世界卫生组织传统医学合作中心2011年年度报告---英文版

1. Implementation of the work plan. For each main activity briefly explain how the activity was implemented, the outcome and impact and, if available, the results of the evaluation (e.g. evaluation of a course by the participants). Also explain difficulties (if any). Do not provide technical results in this form (technical results, if applicable, are to be sent directly to the WHO Department you work with).
 
Activity 1 To carry out clinical research on acupuncture or herbs for validating its safety and efficacy
Explanation: 
1. Clinical manipulative principle of acupuncture analgesia for skull surgeries
The clinical results showed that acupuncture anesthesia can decrease the dose of propofol (an anesthetic), shorten the analepsia time and relieve the postoperative pain in skull surgery. We set up the manipulative principles for further studying and practicing in Clinic.
1.2 Acupuncture for the prevention and treatment of radiation-induced xerostomia
Xerostomia (dry mouth) is a common symptom of cancer patient who have received radiation treatment on the head and neck. Research suggests that acupuncture is useful in treating radiation-induced xerostomia. The patients in the acupuncture group were received acupuncture three times a week during radiotherapy. We evaluate the efficacy of acupuncture by using both subjective and objective methods. The results showed that acupuncture can significantly reduce xerostomia and improve the quality of life during radiotherapy.
1.3 Herbal Therapy in Pancreatic Cancer
Pancreatic adenocarcinoma is one of the most common tumors in digestive tract.  Herbal therapy is applying widely in Shanghai, China. We summarized 8 years of clinic and experimental study based on evidence medicine from 2002-2009. The study showed that Qingyihuaji Formula (QYHJ) had the great effects on anti-pancreatic cancer. Integration of chemotherapy combined with external irradiation and QYHJ-based traditional Chinese herbs together may benefit to patients with advanced pancreatic cancer, offering longer overall survival than other treatments.
 
Activity 2 To carry out experimental research on the action mechanisms of acupuncture in order to improve its usefulness by methods of neurophysiology, neuromorphology, neuropharmcology and molecular biology
Explanation:
2.1 Study of acupuncture analgesia
2.1.1 Involvement of spinal neurotrophin-3 in electroacupuncture (EA) analgesia and inhibition of spinal glial activation in rat model of monoarthritis
The present study demonstrated that the involvement of spinal neurotrophin-3 (NT-3) in EA’s analgesic effects on complete Freund’s adjuvant (CFA)-induced inflammatory pain: 1) repeated EA stimulation of ipsilateral GB30 and GB34 acupoints remarkably suppressed CFA-induced hyperalgesia; 2) EA treatment markedly enhanced the upregulation of spinal NT-3 mRNA and protein levels following CFA injection; 3) antisense oligodeoxynucleotides (ODN) specifically against NT-3 intrathecally administered during EA treatment for 7 days significantly attenuated the EA analgesia; and 4) the suppressed expression of spinal GFAP (astrocytic marker), OX-42 (microglial marker) as well as proinflammatory cytokines, interleukin IL-1β, IL-6 and tumor necrosis factor TNF-α by EA treatment was significantly attenuated following NT-3 antisense ODN delivery. These results suggested that endogenous NT-3 may be involved in the analgesic effect of EA on inflammatory pain in rats, mediated through the inhibition of spinal glial activity as well as proinflammatory cytokine production. The present study may initiate a discussion on the possible roles of NT-3/glia/cytokines in the therapeutic effects of acupuncture and provide insight on the mechanism underlying the analgesic effects of acupuncture on pain associated with arthritis
2.1.2 Pilot study of interleukin-33 and its roles in the central nervous system and acupuncture analgesia
Interleukin-33 (IL-33), a newly recognized IL-1 family member, is expressed by various tissues and cells. Since it can combine with chromosomes, IL-33 is regarded as an intracellular transcription repressor. Upon proinflammatory stimulation, it is released as an extracellular cytokine to function as an alarm into dangerous signals. The IL-33 receptor is a heterodimer complex composed of ST2 and the IL-1 receptor accessory protein, the latter being conserved in other IL-1 family members. The IL-33/ST2 signaling pathway plays critical roles in inflammatory disease and diseases of immune system and central nervous system (CNS). Recently, there has been an increasing focus on IL-33, particularly on its production and functions in the CNS. The present review mainly focuses on progress in research on IL-33, especially its roles in the CNS. It also plays a role and shows potential perspective in research of acupuncture analgesia. 
 
2.1.3 A rat model of bone inflammation-induced pain by intra-tibial complete Freund’s adjuvant injection
It has been reported that, due to differences in afferent innervation, the same stimulus to various tissue types might result in differing patterns of pain response. Hence, the aim of this study is to establish a rat model of bone inflammation-induced pain (BIIP) by injecting complete Freund’s adjuvant (CFA) into the tibial cavity. The results showed that there was evidence of significant inflammation seen in the bone marrow two days after intra-tibial CFA injection, including nuclear condensation and fragmentation, massive neutrophilic granulocytes, and prominent fibrinous exudates. Fourteen days after injection, marked fibrosis of the bone was detected by histological staining. After unilateral CFA injection, behavioral studies showed mechanical allodynia to von Frey hair stimulation, but no thermal hyperalgesia was observed. Celebrex showed significant anti-allodynic effects on the BIIP model. The results demonstrated that CFA is an effective agent for inducing bone inflammation and subsequent pain-related behavior in rat models, and, thus, provides a practical and valuable contrast for BCIP research.
2.2 Study on neuroendocrine regulation by electroacupuncture treatment
2.2.1 Elevated estrogen receptor expression in hypothalamic preoptic area was decreased by electroacupuncture in ovariectomized rats
In this study, effects of EA on estrogen receptor alpha (ERα) and beta (ERβ) mRNA and protein expression in the hypothalamus of ovariectomized (OVX) rats were detected by quantitative real-time reverse transcription PCR (qRT-PCR) and western blot analysis. Gonadotropin-releasing hormone (GnRH) release and GnRH mRNA level in hypothalamic preoptic area (POA) were evaluated by push–pull perfusion and qRT-PCR. Our results showed that elevated mRNA and protein expression of ERα and ERβ in hypothalamus were restrained following EA treatment in OVX rats. EA treatment also inhibited GnRH release and GnRH mRNA levels in OVX rats. These results provide novel evidence that EA treatment down regulates the expression of hypothalamic estrogen receptors (ERs), thus restores the response of GnRH neurons to estrogen depression, and partially resets the negative feedback of estrogen to hypothalamus–pituitary–ovary axis (HPOA) in OVX rats, which may be a critical mechanism for EA on female reproductive disorders.
 
2.2.2 Effects of androgen and leptin on behavioral and cellular responses in female rats and on the role of electroacupuncture
The causes of anxiety and depression in women with polycystic ovary syndrome (PCOS) remain elusive. To identify steps linking androgen signaling to the regulation of affective symptoms in vivo, we compared behavioral responses in female rats continuously exposed to dihydrotestosterone (DHT) from puberty (a model of DHT-induced PCOS) and in rats exposed to DHT for 1 week. Continuous and 1 week of DHT exposure resulted in a general decrease in locomotor activity and time spent on the open arms in the elevated plus maze, indicating anxiety-like behavior. Rats with DHT-induced PCOS have increases in adiposity and circulating leptin levels accompanied by leptin resistance. One week of DHT exposure decreased androgen receptor (AR) expression in the hypothalamus and leptin synthesis and function in adipocytes; it also inhibited signal transducer and activator of transcription 3 (STAT3) and attenuated leptin activity by increasing levels of soluble leptin receptor, a leptin-binding protein, in the hypothalamus. This may affect the androgen-induced anxiety-related behavior in female rats. In conclusion, our results highlight the central role of androgens in behavioral function in female rats and suggest that androgens directly regulate the AR by decreasing its hypothalamic expression. Androgens also increase leptin synthesis in adipocytes, which drives central leptin signaling, and may regulate anxiety related behaviors. Elucidating mechanisms by which androgens modulate female anxiety-like behavior may uncover useful approaches for treating women with PCOS who have symptoms of anxiety. In PCOS rat model, we adopted the “Guilai” (ST 29) and “Sanyinjiao” (SP 6), EA treatment showed no obvious effect on disorders behaviors. 
 
2.3 Study on neuroimmuno-regulation by electroacupuncture treatment
2.3.1 Neuron-Glial Cell Communication in the Traumatic Stress-Induced Immunomodulation
We have previously reported that neuron and glia could collaboratively govern the immunomodulation in traumatic rats. Herein, we characterized the sequential involvement of cortical neuron, microglia, and astrocytes in the traumatic stress mediated neuroimmune modulation. At day 1 of trauma, transient extracellular signal related kinase 1/2 (ERK1/2) activation was initiated in neuron and microglia, which was accompanied by RSK-1 expression in the cytosol. At day 3 of trauma, persistent ERK1/2 activation occurred in astrocytes, which were destined for the nucleus leading to Elk-1 expression. Furthermore, the functional overlap of ERK1/2 and neuroligin 1 in astrocytes was strengthened at day 3 of trauma and responsible for the recovery from the immnosuppression. These effects could be disrupted by β-neurexin blockade. Altogether, we proposed the mechanism underlying the traumatic stress-induced immunosuppression, in which local activity ensured the initial establishment of neural circuitry in the frontal cortex. ERK1/2-signaling events are required for the temporal and spatial coordination between neuron and glial cells.
 
2.3.2 Neuroimmune modulation following traumatic stress in rats: evidence for an immunoregulatory cascade mediated by c-Src, miRNA222 and PAK1
Neuroimmune modulation following traumatic stress is accompanied by cortical upregulation of c-Src expression, but the mechanistic details of the potential regulatory link between c-Src expression and immunosuppression have not been established.  We used a combination of techniques to measure temporal changes in: (i) the parallel expression of c-Src and microRNA222; (ii) levels of PAK1 (p21-activated kinase 1); and (iii) the association between PAK1 and interleukin 1β signaling, both in cortex of rats following traumatic stress and in primary cortical neurons. Techniques included realtime PCR, immunoprecipitation, western blotting and subcellular fractionation by discontinuous centrifugation. We also measured lymphocyte proliferation and natural killer (NK) cell activity.  We confirm robust upregulation of c-Src expression following traumatic stress. c-Src upregulation was accompanied by marked increases in levels of miRNA222; other studied miRNAs were not affected by stress. We also established that PAK1 is a primary target for miRNA222, and that increased levels of miRNA222 following traumatic stress are accompanied by downregulation of PAK1 expression. PAK1 was shown to mediate the association of IL-1RI with lipid rafts and thereby enhance IL-1 signaling. Detailed analyses in cultured neurons and glial cells revealed that PAK1-mediated enhancement of IL-1RI activation is governed to a large extent by c-Src/miRNA222 signaling; this signaling played a central role in the modulation of lymphocyte proliferation and NK cell activity.
 
Activity 3 To provide training opportunities for foreign scientists and medical doctors on both scientific research and clinical practice
Explanation:
3.1 WHO collaborating center for traditional medicine, institute of acupuncture research ,department of integrative medicine and neurobiology, Shanghai Medical College, Fudan University cooperated with the doctors from hospitals affiliated Shanghai Medical College of Fudan University (Zhong-Shan Hospital, Hua-Shan Hospital, Fudan University Shanghai Cancer Center, etc) treated over 10620 person-time patients suffering from various diseases with therapeutic method of integration of Traditional Chinese Medicine and Western Medicine including acupuncture treatment. Four physicians and acupuncturists who came from United States and Germany were trained in the Department of Acupuncture, the Hua-Shan Hospital for one week in 2011.
3.2 Four Ph.D. students fulfilled Ph.D. degree, and one finished her Master degree in this year.
3.3 The course of ‘The outline of fundamental of integrative medicine” was given to 40 graduate and 60 undergraduate students. The course of “The idea and method of integrative medicine” and “Principles of neural sciences” were given to 20 junior or senior graduate students. The course of “How to conceive, write and publish the scientific papers” invited the domestic and aboard famous speakers for 197 master and Ph.D. students.
3.4 Five domestic research fellows and one post-doctor were trained in our center, each for about six months to two years.
3.5 24 undergraduate students carried out their practice or scientific activities with the instruction of teachers in our center for 1 year.
 
2. Other information related to the Collaboration between the centre and WHO. Briefly describe visits by WHO staff to the centre, visits by the centre staff to WHO (HQ and/or Regional Office), use of the centre staff by WHO, support provided by centre staff for courses cosponsored or organized by WHO (HQ and/or Regional Office), WHO financial support to the centre through contractual or Technical Services Agreement or other type of support provided by WHO, any other collaborative activities. Please mention any difficulties encountered in the collaboration and suggestions for increased and improved collaboration with WHO.
On 15th July, 2011, the 5th Director Meeting of Shanghai WHO CCs for TRM was held in Shanghai. Prof. Gencheng Wu and Yi Feng attended this meeting and joined the discussion with other WHO CCs about the next five-year development.
On 8-10th December, 2011, Prof. Gencheng Wu and Yanqing Wang attended the Sixth Meeting of Directors of WHO Collaborating Centers for Traditional Medicine in Beijing. During the meeting, we received the guidance for further work of our center from Dr. Qi Zhang, the director of WHO CC for Traditional Chinese Medicine, and Dr. Narantuya Samdan, the medical manager of WHO WPRO. They both had friend and instructed discussions with us. 
On 8-10th February, 2012, associated Prof. Yi Feng joined the “Directors Meeting of WHO Collaborating Centers in China 2012 and the Launch Ceremony of the China/ WHO Regular Budget  Projects of Biennium 2012-2013 ”.
As a member of WHO Expert Advisory Panel on Traditional Medicine, Prof. Xiao-Ding Cao has been keeping close contact with WHO and giving her suggestions on some issues about the policy of Traditional Medicine or Complementary and Alternative Medicine.
We shall always pay attention to the instructions from WHO and WPRO, and try to do our best for the great goal of world health.
 
3. Collaboration with other WHO Collaborating Centres: Briefly describe the nature and outcome of the collaboration and the name(s) of the other WHO collaborating centre(s) with which the centre has collaborated. If applicable, please mention the name of the network of WHO CCs to which the centre belongs. Also include suggestions for increased and improved collaboration with other WHO CC
Activities of our center also include the collaboration with other WHO collaborating centers in other countries as well as in China. In China, we collaborated and interchanged with other Traditional Medical Centers and did some joint researches, such as Shanghai University of TCM, Chinese Academy of TCM in Beijing and Nanjing University of TCM. Furthermore, we have established the scientific relationship with other WHO collaborating centers for other medical fields in China. We also shared some information with the other WHO collaborating centers in other countries.
 

Publication list in 2011
.Qiong Liu, Bing Li, Hai-Yan Zhu, Yan-Qing Wang, Jin Yu, Gen-Cheng Wu, Glia atrophy in the hippocampus of chronic unpredictable stress-induced depression model rats is reversed by electroacupuncture treatment,Journal of Affective Disorders 128 (2011) 309–313 
.Shulan Ma, Jihong Wu, Yi Feng, Boying Chen,Elevated estrogen receptor expression in hypothalamic preopticarea decreased by electroacupuncture in ovariectomized rats,Neuroscience Letters 494 (2011) 109–113 
.Wen-Li Mi, Qi-Liang Mao-Ying, Xiao-WeiWang, Xiu Li, Chang-Jiang Yang, Jian-Wei Jiang, Jin Yu, Jun Wang, Qiong Liu, Yan-Qing Wang and Gen-Cheng Wu,nvolvement of Spinal Neurotrophin-3 in Electroacupuncture Analgesia and Inhibition of Spinal Glial Activation in Rat Model of Monoarthritis,The Journal of Pain 12(2011) 974-984 
.Chang-Jiang Yang, Xiao-Wei Wang, Xiu Li, Gen-Cheng Wu, Yan-Qing Wang, Qi-Liang Mao-Ying,A rat model of bone inflammation-induced pain by intra-tibial complete Freund’s adjuvant injection,Neuroscience Letters 490 (2011) 175–179 
.Hui Zhao, Ranran Yao, Xiaoding Cao, Gencheng Wu, Neuroimmune modulation following traumatic stress in rats: evidence for an immunoregulatory cascade mediated by c-Src, miRNA222 and PAK1,Journal of Neuroinflammation 8 (2011) 159 
.6.  Hui Zhao, Sheng Xiao, Xiaoyan Kong, Jun Wang, Xiaoding Cao, Gengcheng Wu, Horace Hlon,  Ping-Yee Law,  Neuron-Glial Cell Communication in the Traumatic Stress-Induced Immunomodulation, Synapse 65 (2011) 433–440 
.Ping Han, Wen-Li Mi, Yan-Qing Wang,Research progress on interleukin-33 and its roles in the central nervous system, Neurosci Bull, 27 (2011) 351–357 
.Yi Feng, Ruijin Shao, Birgitta Weijdegård, Tienpei Wang, Julia Johansson, Shan Sun, Wei Wang, Emil Egecioglu, Håkan Billig and Elisabet Stener-Victorin. Effects of androgen and leptin on behavioral and cellular responses in female rats. Horm Behav. 60 (2011) 427-38 

 

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