Objective To investigate the effects of mesenchymal stem cells(MSCs)on the pathological structure and cytokine expression of lung tissue in septic model of diabetic rats. Methods Diabetic rats were ran-domly divided into control,sham-operation,sepsis and MSC-treated groups. The diabetic model was induced by high-sucrose and high-fat diet combined with streptozotocin and cecal ligation and puncture. The pathological changes of lung tissue were observed at 6,12,18 and 24 hours after operation respectively,and the expression of SP-D,TNF-α,IFN-γ and IL-10 in lungs were measured.Results The levels of SP-D,TNF-α and IFN-γ in lung tissue increased gradually with the elongation of time after CLP. The expression of IL-10 in lung tissue increased and then decreased. The trend of MSC intervention increased the content of SP-D,TNF-α and IL-10 in the lung tissue of non-diabetic septic rat model and reduced the content of IFN-γ.MSC intervention reduced the SP-D and TNF-α content.The intervention of MSC had no effect on the content of IFN-γ in the lung tissue of diabetic septic rats.However,it increased and then decreased the content of IL-10.Conclusions The model of sepsis in diabetic rats can be established by feeding combined high-sugar and high-fat diet and streptozotocin combined with cecal ligation and puncture. Mesenchymal stem cells affect sepsis inflammation and organ damage. But its specific role depends on the immune status and the timing of mesenchymal stem cell selection.

ABSTRCT Purpose To explore the evolution of HER2 nega-tive subgroups(IHC Null,Ultra-low and 1+)in breast cancer with hormone receptor(HR)positive before and after neoadju-vant therapy,and the relationship with clinical pathological fea-tures.Methods There were 255 patients who did not achieve pathological complete response(pCR)consecutively after neoad-juvant therapy.Immunohistochemistry was used to detect the ex-pression of ER,PR,HER2 and Ki67 and to evaluate the evolu-tion of HER2-negative subgroups after neoadjuvant therapy and its relationship with clinicopathological characteristics.Results Among the 255 patients included in this study,HER2 expression was 0 and 1+in 116 cases(45.5％)and 139 cases(54.7％)respectively before neoadjuvant therapy,and then HER2 0 was further divided into Null group(61 cases,23.9％)and Ultra-low group(55 cases,21.6％).After neoadjuvant therapy,HER2 expression was 0 and 1+in 117 cases(45.9％)and 138 cases(54.1％)respectively,and then HER2 0 was further di-vided into Null group(64 cases,25.1％)and Ultra-low group(53 cases,20.8％).HER2 status changed in 121 patients(47.5％)after neoadjuvant therapy.The highest conversion rate was from HER2 Ultra-low before neoadjuvant therapy to 1+after neoadjuvant therapy,with a conversion rate of 11.76％(30/255),followed by HER2 1+to the Ultra-low,with a conversion rate of 10.98％(28/255).After the neoadjuvant therapy,44 of 55 cases had transformation in the HER2 Ultra-low group,with the conversion rate of as high as 80％.Chi-square test showed that HER2 expression before neoadjuvant therapy was correlated with the maximum tumor diameter(≤2 cm,＞2cm)after neo-adjuvant therapy(x2=6.106,P=0.047);the tumor of HER21+before neoadjuvant therapy was mostly 2 cm or less in the di-ameter.The HER2 status after neoadjuvant therapy was correla-ted with the tumor thrombus(x2=6.975,P=0.029).Patients with HER2 Ultra-low after treatment were more likely to have vascular invasion.Conclusion In HR positive breast cancer,when the HER2 0 cases are divided into Ultra-low and Null sub-groups,the HER2 conversion rate increases significantly after neoadjuvant therapy,in which the Ultra-low conversion rate is the highest,indicating that the HER2 Ultra-low cases are highly unstable after neoadjuvant therapy.It is important to detect HER2 expression in residual lesions after neoadjuvant therapy and to identify the Ultra-low HER2 expression subgroup.