| [Background]Cancer-related fatigue,because of its severe symptoms,difficult to relieve,and long duration,affects the smooth progress of antitumor therapy while seriously affecting patients’ basic life in both psychological and physical aspects.At present,only a single symptomatic treatment is available and the efficacy is not good.Wenyangbushenjianpi prescription is composed of Astragalus,Radix Angelicae Sinensis,Radix Rehmanniae,Rhizoma Atractylodis Macrocephalae,Herba Cistanches,Epimedium,Radix Bupleurum,Poria and Rhizoma Polygonati.This formula has been used in clinical practice for many years and has been effective in relieving fatigue,loss of appetite and depression after chemotherapy.However,the clinical efficacy of this prescription in treating cancer-related fatigue needs to be further verified,and its specific mechanism of action needs to be further explored and studied.[Objective]1.To observe the efficacy of Wenyangbushenj ianpi prescription in treating patients with cancer-related fatigue of spleen-kidney yang deficiency type through a clinical randomized controlled trial.2.To investigate the mechanism of action related to the treatment of cancer-related fatigue in spleen-kidney deficiency type by Weny angbushenj ianpi prescription by observing the changes of immune and inflammatory cytokines T-lymphocyte subpopulation,NK cells and interleukin-6.3.To explore the mechanism of action of the prescription of Wenyangbushenj ianpi in the treatment of Spleen-kidney yang deficiency type of cancer-related fatigue through network pharmacology,and to provide a new therapeutic idea for the treatment of cancer-related fatigue in Chinese medicine.[Methods]1.60 study subjects who met the inclusion criteria were selected from patients attending the Department of Oncology,Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine from October 2021 to December 2022,and were divided into 30 cases in the control group(symptomatic treatment)and 30 cases in the treatment group(symptomatic treatment+Wenyangbushenj ianpi prescription treatment)according to the random number table method for clinical treatment observation.The Simple Fatigue Scale,Carlsbad Rating Scale,Chinese Medicine Evidence Scoring Scale were recorded as well as T-lymphocyte subpopulation,NK cells,and interleukin-6 laboratory indexes were collected before and after the patients’treatment,and then SPSS 25.0 was used to statistically analyze and compare the data before and after treatment in both groups,and finally GraphPad Prism software was used to visualize the data.2.The TCMSP database,TCM Database@Taiwan,and Uniprot database were used to screen and supplement the active ingredients and potential targets of Wenyangbushenjianpi prescription,and Cytoscape 3.8 software was used to draw the "drug-ingredient-target" diagram.The OMIM,DRUGBANK and Gencards databases were used to collect disease targets for oncogenic fatigue,and the STRING platform was used to analyze protein interactions and map PPI networks.We use Metascape platform for GO and KEGG pathway enrichment analysis and visualization of key targets.[Results]1.Comparison between the two groups before treatment:In this study,there was no significant difference between the two groups before treatment in terms of gender,age,tumor type,tumor stage,basic conditions of underlying diseases,as well as fatigue scale,Chinese medicine evidence scale,KPS score,T-lymphocyte subpopulation,NK cells,and interleukin-6 observation indexes(P>0.05),which were comparable.2.Simple fatigue scale:both groups were significantly relieved after treatment(P<0.05),and the treatment group had better effect than the control group(P<0.01).3.Chinese medicine symptoms scale:The control group did not show significant improvement in deafness/tinnitus and clear and long urine after symptomatic treatment(P>0.05),while the rest of symptoms showed significant improvement(P<0.05).In the treatment group,all symptoms were significantly relieved after treatment(P<0.05).By comparing the two groups after treatment,it was found that there was no significant difference in the symptoms of deafness/tinnitus,lumbar and knee weakness,and spontaneous sweating(P>0.05),while the differences in the remaining symptoms and total scores were statistically significant(P<0.05).4.KPS score:After treatment,the KPS scores of both control and treatment groups were significantly improved,and the treatment group had a better effect on relieving the patients’ physical condition(P<0.05).5.Immunological and inflammatory indexes:CD3+,CD4+,CD4+/CD8+,and NK cells were significantly increased and CD8+was significantly decreased in both control and treated groups after treatment,and the comparison of the two groups after treatment showed significant differences between the two groups except for CD3+(P<0.05).Interleukin-6 levels were significantly lower in both groups after treatment and were significantly lower in the treatment group than in the control group(P<0.01).6.Network pharmacology:There are 63 active ingredients containing 245 target proteins in the treatment of cancer-related fatigue with warm yang tonifying kidney and spleen formula.There were 957 disease targets of cancer-caused fatigue,and finally 37 key targets and 305 KEGG pathways were obtained.The main active ingredients of Wen Yang tonic kidney and spleen formula for cancer-related fatigue are dousterol,β-sitosterol,ivy saponin element,glutathione,kaempferol,quercetin,etc.TP53,CASP3,AKT1,VEGFA,etc.are its key targets,and the main involved signaling pathways may include PI3K-Akt signaling pathway,NF-κB signaling pathway,P53 signaling pathway,tumor necrosis factor etc.[Conclusion]The prescription of Wenyangbushenjianpi can effectively relieve fatigue in patients with cancer-related fatigue and improve symptoms related to Yang deficiency in the spleen and kidney,which may work by promoting apoptosis of tumor cells,improving immune function related to lymphocyte subpopulations and reducing inflammatory cytokine levels. |
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