2013年3月7日 星期四

台灣大學傳統醫學研究社 社課演講 - 中醫是怎麼看病的? - 以望診及問診為例

台灣大學傳統醫學研究社
社課演講

題目:中醫是怎麼看病的? - 以望診及問診為例

日期:2013/03/07

時間:19:30-21:00

地點:台灣大學傳統醫學研究社
            台大校總區 新生大樓102教室

演講者:張清貿醫師
               長庚大學臨床醫學研究所博士班
               台北榮民總醫院傳統醫學中心


https://plus.google.com/u/0/photos/103267355442886687638/albums/5874176710809350305

大綱:


簡介
以前社會對中醫的觀感
從統計學角度看中醫理論
中醫系統論與系統工程學
什麼是中醫?
中醫是怎麼看病的
歷史上望診最有名的中醫
中醫在望什麼?
   –神色形
   –動態四肢
   –面、鼻、唇
   –
   –
中醫為什麼這樣問?
   –問頭痛
   –問腹部
   –問寒熱
   –問汗出
病案發揮
   –風寒感冒
   –風熱感冒

2013年3月4日 星期一

擁核?反核?


擁核?反核?
各有各的立場,大家都想用電,更想用便宜的電,更不想有污染或副作用,
諷刺的是風力發電造成當地居民的噪音污染,誰來承受,
支持核四續建的人,屢屢被激要不要抱一桶核廢料回家,
但我們常常忽略,你要不要也住在風力發電廠旁邊,

自然能源真的很自然嗎?核四廠真的安全嗎?
沒有人知道,也沒有人真正知道,

我想,目前最好的解決方法,
就是把核四廠蓋到釣魚台去,
一兼多顧,就不會有中日互搶釣魚台而忽略台灣!

我贊成公投,但不贊成降低公投門檻,
全台可以投票的人約佔3/4
如果只要一半有投票權的人出席,
再只要一半的人同意或不同意,
所以算下來粗略是2600W*(3/4)*(1/2)*(1/2)約不到500W,
這樣的population怎麼能代表母體呢?

公投門檻高,就是因為困難,
所以大家才要珍惜,
當無法衝過公投門檻人數,
應該不是降低門檻,
而是要教育普羅大眾。

降低公投門檻的作法,
就如同某次參加某單位的行政會議,
某主管要大舉減少學生代表名額,
理由是系上的老師代表少,因為師資嚴重不足,
如果大學部每個年級+碩博班,都各有一個代表,
那學生代表就會有16個,人數會逼近甚至超過老師代表人數,
因而影響系的政策制定,怕某些系務被學生反對而無法推動,
像這樣應該是增加師資,或是讓學生代表支持政策,
而不是把可以投票的學生砍到一半以下,
還好最終決定還沒這麼荒謬!!

但這兩件事都一樣可笑!!

2013年3月3日 星期日

張清貿醫師簡介 (2017/07/30 更新)


中醫藥實證醫學之探討
修格蘭氏症/乾燥症之中醫研究



學歷:
  1. 長庚大學臨床醫學所中醫組醫學博士候選人
  2. 長庚大學中醫學系傳統中醫學碩士班 
  3. 中國醫藥大學中醫系七年制


現職:
  1. 臺北榮民總醫院傳統醫學部主治醫師


經歷:
  1. 臺北榮民總醫院傳統醫學部總醫師
  2. 臺北榮民總醫院傳統醫學部住院醫師
  3. 中國醫藥大學附設醫院中醫部醫師 
  4. 臺灣市立聯合醫院陽明院區中醫科醫師
  5. 臺灣中醫臨床醫學會副秘書長

學會:

  1. 中華民國中醫師公會全國聯合會
  2. 臺北市中醫師公會
  3. 臺灣中醫臨床醫學會
  4. 中華針灸醫學會
  5. 臺灣中醫耳鼻喉科醫學會
  6. 中華國風濕病醫學會
  7. 中華民國免疫醫學會


獲獎:
  1. 106年臺北榮民總醫院最佳教學主治醫師獎, 2017
  2. 台北市中醫師公會2017年第87屆台北國醫節「第87屆國醫節中醫藥著作獎 - 學術論文類」, 2017
  3. 台北市中醫師公會2016年國醫節大會「中醫藥優良學術著作獎」, 2016
  4. 104年度退輔會臺北榮民總醫院「臨床教學績優醫師獎」, 2015
  5. 中國醫藥大附設醫院「優良實習醫學生獎」, 2010
  6. 中國醫藥大學校級研究成果發表會「口頭論文報告特優獎」, 2007

研究專長:
  1. Traditional Chinese Medicine in Allergy, Immunology, Rheumatology:中醫過敏風濕免疫學 
  2. CM Clinical trial:中醫藥臨床試驗 
  3. Sjögren syndrome:修格蘭氏症、乾燥症
  4. Systemic Lupus Erythematosus:紅斑性狼瘡 
  5. Systemic Sclerosis:硬皮症
  6. Bioinformatics:生物資訊

臨床專長:
  1. Sjögren syndrome/Sicca Syndrome (Dry Eye, Dry month):修格蘭氏症 /乾燥症 (口乾、眼乾)
  2. Systemic Lupus Erythematosus:紅斑性狼瘡 
  3. Systemic Sclerosis:硬皮症
  4. Rheumatoid arthritis:類風濕性關節炎 
  5. Autoimmune Rheumatic Diseases:自體免疫風濕疾病
  6. Allergic Rhinitis: 過敏性鼻炎 
  7. Insomnia/ Sleep disorder:失眠/睡眠障礙 
  8. Anxiety/Depressive disorder:焦慮、憂鬱症 
  9. Chronic Fatigue Syndrome: 慢性疲勞症候群 
  10. Sleep Obstructive Disease/Obstructive Sleep Apnea (OSA): 睡眠呼吸中止症 
  11. Gastrointestinal disorder:腸胃道疾病 
  12. Irritable Bowel Syndrome:大腸激躁症 
  13. Dizziness/Vertigo Disorder: 頭昏/眩暈 
  14. Hepatitis B/C: B/C型肝炎 
  15. Myofascial pain syndrome:筋肌膜炎症候群 
  16. Osteoarthritis:退化性關節炎 
  17. Acupuncture & Moxibustion: 針灸

博士論文研究:

 (2012-2017,2014/06/13通過資格考成為博士候選人,2017/07通過博士學位考試)

<中藥臨床試驗暨轉譯醫學研究>

  • 中文:中藥複方治療修格蘭氏症之療效評估及其抗氧化與免疫調控機轉之研究
  • 英文:The Efficacy of Chinese Herbal Formula on Sjögren's syndrome and its Mechanism of Anti-oxidative and Immune Modulatory Effects

聯絡資訊:
  • Ching-Mao Chang  (張清貿, C.M. Chang)
  • Center for Traditional Medicine, Taipei Veterans General Hospital
  • No.201, Sec. 2, Shipai Rd., Beitou District, Taipei City, Taiwan 11217, R.O.C
  • TEL: +886-2-28757453 #304
  • E-Mail: tcmcmc@gmail.com

歷年發表著作 (2016/08/30 更新)

Publication:




A: Referred Paper

  1. Hen-Hong Chang, Shue-Fen Luo, Yin-Tzu Hsue, Ching-Mao Chang, Tzung-Yan Lee, Ming-Ling Hsu, Yu-Chuen Huang, Yu-Jen Chen. Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments. Scientific Reports. 2016 (SCI, 2014 IF=5.578)
  2. Tom Fleischer, Tung-Ti Chang, Jen-Huai Chiang, Ching-Mao Chang, Ching-Yun Hsieh, Hung-Rong Yen*. Adjunctive Chinese Herbal Medicine Therapy Improves Survival of Patients with Chronic Myeloid Leukemia: A Nationwide Population-based Cohort Study. Cancer Medicine. 2016 (SCI, 2014 IF=2.5)
  3. Ching-Ying Huang, Wan-Yu Lai, Mao-Feng Sun, Che-Chen Lin, Bor-Chyuan Chen, Ching-Mao Chang, Hong-Jen Lin,  Chung-Hsien Yang, Kuo-Chin Huang, Hung-Rong Yen*. Prescription Patterns of Traditional Chinese Medicine for Peptic Ulcer Disease in Taiwan: A Nationwide Population-based Study. Journal of Ethnopharmacology. 2015 (SCI, 2014 IF= 2.998) 
  4. Ming-Cheng Huang, Fu-Tzu Paic, Che-Chen Lind, Ching-Mao Chang, Hen-Hong Chang, Yu-Chen Lee, Mao-Feng Sun, Hung-Rong Yen*. Characteristics of traditional Chinese medicine use in patients with rheumatoid arthritis in Taiwan: A nationwide population-based study. Journal of Ethnopharmacology. 2015 (SCI, 2014 IF= 2.998) 
  5. Fang-Pey Chen, Ching-Mao Chang, Jing-Huei Shiu, Jen-Hwey Chiu, Ta-Peng Wu, Jen-Lin Yang, Yen-Ying Kung, Fun-Jou Chen, Chang-Ming Chern* and Shinn-Jang Hwang*: A Clinical Study of Integrating Acupuncture and Western Medicine in Treating Patients with Parkinson's DiseaseThe American Journal of Chinese Medicine. 2015 (SCI, 2014 IF= 2.625) 
  6. Ching-Mao Chang, Hsueh-Ting Chu, Yau-Huei Wei, Fang-Pey Chen, Shengwen Wang, Po-Chang Wu, Hung-Rong Yen, Tzeng-Ji Chen* and Hen-Hong Chang*The Core Pattern Analysis on Chinese Herbal Medicine for Sjögren's syndrome: A Nationwide Population-Based StudyScientific Reports. 2015 (SCI, 2014 IF= 5.578) 
  7. Fang-Pey Chen, Ching-Mao Chang, Shinn-Jang Hwang*, Yu-Chun Chen and Fun-Jou Chen: Chinese herbal prescriptions for osteoarthritis in Taiwan: analysis of national health insurance dataset. BMC Complementary and Alternative Medicine. 2014 (SCI, 2014 IF=2.020)
  8. Ching-Mao Chang, Wen-Hsiang Wu, Benjamin Ing-Tiau Kuo, Tzung-Yan Lee, Chia-Yu Liu, Hen-Hong Chang*: Using A Questionnaire among Patient, Resident Doctor and Senior Supervisor: Are their Answers the Same? Complementary Therapies in Medicine. 2014 (SCI, 2013 IF=2.216)
  9. Hsueh-Ting Chu, Han Lin, Theresa Tsun-Hui Tsao, Chun-Fan Chang, William WL Hsiao, Tze-Jung Yeh, Ching-Mao Chang, Yen-Wenn Liu, Tse-Yi Wang, Ko-Chun Yang, Tsung-Jui Chen, Jen-Chih Chen, Kuang-Chi Chen and Cheng-Yan Kao*: Genotyping of human neutrophil antigens (HNA) from whole genome sequencing dataBMC Medical Genomics. 2013 6(31) (SCI, 2013 IF=3.91)
  10. Hsueh-Ting Chu, William W. L. Hsiao, Theresa Tsun-Hui Tsao, Ching-Mao Chang, Yen-Wenn Liu, Chen-Chieh Fan, Hen-Hong Chang, Tze-Jung Yeh, Jen-Chih Chen, Chaur-Chin Chen and Cheng-Yan Kao*: Quantitative assessment of mitochondrial DNA copies from whole genome sequencing as a biomarker of aging. BMC Genomics 2012, 13(Suppl 7):S5 (SCI, 2013 IF=4.04)


B: Conference Paper


  1. Ching-Mao Chang, Po-Hsuan Shih, Shengwen Wang, Hen-Hong Chang, Fang-Pey Chen, Hsueh-Ting Chu*, A Wiki-Based Traditional Chinese Medicine Formulary Knowledge System for Comparative Herb-Drug Interaction and Formula Zheng Analysis, The 17th International Congress of Oriental Medicine (ICOM): 2014
  2. Ching-Mao Chang, Hsueh-Ting Chu, Yau-Huei Wei, Fang-Pey Chen, Shengwen Wang, Po-Chang Wu, Hung-Rong Yen, Tzeng-Ji Chen*, Hen-Hong Chang*, The Core Pattern of Chinese Herbal Medicines for Sjögren's Syndrome in Taiwan from National Health Insurance Research Database between year 2002 to 2011, 13th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2014
  3. Ching-Mao Chang, Yi-Chung Ling, Po-Chang Wu, Hen-Hong Chang*, The Change of Symptoms in the Treatment of Traditional Chinese Medicine for Systemic Lupus Erythematosus, 13th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2014
  4. Tieh-Cheng Fu, Yi-Chung Ling, Wei-Ling Chou, Ching-Mao Chang, Jong-Shyan Wang*, Hen-Hong Chang*, The Application of TCM Inquiry Diagnosis in the Functional Classification of Heart Failure, 13th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2014
  5. Yu-Yun Huang, Fang-Pey Chen*, Shinn-Jang Hwang, Maw-Shiou Jong, Fun-Jou Chen, Yi-Tsau Huang, Ching-Mao ChangPotential Herb-Drug Interaction between Ginseng and Western Medicine in Taiwan: Analysis of National Health Insurance Dataset, International Conference of Traditional and Complementary Medicine on Health (ICTCMH): 2013 
  6. Ching-Mao Chang, Tin-Yun Ho, Po-Hsuan Shih, Hsueh-Ting Chu*, An Online Platform for Multiple Factors Analysis of Traditional Chinese Medicine, 2012 Cloud Computing Workshop (2012 CCW): 2012
  7. Dun-Ming Huang, Hsueh-Ting Chu, Ching-Mao Chang and Cheng-Yan Kao*: Epitope Prediction for Multi-epitope HCA661 Liver Cancer Vaccines. World Congress on Engineering and Computer Science: 2012
  8. Ching-Mao Chang, Benjamin Ing-Tiau Kuo, Wen-Hsiang Wu, Chia-Yu Liu, Hen-Hong Chang*: The Consistency Among Patients, Resident Doctor and Senior Supervisor in using a Traditional Chinese Medicine Questionnaire. 10th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2011
  9. Ching-Mao Chang, Horng-Sheng Shiue, Yun-Shien Lee, Li-Tzu Chin, Hen-Hong Chang*: The effect of herbal paste treatment on patients with Allergic Rhinitis. 10th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2011
  10. Ching-Mao Chang, Hsueh-Ting Chu, Chia-Cheng Lee, Hsin-Yi Lo, Jaw-Chyun Chen, Chien-Yun Hsiang, Chang,Yung-Hsien, Tin-Yun Ho*: HerbBlast - A program for similarity and ontology analysis of Chinese herbal medicine. Bioinformatics in Taiwan: 2006

C: 中醫論述

  1. 張清貿食療在中醫兒科的應用榮總人. 2016 (33): 3
  2. 謝承運, 張清貿, 陳方佩, 吳大鵬, 楊仁鄰, 龔彥穎*. 雷諾氏症候群的中醫診治病例報告. 北市中醫會刊. 2016, 22(1): 55-64
  3. 蔡承宏, 張清貿, 龔彥穎, 陳方佩, 吳大鵬*. 針刺治療嬰兒臂神經叢麻痺臺灣中醫醫學雜誌. 2015, 13(2): 13-24
  4. 蔡承宏, 張清貿, 龔彥穎, 陳方佩, 吳大鵬*. 針刺緩解粒線體疾病病童疑似肌陣攣發作之病例報告. 中醫藥研究論叢. 2015, 18(2): 117-127
  5. 張清貿, 施柏瑄. 從中醫觀點看產後調理榮總人. 2014 (31): 6
  6. 張清貿, 施柏瑄, 朱學亭, 陳方佩. 該如何理解「證」?- 中醫證型現代研究的定性與定量臨床醫學. 2014 (73):189-195
  7. 張清貿, 侯庭鏞, 朱學亭, 李佳橙, 張永賢* 附子在溫經散寒及清熱瀉火劑之數學模式表現 (A mathematical method to differentiate the effects of “Aconitum carmichaeli Debx” in different prescriptions)Mid-Taiwan Journal of Medicine. 2008 13(3): 152-157
D: 研究計畫


  1. 生物資訊在傷寒方的應用 - 傷寒方組方邏輯之探討 (NSC97-2815-C-039-061-B),大專生專題計畫專題生,2008.07~2009.02,國科會

E: 參與研究計畫

  1. 中藥複方SS-1對乾燥症之隨機雙盲臨床試驗及其作用機轉之研究 (MOST 103-2325-B-182-010、MOST 104-2325-B-039-003),博士生協同研究人員,2014.02~2016.07 (預定),科技部(生技醫藥國家型研究計畫)  (NCT02110446)
  2. Evaluation of the Efficacy and the Mechanism of Chinese Herbal Formula SS-1 for Sjögren's Syndrome, ClinicalTrials.gov: NCT02110446
  3. 中藥複方SS-1治療乾燥症之免疫基因調控機轉研究 (MOST 105-2325-B-039-006),博士生協同研究人員,2016.05~2016.04 (預定),科技部(生技醫藥國家型研究計畫)  (NCT02110446)
  4. Modulation of Immunity-related Gene Expression Under the Chinese Herbal Formula SS-1 Treatment for Sjögren’s Syndrome, ClinicalTrials.gov: NCT02110446


中藥複方SS-1對乾燥症之隨機雙盲臨床試驗及其作用機轉之研究

摘要

目的:探討中藥複方SS-1修格蘭氏症/乾燥症 (Sjögren's syndrome, SJS)患者之療效

方法:
本研究希望藉由隨機雙盲對照交叉設計之臨床試驗,探討中藥複方SS-1治療修格蘭氏症/乾燥症 (Sjögren's syndrome)之抗氧化之能力及調控與氧化壓力相關之cytokines表現,並希望藉由降低氧化壓力觀察到生活品質提昇及臨床症狀減輕等效果。同時也希望藉由細胞實驗,觀察SS-1抗氧化之能力,並從細胞實驗中以Cytokine Assays kit分析套組研究氧化壓力下cytokine被調控的情形,藉以了解SS-1抗氧化之機轉。最後再從受到顯著調控之cytokine篩選出SS-1組成之單方(中藥),建立初步篩選機制。
本研究為兩年期基礎及臨床試驗研究計畫,研究設計為隨機、雙盲、安慰劑對照、交叉設計之臨床試驗,收案患者依亂數表隨機分派為AB兩組,兩組各篩選45人,進入試驗各30人,A組先服用試驗用藥SS-1B組先服用試驗用藥placebo (玉米澱粉加1/100劑量SS-1),治療三個月後中斷服藥1個月進行washout後,將AB兩組藥物交換再治療三個月,最後評估SS-1兩組治療之療效,研究中兩組均維持原有西醫穩定之治療。本臨床試驗用藥SS-1複方,受試者每日三次口服試驗用藥,每次服用6公克,治療12週,停藥4週後,兩組交換,依前述流程再治療12週,總試驗時間共28週。主要評估時間點為治療前(V1),治療12週後(V2)crossover治療前(V3)crossover治療12週後(V4),終止試驗的條件為收案完成或發生嚴重藥物不良反應。

預期成果:
  1. 評估中藥SS-1改善修格蘭氏症/乾燥症 (Sjögren's syndrome)患者臨床症狀及改善生活品質之效果。 
  2. 探討中醫舌診在SS-1治療修格蘭氏症/乾燥症 (Sjögren's syndrome)患者前後之變化。 
  3. 評估中藥SS-1降低修格蘭氏症/乾燥症 (Sjögren's syndrome)患者體內氧化壓力之效果,是否可提高血漿中TAC和白血球內mtDNA copy number含量及抗氧化酵素包括SOD、GPX和CAT的表現量,並降低血漿中8-OHdG的含量及白血球細胞內粒線體DNA 4,977 bp缺失的突變比例。 
  4. 評估中藥SS-1調控修格蘭氏症/乾燥症 (Sjögren's syndrome)患者血液內Cytokine之表現及免疫功能之變化。 
  5. 探討中藥SS-1在IFN-γ及IFN-α誘發人類下顎唾液腺細胞(submaxillary salivary gland, A-253細胞株)改善細胞內氧化壓力、降低Cytokine表現、調控免疫細胞能力及其分子機轉。 
  6. 選擇臨床檢體及細胞實驗中觀察到受顯著調控之ROS及cytokine,並初步建立SJS之中藥篩選機制,以提供實證醫學之證據。

關鍵字:乾燥症、甘露飲、桑菊飲、血府逐瘀湯、氧化壓力、免疫調節


Evaluation of the Efficacy and the Mechanism of Chinese Herbal Formula SS-1 for Sjögren's Syndrome

Abstract

Objective: To evaluate the efficacy of Chinese herbal medicine (SS-1) for the Sjögren’s syndrome (SJS) patients.

Method: 
We take a randomized, double-blinded, placebo-controlled, cross-over design clinical trial to evaluate the effect of Chinese herbal medicine (SS-1) on the regulation of oxidative-related cytokines and the antioxidant capacity for the Sjögren’s syndrome (SJS) patients. Through the oxidative stress reduction, the quality of life and clinical manifestation will be improved. We will also use a SJS cell model to elucidate the antioxidant mechanism of SS-1.
The SJS patients in this clinical trial will be screened and be referred from the out-patient department (OPD) of the Rheumatology Department of Chang Gung Memorial Hospital. The patients will be divided into two groups (A and B) at random and all of them keep the routine treatment in the rheumatology OPD.  Group A patients will receive 12 weeks SS-1 treatment first and stop the SS-1 for 4 weeks to enter the wash-out phase, and then receive 12weeks placebo treatment after the wash-out phase. Group B patients receive 12 weeks placebo first and stop the placebo treatment for 4 weeks to enter the wash-out phase, and then receive 12 weeks SS-1 treatment after the wash-out phase. Patients in both groups take 6 gram of experiment medicine three times per day. We plan to evaluate the associated parameters at the time just before treatment (V1), after treatment for 12weeks (V2), at the end of wash-out phase (V3) and when the crossover treatment is completed (V4).

Expected Results:
  1. SS-1 may improve the clinical manifestation and quality of life for the patients with Sjögren’s syndrome. 
  2. To evaluate the effect of the Chinese medicine on the tongue diagnosis before and after treatment. 
  3. SS-1 may reduce the oxidative stress (8-OHdG and mtDNA 4977 bp deletion) and elevate the antioxidant capacity (TAC , mtDNA copy number, SOD, GPX, CAT). 
  4. SS-1 may have the regulatory effect on cytokine secretion and immune function. 
  5. SS-1 may have the capacity of reducing the oxidative stress, elevating the antioxidant capacity and regulating the immune response in the model of submaxillary salivary gland cell line with the induction of IFN-γand IFN-α. 
  6. Identification of the single herb in the SS-1 mixture that regulates oxidative stress and cytokine and set up of the Chinese herbs screen platform for Sjögren’s syndrome.

Keyword: Sjögren’s syndrome, Gan-Lu-Yin, Sang-Ju-Yin, Xuefu-Zhuyu-Decoction, Oxidative stress, Immune regulation
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中藥複方SS-1治療乾燥症之免疫基因調控機轉研究

摘要

目的:探討中藥複方SS-1治療乾燥症Sjögren's syndrome之免疫基因調控機轉
方法:
本研究前期完成之隨機雙盲對照雙中心臨床試驗可提供中藥複方SS-1調控氧化壓力及cytokine之療效證據,但前期尚無探討到基因調控,也無建立SS-1之健康對照組。因此本研究擬建立健康對照組之氧化壓力與細胞激素(Cytokines)正常值,藉以和SS-1前期臨床試驗收案之72位受試者做比較,並希望藉由Nanostring nCounter immune Panel探討770個免疫相關之基因調控,分析比較「治療前後療效最佳SS-1受試者」至少20名及「健康對照組」至少10名之間的免疫相關基因調控表現,希望能藉此了解受試者臨床症狀、氧化壓力指標與Cytokine指標是如何被基因調控。

預期成果:
1.          建立健康對照組受試者之檢體ROScytokines正常值。
2.          分析比較SS-1受試者與健康對照組受試者之檢體ROScytokines表現。
3.          評估中藥SS-1調控乾燥症患者檢體之免疫相關基因表現。
4.          分析比較治療前後療效最佳SS-1受試者及健康對照組受試者兩組之檢體的770項免疫相關基因之表現。
5.          分析比較中醫舌診與770個免疫相關基因表現之相關性。
6.          綜合分析臨床指標、臨床問卷及免疫相關基因之相關性。


關鍵字:乾燥症、甘露飲、桑菊飲、血府逐瘀湯、氧化壓力、免疫調節、基因調控



Modulation of Immunity-related Gene Expression Under the Chinese Herbal Formula SS-1 Treatment for Sjögren’s Syndrome

Abstract

Objective: To evaluate the modulation of immunity-related gene expression for the Sjögren’s syndrome under Chinese herbal medicine (SS-1) treatment.

Method: 
The evidence of the regulation of oxidative-related cytokines and the antioxidant capacity could be provided from the previous randomized, double-blinded, placebo-controlled, cross-over design, two-center clinical trial for evaluating the effect of Chinese herbal medicine (SS-1) for the Sjögren’s syndrome patients. However, we could not find out the modulation of immunity-related gene expression for SS-1 treatment, and it did set up a healthy control group for SS-1 comparison. We want to establish a healthy control group for evaluating the normal range of oxidative stress and cytokines, which this work could be used to compare with the 72 SS-1 subjects in previous study. And we also want use Nanostring nCounter immune Panel to analyze the 770 immunity-related gene expression for the Sjögren’s syndrome under the SS-1 treatment: (1) The best 10 (at least) efficacy SJS subjects who were evaluated before and after SS-1 treatments. (2) The 10 (at least) healthy control subjects. The findings could provide the evidence on the modulation of immunity-related gene expression for clinical manifestation, oxidative stress and cytokine in Sjögren’s syndrome patients.

Expected Results:
1.          Establish the normal range of oxidative stress and cytokines for healthy control group.
2.          To evaluate the regulatory effect on oxidative stress and cytokine secretion between SS-1 group and healthy control group.
3.          To evaluate the immunity-related gene expression for the Sjögren’s syndrome under the SS-1 treatment.
4.          To evaluate the immunity-related gene expression among the best efficacy SJS subjects and healthy control subjects.
5.          To evaluate the immunity-related gene expression with the characteristic of TCM tongue diagnosis.
6.          To analyze the correlation among clinical manifestations, Sjögren’s syndrome -related clinical questionnaires and immunity-related gene expression.


Keyword: Sjögren’s syndrome, Gan-Lu-Yin, Sang-Ju-Yin, Xuefu-Zhuyu-Decoction, Oxidative stress, Immune regulation, Gene modulation

F: 博士論文  (2012-至今,2014/06/13通過資格考成為博士候選人)


<中藥臨床試驗暨轉譯醫學研究>


  • 中文:中藥複方治療修格蘭氏症/乾燥症 (Sjögren's syndrome)臨床療效評估及其抗氧化與免疫調控機轉之研究
  • 英文:The Clinical Efficacy of Chinese Herbal Formula for Sjögren's Syndrome and the Mechanism of  Anti-oxidative Capability and Immune modulatory effects

歷年發表著作 (2016/08/30 更新)

Publication:




A: Referred Paper

  1. Hen-Hong Chang, Shue-Fen Luo, Yin-Tzu Hsue, Ching-Mao Chang, Tzung-Yan Lee, Ming-Ling Hsu, Yu-Chuen Huang, Yu-Jen Chen. Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments. Scientific Reports. 2016 (SCI, 2014 IF=5.578)
  2. Tom Fleischer, Tung-Ti Chang, Jen-Huai Chiang, Ching-Mao Chang, Ching-Yun Hsieh, Hung-Rong Yen*. Adjunctive Chinese Herbal Medicine Therapy Improves Survival of Patients with Chronic Myeloid Leukemia: A Nationwide Population-based Cohort Study. Cancer Medicine. 2016 (SCI, 2014 IF=2.5)
  3. Ching-Ying Huang, Wan-Yu Lai, Mao-Feng Sun, Che-Chen Lin, Bor-Chyuan Chen, Ching-Mao Chang, Hong-Jen Lin,  Chung-Hsien Yang, Kuo-Chin Huang, Hung-Rong Yen*. Prescription Patterns of Traditional Chinese Medicine for Peptic Ulcer Disease in Taiwan: A Nationwide Population-based Study. Journal of Ethnopharmacology. 2015 (SCI, 2014 IF= 2.998) 
  4. Ming-Cheng Huang, Fu-Tzu Paic, Che-Chen Lind, Ching-Mao Chang, Hen-Hong Chang, Yu-Chen Lee, Mao-Feng Sun, Hung-Rong Yen*. Characteristics of traditional Chinese medicine use in patients with rheumatoid arthritis in Taiwan: A nationwide population-based study. Journal of Ethnopharmacology. 2015 (SCI, 2014 IF= 2.998) 
  5. Fang-Pey Chen, Ching-Mao Chang, Jing-Huei Shiu, Jen-Hwey Chiu, Ta-Peng Wu, Jen-Lin Yang, Yen-Ying Kung, Fun-Jou Chen, Chang-Ming Chern* and Shinn-Jang Hwang*: A Clinical Study of Integrating Acupuncture and Western Medicine in Treating Patients with Parkinson's DiseaseThe American Journal of Chinese Medicine. 2015 (SCI, 2014 IF= 2.625) 
  6. Ching-Mao Chang, Hsueh-Ting Chu, Yau-Huei Wei, Fang-Pey Chen, Shengwen Wang, Po-Chang Wu, Hung-Rong Yen, Tzeng-Ji Chen* and Hen-Hong Chang*The Core Pattern Analysis on Chinese Herbal Medicine for Sjögren's syndrome: A Nationwide Population-Based StudyScientific Reports. 2015 (SCI, 2014 IF= 5.578) 
  7. Fang-Pey Chen, Ching-Mao Chang, Shinn-Jang Hwang*, Yu-Chun Chen and Fun-Jou Chen: Chinese herbal prescriptions for osteoarthritis in Taiwan: analysis of national health insurance dataset. BMC Complementary and Alternative Medicine. 2014 (SCI, 2014 IF=2.020)
  8. Ching-Mao Chang, Wen-Hsiang Wu, Benjamin Ing-Tiau Kuo, Tzung-Yan Lee, Chia-Yu Liu, Hen-Hong Chang*: Using A Questionnaire among Patient, Resident Doctor and Senior Supervisor: Are their Answers the Same? Complementary Therapies in Medicine. 2014 (SCI, 2013 IF=2.216)
  9. Hsueh-Ting Chu, Han Lin, Theresa Tsun-Hui Tsao, Chun-Fan Chang, William WL Hsiao, Tze-Jung Yeh, Ching-Mao Chang, Yen-Wenn Liu, Tse-Yi Wang, Ko-Chun Yang, Tsung-Jui Chen, Jen-Chih Chen, Kuang-Chi Chen and Cheng-Yan Kao*: Genotyping of human neutrophil antigens (HNA) from whole genome sequencing dataBMC Medical Genomics. 2013 6(31) (SCI, 2013 IF=3.91)
  10. Hsueh-Ting Chu, William W. L. Hsiao, Theresa Tsun-Hui Tsao, Ching-Mao Chang, Yen-Wenn Liu, Chen-Chieh Fan, Hen-Hong Chang, Tze-Jung Yeh, Jen-Chih Chen, Chaur-Chin Chen and Cheng-Yan Kao*: Quantitative assessment of mitochondrial DNA copies from whole genome sequencing as a biomarker of aging. BMC Genomics 2012, 13(Suppl 7):S5 (SCI, 2013 IF=4.04)


B: Conference Paper


  1. Ching-Mao Chang, Po-Hsuan Shih, Shengwen Wang, Hen-Hong Chang, Fang-Pey Chen, Hsueh-Ting Chu*, A Wiki-Based Traditional Chinese Medicine Formulary Knowledge System for Comparative Herb-Drug Interaction and Formula Zheng Analysis, The 17th International Congress of Oriental Medicine (ICOM): 2014
  2. Ching-Mao Chang, Hsueh-Ting Chu, Yau-Huei Wei, Fang-Pey Chen, Shengwen Wang, Po-Chang Wu, Hung-Rong Yen, Tzeng-Ji Chen*, Hen-Hong Chang*, The Core Pattern of Chinese Herbal Medicines for Sjögren's Syndrome in Taiwan from National Health Insurance Research Database between year 2002 to 2011, 13th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2014
  3. Ching-Mao Chang, Yi-Chung Ling, Po-Chang Wu, Hen-Hong Chang*, The Change of Symptoms in the Treatment of Traditional Chinese Medicine for Systemic Lupus Erythematosus, 13th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2014
  4. Tieh-Cheng Fu, Yi-Chung Ling, Wei-Ling Chou, Ching-Mao Chang, Jong-Shyan Wang*, Hen-Hong Chang*, The Application of TCM Inquiry Diagnosis in the Functional Classification of Heart Failure, 13th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2014
  5. Yu-Yun Huang, Fang-Pey Chen*, Shinn-Jang Hwang, Maw-Shiou Jong, Fun-Jou Chen, Yi-Tsau Huang, Ching-Mao ChangPotential Herb-Drug Interaction between Ginseng and Western Medicine in Taiwan: Analysis of National Health Insurance Dataset, International Conference of Traditional and Complementary Medicine on Health (ICTCMH): 2013 
  6. Ching-Mao Chang, Tin-Yun Ho, Po-Hsuan Shih, Hsueh-Ting Chu*, An Online Platform for Multiple Factors Analysis of Traditional Chinese Medicine, 2012 Cloud Computing Workshop (2012 CCW): 2012
  7. Dun-Ming Huang, Hsueh-Ting Chu, Ching-Mao Chang and Cheng-Yan Kao*: Epitope Prediction for Multi-epitope HCA661 Liver Cancer Vaccines. World Congress on Engineering and Computer Science: 2012
  8. Ching-Mao Chang, Benjamin Ing-Tiau Kuo, Wen-Hsiang Wu, Chia-Yu Liu, Hen-Hong Chang*: The Consistency Among Patients, Resident Doctor and Senior Supervisor in using a Traditional Chinese Medicine Questionnaire. 10th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2011
  9. Ching-Mao Chang, Horng-Sheng Shiue, Yun-Shien Lee, Li-Tzu Chin, Hen-Hong Chang*: The effect of herbal paste treatment on patients with Allergic Rhinitis. 10th Meeting of Consortium for Globalization of Chinese Medicine (CGCM): 2011
  10. Ching-Mao Chang, Hsueh-Ting Chu, Chia-Cheng Lee, Hsin-Yi Lo, Jaw-Chyun Chen, Chien-Yun Hsiang, Chang,Yung-Hsien, Tin-Yun Ho*: HerbBlast - A program for similarity and ontology analysis of Chinese herbal medicine. Bioinformatics in Taiwan: 2006

C: 中醫論述

  1. 張清貿食療在中醫兒科的應用榮總人. 2016 (33): 3
  2. 謝承運, 張清貿, 陳方佩, 吳大鵬, 楊仁鄰, 龔彥穎*. 雷諾氏症候群的中醫診治病例報告. 北市中醫會刊. 2016, 22(1): 55-64
  3. 蔡承宏, 張清貿, 龔彥穎, 陳方佩, 吳大鵬*. 針刺治療嬰兒臂神經叢麻痺臺灣中醫醫學雜誌. 2015, 13(2): 13-24
  4. 蔡承宏, 張清貿, 龔彥穎, 陳方佩, 吳大鵬*. 針刺緩解粒線體疾病病童疑似肌陣攣發作之病例報告. 中醫藥研究論叢. 2015, 18(2): 117-127
  5. 張清貿, 施柏瑄. 從中醫觀點看產後調理榮總人. 2014 (31): 6
  6. 張清貿, 施柏瑄, 朱學亭, 陳方佩. 該如何理解「證」?- 中醫證型現代研究的定性與定量臨床醫學. 2014 (73):189-195
  7. 張清貿, 侯庭鏞, 朱學亭, 李佳橙, 張永賢* 附子在溫經散寒及清熱瀉火劑之數學模式表現 (A mathematical method to differentiate the effects of “Aconitum carmichaeli Debx” in different prescriptions)Mid-Taiwan Journal of Medicine. 2008 13(3): 152-157
D: 研究計畫


  1. 生物資訊在傷寒方的應用 - 傷寒方組方邏輯之探討 (NSC97-2815-C-039-061-B),大專生專題計畫專題生,2008.07~2009.02,國科會

E: 參與研究計畫

  1. 中藥複方SS-1對乾燥症之隨機雙盲臨床試驗及其作用機轉之研究 (MOST 103-2325-B-182-010、MOST 104-2325-B-039-003),博士生協同研究人員,2014.02~2016.07 (預定),科技部(生技醫藥國家型研究計畫)  (NCT02110446)
  2. Evaluation of the Efficacy and the Mechanism of Chinese Herbal Formula SS-1 for Sjögren's Syndrome, ClinicalTrials.gov: NCT02110446
  3. 中藥複方SS-1治療乾燥症之免疫基因調控機轉研究 (MOST 105-2325-B-039-006),博士生協同研究人員,2016.05~2016.04 (預定),科技部(生技醫藥國家型研究計畫)  (NCT02110446)
  4. Modulation of Immunity-related Gene Expression Under the Chinese Herbal Formula SS-1 Treatment for Sjögren’s Syndrome, ClinicalTrials.gov: NCT02110446


中藥複方SS-1對乾燥症之隨機雙盲臨床試驗及其作用機轉之研究

摘要

目的:探討中藥複方SS-1修格蘭氏症/乾燥症 (Sjögren's syndrome, SJS)患者之療效

方法:
本研究希望藉由隨機雙盲對照交叉設計之臨床試驗,探討中藥複方SS-1治療修格蘭氏症/乾燥症 (Sjögren's syndrome)之抗氧化之能力及調控與氧化壓力相關之cytokines表現,並希望藉由降低氧化壓力觀察到生活品質提昇及臨床症狀減輕等效果。同時也希望藉由細胞實驗,觀察SS-1抗氧化之能力,並從細胞實驗中以Cytokine Assays kit分析套組研究氧化壓力下cytokine被調控的情形,藉以了解SS-1抗氧化之機轉。最後再從受到顯著調控之cytokine篩選出SS-1組成之單方(中藥),建立初步篩選機制。
本研究為兩年期基礎及臨床試驗研究計畫,研究設計為隨機、雙盲、安慰劑對照、交叉設計之臨床試驗,收案患者依亂數表隨機分派為AB兩組,兩組各篩選45人,進入試驗各30人,A組先服用試驗用藥SS-1B組先服用試驗用藥placebo (玉米澱粉加1/100劑量SS-1),治療三個月後中斷服藥1個月進行washout後,將AB兩組藥物交換再治療三個月,最後評估SS-1兩組治療之療效,研究中兩組均維持原有西醫穩定之治療。本臨床試驗用藥SS-1複方,受試者每日三次口服試驗用藥,每次服用6公克,治療12週,停藥4週後,兩組交換,依前述流程再治療12週,總試驗時間共28週。主要評估時間點為治療前(V1),治療12週後(V2)crossover治療前(V3)crossover治療12週後(V4),終止試驗的條件為收案完成或發生嚴重藥物不良反應。

預期成果:
  1. 評估中藥SS-1改善修格蘭氏症/乾燥症 (Sjögren's syndrome)患者臨床症狀及改善生活品質之效果。 
  2. 探討中醫舌診在SS-1治療修格蘭氏症/乾燥症 (Sjögren's syndrome)患者前後之變化。 
  3. 評估中藥SS-1降低修格蘭氏症/乾燥症 (Sjögren's syndrome)患者體內氧化壓力之效果,是否可提高血漿中TAC和白血球內mtDNA copy number含量及抗氧化酵素包括SOD、GPX和CAT的表現量,並降低血漿中8-OHdG的含量及白血球細胞內粒線體DNA 4,977 bp缺失的突變比例。 
  4. 評估中藥SS-1調控修格蘭氏症/乾燥症 (Sjögren's syndrome)患者血液內Cytokine之表現及免疫功能之變化。 
  5. 探討中藥SS-1在IFN-γ及IFN-α誘發人類下顎唾液腺細胞(submaxillary salivary gland, A-253細胞株)改善細胞內氧化壓力、降低Cytokine表現、調控免疫細胞能力及其分子機轉。 
  6. 選擇臨床檢體及細胞實驗中觀察到受顯著調控之ROS及cytokine,並初步建立SJS之中藥篩選機制,以提供實證醫學之證據。

關鍵字:乾燥症、甘露飲、桑菊飲、血府逐瘀湯、氧化壓力、免疫調節


Evaluation of the Efficacy and the Mechanism of Chinese Herbal Formula SS-1 for Sjögren's Syndrome

Abstract

Objective: To evaluate the efficacy of Chinese herbal medicine (SS-1) for the Sjögren’s syndrome (SJS) patients.

Method: 
We take a randomized, double-blinded, placebo-controlled, cross-over design clinical trial to evaluate the effect of Chinese herbal medicine (SS-1) on the regulation of oxidative-related cytokines and the antioxidant capacity for the Sjögren’s syndrome (SJS) patients. Through the oxidative stress reduction, the quality of life and clinical manifestation will be improved. We will also use a SJS cell model to elucidate the antioxidant mechanism of SS-1.
The SJS patients in this clinical trial will be screened and be referred from the out-patient department (OPD) of the Rheumatology Department of Chang Gung Memorial Hospital. The patients will be divided into two groups (A and B) at random and all of them keep the routine treatment in the rheumatology OPD.  Group A patients will receive 12 weeks SS-1 treatment first and stop the SS-1 for 4 weeks to enter the wash-out phase, and then receive 12weeks placebo treatment after the wash-out phase. Group B patients receive 12 weeks placebo first and stop the placebo treatment for 4 weeks to enter the wash-out phase, and then receive 12 weeks SS-1 treatment after the wash-out phase. Patients in both groups take 6 gram of experiment medicine three times per day. We plan to evaluate the associated parameters at the time just before treatment (V1), after treatment for 12weeks (V2), at the end of wash-out phase (V3) and when the crossover treatment is completed (V4).

Expected Results:
  1. SS-1 may improve the clinical manifestation and quality of life for the patients with Sjögren’s syndrome. 
  2. To evaluate the effect of the Chinese medicine on the tongue diagnosis before and after treatment. 
  3. SS-1 may reduce the oxidative stress (8-OHdG and mtDNA 4977 bp deletion) and elevate the antioxidant capacity (TAC , mtDNA copy number, SOD, GPX, CAT). 
  4. SS-1 may have the regulatory effect on cytokine secretion and immune function. 
  5. SS-1 may have the capacity of reducing the oxidative stress, elevating the antioxidant capacity and regulating the immune response in the model of submaxillary salivary gland cell line with the induction of IFN-γand IFN-α. 
  6. Identification of the single herb in the SS-1 mixture that regulates oxidative stress and cytokine and set up of the Chinese herbs screen platform for Sjögren’s syndrome.

Keyword: Sjögren’s syndrome, Gan-Lu-Yin, Sang-Ju-Yin, Xuefu-Zhuyu-Decoction, Oxidative stress, Immune regulation
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中藥複方SS-1治療乾燥症之免疫基因調控機轉研究

摘要

目的:探討中藥複方SS-1治療乾燥症Sjögren's syndrome之免疫基因調控機轉
方法:
本研究前期完成之隨機雙盲對照雙中心臨床試驗可提供中藥複方SS-1調控氧化壓力及cytokine之療效證據,但前期尚無探討到基因調控,也無建立SS-1之健康對照組。因此本研究擬建立健康對照組之氧化壓力與細胞激素(Cytokines)正常值,藉以和SS-1前期臨床試驗收案之72位受試者做比較,並希望藉由Nanostring nCounter immune Panel探討770個免疫相關之基因調控,分析比較「治療前後療效最佳SS-1受試者」至少20名及「健康對照組」至少10名之間的免疫相關基因調控表現,希望能藉此了解受試者臨床症狀、氧化壓力指標與Cytokine指標是如何被基因調控。

預期成果:
1.          建立健康對照組受試者之檢體ROScytokines正常值。
2.          分析比較SS-1受試者與健康對照組受試者之檢體ROScytokines表現。
3.          評估中藥SS-1調控乾燥症患者檢體之免疫相關基因表現。
4.          分析比較治療前後療效最佳SS-1受試者及健康對照組受試者兩組之檢體的770項免疫相關基因之表現。
5.          分析比較中醫舌診與770個免疫相關基因表現之相關性。
6.          綜合分析臨床指標、臨床問卷及免疫相關基因之相關性。


關鍵字:乾燥症、甘露飲、桑菊飲、血府逐瘀湯、氧化壓力、免疫調節、基因調控



Modulation of Immunity-related Gene Expression Under the Chinese Herbal Formula SS-1 Treatment for Sjögren’s Syndrome

Abstract

Objective: To evaluate the modulation of immunity-related gene expression for the Sjögren’s syndrome under Chinese herbal medicine (SS-1) treatment.

Method: 
The evidence of the regulation of oxidative-related cytokines and the antioxidant capacity could be provided from the previous randomized, double-blinded, placebo-controlled, cross-over design, two-center clinical trial for evaluating the effect of Chinese herbal medicine (SS-1) for the Sjögren’s syndrome patients. However, we could not find out the modulation of immunity-related gene expression for SS-1 treatment, and it did set up a healthy control group for SS-1 comparison. We want to establish a healthy control group for evaluating the normal range of oxidative stress and cytokines, which this work could be used to compare with the 72 SS-1 subjects in previous study. And we also want use Nanostring nCounter immune Panel to analyze the 770 immunity-related gene expression for the Sjögren’s syndrome under the SS-1 treatment: (1) The best 10 (at least) efficacy SJS subjects who were evaluated before and after SS-1 treatments. (2) The 10 (at least) healthy control subjects. The findings could provide the evidence on the modulation of immunity-related gene expression for clinical manifestation, oxidative stress and cytokine in Sjögren’s syndrome patients.

Expected Results:
1.          Establish the normal range of oxidative stress and cytokines for healthy control group.
2.          To evaluate the regulatory effect on oxidative stress and cytokine secretion between SS-1 group and healthy control group.
3.          To evaluate the immunity-related gene expression for the Sjögren’s syndrome under the SS-1 treatment.
4.          To evaluate the immunity-related gene expression among the best efficacy SJS subjects and healthy control subjects.
5.          To evaluate the immunity-related gene expression with the characteristic of TCM tongue diagnosis.
6.          To analyze the correlation among clinical manifestations, Sjögren’s syndrome -related clinical questionnaires and immunity-related gene expression.


Keyword: Sjögren’s syndrome, Gan-Lu-Yin, Sang-Ju-Yin, Xuefu-Zhuyu-Decoction, Oxidative stress, Immune regulation, Gene modulation

F: 博士論文  (2012-至今,2014/06/13通過資格考成為博士候選人)


<中藥臨床試驗暨轉譯醫學研究>


  • 中文:中藥複方治療修格蘭氏症/乾燥症 (Sjögren's syndrome)臨床療效評估及其抗氧化與免疫調控機轉之研究
  • 英文:The Clinical Efficacy of Chinese Herbal Formula for Sjögren's Syndrome and the Mechanism of  Anti-oxidative Capability and Immune modulatory effects