臺灣博碩士論文加值系統

背景
　　寬心飲為一傳統中藥複方(成分包含 黃耆;人參;白朮;茯苓;甘草;女貞子;藿香) 在動物實驗的模型裡已證實對癌細胞有細胞毒殺作用 (cytostatic effects) 並且能抑制腫瘤細胞的生長。若以傳統中醫之理論來分析，則寬心飲具有調節陰陽平衡及補氣扶正之功效。臨床上，許多癌症患者均會以中草藥作為輔助替代醫療之選擇，用以緩解癌症諸多相關症候。而因癌症造成的自主神經失調，在中醫理論上即屬陰陽之失衡症候。故本研究嘗試探討寬心飲應用在轉移性大腸癌患者之自律神經失調及癌症相關副作用之臨床療效，暨生活品質之改善評估。
方法
　　本研究採二階段試驗，第一階段為觀察型研究設計(single-group observational experimental scheme),針對符合收案條件之轉移性大腸癌患者，共計收案52位，於化療週期間給予寬心飲複方服用2週，針對服藥前及服藥後 比較自律神經之活性及經絡能量變異:並對癌症副作用及生活品質進行改善評估，第二階段則採對照之方式比較實驗組(有西醫治療及服用寬心飲者)及對照組(僅採納西醫治療，無服用寬心飲者)在自主神經活性(心律變異測量)及經絡能量測量上之變化。以評估其臨床療效。
工具
自律神經之測量以腕式生理監視器-心律大師針對自律神經相關參數 如 HRV, HF, LF, RMMSD, variance 等進行前後測分析;並運用經絡能量儀(meridian electric analysis device :MEAD)對12經脈以代表之十二穴位進行前後測之穴位電阻分析；癌症相關副作用則以美國國家癌症研究所(NCI) 所發表之常見不良事件評價標準(CTCAE) 為標準，另以WHO-BREF版問卷針對生活品質變化進行評量。
結果
　　在第一階段之研究中寬心飲對整體自主活性(HRV)有顯著性之提升(p=0.013):尤以對迷走神經系統之影響較交感神經為顯著；經絡能量的比較上發現寬心飲除對12經絡有不同程度能量(Qi)之提升外，對陰經之調控較陽經為顯著；於癌症相關副作用評估上，多層面如噁心，嘔吐，失眠，疲憊均達有統計意義之改善，於貧血及腹瀉/便祕則無顯著變化。於第二階段對照試驗中則顯示實驗組有服用寬心飲者在經絡能量上有顯著之提升(Yin meridian:p=0.014;Yang meridian:p=0.024) 且總自主神經活性增強 (SDNN:p=0.001)，副交感神經活性增加達顯著意義 (HF:p=0.003;RMMSD:p=0.002). 兩階段試驗中轉移性大腸癌患者之整體生活品質於服用寬心飲後均有顯著統計意義之提升。

結論
　　針對此一以轉移性大腸癌患者之研究標的顯示，寬心飲於臨床應用具安全性並能調整交感—副交感神經系統平衡進而改善相關癌症副作用，且提升經絡之能量及整體生活品質，其機轉與調整中醫陰陽平衡之理論不謀而合，自傳統醫學之角度而言，寬心飲可補助正氣，反映於經絡能量之提升;自西方醫學之角度而言，總自主神經活性之增強及副交感神經活性之之增強有助於能量之保存及自主神經系統之平衡，故而能改善受試患者之自主神經失衡之相關症狀。

Background
The Kuan-Sin-Yin (KSY) is a Traditional Chinese Medicine decoction composed with seven Chinese herbs (Codonopsis pilosula; Atractylodes macrocephala; Poria cocos; Astragalus membranaceus; Agastache rugosa; Ligustrum lucidum; and Glycyrrhiza uralensis) which had been proved with its cytostatic effects on cancer cells and activity of suppression the tumor growth in vivo and in vitro. The mechanism of Kuan-Sin-Yin (KSY) in Traditional Chinese Medicine theory is according to the principle of promoting yin-yang balance and qi enhancement which may benefit the cancer patients. In clinical, Traditional Chinese Medicine has nowadays been well accepted as a complementary therapy. Since many cancer patients suffer from autonomic dysfunction and related symptoms which correspond to yin-yang imbalance according to Chinese medicine theory, the aim of the study is to evaluate the possible effect Kuan-Sin-Yin in metastatic colon cancer (mCRC) patients with autonomic dysfunction.

Methods
We designed two stage study for evaluating the potential effect of Kuan-Sin-Yin in advanced colon cancer patients. In the first stage of the study, we conducted a single-group experiment. The 52 patients who met the inclusion criteria were enrolled with IRB approval. Participants took the KSY daily for two weeks. The primary outcomes was KSY efficacy as reflected in the heart rate variability (HRV) and electrical conductivity (μA) over 12 meridian points. Autonomic function was examined before and after the two-week KSY intervention. The vagal and sympathetic tone and related parameters were recorded by HRV; twelve meridian energy (six yin and six yang meridians) were measured using a Meridian Electric Analysis Device (MEAD). Secondary outcomes were cancer-related symptoms and patient quality of life. In the second stage, a further controlled trial was conducted to evaluate the level of improvement in meridian energy and heart-rate variability (HRV) and to assess whether these observations are compatible with TCM theory. We monitored the meridian electro-conductivity and heart-rate variability (HRV) to compare the efficacy of Kuan-Sin-Yin in the control and experimental groups. We also measured cancer-related symptoms and quality of life as secondary outcomes.

Results
In the first stage study, the results showed that the KSY intervention improved the autonomic function via increasing the vagal tone significantly (HF: p=0.041), but not the sympathetic tone (LF: p=0.154); total autonomic activity was significantly enhanced (HRV activity (SDNN): p=0.013). Intriguingly, energy increased more over the yin meridian (p=0.010) than over the yang meridian (p=0.015). Cancer-related symptoms and quality of life were generally significantly improved (p<0.05).
In the second stage of controlled study, we found that colon cancer patients who received KSY as complementary therapy benefited with enhancement of meridian energy (Yin meridian:p=0.014;Yang meridian:p=0.024) and increases in HRV activity(SDNN:p=0.001) and parasympathetic tone (HF:p=0.003;RMMSD:p=0.002). Cancer-related symptoms decreased, and quality of life was improved with statistical significance.

Conclusion
We concluded that KSY safely and effectively improves autonomic function in mCRC patients via regulating the vagal-sympathetic dynamic balance, which may correspond to the TCM yin-yang concept of energy. From the TCM viewpoint, promotion of Qi leads to meridian energy enhancement, while from a Western medicine viewpoint, an increase in HRV activity and parasympathetic tone preserve energy and lead to better balance in the autonomic nervous system. The correlation of positive results reflected in meridian energy and HRV activity confirms the positive role of complementary medicine of Kuan-Sin-Yin in cancer care. Further study is warranted.

目錄
Abstract I
中文摘要 IV
目錄 VII
Contents of Figures X
Contents of Tables XII
Chapter 1. Introduction 1
1.1 The complementary role of TCM in colon cancer care 1
1.2 The background of Kuan-Sin-Yin 1
1.2.1 Components of Kuan-Sin-Yin 1
1.2.2 Historial background of Kuan- Sin-Yin 2
1.3 Autonomic dysfunction in cancer patients 2
1.4 How to apply TCM-Meridian Theory and Qi in Cancer patients with Autonomic dysfunction 4
1.4.1 The application of TCM-Meridian Theory in Cancer care 4
1.4.2 The meridian theory V.S Autonomic nerve system 5
Chapter 2. Study motivation and Aim of Study 7
2.1 Study Motivation 7
2.2 Aim of the Study 9
Chapter 3. Method and Measurement 10
3.1 Research Design and Participants 10
3.1.1 The inclusion criteria 10
3.1.2 Exclusion criteria 11
3.1.3 Intervention phase 11
3.2 Preparing of Kuan-Sin-Yin decotiction 12
3.2.1 Quality control and safety of Kuan-Sin-Yin 12
3.3 Measurements 13
3.3.1 HRV parameter measurement 14
3.3.2 Meridian energy measurement 15
3.3.3 Cancer-related symptoms and QoL 17
3.4 Statistical analysis 17
Chapter 4. Results 19
4.1The Result in Single group study (First stage) 19
4.1.1 Participants characteristics 19
4.1.2 The effect of KSY on HRV parameters 19
4.1.3 The effect of KSY on electrical conductivity as measured with MEAD 20
4.1.4 The KSY efficacy reflect in cancer related symptom and quality of life improvement 20
4.2 The Result in controlled group study (Second stage) 21
4.2.1 Participant characteristics 21
4.2.2 Effect of KSY on meridian energy as measured with MEAD 21
4.2.3 Comparsion of HRV activity in the control and KSY groups 22
4.2.4 Comparsion of the control and KSY groups in relief of cancer-related symptoms and improvement in QoL 23
Chapter 5. Discussion 25
5.1 TCM concept of Kuan-Sin-Yin 25
5.1.1 The TCM yin/yang theory applied to autonomic dysfunction 25
5.2 KSY regulates the AD via promotion of the vagal/sympathetic dynamic balance 27
5.3 Interpretation of KSY effect on meridian electro-conductivity level and HRV 28
5.4 The possible mechanism of KSY improve cancer related symptom and QoL 30
5.4.1 Through regulating neurotransmitter improve the clinical symptom 30
5.4.2 Complementary TCM-KSY promotes HRV and vagus nerve activity which may correlate with improvement in cancer-related symptoms 31
5.5 Pharmacological explanation for KSY 33
5.5.1 Anti-tumor properties of KSY 33
5.5.2 How KSY regulate the autonomic dysfunction from pharmacological perspective 34
5.6 The possibily efficacy of KSY in other disease 35
5.7Limitation 36
5.7.1 The subtle or ambigus relationship between HRV and meridian energy 36
5.7.2 Demographic considerations and behavior in choosing TCM as complementary therapy. 37
5.7.3 The limitation of sample size 37
Chapter 5. Conclusion 39
Chapter 7. Future direction 40
Reference 41
博士期間參與之研究發表相關文獻 53
 
Contents of Figures
Figure 1.Crude Herb of Kuan- Sin-Yin Ingredient(100ml): 54
Figure 2 The Study flow chart in stage I and stage II 55
Figure 2A. Study flowchart in first stage . 55
Figure 2B. The study flowchart in second stage( controlled study) 56
Figure 3. Kuan-Sin-Yin decotiction 57
Figure 4. ANSWatch wrist monitor. 58
Figure 5. Meridian Energy Analysis Device (MEAD). 59
Figure 6 Acupotints in each meridian of hands and feet 60
Figure 6A. Acupoints in the Yin meridian of the hand. 60
Figure 6B. Acupoints in the Yin meridian of the foot. 60
Figure 6C. Acupoints in the Yang meridian of the hand. 60
Figure 6D. Acupoints in the Yang meridian of the foot. 60
Figure 7 The twelve meridians and representative acupoints in the study 61
Figure 8 The changes of HRV parameters before and after kuan-sin-yin inter vention 63
Figure 8A. Comparison of the high frequency component (HF), and low frequency component (LF) before and after Kuan-Sin-Yin intervention in HRV analysis.Data expressed with mean and (95% confidence interval for mean)…… 63
Figure 8B. Comparison of standard deviation of adjacent peak-to-peak intervals (SDNN which represent the total HRV activity) and the square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMMSD) before and after Kuan-Sin-Yin intervention in Heart Rate Variability analysis. Data expressed with mean and (95% confidence interval for mean) 64
Figure 8C. Comparison of ratio of low frequency component (LF) and high frequency component (HF) before and after Kuan-Sin-Yin intervention in HRV analysis. Data expressed with mean and (95% confidence interval for mean) 65
Figure 9 The inter-group analysis of the difference of SDNN and RMMSD 66
 
Contents of Tables
Table 1.Componment of Kuan-Sin-Yin 67
Table 2. HRV parameter 68
Table 3. Characteristics of the participants, stage I (n=52) 69
Table 4. Comparison of HRV and electrical conductivity before and after the Kuan-Sin-Yin intervention, stage I (n=52) 70
Table 5. Comparison of Yin and Yang meridian energy before and after Kuan-Sin-Yin intervention (measured with Meridian Energy Analysis Device), stage I (n=52) 71
Table 6. Comparison of cancer-related symptoms before and after Kuan-Sin-Yin intervention, stage I (n=52) 72
Table 7. Comparison of Quality of Life (QoL) scores before and after Kuan-Sin-Yin intervention, stage I (n=52) 73
Table 8. Demographic characteristics of the participants, stage II (n=52) 74
Table 9. Comparison of meridian energy before and after Kuan-Sin-Yin intervention, stage II ,N=52 75
Table 10. Comparison of heart rate variability before and after the intervention in Kuan-Sin-Yin and control group, stage II (n=52) 76
Table 11. Comparison of cancer-related symptoms before and after Kuan-Sin-Yin intervention stage II, (n=52) 78
Table 12. Comparison of Quality of Life (QoL) scores before and after Kuan-Sin-Yin intervention, stage II (n=50) 79
Supplementary 80

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