ABSTRACT
OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.
ABSTRACT
Objective To study the application value of radiotherapy optimization after modified radical mastectomy.Methods From January 2012 to January 2015,one hundred and twelve patients treated with modified radical mastectomy in Taizhou Cancer Hospital were enrolled and divided randomly into group A,B and C.40 patients in group A received modulated radiation therapy(MRT) with 2.0Gy/f,25 times,DT50Gy for 33-35d;35 cases in group B received concurrent chemoradiotherapy with MRT and 37 cases in group C received concurrent chemoradiotherapy with large segmentation scheme of 2.66Gy/f,16 times,DT42.56Gy for 22-24d.The recurrence rate,survival rate and the incidence of acute and chronic radiation injury of the 3 groups were compared.The parameters of V5,V10,V20 and V30 of ipsilateral lung was recorded by dose volume histogram(DVH).Results The total recurrence rate in group C was significantly lower than that of the other two groups (16.2％(6/37) vs.28.6％(10/35) vs.42.5％(17/40),x2 =6.409,P=0.041),while the total survival rate was significantly higher than that of the other two groups (89.2％ (33/37) vs.77.1％ (27/35) vs.65.0％ (26/40),x2 =6.313,P =0.043),and there was no significant difference in the local recurrence and distant metastasis rate in the 3 groups (P＞0.05).The incidence of total radiation injury in group C was lower than that of the other two groups (21.6％ (8/37) vs.42.9％ (15/35) vs.50％ (20/40),x2 =6.973,P =0.031),and there was no significant difference in the incidence of acute and chronic injury and the grade of injury in the 3 groups (P＞0.05).The values of VS,V10,V20 and V30 increased gradually in the 3 groups.The V5 and V10 in group C were significantly higher than those of the other two groups ((32.9 ± 7.4) ％ vs.(17.5 ± 5.9) ％ vs.(16.8 ± 6.4) ％,F =18.625,P=0.000,(42.4±7.3)％ vs.(39.3±5.8)％ vs.(35.5±6.0)％,F=15.624,P=0.000),and there was no significant difference in V20 and V30 among the three groups (P＞ 0.05).Conclusion The combination of concurrent chemoradiotherapy and breast cancer after modified radical mastectomy is of great value in improving prognosis and reducing radiation damage.