Study On Radiation Fatigue Of Tumor Based On Metabonomics

Background:With the development of medical science,the continuous improvement of surgery,radiotherapy,chemotherapy,biological and targeted therapy and other technologies have greatly improved the cure rate and survival rate of cancer patients.The treatment of cancer is no longer limited to eliminating and shrinking the tumor entity,but pays more attention to improving the quality of life of cancer patients.Cancer-induced fatigue(CRF)is one of the symptoms that can easily affect the quality of life of patients.Due to insufficient clinical attention and lack of intervention means,fatigue can make patients feel more painful than other symptoms with reliable prevention and treatment measures.Radiotherapy has become an important factor in the development of CRF in cancer patients.Radiotherapy related fatigue will not only reduce patients’ function and emotional state,but also affect patients’ daily living ability and quality of life.Chinese medicine has unique advantages in improving tumor symptoms,and syndrome differentiation and treatment is the essence of it.Firstly,the distribution of cancer-induced fatigue syndrome related to radiotherapy should be clarified,and on this basis,the fatigue state of patients can be more accurately judged and the clinical efficacy can be improved by combining objective metabolic indicators.Objective:1.To investigate the distribution characteristics of radiation-related cancer-induced fatigue syndrome and the dynamic changes of fatigue degree in cancer patients.2.The urine of patients with radiation-related cancer-induced fatigue was analyzed by liquid chromatography-mass spectrometry combined with multi-dimensional statistical analysis method,and the mechanism of radiation-related fatigue was preliminarially discussed,so as to provide objective data for alleviating fatigue in this group of people.Methods:1.The fatigue assessment method using improved fatigue rating scale(Modified Fatigue Impact Scale,MFIS),the scale has 21 projects,each project is divided into5 levels scoring system,according to the criteria of MFIS to evaluate the severity of fatigue.Fatigue status was evaluated 1 day before radiotherapy,4 days after radiotherapy,and 14 days after radiotherapy.2.Syndrome differentiation type investigation method combining with the characteristics of the crowd clinical radiotherapy and the literature research,expert consultation,preliminary investigation and early in colleges and universities teaching material and diagnostics of TCM "TCM diagnosis experiment methodology,on the basis of the content of the four diagnosis in traditional Chinese medicine for common viscera is deficient about TCM four diagnostic data filtering,use of TCM syndrome differentiation table preparation of cost research institute.Doctors with senior experience in the department of traditional Chinese medicine of No.971 Hospital of the Navy complete the form after making professional judgment on the patient.3.Ultra-performance liquid chromatography was used as the separation system,and mass spectrometry was used as the detection system.Urine samples were separated by chromatography and then ionized.The mass spectra of the compounds were detected by mass analyzer of mass spectrometry.Orthogonal least square discriminant analysis(OPLSDA)was used to determine the metabolites of the fatigue patients before and after radiotherapy.Database was used to identify these biomarkers,and the identified biomarkers were input into KEGG database to construct and analyze the corresponding metabolic pathways.Resuilts:1.Univariate repeated measure ANOVA was used to determine the fatigue degree of radiotherapy patients at different time points.After testing,the data of each group obeyed normal distribution,and the fatigue degree scores at three time points of radiotherapy were statistically significant.Further pairwise comparison was made on the fatigue degree of 1day before radiotherapy and 4 days before radiotherapy,4 days after radiotherapy and 14 days after radiotherapy,and 1 day before radiotherapy and 14 days after radiotherapy.The results showed:The fatigue degree of 1 day before radiotherapy was 10.52±4.623,the fatigue degree of 4 days after radiotherapy was 17.67±8.494,and the fatigue degree of 14 days after radiotherapy was 53.10±15.311.The number of fatigue cases were 19.35%(24cases),23.39%(29 cases),121 cases(97.58%).Fatigue degree of patients gradually increased;The fatigue degree of 1 day before radiotherapy was lighter than that of 4 days after radiotherapy,the fatigue degree of 4 days before radiotherapy was lighter than that of14 days after radiotherapy,and the fatigue degree of 1 day before radiotherapy was lighter than that of 14 days after radiotherapy,the differences were statistically significant.2.The main syndromes of fatigue patients after radiotherapy include:God fatigue,less gas lazy words,sallow complexion,shortness of breath,palpitations,dry mouth,mouth pain,muscle weakness,thin food after abdominal distension,lumbar spinal pain,,dizziness,insomnia,forgetfulness,five upset hot,urine urine,stool stem node,spontaneous sweating,night sweating,heart palpitations,pale face,nasal heat,swallowing adverse,pulse fine,red tongue,moss thin,weak pulse,less moss,pulse number,etc.,Compared with before radiotherapy,the changes were obvious.The TCM dialectical classification of radiotherapy related fatigue patients mainly included qi and Yin deficiency type(73.55%,89 cases),lung and stomach Yin deficiency type(18.18%,22 cases),qi stagnation and blood stasis type(5.79%,7 cases),and heat and toxin accumulation type(2.48%,3 cases).Before radiotherapy,there were only 5 cases(4.1%)of Qi and Yin deficiency type,11 cases(9.09%)of lung and stomach Yin deficiency type,69 cases(57.02%)of heat and toxin accumulation type,36 cases(29.75%)of Qi stagnation and blood stasis type.The type group formed by the mutual transformation of TCM syndrome types before and after radiotherapy was relatively complex.Among them,there were two forms of transformation with frequency greater than 10: from excessive accumulation of heat and toxin to deficiency of Qi and Yin in 62 cases,accounting for 51.24%;From qi stagnation and blood stasis to qi Yin deficiency23 cases(19.01%).3.Metabolomics results showed that:4 metabolites(uric acid,4-guanidabutyric acid,citric acid,and hipuric acid,all significantly decreased)in the urine of the pre-radiotherapy group and the post-radiotherapy group under positive ion mode.There are 6 significant metabolic pathways(purine metabolism,arginine and proline metabolism,citric acid cycle,glyoxalate and dicarboxylate metabolism,alanine aspartic acid and glutamate metabolism,phenylalanine metabolism).In the anion mode,there were three metabolites(hemuric acid decreased significantly,glycolcholic acid and cholic acid increased significantly)and two metabolic pathways(primary bile acid biosynthesis,phenylalanine metabolism)with significant difference in urine between the pre-radiotherapy group and the postradiotherapy group.Conclusion:The type of TCM syndrome differentiation of tumor patients changed before and after radiotherapy,from heat and toxin accumulation to deficiency of both Qi and Yin gradually.The fatigue degree of patients increased with the extension of radiotherapy time.Metabonomics tests showed that a variety of metabolites were changed in patients before and after radiotherapy,and a variety of metabolic pathways were involved.