【摘要】：研究背景：隨著醫(yī)學(xué)診斷,外科手術(shù),放化療,生物治療等技術(shù)的發(fā)展,癌癥患者的生存時間得以延長,使得癌癥的治療不再局限于縮小和清除腫瘤的實(shí)體,癌癥生存者數(shù)量增加,醫(yī)學(xué)工作者開始更加重視癌癥患者生存質(zhì)量的提高。癌因性疲乏(cancer related fatigue,CRF),是癌癥最易困擾患者的癥狀之一。由于認(rèn)識相對不足和缺乏有效的干預(yù)手段,其在較長時間內(nèi)未引起重視,相對于已有可靠防治措施的疼痛、嘔吐等癥狀,疲乏更讓患者痛苦,并長期存在。目前其病理機(jī)制尚未明確,也缺乏特異性有效的干預(yù)手段,僅有氧運(yùn)動經(jīng)一級證據(jù)證實(shí)對CRF有改善作用。祖國醫(yī)學(xué)在改善癥狀方面有獨(dú)特的優(yōu)勢,對于各種慢性疾病中的疲勞癥狀經(jīng)驗(yàn)豐富。然而辨證施治是祖國醫(yī)學(xué)的精義所在,首先要明確癌因性疲乏的證候分布情況,在此基礎(chǔ)上精確的辨證才能充分發(fā)揮其因人施治的優(yōu)勢,結(jié)合有氧運(yùn)動的綜合干預(yù)方案將提高臨床療效。研究目的：1.調(diào)查消化系統(tǒng)惡性腫瘤癌因性疲乏患者證候及癥狀分布特點(diǎn)。2.綜合干預(yù)方案治療氣虛證消化系統(tǒng)腫瘤癌因性疲乏患者臨床療效研究。3.運(yùn)用液相色譜質(zhì)譜聯(lián)用方法對氣虛證癌因性疲乏患者血清進(jìn)行代謝物分析,初步探討癌因性疲乏發(fā)生的可能機(jī)制。研究方法：1.參照《中藥新藥臨床研究指導(dǎo)原則-中醫(yī)癥候指導(dǎo)原則》及《中醫(yī)內(nèi)科學(xué)》虛勞病中可能出現(xiàn)疲乏的證候,歸納癌因性疲乏證素,以消化系統(tǒng)腫瘤的穩(wěn)定期及無瘤幸存者為例,調(diào)查其證候分布及伴隨癥狀表現(xiàn)。2.采用分層隨機(jī)方法將納入的氣虛證癌因性疲乏患者隨機(jī)分為：綜合干預(yù)組、單純運(yùn)動組及空白對照組。綜合干預(yù)組采用運(yùn)動處方,中藥口服,穴位按壓等干預(yù)措施。單純運(yùn)動組僅采用與綜合干預(yù)組相同的運(yùn)動處方干預(yù)�？瞻讓φ战M不做干預(yù)。干預(yù)時間為8周,以Piper量表評分為主要療效評價指標(biāo),每4周評價一次疲勞評分。8周時評價證候療效和癥狀積分。3.以超高效液相色譜作為分離系統(tǒng),質(zhì)譜作為檢測系統(tǒng)串聯(lián)分。血清樣品經(jīng)色譜分離后離子化,通過質(zhì)譜的質(zhì)量分析器檢測化合物的質(zhì)譜圖,采用正交最小二乘判別分析(OPLS)的方法確定代謝差異物,通過數(shù)據(jù)庫對比判別康復(fù)期癌因性疲乏組和癌癥非疲乏組患者差異物。研究結(jié)果：1.共調(diào)查142例消化系統(tǒng)腫瘤患者,CRF患者最常出現(xiàn)的疲乏伴隨癥狀有出汗,睡眠差,脘腹脹,氣短,食欲差,頭暈,大便異常。證候分布依次為(陽)氣虛,脾氣虛,血虛,肺氣虛,腎氣虛,肝郁氣滯,濕(熱)困脾,心氣虛,腎陽虛,腎陰虛。2.綜合干預(yù)組,單純運(yùn)動組在干預(yù)后4周和8周疲勞評分均有下降,且綜合干預(yù)組下降更加明顯,空白對照疲勞評分沒有改善,差異有統(tǒng)計學(xué)意義。8周時綜合干預(yù)組和單純運(yùn)動組癥狀積分改善前后差值差異有統(tǒng)計學(xué)意義,綜合干預(yù)組療效改善更佳,綜合干預(yù)組證候有效率高于單純運(yùn)動組。3.經(jīng)檢測及OPLS方法篩選兩組區(qū)分明顯,癌因性疲乏患者組較對照組共21種代謝物發(fā)生顯著性量的改變(P0.05)。其中有10種代謝物相對對照組升高,包括溶血磷脂酰乙醇胺(0:0/20:4),溶血磷脂酰膽堿/磷脂酰膽堿比值,溶血磷脂酰膽堿(20:4),磷脂酰乙醇胺(18:0/0:0),磷酰脂絲氨酸(21:0/0:0),溶血性磷脂酰乙醇胺(0:0/16:0),溶血磷脂酰膽堿(16:0),溶血磷脂酰膽堿(22:4),甘油磷酸膽堿,N-docosahexaenoyl GABA,;11種代謝物相對對照組降低包括：溶血磷脂酰乙醇胺(0:0/22:5),a-CEHC,內(nèi)源性大麻素(南安邁得),19(R)-hydroxy-PGF1α, (19 (R)羥基前列腺素Flα),尿酸,氧化亮氨酸,二氫尿嘧啶,N-(3a,12a-dihydroxy -5β-cholan-24-oyl)-glycine, A 1pha-N-Phenylacetyl-L-glutamine(N-苯乙�；�-L-谷氨酰胺),1-Linoleoylg-lycerophos phocholine(1-亞油酯酰甘油磷酸膽堿),硫酸吲哚酚。結(jié)論：消化系統(tǒng)癌因性疲乏證候分布以虛證為主,虛證中以氣虛類證為主,兼有濕阻及氣滯證。相對于單純運(yùn)動療法,結(jié)合有氧運(yùn)動,口服中藥及穴位按壓的綜合干預(yù)方法對于癌因性疲乏有更好的改善作用,值得臨床應(yīng)用。氣虛證癌因性疲乏患者血清中多種溶血性磷脂含量增多引起的膜磷脂水解破壞,機(jī)體抗氧化能力下降和血清內(nèi)源性大麻素含量下降可能參與癌因性疲乏的發(fā)生。
[Abstract]:Background: With the development of medical diagnosis, surgery, chemotherapy, biological therapy and so on, the survival time of cancer patients is prolonged, so that the treatment of cancer is no longer limited to the reduction and elimination of tumor-related entities, and the number of cancer survivors is increased. Medical workers begin to pay more attention to the improvement of the quality of life of cancer patients. Cancer-induced fatigue (CRF) is one of the most troublesome symptoms of cancer. Due to the lack of awareness and the lack of effective interventions, it has not paid attention for a long period of time, such as pain, vomiting, and the like relative to existing reliable control measures, fatigue makes the patient more painful and persists. At present, the pathological mechanism is not clear, and there is lack of specific effective intervention methods. Only aerobic exercise has been proved to have an improved effect on CRF via primary evidence. The Chinese medicine has unique advantages in improving symptoms, and has rich experience in fatigue symptoms in various chronic diseases. However, the treatment of syndrome differentiation is the essence of the motherland medicine. First, it is necessary to clarify the symptom distribution of cancer due to sex fatigue, and on the basis of this, accurate differentiation can give full play to its advantages as a result of human therapy, and the comprehensive intervention program combining with aerobic exercise will improve the clinical curative effect. Purpose of Study: 1. To investigate the characteristics of syndrome and symptom distribution in patients with malignant tumor of digestive system due to sexual fatigue. Clinical efficacy of integrated intervention regimen in the treatment of cancer of digestive system of digestive system of qi-deficiency syndrome. Using liquid chromatography mass spectrometry (LC-MS) to analyze the serum of patients with qi-deficiency syndrome due to fatigue, the possible mechanism of cancer-induced fatigue was discussed. Study Method: 1. With reference to the Guiding Principles of Clinical Research on New Drugs of Traditional Chinese Medicine, the Guiding Principles of Traditional Chinese Medicine, and the syndrome of fatigue in the Chinese Medicine of Science and Medicine, inductive fatigue syndrome, stable phase of digestive system tumor and non-tumor survivors are summarized. to investigate the distribution of syndrome and its accompanying symptoms. The patients with deficiency of qi-deficiency syndrome were randomly divided into two groups: comprehensive intervention group, simple exercise group and blank control group. The comprehensive intervention group adopts the intervention measures such as exercise prescription, traditional Chinese medicine oral and acupoint pressing. The simple exercise group only adopted the same exercise prescription intervention as the integrated intervention group. The blank control group did not intervene. The intervention time was 8 weeks with the piper scale as the main efficacy evaluation index, and the fatigue score was evaluated every 4 weeks. The efficacy and symptom score were evaluated at 8 weeks. Using ultra-high performance liquid chromatography as the separation system, mass spectrum is used as the detection system in series. the serum sample is ionized after chromatographic separation, the mass spectrum of the compound is detected by mass analyzer of the mass spectrum, and the metabolic difference is determined by adopting the method of orthogonal least squares discriminant analysis (OPLS), A database comparison was used to determine the difference in patients with cancer due to sexual fatigue and non-fatigue groups in cancer. Results of the study: 1. A total of 142 patients with digestive system tumors were investigated. The most frequent symptoms of fatigue associated with CRF were sweating, poor sleep, abdominal distention, anorexia, anorexia, dizziness, and stool abnormalities. syndrome distribution is (yang) qi deficiency, spleen qi deficiency, blood deficiency, lung qi deficiency, kidney qi deficiency, qi stagnation, dampness (heat), spleen deficiency, heart deficiency, kidney yang deficiency, and kidney yin deficiency. In the comprehensive intervention group, the fatigue scores at 4 weeks and 8 weeks after the intervention decreased, and the reduction of the comprehensive intervention group was more obvious, and the blank control fatigue score was not improved. The difference was statistically significant. After 8 weeks, the difference of the difference between the comprehensive intervention group and the symptom score of the simple exercise group was statistically significant. The comprehensive intervention group had better curative effect, and the comprehensive intervention group was more effective than the simple exercise group. Compared with the control group, 21 metabolites in the control group were significantly higher than those in the control group (P <0.05). Among them, 10 metabolites were elevated relative to the control group, including lysin-free ethanolamine (0: 0/ 20: 4), hemolytic phospholipid, choline/ phospholipid, choline ratio, lysin-free choline (20: 4), phospholipid and ethanolamine (18: 0/ 0: 0), liposerine (21: 0/ 0: 0), hemolytic phospholipid and ethanolamine (0: 0/ 16: 0). In contrast to the control group, there were 11 metabolites (0: 0/ 22: 5), a-CEHC, endogenous cannabinoid (Nananmai), 19 (R)-hydroxy-PGF1, respectively. (19 (R) hydroxy prostaglandin Fl retinoic acid), uric acid, oxidized leucine, dihydrocodeine, N-(cis, 12a-dihydroxy-5)-cholan-24-oyl)-glyine, A 1Et-N-Phyllyl-L-glucamine (N-phenoxy-L-lactide), 1-Linoleylg-lycoophys phytoline (1-sub-oil ester, glycerol phosphorylcholine), and sulfophenol. Conclusion: The syndrome of qi deficiency syndrome in digestive system cancer is mainly due to deficiency of qi, and qi deficiency syndrome is the main symptom in the deficiency of qi, and has both wet resistance and qi stagnation syndrome. Compared with simple exercise therapy, combined with aerobic exercise, oral Chinese medicine and acupoint pressing, the comprehensive intervention method has better effect on cancer due to fatigue, and is worthy of clinical application. The degradation of membrane phospholipid, the decrease of body antioxidant capacity and the decrease of serum endogenous cannabinoid content in the serum of patients with qi-deficiency syndrome caused by the increase of the content of various hemolytic phospholipids may be involved in the occurrence of cancer-induced fatigue.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R735

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