Some thoughts on Chinese medical paradigm and review on the 2006 World Congress on Chinese Medicine
http://www.100md.com
《中华医药杂志》英文版
Some thoughts on Chinese medical paradigm and review on the 2006 World Congress on Chinese Medicine(pdf)
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China
Correspondence to Dr William ChiShing Cho,Room 1305, 13/F, Block R, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong
Tel: 852-29585441,Fax: 852-29585455,Email: chocs@ha.org.hk
[Abstract] We are all becoming more and more aware of the benefits of cooperation between countries and the exchange of medical and technological information. Health care is one of the key issues facing the world at large. Chinese medicine (CM) has evolved through five thousand years and still in use today. It is polychemical in composition, multiple targets in terms of its mechanisms and holistic consideration of its action. It is an early form of integrated and personalized medicine. The 2006 World Congress on Chinese Medicine was held in Hong Kong on 23~25 November 2006. With comprehensive gathering of professionals in the field of CM among 23 countries and regions, the congress encompassed basic, translational and clinical research. The theme was centered on charting the course of development of CM. More than 200 abstracts were published in the Congress, the direction, new technologies and some recent progress in CM provided a wealth of information for policymakers, scientists, CM practitioners, clinicians and healthcare professionals regarding globalization and modernization of CM. High standard scientific researches and clinical trials reported in the congress presented good examples for CM studies. Covering a broad range of topics, it provided an excellent platform for delegates to exchange ideas and explore ways to meet the increasing challenge of CM in the new millennium. Delegates could share the latest discoveries and trends across the entire spectrum of CM. For those who did not attend the meeting, this article may serve as a highlight of this important international CM meeting.
[Key words] Chinese medicine;translational and clinical research;evidencebased medicine;randomized controlled trial;complementary and alternative medicine
The 2006 World Congress on Chinese Medicine was held in Hong Kong on 23~25 November 2006. With comprehensive gathering of professionals in the field of Chinese medicine (CM) among 23 countries and regions, the congress encompassed basic, translational and clinical research. The theme was centered on charting the course of development of CM. Some highlights of the congress are reviewed as follows.
GLOBALIZATION OF CHINESE MEDICINE
Encompassing thousands of years of history, CM is a summary of accomplishments comprises an important component within Chinas cultural mosaic. It has flourished under the influence and guidance of its ancient materialism and dialectics to evolve into the major medical theoretical system it is today. The basic theories of CM deal mainly with basic theoretical knowledge such as the etiology, physiology, pathology, pathogenesis, as well as the treatment and prevention of disease. Its content covers yin and yang, the five elements, visceral manifestations, qi, blood, body fluid, validity, meridians, etc. Some of these theories and concepts may not be well understood in modern terminology and explained by scientific methods.
Surprising in clinical studies, it can be shown thata series of herbal drug preparations are therapeutically equivalent to synthetic drugs and superior in terms of safety. The advantages of these drug combinations are that the single components of the mixture can be applied in doses of relatively low concentrations. This new concept of multidrug therapy can be described as a mulitarget therapy, in which each component affects another molecular target, resulting in a multicausal treatment[1].
Within the Western medical paradigm, reports of randomized controlled trials (RCTs) are near the top of the evidence pyramid. Considerable evidence exists to inform the appropriate conduct of RCTs. Within the CM paradigm, there are gaps in this knowledge base. Chinese medicine researchers need to generate the evidence to inform how best to conduct CM RCTs and adopt global standards for their conduct. To improve this situation, the CM community needs to develop the evidencebased reporting standards [2].
It is necessary to adopt multicenter, largescale, and randomized controlled trials based on the principles of evidencebased medicine (EBM), strengthen observation of longterm effect, as well as medical economics estimation and followup of endpoint events in the study of integrative CM and Western medicine (WM) [3].
In the past two decades, there has been a significant increase in demand for complementary medicine. While much needed evidence is gathered, the debate about more widespread integration of CM and WM continues. Conventional clinicians and healthcare managers want to have persuasive evidence that complementary medicine can deliver safe and costeffective treatment. Successfully integration of CM and WM depends on several aspects, including demand from patients, commitment from health authorities and healthcare professionals, education and communication, ongoing evaluation of evidence and services, jointly agreed guidelines and protocol between CM and WM in various diseases, carefully selection and supervision of complementary practitioners, as well as robust scientific data. Problems are likely to arise with unrealistic expectation, a lack of trust, inappropriate referrals, the unresolved differences in perspective between CM and WM practitioners, as well as the lack of evidence for effectiveness [4].
For example, acupuncture was introduced to the US 35 years ago, since then it has become a popular alternative therapy throughout the Western world. Acupuncture originated from China and now has been westernized to fit the culture, business environment, and economic market of the US [5].
On the other hand, there are an increasing number of publications in prestigious English medical journals validating the scientific basis and/or efficacies of CM, as well as more coverage of clinical use of CM, particularly acupuncture for both private and public insurance scheme. It is an urgent need for publication of books and journals, as well as the development of other vehicles to facilities the dissemination of CM knowledge to the West. Nowadays, more major universities offer degree or training program in CM or integrative medicine. More high level international CM conferences were held in recent years, and CM acquires better recognition by government bodies such as the World Health Organization (WHO). There is increasing funding for the development of CM. With the limitations of the current biomedical approach in both research and clinical care, there is more recognition of the patientcentered model in both clinic care and education. Once CM is clothed in modern language derived from innovative research and carefully blended with the conventional medicine, the world will have a new healthcare paradigm that will not only be safe and effective, but also affordable and accessible [6]
MODERNIZATION AND STANDARDIZATION OF CHINESE MEDICINE
The CM modernization can be briefly expressed as a simple formulation, which is standardization plus sciencelization plus internationalization. Standardization is the precondition of sciencelization, and both standardization and sciencelization are the precondition of internationalization [7].
Traditional medicine is a revolutionary medicine that can brighten the future of mankind. Standardization is an essential element in this process. There are several challenges to the task, which include (1) standardization with evidence as the base; (2) standardization raises the levels of quality; (3) standardization helps with the global banding of scientific technology; (4) standardization produces economic development; (5) standardization produces a better level of care for patients; and (6) standardization helps to share information worldwide. In a meeting hold by the WHO, participants from the Asian and west pacific countries/regions reached numerous objectives, which include (1) to reach a consensus on the need to develop the Classification of East Asian Traditional Medicine using the International Classification of Diseases; (2) to join resources to develop the classification to avoid duplication; (3) to conduct clinical trials to facilitate research; (4) to promote the education of traditional medicine worldwide; (5) to facilitate data collection and statistics to promote policy development and allocate resources; and (6) to exchange the electronic or other forms of health information records. The countries agreed that a listing of patterns and syndromes would be compiled and presented in the end of 2006. This process will take several years before completion.
In recent decades, the use of traditional medicine (TM) remains widespread in developing countries (80%), while the use of complementary and alternative medicine (CAM) is increasing rapidly in developed countries (65%). Traditional medicine is a comprehensive term used to refer both to TM systems such as CM, Indian Ayur Vedic medicine and Arabic Unani medicine, and to various form of indigenous medicine. In definition, TM is the knowledge, skills and practices of holistic healthcare, recognized and accepted for its role in the maintenance of health and the treatment of diseases. There are a number of major challenges of TM, which can be summarized as (1) varying degree with which it is recognized by government; (2) lack of sound scientific evidence concerning the efficacy of many of its therapies; (3) difficulties relating to the protection of indigenous TM knowledge; and (4) problems in ensuring its proper use. To overcome these challenges, the Western Pacific Regional Office of WHO has evolved the foci of plan as policy, regulations, standards, clinical practice, researchers, education and information under the theme of standardization with evidencebased approaches. The roles of standards in TM are raising levels of quality, safety, reliability, efficiency and interchangeability of TM, as well as providing the abovementioned benefits at an economical cost. In connection with the theme of standardization with evidencebased approaches, WHO conducts a number of standardization projects in TM, such as terminologies, acupuncture point locations, traditional medicine information including thesaurus, clinical ontology and classification, as well as evidencebased clinical practice guidelines in TM for 28 priority diseases. The WHO TM strategy and activities will secure the proper use of TM [8].
The major stumbling block on the internationalization of CM is the lack of a complete set of quality standard that can be recognized and accepted by the international community through an objective and stringent validation process. Chinese medicine needs to be standardized. The standardization is set by the international regulation authorities that demand scientific proof on the safety, quality and efficacy of CM. There are some existing problems and current strategy to tackle this task based on the uniqueness of CM [9].
The terminology and translation of the CM terms should be addressed. Regarding the preparation of manuscript, apart from the building of Global Assessment Programme base of the drug which still needs to be thought highly of and to be paid a great deal of attention, to define the species, producing area (habitat), medicinal plant (used part), processing method, storage method and decocting (extraction) method of a Chinese drug are several key links in quality standardization of Chinese drug [10].
The Consolidated Standards of Reporting Trials (CONSORT) (http://www.consortstatement.org/) is an international recognized standard to report the results of clinical trials. It has been published for ten years and is endorsed by many international peerreview journals. Although the initial target of CONSORT is to standardize the final results of clinical trial, this standard improves not only reporting methods, but also the methodological standard of clinical trials. Thus, if the CONSORT for CM could be developed and (indorsed) by international and national peerreview journals, it will give an opportunity to CM to improve the quality of RCT in both reporting and methodology [11].
Herbs are natural products and thus, do not have a consistent, standardized composition. Plants contain 50 to several hundred chemical constituents and different parts of the plant contain different profiles of constituents. Furthermore, the content and concentration of constituents can be influenced by climate, growing conditions, time of harvesting and post harvesting factors. One of the most difficult challenges in the herbal industry is how to manufacture the products, batchtobatch, without many variations. The most popular way to standardize the products is to identify the marker compounds in herbal drugs regardless of their intrinsic biological activities. However, when the percentage of the compounds in the product was considered, they vary from batch to batch and company to company. Therefore, quality control of botanicals and herbal preparations is the prerequisite of credible clinical trials. Kim,et al.from the Seoul National University have recently launched a new strategy for the standardization of herbal medicines by introducing not only bioassays or pharmacological studies, but also a genomic approach related to the chemical components in phytomedicines. From these approaches, the concept of pharmacological equivalence was considered in the evaluation of herbal drugs containing many unknown bioactive markers [12].
Consideration for enhancing evidencebased practice of CM was addressed by Lai from the Guangzhou University of Traditional Chinese Medicine. Evidencebased paradigm is the fundamental model or frame for all of science progresses in light of the history of science. The diagnosis and treatment of CM relies mainly on observation, aggregation of experiences and qualitative approaches. It is necessary to incorporate the principles and methods of EBM into the clinical studies and practice of CM in the context of modern society. To innovate a new paradigm of CM, some themes should be considered for a study agenda, which include (1) integrating the holism and reductionism worldview; (2) integrating the syntheses and analyses approaches; (3) integrating the macroapproach and microapproach; (4) integrating the qualitative and quantitative approaches; (5) integrating singlecase observation and populationbased observation; (6) integrating intuition thinking and logic interface; (7) integrating the experiences aggregation and scientific experiments; and (8) shifting singleexpertopinionbased model into experts consensusbased for clinical decisionmaking. The conformation of clinical efficacy is the key and crucial issue for enhancing evidencebased practice of CM. However, many studies of CM are methodologically flawed, making their results equivocal. Besides, there have been dissenting opinions on how to conduct clinical studies of CM among CM professionals. To resolve these problems, it is necessary to keep the essences of CM on one hand, and incorporate the modern scientific principles and methods into clinical assessments of the efficacy on the other hand [13].
The National Institute of Health (US) has pointed out that for alternative therapies to become accepted, they must endure the same degree of scientific scrutiny as conventional therapies [14]. Assessments of clinical efficacy of CM are undoubtedly not an exception. Randomized controlled trials are widely recognized as a gold standard to inference causality between intervention and outcome, because RCT provides the strongest evidence that study outcomes are actually caused by the intervention due to its maximal reduction of both random error by chance and systematic error by bias. Although methods such as blindness and placebo may not always be suitable for the use in CM study, RCTs are as important in efficacy assessment of the CM regimes as it is in the WM. A well designed and wellimplemented RCT can enhance the trial validation of CM and enable the trial result extrapolated. In case if RCTs implementation is impractical, welldesigned nonrandomized controlled studies are needed. It is particularly useful to evaluate nonmedication intervention. The most important thing is that such studies are particularly required to control the confounding variables affecting the outcomes. The CM regimes work mainly through modulating and improving the entire function of human body. The bodys response to the therapy usually reveals synthesized effects. It is necessary to use a multidimension approach to evaluate the comprehensively efficacy of the CM regimes, including physiological function and how CM improves the quality of life [13].
Chinese medicine developed over thousands of years through direct clinical observation and standardization without formal scientific evaluation. Lack of scientific evaluation raises important concerns regarding CM efficacy and safety, also limits its use out of China. Within the realm of clinical research, the best approach consists of implementing pragmatic trials to assess the overall effects of CM practice. Assessing CM safety could take advantage of the large number of patients who are exposed to the Chinese herbal products every day. A webbased system for remote data capture and online monitoring would enable the followup of many patients exposed to different combination of products and the identification of the adverse events [15].
Most western countries, and an increasing number of Asian countries, now require that research projects involving humans have independent ethical review prior to initiating the research. The reviews are conducted to ensure the protection of the welfare and rights of the research participants as well as facilitation of research that will be of benefit to the society and humankind. The ethical responsibilities of researchers revolve around the basic ethical values of respect for human beings, research merit and integrity, weighting of riskbenefit and justice. The World Medical Associations Declarations of Helsinki is used to inform the discussion of issues such as research design, informed consent, use of placebo control and the evaluation of riskbenefit [16].
RESEARCH PROGRESS IN CHINESE MEDICINE
In the postgenomic era, the application of the new "omics" biotechnology becomes a valuable contribution to the research of life science. Wu,et al.from the Hong Kong Baptist University applied matrix assisted laser desorption/ionization timeofflight mass spectrometry for the direct determination of alkaloids profiling in the plant tissues of Chinese herbs. This method is simple, fast and reproducible with the need of small amounts of sample. The direct analysis on plant tissues by mass spectrometry may be valuable for supporting the discovery of new components and the quality control of medicinal herbs [17].
Panax ginseng has been used to treat diabetes mellitus since the ancient time. In view of the complicated pathogenesis of diabetes mellitus and the aim to unravel the mechanism of the antidiabetic effect of ginsenoside Re of Panax ginseng in diabetic rats, the writer has examined the levels of blood glucose, total cholesterol and triglycerides, as well as tissue glutathione and malondialdehyde in the ginsenoside Re treated diabetic rats. The results demonstrated that ginsenoside Re could lower the blood glucose and lipidemic levels, as well as exerted protective effects against the occurrence of oxidative stress in the eye and kidney of the diabetic rats. The data provided evidence that ginsenoside Re could be used as an effective antidiabetic agent, particularly in the prevention of diabetic microvasculopathy [18]. To further explore the protein alterations underlying the antidiabetic effect of ginsenoside Re, serum protein profiling was conducted employing a high throughput proteomic approach named surfaceenhanced laser desorption/ionization timeofflight mass spectrometry [19]. A potential biomarker was detected to have significant alteration corresponding to the ginsenoside Re treatment. This biomarker was found to match with protein database and was subsequently validated by ELISA [20].
Chiu from the University of Hong Kong suggested that dioscin, a saponin extracted from the root of Polygonatum zanlanscianense pamp, exhibited cytotoxicity towards human myeloblast leukemia HL-60 cells through multiple apoptosisincluding pathways. Proteomic analysis revealed that the expression of mitochondrial associated proteins was substantially altered in HL-60 cells corresponding to the dioscin treatment, suggesting that mitochondria were the major cellular target of dioscin. Mitochondrial functional studies validated that mitochondrial apoptotic pathway was initiated by the dioscin treatment. Changes in proteome other than mitochondrial related protein implicated that other mechanisms were also involved in dioscininduced apoptosis in HL-60 cells, including the activity impairment in protein synthesis, alternations of phosphatases in cell signaling, as well as deregulation of oxidative stress and cell proliferation [21].
Magnolol and honokiol, two lignants showing antiinflammatory and antioxidant properties, are abundantly available in the medicinal plants Magnolia officinalis and Magnolia obovata. They were found to enhance HL-60 cell differentiation initiated by low disease of 1,25-Dihydroxyvitamin D3 and alltransretinoic acid by Tse and Fong from the City University of Hong Kong. It is evident that magnolol and honokiol are potential differentiation enhancing agents in the treatment for acute promyelocytic leukemia [22].
Identification of lead compounds is the first and the most important step in drug discovery. Luo,et al.from the Hong Kong University of Science and Technology have generated a molecular biosensor based on the principle of fluorescence resonance energy transfer for detecting the caspase3 activation in apoptotic cells. With this biosensor, they have developed a cellbased high throughput screening platform to select compounds that can rigger apoptosis in cancer cells. This system was used to screen compounds isolated from two herbal plants and several effective compounds for apoptosis induction were identified, including tanshinone IIA isolated from the root of Salvia miltiorrhiza bunge and deoxypodopyllotoxin purified from Podophylum emodi wall [23].
Lin,et al.from the Chinese University of Hong Kong have studied a number of anticancer Chinese herbs for their cytotoxic effects on pancreatic carcinoma cell lines, including PANC-1 and SW-1990. It was found that the treatment of cell lines with Brucea javanica fruit extract caused cell cycle arrest at the G2/M phase, and an induction of apoptosis was involved in the Brucea javanica fruit extract induced growth inhibition as evidenced by the fragmentation of the genomic DNA and activation of caspase-3 after a 72 hourtreatment. Their findings suggest that Bruce javanica fruit is a potential crude drug from antipancreatic cancer agents [24].
Lycium barbarum has been used for thousands of years in China and is believed to be effective as an antiaging agent as well as nourishment of eyes, liver and kidneys. So,et al.from the University of Hong Kong have shown that aqueous extract of Lycium barbarum provides neuroprotection to the eyes against degeneration in an experimental model of glaucoma and to cortical neurons against β-amyloid peptide neurotoxicity in a cell culture model of Alzheimers disease. Using a rat glaucoma model, they have shown that oral administration of Lycium barbarum significantly reduced the retinal ganglion cells loss against elevated intraocular pressure. They have also shown that the neuroprotective effects were, partly, mediated by attracting immunocompetent cells infiltrating into the injured site of retina. Primary cortical neurons exposed to β-amyloid peptides results in apoptosis and necrosis. Extract of Lycium barbarum markedly reduced the number of apoptotic neurons and it may depend on the inhibition of the cJun Nterminal kinase signaling pathway [25].
Hawthorn is a wellknown herb in CM. The hawthorn extract was found to produce an effect in inducing endotheliumdependent nitric oxidemediated relaxation. The extract stimulates a significant increase in the total tissue content of cyclic guanosine monophosphate in arteries with endothelium, an index for the increased generation of nitric oxide. The data suggests that consumption of hawthorn may benefit vascular function via the endotheliumderived nitric oxidedependent mechanisms [26].
Yun from the Korea Institute for Cancer Chemoprevention did a 5year followup epidemiological study on the preventive effects of Panax ginseng against cancer. A cohort of 4,634 participants entered the study. The relative risks in ginseng consumers for gastric cancer and lung cancers were 0.33 and 0.30 respectively, whereas a decreased risk for stomach cancer was observed only in fresh ginseng extract consumers [27].
Danggui buxue tang (DBT) is deemed to be an effective prescription for the relief of menopausal symptoms by raising the vital energy and nourishing the body circulation of individual. Even though the experienced formula has been used for more than 800 years, research is still needed to verify the therapeutic mechanism and to identify the optimal drug ratio of the two main ingredients Radix astragali (RA) and Radix angelicae sinensis (RAS). The formula prepared from different drug ratios was applied onto cultured Tlymphocytes and macrophages. In the cultured Tlymphocytes, DBT induced the cell proliferation markedly, the secretion of interleukin-2 and the phosphorylation of extracellular signalregulated kinase. In addition, the phagocytosis of cultured macrophages was increased by DBT treatment. The immunomodulatory effects of DBT were revealed to be the strongest in extract derived from the drug ratio of 5:1 (RA:RAS). These results verified that the ancient formulation of DBT has been optimized in stimulating the immune responses [28].
Experimental evidences show that compounds isolated from CM of activating blood circulation to remove blood stasis can gain beneficial bioresponses to the interaction of blood flow. The effectiveness of a medicine may be significantly modified when mechanical factors are present. As a consequence of merging the biomechanical and pharmacological factors, a borderline new term “biomechanopharmacology” came into use. Investigation into the shear stress effects of flowing blood together with the CM of activating blood circulation to remove blood stasis may write a new chapter in disease prevention and healthcare [29].
Acupuncture points located along the meridian pathways are suggested as energy connections from the surface of the body to the internal organs and to the environment. Ma,et al.from the University of California used modern technologies to reveal that nitric oxidecyclic guanosine monophosphate is physiologically released over and in the skin with a high level at acupuncture points. The stimulusevoked release is acupuncture point/meridian specific, which plays an important role in meridian functions, inducing signal transduction of therapeutic stimulations and physiological communication with the environment [30].
Lin from the University of California used the latest biomedical technologies to gain a better understanding of the beneficial effects of qigong practices on mindbody functions. Laser flowmetry demonstrated that certain qigong movements when coordinated with deep breathing cycles and mental relaxation are highly effective in enhancing peripheral blood flow. The transcranial measurement of oxyhemoglobin with photo migration spectroscopy showed that the breathholding phase of certain qigong breathing exercises leads to a large increase in brain oxygen content. The heart rate variability analysis of electrocardiograms and independent component analysis of electroencephalograms indicated that qigong medication induces a dual state of mental relaxation and concentration. Qigong practices were found to increase bioenergy emitted from hand in the form of heat (measured by infrared thermography), light (measured by single photon counting), and electricity (measured by gas discharge visualization). Physical strength in a weightlifting test also increased significantly. The electrical conductance at jingwell acupoints of the 12 major meridians was measured with the single square voltage pulse method, it was shown to increase significantly following qigong practices and acupuncture but not physical exercises. These studies showed that qigong practices can lead to measurable enhancement of mindbody functions and bioenergy levels [31].
Huang,et al.from the ChiMei Medical Center (Taiwan) found that Radix astragali extract could stimulate RAW 264.7 cells and splenocytes proliferation via scavenging nitric oxide radical. In addition, it also significantly increased the rate of recovery of white blood cell level in the BALB/c mice model back to a normal status. The data suggest that Radix astragali may be an effective dietary supplement for ameliorating deleterious side effects from chemotherapy in cancer patients [32]. These results were in line with the previous findings of the writer [33].
SYSTEMS BIOLOGY AND CHINESE MEDICINE
Systems biology is a new emerging discipline of active research which aims to understand the system properties of the biological processes from cell level to human physiology. System properties of such complex systems can be revealed with the help of mathematical models which stimulate their dynamic behavior. These mathematical models are solved by numerical methods with supercomputers, so systems biology requires the integration of information technology and biology. Although it seems quite different from the experiencebased traditional methods and qualitative theories of CM, there are important similarities between systems biology and CM. Chinese medicine has always conceived human physiology from a holistic point of view, the body is considered as a system which interacts with the environment. If systems biology would help to explain and verify some fundamental aspects of CM, such scientific explanation may lead to new innovations and breakthroughs in the understanding of human physiology, as well as enhances the development of new therapeutic strategies and medicines. Examples include the similarity of circadian rhythms studied by modern chronobiology and the circulatory activation of medians in CM, as well as the similarity of the stimulation of synergistic effects of multicomponent herbs in CM and the need to develop new macroscopic concepts in systems biology [34].
Chinese medicine is characterized with complexity and holism in both diagnostic and therapeutic principles, a feature very similar to the systems biology bases. Very often, it makes the functional investigation of CM difficult to perform with conventional individual assays. It is believed that the highthroughput functional genomic tools will pave the way for functional screening, at both in vitro and in vivo level, of the compounds isolated from CM for the therapy of different human diseases in a combinatorial manner. On the other hand, the application of these tools will greatly facilitate the elucidation of the functional mechanisms of CM in a systematic way [35].
CONCLUSION
In the 2006 World Congress on Chinese Medicine, the direction, new technologies and some recent progress in CM provided a wealth of information for policymakers, scientists, CM practitioners, clinicians and healthcare professionals regarding globalization and modernization of CM. High standard scientific researches and clinical trials reported in the congress presented good examples for CM studies. Covering a broad range of topics, it provided an excellent platform for delegates to exchange ideas and explore ways to meet the increasing challenge of CM in the new millennium. Delegates could share the latest discoveries and trends across the entire spectrum of CM. For those who did not attend the meeting, this article may serve as a highlight of this important international CM meeting.
REFERENCES
1. Wagner H. Synergy research: A new approach to evaluate the efficacy of multi herbal drug combinations in traditional Chinese medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,3.
2. Moher D. So you want the evidence: challenges facing its generation, synthesis and reporting [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,4.
3. Chen KJ, Xu H. The difficulties and strategies of integrative Western and Chinese medicine in preventing and treating coronary heart disease [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,5.
4. Sung J. Collaboration of Chinese and Western medicine in research [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,6.
5. Li YM. Different perspectives of acupuncture practice in the east and west [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,35.
6. Hui KK. Chinese medicine coming of age for healthcare in the new millennium [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,14.
7. Li YP, Wu TX, Li J, et al. Chinese evidencebased medicine centres strategy and measures about promoting traditional Chinese medicine modernization [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,110.
8. Choi SH. WHO traditional medicine strategy and activities [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,10.
9. Tsim KW. Danggui buxue tang (a Chinese Angelica decoction): A sample trial in traditional Chinese medicine standardization [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,127.
10. Cai SQ. Several key links in quality standardization of Chinese drugs [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006, 53.
11. Bian ZX, Moher D, Li YP, et al. CONSORT of traditional Chinese medicine Opportunities and challenges for traditional Chinese medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,112.
12. Kim YS. A new strategy for the standardization of herbal medicines in Korea [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,63.
13. Lai SL. Considerations of enhancing evidencebased practice of traditional Chinese medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,102-104.
14. Levin JS, Glass TA, Kushi LH, et al. Quantitative methods in research on complementary and alternative medicine. A methodological manifesto. NIH Office of Alternative Medicine. Quantitative methods in research on complimentary medicine: A methodological manifesto. Med Care 1997, 35(11): 1079-1094.
15. Collet JP, Xu WN, Shapiro S. Traditional Chinese medicine strategic development: Importance of pragmatic trials in the evaluation process [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,105.
16. Zaslawski C. Ethical considerations and their impact on Chinese medicine and acupuncture clinical research [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,107.
17. Wu W, Liang ZT, Zhao ZZ, et al. MALDITOF MS for the direct analysis of components in herb tissues [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,51.
18. Cho WC, Chung WS, Lee SK, et al. Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocininduced diabetic rats. Eur J Pharmacol,2006,550(1-3): 173-179.
19. Cho WC. Research progress in SELDITOF MS and its clinical applications. Chin J Biotechnol,2006,22(6): 871-876.
20. Cho WC, Yip TT, Chung WS, et al. Altered expression of serum protein in ginsenoside Re treated diabetic rats detected by SELDI-TOF MS. J Ethnopharmacol,2006,108(2): 272-279.
21. Chiu JF. Proteomic approach to study the cytotoxicity of dioscin, a saponin of Polygonatum zanlanscianenense pamp [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,73.
22. Fong WF, Tse AK, Poon KH, et al. Magnolol and honokiol enhance HL-60 human leukemia cell differentiation induced by 1,25dihydroxyvitamin D3 and retinoic acid. Int J Biochem Cell Biol,2005,37(2): 427-441.
23. Luo K, Tian HL, Ip L, et al. A fluorescence resonance energy transfer (FRET)based high throughput drug screening method for discovery of anticancer compounds from herbal medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,75.
24. Lin ZX, Lau CS, Leung PS, et al. Brucea javanica induces cell cycle arrest and apoptosis in human pancreatic ductal adenocarcinoma cell lines [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,136.
25. So KF, Chang RC. Molecular basis of neuroprotection in glaucoma and Alzheimers disease using gouqizi [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,84.
26. Huang Y, Chen ZY. Medicinal plants and endothelial cell protection [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,129.
27. Yun TK. Epidemiological studies on intakers of Panax ginseng CA Meyer: Can this herb prevent all kings of cancer [Abstract]? In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006, 128.
28. Dong TT, Zhao KJ, Gao QT, et al. Chemical and biological assessment of a Chinese herbal decoction containing Radix Astragali and Radix Angelicae Sinensis: Determination of drug ratio in having optimized properties. J Agric Food Chem,2006,54(7): 2767-2774.
29. Liao FL. Biomechanopharmacological annotation for the therapeutic principle of activating blood circulation to remove stasis [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,86.
30. Ma SX, Li XY, Lim N, et al. Biochemical physiology of nitric oxidecGMP on the skin acupuncture points and meridians: An innovative approach in humans [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,40.
31. Lin S. New approaches to this study of physiological and bioenergetic changes associated with qigong/tai chi practices [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU,2006,46.
32. Huang GC, Weng BC, Lee CJ, et al. Immunomodulatory effects of Radix astragali (Huangqi) extracts on nitric oxide inhibition and splenocytes proliferation [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,158.
33. Cho WC, Leung KN. In vitro and in vivo antitumor effects of Astragalus membranaceus. Cancer Lett; in press.
34. Heiskanen T. Systems biology and traditional Chinese medicine: What they have in common and what they can learn and benefit from each other [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,76.
35. Hu YH. Development of highthroughput functional genomic tools a potential application for the research and development of Chinese medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,70.
(Editor Hou)(William ChiShing Cho)
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China
Correspondence to Dr William ChiShing Cho,Room 1305, 13/F, Block R, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong
Tel: 852-29585441,Fax: 852-29585455,Email: chocs@ha.org.hk
[Abstract] We are all becoming more and more aware of the benefits of cooperation between countries and the exchange of medical and technological information. Health care is one of the key issues facing the world at large. Chinese medicine (CM) has evolved through five thousand years and still in use today. It is polychemical in composition, multiple targets in terms of its mechanisms and holistic consideration of its action. It is an early form of integrated and personalized medicine. The 2006 World Congress on Chinese Medicine was held in Hong Kong on 23~25 November 2006. With comprehensive gathering of professionals in the field of CM among 23 countries and regions, the congress encompassed basic, translational and clinical research. The theme was centered on charting the course of development of CM. More than 200 abstracts were published in the Congress, the direction, new technologies and some recent progress in CM provided a wealth of information for policymakers, scientists, CM practitioners, clinicians and healthcare professionals regarding globalization and modernization of CM. High standard scientific researches and clinical trials reported in the congress presented good examples for CM studies. Covering a broad range of topics, it provided an excellent platform for delegates to exchange ideas and explore ways to meet the increasing challenge of CM in the new millennium. Delegates could share the latest discoveries and trends across the entire spectrum of CM. For those who did not attend the meeting, this article may serve as a highlight of this important international CM meeting.
[Key words] Chinese medicine;translational and clinical research;evidencebased medicine;randomized controlled trial;complementary and alternative medicine
The 2006 World Congress on Chinese Medicine was held in Hong Kong on 23~25 November 2006. With comprehensive gathering of professionals in the field of Chinese medicine (CM) among 23 countries and regions, the congress encompassed basic, translational and clinical research. The theme was centered on charting the course of development of CM. Some highlights of the congress are reviewed as follows.
GLOBALIZATION OF CHINESE MEDICINE
Encompassing thousands of years of history, CM is a summary of accomplishments comprises an important component within Chinas cultural mosaic. It has flourished under the influence and guidance of its ancient materialism and dialectics to evolve into the major medical theoretical system it is today. The basic theories of CM deal mainly with basic theoretical knowledge such as the etiology, physiology, pathology, pathogenesis, as well as the treatment and prevention of disease. Its content covers yin and yang, the five elements, visceral manifestations, qi, blood, body fluid, validity, meridians, etc. Some of these theories and concepts may not be well understood in modern terminology and explained by scientific methods.
Surprising in clinical studies, it can be shown thata series of herbal drug preparations are therapeutically equivalent to synthetic drugs and superior in terms of safety. The advantages of these drug combinations are that the single components of the mixture can be applied in doses of relatively low concentrations. This new concept of multidrug therapy can be described as a mulitarget therapy, in which each component affects another molecular target, resulting in a multicausal treatment[1].
Within the Western medical paradigm, reports of randomized controlled trials (RCTs) are near the top of the evidence pyramid. Considerable evidence exists to inform the appropriate conduct of RCTs. Within the CM paradigm, there are gaps in this knowledge base. Chinese medicine researchers need to generate the evidence to inform how best to conduct CM RCTs and adopt global standards for their conduct. To improve this situation, the CM community needs to develop the evidencebased reporting standards [2].
It is necessary to adopt multicenter, largescale, and randomized controlled trials based on the principles of evidencebased medicine (EBM), strengthen observation of longterm effect, as well as medical economics estimation and followup of endpoint events in the study of integrative CM and Western medicine (WM) [3].
In the past two decades, there has been a significant increase in demand for complementary medicine. While much needed evidence is gathered, the debate about more widespread integration of CM and WM continues. Conventional clinicians and healthcare managers want to have persuasive evidence that complementary medicine can deliver safe and costeffective treatment. Successfully integration of CM and WM depends on several aspects, including demand from patients, commitment from health authorities and healthcare professionals, education and communication, ongoing evaluation of evidence and services, jointly agreed guidelines and protocol between CM and WM in various diseases, carefully selection and supervision of complementary practitioners, as well as robust scientific data. Problems are likely to arise with unrealistic expectation, a lack of trust, inappropriate referrals, the unresolved differences in perspective between CM and WM practitioners, as well as the lack of evidence for effectiveness [4].
For example, acupuncture was introduced to the US 35 years ago, since then it has become a popular alternative therapy throughout the Western world. Acupuncture originated from China and now has been westernized to fit the culture, business environment, and economic market of the US [5].
On the other hand, there are an increasing number of publications in prestigious English medical journals validating the scientific basis and/or efficacies of CM, as well as more coverage of clinical use of CM, particularly acupuncture for both private and public insurance scheme. It is an urgent need for publication of books and journals, as well as the development of other vehicles to facilities the dissemination of CM knowledge to the West. Nowadays, more major universities offer degree or training program in CM or integrative medicine. More high level international CM conferences were held in recent years, and CM acquires better recognition by government bodies such as the World Health Organization (WHO). There is increasing funding for the development of CM. With the limitations of the current biomedical approach in both research and clinical care, there is more recognition of the patientcentered model in both clinic care and education. Once CM is clothed in modern language derived from innovative research and carefully blended with the conventional medicine, the world will have a new healthcare paradigm that will not only be safe and effective, but also affordable and accessible [6]
MODERNIZATION AND STANDARDIZATION OF CHINESE MEDICINE
The CM modernization can be briefly expressed as a simple formulation, which is standardization plus sciencelization plus internationalization. Standardization is the precondition of sciencelization, and both standardization and sciencelization are the precondition of internationalization [7].
Traditional medicine is a revolutionary medicine that can brighten the future of mankind. Standardization is an essential element in this process. There are several challenges to the task, which include (1) standardization with evidence as the base; (2) standardization raises the levels of quality; (3) standardization helps with the global banding of scientific technology; (4) standardization produces economic development; (5) standardization produces a better level of care for patients; and (6) standardization helps to share information worldwide. In a meeting hold by the WHO, participants from the Asian and west pacific countries/regions reached numerous objectives, which include (1) to reach a consensus on the need to develop the Classification of East Asian Traditional Medicine using the International Classification of Diseases; (2) to join resources to develop the classification to avoid duplication; (3) to conduct clinical trials to facilitate research; (4) to promote the education of traditional medicine worldwide; (5) to facilitate data collection and statistics to promote policy development and allocate resources; and (6) to exchange the electronic or other forms of health information records. The countries agreed that a listing of patterns and syndromes would be compiled and presented in the end of 2006. This process will take several years before completion.
In recent decades, the use of traditional medicine (TM) remains widespread in developing countries (80%), while the use of complementary and alternative medicine (CAM) is increasing rapidly in developed countries (65%). Traditional medicine is a comprehensive term used to refer both to TM systems such as CM, Indian Ayur Vedic medicine and Arabic Unani medicine, and to various form of indigenous medicine. In definition, TM is the knowledge, skills and practices of holistic healthcare, recognized and accepted for its role in the maintenance of health and the treatment of diseases. There are a number of major challenges of TM, which can be summarized as (1) varying degree with which it is recognized by government; (2) lack of sound scientific evidence concerning the efficacy of many of its therapies; (3) difficulties relating to the protection of indigenous TM knowledge; and (4) problems in ensuring its proper use. To overcome these challenges, the Western Pacific Regional Office of WHO has evolved the foci of plan as policy, regulations, standards, clinical practice, researchers, education and information under the theme of standardization with evidencebased approaches. The roles of standards in TM are raising levels of quality, safety, reliability, efficiency and interchangeability of TM, as well as providing the abovementioned benefits at an economical cost. In connection with the theme of standardization with evidencebased approaches, WHO conducts a number of standardization projects in TM, such as terminologies, acupuncture point locations, traditional medicine information including thesaurus, clinical ontology and classification, as well as evidencebased clinical practice guidelines in TM for 28 priority diseases. The WHO TM strategy and activities will secure the proper use of TM [8].
The major stumbling block on the internationalization of CM is the lack of a complete set of quality standard that can be recognized and accepted by the international community through an objective and stringent validation process. Chinese medicine needs to be standardized. The standardization is set by the international regulation authorities that demand scientific proof on the safety, quality and efficacy of CM. There are some existing problems and current strategy to tackle this task based on the uniqueness of CM [9].
The terminology and translation of the CM terms should be addressed. Regarding the preparation of manuscript, apart from the building of Global Assessment Programme base of the drug which still needs to be thought highly of and to be paid a great deal of attention, to define the species, producing area (habitat), medicinal plant (used part), processing method, storage method and decocting (extraction) method of a Chinese drug are several key links in quality standardization of Chinese drug [10].
The Consolidated Standards of Reporting Trials (CONSORT) (http://www.consortstatement.org/) is an international recognized standard to report the results of clinical trials. It has been published for ten years and is endorsed by many international peerreview journals. Although the initial target of CONSORT is to standardize the final results of clinical trial, this standard improves not only reporting methods, but also the methodological standard of clinical trials. Thus, if the CONSORT for CM could be developed and (indorsed) by international and national peerreview journals, it will give an opportunity to CM to improve the quality of RCT in both reporting and methodology [11].
Herbs are natural products and thus, do not have a consistent, standardized composition. Plants contain 50 to several hundred chemical constituents and different parts of the plant contain different profiles of constituents. Furthermore, the content and concentration of constituents can be influenced by climate, growing conditions, time of harvesting and post harvesting factors. One of the most difficult challenges in the herbal industry is how to manufacture the products, batchtobatch, without many variations. The most popular way to standardize the products is to identify the marker compounds in herbal drugs regardless of their intrinsic biological activities. However, when the percentage of the compounds in the product was considered, they vary from batch to batch and company to company. Therefore, quality control of botanicals and herbal preparations is the prerequisite of credible clinical trials. Kim,et al.from the Seoul National University have recently launched a new strategy for the standardization of herbal medicines by introducing not only bioassays or pharmacological studies, but also a genomic approach related to the chemical components in phytomedicines. From these approaches, the concept of pharmacological equivalence was considered in the evaluation of herbal drugs containing many unknown bioactive markers [12].
Consideration for enhancing evidencebased practice of CM was addressed by Lai from the Guangzhou University of Traditional Chinese Medicine. Evidencebased paradigm is the fundamental model or frame for all of science progresses in light of the history of science. The diagnosis and treatment of CM relies mainly on observation, aggregation of experiences and qualitative approaches. It is necessary to incorporate the principles and methods of EBM into the clinical studies and practice of CM in the context of modern society. To innovate a new paradigm of CM, some themes should be considered for a study agenda, which include (1) integrating the holism and reductionism worldview; (2) integrating the syntheses and analyses approaches; (3) integrating the macroapproach and microapproach; (4) integrating the qualitative and quantitative approaches; (5) integrating singlecase observation and populationbased observation; (6) integrating intuition thinking and logic interface; (7) integrating the experiences aggregation and scientific experiments; and (8) shifting singleexpertopinionbased model into experts consensusbased for clinical decisionmaking. The conformation of clinical efficacy is the key and crucial issue for enhancing evidencebased practice of CM. However, many studies of CM are methodologically flawed, making their results equivocal. Besides, there have been dissenting opinions on how to conduct clinical studies of CM among CM professionals. To resolve these problems, it is necessary to keep the essences of CM on one hand, and incorporate the modern scientific principles and methods into clinical assessments of the efficacy on the other hand [13].
The National Institute of Health (US) has pointed out that for alternative therapies to become accepted, they must endure the same degree of scientific scrutiny as conventional therapies [14]. Assessments of clinical efficacy of CM are undoubtedly not an exception. Randomized controlled trials are widely recognized as a gold standard to inference causality between intervention and outcome, because RCT provides the strongest evidence that study outcomes are actually caused by the intervention due to its maximal reduction of both random error by chance and systematic error by bias. Although methods such as blindness and placebo may not always be suitable for the use in CM study, RCTs are as important in efficacy assessment of the CM regimes as it is in the WM. A well designed and wellimplemented RCT can enhance the trial validation of CM and enable the trial result extrapolated. In case if RCTs implementation is impractical, welldesigned nonrandomized controlled studies are needed. It is particularly useful to evaluate nonmedication intervention. The most important thing is that such studies are particularly required to control the confounding variables affecting the outcomes. The CM regimes work mainly through modulating and improving the entire function of human body. The bodys response to the therapy usually reveals synthesized effects. It is necessary to use a multidimension approach to evaluate the comprehensively efficacy of the CM regimes, including physiological function and how CM improves the quality of life [13].
Chinese medicine developed over thousands of years through direct clinical observation and standardization without formal scientific evaluation. Lack of scientific evaluation raises important concerns regarding CM efficacy and safety, also limits its use out of China. Within the realm of clinical research, the best approach consists of implementing pragmatic trials to assess the overall effects of CM practice. Assessing CM safety could take advantage of the large number of patients who are exposed to the Chinese herbal products every day. A webbased system for remote data capture and online monitoring would enable the followup of many patients exposed to different combination of products and the identification of the adverse events [15].
Most western countries, and an increasing number of Asian countries, now require that research projects involving humans have independent ethical review prior to initiating the research. The reviews are conducted to ensure the protection of the welfare and rights of the research participants as well as facilitation of research that will be of benefit to the society and humankind. The ethical responsibilities of researchers revolve around the basic ethical values of respect for human beings, research merit and integrity, weighting of riskbenefit and justice. The World Medical Associations Declarations of Helsinki is used to inform the discussion of issues such as research design, informed consent, use of placebo control and the evaluation of riskbenefit [16].
RESEARCH PROGRESS IN CHINESE MEDICINE
In the postgenomic era, the application of the new "omics" biotechnology becomes a valuable contribution to the research of life science. Wu,et al.from the Hong Kong Baptist University applied matrix assisted laser desorption/ionization timeofflight mass spectrometry for the direct determination of alkaloids profiling in the plant tissues of Chinese herbs. This method is simple, fast and reproducible with the need of small amounts of sample. The direct analysis on plant tissues by mass spectrometry may be valuable for supporting the discovery of new components and the quality control of medicinal herbs [17].
Panax ginseng has been used to treat diabetes mellitus since the ancient time. In view of the complicated pathogenesis of diabetes mellitus and the aim to unravel the mechanism of the antidiabetic effect of ginsenoside Re of Panax ginseng in diabetic rats, the writer has examined the levels of blood glucose, total cholesterol and triglycerides, as well as tissue glutathione and malondialdehyde in the ginsenoside Re treated diabetic rats. The results demonstrated that ginsenoside Re could lower the blood glucose and lipidemic levels, as well as exerted protective effects against the occurrence of oxidative stress in the eye and kidney of the diabetic rats. The data provided evidence that ginsenoside Re could be used as an effective antidiabetic agent, particularly in the prevention of diabetic microvasculopathy [18]. To further explore the protein alterations underlying the antidiabetic effect of ginsenoside Re, serum protein profiling was conducted employing a high throughput proteomic approach named surfaceenhanced laser desorption/ionization timeofflight mass spectrometry [19]. A potential biomarker was detected to have significant alteration corresponding to the ginsenoside Re treatment. This biomarker was found to match with protein database and was subsequently validated by ELISA [20].
Chiu from the University of Hong Kong suggested that dioscin, a saponin extracted from the root of Polygonatum zanlanscianense pamp, exhibited cytotoxicity towards human myeloblast leukemia HL-60 cells through multiple apoptosisincluding pathways. Proteomic analysis revealed that the expression of mitochondrial associated proteins was substantially altered in HL-60 cells corresponding to the dioscin treatment, suggesting that mitochondria were the major cellular target of dioscin. Mitochondrial functional studies validated that mitochondrial apoptotic pathway was initiated by the dioscin treatment. Changes in proteome other than mitochondrial related protein implicated that other mechanisms were also involved in dioscininduced apoptosis in HL-60 cells, including the activity impairment in protein synthesis, alternations of phosphatases in cell signaling, as well as deregulation of oxidative stress and cell proliferation [21].
Magnolol and honokiol, two lignants showing antiinflammatory and antioxidant properties, are abundantly available in the medicinal plants Magnolia officinalis and Magnolia obovata. They were found to enhance HL-60 cell differentiation initiated by low disease of 1,25-Dihydroxyvitamin D3 and alltransretinoic acid by Tse and Fong from the City University of Hong Kong. It is evident that magnolol and honokiol are potential differentiation enhancing agents in the treatment for acute promyelocytic leukemia [22].
Identification of lead compounds is the first and the most important step in drug discovery. Luo,et al.from the Hong Kong University of Science and Technology have generated a molecular biosensor based on the principle of fluorescence resonance energy transfer for detecting the caspase3 activation in apoptotic cells. With this biosensor, they have developed a cellbased high throughput screening platform to select compounds that can rigger apoptosis in cancer cells. This system was used to screen compounds isolated from two herbal plants and several effective compounds for apoptosis induction were identified, including tanshinone IIA isolated from the root of Salvia miltiorrhiza bunge and deoxypodopyllotoxin purified from Podophylum emodi wall [23].
Lin,et al.from the Chinese University of Hong Kong have studied a number of anticancer Chinese herbs for their cytotoxic effects on pancreatic carcinoma cell lines, including PANC-1 and SW-1990. It was found that the treatment of cell lines with Brucea javanica fruit extract caused cell cycle arrest at the G2/M phase, and an induction of apoptosis was involved in the Brucea javanica fruit extract induced growth inhibition as evidenced by the fragmentation of the genomic DNA and activation of caspase-3 after a 72 hourtreatment. Their findings suggest that Bruce javanica fruit is a potential crude drug from antipancreatic cancer agents [24].
Lycium barbarum has been used for thousands of years in China and is believed to be effective as an antiaging agent as well as nourishment of eyes, liver and kidneys. So,et al.from the University of Hong Kong have shown that aqueous extract of Lycium barbarum provides neuroprotection to the eyes against degeneration in an experimental model of glaucoma and to cortical neurons against β-amyloid peptide neurotoxicity in a cell culture model of Alzheimers disease. Using a rat glaucoma model, they have shown that oral administration of Lycium barbarum significantly reduced the retinal ganglion cells loss against elevated intraocular pressure. They have also shown that the neuroprotective effects were, partly, mediated by attracting immunocompetent cells infiltrating into the injured site of retina. Primary cortical neurons exposed to β-amyloid peptides results in apoptosis and necrosis. Extract of Lycium barbarum markedly reduced the number of apoptotic neurons and it may depend on the inhibition of the cJun Nterminal kinase signaling pathway [25].
Hawthorn is a wellknown herb in CM. The hawthorn extract was found to produce an effect in inducing endotheliumdependent nitric oxidemediated relaxation. The extract stimulates a significant increase in the total tissue content of cyclic guanosine monophosphate in arteries with endothelium, an index for the increased generation of nitric oxide. The data suggests that consumption of hawthorn may benefit vascular function via the endotheliumderived nitric oxidedependent mechanisms [26].
Yun from the Korea Institute for Cancer Chemoprevention did a 5year followup epidemiological study on the preventive effects of Panax ginseng against cancer. A cohort of 4,634 participants entered the study. The relative risks in ginseng consumers for gastric cancer and lung cancers were 0.33 and 0.30 respectively, whereas a decreased risk for stomach cancer was observed only in fresh ginseng extract consumers [27].
Danggui buxue tang (DBT) is deemed to be an effective prescription for the relief of menopausal symptoms by raising the vital energy and nourishing the body circulation of individual. Even though the experienced formula has been used for more than 800 years, research is still needed to verify the therapeutic mechanism and to identify the optimal drug ratio of the two main ingredients Radix astragali (RA) and Radix angelicae sinensis (RAS). The formula prepared from different drug ratios was applied onto cultured Tlymphocytes and macrophages. In the cultured Tlymphocytes, DBT induced the cell proliferation markedly, the secretion of interleukin-2 and the phosphorylation of extracellular signalregulated kinase. In addition, the phagocytosis of cultured macrophages was increased by DBT treatment. The immunomodulatory effects of DBT were revealed to be the strongest in extract derived from the drug ratio of 5:1 (RA:RAS). These results verified that the ancient formulation of DBT has been optimized in stimulating the immune responses [28].
Experimental evidences show that compounds isolated from CM of activating blood circulation to remove blood stasis can gain beneficial bioresponses to the interaction of blood flow. The effectiveness of a medicine may be significantly modified when mechanical factors are present. As a consequence of merging the biomechanical and pharmacological factors, a borderline new term “biomechanopharmacology” came into use. Investigation into the shear stress effects of flowing blood together with the CM of activating blood circulation to remove blood stasis may write a new chapter in disease prevention and healthcare [29].
Acupuncture points located along the meridian pathways are suggested as energy connections from the surface of the body to the internal organs and to the environment. Ma,et al.from the University of California used modern technologies to reveal that nitric oxidecyclic guanosine monophosphate is physiologically released over and in the skin with a high level at acupuncture points. The stimulusevoked release is acupuncture point/meridian specific, which plays an important role in meridian functions, inducing signal transduction of therapeutic stimulations and physiological communication with the environment [30].
Lin from the University of California used the latest biomedical technologies to gain a better understanding of the beneficial effects of qigong practices on mindbody functions. Laser flowmetry demonstrated that certain qigong movements when coordinated with deep breathing cycles and mental relaxation are highly effective in enhancing peripheral blood flow. The transcranial measurement of oxyhemoglobin with photo migration spectroscopy showed that the breathholding phase of certain qigong breathing exercises leads to a large increase in brain oxygen content. The heart rate variability analysis of electrocardiograms and independent component analysis of electroencephalograms indicated that qigong medication induces a dual state of mental relaxation and concentration. Qigong practices were found to increase bioenergy emitted from hand in the form of heat (measured by infrared thermography), light (measured by single photon counting), and electricity (measured by gas discharge visualization). Physical strength in a weightlifting test also increased significantly. The electrical conductance at jingwell acupoints of the 12 major meridians was measured with the single square voltage pulse method, it was shown to increase significantly following qigong practices and acupuncture but not physical exercises. These studies showed that qigong practices can lead to measurable enhancement of mindbody functions and bioenergy levels [31].
Huang,et al.from the ChiMei Medical Center (Taiwan) found that Radix astragali extract could stimulate RAW 264.7 cells and splenocytes proliferation via scavenging nitric oxide radical. In addition, it also significantly increased the rate of recovery of white blood cell level in the BALB/c mice model back to a normal status. The data suggest that Radix astragali may be an effective dietary supplement for ameliorating deleterious side effects from chemotherapy in cancer patients [32]. These results were in line with the previous findings of the writer [33].
SYSTEMS BIOLOGY AND CHINESE MEDICINE
Systems biology is a new emerging discipline of active research which aims to understand the system properties of the biological processes from cell level to human physiology. System properties of such complex systems can be revealed with the help of mathematical models which stimulate their dynamic behavior. These mathematical models are solved by numerical methods with supercomputers, so systems biology requires the integration of information technology and biology. Although it seems quite different from the experiencebased traditional methods and qualitative theories of CM, there are important similarities between systems biology and CM. Chinese medicine has always conceived human physiology from a holistic point of view, the body is considered as a system which interacts with the environment. If systems biology would help to explain and verify some fundamental aspects of CM, such scientific explanation may lead to new innovations and breakthroughs in the understanding of human physiology, as well as enhances the development of new therapeutic strategies and medicines. Examples include the similarity of circadian rhythms studied by modern chronobiology and the circulatory activation of medians in CM, as well as the similarity of the stimulation of synergistic effects of multicomponent herbs in CM and the need to develop new macroscopic concepts in systems biology [34].
Chinese medicine is characterized with complexity and holism in both diagnostic and therapeutic principles, a feature very similar to the systems biology bases. Very often, it makes the functional investigation of CM difficult to perform with conventional individual assays. It is believed that the highthroughput functional genomic tools will pave the way for functional screening, at both in vitro and in vivo level, of the compounds isolated from CM for the therapy of different human diseases in a combinatorial manner. On the other hand, the application of these tools will greatly facilitate the elucidation of the functional mechanisms of CM in a systematic way [35].
CONCLUSION
In the 2006 World Congress on Chinese Medicine, the direction, new technologies and some recent progress in CM provided a wealth of information for policymakers, scientists, CM practitioners, clinicians and healthcare professionals regarding globalization and modernization of CM. High standard scientific researches and clinical trials reported in the congress presented good examples for CM studies. Covering a broad range of topics, it provided an excellent platform for delegates to exchange ideas and explore ways to meet the increasing challenge of CM in the new millennium. Delegates could share the latest discoveries and trends across the entire spectrum of CM. For those who did not attend the meeting, this article may serve as a highlight of this important international CM meeting.
REFERENCES
1. Wagner H. Synergy research: A new approach to evaluate the efficacy of multi herbal drug combinations in traditional Chinese medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,3.
2. Moher D. So you want the evidence: challenges facing its generation, synthesis and reporting [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,4.
3. Chen KJ, Xu H. The difficulties and strategies of integrative Western and Chinese medicine in preventing and treating coronary heart disease [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,5.
4. Sung J. Collaboration of Chinese and Western medicine in research [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,6.
5. Li YM. Different perspectives of acupuncture practice in the east and west [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,35.
6. Hui KK. Chinese medicine coming of age for healthcare in the new millennium [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,14.
7. Li YP, Wu TX, Li J, et al. Chinese evidencebased medicine centres strategy and measures about promoting traditional Chinese medicine modernization [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,110.
8. Choi SH. WHO traditional medicine strategy and activities [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,10.
9. Tsim KW. Danggui buxue tang (a Chinese Angelica decoction): A sample trial in traditional Chinese medicine standardization [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,127.
10. Cai SQ. Several key links in quality standardization of Chinese drugs [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006, 53.
11. Bian ZX, Moher D, Li YP, et al. CONSORT of traditional Chinese medicine Opportunities and challenges for traditional Chinese medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,112.
12. Kim YS. A new strategy for the standardization of herbal medicines in Korea [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,63.
13. Lai SL. Considerations of enhancing evidencebased practice of traditional Chinese medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,102-104.
14. Levin JS, Glass TA, Kushi LH, et al. Quantitative methods in research on complementary and alternative medicine. A methodological manifesto. NIH Office of Alternative Medicine. Quantitative methods in research on complimentary medicine: A methodological manifesto. Med Care 1997, 35(11): 1079-1094.
15. Collet JP, Xu WN, Shapiro S. Traditional Chinese medicine strategic development: Importance of pragmatic trials in the evaluation process [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,105.
16. Zaslawski C. Ethical considerations and their impact on Chinese medicine and acupuncture clinical research [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,107.
17. Wu W, Liang ZT, Zhao ZZ, et al. MALDITOF MS for the direct analysis of components in herb tissues [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,51.
18. Cho WC, Chung WS, Lee SK, et al. Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocininduced diabetic rats. Eur J Pharmacol,2006,550(1-3): 173-179.
19. Cho WC. Research progress in SELDITOF MS and its clinical applications. Chin J Biotechnol,2006,22(6): 871-876.
20. Cho WC, Yip TT, Chung WS, et al. Altered expression of serum protein in ginsenoside Re treated diabetic rats detected by SELDI-TOF MS. J Ethnopharmacol,2006,108(2): 272-279.
21. Chiu JF. Proteomic approach to study the cytotoxicity of dioscin, a saponin of Polygonatum zanlanscianenense pamp [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,73.
22. Fong WF, Tse AK, Poon KH, et al. Magnolol and honokiol enhance HL-60 human leukemia cell differentiation induced by 1,25dihydroxyvitamin D3 and retinoic acid. Int J Biochem Cell Biol,2005,37(2): 427-441.
23. Luo K, Tian HL, Ip L, et al. A fluorescence resonance energy transfer (FRET)based high throughput drug screening method for discovery of anticancer compounds from herbal medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,75.
24. Lin ZX, Lau CS, Leung PS, et al. Brucea javanica induces cell cycle arrest and apoptosis in human pancreatic ductal adenocarcinoma cell lines [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,136.
25. So KF, Chang RC. Molecular basis of neuroprotection in glaucoma and Alzheimers disease using gouqizi [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,84.
26. Huang Y, Chen ZY. Medicinal plants and endothelial cell protection [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,129.
27. Yun TK. Epidemiological studies on intakers of Panax ginseng CA Meyer: Can this herb prevent all kings of cancer [Abstract]? In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006, 128.
28. Dong TT, Zhao KJ, Gao QT, et al. Chemical and biological assessment of a Chinese herbal decoction containing Radix Astragali and Radix Angelicae Sinensis: Determination of drug ratio in having optimized properties. J Agric Food Chem,2006,54(7): 2767-2774.
29. Liao FL. Biomechanopharmacological annotation for the therapeutic principle of activating blood circulation to remove stasis [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,86.
30. Ma SX, Li XY, Lim N, et al. Biochemical physiology of nitric oxidecGMP on the skin acupuncture points and meridians: An innovative approach in humans [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,40.
31. Lin S. New approaches to this study of physiological and bioenergetic changes associated with qigong/tai chi practices [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU,2006,46.
32. Huang GC, Weng BC, Lee CJ, et al. Immunomodulatory effects of Radix astragali (Huangqi) extracts on nitric oxide inhibition and splenocytes proliferation [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,158.
33. Cho WC, Leung KN. In vitro and in vivo antitumor effects of Astragalus membranaceus. Cancer Lett; in press.
34. Heiskanen T. Systems biology and traditional Chinese medicine: What they have in common and what they can learn and benefit from each other [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,76.
35. Hu YH. Development of highthroughput functional genomic tools a potential application for the research and development of Chinese medicine [Abstract]. In: World Congress on Chinese Medicine: Charting the Course of Development. Hong Kong: School of Chinese Medicine, HKBU, 2006,70.
(Editor Hou)(William ChiShing Cho)