D: 中醫論述
- 張凱惟, 張清貿, 陳方佩, 龔彥穎*. 中醫治療主動脈瓣狹窄病例之理論與病例報告. 中醫藥研究論叢. 2018, 21(1): 171-190 (in Chinese)
- 張凱惟, 施柏瑄, 謝承運, 曾元卜, 陳方佩, 龔彥穎, 張清貿*. 各國中草藥質量標準比較：以藥材三七為例. 台北市中醫醫學雜誌. 2017 (in Chinese)
- 張清貿#, 施柏瑄#, 楊仕哲*. 心腦主神明學說的沿革. 中醫藥雜誌. 2017, 28(1): 2801001
- 施柏瑄#, 洪國棟#, 林奕中, 張清貿*. 僵直性脊椎炎之中醫藥文獻回顧. 中醫藥研究論叢. 2016, 19(2):99-112
- 張清貿. 食療在中醫兒科的應用, 榮總人. 2016 (33): 3
- 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
- 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
- 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
- 張清貿, 施柏瑄. 從中醫觀點看產後調理, 榮總人. 2014 (31): 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
- 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
E: 研究計畫
- 利用DNA Exome sequencing技術探索修格蘭氏症之基因序列與中醫體質、舌診、脈診之相關性研究 (第二年：整合功能性蛋白質體學及口腔微生物菌相) (V109B-034)，主持人，2020.01~2020.12，臺北榮民總醫院院內計畫，ClinicalTrials.gov：NCT03935373
- 利用DNA Exome sequencing技術探索修格蘭氏症(Sjögren's syndrome)之基因序列與中醫體質、舌診、脈診之相關性研究(V108B-031)，主持人，2019.01~2019.12，臺北榮民總醫院院內計畫，ClinicalTrials.gov：NCT03935373
- 利用IFN-γ誘導人類下顎唾液腺細胞模型探討修格蘭氏症中醫健保資料庫前十大中藥單方之粒線體抗氧化機轉(V106A-006)，主持人，2017.01~2017.12，臺北榮民總醫院院內計畫
- 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
F: 參與研究計畫
- 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)
- Evaluation of the Efficacy and the Mechanism of Chinese Herbal Formula SS-1 for Sjögren's Syndrome, ClinicalTrials.gov: NCT02110446
- 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) (NCT02855658)
- Modulation of Immunity-related Gene Expression Under the Chinese Herbal Formula SS-1 Treatment for Sjögren’s Syndrome, ClinicalTrials.gov: NCT02855658
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對修格蘭氏症/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A、B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-1，B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A、B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：
- 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。
- 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。
- 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。
- 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。
- 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。
- 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:
- SS-1 may improve the clinical manifestation and quality of life for the patients with Sjögren’s syndrome.
- To evaluate the effect of the Chinese medicine on the tongue diagnosis before and after treatment.
- 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).
- SS-1 may have the regulatory effect on cytokine secretion and immune function.
- 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.
- 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
------------------------------------------------------------------------------------------------------
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ROS與cytokines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ROS與cytokines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
G: 博士論文 (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，並取得臨床醫學博士學位)
<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