| Objective: To retrospectively analyze the clinical medication characteristics and efficacy of Qilian Yisui Qingdu Granule in the treatment of myelodysplastic syndromes(MDS),and to explore the potential mechanism of Qilian Yisui Qingdu Granule in the treatment of MDS based on network pharmacology.Methods:(1)Retrospective study: the data of MDS patients hospitalized in the Department of Hematology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2017 to November2021 were collected,and the basic demographic characteristics of patients,the revised international prognostic scoring system(IPSS-R)group,Traditional Chinese medicine(TCM)syndrome types,Qilian Yisui Qingdu granules combined with drugs or therapies were counted;Patients who took Qilian Yisui Qingdu Granule were set as the exposed group,while patients did not take Qilian Yisui Qingdu Granule were set as the nonexposed group.The baseline characteristics of the exposed group and the non-exposed group were balanced by the method of propensity score matching(PSM).The blood routine examination,western medicine efficacy,TCM syndrome score,TCM syndrome efficacy and adverse reactions were compared between the two groups.SPSS Statistics 26.0 software was applied for statistical analysis of clinical data,and SPSS Clementine12.0 software for association rule analysis of combined drugs or therapies.(2)Network pharmacology research: Collecting Chinese medicine ingredients of Qilian Yisui Qingdu Granule through HERB database,build“Chinese medicine-ingredient network”,and collect Chinese medicine ingredient targets based on CTD and Swiss Target Prediction database;Collecting MDS-related targets through Mala Cards database,screening intersection targets of Chinese medicine components and diseases,defining them as treatment-related targets,building “proteins interaction networks” of treatment-related targets based on STRING database,analyzing topological structures of “Chinese medicinecomponent networks” and “proteins interaction networks” of treatmentrelated targets,identifying hub components and hub targets,defining hub components as ligands and hub targets as receptors,and using SYBYL-X for molecular docking analysis to evaluate their affinity;g:profiler was used to enrich and analyze the treatment-related targets,to explore the potential pathways and biological processes of Qilian Yisui Qingdu Granule in the treatment of MDS.Results:(1)Retrospective study:(1)A total of 163 MDS patients were enrolled,63 of whom took Qilian Yisui Qingdu Granule,with a male-female ratio of 1.52:1 and a median age of 61.5(16-81)years.There were 35 cases in the low-middle risk group of IPSS-R and 37 cases in the highrisk group of IPSS-R.Most of the TCM syndromes were spleen-kidney deficiency and blood stasis block syndrome.(2)In the IPSS-R low and medium risk group,Qilian Yisui Qingdu Granule was combined with red blood cell infusion,thalidomide and Chinese herbs for invigorating qi and invigorating spleen,while in the IPSS-R high risk group,Qilian Yisui Qingdu Granule was combined with azacytidine,red blood cell infusion and Chinese herbs for invigorating qi and invigorating spleen,clearing away heat and toxic materials.(3)In IPSS-R low and medium risk group,exposed group and non-exposed group matched 23 pairs,and the baseline characteristics of the two groups were comparable(P>0.05).After treatment,there was no significant difference between the western medicine curative effect of exposed group and non-exposed group(P>0.05).After treatment,the hemoglobin improvement of exposed group was better than that of non-exposed group(P<0.05),and the improvement of TCM syndrome score and TCM syndrome curative effect of exposed group were better than that of non-exposed group(P<0.05)(4)In IPSS-R high-risk group,16 pairs were matched between the exposed group and the nonexposed group,and the baseline characteristics of the two groups were comparable(P>0.05).There was no significant difference between the western medicine curative effect of the exposed group and the non-exposed group(P>0.05).After treatment,the hemoglobin and neutrophil counts of the exposed group increased significantly,and the improvement was better than that of the non-exposed group,and the difference was statistically significant(P<0.05).The TCM syndrome score of the exposed group was statistically significant.(2)Research on network pharmacology:(1)The prescription of Qilian Yisui Qingdu Granule including two parts: Fuzheng prescription and Quxie prescription,in which 819 components are identified by Fuzheng prescription and 173 components are identified by Quxie prescription.There are 43 overlapping components between them,totally 949 components.β-sitosterol,oleanolic acid,rutin,2-hydroxy-3-methyl anthraquinone and apigenin are the hub components in the“Chinese medicine-component networks”.(2)There are 200 potential targets of MDS treated by Fuzheng recipe and 115 potential targets of MDS treated by Quxie recipe.In the treatment-related target “proteins interaction network”,tumor protein P53(Cellular tumor antigen p53,TP53),Myc proto-oncogene protein,MYC),RAC-α serine/threonine protein kinase(AKT1),signal transducer and activator of transcription 3(STAT3)and GTPase HRAS(HRAS)are the hub targets.(3)The molecular docking between hub components and hub targets showed that 2-hydroxy-3-methylanthraquinone had the best affinity with TP53.(4)Enrichment analyses showed that the potential mechanism of Qilian Yisui Qingdu Granule for treating MDS mainly involved biological processes such as hematopoietic stem cell lineage,JAK-STAT signaling pathway and PI3K/Akt signaling pathway.Conclusion: Qilian Yisui Qingdu Granule is mostly used for MDS with deficiency of spleen and kidney,stagnation of toxin and blood,deficiency of qi and yin,stagnation of toxin and blood,and is suitable for IPSS-R groups,which can reduce TCM syndrome score and improve TCM syndrome curative effect with good safety.In IPSS-R low and medium risk group,Qilian Yisui Qingdu Granule focused on combined supportive treatment,which could improve hemoglobin.In IPSS-R high-risk group,Qilian Yisui Qingdu Granule focused on reducing toxicity and increasing efficiency of azacytidine.The mechanism of Qilian Yisui Qingdu Granule for strengthening body resistance and eliminating pathogenic factors involves multiple components,multiple targets and multiple pathways. |
