Only after more than half a year, on March 14 this year, the team led by Academician Zhu Chen published a paper in the Proceedings of the National Academy of Sciences (PNAS), and systematically analyzed the molecular mechanism of compound Huangdai tablet in treating acute promyelocytic leukemia. Using biochemical methods, the multi-component and multi-target mechanism of compound Huangdai tablet in the treatment of leukemia is expounded at the molecular level, which is completely based on the theory of traditional Chinese medicine.
On March 17, the National People's Congress drew to a close. Academician Zhu Chen, who was appointed as the Minister of Health of the new government, spent nearly two hours in an exclusive interview with our reporter, expounding the research and its achievements in detail, and talking about his own understanding of the modernization of traditional Chinese medicine.
Chinese medicine can "speak clearly and clearly"
As a scientist, Zhu Chen's most acclaimed research achievement is the synergistic treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid and arsenic trioxide. According to this method, the 5-year disease-free survival rate of patients can exceed 90%. APL is expected to be the first curable adult acute myeloid leukemia.
It is reported that acute promyelocytic leukemia is considered as the most dangerous type of leukemia. A large number of immature promyelocytes accumulate in the bone marrow of patients with severe bleeding symptoms. The etiology of the disease has been clearly studied, mainly due to the translocation of two chromosomes, that is, the chromosome arm breaks and exchanges with each other, and a new fusion gene PML-RARα appears at the junction, encoding a fusion protein, which eventually leads to cell canceration.
Ordinary blood cells will differentiate and mature after a certain number of passages and become cells with various specific structures and functions. However, after cancer, cells lose their ability to differentiate and will continue to "grow wildly". All-trans retinoic acid (ATRA) modifies the metabolic cancer protein PML-RARα, which makes cancer cells differentiate again, "reform evil" and stop "crazy growth". Arsenic trioxide can cause the degradation of this cancer protein, make cancer cells partially differentiate and finally enter programmed death (apoptosis).
When introducing his research, Zhu Chen, who has the background of western medical education, always emphasized that he was inspired by China's traditional medical thought. Synergistic compound therapy, fighting poison with poison, eliminating evil and strengthening the body resistance, turning decay into magic, shines with the wisdom of oriental philosophy everywhere. It is not difficult to understand that he is keen to explain the compound prescription of traditional Chinese medicine with modern molecular biology methods.
He said that as early as the 1980s, when the molecular research of acute promyelocytic leukemia had not started and the cancer protein PML-RARα was unknown, Professor Huang Shilin, a Chinese medicine expert in Dalian 2 10 Hospital of the People's Liberation Army, designed a compound yellow belt tablet composed of realgar, indigo naturalis, salvia miltiorrhiza and radix Pseudostellariae on the basis of syndrome differentiation. Since then, Anhui Tiankang Pharmaceutical Co., Ltd. has carried out mass production according to strict modern technology. In recent years, multi-center clinical studies have confirmed the efficacy of compound Huangdai tablet, and its 5-year survival rate in the treatment of acute promyelocytic leukemia can reach 87%. It was also found that the effective components of realgar, indigo naturalis and salvia miltiorrhiza were tetraarsenic tetrasulfide, indirubin and tanshinone IIA, respectively. However, the molecular mechanism of Compound Huangdai Tablet has not been revealed.
Therefore, several research groups, such as Ruijin Hospital of Shanghai Jiaotong University and Guangzhou Institute of Biomedicine and Health of China Academy of Sciences, led by academicians, found that arsenic sulfide alone can prolong the survival time of mice with acute promyelocytic leukemia, and the therapeutic effect of the combination of three drugs can be significantly stronger than that of the two drugs alone or in combination. In the leukemia cell model, arsenic sulfide and tanshinone can differentiate leukemia cells to a certain extent when used alone, while the combination of the three drugs can make leukemia cells "turn evil into right" and differentiate and mature to a certain extent.
Under normal circumstances, during the differentiation of hematopoietic cells from infancy to maturity, the genes and "positive" factors that promote cell differentiation are bound to increase gradually, while the genes and "evil" factors that inhibit cell differentiation are bound to decrease accordingly; In the regulation of cell cycle, the protein "Yang" promoting cell cycle and the factor "Yin" inhibiting cell cycle must be kept in balance. Suffering from leukemia, "healthy qi" is often suppressed, "evil" is abundant, "yang is hyperactive" and "yin deficiency".
At the molecular level, the combination of three drugs can significantly enhance the degradation and destruction of arsenic sulfide on pathogenic PML-RARα cancer protein, so it has the effect of "eliminating evil", and arsenic sulfide is the "monarch drug". Under the action of drugs, the expression of genes promoting cell differentiation increased significantly, while the expression of genes inhibiting cell differentiation decreased significantly, and tanshinone played an important role in it. Protein, which promotes cell cycle, is obviously inhibited, while protein, which inhibits cell cycle, is significantly increased, among which indirubin plays an important role. Studies have confirmed that tanshinone is a "minister medicine" and indirubin is an "adjuvant medicine". It was also found that tanshinone and indirubin promoted arsenic sulfide to enter leukemia cells by increasing the content of aquaglycerol channel protein 9, which is responsible for transporting arsenic sulfide, so both of them played a "drug" role. The combined application of compound yellow belt tablets has synergistic effect.
The vitality of TCM lies in openness and innovation.
"This is a very interesting and highly scientific research, which has opened a precedent for designing a combined treatment plan with the principles of traditional Chinese medicine, and will surely attract great attention from the academic community." An authoritative expert in international pharmacology gave such affirmation to the paper.
Many experts believe that from the perspective of molecular biology and biochemistry, this research is almost impeccable and can be called "perfect". It is very classic to analyze and clarify the clear target and mechanism of action of a Chinese medicine compound developed in full accordance with the theory of traditional Chinese medicine at the cellular and molecular levels. Moreover, the role of each medicine at the molecular level echoes the Chinese medicine's understanding of the position and role of each medicine in the compound prescription, which is amazing!
The mainstream scientific community in the world also gave positive comments on this research achievement. For example, Nature published a review entitled "Traditional Chinese Medicine: Modern New Explanation of Ancient Compound Prescriptions", arguing that this study shows "how the main components of ancient prescriptions' work together' to treat diseases, which is of great significance to the communication between traditional medicine and modern medicine in China"; Science magazine also reported this article when interviewing Zhu Chen.
On the other hand, Zhu Chen thinks it is very lucky that this research can achieve such a result!
"We have a suitable material basis, including purified effective compounds, cell models and animal models," Zhu Chen said. "Of course, the most important thing is that Compound Huangdai Tablet has a very good clinical effect, which is confirmed by multi-center clinical research. Without this foundation, all subsequent research is passive water. From this perspective, the innovation and development of Chinese medicine itself is still the most important. "
The rich development of theoretical system of TCM and the improvement of practical ability are the basis of the development of TCM, which requires both innovation and inheritance. Zhu Chen said: "I support advocating the development of original Chinese medicine in Chinese medicine education and clinical practice!"
Zhu Chen believes that the modernization of TCM also needs an open mind. The history of Chinese medicine for thousands of years has never been a history of complacency, and its connotation has been constantly enriched and improved. The introduction of Persian medicine and the introduction of "Hu medicine" and "Southern medicine" have made important contributions to the development of Chinese medicine. Using modern scientific and technological means and multidisciplinary methods to study Chinese medicine will support and promote the development of Chinese medicine.
In recent years, western medicine has gradually realized the benefits of combined therapy, while Chinese medicine has advocated combined therapy through nearly 65438+ ten thousand compounds for 2500 years. Although some clinical effects have been achieved in traditional Chinese medicine, the effective components of most of them are still unclear, and the mechanism of action is not clear, which limits their popularization and application. "On the basis of determining the clinical efficacy, carrying out mechanism research is not only conducive to the modernization and internationalization of traditional Chinese medicine, but also provides a basis for optimizing the compatibility of prescription and medicine."
Zhu Chen believes that the system of traditional Chinese medicine should be more open in innovation and better at absorbing the crystallization of human wisdom. The latest research achievements in genomics, protein's genomics and metabonomics, nuclear magnetic resonance, bioelectricity, thermal imaging and gene knockout ... All physical, chemical and biological technologies, animal models and human imaging, whatever they are, can be used in the research of traditional Chinese medicine, and the related systems must be strictly tested by biomedical statistics. Modern life science is not surnamed "Xi"! It is necessary to create conditions to attract outstanding scientists and scientific research institutions in the field of life sciences in China to the modernization and innovation system of traditional Chinese medicine.
Now systems biomedicine has created an unprecedented opportunity and platform for the integration of Chinese and Western medicine. The combination of traditional Chinese and western medicine is a very good way to promote the modernization of traditional Chinese medicine. Zhu Chen expects Chinese medicine to better integrate modern science and technology while maintaining its own characteristics, so as to create a brand-new medicine higher than Chinese medicine and western medicine.
Symptoms of acute promyelocytic leukemia
Dizziness, fatigue, nausea, persistent high fever, cough, gingival bleeding, gingival swelling and pain, gingival atrophy, fundus hemorrhage, palpitation, spleen deficiency, bloody stool, anemia.
chemotherapy
The remission rate of all-trans retinoic acid, arsenic trioxide, soft red and cytarabine VP 16 combined chemotherapy reached 90%
psychology
Don't be afraid to get angry. Everyone who has experienced it knows that this is an episode in life and a good opportunity to experience the soul. I believe he can do it.
affect
I feel good, no different from normal people. I can basically cure it, and it doesn't matter if it recurs. I can continue chemotherapy to get remission.