Objective To investigate the effect of pramlintide,a pancreatic amyloid peptide analog,on learning and memory of Alzheimer's disease(AD)mice through antioxidant stress,and to determine the expression of phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Methods The APP/PS1 mice were divided into a pramlintide treatment group(intraperitoneal injection of 0.5 μmol/L per day for 10 weeks)and an AD group(same dose of PBS),with 5 mice in each group.The learning and memory abilities were detected with water maze test,the pathological changes of the hippocampus were observed with HE staining and immunohistochemistry,the morphological characteristics of dendritic spines in hippocampus were observed after Golgi staining,and the ultrastructure of hippocampal neurons was observed through transmission electron microscopy(TEM).The content of malondialdehyde(MDA)and the level of superoxide dismutase(SOD)in the hippocampal tissue were detected by biochemical assay,and the levels of inflammatory factors IL-6,TNF-α and IL-1β were determined with ELISA.Western blotting was applied to measure the expression of PI3K/Akt signaling pathway related proteins in the hippocampus.In the cell experiment,SH-SY5Y cells were added with Aβ 1-42 to establish a cell model of AD.After the cells were treated with pramlintide,the levels of oxidative stress and inflammatory response were detected,and cell apoptosis was detected by immunofluorescence.Results The animal experiments showed that pramlintide treatment resulted in significantly shortened escape latency(P<0.01),increased platform crossings(P<0.01),and prolonged time to exploring hidden platform(P<0.01).In the hippocampal tissue of the pramlintide treatment group,HE staining displayed hippocampal neurons in high density and neat arrangement(P<0.05),immunohistochemical results showed significantly reduced Aβ protein(P<0.01),Golgi staining results demonstrated more dendritic spines(P<0.05),TEM revealed almost intact neuronal mitochondrial structure,with reduced vacuolization and clear and identifiable morphology.When compared with the AD group,the levels of oxidative stress and inflammatory response were decreased(P<0.01),and the relative expression of p-PI3K/PI3K and p-Akt/Akt proteins was increased(P<0.01)in the treatment group.In cell experiments,the levels of oxidative stress and inflammatory response were decreased in AD cell model after pramlintide treatment(P<0.01),and the results of immunofluorescence showed that cell apoptosis was declined(P<0.01).Conclusion Pramlintide can improve the cognitive function,reduce the hippocampal deposition of Aβ,reduce oxidative stress and inflammatory response,alleviate the pathological changes of neuronal ultrastructure,and enhance the expression of PI3K/Akt signaling pathway in AD mice.

Objective To investigate the expression level of circular RNA circ-Tns3 in Alzheimer's disease(AD)mice and its role in Aβ-induced neuronal damage.Methods Five APP/PS1 transgenic AD mice and 5 wild-type(WT)mice,weighting of 23～26 g and aged 6 months were subjected in the study.Morris water maze test was used to assess learning and memory abilities,and immunohistochemical staining was performed to observe the number of Aβ plaques in the hippocampal tissue.Subsequently,total RNA was extracted from the brains to detect the differential expression of circRNAs between AD and WT mice,and the results were further analyzed with Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.The top 6 differentially expressed circRNAs were validated by real-time quantitative PCR(RT-qPCR).In in vitro experiments,Aβ1-42 was used to treat neuronal cells to establish AD cell model,and si-circ-Tns3 was transfected into Aβ1-42-treated neuronal cells to knock down circ-Tns3.RT-qPCR was used to determine the expression levels of circ-Tns3 and miR-671-5p.Cell viability and apoptotic rate were detected by CCK-8 assay and TUNEL staining,respectively.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)were measured using corresponding kits,and the levels of inflammatory factors IL-6,IL-1β,and TNF-α were detected with ELISA.The interaction between circ-Tns3 and miR-671-5p was verified by dual-luciferase reporter assay and RNA-binding protein immunoprecipitation(RIP)assay.The expression level of Sirt1 protein was detected by Western blotting.Results The 6-month-old AD mice exhibited significant cognitive impairment and Aβ deposition(P<0.01).There were 269 differentially expressed circRNAs identified between AD and WT mice,of which 159 were up-regulated and 110 down-regulated.GO and KEGG enrichment analyses showed that these differentially expressed circRNAs were mainly involved in synaptic transmission,memory,and cholinergic synapse signaling pathways.The expression of circ-Tns3 was significantly increased not only in the brain tissue of AD mice but also in neuronal cells after Aβ1-42 treatment.In cellular experiments,knockdown of circ-Tns3 significantly reduced cell viability and number of apoptotic cells in Aβ1-42-treated neuronal cells,decreased MDA content,increased SOD activity,and reduced the levels of IL-6,IL-1β,and TNF-α(P<0.01).The starBase database predicted that circ-Tns3 and miR-671-5p have complementary sequences,and dual-luciferase reporter and RIP assays confirmed their interaction.The bioinformatics database predicted that miR-671-5p and sirt1 have complementary sequences.Western blotting indicated that in neuronal cells treated with Aβ1-42,the expression of sirt1 was increased after knockdown of circ-Tns3(P<0.01).In Aβ1-42-treated neuronal cells,after knockdown of circ-Tns3,addition of miR-671-5p inhibitor significantly decreased the expression level of sirt1 protein(P<0.01).Conclusions circ-Tns3 is highly expressed in AD mice and cell model of AD.Knocking circ-Tns3 down improves neuronal damage.circ-Tns3 may be involved in the neuronal damage through regulating sirt 1 protein by binding to miR-671-5p.

Objective To establish a method for determining the content of Gd³⁺ in gadoteric acid meglumine salt injection. Methods ICP-MS was used. The separation column was a metal chelate column (1-ml Chelating Sepharose column), column temperature was normal temperature. Flow rate was 1 ml/min. Injection volume was 500 μl. Atoms were measured by ICP-MS with a molecular weight of 157 (The molecular weight of Gd was 157). The carrier gas was argon. Results The linear range of Gd³⁺ mass concentration was 0-500 ng/ml (r=1.000); The precision, stability and repeatability of the sample recovery test were all in accordance with the requirements. Conclusion The method was simple in operation, accurate in results and good in repeatability, which could be used to determine the content of Gd³⁺ in gadoteric acid meglumine salt injection.

Objective To evaluate the effect of compound glycyrrhizin on the prevention and cure of cytarabine syndromes. Methods A total of 130 patients with hematological malignancies treated by moderate or high dose of cytarabine in the 303th Hospital of PLA from July 2010 to July 2016 were included. Patients were randomly divided into the control group and the experiment group by using random number table method, and each group had 65 patients. In the control group, patients were treated with cytarabine alone. In the experiment group, patients were treated with cytarabine plus compound glycyrrhizin. Skin rash and fever in patients of the two groups were also recorded. Results of blood routine tests, liver and kidney function tests were monitored during the treatment. Results Sixty-one patients in the experiment group and 63 patients in the control group were enrolled finally. In experiment group and control group, the differences in the incidence of cytarabine syndromes [8.2 % (5/61) vs. 41.3 % (26/63), χ2＝ 18.1, P < 0.001], skin rash [1.6 % (1/61) vs. 12.7 % (8/63), χ2＝16.3, P <0.001], and fever [6.6 % (4/61) vs. 36.5 % (23/63), χ2＝5.63, P <0.017] were statistically significant. There was no significant difference of the incidence of liver injury and minimum blood cell count between the two groups (P＞ 0.05). Conclusion Compound glycyrrhizin can effectively reduce the incidence of cytarabine syndromes, but the larger size and multiple center studies are needed to further verify the effect.

China ; Communicable Diseases ; Pediatrics ; Societies, Medical

Objective To analyze the usage of basic drugs in non-primary health care institutions in Luzhou,Sichuan,to comment on the performance of the basic drug system,and to provide reference data for relevant ministries and departments.Methods To collect and to statistically analyze the data of the categories and sales amount of the basic drugs used by three level-3A health care institutions and nine level-2 health care institutions from Jan 1,2010 to Dec 31,2012. Results The purchasing proportion of the basic drugs in the level-3A institutions for 2010,2011,and 2012 are respectively 15.62%,17.84%,20.01%;similarly,the data for the level-2A institutions are respectively 29.35%,32.16%,35.07%;the data for the level-2B institutions are respectively 34.73%,37.05%,40.02%.The sales proportion ofthe basic drugs for the years of2010,2011,and 2012 are respectively 10.43%,12.38%,15.04% for the level-3A institutions,25.08%,27.24%,30.12% for the level-2A institutions,and 29.24%,32.08%,35.03%for the level-2B institutions.Conclusion Non-primary health care institutions should firmly execute the basic drug system, enhance the propaganda of this policy,try to increase the purchasing proportion of the basic drugs,supervise the prescription behavior of the doctors, and optimize the basic drug index in order to use drugs more appropriately and efficiently.