ABSTRACT
We explored the pharmacodynamic material basis and network regulatory mechanism of Fufang Yuxingcao Mixture (FYM) for the treatment of fever and inflammation. Targets of the 25 compounds in FYM were predicted according to the reverse pharmacophore method and TCMSP, UniProt database. Gene ontology (GO) function enrichment and pathway analysis of the targets was analyzed by Omicsbean software and the Kyoto Gene and Genome Encyclopedia (KEGG) database. A "compound-target-pathway-pharmacological action-effect" network was established with Cytoscape 3.6.1 software. The lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was used to verify the anti-inflammatory effects of FYM and its 10 important components. The network pharmacology experiment showed that 25 compounds affected 97 pathways through 211 targets, of which 15 key targets [including RAC-alpha serine/threonine-protein kinase (AKT1), insulin (INS), vascular endothelial growth factor A (VEGFA), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), tumor necrosis factor (TNF), transcription factor AP-1 (JUN), caspase-3 (CASP3), matrix metalloproteinase-9 (MMP9), interleukin-8 (IL-8), prostaglandin G/H synthase 2 (PTGS2), proto-oncogene c-Fos (FOS), tyrosine-protein kinase SRC (SRC), c-Jun N-terminal kinase 1 (MAPK8), estrogen receptor 1 (ESR1)] and 46 pathways (including NF-kappa B signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, arachidonic acid metabolism, cAMP signaling pathway, T cell receptor signaling pathway, calcium signaling pathway, inflammatory mediator regulation of TRP channels, chemokine signaling pathway, Th1 and Th2 cell differentiation, natural killer cell mediated cytotoxicity, etc.) were related to anti-inflammatory, antipyretic, immune regulation, and analgesia. In vitro cell experiments showed that FYM and the 10 components (including isoquercitrin, luteoloside, baicalein, wogonin, wogonoside, phillyrin, forsythoside A, chlorogenic acid, isochlorogenic acid A, and sweroside) could significantly reduce the expression of nitric oxide (NO), TNF-α and IL-6 in cell supernatants, indicating that the above 10 components may be the key pharmacodynamic material basis of FYM.
ABSTRACT
OBJECTIVE@#To study the effects of clinicopathological features, laboratory parameters and treatment regimens on the prognosis of patients with multiple myeloma.@*METHODS@#The clinical data of 97 patients with multiple myeloma treated with chemotherapy in Department of Hematology, the 1st Hospital of Hainan Medical College were analyzed retrospectively. The clinicopathological features (age, sex, severe anemia, light chain type, hypoproteinemia, paraplegia, renal injury, amyloidosis, complex karyotype, bone disease classification, Eastern Cooperative Oncology Group (ECOG) physical status score, complete remission, etc.), laboratory parameters (C-reactive protein, lactate dehydrogenase, blood calcium, serum β2 microglobulin, etc.), and treatment schemes (thalidomide maintenance treatment) were recorded. The patients were followed up for 1-60 months, and their total survival time were recorded. A single factor and multiple factors were used to analyze the factors affecting the total and early mortality of the patients. The survival curves were plotted by the Kaplan-Meier method and the survival analysis was carried out by Log-rank test.@*RESULTS@#Among 97 patients, 29 cases (29.90%) achieved complete remission, and 56 cases (57.73%) achineved partial remission. The total effective rate was 87.63% (85/97). At the end of the follow-up, 19 cases (19.59%) died, and 1, 3 and 5 year survival rates were 80.41%, 71.13% and 37.11% respectively. The median overall survival time was 29 (1-60) months. The results of single factor analysis showed that age, hypoproteinemia, severe anemia, paraplegia, renal injury, amyloidosis, complex karyotype, complete remission and thalidomide maintenance therapy were the factors affecting the prognosis of the patients (all P＜0.05). Further multiple factor Logistic regression analysis showed that age and hypoproteinemia, severe anemia, paraplegia, amyloidosis, complex karyotype and thalidomide maintenance treatment were factors affecting the prognosis (P＜0.05). Of the 97 patients, 8 cases died early. The results of single factor analysis showed that amyloidosis and severe anemia were risk factors for early death (all P＜0.05), and further multivariate Logistic regression analysis showed that amyloidosis was an independent risk factor for early death (P＜0.05).@*CONCLUSION@#There are many adverse factors affecting the prognosis of patients with multiple myeloma, such as age, hypoproteinemia, severe anemia, paraplegia, amyloidosis, complex karyotype and so on. The risk of early death in the patients with amyloidosis is higher, and salidomide maintenance therapy can help to prolong the life span of the patient.