Objective To investigate the effects of the two major conjugated linoleic acid(CLA) isomers on serum lipoprotein composition in fatty rats.Method Eighteen male OLETF rats were randomly divided into three groups.The control group fed with AIN76 diets,CLA groups were fed with 1% 9c,11t-CLA (9ct group) or 1%10t,12c-CLA (10tc group) containted AIN76 diets.After two weeks,serum triglyceride (TG),total cholesterol (TC),and high density lipoprotein cholesterol (HDL-c) were determined by commercial kits.On the other hand,serum lipoprotein were separated into chylomicron(CM),very low density lipoprotein(VLDL),low density lipoprotein(LDL) and HDL by HPLC according to the different particle sizes,and the TC and TG levels were measured in each lipoprotein.Results 10t,12c-CLA feeding reduced the concentrations of rat serum TG significantly,and increased the concentration of serum TC (26.1%) by increasing TC levels of the small particle size LDL and the big particle size HDL.While 9c,11t-CLA feeding increased the serum TG by 22.6%,and had no effect on the serum TC.Conclusion 10t,12c-CLA can reduce the concentration of serum TG and increase the concentration of HDL-c,but the effect on the improvement of atherosclerosis still need further investigation.

Tolvaptan is a novel oral selective arginine vasopressin V2 receptor antagonist.Tolvaptan improves heart failure signs and symptoms without serious adverse events.Tolvaptan has no effect on all-cause mortality and cardiovascular death or admission rate for heart failure.But in heart failure patients with hyponatremia,tolvaptan can decrease cardiovascular death and admission rate for heart failure.

Background and purpose:Gastric cancer is one of the leading causes of cancer death throughout the world.When compared with optimal supportive care alone,combination chemotherapy yields a significant advantage in the management of advanced gastric cancer.However,no single regimen has emerged or been accepted as being clearly superior over another.Here we investigated the efficacy and safety of "docetaxel+ cisplatin + fluorouracil" 5-day combination chemotherapy as treatment in patients with advanced gastric cancer.Methods:Between 2004 January and 2005 July,we enrolled 30 patients [males 22,median age 53 years(range 28-72)] with advanced gastric cancer.The regimen consisted of docetaxel 75 mg/m~(2) on day 1,cisplatin 15 mg/ m~(2) on days 1-5,and fluorouracil 500 mg/ m~(2) on days 1-5,every 3 weeks.All patients received over two cycles of this regimen.Results:A total of 99 cycles were administered.Mean cycle number per patient was 3.3.The administered dose intensity of docetaxel was 23.5 mg/m~(2)/week,fluorouracil 735 mg/ m~(2)/week and cisplatin 14.7 mg/ m~(2)/week,which corresponded to 94%,97.5% and 92.3% of planned doses.Of these patients,16(53.3%) achieved a partial response,8(26.6%) stable disease,and 6 patients(20%) showed progressive disease.The median time to progression was 5.1 months.(95% CI 4.1-6.0 months).Median overall survival was 9.9 months.(95% CI 8.1-11.6 months).Leukopenia occurred during 36.7% of cycles(36 of 99 cycles);18.2% grade Ⅰ,10.1% grade Ⅱ,5.0% grade Ⅲ and 3.0% grade Ⅳ.Anemia occurred in 12.1%(12 of 99 cycles);7.1% grade Ⅰ and 5.0% grade Ⅱ.Thrombocytopenia was 15.2%(15 of 99 cycles) and all were grade Ⅰ or Ⅱ.Diarrhea,stomatitis and hypersensitivity occurred in 16.7%(5 out of 30 patients),respectively.Neutropenic fever occurred in two patients(6.7%) and myalgia in nine(30%).Conclusions:Docetaxel combined with fluorouracil and cisplatin is an active and tolerable regimen for the treatment of patients with advanced gastric cancer.

Objective To make a systematic evaluation of the efficacy and safety of Eszopiclon and Alprazolam in the treatment of insomnia.Methods By searching the PubMed,Cochrance Library,CNKI, WANFANG,and VIP database,we studied the literature published between 2005 to 2016 on the efficacy and safety of Eszopiclon and Alprazolam in the treatment of insomnia.We collected the randomized controlled trials (RCTs), evaluated the quality of methods and then analyzed the data using RevMan5.3 software.Results A total of 18 RCTs were included,involving 2088 patients.According to Meta-analysis,Eszopiclon group had a significantly higher total efficacy rate [RR=1.07,95% CI (1.02,1.11),P=0.003],lower severity of adverse reactions [MD=-0.43,95% CI(-0.75,-0.12),P=0.008]and incidence of adverse reactions [RR=0.46,95% CI(0.32, 0.66),P<0.0001]than Alprazolam group.However,the two groups did not significantly differ in sleep quality scores after 4-week teatment [MD=-0.05,95% CI(-0.22,0.12),P=0.54].Conclusion Eszopiclon is more effective on insomnia than Alprazolam,with better safety,and it deserves wide clinical use.

Objective To investigate the effect of gypenoside on lipopolysaccharide (LPS)-mediated inflammatory response. Methods The BV2 microglia cell line was cultured in vitro. The BV2 microglia cells were divided into four groups: normal control, LPS (10 ng/ml), GP + LPS (GP 20 μg/ml, LPS 10 ng/ml), and GP (20 μg/ml). After 24 h cultivation, ELISA was used to detect the levels of tumor necrosis factor α(TNF-α), interleukin (IL)-1β, and IL-6. Immunocytochemistry staining and Western blot were used to detect the expression levels of nuclear factor (NF-κB) and suppressor of cytokine signaling 1 (SOCS-1). Results Compared with the normal control group, the release of TNF-α, IL-1β and IL-6, as well as the expression level of NF-κB in the LPS group were increased significantly (all P < 0. 001). Compared with the LPS group, the release of TNF-α, IL-1β and IL-6, as well as the expression level of NFκB were decreased significantly, while the expression level of SOCS-1 was increased significantly (P < 0. 001). There were no significant differences in the release of TNF-α, IL-1β and IL-6, as well as the expression levels of NF-κB and SOCS-1 between the GP group and normal control group (all P > 0. 05 ). Conclusions GP can significantly inhibit the LPS-mediated microglial inflammatory response. SOCS-1 protein may be involved in GP inhibiting LPS-mediated microglial inflammatory response.

Abstract： Objective To evaluate the filtration effects of various nanofiltration systems on intravenous human immunog⁃ lobulin（IVIG）in order to screen the optimal nanofiltration system. Methods Various nanofilters were used for IVIG filtration to determine the best one and then various prefilters were selected to combine with the optimal nanofilter for IVIG filtration to determine the optimal nanofiltration system. Results The tangential flow（cross flow）nanofilter showed better filtering effect than dead end（direct current）nanofilter，and nanofilter C was the best one. The effect of deep filtration prefilter was better than that of absolute filtration prefilter，and prefilter Y1 in series with nanofilter C was the optimal nanofiltration system. Conclusion The optimal nanofiltration system was determined through the effect evaluation of various nanofiltration systems filtering for IVIG.

Aim To investigate the effect of liver X receptor (LXR) activation on the proliferation of hippocampal neural stem cells in global cerebral ischemia/reperfusion (I/R) mice,and its mechanisms.Methods A total of 75 C57BL/6 mice were randomly divided into three groups,namely the sham operation group,the cerebral I/R group and the cerebral I/R with TO901317 treatment (I/R + TO90) group.The I/R mouse model was induced via the bilateral common carotid artery occlusion.HE staining was used to detect the pathological changes in hippocampal CA1 region.Immunohistochemistry was executed to detect hippocampus DCX + cells.Immunofluorescence of BrdU was implemented to detect the proliferation neural stem cell.Morris water maze test was used to assess spatial learning and memory in mice.Western blot was used to detect the expression of hippocampus LXRα,LXRβ,ABCA1,p-ERK1/2,t-ERK1/2,p-CREB,t-CREB,BDNF.Results LXR activation improved cognitive recovery(P ＜0.01),and induced the proliferation of neural stem cells (P ＜ 0.01) in I/R mice.The expressions of hippocampal ABCA1,p-ERK1/2,p-CREB,BDNF in I/R + TO90 group mice also increased (P ＜ 0.01).Conclusions LXR activation can induce the proliferation of hippocampal neural stem cells and facilitate cognitive recovery following global cerebral I/R in mice,which may be related to the activation of hippocampal ERK1/2-CREB-BDNF pathway and then promoting endogenous neurogenesis in the hippocampus DG region of I/R mice.

OBJECTIVETo optimize the synthetic pathway and fermentation process of yeast cell factories for production of oleanoic acid.

METHODUsing the DNA assembler method, one copy of Glycyrrhiza glabra beta-amyrin synthase (GgbAS), Medicago truncatula oleanolic acid synthase (MtOAS) and Arabidopsis thaliana cytochrome P450 reductase 1 (AtCPR1) genes were introduced into Saccharomyces cerevisiae strain BY-OA, resulting in strain BY-20A. YPD medium with different glucose concentration were then used to cultivate strain BY-2OA.

RESULTIncreasing gene copies of GgbAS, MtOAS and AtCPR1 resulted in increased beta-amyrin and oleanolic acid production. The strain BY-2OA produced 136.5 mg x L(-1) beta-amyrin and 92.5 mg x L(-1) oleanolic acid, which were 54% and 30% higher than the parent strain BY-OA. Finally, the titer of oleanolic acid increased to 165.7 mg x L(-1) when cultivated in YPD medium with 40 mg x L(-1) glucose.

CONCLUSIONProduction of oleanoic acid increased significantly in the yeast strain BY-2OA, which can provide the basis for creating an alternative way for production of oleanoic acid in place of extraction from plant sources.

Biomass ; Biotechnology ; methods ; Dose-Response Relationship, Drug ; Fermentation ; Glucose ; pharmacology ; Oleanolic Acid ; biosynthesis ; Saccharomyces cerevisiae ; cytology ; drug effects ; metabolism

Lysine decarboxylase is a key enzyme involved in the upstream biosynthesis of lycopodium alkaloids (LAs) such as huperzine A, contributing to the decarboxylation of lysine to 1,5-pentanediamine (cadaverine). Three lysine decarboxylase genes (HsLDC-L1, HsLDC-L2, HsLDC-L3) were successfully cloned from Huperzia serrata using transcriptomic sequence data mining strategy combined with reverse transcription PCR. The physicochemical properties, secondary and tertiary structures, amino acid identities, and evolutionary relationship of the three LDCs were analyzed by online bioinformatics analysis platforms and DNAMAN, MEGA 7.0 software, revealing that all of these proteins had the conserved PLP binding domain and active site residues were completely conserved in LDCs. Phylogenetic analysis showed that these LDCs were located in the same branch as other known LDCs from LA-producing plants. Accordingly, the ORFs of these three HsLDCs were inserted into different expression plasmids for further expression in E. coli. However, only HsLDC-L1 was successfully expressed in E. coli BL21 (DE3) by inserting into a pCold TF vector. The recombinant protein was purified by Ni²⁺ affinity chromatography purification. HsLDC-L1 contains 469 amino acid residues, with a calculated molecular weight of 50.50 kDa. HsLDC-L1 expectedly catalyzed the decarboxylation of lysine to produce cadaverine. In addition, HsLDC-L1 can also catalyze the generation of putrescine from ornithine. However, it cannot catalyze the decarboxylation of tyrosine, phenylalanine, tryptophan and histidine. The results not only provide insight into the biosynthesis of LAs including huperzine A, but also provide a critical genetic element for the overproduction of Δ¹-piperideine and pelletierine, the essential biosynthetic precursors of LAs, using synthetic biology strategies.

OBJECTIVETo assess the value of determination of urine kidney injury molecule-1 (KIM-1) protein content in the early diagnosis of radiocontrast-induced nephropathy (RCIN) in rats.

METHODSSeventy-two adult male SD rats were randomly divided into groups A, B, C (n=8) and D group (which was subdivided into 2, 6, 12, 24, 48 h and 7 days groups, n=8). Group A was subject to injections via the tail vein of PBS and normal saline (NS), group B received injections of PBS, NS, and contrast medium (CM), group C with indomethacin (INDO), nitric oxide synthase inhibitor (L-NAME), and NS, and group D with INDO, L-NAME and CM. Each injection was given at the interval of 15 min.

RESULTSIn group D, serum creatinine (Scr) and urea nitrogen (BUN) were significantly increased at 6 h after the injections (P<0.001), peaked at 24 h and recovered normal levels at 48 h. Histological examination revealed significant pathological changes in the kidneys at 6 h, showing diffuse tubulointerstitial hyperemia and hemorrhage, marked tubular necrosis and tubular structure destruction; at 12 h, significant tubular necrosis was still present with tubular structure destruction, but the tubulointerstitial hemorrhage was alleviated; at 24 h, tubular regeneration occurred in the renal medulla, but even till 7 days the tubular structures failed to show full recovery. In group D, urine KIM-1 level began to increase at 2 h, reached the peak level at 24 h, and lasted till 7 days (P<0.001); urine N-acetly-β-D-glucosaminidase (NAG) value began to increase at 6 h and became normal at 48 h. Urine MMP-9 level underwent no significant changes in group D over the time points of observation.

CONCLUSIONThe results show that urinary KIM-1 levels can be used as an indicator for early diagnosis of RCIN.

Animals ; Biomarkers ; urine ; Cell Adhesion Molecules ; urine ; Contrast Media ; adverse effects ; Early Diagnosis ; Kidney Diseases ; chemically induced ; diagnosis ; urine ; Male ; Radiopharmaceuticals ; adverse effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley