World Integrated Medicine Master Wu Yiling

INTRODUCTION OF WU YILING

Academician Wu Yiling (1949- ), is the doctoral supervisor and academician of the Chinese Academy of Engineering. He is also the chief physician, professor, chief scientist of the National 973 Plan, supervisor of Post-doctoral Researcher Center of Ministry of Human Resources and Social Security with special government allowances of the State Council, member of the National Committee of Chinese People's Political Consultative Conference, executive director of Chinese Association of Integrative Medicine, vice president of Hebei Association of Integrative Medicine, Editor in Chief of World Journal of Integrated traditional and Western Medicine and associate editor of Hebei Journal of Traditional Chinese Medicine, Editor in Chief of Chinese Journal of Difficult and Complicated Cases. On December 17, 2011, he was elected as the vice chairman of the 8th Provincial Committee of Hebei Association for Science and Technology.He is also the founder of Yiling Pharmaceutical - the key High-tech enterprise in China.

Professor Wu has stuck to his post in scientific research and medical treatment. Since the 1980s, he has devoted himself to the innovative research of theory of collateral diseases in traditional Chinese medicine (TCM). He was appointed as the chief scientist of "Basic Research on the Prevention and Treatment of Vascular Diseases Guided by Theory of Collateral Diseases" of the National 973 Plan, and presided over 20 national and provincial scientific research projects of 863 Program, National Key Project of 10thFive-year Plan, and the 11thFive-year Plan. The monograph on collateral diseases under his general editorship was awarded the first prize of scientific and technological works of the China Association of Chinese Medicine in 2005, on this basis of which the innovative textbook Theory of Collateral diseases was compiled for colleges and universities of TCM in the new century. Systematically he constructed collateral disease system, established "three-dimensional network system" of the theoretical framework of research of collateral diseases, and studied onset, pathogenesis, syndrome differentiation, and treatment, which initially constituted the syndrome and treatment system of collateral diseases.

Prof. Zou:Hello! Academician Wu. Thank you so much to accept the interview of the World Journal of Integrated traditional and western Medicine during the 4thSummer Summit of World Congress of Chinese Medicine.We would like you to introduce your experiences and achievements in the field of integrated medicine, and give some guidance for young researchers so as to promote the development of integrated medicine in the world.

Academician Wu Yiling and the Interviewer

As we all know, through systematically sorting out the academic experiences and achievements of your predecessors, you have creatively put forward theory of collateral diseases, scientifically clarifying the cause,pathogenesis, diagnosis and treatment, which first renders the systematic theory of collateral diseases come into being in the history of TCM development. Therefore,you have won the second prize of National Science and Technology Progress Award in 2006 for making a major innovative achievement in the basic theory of TCM since the founding of China, providing a new perspective of pathogenesis and treatment of cardiovascular and cerebrovascular diseases, malignant tumors, and diabetes for the medical community. Now would you please give us a detailed introduction to what you have achieved with the concept of translational medicine.

Academician Wu:All I have done is to combine the innovative research of the basic TCM theory with the improvement of the efficacy of clinically significant diseases and with the development of innovative drugs.Research on life sciences in the world is experiencing a review from reductionism to holism, which should be taken into consideration in terms of the development of the combination of traditional Chinese and Western medicine.

It is the loyal to the innovation of academic theory that pushes the academic development of TCM. Thus,in the development of TCM, emphasis should be placed especially upon innovation of basic theory. It attached great significance to the settlement of patients' clinical problems in translational medicine, as a result of which we have, over the years, insisted on combining theoretical innovation with clinical treatment of major diseases and with research and development of innovative drugs. In the process of innovation and transformation, there are four crucial parts in TCM syndrome differentiation and treatment including principle, methods, formula, and medicines. We should overcome the existing tendency of emphasis on recipe and medicines rather than principle and method, and strengthen innovative research on basic theories, which is why there are three directions of the research direction and construction goal of our State Key Laboratory, including theoretical research, clinical research and innovative drug research, reflecting the organic combination of principle, method, recipe, and medicines.

The collateral disease theory was not a new concept we created. As early as in Huangdi's Canon of Medicine,the concepts of meridian and collateral and collateral disease was proposed. However, in general, it still came from the clinical situation. It was believed by the ancients that chronic diseases and pain, which had relapse, a long clinical course, and difficulty in treatment, would transmit to collaterals. Searching from the literature, the diseases included qi blockage in the chest, stroke, abdominal mass, and wasting-thirst disorder, etc., corresponding to cardiovascular and cerebrovascular diseases, malignant tumors, diabetes and other major diseases in modern medicine. The ancients believed that it was difficult to treat these diseases, the efficacy of which would be improved through meridian activating method. Pitifully,the system for systematic argumentation was never formed.

With the joint efforts of domestic experts, we have done nearly 40 years of work, preliminary constructing the system of collateral disease theory, of which the theory of collateral disease expounds syndrome and treatment,the collateral theory guides the system of vasculopathy for the first time, the qi channel theory studies the theory of qi channels. And the textbooks on collateral diseases currently used in colleges and universities basically reflect the syndrome and treatment of collateral diseases.

The syndrome and treatment of collateral diseases is a system of clinical syndrome differentiation and treatment methods for the study of diseases known as collateral diseases by the ancients, including causes,pathogenesis, clinical symptom types, syndrome differentiation, treatment principles, and drug classifications. Prescriptions are proposed based on the treatment of each type of syndrome and the principles of addition and subtraction of medicines, which is also combined with some diseases.

Prof. Zou:Academician Wu, would you please introduce something about your achievements in the large number of clinical drugs developed to solve the needs of the people?

Academician Wu:For example, during the SARS spreading period in 2003, we put forward the therapeutic viewpoint of "active intervention" for external contraction of a warm pathogen diseases based on the syndrome and treatment of collateral diseases.The former prescriptions of Maxing Shigan Decoction and Yinqiao Poweder, with Radix et Rhizoma Rhei and Herba Rhodiolae, formed the prescription of Lianhua Qingwen Capsule, whose significant inhibitory effect on the SARS virus that had just been isolated at that time was confirmed in our experiments at the Third Laboratory of the Academy of Military Medical Sciences. Then the drug directly entered the drug test.And it continued to show important broad-spectrum antiviral effects on H1N1, H3N2, etc., as well as antibacterial, anti-inflammatory, antipyretic, thirstquenching, and immune-modulating effects.

During the period of H1N1 flu, the drug played a positive role in the prevention and control of the epidemic. Experiments of evidence-based medicine led by Beijing You'an Hospital confirmed that the drug's ability to transfer nucleic acid was comparable to that of Tamiflu,and its abilities of antipyretic and relieving symptoms were significantly better than those of Tamiflu. However,the cost was equivalent to 1/8 of Tamiflu yet without side effects. Currently, this drug is also used as a new drug in the United States which is the stage of clinical research.

As flu broke out again this year, this drug was regarded as representative drugs by the National Health Commission and State Administration of TCM for the 16thtime on incidents of respiratory public health including H1N1 flu, influenza B, human-avian influenza, and MERS.

Prof. Zou:We all know that you have been appointed as the chief scientist of "Basic Research on the Prevention and Treatment of Vascular Diseases Guided by Theory of Collateral Diseases" of the National 973 Plan.Can you tell us about the ideas and methods of combining the content with the development of new drugs?

Academician Wu:We summarized eight types of clinical syndromes and established the entire system of syndrome differentiation and treatment of collateral diseases, and among the eight types of syndromes,there were overlapping only in collateral obstruction syndrome with blood stasis syndrome; we summarized seven types of collateral activating drugs, and there were overlapping only in drugs of removing blood stasis and activating collaterals with drugs of promoting blood circulation to remove blood stasis. In conclusion, there were overlapping in collateral diseases with blood stasis syndrome, which are relatively independent and different conglomerate concepts and researching areas.

Afterwards, our research specialized in constructing the theory of collateral diseases and guiding the basic research of prevention and treatment of vascular diseases.In the whole project were a group of well-known experts of Western medicine in China, including Academician Zhang Yun from Shandong, Professor Yang Yuejin from Fuwai Hospital, Professor Huang Congxin from Wuhan University, and so on.

We carefully combed the literature of TCM in Qin and Han Dynasties which was the formation period of TCM. The results found that collateral theory of TCM was complete, which included both meridians and channels that was precisely a theory that guides the treatment of vascular diseases. Unfortunately, the theory was not established, rendering itself lose its effects.

The classification of diseases in Zhang Zhongjing's Treatise on Cold-Induced and Miscellaneous Diseases was according to the meridians and channels, as well as blood vessels, which was not only very scientific, but proved that meridians and channels, and blood vessels were two relatively independent but closely related researching fields before Han Dynasty. In the literature before Han Dynasty, we could find the study of the theory of collaterals, such as stroke corresponding to cerebrovascular disease, heart pain to angina, palpitation to arrhythmia, obstruction of Heart Meridian to heart failure, heart impediment to rheumatic heart disease,thoracic retained morbid fluid to pulmonary heart disease, as well as digital gangrene to peripheral vascular occlusive disease. According to modern medicine,vascular diseases are major diseases whose treatment experiences have been recorded in great number in literature before Han Dynasty. Unfortunately, the theory of collaterals has not been established.

We are still discussing treatment today and trying to find how the ancients studied it. I find one sentence in The Book of Changes very enlightening. "That which is antecedent to the material form exists, we say,as an ideal method[1]." The research of Tao is on the philosophical level. While in TCM, the philosophical idea of qi and theory of yin and yang as well as five elements are used to explore the laws of life movement and prevention and treatment of diseases. "That which is subsequent to the material form exists, we say, as a definite thing[1]." The study of qi belongs to the category of natural sciences. It was the ancients' belief to obtain knowledge from investigation of things. TCM and anatomy, including clinical practices, were superior to Western medicine before Song Dynasty. Therefore, when the word "science" had just come to China, it was called"Gezhixue" in Chinese that meant "to obtain knowledge from investigation of things". Then it was changed to"science".

"Transformation and shaping is what we call change; carrying this out and operating with it is what we call generalizing the method; taking the result and setting it forth for all the people under heaven is, we say, (securing the success of) the business of life[1]." Scholars combine that which is antecedent to the material form with that which is subsequent to the material form and delve into them, which is unique in thinking and researching.Whether the characteristics of the theory of collaterals conforms to such a law needs further discussion.First, the concepts of blood vessels and meridians are from anatomy. It was recorded in Huangdi's Canon of Medicine that the length of meridians can be seen through dissection of the dead bodies. In fact,the meridians they saw through dissection of dead bodies were blood vessels. Therefore, the functions of meridians in TCM including running blood, nutrient metabolism, menstrual blood exchange, and supply of blood and qi are equivalent to those of circulatory system in modern medicine.

But our predecessors did not confine themselves to anatomy, but extended their vision to philosophy. In the study of qi theory in ancient times, qi was found as the most representative word. The concept of qi was included in TCM with epoch-making effects, which not only retained its philosophical attributes, but also gave it medical connotations including defense and maintenance,information transmission, and regulation and control,etc., enabling the intangible qi from philosophy and the tangible qi from anatomy become the two cornerstones of TCM academic theory.

Combined with clinical syndrome differentiation and treatment, we analyze the three elements of the formation of the theory of collaterals, including philosophy, clinical cases, and anatomy, which concerns the formation of the entire academic theory system of TCM.

The meridians we see from anatomy in TCM are corresponding to blood vessels in Western medicine in terms of morphology, which helps us find the point where we combine theories of traditional Chinese and Western medicine. However, it is believed that the movement of blood in meridians is driven by qi in TCM. And which kind of qi is most closely related to blood circulation? It was nutrient qi and defensive qi. They are very important concepts of TCM, which were used in Zhang Zhongjing's theory of syndrome differentiation of six channels referring to the superficial and the internal, and yin and yang; in Ye Tianshi's syndrome differentiation of weifen qifen yingfen xuefen referring to four different pathological periods ranging from the superficial to the internal, and from shallow to deep; in the theory of collaterals referring to "the function of qi and blood is for circulation". It was recorded in Huangdi's Canon of Medicine that nutrient qi was in the meridians while defensive qi was outside the meridians,in Treatise on Cold-Induced and Miscellaneous Diseases that the isolation of nutrient qi and defensive qi resulted in blood stasis; in Synopsis of the Golden Chamber that pathogenetic factors transmitted to blood and meridians would lead to internal obstruction; and in Classics of Difficulties that those whose Heart Meridian was damaged should be treated from the regulation of nutrient qi and defensive qi.

When we put together the above theories in these four classics, we might be surprised at the wisdom of our predecessors who had explained physiology, pathology,and treatment of vascular diseases clearly with the theory of nutrient qi and defensive qi.

I summed up Zhang Zhongjing's prescriptions for cardiovascular and cerebrovascular diseases and made a table according to the theory of nutrient qi and defensive qi, which would help to improve clinical efficacy if used in clinical prescription.

Prof. Zou:Under the guidance of the theory of collaterals in combination with the actual situation of patients, you have developed new drugs of TCM such as Tongxinluo Capsules. Could you introduce your experiences?

Academician Wu:We combined the characteristics of theory of collateral diseases and three diseases of cardiovascular ischemia, arrhythmia, and heart failure to form three prescriptions including Tongxinluo Capsules,Shensong Yangxin Capsules, and Qili Qiangxin Capsules which were taken into use after 15 to 20 years. And the theory was used to guide the construction of clinical specialties in hospitals. The cardiovascular department of Yiling Hospital, which is the national key clinical specialty of the Ministry of Health, focuses on coronary heart disease, arrhythmia, and heart failure.

The prescription of Tongxinluo Capsules was the optimal for arteriosclerosis and ischemic cardiovascular and cerebrovascular diseases, summarizing astringent,removal, dispersing, and dredging. Academician Zhang Yun of Shandong Province conducted a study on this drug and confirmed that Tongxinluo Capsules could inhibit and stabilize plaque to reduce the occurrence of vascular events, whose efficacy was equivalent to the large dose of simvastatin. A simultaneous evidence-based study of 1200 cases confirmed that Tongxinluo Capsules could stabilize the plaque and reduce the occurrence of acute myocardial infarction. President Yang Yuejin of Fuwai Hospital, who used Tongxinluo Capsules to intervene, confirmed that Tongxinluo Capsules protected the integrity of the microcirculation in the ischemic area after myocardial infarction, thereby inhibiting reflow and reducing the area of myocardial infarction.Simultaneous clinical evidence-based studies also confirmed that Tongxinluo Capsules effectively treated acute myocardial infarction without reflow and declared its value of application in this difficult problem in the international medical community.

The study of Professor Dong Qiang of Shanghai Huashan Hospital confirmed that Tongxinluo Capsules could obviously protect capillaries, blood-brain barrier,and nerve cells, reduce the volume of cerebral infarction,and improve neurological function in the experiment of acute cerebral infarction. The clinical evidencebased study of 2000 cases conducted by Beijing Tiantan Hospital confirmed that Tongxinluo Capsules could significantly improve the self-care ability of patients with cerebral infarction and improve neurological function.

The systematic effects from blood protection to ischemic tissue protection are characteristics and advantages of the intervention of TCM prescriptions.For arrhythmia, we proposed the drugs regulating arrhythmia, reflecting the change of thought from allopathy to regulation. Why there were no drugs developed in the past two decades when the research of arrhythmia progressed? It was because of the thought of allopathy. According to Ye Tianshi's academic viewpoint of dredging and tonifying, the principles of prescriptions of warming, clearing, tonifying, and dredging were used to conduct a clinical confirmation of this drug with 1476 cases, which achieved a significant clinical effect on premature atrial contractions, atrial fibrillation, and sinus bradycardia.

Arrhythmia accompanied by heart failure is a thorny problem in the international medical community.Evidence-based research by Professor Huang of Wuhan University confirmed that Shensong Yangxin Capsules could improve cardiac function while effectively treating arrhythmia. Patients whose basic heart rhythm is relatively slow with forty to fifty times, and with many premature atrial contractions, are difficult to be cured.At present, there are no effective drugs, and it is often necessary to press the pacemaker first and then add new drugs. Evidence-based research conducted by Professor Cao Hejiang of Nanjing Medical University confirmed that Shensong Yangxin Capsules can improve slow heart rhythm while effectively treating premature atrial contractions.

Comprehensive experiments conducted by domestic experts and experts of project teams confirmed that this drug could organize multiple ion channel and mediate autonomic nerves, so it could be used for acute and chronic diseases, and could improve myocardial ischemia and cardiac function at the same time. Therefore, it was used to the treatment of chronic heart failure.

A comparison was made between Qili Qiangxin Capsules and four drugs used for heart failure in Western medicine. The results showed that it was superior to three of them and was comparable with only one of them. A clinical evidence-based study of this drug by experts from Chinese Society of Cardiology revealed that it achieved remarkable effects.

This paper was published on Journal of the American College of Cardiology (JACC), whose effect was first of the world's circulating magazines. The editorial comments were that it made the attenuated heart stronger, which was inspired by TCM. American experts said this was a challenge which should be also embraced.Now experts from the United States, the Netherlands, and many other foreign countries also joined the study, which was, at the same time, included in the annual academic highlights by JACC.

Trials that are multicentered and double-blind compared with control group with placebo confirmed the reliable efficacy of Qili Qiangxin Capsules in the treatment of chronic heart failure and that more significant effects would be achieved when combined with therapy of Western medicine. Mainstream medical journals like Nature and JACC also commented on the clinical research of Chinese patent drugs. And positive evaluations of evidence-based studies were presented in these comments, which also showed that what Chinese experts had been doing in these years attracted the attention of the international academic community.

Through experiments and clinical studies scientific connotations of these drugs were revealed, which were also included in the guidelines for clinical diagnosis and treatment of the Chinese Medical Association and other relevant societies. Because of the time limits, let's introduce these for now. Thank you.

Prof. Zou:Finally, I would like to thank you again for your contribution to the development of integrated traditional Chinese and Western medicine. Thank you for your support and contribution to the development of the World Journal of Integrated traditional and western Medicine.