1. Work performed in relation to the Terms of Reference
1.1 To develop clinical research on acupuncture for validating its safety and efficacy;
1.2 To carry out the experimental research on the mechanisms of acupuncture to improve its application, with particular reference to its neurophysiological, neuromorphological, neuropharmacological and molecular biological techniques;
1.3 To provide training opportunities for foreign scientists and medical doctors on both scientific research and clinical practice. 
2. Main performance in 2010
2.1 Clinical trials
2.1.1 Doctors from hospitals affiliated Shanghai Medical College of Fudan University (Zhong-Shan Hospital, Hua-Shan Hospital, etc) treated over 8851 person-time patients suffering from various diseases with therapeutic method of integration of Traditional Chinese Medicine and Western Medicine including acupuncture treatment.
2.1.2 Four physicians and acupuncturists who came from United States and Germany were trained in the Department of Acupuncture, the Hua-Shan Hospital in 2010 for one week.

2. 2 Experimental researches
2.2.1 Study of acupuncture analgesia To observe the effects of electroacupunture ( EA) on the abnormal hypothalamus-pituitary- adrenal ( HPA) axis and the expression of hypothalamic corticotrophin-releasing factor ( CRF) peptides family and CRF receptor( R) 1 mRNA in traumatized rats, so as to study its underlying mechanism in improving traumatic injury. The results showed EA of Zusanli( ST 36) and Sanyinjiao (SP 6) can improve surgical trauma-induced HPA disorders, which is probably related to its effects in upregulating CRF mRNA expression and downregulating Ucn1 mRNA expression in the hypothalamus. High density Nociceptin/Orphanin FQ (N/OFQ) and its receptor (NOPr) have been found in the ventrolateral periaqueductal gray (vlPAG), a main output pathway involved in the descending pain-control system. The present work was to further provide evidence for the supraspinal mechanisms of action for N/OFQ-mediated nociceptive facilitation by examining the effect of N/OFQ in the vlPAG on neurotransmitter release in the descending pain-control system. The results showed that the microinjection of N/OFQ into the vlPAG produced robust decreases in 5-hydroxytryptamine (5-HT, serotonin), norepinephrine (NE), and γ-aminobutyric acid (GABA), and increase in glutamate (Glu) release in the spinal dorsal horn. Spinal application of 5-HT, 2-Me-5-HT (5-HT3 receptor agonist), muscimol (GABAA receptor agonist), and baclofen (GABAB receptor agonist) significantly blocked intra-vlPAG-induced facilitation on nociceptive responses. These findings provide direct support for the hypothesis that intra-PAG of N/OFQ-induced facilitation of nociceptive responses is associated with the release of 5-HT, NE, and amino acids. Accumulated evidence shows that endogenous formaldehyde concentrations are elevated in the blood or urine of patients with breast, prostate or bladder cancer. These cancers are frequently associated with cancer pain especially after bone metastasis. It is well known that transient receptor potential vanilloid receptor 1 (TRPV1) participates in cancer pain. The present study aims to demonstrate that the tumor tissue-derived endogenous formaldehyde induces bone cancer pain via TRPV1 activation under tumor acidic environment.
2.2.2 Study on neuroendocrine regulation by EA treatment and Chinese herbs The present study aims to investigate the effect of nourishing “Yin”-removing “Fire” herbal mixture, a Chinese herb-based formulation, on hypothalamic kisspeptin expression in danazol-induced female precocious model rats. The female Sprague–Dawley rats were divided into intact normal (N), central precocious puberty (CPP) model (M), vehicle without CPP (V), CPP model exposed to herbal mixture (HM) and CPP model exposed to saline (S) groups. The day of vaginal opening and establishment of two regular estrous cycles were delayed in the HM group compared with M and S groups. The level of hypothalamic Kiss-1 mRNA and the number of kisspeptin-immunoreactive (kisspeptin-ir) cells in the arcuate nucleus (ARC), preoptic area (POA) and periventricular nucleus (PeN), were decreased significantly in the HM group on the day of onset-puberty. These results indicate that the kisspeptin signaling pathway might be involved in the effect of herbal mixture treatment on CPP.. Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance, possibly reflecting defects in skeletal muscle and adipocyte insulin signaling. Low-frequency (2 Hz) electro-acupuncture (EA) increases insulin sensitivity in female rats with dihydrotestosterone (DHT)-induced PCOS, but the mechanism is unclear. We hypothesized that low-frequency EA regulates mediators involved in skeletal muscle glucose uptake and metabolism and alters the lipid profile in rats with DHT-induced PCOS. Thus, in rats with DHT-induced PCOS, low frequency EA has systemic and local effects involving intracellular signaling pathways in muscle that may, at least in part, account for the marked improved insulin sensitivity. Based on the previous study of electro-acupuncture on polycystic ovary syndrome (PCOS), in this report, we showed that the distribution of AR immunoreactivity in the female rat brain is consistent with reported AR mRNA hybridisation signals in the male brain, except for the dentate gyrus of the hippocampus. Immunohistochemical and Western blot analyses performed herein revealed that the onset of region-specific changes in AR proteins was strongly correlated with circulating and ovarian levels of estradiol and testosterone across the oestrous cycle. During the metestrus and diestrus stages, however,the highest levels of AR expression were abolished by chronic dihydrotestosterone (DHT) treatment. This demonstrates that fluctuations in endogenous androgens are required for the regulation of AR expression in the female rat brain.
2.2.3 Study of acupuncture and drug against depression. 
Growing evidence indicates that glia atrophy contributes to the pathophysiology and possibly the pathogenesis of major depressive disorder. Electroacupuncture (EA), has potent antidepressant-like effect in many clinical studies. The mechanism by which EA improves behavioral deficits is still unclear.  Chronic unpredictable stress (CUS)-induced depression model rats were used to study the effect of EA treatment. EA was performed on acupoints ‘Bai-Hui’ (Du 20) and unilateral ‘An-Mian’ (EX 17) once daily for three consecutive weeks two weeks post CUS procedure. The antidepressant-like effect of EA treatment was analyzed by physical state (PS) and open field test. Results showed exposure to CUS resulted in a decrease of behavioral activity, whereas a daily session of EA treatment significantly reversed the behavioral deficit of these depression model rats. Moreover, the levels of GFAP mRNA and protein were decreased in the hippocampus of depression model rats. Intriguingly, EA treatment blocked effectively the decreased GFAP level. Therefore,EA has potential antidepressant-like effect on CUS-induced depression model rats, which might be mediated by affecting the glial atrophy in the hippocampus.
2.2.4 Study on neuroimmuno-regulatory effect of EA
Immunological changes initiated by major operative injury may result in inflammatory responses in both peripheral and central nervous system, which may lead to organ dysfunction. Recent studies indicate that β-adrenergic receptors (β-ARs) may mediate production of pro-inflammatory cytokines in the brain. In the present study propranolol (β-AR antagonist), but not prazosin (α1-AR antagonist), antagonized surgical trauma induced pro-inflammatory cytokine production in microglia cells isolated from rats. Both ERK1/2 and P38 MAPK inhibitor, but not PKA and JNK1/2 inhibitor abrogated isoproterenol-induced IL-1β and IL-6 production in microglia cells. In conclusion, the results suggest that β-ARs possess pro-inflammatory properties by modulating the functions of microglia cell.
2.2.5 The English monograph “Acupuncture Therapy for Neurological Diseases”,which was edited by Prof. Ying Xia, Gen-cheng Wu, Xiao-ding Cao and Jie-shi Cheng was published by Springer Publishing House (Germany) and Tsing Hua Publishing House (China). This book will be an important tool for Acupuncture Therapy for international acupuncturists.
In 2010, our center published 9 research articles totally, 8 of them are SCI papers in English. 

2.3 Training program
2.3.1 Two Ph.D. students (Xiu Li and Xiaomin Feng) fulfilled Ph.D. degree, and one finished her Master degree in this year (Yan Zhang).
2.3.2 The course of ‘The outline of fundamental of integrative medicine” was given to 40 graduate and 80 undergraduate students. The course of “The idea and method of integrative medicine” and “Principles of neural sciences” were given to 10 junior or senior graduate students.
2.3.3 Five domestic research fellows (Shudong Yu, Cuicui Wang, Xia Xiao, You Ning and Bing Wu) were trained in our center, each for one to six months. One post doctor was trained for her second year in our center.
2.3.4 20 undergraduate students carried out their practice or scientific activities with the instruction of teachers in our center.
2.3.5 In June of 2010, our center held “The 10th Symposium on Acupuncture Anesthesia and Acupuncture Analgesia in China” in shanghai, providing an opportunity for 80 deputies to communicate and cooperate, as well as summarize the performance of above research.
2.3.6 Four physicians and acupuncturists from United States and Germany were trained in the department of acupuncture, the Hua-Shan hospital for one week

2.4 Academic exchange  
2.4.1 International and Domestic Exchange 
In January 2010, Associated Prof. Hui Zhao went to University of Minnesota as an advanced visiting scholar.
In February, Ph.D. student Bing Li took part in the meeting and training in Hongkong.
In February, Ph.D. student Xiaomin Feng and Xiaowei Wang participated in the IBRO (International Brain Research Organization) training in Japan.
In March, Assistant Prof. Yi Feng attended the 14th International Endocrinology Conference in Kyoto, Japan.
In May, Prof. Boying Chen and Prof. Yanqing Wang, as well as Dr. Yi Feng (assistant prof.) and Dr. Wenli Mi (assistant Prof.) attended the 4th Yale-China Acupuncture Symposium.
In August, Assistant Prof. Yi Feng took part in the short-time cooperation on acupuncture with Hamburg University in Germany and Gothenburg University in Sweden. 
       In November, Prof. Gencheng Wu and Prof. Yanqing Wang visited Taiwan and gave the speeches of Acupuncture on Analgesia and Immunologic Regulation in Tzu Chi University.
In 2010, some teachers and graduated students attended academic meetings domestically for 15 person-times.
2.4.2 International visiting to our center
In April, 2010, senior investigator Dr. Bonnie N. Dittel, Blood Center of Wisconsin University visited our center.
In October, 2010, Prof. Jochen Mau (Youcheng Mao), Dusseldorf University, Germany visited our center.
In 2010, Prof. Ying Xia, Medical Center, Yale University (currently in Medical Center, Texas University), USA, visited our center for three times, and cooperated to write the monograph about acupuncture research (English issue).
2.4.3 International consultation
In 2010, as a consultant of traditional medicine program in WHO, Prof. Xiao-Ding Cao received some documents inquiring the policy of Traditional Medicine and Complementary/Alternative Medicine from WHO, and gave some suggestions.

2.5 Evaluation
In 2010, through the efforts of all members of our center, we obtained some achievements in carrying on clinical practice and basic scientific research of acupuncture, and academic exchange and training at home and abroad.
3. Collaboration between the center and WHO 
On 15th June, 2010, the 4th Director Meeting of Shanghai WHO CCs for TRM was held in Shanghai. Dr. Shin Young-soo, WHO/WPRO director and H.E. Mr. Michael O'Leary, WHO represent in China, gave the speeches. Prof. Xiaoding Cao and Yangqing Wang attended this meeting.
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.
4.  Collaboration with other WHO collaborating centers
Activities of our center also include the collaboration with other WHO collaborating centers in other countries as well as in China. In China, we visited 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.
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.
5. Proposal in 2011
5.1 To establish new websites including Chinese and English versions to link to websites of WHO TRM directly.
5.2 To Further enhance the cooperation with Texas University of United States, Gothenburg University of Sweden and Hamburg University of Germany. We plan to dispatch 15 person-times to go abroad. They will join the conference, exchange the experience and promote the cooperation. Meanwhile, we will also give the training chances in the clinical treatment and scientific research from all over the world.
5.3 To revise the textbook ‘the outline of fundamental integrative medicine” and open new courses for general education for freshman in university and new elective courses for post-graduate students.
5.4 To finish the new writing of an English monograph “Translational Research on Acupuncture”,which will be published by Springer Publishing House again. This book will provide a great deal evidence for acupuncture research and application.
5.5 To develop the survey on “How to improve the teaching and disciplinary construction of integrated medicine in west medicine schools in modern China”, further deepen the concept of developing traditional medicine in west medicine schools.

Publication List in 2010: 
.Zhiqian Tong., Wenhong Luo., Yanqing Wang, Fei Yang, Ying Han, Hui Li, Hongjun Luo, Bo Duan, Tianle Xu, Qiliang Maoying, Huangying Tan, Jun Wang, Hongmei Zhao, Fengyu Liu, You Wan, Tumor Tissue-Derived Formaldehyde and Acidic Microenvironment Synergistically Induce Bone Cancer Pain. PLoS ONE 2010; 5(4): e10234. 
.Li Sun, Zhanzhuang Tian, Jianping Wang. A Direct Cross-talk Between Interferon-c and Sonic Hedgehog Signaling That Leads to the Proliferation of Neuronal Precursor Cells. Brain, Behavior, and Immunity 2010; 24: 220–228. 
.Julia Johansson, Yi Feng, Ruijin Shao, Malin Lönn, Håkan Billig, Elisabet Stener-Victorin, Intense Electro-Acupuncture Normalizes Insulin Sensitivity, Increases Muscle GLUT4 Content, and Improves Lipid Profile in a Rat Model of Polycystic Ovary Syndrome , Am J Physiol Endocrinol Metab 2010 Oct;299(4):E551-9. 
.Ning Lü, Mei Han, Zhi-Lan Yang, Yan-Qing Wang, Gen-Cheng Wu, Yu-Qiu Zhang, Nociceptin/Orphanin FQ in PAG modulates the release of amino acids, serotonin and norepinephrine in the rostral ventromedial medulla and spinal cord in rats. Pain 2010; 148: 414–425. 
.Yi Feng, Birgitta Weijdeg, Tienpei Wang, Emil Egecioglua, Julia Fernandez-Rodriguezd, Ilpo Huhtaniemie, Elisabet Stener-Victorina, Han Billig, Ruijin Shao, Spatiotemporal expression of androgen receptors in the female rat brain during the oestrous cycle and the impact of exogenous androgen administration: A comparison with gonadally intact males. Molecular and Cellular Endocrinology 2010; 321: 161-174. 
.Magdalena Nutu, Yi Feng, Emil Egecioglu, Birgitta Weijdegård, Elisabet Stener-Victorin, Ruijin Shao, Stromal cell–specific apoptotic and antiestrogenic mechanisms may explain uterine defects in humans after clomiphene citrate therapy. American Journal of Obstetrics & Gynecology 2010 203(1):65.e1-65. 
.Yan Sun, Genevieve Neal Perry, Jian Yu, Boying Chen, Zhanzhuang Tian, Effect of nourishing “Yin”-removing “Fire” Chinese herbal mixture on hypothalamic kisspeptin expression in female precocious rats, Journal of Ethnopharmacology 2010;127: 274–279. 
.Jun Wang, Jing Li, Sheng Xiao, Hui Zhao, Xiao-Ding Cao, Yan-Qing Wang, Gen-Cheng Wu, β-adrenoceptor mediated surgery-induced production of pro-inflammatory cytokines in rat microglia cells, Journal of Neuroimmunology 2010; 223:77–83. 
. Yan Zhang, Shulan Ma, Boying Chen and Zhanzhuang Tian. Effects of Electroacupuncture on the Expression of Corticotropin-releasing Factor (CRF) Family and CRF Receptor 1 in Traumatic Injury Rats. Acupuncture Research 2010; 35(3):163-169. (in Chinese)

Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences of Fudan University copyright © 2014

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