Objective To analyze the effects of alprostadil combined with benazepril in the treatment of diabetes and the effect on blood glucose fluctuation.MethodsEighty cases with diabetes were randomly divided into the control group and the observation group with 40 cases in each group.The control group was treated with benazepril while the observation group was additionally treated with alprostadil.The treatment effects, the changes of blood glucose, blood lipids and renal function were compared between the two groups, and the incidence of adverse reactions was recorded.ResultsThe total effective rate in the observation group was higher than that in the control group (P<0.05).After treatment, the fasting plasma glucose (FPG), postprandial 2h plasma glucose (2hPG) and glycosylated hemoglobin (HbA1c) were reduced to the normal level but the volatility differences of FPG and 2hPG in the observation group were lower than those in the control group (P<0.05).After 4 weeks of treatment, the total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) decreased while high-density lipoprotein cholesterol (HDL-C) increased (P<0.05) but the differences between the two groups showed no statistical significance.After treatment, the improvement of renal function indexes in the observation group was better than that in the control group (P<0.05), and the incidence of adverse reactions showed no significant difference between the two groups.ConclusionThe application of alprostadil combined with benazepril in the treatment of diabetes can reduce blood glucose fluctuation, improve renal function, and reduce the risk of diabetic nephropathy.

Objective To study the effect of hypoxia on the mRNA expression of osteoprotegerin(OPG) and receptor activa‐tor for nuclear factor‐κB ligand(RANKL) in human periodontal ligament cells(hPDLCs) and to explore the role of hypoxia in the orthodontic bone resorption in pressure side .Methods The primary hPDLCs were cultivated with enzyme digestion assay and tis‐sue cultivation .The 3-5 generations of hPDLCs were respectively cultured 3 ,6 ,12 and 24 h in normoxia condition (20% O2 ) or in hypoxia condition (2% O2 ) .The mRNA expression of OPG and RANKL were detected with RT‐PCR .The experimental data was analyzed by one way ANOVA using SPSS15 .0 .Results After cultivated in hypoxia condition for 3 h or 6 h ,the mRNA expression of OPG and RANKL in hPDLCs didn′t change significant(P> 0 .05) .After cultivated in hypoxia condition for 12 h or 24 h ,the mRNA expression of OPG in hPDLCs decreased while the RANKL increased .Thus the ratio of RANKL/OPG increased and the difference was significant(P<0 .05) .Conclusion Hypoxia can regulate the mRNA expression of OPG and RANKL in hPDLCs and will promote the orthodontic bone resorption in pressure side .

Objective Benzoquinone ansamycin antibiotic, geldanamycin (GA), is a new anticancer agent that could inhibit Hsp90 by occupying its NH2-terminal ATP-binding site. This study was to investigate the antitumor efficacy of GA on Her2/neu tyrosine kinase overexpressing human breast cancer cell line SKBr3. Methods The degradation of Her2/neu tyrosine kinase was analyzed by Western blotting, the proliferation index was determined by MTT assay,cell cycle distribution was detected by flow cytometry, Cyclin D1 mRNA transcription was measured by RT-PCR and real-time PCR, and cell motility was evaluated by the cell culture insert model. Results GA induced a dose- and a time-dependent degradation of the Her2/neu tyrosine kinase protein and concurrently, the inhibition of cancer cell proliferation. The antitumor effects mediated by GA included: GA treatment decreased the survival rates of cancer cells,and led to a dase-dependent G1 arrest. Furthermore, this antitumor effect was proved to be related to declined transcription of Cyclin D1. Concurrently, the motility of cancer cells was reduced by GA. Conclusion GA treatment could induce the degradation of Her2/neu tyrnsine kinase efficiently, inhibit cancer cell proliferation and reduce motility in Her2/nen tyrosine kinase overexpressed human breast cancer cell line SKBr3.

OBJECTIVETo verify the existence and significance of calcium/calmodulin dependent serine protein kinase/inhibitors of differentiation 1 (CASK/Id1) pathway in fibroblasts of human keloid.

METHODSImmunofluorescence laser was used to confirm CASK and Id1 protein expression and localization in fibroblasts of the keloid and normal skin. RT-PCR and Western-blot were adopted to analysis the CASK and Id1 expression and differences between keloid and normal skin fibroblasts. The natural combination of CASK and Id1 protein of keloid fibroblasts was tested by immunoprecipitation.

RESULTSCASK and Id1 protein expression were both found in fibroblast cells of keloid and normal skin under normal circumstances. Most of CASK and Id1 were distributed in the cytoplasm and nucleus of fibroblasts. The results of RT-PCR showed that the expression of CASK mRNA in the keloid group was 0.658 +/- 0.024, which was lower than that in the normal control group (1.076 +/- 0.008, t = 11.159, P < 0.05). The expression of Id1 mRNA was 0.497 +/- 0.014, which was higher than that in the normal control group (0.307 +/- 0.017, t = 15.148, P < 0.05). The results of Western-blot showed that the expression level for CASK protein in the keloid group was 0.057 +/- 0.006, which was lower than that in the normal control group (0.168 +/- 0.012, t = 13.524, P < 0.05); the expression of Id1 protein was 0.812 +/- 0.035, which was higher than that in the normal control group (0.368 +/- 0.031, t = 16.356, P < 0.05). The results of immunoprecipitation showed that Id1 could be detected in the CASK precipitate, while CASK also could be detected in the Id1 precipitate. There was a natural binding of CASK and Id1 in keloid fibroblasts.

CONCLUSIONCASK/Id1 signal pathway may be existed and involved in the proliferation of keloid fibroblasts, which is related with the occurrence of keloid.

Cell Proliferation ; genetics ; Cyclin-Dependent Kinase Inhibitor Proteins ; genetics ; metabolism ; Fibroblasts ; metabolism ; Humans ; Inhibitor of Differentiation Protein 1 ; genetics ; metabolism ; Keloid ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Signal Transduction

Objective To explore the value of echocardiography in the diagnosis of the parachute mitral valve(PMV).Methods The echocardiographic characteristics of 12 patients with PMV between 2005 and 2012 were reviewed retrospectively,including the morphology,movement and blood flow of mitral valve apparatus,and other associated cardiac abnormalities.Results Of the mitral valve leaflets in these 12 cases,all were thickened and opened restricted in diastole.Axial view showed that in all cases mitral valves opened eccentrically and in 2 cases they didn't close tightly.Each patient only had single papillary muscle in left ventricle,which received all chords of mitral valves.Of papillary muscles in these patients,4 were located at posteromedial wall,3 at anterolateral wall,2 at middle posterior wall,2 at apical wall,and 1 at posterolateral wall.Of the 12 patients,only one were simple PMV,11 had associated cardiovascular anomalies,2 had mild regurgitation in systolic period and 11 had increased trans-valve peak flow velocity.Conclusions Echocardiography is reliable in the diagnosis of PMV,which could provide a comprehensive evaluation of valvular lesions and other associated cardiovascular anomalies.

Objective To explore the risk factors for clinical anastomotic leakage after resection of rectal cancer in China. Methods By meta-analysis we made a comprehensive analysis of the risk factors for clinical anastomotic leakage after resection of rectal cancer based on 19 articles published in China between January 1999 and January 2009. Results The anastomotic leakage rate was higher in the patients aged 60 years old and above than in those younger, with the combined odds ratio (OR) value being 0.50 (95% CI: 0.33-0.76) (P<0.01). The incidence rate was higher in the male patients than in the female ones, with the combined OR value being 2.17 (95% CI: 1.38-3.42) (P<0.01). The incidence rate in the patients with the distance of tumor from the lower margin to anal verge being 7cm and shorter was higher than that with longer distance, with the combined OR value being 1.79 (95% CI: 1.37-2.35) (P<0.01). The incidence rate in the patients who had received radiotherapy preoperatively was higher than that in those who had not, with the combined OR value of 3.66 (95% CI: 2.19-6.09) (P<0.01). The incidence rate in the patients who had received stapler anastomosis was higher than that in the patients who had received manual anastomosis, with the combined OR value being 0.70 (95% CI: 0.47-1.05), but there was no significant difference between them (P>0.05). The incidence rate was higher in the patients with diabetes mellitus than in the healthy ones, with the combined OR value being 3.16 (95% CI: 2.27-4.39) (P<0.01). The incidence rate was lower in the patients with Dukes A and B stages than in those with Dukes C and D stages, with the combined OR value being 0.61 (95% CI: 0.45-0.83) (P<0.01). The incidence rate in the patients with high malignance degree in clinicopathological types was higher than that with low malignance degree, with the combined OR value being 2.17 (95% CI: 1.38-3.42) (P<0.01). The incidence rate was lower in the patients who had received preventive colostomy than in those who had not, with the combined OR value being 0.39 (95% CI: 0.14-1.05), but there was no significant difference between them (P>0.05). The incidence rate was higher in the patients who had got selective operation than in those who had got emergency operation, with the combined OR value being 0.27 (95% CI: 0.13-0.56). Conclusion The risk factors of anastomotic leakage after resection of rectal cancer are as follows: 60 years old and above, male patients, diabetes mellitus, preoperative neo-adjuvant radiotherapy, the distance of tumor from the lower margin to the anal verge being shorter than 7cm, Dukes C and D stages, high malignance degree in clinicopathological types, and emergency operation.

Objective To investigate ectopic expression of key elements of Wnt/?-catenin signaling pathway,including E-cadherin,?-catenin and Cyclin D1,as well as the relationship between ectopic expression of ?-catenin and overexpression of Her2 in human breast carcinoma tissues.Methods Immunohistochemical technique(Elivision) was used to detect the expression of Her2 and three elements of Wnt/?-catenin signaling pathway(?-catenin,E-cadherin,Cyclin D1) in 90 samples of human breast carcinoma.Results In E-cadherin normally-expressed group,the ectopic expression rate of ?-catenin(27.3%) was significantly lower than that(75.0%) in E-cadherin negative breast carcinoma;in ?-catenin ectopic expression group,overexpression rate of Cyclin D1(83.3%) was significantly higher than that(40.7%) in the other group.In Her2 overexpressed-breast carcinoma tissue,the ectopic expression rate of ?-catenin(73.5%) was significantly higher than that(19.6%) in Her2 negative breast carcinoma.Her2 overexpression could coexist with ectopic expression of Wnt/?-catenin in promoting axillary lymph node metastasis in human breast carcinoma.Conclusion Ectopic expression of Wnt/?-catenin signaling pathway does exist in some human breast carcinoma tissues,and the abnormal expression correlates with overexpression of Her2.Furthermore,the instantaneous activation of them could present synergism in promoting metastasis of axillary lymph nodes.

Objective:To evaluate the efficacy of chemotherapy for advanced biliary tract carcinoma and the factors that influence sur-vival. Methods:A total of 91 cases of advanced biliary tract carcinoma from January 2010 to April 2015 were enrolled in our study. The patients' characteristics, chemotherapy regimens, and effects were analyzed. Results:We enrolled 56 males and 35 females with a me-dian age of 57 years. A total of 90 patients were assessable for their responses to first-line chemotherapy. A total of 69 patients re-ceived the GP regimen, whereas 21 patients received some other regimens. The disease control rate (DCR), median progression free survival (mPFS), and median overall survival (mOS) were 68.1%versus 52.4%, 5.10 months versus 2.50 months (P=0.025), and 13.00 months versus 7.20 months, respectively. Only 31 patients received S-1 based regimens, and 12 patients received some other regi-mens as second-line chemotherapy. The DCR, median PFS, and median OS showed no statistical differences. Only four patients re-ceived S-1 based regimen plus bevacizumab as second-line chemotherapy (median PFS 5.3 months;median OS 7 months). Hematologi-call toxicity was the most common side effect in the first-line GP regimen. The side effects of the S-1 based chemotherapy regimen was relatively less. Conclusion:The GP regimen is an effective first-line chemotherapy for advanced biliary tract carcinoma, whereas S-1 ap-pears as an effective second-line chemotherapy drug. Bevacizumab-based regimens may be effective and require further validation.

Objective Subarachnoid hemorrhage ( SAH) is a devastating disease with a high mortality.This study was to in-vestigate the effect of Nrf2 on secondary brain injury following SAH and its action mechanism in mice. Methods SAH models were established in wild-type ( WT) and Nrf2 knockout ( KO) ICR male mice by injecting fresh blood drawn from the femoral artery into the pre-chiasmatic cistern.The animals were divided into four groups, WT sham, WT SAH, KO sham, and KO SAH.At 24 hours after modeling, the expression levels of malondialdehyde ( MDA) , GSH/GSSG, TNF-αand IL-1β, the volume of brain water, and content of Evans blue were measured, the activity scores obtained, and cerebral vasospasm of the anterior and middle cerebral arteries ( ACA and MCA) detected. Results At 24 hours, the expressions of MDA, TNF-α, and IL-1βwere (3.299 ±0.335), (1.187 ± 0.436), and (59.330 ±21.787) mg/g in the WT sham group, (4.339 ±0.328), (2.432 ±0.434), and (121.584 ±21.675) mg/g in the WT SAH group, (3.488 ±0.634), (1.170 ±0.312), and (58.497 ±15.608) mg/g in the KO sham group, and (5.335 ±0.499), (3.132 ±0.548), and (171.117 ±50.479) mg/g in the KO SAH group, markedly increased in the SAH groups as compared with the sham controls (P<0.05), while the GSH/GSSG levels were significantly higher in the former two groups than in the latter (0.553 ±0.100 and 0.375 ±0.068 vs 0.714 ±0.091, 0.761 ±0.114, P<0.01).The contents of brain water and Evans blue were (0.784 ±0.005) and (7.055 ±1.046) μg/g in the WT sham group, (0.808 ±0.004) and (7.230 ±1.192) μg/g in the WT SAH group, (0.784 ±0.004) and (9.620 ±1.290) μg/g in the KO sham group, and (0.819 ±0.004) and (11.628 ±1.040)μg/g in the KO SAH group, remarkably increased in the SAH groups in comparison with the sham groups (P<0.05).The apoptosis rate 8.916 and 82.100 ±6.870 vs 70.833 ±8.750 and 51.767 ±13.006), ACA radius/wall thickness value (13.885 ±3.360 and 14.212 ±3.2545 vs 8.024 ±2.780 and 6.861 ±2.702), MCA radius/wall thickness value (18.648 ±2.893 and 19.435 ±2.775 vs 6.337 ±3.993 and 5.107 ±3.805), and activity score (2.733 ±0.450 and 2.767 ±0.430 vs 1.967 ±0.928 and 1.433 ±0.679) (all P<0.01). Conclusion Nrf2 knockout increases oxidative stress and inflammatory reaction following SAH and consequently aggravates secondary brain injury.Nrf2 has a protective effect against SAH-induced brain injury.

(3S)-Linalool synthase (LIS) is a key enzyme involved in the monoterpene biosynthetic pathway. Based on our previous transcriptome study, the expression level of LIS gene was exceedingly related to glycyrrhizic acid (GA) biosynthesis. Therefore, we used hairy root culturing to further investigate the effect of LIS on the GA biosynthesis. A LIS gene (GenBank accession number: MZ169552) was cloned from Glycyrrhiza uralensis. The plant binary overexpression vector pCA-LIS was constructed by gene fusion. G. uralensis hairy roots overexpressing LIS were induced by the Agrobacterium rhizogenes ATCC15834. The expression levels of LIS were analyzed by real-time quantitative PCR (RT-qPCR) and the contents of GA in hairy root lines were determined by UPLC. It was found that in the hairy root lines overexpressing LIS, the expression levels of LIS were significantly higher than that in the wild type, while the contents of GA were remarkably lower than those in the wild type and negative control. These findings indicate that the expression level of LIS is negatively correlated with the accumulation of GA. In this study, LIS was cloned from G. uralensis for the first time and the negative regulatory effect of LIS on GA biosynthesis was confirmed by reverse genetics. This work provides support for further improvement of the molecular regulatory network of GA biosynthesis in G. uralensis.