Biophotonics as early as the early days of photonics, the dynamic biological science and photonics intersected with each other, which promoted the growth of biophotonics, a frontier discipline, and quietly emerged. In the early 1980s, based on the discovery and research results of ultra-weak photon radiation (BPE) in biological systems, this new field was proposed. So far, people have had some preliminary understanding of BPE, for example, it is considered that BPE is a common phenomenon in nature and an inherent function of organisms. It is the reflection of comprehensive information of organisms under different physiological and biochemical conditions. Except for a few lower organisms such as protozoa and algae, most plants and animals can produce BPE. Moreover, the higher the degree of biological evolution, the greater the BPE value. The spectral range of BPE is ultraviolet and visible infrared bands. In addition, the higher the level of biological evolution, the more the wavelength of radiation extends to infrared. BPE has the characteristics of high coherence and Poisson coherent field. It is a low-level chemiluminescence with extremely low quantum efficiency. If photonics is a technology that uses photons as quantization unit to generate and utilize radiation, and its application scope extends from the generation and detection of energy to the extraction, transmission and processing of information, then biophotonics involves the biological system releasing energy in the form of photons and detecting photons from the biological system, as well as the information about the structure and function of the biological system carried by these photons, including the processing and transformation of the biological system by using photons.
Photon emission of biological system
Spontaneous ultra-weak luminescence of biological systems, as large as bacteria, microorganisms, various animal and plant cells, as large as plants, animals and even people, all living creatures have spontaneous photon radiation. Usually, this kind of photon emission is extremely weak, only a few to several thousand photons per square centimeter per second, so it is called spontaneous ultra-weak luminescence of the system. Its spectral range is quite wide, extending from ultraviolet to near infrared, and it must be detected by sensitive photoelectric detectors. The research in recent 30 years shows that the ultra-weak luminescence of organisms is intrinsically related to many basic life processes, such as oxidative metabolism, cell division and death, photosynthesis, canceration and growth regulation. Because it is closely related to biochemical processes, physiological and pathological conditions of organisms, it has potential diagnostic value in medicine, agriculture, environment and many other aspects.
The essence of ultra-weak luminescence of biological system The photon source of ultra-weak luminescence of biological system has always been the focus of researchers. At present, it is believed to come from the following aspects: 1. Reactive oxygen species (ROS) are constantly produced in biological system due to oxidative metabolism, which generates singlet oxygen and stimulates carbon-based, which is influenced by antioxidant defense system and immune system in organisms. 2. Stimulated molecules formed by enzymatic reactions in organisms; 3. The excited state and excited state complex of important biological macromolecules (such as DNA and its end-capping groups) formed by aggregation effect, because its energy level distribution is far from Boltzmann distribution, make the biological system in the state of high energy level inversion, and emit photons with a certain degree of coherence through interaction. The degree of coherence may be a feature of life. Does the ultra-weak photon radiation of biological system carry information and constitute a communication mode between biological system and internal cells? These are all important issues that attract attention. It is one of the basic tasks of biophotonics to deeply understand the essence of ultra-weak luminescence and develop its application potential.
The important application of ultra-weak luminescence in biological system has important applications in clinical diagnosis, crop genetic diagnosis, environmental monitoring and so on. Because ultra-weak luminescence is related to the physiological and pathological state of organisms, it has potential application value in clinical diagnosis. For example, studies have shown that the ultra-weak luminescence of blood and many organs and tissues of tumor patients is higher than that of healthy people. In addition, the study also found that the dependence of ultra-weak luminescence of seeds and buds on temperature, humidity and salinity reflected the cold resistance, drought resistance and salt resistance of crops to some extent, which showed the important application prospect of biological ultra-weak luminescence in agricultural seed selection and breeding. Environmental monitoring by physical and chemical methods can only give the pollution degree measured at that time. Because the ultra-weak luminescence of biological system is extremely sensitive to environmental water and chemical pollution in the atmosphere, it can be used as a biological indicator of environmental pollution and provides a new and simple means for environmental monitoring.
Biological ultra-weak luminescence imaging uses high-sensitivity photon detection and imaging technology, combined with photon statistics and photon correlation measurement technology, to obtain two-dimensional images of biological ultra-weak luminescence in visible light or near infrared band, thus measuring human metabolic function and anti-oxidation and anti-aging body defense function. Therefore, it is expected to get important application in disease and clinical diagnosis.
It is generally believed that the optical communication between biological systems and cells is always realized by some special "messenger molecules". Messenger molecules include hormones, antibodies, growth factors and neurotransmitters, as well as some inorganic ions. In essence, this kind of communication is "chemical communication" through the interaction between molecules, such as the interaction between messenger and receptor protein on cell membrane. Is there "physical communication" between cells? Is there any modern information transmission between cells through electromagnetic field or photon interaction? At present, there is experimental evidence that cells, tissues and even organisms may transmit information through the divergence and reception of photons. The study of intercellular optical communication will reveal the little-known side of life phenomena and may be applied to medicine, fitness and agriculture.
Induced luminescence of biological system Short-term intense light irradiation can induce photon divergence of biological system, and the intensity of this induced luminescence is usually much higher than that of spontaneous luminescence, and it decays with time. The spectrum and intensity of induced luminescence depend on the type and content of excitable molecules that make up the biological system, as well as on the interaction and energy transfer between molecules. Therefore, induced luminescence will provide information about the structure of biological system, which has long been used in the study of plant photosynthesis. Recent research shows that this induced luminescence has a very attractive application prospect in disease diagnosis and food quality detection.
Application of Photon Technology in Biological Sciences With the rapid development of laser technology, spectroscopy technology, microscopy technology and optical fiber technology, their application in biological science research and medical diagnosis has become more and more in-depth and extensive, and they have become an important tool of modern life science, bringing revolutionary changes to it.
Fluorescence probe and laser scanning focusing microscopy The basic principle of laser scanning focusing microscopy is to focus the laser beam into a tiny spot with linearity close to that of a single molecule at any selected depth in the cell, and scan it at a certain depth in the cell, so that a clear image of the cell layer can be obtained through the optical system. Continuously changing the focal depth of the laser, scanning on a series of layers, and finally obtaining a three-dimensional image of the whole cell. By using thousands of fluorescent probes that specifically bind to different molecules (or ions) in cells, people can directly observe the position, movement and interaction of various important biomolecules in living cells. For example, we can observe microtubules, microfilaments and intermediate fibers in cytoskeleton, observe various important enzymes and messenger molecules in signal transduction pathways, introduce our own fluorescent proteins into cells through gene recombination technology, and study gene expression, intracellular protein interaction and intracellular "communication" through laser scanning confocal microscope. The combination of fluorescent probe and fluorescent protein with laser confocal microscope makes people see the complex and colorful world in cells.
Multi-photon fluorescence imaging technology At present, the focusing microscope uses argon ion laser in visible light band, which may cause damage to living cells. Using multiphoton, such as multiphoton excitation, has at least the following three advantages: first, the damage to living cells is greatly reduced due to near-infrared excitation; Second, because the transmittance of near-infrared light in tissue is higher than that of visible light, deeper fluorescence imaging can be observed in the sample; Thirdly, many fluorescent probes used in the visible region or even the ultraviolet region can still be used. This technology mainly uses high-intensity infrared laser to make the excitation efficiency of two-photon equal to that of single photon with short wavelength. Now there are some lasers that meet this requirement.
Optical tweezers and optical tweezers technology were born in 1980s and developed in 1990s. The basic principle is that when a particle (such as silicon beads combined with biological macromolecules) is in a laser beam with Gaussian intensity distribution, due to the spatial variation of light field intensity, the beam will generate gradient pressure on the particle, driving it to move to the center of the beam and stabilize there. In this way, the laser beam is like a "vice" to firmly hold the particles and let them move artificially with the beam. The pressure exerted by optical tweezers on particles depends on the wavelength of light, the width and power of light beam, etc. When the laser power is several milliwatts to several watts, the force acting on micron-sized particles is about several hundred piconewtons (10- 10). In order to prevent laser from being strongly absorbed by biological tissues, optical tweezers generally use near-infrared laser light source. The important application of optical tweezers technology is to study and observe a protein molecular motor closely related to muscle contraction, cell division and protein synthesis. In the research, a micron-sized silicon bead or polystyrene bead is connected with these molecular motors, and the force generated by the molecular motors can be measured by clamping the beads with optical tweezers under the microscope and starting the molecular motors. German scholars have used laser to punch holes in the egg cell membrane and optical tweezers to capture sperm and send them to the egg cell, which greatly improves the success rate of in vitro fertilization. In the future, the new generation of optical tweezers will have a force feedback mechanism, so that the force exerted by optical tweezers on trapped ions can be changed, thus studying various factors affecting molecular motors. Optical tweezers can also be used to treat cells in various ways. Therefore, optical tweezers will play an important role in cell engineering technology.
Medical photonics
Nowadays, medicine is in a period of great change. The focus of medicine is changing from the traditional symptom-based treatment mode to the information-based treatment mode. People have realized that symptoms are just a rough abnormal reaction of human body, which is delayed by disease. At present, the research of some major medical topics focuses on exploring the laws of biological information that lead to diseases from the beginning, so as to control the biological logic information in a healthy state and then achieve the purpose of treating diseases. Therefore, people explore new medical diagnosis and treatment methods from various disciplines (magnetism, acoustics, chemistry, optics, etc.). At present, it is believed that photonics will play an important role in today's great medical revolution. Understanding the propagation law of light in biological tissues and the successful development of high-performance light source and high-sensitivity optical detector represented by laser are the theoretical and material basis of this cognition respectively. The combination of emerging photonics and modern medicine has formed a new interdisciplinary growing point: medical photonics. The driving force for the development of medical photonics mainly comes from the urgent need for medicine. Many specific applications of clinical phototherapy and photodiagnosis, such as photometry, optical imaging diagnosis, tumor diagnosis and treatment in laser medicine. There is an urgent need for satisfactory answers from medical photonics, which greatly promotes the rapid development of medical photonics. The direct object of medical photonics research is biological tissue, especially living biological tissue. Its research results will directly serve human medicine, and may create new high-tech industries and contribute to human civilization and social progress. Medical photonics is on the rise. Although the domestic research foundation and conditions are relatively backward, we have many advantages in practice and are at a starting line with foreign countries. Therefore, as long as it is well organized and properly selected, it will certainly make breakthroughs in some aspects such as theory, calculation and clinic, and occupy a leading position in the world.
The basic knowledge of medical photonics about the interaction between light, especially laser, and biological tissues has attracted international attention, and has become the application foundation and premise of the booming laser biomedicine. For example, how to design and confirm the light distribution in human tissues is one of the key problems in the photodynamic therapy and diagnosis of tumors on the edge of clinical application, which involves many theoretical and experimental problems, among which the most important ones are the special way of light propagation in tissues, the description of optical characteristics of tissues and the development and perfection of related experimental technologies. All new problems in these research work must be solved with new ideas and means. Although the propagation model of light in biological tissues has been initially established, the unified optical theory of biological tissues is far from mature. In this context, "tissue optics" came into being as a special subject to study the optical characteristics of biological tissues, which involves the most basic theoretical problems in medical photonics and is also the premise for further development of photomedicine (including photodiagnosis and phototherapy). Tissue optics is the theoretical basis of medical photon technology. The kinematics (such as light propagation) and dynamics (such as light detection) of light in biological tissues are the main contents of research. At present, the main research task is to study the optical characteristics of biological tissues and determine the light energy flow rate per unit area of the target. The former involves determining the basic optical parameters of tissue from the measured light distribution and some light propagation model, which is called "positive" problem; The latter deduces the light distribution in tissue from the basic optical parameters and light propagation model of tissue, which is an "inverse" problem at present. Considering the international development trend and the possibility provided by domestic reality, research work should be carried out in the following aspects:
Research on the theory of light propagation in biological tissues Although the propagation model of light in biological tissues has been initially established based on the neutron propagation theory, it is far from establishing a unified theoretical framework of tissue optics. The optical theory of biological tissue is far from mature, and there are many theoretical gaps to be filled. On the one hand, this situation naturally stems from the diversity and complexity of biological tissue structure itself, on the other hand, it is also the result of insufficient theoretical tools. It is necessary to have a finer and more accurate theory to replace the oversimplified existing model, that is, to use a more complex theory to describe the optical characteristics of biological tissues and the propagation behavior of light in them. One of the tasks to be done is to establish an accurate tissue optical model, which can reflect the spatial structure and size distribution of biological tissue, the scattering and absorption characteristics of various parts of tissue and the change of refractive index under certain conditions; The second is to transform the transmission equation to adapt it to the new conditions and find out the basic properties of light transmission in biological tissues in some cases.
Monte Carlo simulation method of optical transmission has played an irreplaceable role in many fields. There have been some successful algorithms, but we should continue to develop new and more effective algorithms to meet the requirements of diversity and complexity of biological tissues. In addition to understanding the distribution of light in tissues, we are also exploring the empirical relationship between the macroscopic distribution of light in biological tissues and the basic parameters of optical properties from a large number of digital simulations. In addition, the development of Monte Carlo simulation method of unsteady optical transmission is also an important research direction, from which more information can be obtained than under steady-state conditions.
Methods and techniques for measuring optical parameters of tissues After the theory of light transmission in tissues is established, a key task is to determine the basic optical parameters of tissues, especially human bodies, that is, absorption coefficient, scattering coefficient and scattering phase function or average scattering cosine g and refractive index n, etc. Once the interaction parameters between light and tissue are known, the distribution of light energy flow rate or other parameters, such as total reflectivity r and total transmittance t, can be uniquely determined by the relevant transmission model under given illumination mode and boundary conditions. At present, the measurement methods of optical properties of biological tissues need to be further developed and improved, among which nondestructive testing in vivo is particularly important. In this respect, the measurement methods of time resolution and frequency resolution attract attention.
The relationship between refractive index and dispersion of biological tissue People use hypothetical refractive index data (1.33- 1.38) in various situations, but the research on refractive index of biological tissue is still ignored to some extent. So far, people haven't analyzed the refractive index of biological tissues in depth conceptually, and haven't fully mastered the accurate measurement method of refractive index of living or even isolated tissues. Because of the strong scattering of tissues, it is difficult to measure accurately, and people have not obtained reliable experimental data of various human tissues. Practice has proved that the refractive index and dispersion parameters of biological tissues are very important for the in-depth study of tissue optics both theoretically and experimentally. In view of this, the measurement and method of refractive index and dispersion parameters of biological tissues should be studied as one of the key points.
Some thoughts on the theoretical work of tissue optics
To sum up, as the basis of medical photonics, tissue optics should not only develop measurement technology and establish a database of tissue optical parameters, but also focus on solving the following problems in theory: a. continue to improve the optical transmission model of biological tissues, first, develop a fast, accurate and less restrictive model; Secondly, the optical model of tissue should be accurate to make it similar to the state of biological tissue, especially living tissue; B) Study the propagation behavior of short pulse light in tissue and the time variation characteristics of diffused light, so as to make full theoretical preparation for optical imaging; The propagation characteristics of modulated light in biological tissues are studied. For example, when the amplitude-modulated light irradiates the tissue, it will produce a slowly scattered photon density wave, and the slowly scattered photon density wave will also reflect, refract, diffract, scatter and disperse, so as to detect the optical property parameters of the tissue nondestructive and can also be used for imaging. D. Study the influence of optical characteristics of biological tissue scattering and absorption on measuring fluorescence and its spectrum. The preliminary study of numerical simulation shows that this effect can not be ignored. E. Computer simulation of light transmission process in complex tissue structure, through a large number of simulations, find out simple and effective laws to explain the basic characteristics of light transmission in tissue, establish the relationship between various parameters, and provide basis for the measurement of optical characteristics of tissue; F unify the description of optical characteristic parameters of biological tissues and establish a perfect theoretical system of tissue optics.
Medical photon technology
Medical photon technology can be divided into two categories: photon diagnosis medical technology and photon treatment medical technology. The former takes photons as the information carrier, while the latter takes photons as the energy carrier. At present, both optical diagnosis and optical treatment technology use laser as light source. If we focus on human application, these two technologies belong to the category of laser medicine. Laser medicine is a unique and important application field of medical photon technology, and it is also a new branch of discipline that has risen rapidly in recent years (see point 3 in this section for details).
According to the international and domestic development, the following are the main research contents of medical photonic technology:
Medical Spectroscopy Laser spectroscopy has become an important research field of medical photonics because of its high spectral and time resolution, high sensitivity, high accuracy, nondestructive, safe and fast. With the in-depth development of laser spectroscopy technology in the medical field, a "medical spectroscopy" with development potential and application prospect has gradually formed.
1. Autofluorescence and drug fluorescence spectra of biological tissues. The role of laser-induced autofluorescence and drug fluorescence in the diagnosis of atherosclerotic plaques and malignant tumors has been studied before clinic. The content involves the absorption spectra, excitation and emission fluorescence spectra of photosensitizers, and the characteristic spectra of endogenous fluorescent groups in normal tissues and pathological tissues excited by lasers of various wavelengths. On this basis, a real-time fluorescence image processing system for cancer diagnosis and location is also studied.
The research of laser fluorescence spectroscopy in tumor diagnosis has always been concerned, and the sensitivity of spectral testing method is very high. If we can find the characteristic fluorescence peak of tumor cells to diagnose the existence of cancer cells, it will play a great role in the early diagnosis and treatment of tumors. But so far, this technology can not be used as the basis for cancer cell detection alone in clinic. The key reason is that the real characteristic fluorescence peak of cancer cells has not been found. At present, the so-called characteristic fluorescence peak is actually only the fluorescence peak of porphyrin molecule. It is necessary to objectively and scientifically judge the diagnostic criteria of laser fluorescence spectroscopy for tumors. At present, the drug fluorescence diagnosis of some cancers has entered clinical trials, and the application of autofluorescence is still in the process of exploration. It is necessary to study the laser excitation mechanism of biological tissues and intracellular substances, explore the correlation between laser-induced tissue autofluorescence and pathological types of cancer tissues, and study the fluorescence spectrum, fluorescence yield and optimal excitation wavelength of new photosensitizers in order to obtain extremely stable and reliable characteristic data and provide scientific basis for the development of diagnostic technology. 2. Raman spectra of biological tissues. In recent years, the application of Raman spectroscopy in medicine shows its advantages in sensitivity, resolution and non-damage, and overcomes the problem that the fluorescence spectrum affects the accurate diagnosis because of the fluorescence bandwidth and easy overlap of biomacromolecules. At present, this research field is still in its infancy, and the following research work should be stepped up: first, study the Raman spectra of important medical substances and establish their spectral database (including sensitive characteristic lines and the intensity of their corresponding molecular components and structures); Secondly, the Raman spectrum of the disease is studied, and the changes of biological components and pathogenesis from normal to pathological changes are analyzed. Thirdly, develop a small, efficient, medical Raman spectrometer and diagnostic instrument suitable for body surface and body. 3. Ultrafast time-resolved spectra of biological tissues. Ultrafast time-resolved spectrum is more sensitive, objective and selective than steady-state spectrum in technology. Therefore, the application of ultrashort laser pulse light source with pulse width of ps and fs in medicine has attracted wide attention. Firstly, ultrafast time-resolved fluorescence spectroscopy should be developed to measure the fluorescence decay time of biological tissues and biomolecules and analyze the molecular relaxation kinetics of tumor tissues, so as to provide basic data for further study on autofluorescence diagnosis of malignant tumors. Secondly, it is necessary to develop ultra-fast time-resolved diffuse reflection (transmission) spectroscopy technology. The diffuse reflection of tissue is measured in time domain, thus indirectly determining the optical characteristics of tissue. This is a brand-new, nondestructive and real-time measurement method suitable for living bodies, which opens up a new way to understand the interaction between light and biological tissues and solve the basic measurement problems in medical photonics. We should pay close attention to the study of principle and technology in order to obtain valuable optical parameters in vivo and provide basis for the development of photodiagnosis and phototherapy technology.
The goal of medical imaging technology is to develop high-resolution optical imaging methods and technologies without radiation damage to biological tissues, and at the same time, it should be non-invasive, real-time, safe, economical and small-scale, and can monitor chemical components in living tissues in a natural state. At present, the research work mainly focuses on the following aspects:
1. Time-resolved imaging technology, using ultrashort pulse laser as light source, according to the time-resolved characteristics of light pulse propagation in tissue, using gating technology to separate the so-called early light that is not scattered in diffuse reflection pulse for imaging. The typical time gates being studied are fringe camera, Kerr gate, electron holography and so on. This technique is one of the most important optical tomography techniques. 2. Coherent resolution imaging technology (OCT). It uses weak coherent light source (such as weak coherent pulse laser or broadband incoherent light source), and the coherence length is very short (such as 20μm). Using the low coherence of light source to realize imaging through scattering medium, including interferometer, holography and so on. 3. Diffuse photon density wave imaging technology. Scattered light passing through biological tissues accounts for a considerable proportion, and it can also be used for medical imaging. High-frequency modulated light is injected into biological tissues, and diffuse photons are distributed periodically in biological tissues, forming diffuse photon density waves. This kind of photon density wave propagates in biological tissue with a certain phase velocity and amplitude attenuation coefficient, and after refraction, diffraction, dispersion and scattering, its emergent light carries the information of the internal structure of biological tissue. By measuring its amplitude and phase, the relevant images of biological tissues can be obtained after computer data processing. 4. Image reconstruction technology. The structural characteristic information of biological scattering medium is hidden in scattered light. If we can find the law describing the light migration in the medium and trace the scattering path of the eyes by testing the relevant parameters of scattered light, we should be able to reconstruct the structural image of the scattering medium. If the locked laser is used as the light source, the fringe camera tests the time-resolved parameters of the scattered light around the scatterer, and then uses the inverse problem algorithm to reconstruct the image. At present, there are two kinds of inverse problem algorithms: one is Monte Carlo method, which has high accuracy of image reconstruction but complicated calculation; The other is based on the optical transmission equation, according to the scattered light signal with time resolution around the test, the image is reconstructed by using the optimization algorithm.
In addition to the above four technologies, other biological tissue imaging technologies have been developed in recent years, such as spatial gating imaging technology, time-resolved fluorescence imaging, stimulated Raman scattering imaging and photoacoustic medical imaging technology. At present, the international optical medical imaging technology is still in the preliminary research stage, which is still far from practical application, but people have seen its dawn.
Medical semiconductor laser and its application technology Because semiconductor laser has a series of remarkable advantages, such as small size, high efficiency, and many wavelengths to choose from in long-life occasions, it has a tendency to gradually replace other lasers in laser diagnostic medical technology, so it may become the most important light source of laser medical instruments. At present, the low-power semiconductor laser with the wavelength of 800nm~900nm and the power of 3~ 10mW has gradually replaced He-Ne laser for irradiation therapy, light acupuncture therapy and various indicating light sources. Medium power device, with wavelength of 652nm~690nm and power of 1~5W, has gradually replaced dye laser in photodynamic therapy and can treat deep tumors. High-power semiconductor laser may also replace Nd: YAG laser therapy machine. For example, a high-power semiconductor laser with a wavelength of 800nm~900 and a power of 30W can penetrate deep into tissues and is suitable for most diseases that can be treated by Nd: YAG laser.
Other development trends of medical laser technology in recent years, there are also noteworthy research trends: first, develop laser medical instruments with new working wavelengths; Secondly, ho: YAG and er: YAG laser scalpel are put into practical use; The third is to develop fiber optic endoscopic laser medical technology suitable for endovascular treatment; Fourth, the laser medical equipment is intelligent.
Laser medicine
Photodiagnosis and phototherapy technology with laser as light source and human application as the center has opened up an important new field of laser medicine. Over the years, laser technology has become an effective means of clinical treatment and a key technology to develop medical diagnosis. It has solved many difficult problems in medicine and contributed to the development of medicine. At present, it has maintained a sustained and vigorous development momentum in basic research, new technology development, new equipment development and production. At present, the prominent application research of laser medicine is mainly manifested in the following aspects:
1. photodynamic therapy (PDT) for the treatment of cancer PDT for the treatment of tumors is a major topic of concern all over the world. After human body is injected with photosensitizer which can aggregate tumor, laser irradiation produces photochemical effect, which can selectively kill tumor cells. At present, there are two main problems: first, the skin has great photosensitive side effects, so it should be kept away from light for a long time; However, the depth of laser penetration into human body is too shallow, and deep tumors cannot be photochemical, so there is a great possibility of recurrence. At present, we are actively developing photosensitizers with excellent performance and lasers that can penetrate deep tissues and have good interaction with photosensitizers. The prospect of this therapy is still very optimistic.
2. Laser treatment of cardiovascular diseases Percutaneous laser coronary angioplasty has made great progress in the treatment of coronary artery stenosis and occlusion. Excimer laser coronary angioplasty has become the first choice. However, it is difficult to effectively promote this technique at present because of the problems such as lumen restenosis that need to be further solved. In addition to the above-mentioned coronary angioplasty, myocardial vascular reconstruction, laser direct ablation of abnormal rhythm points of the heart and treatment of severe arrhythmia are also research hotspots at present.