Abstract:Objective To investigate the expressions and significance of microRNA (miR)-92a and hypoxia inducible factor (HIF)-1α in refractory diabetic foot ulcer (DFU) of patients with diabetes mellitus (DM).Methods A total of 90 DM patients with DFU treated from April 2018 to April 2019 were selected as observation group,and 40 DM patients without DFU were served as control group at the same time.The levels of miR-92a and HIF-1α mRNA were detected by quantitative polymerase chain reaction (qPCR),and HIF-1α protein expression was detected by immunohistochemical staining.The cultured human skin fibroblasts were divided into negative control (NC) group (transfected with empty plasmid),mimic group(transfected with miR-92a mimic),mimic+HIF-1α group(transfected with miR-92a mimic and HIF-1α overexpression plasmid) and HIF-1α group(transfected with HIF-1α overexpression plasmid).The levels of miR-92a and vascular endothelial growth factor (VEGF) were respectively detected by qPCR and Western blot.Results In 90 patients,31 patients with poor wound healing of DFU were designed as poor DFU group,and the others were classified as favorable wound healing of DFU group (favorable DFU group).There were significant differences in miR-92a and HIF-1α mRNA levels among control group,poor DFU group and favorable DFU group (P<0.01 ).The level of miR-92a statistically decreased in the order of poor DFU group,favorable DFU group and control group(P<0.05 ),and HIF-1α mRNA level decreased in the order of favorable DFU group,poor DFU group and control group(P<0.05 ).HIF-1α was almost not expressed in normal tissues,but was significantly up-regulated in the wounds of DFU patients (P<0.05 ).The scores of HIF-1α staining intensity were the highest(5.24±1.05)in favorable DFU group,followed by poor DFU group (2.79±0.68) and control group(0.91±0.25) (P<0.05 ).There was a negative correlation between miR-92a and HIF-1α mRNA and protein levels in wound healing marginal tissues (r=-0.441,-0.392,P<0.05 ).miR-92a can bind to 3′-untranslated region (UTR) of HIF-1α mRNA and inhibit the levels of HIF-1α mRNA and protein.The levels of HIF-1α and VEGF protein were the highest in HIF-1α group,followed by mimic+HIF-1α group,NC group and mimic group(P<0.05 ).Conclusion The wound healing disorder in DFU patients is related to the increase of miR-92a and the decrease of HIF-1α,and miR-92a can decrease the level of VEGF by targeting the expression of HIF-1α,thereby inhibiting angiogenesis.To evaluate the clinical efficacy of photodynamic therapy combined with endobronchial stent implantation or with cryotherapy in the treatment of malignant central airway stenosis.Methods Forty-five patients with central airway stenosis caused by malignant tumor in Zhejiang Provincial People′s Hospital from October 2009 to October 2019 were retrospectively analyzed.According to the different interventional therapy,patients were divided into stent group(treated with stent implantation after photodynamic therapy, n=20) and cryotherapy group (treated with photodynamic therapy after cryotherapy, n=25).The increase of airway diameter,dyspnea score,clinical manifestation score,physical condition score［karnofsky performance scale index(KPS)］,respiratory function,complications,survival rate and average survival time after treatment were compared between two groups.Results After treatment,the diameters of trachea,left main bronchus and right main bronchus increased in cryotherapy group compared with stent group ( P<0.01).The degrees of stenosis were decreased after treatment in two groups and were decreased in cryotherapy group than those in stent group( P<0.05, P<0.01).The dyspnea score and the clinical manifestation score were lower,and the forced expiratory volume in the first second cryotherapy(FEV1),forced vital capacity (FVC) and KPS score were higher than those before treatment in two groups ( P<0.01),but there were no significant differences in these indicators between two groups ( P>0.05).No serious complications occurred in both groups,and there were no significant differences in survival rate and average survival time between two groups ( P>0.05).Conclusions Photodynamic therapy combined with stent implantation or cryotherapy are effective treatments to alleviate the symptoms of malignant airway stenosis.Both methods can rapidly dilate the narrow lumen,relieve the symptoms of dyspnea,and improve the respiratory function and the quality of life of patients.