[Long-term high-fat diet inhibits hippocampal expression of insulin receptor substrates and accelerates cognitive deterioration in obese rats].

OBJECTIVE: To assess the effect of long-term high-fat diet on the expressions of insulin receptor substrates in the hippocampus and spatial learning and memory ability of obese rats. METHODS: A total of 100 4-week-old male SD rats were randomly divided into two groups and fed with common diet (CD group, n=40) or high-fat diet (HFD group, n=60) for 16 weeks. At 4, 8, 12, 16 and 20 weeks, 8 rats were randomly selected from each group for testing their spatial learning and memory function using Morris water maze. After the tests, the rats were sacrificed for measurement of the metabolic parameters and detection of the expressions of insulin receptor substrate-1 (IRS-1) and IRS-2 mRNAs in the CA1 region of the hippocampus. RESULTS: Compared with those in CD group, the rats in HFD group showed a prolonged escape latency, longer swimming distance, faster average swimming speed, and shorter stay in the platformat 12 weeks. In HFD group, the serum levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and fasting insulin were all significantly increased (P<0.05) and the level of high-density lipoprotein cholesterol decreased (P<0.01) in comparison with those in CD group at each of the time points. No significant difference was found in fast glucose levels between the two groups (P>0.05), but the expressions of IRS-1 and IRS-2 mRNAs were significantly decreased in HFD group at 12 weeks (P<0.05). CONCLUSION: In obese rats, long-term feeding with high-fat diet leads to insulin resistance, which interferes with hippocampal expression of insulin receptor substrates and insulin metabolism to cause impairment of the cognitive function and accelerate cognitive deterioration.

Rational Consideration on Canceling Drug Addition / 中国卫生经济

Objective: Through deeply analyzing “Canceling Drug Addition” policy in the pilot public hospitals, it manages to confront the challenges of “drug maintaining medicine, pharmaceuticals government tenders, pharmaceutical services and essential drug system”, provides advices and suggestions for deepening medical reform. Methods: From systemically learning and understanding the current medical reform policies, closely connected with practice, sketch out a good policy of “addressing both the symptoms and root causes”. Results: Canceling Drug Addition is an operation in the “deep water area” of health care reform, affecting the situation as a whole, which must be supported by relevant reform policies and implementation measures. Conclusion: It is necessary to discuss Canceling Medicine Markup, to innovate the current drug pricing policy and to improve the current price of medical services system, to build hospital quality mechanisms.

Novel potent orally active multitargeted receptor tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of 2-indolinone derivatives.

The inhibition of receptor tyrosine kinases (RTKs) has become a successful approach in the development of anticancer agents. Many potent small-molecule kinase inhibitors have been discovered. We report herein a series of pyrrolo-fused-heterocycle-2-indolinone analogues as inhibitors of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and c-Kit. Among them, some pyrrolo-fused six- and seven-membered-heterocycle derivatives such as 9, 15, 23, and 25 are potent inhibitors of VEGFR, PDGFR, and c-Kit both enzymatically (<50 nM) and cellularly (<50 nM). Furthermore, compounds 9 and 25 possess favorable pharmacokinetic profiles and demonstrate good efficacies against human HT-29 cell colon tumor xenografts in nude mice. Further evaluations are in progress.

Synthesis and biological evaluation of azobicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes.

A series of novel azobicyclo[3.3.0]octane derivatives were synthesized and evaluated as dipeptidyl peptidase 4 (DPP-4) inhibitors. The effort resulted in the discovery of inhibitor 2a, which exhibited excellent efficacies in an oral glucose tolerance test. Introduction of methyl group (2j) could prolong the inhibition of serum DPP-4 activity.

Preparation and evaluation of DEET-ethylcellulose microsphere / 第二军医大学学报

Objective:To prepare DEET-ethylcellulose microsphere(DEET-EC) and observe its properties to retard volatilization of DEET. Methods: DEET-EC was prepared with solvent evaporation method. DEET was dissolved in CH 2Cl 2 with EC served as dispersed phase and 1% PVA water solution as continuous phase. The dispersed phase was added into the continuous phase with stirring rate at 1 000 r/min. The stirring rate was changed into 600 r/min after 30 min, and was kept until CH 2Cl 2 was entirely volatilized. After being watered, precipitated and lyophilized for 12 h, DEET-EC was derived, and the shape was observed with electron microscope. The particle size distribution was detected in 500 microspheres with optical microscope. HPLC method was established to determine the embedding ratio and loaded ratio of DEET-EC microsphere. Chromatograph conditions: Diamonsil ODS column (150 mm?4.6 mm), CH 3OH∶H 2O=65∶35 as mobile phase at 1 ml/min, the detected wavelength 210 nm. Results: The DEET-EC was egg-white and had spherical shape. Almost 90% of the MS distributed in 30-70 ?m, while ( ar ) and ( v ) were 49.6 ?m and 51.2 ?m, respectively. The loading ratio was 18.7% and the embedding ratio was 56.1%(n=6). Conclusion: The solvent evaporation method is convenient and simple to prepare DEET-EC microsphere.

Preparation and characterization of magnetic poly D,L-lactide-co-glycolide phenylarsine oxide nanoparticles / 第二军医大学学报

Objective:To study the preparation technique for magnetic poly D,L-lactide-co-glycolide phenylarsine oxide nanoparticles (M-PLGA-PAO-NPs) and to characterize the resultant product. Methods: M-PLGA-PAO-NPs were prepared by using emulsion-evaporation process. The morphology of the prepared nanoparticles were observed by transmission electron microscope and the magnetism of the particles was determined by vibrating sample magnetometer. Meanwhile, we also evaluated the mean diameter, encapsulation ratio, and drug loading rate of the particles. Results: The nanoparticles had a regular spherical surface, with 80% of them having a diameter of 140-500 nm. We also found that the drug loading rate of the particles was 3.2% and the mean encapsulation ratio was 34.2%. The drug had satisfactory magnetic property. Conclusion: Our method can obtain M-PLGA-PAO-NP with satisfactory quality, it is simple-to-use and the prepared particles can meet the requirement of pharmaceutics.