embodiment 6:
Whole-heartedly room simulation unit described in present embodiment, by inputting whole-heartedly room electro photoluminescence size and location, whole-heartedly room
Geometry, the type of cell, iuntercellular conductance, cell membrane potential；Realize the information that operation of recording current potential conducts in ventricle；
Whole-heartedly room simulation unit exports whole-heartedly chamber surface current potential simultaneously.Whole-heartedly simulation unit Simulation Interface in room is as shown in figure 17.
Whole-heartedly room simulation unit, for the information that operation of recording current potential conducts in ventricle, including ventricle surfaces current potential, wave
The frequency of peak action potential and wave crest action potential.The specific implementation process is as follows:
Input: whole-heartedly room electro photoluminescence size and location, the whole-heartedly type, iuntercellular conductance of the geometry, cell of room, thin
After birth changes current potential (itot)
Output: whole-heartedly chamber surface current potential
Programming code is as follows:
Other modules, unit and parameter are identical as one of specific embodiment one to five.
In organisational level, by obtaining the frequency of whole-heartedly chamber surface action potential, the easy of arrhythmia cordis is measured with this
Perception, Figure 18-19 are that the figure for obtaining data and being drawn is emulated by this system.
Figure 18 is the action potential of whole-heartedly chamber surface；
Figure 19 is the frequency of whole-heartedly chamber surface action potential.
Specific embodiment 7:
A kind of analogue system causing ventricular arrhythmia for analyzing CaMKII described in present embodiment further includes emulation view
Frequency control module (MovieControl), the input and output control of the simulation video for analogue system dynamic process；Including defeated
Enter catalogue (inputDir), output directory (outputDir), start file index (startindex), ends file index
(endindex), the broadcasting and printing of video.
Other modules, unit and parameter are identical as one of specific embodiment one to six.
Claims (7)
1. a kind of analogue system for causing ventricular arrhythmia for analyzing CaMKII, which is characterized in that the analogue system packet
It includes: electro photoluminescence setup module and simulation object setting and output module；
The electro photoluminescence setup module, region setting and stimulation parameter setting, specific stimulation parameter for electro photoluminescence include:
Cell type, intensity of electric stimulus, the electricity that simulation time, iuntercellular conductance, simulation step length, stimulus type title, electro photoluminescence are directed to
Stimulate initial time and deadline；
The simulation object setting and output module, for the parameter of simulation object to be arranged, and combine electro photoluminescence setup module
The information of electro photoluminescence information output simulation object；Include:
Typing, including cell membrane ion are checked, modify and edited to subcellular simulation unit for CaMKII modulin information
The modification and typing of channel protein information and intracellular Ca2+ GAP-associated protein GAP information；
Cell simulation unit, for recording the information of cell membrane action potential, including resting potential, maximum Depolarization rate, most
Big depolarising current potential and Action Potential Duration；
Fiber simulation unit, for the information that operation of recording current potential conducts in the fibre, including it is conduction of velocity, Repolarization time, multiple
Pole dispersion and pseudo- electrocardiogram；
Simulation unit is organized, for the information that operation of recording current potential conducts in the tissue, including tissue surface current potential, the rail of wave crest
Mark, the frequency of wave crest action potential and wave crest action potential；
Whole-heartedly room simulation unit, for the information that operation of recording current potential conducts in ventricle, including ventricle surfaces current potential, wave crest is dynamic
Make the frequency of current potential and wave crest action potential.
2. a kind of analogue system for causing ventricular arrhythmia for analyzing CaMKII according to claim 1, feature exist
In the subcellular simulation unit regulates and controls parameter by input CaMKII, regulates and controls what parameter exported by input CaMKII
The activation amount and gating parameter of CaMKII, that realizes CaMKII modulin information checks, modifies and edits typing；It is sub- simultaneously thin
Born of the same parents' simulation unit exports ion channel current.
3. a kind of analogue system for causing ventricular arrhythmia for analyzing CaMKII according to claim 2, feature exist
In, the cell simulation unit, by ion channel current all on input cell type, extracellular electro photoluminescence, cell membrane,
Realize the information of record cell membrane action potential；Cell simulation unit exports cell membrane potential simultaneously.
4. a kind of analogue system for causing ventricular arrhythmia for analyzing CaMKII according to claim 3, feature exist
In the fiber simulation unit passes through input fiber electro photoluminescence size and location, cell type, cell number, iuntercellular electricity
It leads, cell membrane potential, realizes the information that operation of recording current potential conducts in the fibre；Fiber simulation unit output fiber surface simultaneously
Current potential.
5. a kind of analogue system for causing ventricular arrhythmia for analyzing CaMKII according to claim 4, feature exist
In, the tissue simulation unit, pass through input tissue electro photoluminescence size and location, the type, thin of the geometry of tissue, cell
Intercellular conductance, cell membrane potential；Realize the information that operation of recording current potential conducts in the tissue；Simulation unit output group is organized simultaneously
Knit surface potential.
6. a kind of analogue system for causing ventricular arrhythmia for analyzing CaMKII according to claim 5, feature exist
In, the whole-heartedly room simulation unit, by inputting whole-heartedly room electro photoluminescence size and location, the whole-heartedly geometry, cell of room
Type, iuntercellular conductance, cell membrane potential；Realize the information that operation of recording current potential conducts in ventricle；Whole-heartedly room emulates simultaneously
Unit exports whole-heartedly chamber surface current potential.
7. a kind of analogue system that ventricular arrhythmia is caused for analyzing CaMKII according to one of claims 1 to 6,
It is characterized in that, the analogue system further includes simulation video control module, the simulation video for analogue system dynamic process
Input and output control；Broadcasting and printing including input directory, output directory, start file index, ends file index, video.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101782943A (en) * | 2010-03-09 | 2010-07-21 | 哈尔滨工业大学 | ECG simulation method based on true anatomical data of human body |
| CN105636541A (en) * | 2013-03-15 | 2016-06-01 | 圣纳普医疗(巴巴多斯)公司 | Planning, navigation and simulation systems and methods for minimally invasive therapy |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101782943A (en) * | 2010-03-09 | 2010-07-21 | 哈尔滨工业大学 | ECG simulation method based on true anatomical data of human body |
| CN105636541A (en) * | 2013-03-15 | 2016-06-01 | 圣纳普医疗(巴巴多斯)公司 | Planning, navigation and simulation systems and methods for minimally invasive therapy |
Non-Patent Citations (1)
| Title |
|---|
| Calcium calmodulin dependent protein kinase II (CaMKII) contribute to arrhythmias after acidosis: Simulation study;Huanling Liu et.al.;《2016 Computing in Cardiology Conference (CinC)》;20160914;第2016年卷;全文 |
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