| Objective:observe the immune and miRNA characteristics of different syndrome types of the advanced TNBC and the clinical efficacy of traditional Chinese medicine. Explore the possible mechanism of traditional Chinese medicine in the treatment of TNBC patients with advanced stageMethods:This study collected 64 patients with advanced TNBC, type of syndrome is spleen deficiency with phlegm dampness, qi stagnation and blood stasis type and yin deficiency of liver and kidney. Recorded patients’immune function (observation index CD4+/CD25+/CD127-T cells, the cells CD8+/CD28-T, cells CD8+/CD28+T, NK four immune cells) before treatment in, exploring advanced TNBC immunological characteristics in different syndrome types。At the same time, in each type of syndrome of patients, the selected three cases of detection of peripheral blood miRNA situation, explore the different syndrome types and differences in the expression of peripheral blood miRNA and function prediction. Then to the group of patients with traditional Chinese medicine treatment in February, and record the quality of life of patients before and after treatment, treatment of immune cells and patients with progression free survival, to explore the clinical efficacy of drug treatment.Results:1. After multivariate variance test, we found that there were differences in the immune cells of different syndrome types. The F values were 0.565,5.391,5.941,4.336,0.07,0.571, 0.04,0.017。Showing that CD4+/CD25+/CD127-T cell P>0.05, the difference was not statistically significant. CD8+/CD28-T cell, D8+/CD28+T cell and NK cell P<0.05, difference was statistically significant.CD8+/CD28-T cells in different syndrome types is different, CD8+/CD28-T cells of different syndrome types were compared, the results show deficiency, spleen deficiency with phlegm dampness contrast with qi stagnation and blood stasis type and yin deficiency of liver and kidney, the value oft, respectively, is-2.147,0.84; P is 0.038,0.045< 0.05, the difference is statistically significant; Qi stagnation and blood stasis type contrast with yin deficiency of liver and kidney, t is 2.91. P is 0.006<0.05, the difference was statistically significant. It shows that the CD8+/CD28-T cells of qi stagnation and blood stasis type> spleen deficiency with phlegm dampness> yin deficiency of liver and kidney.CD8+/CD28+T cells in different syndrome types is different, CD8+/CD28+T cells of different syndrome types were compared, the results show deficiency, spleen deficiency with phlegm dampness contrast with qi stagnation and blood stasis type and yin deficiency of liver and kidney, the value of t is 1.646,-1.608; Pis 0.041,0.016< 0.05, the difference is statistically significant. Comparison of qi stagnation and blood stasis and liver kidney yin deficiency type t is-3.568, P value is 0.00<0.05, the difference was statistically significant. It shows that the CD8+/CD28-T cells of yin deficiency of liver and kidney> spleen deficiency with phlegm dampness>qi stagnation and blood stasis type.NK cells in different syndrome types is different, NK cells of different syndrome types were compared, the results show deficiency, spleen deficiency with phlegm dampness contrast with qi stagnation and blood stasis type and yin deficiency of liver and kidney? the value of t is 1.467,1.453; P values were 0.151>0.05 difference was not statistically significant, 0.034<0.05 the differences have statistically significant; Qi stagnation and blood stasis type and yin deficiency of liver and kidney, t is-2.89, P is 0.006<0.05, the difference was statistically significant. It shows that the NK cells of yin deficiency of liver and kidney> qi stagnation and blood stasis type, yin deficiency of liver and kidney> spleen deficiency with phlegm dampness.In summary, by analysis of results of numerical statistics analysis, In three kinds of syndrome type, qi stagnation and blood stasis type of immune system in patients is the worst, yin deficiency of liver and kidney is the best,, spleen dampness type of immune status is in the middle.2. Qi stagnation and blood stasis type compares with spleen deficiency and phlegm dampness syndrome type, the number of upregulation miRNA is 68, the cut is 101;the number of upregulated pathway is 17,involving chemical carcinogenicity, delivery of olfactory, lipoic acid metabolism and so on;the downregulated is 17,involving in the RNA polymerase, glutathione metabolism and so on;Qi stagnation and blood stasis type compares with liver and kidney yin deficiency type, the number of upregulation miRNA is 91, the cut is 105;the number of upregulated pathway is 20,involving mucopolysaccharide biosynthesis, oxidative phosphorylation and so on;the downregulated is 18,involving in regulate autophagy and methane metabolism and so on; Spleen deficiency and phlegm damp type compared with Yin deficiency of liver and kidney, the number of upregulation miRNA is 67.the cut is 94;the number of upregulated pathway is 19,involving glutathione metabolism, cytochrome P450 metabolism of exogenous substances, chemical carcinogens and so an,17 downregulated pathway is involved in the RNA degradation, glycosphingolipid biosynthesis pathway and so on. May be it is the up and down miRNA makes the differences in different syndromes.3. There are 40 patients with the immune cells examination before and after treatment, make the paired t-test of the immune cells before and after, t value are 12.78,11.62,-15.83,-14.52; P are less than 0.05, the difference was statistically significant. Dialectical treatment of Chinese medicine can reduce the CD8+/CD28-T cell CD4+/CD25+/CD127-T cells, and increase the CD8+/CD28+T cell and NK cell.4.64 patients were completed the quality of life scale before and after treatment, that is, FACT-B quality of life scale. The results using the paired t-test method were compared, physiological status, social/family status, emotional status, functional status, pay more attention to the additional. The total score of the scale, before and after comparison, the value of T, respectively-27.17,0.57,-16.10,-24.24,-11.67,-41.56, social/family status before and after comparison, P values is 0.568>0.05, difference was not statistically significant, physiological status, emotional status, functional status, pay more attention to the additional, scale score of P values were less than 0.05, the difference is statistically significant.5. To make analysys of atient’s age, four groups of immune cells, differentiation into type, age, transfer (organ/non organ) and other parts through the multivariate Cox regression analysis. The results show that the CD4+/CD25+/CD127-T cells, NK cells is the effect of patients with PFS independent influence factors (P< 0.05), age, differentiation of symptoms and signs, CD8+/CD28-T cells, CD8+/CD28+T cells are not affected patients PFS independent factors.6. The mean value of PFS for all patients was 11.9 months, and the median survival time was 11. To make analysis of each type of syndrome of PFS, the result is that, phlegm dampness patients with PFS of mean value is 12.3 months. The median survival time value is 11.5 months; syndrome types of patients with qi stagnation and blood stasis type of mean PFS was 11.9 months. The median survival time value is 11 months; syndrome types for the mean PFS of patients with liver kidney yin deficiency type value is 13.5 months and the median survival time value is 12 months. There is no significant difference in PFS between the three types of syndrome patientsConclusion:1. In the three kinds of syndrome type, yin deficiency of liver and kidney in patients is with immune best, qi stagnation and blood stasis type is the worst,Spleen deficiency phlegm dampness type of immunity in the center2. The expression profile of miRNA in peripheral blood of patients of different syndrome types was different. Qi stagnation and blood stasis type compares with spleen deficiency and phlegm dampness syndrome type, the number of upregulation miRNA is 68, the cut is 101;the number of upregulated pathway is 17,;the downregulated is 17; Qi stagnation and blood stasis type compares with liver and kidney yin deficiency type, the number of upregulation miRNA is 91, the cut is 105;the number of upregulated pathway is 20,;the downregulated is 18; Spleen deficiency and phlegm damp type compared with Yin deficiency of liver and kidney, the number of upregulation miRNA is 67.the cut is 94;the number of upregulated pathway is 19, the downregulated is 17. May be it is the up and down miRNA makes the differences in different syndromes.3. Metastatic site, CD4+/CD25+/CD127-T cells, NK cells were independent influencing factors of patients PFS.4. Syndrome differentiation of traditional Chinese medicine therapy can improve the deficiency, phlegm dampness, liver kidney yin deficiency type and qi stagnation and blood stasis in patients with immune function and quality of life. |
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