消化系统肿瘤患者癌因性疲乏综合干预疗效及血清代谢物分析
发布时间：2018-10-21 11:17
【摘要】：研究背景：随着医学诊断,外科手术,放化疗,生物治疗等技术的发展,癌症患者的生存时间得以延长,使得癌症的治疗不再局限于缩小和清除肿瘤的实体,癌症生存者数量增加,医学工作者开始更加重视癌症患者生存质量的提高。癌因性疲乏(cancer related fatigue,CRF),是癌症最易困扰患者的症状之一。由于认识相对不足和缺乏有效的干预手段,其在较长时间内未引起重视,相对于已有可靠防治措施的疼痛、呕吐等症状,疲乏更让患者痛苦,并长期存在。目前其病理机制尚未明确,也缺乏特异性有效的干预手段,仅有氧运动经一级证据证实对CRF有改善作用。祖国医学在改善症状方面有独特的优势,对于各种慢性疾病中的疲劳症状经验丰富。然而辨证施治是祖国医学的精义所在,首先要明确癌因性疲乏的证候分布情况,在此基础上精确的辨证才能充分发挥其因人施治的优势,结合有氧运动的综合干预方案将提高临床疗效。研究目的：1.调查消化系统恶性肿瘤癌因性疲乏患者证候及症状分布特点。2.综合干预方案治疗气虚证消化系统肿瘤癌因性疲乏患者临床疗效研究。3.运用液相色谱质谱联用方法对气虚证癌因性疲乏患者血清进行代谢物分析,初步探讨癌因性疲乏发生的可能机制。研究方法：1.参照《中药新药临床研究指导原则-中医症候指导原则》及《中医内科学》虚劳病中可能出现疲乏的证候,归纳癌因性疲乏证素,以消化系统肿瘤的稳定期及无瘤幸存者为例,调查其证候分布及伴随症状表现。2.采用分层随机方法将纳入的气虚证癌因性疲乏患者随机分为：综合干预组、单纯运动组及空白对照组。综合干预组采用运动处方,中药口服,穴位按压等干预措施。单纯运动组仅采用与综合干预组相同的运动处方干预。空白对照组不做干预。干预时间为8周,以Piper量表评分为主要疗效评价指标,每4周评价一次疲劳评分。8周时评价证候疗效和症状积分。3.以超高效液相色谱作为分离系统,质谱作为检测系统串联分。血清样品经色谱分离后离子化,通过质谱的质量分析器检测化合物的质谱图,采用正交最小二乘判别分析(OPLS)的方法确定代谢差异物,通过数据库对比判别康复期癌因性疲乏组和癌症非疲乏组患者差异物。研究结果：1.共调查142例消化系统肿瘤患者,CRF患者最常出现的疲乏伴随症状有出汗,睡眠差,脘腹胀,气短,食欲差,头晕,大便异常。证候分布依次为(阳)气虚,脾气虚,血虚,肺气虚,肾气虚,肝郁气滞,湿(热)困脾,心气虚,肾阳虚,肾阴虚。2.综合干预组,单纯运动组在干预后4周和8周疲劳评分均有下降,且综合干预组下降更加明显,空白对照疲劳评分没有改善,差异有统计学意义。8周时综合干预组和单纯运动组症状积分改善前后差值差异有统计学意义,综合干预组疗效改善更佳,综合干预组证候有效率高于单纯运动组。3.经检测及OPLS方法筛选两组区分明显,癌因性疲乏患者组较对照组共21种代谢物发生显著性量的改变(P0.05)。其中有10种代谢物相对对照组升高,包括溶血磷脂酰乙醇胺(0:0/20:4),溶血磷脂酰胆碱/磷脂酰胆碱比值,溶血磷脂酰胆碱(20:4),磷脂酰乙醇胺(18:0/0:0),磷酰脂丝氨酸(21:0/0:0),溶血性磷脂酰乙醇胺(0:0/16:0),溶血磷脂酰胆碱(16:0),溶血磷脂酰胆碱(22:4),甘油磷酸胆碱,N-docosahexaenoyl GABA,;11种代谢物相对对照组降低包括：溶血磷脂酰乙醇胺(0:0/22:5),a-CEHC,内源性大麻素(南安迈得),19(R)-hydroxy-PGF1α, (19 (R)羟基前列腺素Flα),尿酸,氧化亮氨酸,二氢尿嘧啶,N-(3a,12a-dihydroxy -5β-cholan-24-oyl)-glycine, A 1pha-N-Phenylacetyl-L-glutamine(N-苯乙酰基-L-谷氨酰胺),1-Linoleoylg-lycerophos phocholine(1-亚油酯酰甘油磷酸胆碱),硫酸吲哚酚。结论：消化系统癌因性疲乏证候分布以虚证为主,虚证中以气虚类证为主,兼有湿阻及气滞证。相对于单纯运动疗法,结合有氧运动,口服中药及穴位按压的综合干预方法对于癌因性疲乏有更好的改善作用,值得临床应用。气虚证癌因性疲乏患者血清中多种溶血性磷脂含量增多引起的膜磷脂水解破坏,机体抗氧化能力下降和血清内源性大麻素含量下降可能参与癌因性疲乏的发生。
[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.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735
[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.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735
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