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北京京煤集团总医院                                                          第十一届·2023 学术年会论文集

                   Figure 5: Nomogram model. (A) SMARCC1, SETD2, KMT2B, and CHD8 were used to construct a
                   nomogram model to predict the prognosis of patients with severe asthma. (B) Receiver operating

                   characteristic curve to determine the performance of the nomogram model. (C) Calibration curve.
                   3.4 Potential drugs for treating severe asthma
                       DSigDB was used to predict drugs for the treatment of severe asthma, and the results showed
                   that the ten most effective drugs would be lanatoside C, cefepime, methapyrilene, sulpiride, vitamin

                   E, ouabain, metoclopramide, pramocaine, dirithromycin, and tamibarotene.
                   3.5 Construction of an miRNA-mRNA interaction network
                       We predicted the miRNAs upstream those genes used for the nomogram model and used them
                   to  construct  an  miRNA-mRNA  interaction  network  (Figure  6). According  to  our  predictions,

                   SMARCC1 is regulated by seven miRNAs (hsa-miR-1295, hsa-miR-1247, hsa-miR-1268, hsa-miR-
                   3917, hsa-miR-585, hsa-miR-3200-3p, and hsa-miR-1268b), CHD8 is regulated by five (hsa-miR-
                   4632, hsa-miR-662, hsa-miR-4465-3p, hsa-miR-3713, and hsa-miR-4738-5p), SETD2 is regulated
                   by two (hsa-miR-3200-3p and hsa-miR-993), and KMT2B is only regulated by one (hsa-miR-4440).





















                   Figure 6: MiRNA-mRNA interaction network involving SMARCC1, SETD2, KMT2B, and CHD8.
                   4 Discussion
                       Approximately 10% of individuals with asthma are classified as having severe asthma. People
                   with  severe  asthma  not  only  have  a  heavy  psychological  and  financial  burden  but  also  a  high

                   mortality  rate   [5].   Defects  in  chromatin  regulation  are  involved  in  the  development  of  various
                   diseases   [21] . To  investigate  the  role  of  CRs  in  severe  asthma,  we  screened  for  CRs  that  were
                   differentially expressed between patients with severe asthma and healthy individuals. These CRs
                   were subjected to enrichment and immunological analyses. A risk score was also constructed to

                   assess the association between CRs and prognosis in patients with severe asthma.
                       The 80 differentially expressed CRs were mainly enriched in histone modification, chromatin
                   organization, transcription regulator complex, transcription coregulator activity, lysine degradation,
                   and cell cycle. Specialized histone modifications, as the core of chromatin control, can be removed,

                   adjusted, or added to histone units  [22] . It is known that, under specific conditions, naive CD4+ T
                   cells are atypically activated, thus, they differentiate into a Th subpopulation cell type that drives
                   the disease; this is a typical feature of asthma. Moreover, histone modification regulates cell lineage



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