World Integrated Medicine Master Shen Ziyin

Zou Jinhu (邹建华), Dong Jingcheng (董竟成)

a: Associate Editor in Chief of World Journal of Integrated Chinese and Western Medicine, Center for Translation, World Federation of Chinese Medicine Societies, Beijing 100101, China

b*: Corresponding author: Dong Jingcheng, MD, professor in the Institutes of Integrative Chinese and Western Medicine, Fudan University, Tel:52888301, E-mail: jcdong2004@126.com

Academician Shen Ziyin(1928- ), ethnic Han, born in Zhenhai, Zhejiang Province,graduated from Shanghai Medical School as a medical undergraduate in 1952 and started learning traditional Chinese medicine with Prof. Jiang Chunhua since 1955. He was rewarded the gold medal of "Carry forward Chinese Medical Heritage"with his tutor in 1959 and became academician of Chinese Academy of Sciences in 1997. Academician Shen was rated as Shanghai famous doctors in 1995 and won the honorary title of "National Famous Doctor of Traditional Chinese Medicine" in 2017. Academician Shen served as professor and doctoral supervisor of Shanghai Medical School, the director of traditional Chinese medicine department, the head of the Institutes of Integrative Chinese and Western Medicine, the head of the department of Integrative Chinese and Western Medicine of Huashan Hospital affiliated to Fudan University, the member of degree and academic committee in the university and the hospital, the member of medical evaluation by the academic degree committee of state council, the chairman of Chinese medicine evaluation committee of ministry of health, the vice president of Chinese Association of Integrative Medicine, president of Shanghai Association of Integrated Chinese and Western Medicine. At present,he is the honorary dean of the Institutes of Integrative Chinese and Western Medicine of Fudan University and lifetime professor of Huashan Hospital Affiliated to Fudan University. Academician Shen's study is mainly based on the exploration of integrated Chinese and Western Medicine, the nature of kidney and traditional geriatric medicine.

Academician Shen Ziyin

Since 1950s, his study on "mingmen fire" of kidney yang in Traditional Chinese Medicine (TCM) took the lead of related study, and found that it was totally different disease in western medicine. According to the agreed standard of syndrome differentiation, patients with kidney-yang deficiency always present obvious decreasing of 17-hydroxy corticosteroid in urine which reflects the function of adrenal cortex and the result has been repeated and recognized by research organizations at home and abroad. Since 1979, the observation on functional comparison of hypothalamic- pituitarytarget gland axis in same disease with different patterns group indicates that the main pathogenesis of kidneyyang deficiency is hypothalamic, the significance of which is the certain material basis of kidney-yang deficiency has been firstly proved by modern scientific method throughout the whole world. Over 40 years'study combined detection methods at molecular level has proved that only kidney-nourishing medicine can improve the affinity of dihydrotestosterone recipient in hypothalamus and the expression ability of CRF as well as messenger RNA, which is powerful evidence on the principle and hubs of kidney yang deficiency syndrome,and not only scientifically and objectively testified the existence of "pattern" in traditional Chinese medicine, but also explained the nature of kidney yang deficiency from the scientific point of view.

At the beginning of 1970s, based on great amount of clinical cases and scientific trails, Academician Shen first raised the idea on the combination of the disease differentiation and syndrome differentiation as the way of integrated traditional Chinese medicine and western medicine, and thus changed the statement for just simply combining medicines in this two medical forms.Furthermore, his idea of meticulous differentiation and microscopic differentiation has positive effects on promoting the scientifical and objective development of syndrome differentiation in TCM.

MEDICAL PRACTICE ACHIEVEMENTS

Traditional Chinese medicine is not the original major of Academician Shen Ziyin. However, Dr. Shen paid great efforts on study aiming to carry forward the essence of it, to explore a way of integrated Chinese and western medicine, and to relieve patients' suffering. He systemically studied the classics and clinical practices in TCM, including Shanghan Lun, Jingui Yaolüe, Huangdi Neijing, Bencao Gangmu, Waitai Miyao, Qianjin Fang,etc., and kept doing clinical practice. He drawn on, as the old saying puts, "learning widely from others' successful experience" and "not stick to one pattern" under the direction of the basic theory in TCM. He was creative enough to study the nature of kidney and symptoms,and the principle of the treatment in TCM with modern scientific methods.

His ability at observation and extraction is good enough to sublimate arguments with regularity and published over 100 pieces of influential papers, including The Combination of Disease Differentiation and Syndrome Differentiation, Meticulous Differentiation and Microscopic Differentiation, Preliminary Study on the Way of Integrated Chinese and Western Medicine in Internal Medicine, The Regulation on Threshold of Yin and Yang, Preliminary Study on the Regulation of Syndrome Differentiation on Kidney Yin and Kidney Yang by Integrated Chinese and Western Medicine, Study on Orientation of Kidney Yang Deficiency Syndrome,7 Comparisons on Nourishing Kidney and Tonifying Spleen in Delaying Senescence, Study on Nourish Kidney of Traditional Chinese Medicine in Treating Bronchial Asthma, Observation on The Method of Nourishing Kidney in Traditional Chinese Medicine of Intractable Asthma Patients Withdraw Long-Term Cortical Hormone. He compiled dozens of works with academic value including Study on Kidney, Study on Deficiency Syndrome, Study on Principle of Treatment in Traditional Chinese Medicine, Modern Study on Principles in Traditional Chinese Medicine and Traditional Chinese Medicine etc. All those works drew great attention from home and abroad, and promoted the development of traditional Chinese medicine and the integration of Chinese medicine and western medicine.

ACADEMIC ATTAINMENTS

Since 1950s, Academician Shen first started the theoretical study on the nature of kidney in TCM in China. In 1960, his summarization on "treating same disease with different methods" and "treating different diseases with same method" in the study of kidney which broke the gap of systematic integration of Chinese medicine and western medicine. He first proved that the kidney yang deficiency syndrome in traditional Chinese medicine has material basis with special functions in 1960. He put forward the idea of "combining disease differentiation with syndrome differentiation" according to great amount of clinical cases and scientific tests in 1970, denying the integration of Chinese medicine and western medicine to be easily combination of medicines.He proposed the theory of meticulous differentiation and microscopic differentiation in 1980, which promoted the scientific and objective development of TCM. He proved that only kidney-nourishing medicines can improve the expression of CRF mRNA gene in hypothalamus with detection methods of molecular level in 1990, which offered evidence on qualitative and quantitative analysis on kidney yang deficiency syndrome and the hub of this syndrome is hypothalamus, which means China firstly verified that kidney yang deficiency syndrome had specific material basis with modern scientific method.

Recently researches found that nourishing the kidney can make Tlymphocyte decreas the expression of pro-apoptotic gene of elder people and rats while increas the expression of anti-apoptotic gene, which will re-establish the balance of genes and decrease the over apoptotic of Tlymphocyte of the elder and delay immunosenescence, and those researches took the leading position in regulating and controlling senility throughout the world. He also drew two major guideline maps of gene network including the neuro-endocrine-immune network and neuro-endocrine-bone metabolism on the basis of system biology and the gene expression map of kidney deficiency syndrome. He published over 100 papers, edited books of Study on Kidney (1stedition in 1964 and 2ndedition in 1982), Sequel of Study on Kidney(1stedition in 1990), Study on Principle of Treatment in Traditional Chinese Medicine (1stedition in 1960 and 2ndedition in 1983), Modern Study on Principles in Traditional Chinese Medicine (1stedition in 1988), Study on Deficiency Syndrome (1stedition in 1991), and took part in the editing works of Practical Internal Medicine and Bronchial Asthma. Moreover, the book of Study on Kidney has been translated and published twice in Japan.Academician Shen won a total of 23 prizes including major scientific and technological achievements of National Conference on Medical and Health Sciences in 1979, science and technology achievement (Grade B)of Ministry of Health in 1981, 1983, 1985 and 1987,scientific progress awards of Shanghai in 1980, 1982,1984, 1986, 1988, 1990 and 1991. He went to Japan to give lectures and attended academic conferences in 1979, 1982 and 1989. Academician Shen accessed the awards of scientific progress achievement of State Education Commission in 1992 and 1997, Science and Technology Prize of Chinese Association of the Integration of Traditional and Western Medicine in 2005,the second prize of national scientific and technological progress award in 2010, realistic reward of technical achievement and Lifu academic award of Chinese medicine, etc.

CONTRIBUTIONS

Academician Shen trained the first Chinese doctorate of integrated Chinese medicine and western medicine, and a total of 7 master students, 8 doctoral students and 6 post-doctoral since 1978. He made great contribution in the integrated Chinese medicine and western medicine, and has high prestige at home and abroad. He loves the motherland of socialism and supports the leadership of Chinese communist party. He is a meticulous scholar with noble characteristics, and has been rewarded as "advanced medical servicers" and"advanced educators" in the levels of school, university and city. Academician Shen was invited to give lectures to the Chinese University of Hong Kong in 1985, to Fujiyama University of medical and pharmaceutical in Japan for one year as a visiting professor in 1990, and to Harvard University in America in 2006.

ACADEMIC VIEW POINTS

Flexible combination of disease differentiation and syndrome differentiation.

The principal method of TCM is syndrome differentiation, which means syndrome is the essence of traditional Chinese medicine. However, the concept of syndrome is hard to understand accept for western medicine, which not only affects the development of traditional Chinese medicine, but also influences the international academic communication.

Academician Shen tried so hard on this problem,and he combined the advantages of this 2 medical systems based on great amount of clinical cases and scientific experiments. In his opinion, for one disease or one patient, high differentiation and analysis in both Chinese medicine and western medicine should be taken after the in-depth knowledge of the various developments on the cause of disease, pathology, physiology, biochemistry and the evolution on patterns during the disease development,trying to find out the combination point of disease and syndrome, making good for both sides and identifying the manifestation and root. The combination point of disease and syndrome should be found the disease and syndrome can be mutual references with methods like precedence of syndromes over the disease or precedence of disease over the syndromes, which can effectively improve the quality of clinical practice. For example, persistent hepatitis without jaundice and chronic hepatopathy is a common diseases internal medicine, usually refering to pathological differences of unsmooth perfusion of the liver and hepatomegaly and splenomegaly caused by hepatocyte inflammatory swelling after virus infection.So far, there is no effective therapy in western medicine yet, except the palliative hepatoprotective therapy, and a lot of patients developed cirrhosis of liver due to the lack of effective treatment.

In traditional Chinese medicine, hepatopathy refers to abdominal masses caused by qi and blood with long-terms of unsmooth running entering the collateral, which is the result of internal retention of damp-heat liver depression and qi stagnation. Academician Shen believes that the major cause of hepatopathy is damp-heat accumulation in the liver and gallbladder, which will easily lead to qi-yin consumption and make the hepatopathy more difficult to be cured, and form abdominal masses as time goes by. Patients are difficult to recover without dispelling the evil of dampness and heat. According to the principle of treatment aiming at its root causes in traditional Chinese medicine, Academician Shen decided to observe syndromes rather than the disease, and treatment based on pattern differentiation under the rules of clearing heat and drain dampness, boosting qi and nourish yin,and invigorating blood and dissolve stasis. Dampness heat is the principal syndrome of patients with persistent hepatitis or chronic hepatopathy and complicating with active changes in ALT. Treatment should base on clearing heat and draining dampness with medicines like Longdan Xiegan Decoction or Danzhixiaoyao Pills, adding Herba Sedi, Radix Isatidis, Herba Artemisiae Scopariae, Rhizoma Polygoni Cuspidati, Herba PogoStemonis, etc., when ALT turned normal and the dampness heat has been dispelled,use qi reinforcing medicines like Radix Codonopsis and Radix Astragali seu Hedysari, yin replenishing medicines like Carapax Trionycis, blood enriching and activating medicines like Radix Angelicae Sinensis and Radix Salviae Miltiorrhizae, and herbs acting to remove heat and dampness like Rhizoma Atractylodis and Pericarpium Cirri Reticulatae. If the ultrasonography indicates the light spots in the liver are thickened, or there is cirrhosis of the liver, or there is a tendency of fat infiltration, using Taohong Siwu Decoction, adding herbs acting to soften hard masses like soft Carapax Trionycis, Squama Manis and Concha Ostreae according to the idea of breaking up blood and expelling stasis recorded in Jingui Yaolue. Modern pharmacological studies have confirmed that blood-activating and stasisremoving medicines have anti-fibrosis effects. The disease can be effectively controlled under such treatment, and some patients can reconstruct their liver function in a short time.

For another example, the proliferative and mixed type of chronic nephritis and nephrotic syndrome belong to the dysfunction of liver, spleen and kidney in TCM syndrome differentiation, while poor effects in eliminating proteinuria under this treatment are received. However, in western medicine, its pathology is due to the proliferation of glomerular vascular endothelial cells which leading to stenosis of the lumen and obstruction of fibril. Although there were not obviously stasis syndrome in clinical practice, so that it is necessary to testify the disease,and improved the condition of urinary protein loss with treatment of removing blood stasis and treat with method of clear heat and cool the blood. Although there is no obvious evidence of stasis syndrome in the clinic,it has a nature of stasis syndrome from its pathological mechanism, Professor Shen takes the "disease" in Western medicine as the path and "syndrome" in TCM as the latitude to find out the point of integration of Chinese and Western medicine at the intersection, and raised up the academic viewpoint of the combination of disease differentiation and syndrome differentiation.

He took the advantages of the 2 medical theoretical systems, and extracted the specific method of observing the syndromes rather than diseases, observing the diseases rather than syndromes, or mutually reference of diseases and syndromes, which alternated the conditions of simple addition of Chinese and Western medicines, more importantly, it makes up for the one-sidedness of Chinese and Western medicine on diseases, and effectively improve the level of diagnosis and treatment of Chinese medicine, and lay a foundation for the development of Chinese medicine and the integration of Chinese and Western medicine.

Organic combination of macroscopic syndrome differentiation and microscopic syndrome differentiation

TCM syndrome differentiation focuses on functional aspects. Professor Shen believes that any functional change must be based on morphological and metabolic changes. The "syndrome" also has its microscopic performance and material basis, and its function, form and metabolism are unified. How to confirm the shape and metabolic changes were due to changes of function,and clarifying the material basis of "syndrome".

In collecting dialectical materials in clinical practice, Professor Shen introduced modern science,especially advanced modern medical technology, to microscopically recognize the features of form, metabolic changes and functional characteristics of the organism,and to clarify the basis of "syndrome" in a more complete,accurate and fundamental way. Microscopic indexes are used to recognize and distinguish "syndrome" based on the macroscopic syndrome differentiation of traditional Chinese medicine. He collected micro-disciplinary information to effectively guide the clinical practice.For example, in the study of asthma prevention and treatment, Shen found that some patients with asthma have no clinical manifestations of kidney deficiency, but the adrenal cortex has similar changes in the stagnation of kidney yang, so its essence is still kidney yang deficiency,the recurrence of asthmatic diseases has been effectively controlled after nourishing the kidney yang.

EXPERIENCE IN TREATING THE SYNDROMES

Preventing the seasonal attacks of bronchial asthma

The ancients said that "the main thing is to support the healthy qi before the attack, and to repel the evil qi after the attack" and "The treatment of asthma and cough should concern about the lung, while not just the lung","treating the lung during the disease, and taking care of the kidney when somebody is healthy". There is a principle of "treating the acute symptoms first and when these are relieved, the fundamental cause is dealt with." in traditional medicine.

Professor Shen believes that there should be a transitional stage in the treatment of asthma syndrome,so that the disease will not easy to repeat, and offers connections in treatment. In order to reduce or relieve the frequency and degree of the recurrence of asthma, the treatment is divided into three stages.

1. To treat the manifestation syndrome at the beginning of the disease, or a chronic or acute attack,or the transition of spring and autumn. It is mainly based on diffuse the lung. Heat pattern should be treated by modified Maxing Shigan decoction, or Dingchuan Decoction, etc., cold pattern should be treated by modified Sanao Decoction, Xiaoqinglong Decoction, etc.

2. To treat both the manifestation and root in remitting stage. Treatment should be based on diffusing the lung and nourishing the kidney at the same time.Syndrome of yin deficiency of lung and kidney should be treated by modified Sanao decoction plus Zuogui Pill,syndrome of yang deficiency of lung and kidney should be treated by modified Sanao decoction plus Yougui Pill .

3. To treat the root when the manisfaction and root are gradually recovery mainly based on nourishing the kidney.Syndrome of kidney yin deficiency should be treated by modified Zuogui pill plusYupingfeng powder, syndrome of kidney yang deficiency should be treated by modified Wenyang tablets,or Yougui pill plus Yupingfeng powder.

MEDICATION CHARACTERISTICS

Herba Epimedii

Professor Shen found in the clinical study that Herba Epimedii can improve the function of hypothalamic-pituitary-adrenal axis and protect the exogenous corticosteroids from inhibiting neuroendocrine immunity, it also has direct protective and promoting effects on the adrenal cortex. According to the records in ancient books and the mechanism of modern medicinal study, use Herba Epimedii with Radix Aconiti Lateral is Preparata, Fructus Psoraleae, Semen Cuscutae, Radix Rehmanniae Recens and Radix Rehmanniae Preparata etc. in preventing seasonal attack of bronchial asthma and chronic bronchitis of the elder.

Herba Epimedii (dosage is 20～30g) with kidney yang warming medicines like Rhizoma Curculigins, Radix Morindae Officinalis, etc. can treat sexual impotence.With the method of increasing the amount of Herba Epimedii, combined with Radix Rehmanniae Recens,it could eliminate hormonewithdraw. It can be used in treating Parkinson's syndrome with Radix Rehmanniae Recens, Radix Angelicae Sinensis, Radix Paeoniae Alba,Radix Polygoni Multiflori and Sanjia decoction or antlers only. Combining Herbas Epimedii with Radix Aconiti Lateral, Preparata, Ramulus Cinnamomi, Pericarpium Zanthoxyli, Rhizoma Alismatis,Semen Plantaginis,etc.could be used for the treatment of ureteral calculi incarcerated renal calcification. Radix Rehmanniae Preparata, Radix Morindae Officinalis, Fructus Psoraleae,Cortex Eucommiae, Rhizoma Drynariae etc. could be used for treatment of osteoporosis, and with Zuogui Decoction or Yougui Decoction to delay aging, and improve clinical efficacy.

RESEARCH RESULTS

Introduction

Professor Shen studied on the essence of traditional Chinese medicine with the belief of glory for the nation,and persisted in persevering in his career. He broke through many difficulties in medical and scientific research and made gratifying achievements. Shen was awarded the Golden Medal of "Medical Heritage"by the Ministry of Health in 1959, Shanghai Major Scientific and Technological Achievement Award on"The Study of Kidney Essence" in 1978, the National Science and Technology Achievement Award of the National Medical and Health Sciences Conference of the Ministry of Health on the "Kidney" study in 1979. In 1981, 1983, and 1985, Shen's study on the "functional comparison of hypothalamic-pituitary-thyroid, gonad, and adrenal cortical in kidney yang deficiency syndrome","study on the mechanism of yang warming pills in preventing seasonal attacks of bronchial asthma", and"study on the mechanism of warm kidney and draining water method for treatment of hydronephrosis" were respectively sanitizing Department B major scientific and technological achievements award.

He also won the second-class scientific and technological progress award of the State Administration of Traditional Chinese Medicine on "Clinical and experimental study on the effect of kidney nourishing method on gonad axis of senile (male)" in 1987, the second-class scientific and technological progress award from the State Education Commission on "Study on delaying aging by nourishing kidney and replenishing qi" in 1992, the first pioneers of the world's major achievements in Chinese medicine since the founding of the People's Republic of China, and the first and recognized pioneers of Zhongjing Chinese Medicine Distinguished Achievement Award in Guangzhou, China.He has won 21 national and Shanghai major scientific and technological achievements awards.

Examples

Study on the mechanism of yang warming pills in preventing seasonal attacks of bronchial asthma.In long-term clinical research, Professor Shen found that most patients with bronchial asthma presents a deficiency syndrome as root while excess syndrome as manifestation, and 70% with signs of kidney deficiency.The kidney-nourishing method can provide long-term results for asthma patients (data (1957-1965) showed that the effective rate of asthma by kidney-nourishing method was 57.7%-86.9%), the study on endocrine function of asthma patients confirmed that there were different degrees of hypothalamic-pituitary-adrenal axis changes in asthmatic patients with or without kidney deficiency,which made chronic allergic airway inflammation not easy to subside. The former condition is more serious than the latter, especially kidney yang deficiency.

Asthma patients without kidney deficiency also have potential dysfunction of adrenal cortical axis, while the adrenal cortical axis function is particularly low in asthma patients with kidney yang deficiency. Kidneyyang warming and nourishing medicines can improve the function of the adrenal cortical axis, thus Professor Shen took the method of warming kidney yang as a measure in preventing seasonal attacks of bronchial asthma,(patients with apparent yin deficiency with internal heat should use the method of nourishing kidney yin rather than warming the kidney-yang). Self-made yang warming pills are composed of Radix Aconiti Lateral, Preparata,Radix Rehmanniae Recens, Radix Rehmanniae Preparata,Rhizoma Dioscoreae, Fructus Psoraleae, Herba Epimedii,Semen Cuscutae, Pericarpium Cirri Reticulatae, etc., 3 times a day, 5 pills each time.

According to Siqi Tiaoshen Dalun in Su Wen, the method of treating the diseases which usually attack in winter at the season of summer can nourish yang,taking the medicine from the beginning of August to the end of October every year. A total of 365 patients with seasonal bronchial asthma were selected, in which 284 were divided into yang nourishing pills group, and 81 in Xiaoqinglong Decoction control group and blank control group, some patients were detected the function of serum IgE and Ts cell. The results shows that effective rate in preventing seasonal attacks of asthma in yang nourishing pills group was 63.4%-75% while the effective rate of Xiaoqinglong Decoction control group and blank control group were only 18.5%-22.2%. There was significant difference between yang nourishing pills group and other groups. (P ＜ 0.001).

Over the past years, the total effective rate of yang nourishing pills was 83.0-95.6%, and the remarkable effective rate was 57.5%-86.9% contrast with 10.6-22.7%in the control group. The level of serum IgE increased seasonally and the function of Ts cell was significantly lower before the treatment, and there was no significant difference between the groups. Compared with the control group, the seasonal elevation of serum IgE in the yang nourishing pills group was significantly reduced, and the Ts cells were significantly increased after the treatment(P ＜ 0.05). It has been confirmed that the method of kidney-yang warming and nourishing can significantly improve clinical efficacy and is an effective way to prevent recurrence of asthma by the past clinical efficacies, and the changes in laboratory indicators and previous studies. The mechanism might on regulating the neuroendocrine immune integration network and improving the body's disease resistance through the function of the hypothalamic-pituitary-target gland axis which mainly acts on the hypothalamus, so to improve allergies and prevent seasonal evoked effects of asthma from harmful stimuli such as pollen.

STUDY ON SYNDROMES

Great contributions

Academician Shen Ziyin followed the law of the development of Chinese medicine, and studied kidney yang deficiency for nearly half a century. He finally confirmed the kidney yang deficiency syndrome has a specific material basis and located the main regulatory hub in the hypothalamus as the first man in the world,which made important contributions to the modernization of Chinese medicine. His research methods and research results may give people some inspiration.

Academician Shen Ziyin graduated from the Medical Department of Shanghai First Medical College in 1952. He systematically studied classics in traditional Chinese medicine and clinical consultation with the famous Chinese doctor of Jiang Chunhua since 1955. The experience on learning traditional Chinese medicine as a western doctor made his research on the "syndrome"of Chinese medicine integrate the research ideas of traditional Chinese medicine and modern medicine. He believes that the various ways of syndrome differentiation in history made the understandings and recognitions of"syndrome" is various. The concept of zang fu pattern differentiation originates from Huangdi Nei Jing, which inferred the syndrome from the external manifestation of patients based on "zang organs sit in the inner side, and the related manifestation could see from the outside".Huangdi Neijing was born on the prevalence of Yin Yang theory and five elements theory in Zhou and Qin Dynasty which means zang-fu pattern differentiation has a distinct philosophical character. Then Zhang Zhongjing specifically combined the philosophical thinking of syndrome differentiation with clinical practice and widely studied the advantages of different doctors aiming for effectiveness, each decoction is pertinence to corresponding syndrome. as long as this syndrome appears, the decoction can be used, which always be called "Tang Zheng". The idea of syndrome differentiation on decoctions also belongs to syndrome differentiation,so that it is called prescription differentiation. Shen Ziyin studied, with the kidney yang deficiency syndrome as the entry point, from the nature of kidney to the nature of syndromes based on these 2 methods of syndrome differentiations.

Zang-fu syndrome differentiation

Academician Shen Ziyin started from zang-fu syndrome differentiation. The study of "syndrome"is to explore the nature of zang-organs and fu-organs through the outside manifestations. That means to establish a standard of syndrome differentiation, to select typical patients of kidney yang deficiency syndrome with the outside manifestations while without other syndromes mingled with, and patients without the outside manifestations, screening for specific indicators reflecting visceral function. The result shows no specific index(also known as gold index) of kidney yang deficiency syndrome while the kidney yang deficiency syndrome has different levels of hypothalamic-pituitary-adrenal axis and different degrees of dysfunction, which belonging to a kind of hidden changes in potential and it means that the "syndrome" has material basis. Therefore, as long as the "syndrome" is materially based, from the perspective of scientific research, related quantitative and qualitative research can be achieved.

Academician Shen Ziyin further studied on the function of thyroid axis and gonadal axis, and established a comparison of the same disease with different patterns group to avoid the influence of disease by the indexes,and compared the patients with kidney yang deficiency syndrome with the elder people over 65 years old. The result shows that the kidney yang deficiency syndrome had multiple dysfunction of the target gland (all 3 axes involved). The parallel observation on the two axes showed no evidence of mutual influence between the axes.From the perspective of zang fu syndrome differentiation,the main pathogenesis of kidney yang deficiency syndrome may be the dysfunction of hypothalamus (or higher center). The abnormal performance of the elderly group on the two axes is very similar to the kidney yang deficiency group, which indicates that the manifestation of the kidney yang deficiency syndrome refers to a certain degree of immortality of the hypothalamus-pituitary gland and a certain target gland axis. The growing and declining of human beings are determined by the statement of kidney essence and kidney qi, and aging is physiological kidney deficiency.

EXPERIENCE

From this stage of studies, we can know that:

1. The study of "syndrome" of TCM shouldn't be a single specific index. If the "syndrome" can be diagnosed as a single specific index, it means that it has met the diagnostic criteria of the disease and already belonged to the category of "disease".

2. Syndrome is a comprehensive functional state,it is dynamic, developable, and, transformable. Human body has a strong ability in regulation, it can achieve a homeostasis state by constantly feedback mechanism,and the pathological performance is the abnormal of regulation and control ability.

3. The studying on zang fu syndrome differentiation can inferred to the origin of pathology, while it is still impossible to find specific entities corresponding to the syndrome and its control centers.

Discovery and innovation

In 1986, Academician Shen Ziyin observed that Bushen Yishou Tablets can significantly improve the serum testosterone in the elder, while Sijunzi decoction has no effect. Therefore, 24-month-old aged rats were divided into kidney nourishing group (using Bushen Yishou Pills) and control group, compared with 4-month-old adult rats, all the rats were specifically drawn from the hypothalamus.The result shows that the affinity of hypothalamic dihydrotestosterone receptor in aged rats was significantly lower than that in adult rats. Bushen Yishou Pills can effectively improve the affinity of dihydrotestosterone receptor in the hypothalamus of aged rats, which indicates that the kidney nourishing medicines can directly act on the hypothalamus. That has become 1stevidence on the location of kidney yang deficiency syndrome.

In 1990, Academician Shen Ziyin found that the kidney nourishing medicines can improve the aging of the hypothalamic catecholamine neuron function in the comparative study on kidney nourishing medicines and spleen fortifying medicines while the spleen fortifying medicines has no obvious effects, which is the 2ndbasis for the study on the location of kidney yang deficiency syndrome.

In 1995, Academician Shen Ziyin used corticosterone rats (hypothalamic-pituitary-adrenalthymus HPAT axis suppression model, in fact, it is the neuroendocrine-immune NEI network suppression model) to observe the regulating function of kidney yang warming medicines of You Gui decoction and self-made Mingmen mixture decoction. The result shows that both 2 decoction can effectively improve the disorder of monoamine neurotransmitters in the hypothalamus of the model rats, while the morphology and function of the HPAT axis and cellular immune function were overall inhibited. The result indicates that the kidney yang deficiency syndrome has intrinsic connection with NEI network, warming kidney yang is an effective measure to regulate hypothalamus, NEI network, HPAT axis, which has become the 3rd basis for the study on the location of kidney yang deficiency syndrome.

In 1996, Academician Shen Ziyin used the main component of aconitine, a representative aconite of warming kidney and yang, and observed its effect on the morphology and function of CRH in hypothalamus of normal rats. The results further confirmed the specific regulation on hypothalamus by kidney yang warming medicines, and became the 4th basis for the location of kidney yang deficiency syndrome in the hypothalamus.

Academician Shen Ziyin started from the zang fu syndrome differentiation, and inferred the dysfunction of the kidney yang deficiency syndrome is in the hypothalamus from the dysfunction of the 3 axes. Academician Shen thinks, from the syndrome differentiation point of view, the kidney yang deficiency syndrome covering the NEI network, and its regulation center is in the hypothalamus. Therefore, it can be envisaged that for studies on the nature of the syndrome,take the kidney yang deficiency syndrome as an example, maybe can be analogized as the syndrome is a comprehensive functional state with specific functional networks and control centers. The kidney nourishing medicines can specifically increase the expression of CRF gene which is the key functional gene in hypothalamus,and promote the hypothalamus in regulating the NEI functional network. The NEI network theory has already been established by modern scientific studies, while it still lacks of the methods of regulation. Although there is specific gene therapy for monogenic diseases (disease genes or variant genes), while no overall regulation of functional genes in polygenic diseases.

The research of Academician Shen Ziyin on the kidney yang deficiency syndrome shows that Chinese medicine can make up for the shortcomings of modern medicine, for which the advantages in regulating functional networks and functional genes will be a the feature of the future research and application.

SCIENTIFIC ACHIEVEMENTS

Academician Shen published more than 100 papers as the first author, and edited 6 academic monographs of integrated Chinese and Western medicine, including Study on Kidney, etc.. He won a total of 16 awards including the National Science and Technology Achievement by the National Medical Health Science Conference in 1979, the Grade B Science and Technology Achievement by the Ministry of Health, and Shanghai Science and Technology Progress for many times in 1981, 1983, 1985 and 1987,the Science and Technology Progress by the State Education Commission in 1992, and the 1stoutstanding achievement by Guangzhou Zhongjing Chinese Medicine in 1996, which was awarded in the folk form to the first and recognized pioneers with internationallyrecognized achievements of Chinese medicine.

MAJOR ACADEMIC WORKS

Study on the Regulation Mode of Transcription for Related Gene Group of T Cell Apoptosis of the Elder by Kidney Nourishing Decoction

Study on Gene Expression Map of EF in Delaying Senescence of HPAT Axis

Study on Gene Expression Map of Hypothalamic-Pituitary-Adrenal-Thymus Axis In Aged Rats

The Exploration on Total Flavonoids of Epimedium Corresponding to a Medicine Target

Comparison on Total Flavonoids of Epimedium and Bushen Recipe in Regulating Related Genes of T Cell Apoptosis in Corticosterone Rats

Re-exploration on the complementarity of Chinese and Western medicine from the study of syndrome

Thinking and Practicing from Study on the Nature of Kidney to Study on the Nature of Syndrome

Study on the Molecular Network Regulation of HPAT Axis in Senescence -Physiological Kidney Deficiency Syndrome

Kidney-Nourishing Delays Aging: Study on the Regulation on Single Gene To Multiple Genes

Clinical and Experimental Study on Kidney Nourishing Method in Delaying Immunosenescence