ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Exosomes are nanoscal-scale vesicles containing a variety of proteins(HSP70, actin, Alix, etc.), lipids, mRNAs and miRNAs.They are commonly found in various tissues and cells of the organism.They are involved in processes such as intercellular communication, immune regulation and cell signaling pathway regulation, and then play an important role.Recent studies have shown that exosome-mediated intercellular signaling plays an important role in the progression of Alzheimer's disease(AD). This paper reviewed the general characteristics of exosomes, clarifies the possible role of exosomes in the pathogenesis of AD, and also discussed the application prospect and the related challenges of exosomes as a new potential option in the future treatment of AD.

Galectin-3 (Gal3) is a multipotent protein involved in cell activation, proliferation and migration, which plays an important role in a variety of physiological and pathological processes. Recent studies have shown that Gal3 plays an important role in the pathogenesis of central nervous system degenerative diseases, but its specific mechanism is not clear. This article reviews the research progress on the mechanism and expression of Gal3 in central nervous system degenerative diseases, and discusses the application value of Gal3 as a new therapeutic target in central nervous system degenerative diseases, so as to provide new scientific basis for early prevention and treatment of central nervous system degenerative diseases.

One hundred Alzheimer′s disease (AD) patients with behavioral and psychological symptoms of dementia (BPSD) treated with donepezil+risperidone group ( n=50, group 1) or hydrochloride memantine+risperidone group ( n=50, group 2) in geriatric departments of Hangzhou Seventh People′s Hospital were enrolled in the study. Montreal cognitive assessment scale (MoCA), positive and negative syndrome scale (PANSS), treatment emergent symptom scale (TESS) were applied for evaluation; and blood routine examination, blood biochemistry, eletrocardiogram were performed in two groups before and after treatment. After treatment, MoCA score in group 2 (16.10±3.90) was significantly higher than that in group 1 (18.14±3.71)( t=-3.99, P<0.01), and PANSS score in group 2 (86.66±6.62) was significantly lower than that in group 1 (109.50±11.51; t=12.67, P<0.01). The incidence rates of dry mouth (16%,8/50), extrapyramidal side effects (10%,5/50) and the total score of TESS (3.92±2.02) in group 2 were markedly lower than those of group 1 [44%(22/50), 36%(18/50), (12.49±1.45);χ 2=9.33,9.54, t=17.90,all P<0.01]. Meanwhile, group 2 had significantly lower influences on the levels of blood lipids and fasting blood glucose (all P<0.01). The risperidone dose used in group 2 was significantly lower than that in group 1 [(2.06±0.50) vs. (3.85±0.89)mg, t=14.40, P=0.04].The results suggest that hydrochloridememantine combined with risperidone is more effective with less side effects compared to donepezil combined with risperidone for AD patients with BPSD.

To investigate the effect and possible mechanisms of triterpenic acid-enriched fraction from Cyclocarya paliurus(TAE)on glucagon secretion in insulin-resistance pancreatic α cells, the model of insulin resistance in αTC1-6 cells was induced by long term exposure to high glucose. Experimental groups were divided as follow: control(5. 5 mmol/L glucose), model(25 mmol/L), TAE(1, 5, 10 μg/mL), and TAE(10 μg/mL)plus wortmannin(10 nmol/L)group. The supernatant and lysate of treated cells were collected to determine glucagon secretion by ELISA kit. The mRNA and protein abundance of IRS-1, PI3K and Akt were measured by qPCR and Western blot analysis. Results showed that TAE could not only significantly reduce glucagon secretion induce by high glucose in a dose-dependent manner, but also remarkably increased the mRNA and protein abundance of IRS-1, PI3K and Akt in αTC1-6 cells. However, these effects of TAE were reversed by PI3K inhibitor wortmannin. In conclusion, it suggested that TAE could improve the insulin resistance induced by high glucose in pancreatic α cells which may be related with the activation of IRS-1/PI3K/Akt signaling pathway.

The purpose of this study was to investigate the hypoglycemic effect and the safety of medicinal formula composed of Cyclocarya paliurus and Mulberry leaves. An experimental diabetic rat model was established by high energy diet plus small dosage of auoxan(ALX). At the same time, each group rats were given distilled water(blank and model), metformin(Met), Cyclocarya paliurus aqueous extract(CP), Mulberry leaves aqueous extract(ML)and the different proportions of aqueous extract mixtures of Cyclocarya paliurus and Mulberry leaves(CM1, CM2 and CM3), respectively. Fasting blood glucose(FBG), OGTT, TC, TG, LDL-C, HDL-C, insulin and liver and kidney function related index were gauged to evaluate the hypoglycemic effect and the safety of samples. The results showed that FBG level of the rats in CM1, CM2 and CM3 groups decreased 21. 64%, 16% and 12. 55%, respectively, comparing with that of model group. Moreover, FBG, glucose tolerance and pancreatic tissue morphology were remarkably improved in CM1 group. TC and LDL-C levels of rats in ML and CM3 groups decreased significantly compared with the those of Model group(P< 0. 05), which showed ML and CM3 were beneficial to regulate the blood lipid level in diabetic rats. Furthermore, all the administration groups had no adverse effect on liver function index. The down regulation of kidney function index of CP, ML, CM1, CM2 and CM3 groups comparing with model group indicated that Cyclocarya paliurus and Mulberry leaves could alleviate the injury of liver and kidney. Our results demonstrated that the medicinal formula composed of Cyclocarya paliurus and Mulberry leaves were favorable to reduce blood glucose and can regulate lipid metabolism without liver and kidney toxicity.

Objective To investigate demographic factors implicated in the functional maturation of autologous arteriovenous fistula in a population of patients with end-stage renal disease. Methods The data of 335 consecutive patients with end-stage renal disease who were performed autologous arteriovenous fistula from January 2010 to December 2015 were analyzed retrospectively. The parameters affecting autologous arteriovenous fistula functional maturation were screened. Results Overall arteriovenous fistula functional maturation rate was 78.14%(218/279). The arteriovenous fistula functional maturation rate was 68.33%(82/120) in diabetes and 85.54%(136/159) in non-diabetes, and there was significant difference (χ2=11.844, P<0.01). The arteriovenous fistula functional maturation rate was 62.26%(33/53) in hypoproteinemia and 81.86%(185/226) in non-hypoproteinemia, and there was significant difference (χ2=9.648, P<0.01). Diabetes and hypoproteinemia were the risk factors to promote functional maturation (OR=6.003, 8.476). The arteriovenous fistula functional maturation rate was 87.10%(81/93) in calcium channel blockers using and 73.66%(137/186) in non-calcium channel blockers using, and there was significant difference (χ2=6.556, P<0.05). Calcium channel blockers was the protective factor for promoting functional maturation (OR=0.086). Conclusions Diabetes and hypoproteinemia are found to be associated with functional non-maturation, while calcium channel-blocker agents are associated with better functional maturation.

Objective To investigate the knowledge of chronic heart failure (CHF) and influencing factors in general practitioners (GP) in Beijing.Methods A self-designed questionnaire contained total 28 items,including basic knowledge of CHF,non-drug management,drug management and other management ; clinical cases were used to test clinical ability in 7 items.The questionnaire survey was conducted among GPs who participated in continuing education courses from 16 counties/districts in Beijing during January to June 2013.Results Total 720 questionnaires were distributed and 657 valid questionnaires were returned with a recovery rate of 91.3％.Total scores was 60.6.Scores of basic knowledge,non-drug management,drug management and other management was 63.1,76.9,44.0 and 56.9,respectively.There were statistical differences in scores of basic knowledge,non-drug management,drug management and other management between GPs with different diploma (F value:36.8,5.8,21.6,12.2,respectively; P ＜0.01) ; there were significant differences in scores of basic knowledge and drug management among GPs with different working years (F value:15.1 and 17.4,respectively ; P ＜ 0.01) ; there was significant difference in scores of drug management among GPs with different professional title (F =7.69,P ＜ 0.01).Only for GPs with junior college diploma,the scores of basic knowledge and drug management in GPs with working ≥20 y were higher than those working ＜ 20 y(P ＜ 0.01).The accuracy of clinical ability in GPs with junior college diploma,undergraduate diploma and post-undergraduate diploma was 39.6％,41.6％,41.8％ (P ＞ 0.05).Conclusions The knowledge of CHF is less desirable in GPs of Beijing,so that measures should be taken to improve the GP's knowledge of CHF.

A survey on clinical knowledge of coronary artery disease (CAD) management in general practitioners (GPs) in Beijing was conducted from March to September,2013.The questionnaire contained 4 cases (stable angina pectoris,post-percutaneous coronary intervention,acute anterior myocardial infarction and acute inferior myocardial infarction) and related clinical questions.Five hundred questionnaires were distributed and 471 valid questionnaires were returned with a recovery rate of 94.2％.The correct rate was 87.3％ and 61.8％ for diagnosis and treatment of emergent events in acute anterior myocardial infarction; however,the correct rate for other knowledge was ranged between 23.4％ and 40.6％.The correct rate increased with the educational levels in 5/11 items(P ＜ 0.01)and increased with the professional titles(P ＜ 0.001)in 3/11 items,which was not associated with the attendance of training or frequency of training attendance.The results indicate that clinical knowledge of CAD management for GPs in Beijing should be improved and the training methods should be focused on the clinical capacity.

To construct, express, purify and identify the Myc-R9-EGFP fusion protein and validate its transduction activity in the cultured porcine embryo fibroblasts. cDNA of pig c-Myc gene was amplified by RT-PCR with specific primers of 9 arginine (R9) from the primordial genital ridges and inserted into prokaryotic expression vector pET-28a-EGFP. After DNA sequencing confirmation, the recombinant plasmid was then transformed into BL21 (Escherichia coli) strain. After IPTG induction, the target fusion protein was efficiently induced to express, successfully purified by Novagen His-Bind kit, identified by SDS-PAGE and Western blotting. Finally, its high transduction activity in the porcine embryo fibroblasts was validated. The purified Myc-R9-EGFP fusion protein and the validation of its transduction activity in fibroblasts have provided an experimental foundation for further studies on the biological characterization of Myc protein, and soundly facilitated the further study of establishing pig induced pluripotent stem cells by recombinant protein.
Animals ; Arginine ; genetics ; metabolism ; Cell Line ; Cell Membrane Permeability ; drug effects ; Escherichia coli ; genetics ; metabolism ; Fibroblasts ; cytology ; metabolism ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; pharmacokinetics ; Swine