Aim To investgate the mechnism through which ginkgolides affect learning and memory capabilities of the Alzheimers disease-like rats. Methods Okadaic acid(OA)was injected into the CA1 region of the rat hippocampus and the rats were gavaged with ginkgolides. The learning and memory abilities of the rats were assessed through Morris water maze behavioral test, and the expressions of nicotinic acetylcholine receptors and ChAT were observed by Western blotting and immunohistochemistry, respectively.Results Compared with the control rats, the capabilities of learning and memory were lowered significantly(P

OBJECTIVETo analyze the clinical results and complications of three methods for microgenia, including chin augmentation with silicone implant, bone autograft, and genioplasty.

METHODSThe advantages and disadvantages of the three methods for microgenia were assessed through 3-D CT reconstruction, X-ray and intraoperative observation during the second operation. The indications for each technique were also studied.

RESULTSThe frequently observed problems for chin augmentation with silicone implants were implant malposition, underlying bone absorption, periosteal reaction and undercorrection. Chin augmentation with bone autograft had a great long-term bone graft absorption which led to undercorrection. Genioplasty showed a satisfactory cosmetic result with no serious complication.

CONCLUSIONSChin augmentation with silicone implant is suitable for mild microgenia with a shallow mentolabial groove, but without facial vertical insufficient and facial asymmetry. Genioplasty can be used in all kinds of microgenia in any severity, especially those with deviated chin and facial asymmetry. Chin augmentation with bone autograft can't achieve good long-term result and should be applied prudently.

Adult ; Chin ; abnormalities ; surgery ; Female ; Humans ; Prostheses and Implants ; Silicone Elastomers ; Surgery, Plastic ; methods ; Young Adult

Objective To investigate the application of clinical nursing pathway in health education for hemodialysis patients. Methods 84 hemodialysis patients who received holistic nursing practice were divided into test group(n =42) and control group(n =42) according to bed numbers. Test group received health education procedure of clinical nursing pathway, while control group received conventional health education procedure.Compliance rate of health education, compliance rate of dialysis and satisfaction rate of dialysis in the two groups were observed and analyzed. Results Compliance rate of health education, compliance rate of dialysis and satisfaction rate of dialysis were all significantly higher than those of the control group (P < 0. 05). Conclusions Clinical nursing pathway is feasible for Chinese maintenance hemodialysis patients. It contributes to the effect of medical, nursing and health education, thus improves the patients' quality of life.

Objective To evaluate the efficacy and safety of pioglitazone /metformin hydrochloride in the treatment of type 2 diabetes mellitus patients. Methods A randomized, double-blind, metformin and pioglitazone hydrochloride-controlled, and multicenter clinical trial was conducted. A total of 240 patients with type 2 diabetes mellitus were enrolled in this study, in which 120 patients received pioglitazone/ metformin, and 120 patients received metformin and pioglitazone. Result Comparing to the baseline, the fasting blood glucose ( FBG) , 2 h postprandial blood glucose (P2hBG) and HbAlc levels in tow groups were significantly reduced after 16-week treatment ( P < 0. 01 ) . In pioglitazone/metformin group, the mean reductions of FBG, P2hBG and HbAlc levels were (1. 92 ± 1. 77 ) mmol · L~(-1), ( 2. 49 ± 3. 13 ) mmol · L~(-1), (1. 27 ± 1. 45 ) % respectively. In metformin and pioglitazone group, the mean reductions of FBG, P2hBG and HbAlc levels were (2. 24 ±2. 11) mmol · L~(-1), (2. 89 ± 3. 71) mmol · L~(-1), ( 1. 49 ± 1. 52)% respectively. The differences in reductions of FBG, P2hBG and HbAlc level between the groups were not statistically significant. The incidence of adverse drug reaction in two groups was similar (10% vs 12%). Conclusion This result provides an efficacy and safety of pioglitazone /metformin in the treatment of type 2 diabetes mellitus.

Objective To evaluate the safety and efficacy of cefaze-done injection ( CZD) compared with cefazolin injection ( CZL) in the treatment of acute bacterial respiratory infections.Methods Eligible subjects were divided randomly to receive 2.0 g cefazedone injection or cefazolin injection twice a day for 7 to 14 days.Efficacy and safety evaluation were done in accordance with the clinical trial protocol.Results Two hundred and sixty patients in 11 hospitals were en-rolled, 126 in CZD group( trial) and 134 in CZL group( control).There were no statistical differences in basic conditions between two groups( P >0.05 ).Cure rates of CZD group and CZL group were 95.5% and 94.9% in PPS ( P>0.05 ).Bacteria clearance rates of CZD group and CZL group were100% and 91.7% in BPPS and the total cure rates of CZD group and CZL group were 94.4% and 91.7% in BPPS, respectively ( P>0.05).Ten out off 126 patients in CZD group and 14 out off 134 in CZL group developed adverse events( AE ).Six and eleven events in CZD group and CZL group
were evaluated to be related with study drugs.One case in CZL group developed severe AE , which was considered not related with study drug.Conclusion Cefazedone injection is safe and effective in the treatment of respiratory infections.

Objective To explore the role of integrin αvβ3 in the promotion of the development of choroidal neovascularization (CNV) by SDF-1/CXCR4.Methods This study was divided into two parts in vitro and in vivo.As for the in vivo study,a CNV model was induced by laser on C57BL/6J mice,and then assigned into 4 groups:mice with solely CNV modeling as control group,with intravitreal injection of SDF-1 after immediate CNV modeling as SDF-1 group,with intravitreal injection of SDF-1 + CXCR4 inhibitor (AMD3100) after CNV modeling as SDF-1 + AMD3100 group,and mice with intravitreal injection of SDF-1 + αvβ3 inhibitor (SB273005) after modeling as SDF-1 + SB273005 group.CXCR4 and αvβ3 expression levels in laser-induced eyes were quantified by qRT-PCR at time points of day 1,3,5,7,10 and 14 after modeling,and immunofluorescence staining was applied to detect αvβ3 expression in regional CNV and its endothelial cells in the four groups.Finally,OCT was used to observe the height of retinal pigment epithelial (RPE) layers in CNV after treatment in the four groups.Moreover,in the experiment in vitro,Western blot was used to measure the expression of CXCR4 protein of RF/6A cells in normal control group,Si-CXCR4 knockdown group and Si-NC knockdown model group.Meanwhile,the expression of integrin subunit β3 protein was determined in the normal control group,SDF-1 group,SDF-1 + AMD3100group,SDF-1 + Si-NC group and SDF-1 + Si-CXCR4 group.Transwell assay was conducted to detect the migration ability of RF/6A cells in the normal control group,SDF-1group,SDF-1 +AMD3100 group,SDF-1 + SB273005 group.Results On the one hand,the study in vivo,qRT-PCR showed that the expression of CXCR4 and integrin subunit β3 mRNA was up-regulated at first,and then down-regulated with time passed after CNV induction,with the highest expression level of CXCR4 mRNA (4.263 ± 0.464) on day 3,and the peak expression of β3 mRNA (3.678 ±0.364) on day 7 after CNV modeling.The results of immunofluorescence staining showed that the β3 fluorescence intensity of SDF-1 group was significantly enhanced,and the ratio of β3/CD31 was also significantly increased,which both were significantly higher than those of the control group (P ＜ 0.01).However,the β3 fluorescence intensity and β3/CD31 ratio of SDF-1 +AMD3100 group and SDF-1 + SB273005 group were significantly weakened and decreased,respectively (P ＜0.05).OCT showed that the elevation level of RPE layer inSDF-1 group was significantly higher than that in the control group [(135.503 ± 10.301) μm vs.(94.443 ± 12.156) μm](P＜0.05).The height of RPE uplift in SDF-1 + AMD3100 group [(95.283 ±20.062) μm] and SDF-1 + SB273005 group [(99.807 ± 10.403) μm] was significantly decreased (P ＜ 0.05).On the other hand,in experiment in vitro,Western blot showed that the expression levels of integrin β3 in SDF-1 group and SDF-1 + Si-NC group were significantly higher than those in the control group [(1.301 ± 0.043) and (1.273 ± 0.077) vs.(0.244 ± 0.069)] (P ＜ 0.01).The levels of integrin subunit β3 protein in SDF-1 + si-CXCR4 group (0.322 ± 0.042) and SDF-1 + AMD3100 group (0.336 ± 0.077) were significantly down-regulated (P ＜ 0.01).Transwell assay showed that the amount of migrating cells in SDF-1 group increased,which was significantly higher than that of the control group (P ＜ 0.01),while the number of migrating cells in SDF-1 +AMD3100 group and SDF-1 + SB273005 group was significantly decreased.Conclusion Integrin αvβ3 can promote the development of CNV by mediating SDF-1/CXCR4 signaling in endothelial cells.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.