Objective To explore the effect of Osthole on neuroinflammation in Alzheimer's disease(AD)by regulating the lactylation of pyruvate kinase M2(PKM2).Methods(1)Animal experiments:18 mice were divided into three groups,namely wild-type(WT)group,APP/PS1 group and APP/PS1+Osthole group.Learning-and memory-related biobehavioral indicators were compared among the three groups.Immunohistochemistry was used to detect the positive expression of Iba1 in brain tissue,enzyme-linked immunosorbent assay(ELISA)was employed to detect the levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,and IL-1β in brain tissue,and Western Blot was used to detect the protein expression levels of Pan lactylation(Pan-kla)and PKM2 lactylation(PKM2-kla)in brain tissue.(2)Cell experiments:an in vitro AD model was constructed by treated in mouse microglia(BV2 cells)with LPS/Aβ1-42,and followed by treatment with Osthole.Cell viability was detected by methyl thiazolyl tetrazolium(MTT),expression of Iba1(a marker of microglial activation)was detected by Western Blot,nitric oxide(NO)production was assessed by Griess reagent,and levels of IL-6,TNF-α and IL-1β were detected by ELISA.BV2 cell-conditioned medium(CM)was co-cultured with neuroblastoma cells(Na2 cells)to assess the protective effect of Osthole on Na2 cells.(3)Molecular docking was performed between Osthole and PKM2,and experimental verification was conducted.Results In animal experiments,deficits of learning and memory in mice were aggravated in APP/PS1 group compared with that in WT group,which were improved upon treatment with Osthole.Furthermore,the APP/PS1 group mice showed an increase in Iba1 positive cells in brain tissue,an increase in the levels of pro-inflammatory factors IL-6,TNF-α and IL-1β,as well as an increase in the levels of Pan-kla and PKM2-kla compared with the WT group,while the above indexes were inhibited by the Osthole treatment.In cell experiments,Osthole had no significant effect on BV2 cell viability at concentrations up to 100 μmol/L.Treatment with LPS/Aβ1-42 upregulated the expression of Iba1,NO production,and levels of pro-inflammatory factors IL-6,TNF-α,and IL-1β in BV2 cells,while Osthole significantly inhibited the expression of these LPS/Aβ1-42-induced indicators.Meanwhile,Osthole attenuated the damage of BV2-CM on Na2 cells.The molecular docking results indicated a good binding affinity between Osthole and PKM2.Treatment with Osthole can down-regulated the levels of lactate,Pan-kla and PKM2-kla in the AD cell model.Conclusion Osthole can improve the condition of AD and reduce neuroinflammation by inhibiting the lactylation of PKM2.

Objective To investigate the application value of γ-glutamyltransferase(GGT),alkaline phosphatase(ALP)and peripheral blood neutrophil to lymphocyte ratio(NLR)in liver cancer.Methods 100 patients with liver cancer admitted to Wuming Hospital Affiliated to Guangxi Medical University from January 2012 to December 2020 were retrospectively selected to be included in liver cancer group,100 patients with cirrhosis to be included in cirrhosis group,100 patients with hepatitis to be included in hepatitis group,and 100 healthy physical examination subjects from our hospital during the same period were included in physical examination group.The GGT,ALP and NLR levels of the four groups were compared.Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of each index for liver cancer.Results The levels of NLR,GGT and ALP in liver cancer group were significantly higher than those in cirrhosis group,hepatitis group and physical examination group(P<0.05).The NLR in cirrhosis group was significantly higher than that in physical examination group and hepatitis group(P<0.05).GGT and ALP in cirrhosis group and hepatitis group were significantly higher than those in physical examination group(P<0.05).Spearman correlation analysis showed that NLR was positively correlated with GGT and ALP,and GGT was positively correlated with ALP(P<0.05).When NLR,GGT and ALP were detected separately,area under the curve(AUC)of NLR was the largest(0.943,95％CI:0.901-0.971,P<0.001),and AUC of ALP was the smallest.The AUC of three combined detections was 0.987(95％CI:0.959-0.998),and the sensitivity was 99.0％.Conclusion The combined detection of NLR,GGT and ALP can significantly improve the detection rate of liver cancer,and the combined detection has better application value.

OBJECTIVE：To investigate the effect of increasing efficacy and decreasing toxicity of Limax extract （LE）on cyclophosphamide（CTX）in the treatment of hepatocellular carcinoma. METHODS ：The mice were randomly divided into normal group，model group ，CTX group （0.02 g/kg），LE low-dose ，medium-dose and high-dose groups （LEL，LEM，LEH group ，0.6，1.2，2.4 g/kg），CTX+LE low-dose ，medium-dose and high-dose combination groups （CTX+LEL，CTX+LEM，CTX+ LEH group ，the same dose as single drug group ），with 10 huangrenbin518@163.com mice in each group. Except for normal group ，other groups were inoculated with hepatoma cells H 22 in the left ar mpit to establish tumor bearing models. After 24 h of inoculation ，normal group and model group were intragastrically given normal saline ， and administration groups were intragastrically given corresponding drugs ，once a day ，for 10 days. On the second day after the last administration ，the general conditions of mice in each group were observed ；the body mass ，thymus index （LI），spleen index （SI）were measured ；the tumor inhibition rate was detected. The effect （q）of combination therapy was evaluated by King ’s formula . The counts of WBC ，RBC and PLT ，serum contents of ALT ，ALT，Scr and BUN were detected in model group ，CTX group and combination groups ，and the contents of MDA，SOD and GSH ，the levels of VEGF ，TNF-α and IL-6 in the tumor tissue were detected by colorimetry and ELISA in above groups. The protein expression of oncogenes （p53，Bcl-2 and Bax ）were detected by immunohistochemical method in model group，CTX group and CTX+LEM group. RESULTS ：The mice in the model group were in poor spirit and had symptoms of excessive drinking and eating ；although the body weight ，TI and SI were not significantly abnormal compared with normal group （P＞0.05），WBC count and AST content were significantly increased ，ALT and BUN contents were significantly decreased （P＜ 0.05 or P＜0.01）. Compared with model group ，above symptoms of mice were all improved in administration groups. The tumor weight of administration groups ，TI and SI of CTX group and TI of combination groups were decreased significantly ，but tumor weight of LEL group and LEH group ，TI and SI of LE single groups and combination groups were significantly higher than CTX group；tumor weight of combination groups were significantly lower than CTX group （P＜0.05 or P＜0.01）. The tumor inhibition rates of administration groups were 29.58％-72.08％. The q values of CTX+LEL group ，CTX+LEM group and CTX+LEH group were 1.03，0.97 and 0.86，respectively. Compared with model group ，WBC count ，AST and BUN contents of CTX group ，MDA contents of combination groups ，VEGF，TNF-α and IL-6 levels of administration groups ，the protein expression of Bcl- 2 in CTX group and CTX+LEM group were decreased significantly ；the activities of SOD and GSH of administration groups ，the protein expression of p 53 in CTX+LEM group and Bax in CTX group ，CTX+LEM group were increased significantly （P＜0.05 or P＜ 0.01）；WBC counts and AST contents of administration groups ，ALT content of CTX+LEM group ，SOD activity of CTX+LEH group and GSH activity of CTX+LEM group were all significantly higher than those of CTX group ；MDA content of CTX+LEH group，VEGF and TNF-α levels of CTX+LEM group and CTX+LEH group，IL-6 levels of administration groups were all significantly lower than CTX group （P＜0.05 or P＜0.01）. CONCLUSIONS ：LE combined with CTX can increase the anti-tumor effect，and LE can reduce the toxicity of CTX induced immunosuppression and bone marrow suppression in mice ，with effect of increasing efficacy and decreasing toxicity. The effect may be related to antioxidant stress ，inhibition of angiogenesis and secretion of inflammatory factors ，and regulation of apoptosis protein expression.

Objective To discuss effect of mechanical oiling and manual oiling in rust protection of coupling surgical instruments.Methods A total of 68 surgical instruments were divided into observation group and control group,with 34 surgical instruments in each group.The control group was treated with mechanical oiling,and the observation group used manual oiling,cleaning qualified rate,the rust rate after 3 months,lubricant amount and the average cost per month were observed.Results The qualified rate of surgical instruments by visual inspection in the control group was 99.09％,and was 98.77％ by magnifier,and the observation group were 99.23％ and 98.89％,respectively,but there was no significant difference between the two groups (P ＞ 0.05).Rust rate after 3 months was 8.94％ in the control group,and was 1.40％ in the observation group,there was significant difference between two groups (P ＜ 0.05).Lubricating oil amount and total cost of two groups in the control group were (28 800.00 ±618.96)mL,(12 180.00±256.78) RMB,and were (5 600.00 ±489.71) mL,(2 216.00 ± 189.93) RMB,respectively,in the observation group,and there was significant difference between two groups (P ＜ 0.05).Conclusion Compared with mechanical oiling,manual oiling has better lubrication effect and can significantly reduce cost and corrosion of equipment,improve the maintenance effect,and ensure the quality of disinfection equipment.

Objective To discuss effect of mechanical oiling and manual oiling in rust protection of coupling surgical instruments.Methods A total of 68 surgical instruments were divided into observation group and control group,with 34 surgical instruments in each group.The control group was treated with mechanical oiling,and the observation group used manual oiling,cleaning qualified rate,the rust rate after 3 months,lubricant amount and the average cost per month were observed.Results The qualified rate of surgical instruments by visual inspection in the control group was 99.09％,and was 98.77％ by magnifier,and the observation group were 99.23％ and 98.89％,respectively,but there was no significant difference between the two groups (P ＞ 0.05).Rust rate after 3 months was 8.94％ in the control group,and was 1.40％ in the observation group,there was significant difference between two groups (P ＜ 0.05).Lubricating oil amount and total cost of two groups in the control group were (28 800.00 ±618.96)mL,(12 180.00±256.78) RMB,and were (5 600.00 ±489.71) mL,(2 216.00 ± 189.93) RMB,respectively,in the observation group,and there was significant difference between two groups (P ＜ 0.05).Conclusion Compared with mechanical oiling,manual oiling has better lubrication effect and can significantly reduce cost and corrosion of equipment,improve the maintenance effect,and ensure the quality of disinfection equipment.