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6 Phenstatin or isophenstatin-containing esters of oleic, linoleic and stearic acid of type (VII) or (VIII) are prepared by a reaction sequence as outlined for (VII).

In this study we investigated the effect of linsitinib on the reversal of multidrug resistance (MDR) mediated by the overexpression of the ATP-binding cassette (ABC) subfamily members ABCB1, ABCG2, ABCC1 and ABCC10. Our results indicate for the first time that linsitinib significantly potentiate the effect of anti-neoplastic drugs mitoxantrone (MX) and SN-38 in ABCG2-overexpressing cells; paclitaxel, docetaxel and vinblastine in ABCC10-overexpressing cells. Linsitinib moderately enhanced the cytotoxicity of vincristine in cell lines overexpressing ABCB1, whereas it did not alter the cytotoxicity of substrates of ABCC1. Furthermore, linsitinib significantly increased the intracellular accumulation and decreased the efflux of [(3)H]-MX in ABCG2-overexpressing cells and [(3)H]-paclitaxel in ABCC10-overexpressing cells. However, linsitinib, at a concentration that reversed MDR, did not significantly alter the expression levels of either the ABCG2 or ABCC10 transporter proteins. Furthermore, linsitinib did not significantly alter the intracellular localization of ABCG2 or ABCC10. Moreover, linsitinib stimulated the ATPase activity of ABCG2 in a concentration-dependent manner. Overall, our study suggests that linsitinib attenuates ABCG2- and ABCC10-mediated MDR by directly inhibiting their function as opposed to altering ABCG2 or ABCC10 protein expression.

AST1306, an inhibitor of EGFR and ErbB2, is currently in phase I of clinical trials. We evaluated the effect of AST306 on the reversal of multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters. We found that AST1306 significantly sensitized the ABC subfamily G member 2 (ABCG2)-overexpressing cells to ABCG2 substrate chemotherapeutics. AST1306 significantly increased intracellular accumulation of [(3)H]-mitoxantrone in ABCG2-overexpressing cells by blocking ABCG2 efflux function. Moreover, AST1306 stimulated the ATPase activity of ABCG2. Homology modeling predicted the binding conformation of AST1306 to be within the transmembrane region of ABCG2. In conclusion, AST1306 could notably reverse ABCG2-mediated MDR.

BackgroundHepatitis E is caused by two viral genotype groups: human types and zoonotic types. Current understanding of the epidemiology of the zoonotic hepatitis E disease is founded largely on hospital-based studies.MethodsThe epidemiology of hepatitis E was investigated in a community-based surveillance study conducted over one year in a rural city in eastern China with a registered population of 400,162.ResultsThe seroprevalence of hepatitis E in the cohort was 38%. The incidence of hepatitis E was 2.8/10,000 person-years. Totally 93.5% of the infections were attributed to genotype 4 and the rest, to genotype 1. Hepatitis E accounted for 28.4% (102/359) of the acute hepatitis cases and 68.9% (102/148) of the acute viral hepatitis cases in this area of China. The disease occurred sporadically with a higher prevalence during the cold season and in men, with the male-to-female ratio of 3∶1. Additionally, the incidence of hepatitis E increased with age. Hepatitis B virus carriers have an increased risk of contracting hepatitis E than the general population (OR = 2.5, 95%CI 1.5-4.2). Pre-existing immunity to hepatitis E lowered the risk (relative risk = 0.34, 95% CI 0.21-0.55) and reduced the severity of the disease.ConclusionsHepatitis E in the rural population of China is essentially that of a zoonosis due to the genotype 4 virus, the epidemiology of which is similar to that due to the other zoonotic genotype 3 virus.

To investigate the effect of partial internal sphincter myomectomy on transanal one-stage pull-through operation for Hirschsprung disease (HD).A prospective group of 153 pediatric patients with HD in Guangdong Dongguan People's Hospital between 2003-2012 were enrolled, who underwent transanal one-stage pull-through operation. Children were divided into partial resection group (77 cases) undergoing partial internal sphincter myomectomy and simple incision group (76 cases) undergoing simply internal sphincter dissection, respectively. Differences of postoperative complications and continence between two groups were compared.Postoperative complications such as rectal muscularis infection [1.3% (1/77) vs. 11.8% (9/76), P0.05], enterocolitis [2.6% (2/77) vs. 13.2% (10/76), P0.05], anastomosis stenosis[3.9% (3/77) vs. 22.4% (17/76), P0.01] and abdominal distension [10.4% (8/77) vs. 25.0% (19/76), P0.05] were lower in partial resection group as compared to simple incision group. The time of antibiotics administration was also lower in partial resection group [(3.9±1.1) d vs. (4.6±1.1) d, P0.01]. Difference in the continence between the two groups was not statistically significant (kelly score, 5.1±0.5 vs. 5.2±0.6, P0.05).Compared with simply internal sphincter dissection in operation, partial internal sphincter myomectomy with transanal one-stage pull-through operation for HD can reduce the postoperative complications and does not increase the damage of the continence.

Multi-view three-dimensional (3-D) displays using directional beam splitter array were proposed to achieve a perfect 3-D perception with low cross-talk. The multi-direction collimated light may project different images to different viewing zones to form the multi-view autostereoscopic display. Furthermore, a high resolution 3-D display can be realized with a sequential beam splitter array and a sequential liquid crystal display. By optimization, the cross-talk of the directional beam splitter backlight system was lowered to 5% to improve the perception of the 3-D displays.

An infusion-dialysis based procedure has been developed as an approach to isolate organic nanoparticles from green tea. Tea nanoparticle (TNP) can effectively load doxorubicin (DOX) via electrostatic and hydrophobic interactions. We established an ABCB1 overexpressing tumor xenograft mouse model to investigate whether TNP can effectively deliver DOX into tumors and bypass the efflux function of the ABCB1 transporter, thereby increasing the intratumoral accumulation of DOX and potentiating the anticancer activity of DOX. MTT assays suggested that DOX-TNP showed higher cytotoxicity toward CCD-18Co, SW620 and SW620/Ad300 cells, as compared to DOX. Animal study revealed that DOX-TNP resulted in a greater inhibitory effect on the growth of SW620 and SW620/Ad300 tumors than DOX alone. The cTnI levels in mice showed that TNP had no cardiotoxicity and DOX-TNP had moderate cardiotoxicity. Blood Smear tests demonstrated that TNP and DOX-TNP did not cause neutropenia or thrombocytopenia in mice. Therefore, TNP is a safe nanocarrier with excellent biocompatibility and minimal toxicity. In pharmacokinetics study, DOX-TNP greatly increased the SW620 and SW620/Ad300 intratumoral concentrations of DOX, as compared to DOX alone. But DOX-TNP had no effect on the plasma concentrations of DOX up to 240 min after administration. Furthermore, ex vivo IHC analysis of SW620 and SW620/Ad300 tumor sections revealed evidence of prominent antitumor activity of DOX-TNP. In conclusion, our findings suggested that natural nanomaterials could be useful in combating multidrug resistance (MDR) in cancer cells and potentiating the anticancer activity of chemotherapeutic agents in cancer treatment. Citation Format: Yi-Jun Wang, Yujian Huang, Nagaraju Anreddy, Guan-Nan Zhang, Yun-Kai Zhang, Meina Xie, Derrick Lin, Dong-Hua Yang, Mingjun Zhang, Zhe-Sheng Chen. Tea nanoparticle, a safe and biocompatible nanocarrier, greatly potentiates the anticancer activity of doxorubicin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2201.

Cabozantinib (XL184) is an oral tyrosine kinases receptor inhibitor which inhibits MET and vascular endothelial growth factor receptor 2 (VEGFR2). Cabozantinib has been approved by Food and Drug Administration for treating advanced medullary thyroid cancer and it is also tested in clinical trials on other solid tumors, including prostate, bladder, ovarian and breast cancer. In the present study, we evaluated the ability of cabozantinib in modulating the function of ABCG2 transporter in drug-selected H460/MX20 cell line and ABCG2 stable transfected cell lines ABCG2-482-R2, ABCG2-482-G2 and ABCG2-482-T7. Cabozantinib at non-toxic level can sensitize the ABCG2-overexpressing cells to antineoplastic drugs mitoxantrone, SN-38 and topotecan. Our results indicated that cabozantinib reversed ABCG2 mediated multi-drug resistance by antagonizing the drug efflux function of ABCG2. However, this reversal effect was not attributed to reduced expression of ABCG2 protein, because ABCG2 protein level was unchanged after treatment of 4μM cabozantinib for 72 hours. Immunofluorescence result showed that cabozantinib did not alter the cellular localization of ABCG2 transporter. Docking analysis indicated that cabozantinib binds to the drug-binding site of ABCG2 transporter. Finally, cabozantinib at 4μM did not significantly change the resistance of ABCB1 overexpressing cell line SW620/AD300 to antineoplastic drug paclitaxel. Overall, our finding demonstrated that cabozantinib potentiates the cytotoxic effects of various antineoplastic drugs that are substrates of ABCG2 and that this is due to modulating the function of ABCG2 transporter. Keyword: Cabozantinib; ABCG2; Multidrug resistance; Citation Format: Guannan Zhang, Yun-Kai Zhang, Yi-Jun Wang, Zhe-Sheng Chen. Modulating the function of multidrug resistance ABCG2 transporter by tyrosine kinases receptor inhibitor cabozantinib. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4684.

Serum Golgi protein 73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and its correlation with clinicopathological parameters.Tissue GP73 (tGP73) levels were detected in specimens of group A (n = 186) including HCC, peritumoral tissue (PTL), high/low-grade hepatic atypical hyperplasia (AH), chronic hepatitis B (CHB) and normal controls (NC) by immunohistochemistry, and GP73 expression in group B (n = 159) and group C (n = 16) were detected by reverse transcription polymerase chain reaction and western blot, respectively. sGP73 levels were detected in subjects of group D (n = 287) by enzyme-linked immunoassay.GP73 expression increased gradually from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P 0.05), while sGP73 in the HCC group was lower than in the liver cirrhosis (LC) group (P 0.001). Both tGP73 and sGP73 levels were negatively associated with tumor size and tumor-node-metastasis stage, and tGP73 levels were positively associated with tumor differentiation. The high-tGP73 group showed significantly better overall and disease-free survival than the low-tGP73 group (P = 0.008, P = 0.018). Multivariate analysis revealed that the tGP73 level was an independent prognostic factor for HCC, but not sGP73.GP73 expression pattern suggests that the regulatory mechanism of GP73 is related to the progression of chronic liver diseases. Furthermore, a high level of tGP73 is a favorable prognostic factor for HCC.

To investigate the risk factors of postoperative hemodialysis in patients undergoing off-pump coronary artery bypass grafting (OPCAB).The perioperative data of 2379 consecutive patients undergoing OPCAB from November 2007 to February 2009 were analyzed retrospectively. Patients were divided into dialysis group and non-dialysis group according to their use of hemodialysis therapy or not.Fifty-four patients experienced hemodialysis postoperatively. The incidence of hemodialysis was 2.3%, the mortality rate of dialysis group and non-dialysis group was 18.5% and 0.9% respectively. Univariate analysis showed that these factors significantly related with the postoperative dialysis:intraoperative ventricular fibrillation, emergent cardiopulmonary bypass, preoperative atrial fibrillation, intraoperative atrial fibrillation, preoperative renal dysfunction, intraoperative high-dose adrenaline usage, ventricular aneurysm, combined valvular disease, hypertension, age and numbers of grafting vessels. Multivariate logistic regression showed that intraoperative ventricular fibrillation, intraoperative high-dose adrenaline usage, hypertension, age and the numbers of grafting vessel were the risk factors of postoperative hemodialysis for patients undergoing OPCAB surgery.Intraoperative ventricular fibrillation, intraoperative high-dose adrenaline usage, hypertension, age and the numbers of grafting vessels were the independent predictors of postoperative hemodialysis in patients undergoing OPCAB surgery.

For patients undergoing off-pump coronary artery bypass grafting (OPCABG), it is important to establish a hemodynamic monitoring system to obtain powerful parameters for better intraoperative treatment. This study aimed to observe the clinical feasibility of arterial pressure-based cardiac output (APCO) for cardiac output (CO) monitoring and to evaluate the correlation between APCO and pulmonary artery catheter (PAC) for CO measurement for patients undergoing OPCABG intraoperatively.Fifty patients of American Society of Anaesthesiologists (ASA) classification II-III, undergoing elective OPCABG at Beijing Anzhen Hospital were randomly enrolled into this study. All patients were assigned to CO monitoring by PAC and APCO simultaneously. Patients with pacemaker, severe valvular heart disease, left ventricular ejection fraction (EF)40%, cardiac arrhythmias, peripheral vascular disease, application of intra-aortic balloon pump (IABP) and emergent diversion to cardiac pulmonary bypass were excluded. The radial artery waveform was analyzed to estimate the stroke volume (SV) and heart rate (HR) continuously. CO was calculated as SV ' HR; other derived parameters were cardiac index (CI), stroke volume index (SVI), systemic vascular resistance (SVR), and systemic vascular resistance index (SVRI). PAC was placed via right internal jugular vein and the correct position was confirmed by PAC waveforms. Continuous cardiac output (CCO), CI and other hemodynamic parameters were monitored at following 5 time points: immediate after anesthesia induction (baseline value), anastomosis of left internal mammary artery to left anterior descending artery (LAD), anastomosis of left circumflex (LCX), anastomosis of posterior descending artery (PDA) and immediate after sternal closure.In the 50 patients, preoperative echocardiography measured left ventricular EF was (52.8 ± 11.5)%, and 35 patients (70%) showed regional wall motion abnormalities. The correlation coefficient of CO monitored by APCO and PAC were 0.70, 0.59, 0.78, 0.74 and 0.85 at each time point. The bias range of CI monitored from both APCO and PAC were (0.39 ± 0.06) L×min(-1)×m(-2), (0.48 ± 0.12) L×min(-1)×m(-2), (0.26 ± 0.06) L×min(-1)×m(-2), (0.27 ± 0.06) L×min(-1)×m(-2), (0.30 ± 0.05) L×min(-1)×m(-2) at each time point. The results of SVR by two hemodynamic monitoring techniques had good correlation during OPCABG. The variation trends of SVR were opposite comparing with the results of CO. SVR collected from PAC obtained the highest value of (1220.0 ± 254.0) dyn×s×cm(-5) at PDA anastomosis, but the highest value obtained from APCO was (1206.0 ± 226.5) dyn×s×cm(-5) in LCX anastomosis.APCO is feasible in hemodynamic monitoring for patients undergoing OPCABG. The results of hemodynamic monitoring derived from APCO and PAC are closely correlated. Its characterizations of timely, accurate and continuous display of hemodynamic parameters are also obviously demonstrated in the present study.

To explore the effects and mechanism of thymoquinone in the growth inhibition of bladder cancer both in vitro and in vivo.After the treatment of thymoquinone, the cellular proliferation of human bladder cancer cell line BIU-87 was detected by the method of methyl thiazolyl tetrazolium (MTT). Flow cytometry (FCM) was used to determine the cellular apoptosis. And the location of nuclear factor (NF)-κB was identified by the method of immunofluorescent histochemistry. Western blotting was employed to detect the cellular expressions of NF-κB, survivin and XIAP. BIU-87 cells were injected subcutaneously into nude mice to establish a xenograft model. After 2 weeks of implantation, the mice were randomized into 2 groups (n = 8): (a) vehicle alone (control), (b) thymoquinone (5 mg/kg daily by intragastric intubation). All treatments lasted for 2 weeks. At Week 7 post-implantation, the mice were sacrificed and their tumor weights and inhibition rates evaluated. Immunohistochemistry was used to detect the positive expressions of Ki-67, NF-κB and XIAP in tumors.The proliferation of bladder cancer cells was inhibited significantly by thymoquinone at 20, 40, 80 µmol/L (81.2% ± 4.6%, 72.5% ± 6.5%, 58.4% ± 8.9% vs 100%, all P0.05). Apoptosis rate induced by thymoquinone was more significant than that of the control (7.6% ± 1.6%, 11.2% ± 2.1%, 14.3% ± 2.8%vs 1.6% ± 0.5%, all P0.05). Immunofluorescent histochemistry showed that thymoquinone could significantly lower the nuclear expression of NF-κB. The expressions of NF-κB and XIAP were down-regulated in BIU-87 cells after the treatment of thymoquinone. But thymoquinone had no effect on the expression of survivin. The final tumor weight showed significant decrease in the test group versus the control group ((0.41 ± 0.12) vs (0.89 ± 0.23) g, P0.05). Furthermore, the positive expressions of Ki-67, NF-κB and XIAP decreased in tumors after the administration of thymoquinone.Thymoquinone exerts anti-tumor effects on bladder cancer both in vitro and in vivo through the down-regulations of NF-κB and its regulated molecules such as XIAP.

To investigate the correlation between FoxP3+ regulatory T lymphocytes (Tregs) in hepatocellular carcinomas (HCCs) and peritumoral tissues with CD34 expression and patient prognosis.Fifty-five sets of patient-matched tumors and peritumoral tissues were obtained during curative resection for HCC. In situ immunohistochemistry was used to assess and comparatively analyze Treg presence and CD34 expression in each specimen set. The relation between quantified Tregs values and various clinicopathologic factors were evaluated by the Spearman Rank Correlation test. Univariate (Log Rank test) and multivariate (Cox Regression model) analyses were used to determine the potential prognostic value of each factor.The average number of intratumoral Tregs was significantly higher than that in corresponding peritumoral tissues (10.8 (range: 4.4 to 19.4) vs. 1.4 (0.6 to 3.2), respectively; P less than 0.01). The presence of intratumoral Tregs correlated with up-regulated CD34 expression (r = 0.279, P less than 0.05). Increased number of intratumoral Tregs were significantly associated with decreased rates of overall survival (OS, P less than 0.05) and disease-free survival (DFS, P less than 0.05), and was identified as an independent prognostic factor (OS, hazard ratio (HR) = 3.310, 95% confidence interval (CI): 1.368-8.007, P less than 0.01; DFS, HR = 2.666, 95% CI: 1.321 to 6.394, P less than 0.01).Intratumoral infiltration by Tregs is a marker of poor prognosis in HCC patients.

Bismuth-based nanostructures have attracted growing interest because of their promising thermoelectric properties and applications in optics and electronics. Pulsed sonoelectrochemical technique was selected to fabricate bismuth–antimony (BiSb) flake-like alloy in ethylene glycol aqueous solution. The formation mechanism for the BiSb alloy was discussed. Ultrasonic played an important role in regenerating electrode and promoting the formation of BiSb nanoflakes. Citrate and polyvinylpyrrolidone (PVP) were introduced as mixed controlling agents during the nucleation and growth process.

Purpose: Tumor-infiltrating lymphocytes are considered to represent a host immune response against tumor. This study was carried out to analyze the effect of both FoxP3+ regulatory T cells (Tregs) and CD8+ T lymphocytes in prognostic value of hepatocellular carcinoma (HCC) patients. Methods: Expressions of FoxP3, CD4, CD8 and CD34 in patient-matched tumors and peritumoral tissues were assessed by immunohistochemistry for 54 HCC patients. The prognostic effect of groups with high and low numbers was evaluated by the Kaplan-Meier and Cox model analysis using median values as a cutoff. Results: Compared with the corresponding peritumoral tissue, the density of intratumoral Tregs was significantly higher, while the density of intratumoral CD8+ T cells was lower (p < 0.001 and p = 0.013, respectively). In addition, tumor-infiltrating Tregs were positively correlated with microvessel density in tumors (r = 0.334, p = 0.020). The high intratumoral Tregs density group showed a significantly lower survival rate (overall survival, p = 0.018; disease-free survival, p = 0.029). Multivariate Cox analysis revealed that intratumoral Tregs density was an independent prognostic factor for HCC. Conclusions: Tumor-infiltrating Tregs may promote HCC progression by fostering angiogenesis and decreasing CD8+ T cells. High tumor-infiltrating Tregs are thought to be an unfavorable prognostic indicator for HCC.

This study proposes a "pure skill-based" fuzzy logic control (FLC) approach to reverse a car-like mobile robot(CLMR) into an empty parking bay automatically. The FLC approach was expressed in the form of fuzzy rules based on the knowledge of skilled human drivers. Range measurements were provided to help the CLMR avoid collisions during the parking. Simulations proved the effectiveness of the proposed FLC.

AIM: To investigate the methylation status of secreted protein acidic and rich in cysteine (SPARC) in human hepatocellular carcinoma (HCC) and evaluate its clinical implication. METHODS: The methylation status of SPARC was analyzed in one HCC cell line (SMMC-7721) and 60 pairs of HCC and corresponding nontumorous tissues by methylation-specific polymerase chain reaction and bisulfite sequencing. The expression of SPARC mRNA and protein were examined by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. The correlations between the methylation status and the gene expression, the clinicopathological parameters, as well as the prognosis after surgery were analyzed. RESULTS: In the SMMC-7721 cell line, the loss of SPARC expression was correlated with the aberrant methylation and could be reactivated by the demethylating agent 5-aza-2’-deoxycytidine. Methylation frequency of SPARC in HCC was significantly higher than that in the corresponding nontumorous tissues (45/60 vs 7/60, P < 0.001), and it was correlated with the pathological classification (P = 0.019). The downregulation of the SPARC mRNA expression in HCC was correlated with the SPARC methylation (P = 0.040). The patients with methylated SPARC had a poorer overall survival than those without methylated SPARC (28.0 mo vs 41.0 mo, P = 0.043). CONCLUSION: Aberrant methylation is an important mechanism for SPARC inactivation in HCC and SPARC methylation may be a promising biomarker for the diagnosis and prognosis of HCC.

To identify genes expressed in normal human melanocytes but not in malignant melanomas, we previously applied subtractive cDNA hybridization combined with PCR amplification, which led to the isolation of several human melanocyte-enriched partial cDNAs. Three of these cDNA clones were used to isolate their corresponding genomic clones. The chromosomal location of each of the three genes encoded by the individual genomic clones was determined by fluorescent in situ hybridization. The first gene mapped to human chromosome 3p14, the second gene to chromosome 19q13.1, and the third to 2p16-14. In addition, RNase A protection and in situ hybridization analyses documented expression of the gene, located on 3p14, in normal human melanocytes but not in malignant melanomas.

To investigate whether Astragalus membranaceus (AM) can protect endothelium-dependent vasodilatation (EDV) function of aorta from the damage induced by high level of free fatty acid (FFA).Ten male SD rats, 8 weeks old and 250-300 g in weight, were sacrificed and thoracic aorta were harvested. Aorta rings incubated in organ baths were divided into three groups, Control group, FFA group and FFA+ AM group. The control group was incubated in 20 mL Krebs-Henseleit solution; the FFA group was incubated in 20 mL KH solution mixed with FFA(800 micromol/L) the FFA + AM group was incubated in 20 mL KH solution mixed with FFA (800 micromol/L) and AM (4 g/L). The relaxation levels of aorta rings response to acetylcholine and sodium nitroprusside were measured, the expression of NF-kappaB and the level of NOx in the organ bath were analyzed by immunohistochemistry.Severe endothelial dysfunction were induced in FFA group (maximal vasorelaxation in response to Ach: 61.1% +/- l6.9% vs. 93.1% +/- 2.7% in control, P0.05), while EDV in FFA+AM group was significantly improved by the incubation with AM (P0.05). Compared with the control group (104.1 +/- 14.2) micromol/g, NOx levels of FFA group was (83.1 +/- 8.4) micromol/g (P0.05), and the treatment of AM increased the levels of NOx (98.8 +/- 10.7) micromol/g (P0.05). The control vascular ring had a little NF-kappaB expression in endothelial nucleus, FFA increased the activation of NF-kappaB, while the treatment of AM lower the elevated NF-kappaB level.FFA can directly injure EDV, while AM may ameliorate it, with the possible mechanism related to the signal pathway of NF-kappaB and NO.

To analyze the impact of parental Metabolic Syndrome (MS) on adolescents, and to explore the familial aggregation of MS with its components.Using a 1:3 case-control familial study design to choose 26 MS male patients as proband and 78 healthy men as controls. Data regarding phenotype of their adolescence offspring were collected. Height, weight, waist circumference (WC), blood pressure, body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were measured or calculated. FPG, TC, TG, HDL-C and LDL-C were detected by automatic biochemical analyzer and hs-CRP was detected.WC, WHtR, WHR, DBP and hs-CRP of those adolescents with paternal MS were significantly higher than in controls (P0.05). Rates of MS, Obesity depend WC, low level of HDL-C of adolescent with paternal MS were significantly higher than in controls (P0.05). The rate of number on MS was significantly higher in case group than in control (r = 0.231, P0.05).The phenotypes of MS were different between adolescents with or without parental MS, indicating that the familial aggregation of MS had been existed in their adolescent offspring, and mainly presented in central obesity, increased blood pressure and inflammation.

To explore multi-slice spiral CT (MSCT) virtual endoscopy (CTVE) in the detection of Vater’s ampulla lesions. In addition to 30 healthy volunteers, 18 cases of common bile duct stones, and 7 cases of ampullary carcinoma were scanned with MSCT including virtual endoscopy (VE) reconstruction. Patterns of the duodenal papilla were then observed, and its size was measured. Reconstructed images of CTVE in the volunteers showed that the normal type of the duodenal papilla was nodular in 16 cases, V-shaped in 8 cases, and Y-shaped in 6 cases. Its mean diameter was 0.84 ± 0.17 cm in the healthy volunteers; in patients with common bile duct stones of nodular type, mean diameter was 1.72 ± 0.32 cm. In ampullary cancer patients with an irregular protruded type, its diameter was 2.30 ± 0.85 cm, Overall the mean differences between the groups were statistically significant (P

Interaction of costimulatory molecules and their receptors is crucial for tumor lysate-pulsed dendritic cells (sensitized DC, sDC) to promote T cell activation, clonal expansion and its antitumor immunity. To augment the costimulatory signal may regulate the interaction between DC and cytotoxic T lymphocyte (CTL) and consequently enhance the antitumor response. The costimulatory ligand and receptor pair of 4-1BB/4-1BBL is one of the main factors in the costimulation of CTL. We explored the adjuvant role of a recombinant human 4-1BBL extracellular domain (ex4-1BBL) in modulating CTL activation induced by HepG2 antigen-loaded DC (sDC). The augment effects of sDC in combination with ex4-1BBL on the proliferation, activation, cell survival and cytotoxicity against HepG2 cells of CTL were examined. In the presence of ex4-1BBL, sDC exhibited markedly augmented effects on the above four functions of CTL. These results demonstrate that ex4-1BBL plays an important role in the costimulation pathway for DC-mediated CTL’s activation, which might be a useful adjuvant factor for DC-based cancer biotherapy.

Summary Background Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial. Methods Healthy adults aged 16–65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 μg of purified recombinant hepatitis E antigen adsorbed to 0·8 mg aluminium hydroxide suspended in 0·5 mL buffered saline) or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-generated permuted blocks and stratified by age and sex. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose. Analysis was based on participants who received all three doses per protocol. Study participants, care givers, and investigators were all masked to group and vaccine assignments. This trial is registered with ClinicalTrials.gov, number NCT01014845. Findings 11 165 of the trial participants were tested for hepatitis E virus IgG, of which 5285 (47%) were seropositive for hepatitis E virus. Participants were randomly assigned to vaccine (n=56 302) or placebo (n=56 302). 48 693 (86%) participants in the vaccine group and 48 663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100·0% (95% CI 72·1–100·0). Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted. Interpretation HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16–65 years. Funding Chinese National High-tech R&D Programme (863 programme), Chinese National Key Technologies R&D Programme, Chinese National Science Fund for Distinguished Young Scholars, Fujian Provincial Department of Sciences and Technology, Xiamen Science and Technology Bureau, and Fujian Provincial Science Fund for Distinguished Young Scholars.

To evaluate the efficiency of self-made paste on gingival retraction in dogs as well as its potential clinical application.Forty teeth from two mature dogs were prepared with 0.5 mm wide shoulder in the lip and buccal sides of the teeth, and then divided into four groups randomly. The gingival grooves of the four groups were filled with self-made colloid paste, Expasyl gingival retraction paste, gingival retraction cord, and medicated (15.5% Fe2SO4 solution) gingival retraction cord, respectively. The gingival grooves models before and after gingival retraction were analyzed using the image precise mapper instrument; the gingival width and height of the gingival groove were compared using SAS6.12 software package.The changes of gingival width of the gingival groove before and after gingival retraction were not significant between the four groups. However, the gingival height of the gingival groove in the medicated gingival retraction cord group increased significantly [(0.423 + or - 0.348) mm before gingival retraction and (0.623 + or - 0.278) mm after gingival retraction] compared with the other three groups.The self-made colloid paste for gingival retraction is efficient like Expasyl gingival retraction paste and gingival retraction cord with potential clinical application, while the medicated gingival retraction cord can induce gingival shrinkage. Supported by Research Fund of Science and Technology Bureau of Huangpu District,Shanghai.

To investigate the prevalence and time of Dickkopf (DKK) family methylation and its clinical significance in hepatocarcinogenesis.Methylation of DKK family genes was quantitatively analyzed in 115 liver tissue samples, including 50 pairs of primary hepatocellular carcinoma (HCC) and matched noncancerous cirrhotic tissue samples, as well as 15 liver cirrhosis biopsy samples.The methylation level of DKK3 was significantly higher in HCC tissue samples than in matched noncancerous cirrhotic tissue samples (P0.0001) or in liver cirrhosis biopsy samples (P = 0.0139). Receiver operator characteristic curve analysis confirmed that the percent of methylated reference (PMR) values of DKK3 could effectively discriminate HCC tissue samples from noncancerous tissue samples (AUC = 0.8146) or liver cirrhosis biopsy samples (AUC = 0.7093). Kaplan-Meier survival curves revealed that the progression-free survival time of patients with a higher DKK3 methylation level (PMR1%) was significantly shorter than that of those with a lower DKK3 methylation level (PMRor = 1%) (P = 0.0255). Multivariate Cox analysis indicated that methylated DKK3 was significantly and independently related with a shorter survival time (relative risk = 2.527, 95% CI: 1.063-6.008, P = 0.036) of HCC patients.Methylation of DKK3 is an important event in early malignant transformation and HCC progression, and therefore might be a prognostic indicator for risk assessment of HCC.

To screen and determine the regions of copy number variation (CNV) associated with hepatocellular carcinoma (HCC) using SNP array and fluorescence quantitative PCR.The CNV from HCC cell line TJ3ZX-01 was analyzed using GeneChip Human Mapping 500K SNP array. According to the data obtained by SNP array analysis, four candidate amplification regions were verified in 41 primary HCC samples by fluorescence quantitative PCR.Four regions of copy number amplification at 1q21.2, 1q22 approximately 23.1, 7p22.1 and 22q13.1 were detected by SNP array analysis. The four candidate amplicons occurred in 56.1% (23/41) of HCC samples at 1q21.2; 80.5% (33/41) at 1q22 approximately 23.1; 75.6% (31/41) at 7p22.1 and 31.7% (13/41) at 22q13.1 analyzed with sequence tagged site (STS) markers by quantitative PCR.In four candidate amplification regions selected by SNP array analysis and detected by fluorescence quantitative PCR, three amplification regions show increased copy number in more than 50.0% HCC tissues. This result indicates that these amplification regions are associated with pathogenesis of hepatocellular carcinoma.

To investigate the methylation frequencies of multiple tumor suppressor genes (TSGs) in hepatocellular carcinoma (HCC) and the clinical implication of aberrant DNA methylation in molecular carcinogenesis of HCC.Sixty samples of HCC and the paired adjacent liver tissue, 16 samples from post-hepatitis cirrhotic livers, 5 from livers with chronic hepatitis and 5 from normal livers were collected. Eight TSGs frequently silenced by hypermethylation of their promoters in various types of digestive tumors were selected, including APC, RASSF1A, p16, GSTP1, MGMT, DAPK, SOCS-1 and RIZ1. The status of promoter methylation in these 8 genes was investigated using methylation-specific polymerase chain reaction. The clinicopathological data of HCC were also analyzed in order to evaluate the clinical implication of aberrant methylation in HCC.Methylation of the 8 TSGs was quite frequent in HCC, with a methylation rate of 95.0% in RASSF1A, 90.0% in APC, 73.3% in GSTP1, 65.0% in p16, 61.6% in RIZ1 and 60.0% in MGMT. Methylation of the 6 genes was more frequent in HCC than that in adjacent tissues (P0.05). The methylation rate of MGMT, GSTP1 and RIZ1 in the adjacent tissues was 41.6%, 40.0% and 25.0%, respectively, significantly higher than that in cirrhotic liver (P0.05). p16 methylation was more frequently observed in HCC in elderly patients. The frequency of MGMT methylation was tended to be higher in giant HCC than that in the other types of HCC. Patients with MGMT methylation in the tumor were found to have a shorter disease free survival.Different frequency of methylation in hepatocellular carcinomas, adjacent liver tissues and cirrhotic livers implies that epigenetic alteration in the hepatocellular carcinogenesis may be a gradually progressive process. Methylation status of MGMT, GSTP1 and RIZ1 may be promising in risk assessment of hepatocellular carcinoma and in early diagnosis. Furthermore, MGMT methylation might be also used as a potential prognostic biomarker for hepatocellular carcinoma patients.

To investigate the practical possibility of inducing dendritic cells (DCs) from mononuclear cells in the lost blood during operation of hepatocellular carcinoma (HCC) patients, and attempted to find a new source of precursor cells for the personalized immunotherapy based on DCs.Collected lost blood during hepatectomy from 9 HCC patients and human cord blood from 8 cases of healthy donors undergoing caesarean section. Their mononuclear cells were divided into monocytes and nonadherent lymphocytes. RhGM-CSF and rhIL-4 were administered to induce the monocytes differentiation into DCs, and then loaded with different antigens (lysate antigen of autologous liver cancer cells and cell line SMMC-7721 cells). The lymphocytes were induced into cytokine-induced killer cells (CIK) with IL-2, CD3-Ab, gamma-IFN and PHA. MTT assay was performed to detect the proliferation rate of T lymphocytes mediated by DC and the cytotoxicity of CIK to liver cancer cells.DCs induced from monocytes of the intra-operative lost blood possessed typical morphology and phenotypes. Compared with the DCs from cord blood, the DCs from intra-operative lost blood expressed lower level of surface markers, but both could effectively induce proliferation of CIK and enhance the cytotoxicity of activated CIK against liver cancer cells at similar levels. When the DCs from lost blood and their counterpart from cord blood were both loaded with autologous tumor cell antigen, the proliferation rates of CIK were (388.9 +/- 137.3)% and (315.1 +/- 44.5)%, respectively, and the killing rates against tumor cells were (87.1 +/- 8.0)% and (90.0 +/- 5.1)%, respectively. When the two similar DC groups were loaded with lysate antigen of SMMC-7721 cells, the proliferation rates of CIK were (239.9 +/- 48.7)% and (226.3 +/- 32.3)%, respectively, and the killing rates against tumor cells were (76.4 +/- 7.9)% and (81.1 +/- 4.3)%, respectively. There were no significant differences between those two DC groups. The data also showed that the proliferation and cytotoxicity of CIK induced by DCs loaded with autologous antigen were higher than that of DCs loaded with SMMC-7721 antigen.Mononuclear cells separated from intra-operative lost blood of HCC patients can be induced into mature DCs, which can effectively activate CIK and significantly increase its killing effect on the liver cancer cells, and may become a new source of DCs to study and develop vaccines for clinical application.

To study the effects of demographic variables, surgery-related uncertainty and other related variables on preoperative anxiety and depression in patients undergoing selective cardiac surgery.103 patients who were scheduled for cardiac surgery were investigated by using Hospital Anxiety and Depression Scale (HADS) and a self-made questionnaire, and the related influencing factors were analyzed.The positive rates of anxiety, depression, and both anxiety and depression were 27%, 20%, and 14% respectively. The anxiety score of the female patients was (7.3 +/- 3.8), significantly higher than that of the male patients [(4.3 +/- 3.2), T(97) = 3.41, P0.01]. The depression score of the female patients was (6.4 +/- 3.4), significantly higher than that of the male patients [(4.3 +/- 3.2), T(97) = 2.98, P0.01]. The education background had no significant influence on anxiety score [F(3, 98) = 1.06, P = 0.37] while had significant difference on depression score [F(3, 98) = 4.10, P0.01]. The three factors reflecting the recognition of surgery-related uncertainty, "what I thought is all about the surgery", "I'm worrying about the possible failure of surgery" and "I'm worrying about the possible unsatisfied convalescence", showed very significant effects on the anxiety and depression scores (all P0.01).The state of preoperative anxiety and depression of the cardiac surgical patients are influenced by multiple factors, which should be considered in clinical practice. Recognition of surgery-related uncertainty is one of the most important influencing factors that can predict the state of preoperative anxiety and depression.

To study the effect of Streptococcus sanguis on corrosion resistance of magnetic retainers in which are encapsulated with stainless steel artificial saliva.A magnetic retainer was put in one culture flask,which was filled with artificial saliva.Ten of them were added Streptococcus sanguis suspension,the others were added PBS as control.The culture flasks were cultivated in incubator(36 degrees centigrade). 5 ml suspension was dislodged from each flask at the 3rd, 10th and 20th day. The quantity of Fe(3+) and Mn(2+) was detected.Statistical analysis of paired t test was performed with SPSS10.0 software package.When Streptococcus sanguis existed, the quantity of Fe(3+) and Mn(2+) was significantly higher than that in the control (P0.01).The existence of Streptococcus sanguis destroys the corrosion resistance of magnetic retainers remarkably.

To study the effects of two specific cyclooxygenase inhibitors (SCI), rofecoxib and celecoxib, combined with chemotherapeutic drugs 5-Fu, DDP and VP-16 on gastric cancer cell line BGC-823, and to evaluate whether specific cyclooxygenase inhibitors can be used as a synergetic agent in chemotherapy.The gastric cancer cell line BGC-823 cells were incubated for 48 hours with rofecoxib and celecoxib, 5-Fu, DDP and VP-16 (concentration gradient of 5-Fu, DDP and VP-16:1 microg/ml, 10 microg/ml and 100 microg/ml), or in combination, respectively. MTT working solution was added to each culture and calculated the survival rates of gastric cancer cells. Median-effect principle and Professor Jin's evaluation methods were applied to detect the interaction between the specific cyclooxygenase inhibitors and chemotherapeutic agents.The inhibition rates of gastric cancer cells were 42.63% +/- 1.26% and 50.67% +/- 2.35% by treatment with 0.1 micromol/L rofecoxib and 50 micromol/L celecoxib, respectively. The inhibition rates of gastric cancer cells by treatment with 5-Fu, DDP and VP-16 at different concentrations (1 microg/ml, 10 microg/ml and 100 microg/ml) were 39.75% +/- 3.14%, 49.96% +/- 2.08%, 87.93% +/- 3.66%; 48.28% +/- 2.08%, 59.46% +/- 1.69%, 88.23% +/- 4.81%; and 29.23% +/- 3.27%, 49.34% +/- 3.75%, 79.24% +/- 2.44%, respectively. However, the inhibition rates showed a synergetic role while combined the two SCI (0.1 micromol/L rofecoxib and 50 micromol/L celecoxib) with chemotherapeutic agent at different concentrations (P0.05).Both rofecoxib and celecoxib have an ability to suppress gastric cancer cells in vitro, and the synergetic role becomes evident when rofecoxib and celecoxib are combined with chemotherapeutic agents at different concentrations, which indicate that the two specific cyclooxygenase inhibitors may be used as a chemotherapeutic sensitizer.

ABCG2 is a member of the ABC transporter superfamily, which has been implicated in the development of multidrug resistance (MDR) in cancer. Its diverse range of substrates includes many antineoplastic agents such as topotecan, doxorubicin and mitoxantrone. ABCG2 expression has been significantly increased in some solid tumors and hematologic malignancies, which is correlated to poorer clinical outcomes. In addition, ABCG2 expression is a distinguishing feature of cancer stem cells, whereby this membrane transporter impacts resistance to the chemotherapeutic drugs. To enhance the chemosensitivity of cancer cells, attention has been focused on MDR modulators. In this study, we investigated the ability of a tetrodotoxin-resistant sodium channel blocker, A-803467 to reverse ABCG2-mediated MDR. We found that A-803467 at non-toxic concentration could significantly increase the cellular sensitivity to ABCG2 substrates in drug-resistant cells overexpressing either wild-type or mutant ABCG2. Mechanistic studies indicated that A-803467 (7.5 μM) significantly increased the intracellular accumulation of mitoxantrone by inhibiting the transport activity of ABCG2, without altering its expression level. In addition, A-803467 stimulated the ATPase activity of ABCG2 in a concentration-dependent manner, indicating that A-803467 might be a substrate of ABCG2. Binding interactions of A-803467 were found to be in transmembrane region of homology modeled human ABCG2. Interactions of A-803467 with ABCG2 were relatively stronger when compared to the interactions of topotecan with ABCG2. Furthermore, A-803467 (30 mg/kg) with topotecan (3 mg/kg) significantly decreased the growth rate and tumor size of ABCG2 overexpressing tumors in a xenograft nude mouse model. Our findings indicate that A-803467 has the potential to be used in combination with ABCG2 chemotherapeutic substrates to improve the response in drug resistant cancers. Citation Format: Nagaraju Anreddy, Atish Patel, Yun-Kai Zhang, Yi-Jun Wang, Suneet Shukla, Rishil J. Kathawala, Priyank Kumar, Pranav Gupta, Suresh V. Ambudkar, John ND Wurpel, Zhe-Sheng Chen. A-803467, a tetrodotoxin-resistant sodium channel blocker, modulates ABCG2-mediated MDR in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4432. doi:10.1158/1538-7445.AM2015-4432

Cancer cells often exhibit either intrinsic or acquired resistance to chemotherapy through a phenomenon known as multidrug resistance (MDR). Different mechanisms contribute to the development of MDR, preeminent among them being the accelerated drug efflux mediated by overexpression of ATP-binding cassette (ABC) transporters. Currently, it has been found that some small molecule tyrosine kinase inhibitors (TKIs), such as motesanib, linsitinib, masitinib and nilotinib, were able to modulate the activity of ABC transporters. Thus, the aim of this study was to determine whether TTT-28, a newly synthesized thiazole-valine peptide, could reverse ABCB1-mediated MDR. The results showed that TTT-28 significantly sensitized both ABCB1-transfected and drug-selected cell lines overexpressing this transporter to its substrate anticancer drugs. Using calcein-AM efflux assay, we identified TTT-28 (IC50 = 1.0 μM) carrying 3,4,5-trimethoxybenzoyl and 2-aminobenzophenone groups, respectively, at the amino and carboxyl termini of the monothiazole zwitterion. TTT-28 significantly increased the accumulation of [3H]-paclitaxel in ABCB1 overexpressing cells by blocking the efflux function of ABCB1 transporter. Furthermore, TTT-28 inhibited the photolabeling of ABCB1 with [125I]-iodoarylazidoprazosin with IC50 = 0.75 μM and stimulated the basal ATP hydrolysis of ABCB1 in a concentration-dependent manner (EC50 ATPase = 0.027 μM). Consistent with these findings, biochemical and docking studies showed site-1 to be the preferable binding site for TTT-28 within the drug-binding pocket of human ABCB1. Therefore, we report that TTT-28 antagonizes MDR by inhibiting the efflux activity of the ABCB1 transporter. These findings reveal high clinical values for the co-administration of TTT-28 and ABCB1 substrate chemotherapeutic drugs in cancer patients that overexpress ABCB1 and stimulate further research on circumventing the ABCB1-mediated MDR in cancers. Citation Format: Yi-Jun Wang, Nagaraju Anreddy, Bhargav A. Patel, Eduardo E. Chufan, Satyakam Singh, Guan-Nan Zhang, Yun-Kai Zhang, Anna Maria Barbuti, Suresh V. Ambudkar, Tanaji T. Talele, Zhe-Sheng Chen. TTT-28, a newly synthesized thiazole-valine peptide, antagonizes multidrug resistance by inhibiting the efflux activity of the ABCB1 transporter. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4422. doi:10.1158/1538-7445.AM2015-4422

Abstract: Despite the current advances in cancer drug discovery, cancer cells often develop resistance to chemotherapeutic agents leading to poor clinical outcomes. The phenomenon of multidrug resistance (MDR) is prevalent among tumor populations; wherein cancer cells are rendered resistant to structurally and mechanistically unrelated drugs. Of the several factors responsible for the development of MDR, the overexpression of ATP-binding cassette (ABC) efflux transporters poses a serious threat towards attaining a successful chemotherapeutic outcome. The second member of the G sub-family of ABC transporters (ABCG2) is one such efflux transporter that renders the cancer cells resistant to several chemotherapeutic drugs, in turn limiting their intracellular accumulation. The blockade of this efflux pump offers a strategic approach towards increasing the efficiency of chemotherapy. Here we demonstrate the biological activity of a novel N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide analog, CCTA-1650 that blocks the efflux function of ABCG2 in vitro and in vivo in a preclinical tumor xenograft nude mouse model. Cell cytotoxicity assays performed by combining the chemotherapeutic agents with CCTA-1650 at concentrations of up to 5 μM significantly increased the sensitivity of resistant cancer cells overexpressing both the wild-type and mutant variants of ABCG2. CCTA-1650 inhibits the function of the transporter by decreasing the efflux of substrate chemotherapeutic agents as evident from accumulation and efflux studies with [3H]-mitoxantrone. Furthermore CCTA-1650 at concentrations of up to 5 μM did not affect the expression of ABCG2 transporter upon treatment with CCTA-1650. In addition, CCTA-1650 increased the ATPase activity of ABCG2 in a concentration-dependent manner. CCTA-1650 also displayed inhibition of function of the ABCG2 transporter in an in vivo tumor xenograft nude mouse model. CCTA-1650 at a dose of 30 mg/kg significantly sensitized the resistant tumors to doxorubicin. This effect obtained with combining chemotherapeutic agents with an inhibitor of ABCG2 function both in vitro and in vivo demonstrates the usefulness of CCTA-1650 for the treatment of drug-resistant tumors in the clinic. Citation Format: Atish S. Patel, Tianwen Li, Nagaraju Anreddy, Yufen Zhao, Rishil J. Kathawala, Yijun Wang, Suresh V. Ambudkar, Zhe-Sheng Chen, Changmei Cheng. Design, synthesis and biological evaluation of N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide analog as a promising inhibitor of the multidrug resistance-linked ABCG2 transporter. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4419. doi:10.1158/1538-7445.AM2015-4419

The total internal reflection (TIR) effect in conventional electroluminescent devices causes a large amount of light energy trapped in the devices and result in heat energy that adversely affects the performance of the device. In order to enhance the light out-coupling efficiency without sacrificing the electrical properties, a micro-rod array (MRA) structure fabricated by a femtosecond laser was demonstrated. Green, blue, and red organic light-emitting diodes were employed to verify the effect of the proposed method, which increases out-coupling efficiencies by a factor of 1.9, 1.7, and 1.82, respectively, compared with conventional devices. This highly effective method is compatible with current device fabrication processes and is applicable to full-color electroluminescent devices.

To evaluate the efficacy of using sonic electric toothbrush to clean the teeth and control dental plaque in children.50 children aged 6 to 7 years old were selected and divided into 2 groups according to the use of sonic electric toothbrush and traditional manual toothbrush (control group). The numbers of dental plaque surface and PLI before and after tooth brushing were recorded. The data of the two groups were analyzed with SPSS10.0 software package for student's t test and chi(2) test.The ratio of dental plaque removal was 70.22% by using sonic electric toothbrush and 39.08% in the control group. The efficacy of dental plaque removal on the lingual and mesial buccal surface by using sonic electric toothbrush was 2 times greater than the control group. The PLI and the ratio of dental plaque removal were significantly different between the 2 groups (P0.001).Sonic electric toothbrush can help children effectively remove dental plaque. It's an efficient instrument for oral care of children.

To explore the ideal method for conservative therapies of posterior teeth with longitudinal fracture.The records of 297 cases undergoing conservative treatment of posterior teeth with longitudinal fracture were analyzed regarding to the position, etiology and the time of treatment from fracture and the causes of failure.258 cases were conserved effectively and 39 cases were extracted due to failure.16 cases had failure 1 week after treatment. All the patients were followed up for 2 to 10 years, and the rate of success was 86.87%.With fixed early and appropriate treatment, the teeth can be conserved effectively and exert good masticatory function .

To study maturation of the metacarpal bone in puberty children during their growth spurt period and its difference between urban and rural areas.Totally, 560 pupils/students were selected from primary and secondary schools in urban and rural areas each, with 35 children in each gender and age group, ranging 12 - 15 years of age for boys and 10 - 13 for girls. An X-ray film of left hand-wrist site was taken for each of them. Length and width of the metacarpal bone were measured and the metacarpal index was calculated.Increment of length of the metacarpal bone was great in puberty children both in urban and rural areas, (6.26 - 9.31) mm in boys and (5.28 - 9.12) mm in girls. Mean length of the metacarpal bone was longer in children of urban areas than that of rural ones, regardless of their age and gender. There was significant difference in mean length of the metacarpal bone between boys aged 14 - 15 years and girls aged 12. Mean width of the metacarpal bone in most children was wider in rural areas than that in urban ones. Mean metacarpal index in children was higher in urban areas than that in rural ones, with very statistical significance, except for girls of 13 year age group. The peak age of metacarpal maturation was 1 year earlier in urban areas than in rural ones.Maturation of the metacarpal bone was rapid during puberty growth spurt period, with relatively significant difference in urban and rural ares.

Solids flow pattern in the bottom zone of a rectangular cross-section CFB was investigated by using hot particles as the tracer. The experiments were carried out in a cold model circulating fluidized bed. The riser has an inner cross-section of 0.3 m by 0.5 m and a height of 5.8 m. The solids were returned into the riser at a height of 0.75 m above the air distributor within an angle of about 40 degree. Quartz sand was used as the bed material. The hot particles were also quartz sand but with a little smaller size. Specially designed miniature electrically heating devices were installed flush with the inner bed wall or inside the bed. At each run, about 10–15 cm3 hot particles were slowly pulled into the bed. The temperature response around the device was measured with four copper-constantan thermocouples. Based on the experimental results, a 3-D core-annulus model describing the solids flow pattern in the bottom zone of the CFB riser is proposed.Copyright © 2003 by ASME

The ATP-binding cassette, subfamily G, isoform 2 protein (ABCG2) is a vital member of the ABC transporter superfamily, which has been involved in multidrug resistance (MDR) in cancer. Its diverse range of substrates includes many antineoplastic agents such as doxorubicin and mitoxantrone. ABCG2 expression has been significantly increased in some solid tumors and hematologic malignancies, which is correlated to poorer clinical outcomes. In addition, ABCG2 expression is a distinguishing feature of cancer stem cells, whereby this membranous transporter imparts resistance to the chemotherapeutic drugs. To enhance the chemosensitivity of cancer cells, attention has been focused on MDR modulators. In this study, we investigated the ability of sodium channel blocker, A-803467 to reverse ABCG2-mediated MDR. We found that A-803467 at non-toxic concentration could significantly increase the cellular sensitivity to ABCG2 substrates in drug-resistant cells overexpressing either wild-type or mutant ABCG2. Mechanistic studies indicated that A-803467 (7.5 μM) significantly increased the intracellular accumulation resulted from inhibition of the efflux of mitoxantrone by inhibiting the transport activity without altering expression level of ABCG2 protein. Furthermore, ATPase analysis indicates that A-803467 stimulates the ATPase activity in membranes overexpressing ABCG2. in-vivo results indicating that tumor volume was significantly decreased by combination of A-803467 with topotecan when compared to the topotecan and A-803467 alone group. Our findings suggest that A-803467 has the potential to be used in combination with ABCG2 chemotherapeutic substrates to augment the response in drug resistant cancers. Citation Format: Nagaraju Anreddy, Priyank Kumar, Atish Patel, Yun-Kai Zhang, Yijun Wang, Rishil Kathawala, John D. Wurpel, Zhe-Sheng Chen. A-803467, a sodium channel blocker, reverses ABCG2-mediated MDR in vitro as well as in vivo. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A01.

TAG-1 is a neural recognition molecule in the immunoglobulin superfamily that is predominantly expressed in the developing brain. Several lines of evidence suggest that TAG-1 is involved in the outgrowth, guidance, and fasciculation of neurites. To directly assess the function of TAG-1 in vivo, we have generated mice with a deletion in the gene encoding TAG-1 using homologous recombination in embryonic stem cells. Gross morphological analysis of the cerebellum, the spinal cord, and the hippocampus appeared normal in TAG-1-deficient mice. However, TAG-1 (−/−) mice showed the upregulation of the adenosine A1 receptors determined by [3H]cyclopentyl-1,3-dipropylxanthine in the hippocampus, and their greater sensitivity to convulsant stimuli than that in TAG-1 (+/+) mice. We suspect that the subtle changes in neural plasticity induced by TAG-1 deficiency during development cause the selective vulnerability of specific brain regions and the epileptogenicity in TAG-1 (−/−) mice.

The aim of this study was to investigate the effect of cholecystokinin (CCK) receptor antagonist on the abnormal behavior and dopamine (DA) transmission of tenascin (TN)-gene knockout mice. Recently, we demonstrated that TN-gene deficient mice show hyperlocomotion that is related to reduced DA transmission and tyrosine hydroxylase (TH) activities in the brain. In this report, we show that the intraperitoneal administration of a CCK-B receptor antagonist, PD135158 (0.1 mg/kg), but not a CCK-A receptor antagonist, lorglumide, inhibited hyperlocomotion. Moreover, PD135158 reversed the low levels of DA turnover rate and TH activities in the striatum of TN-gene knockout mouse brain. These results suggest that CCK-B receptor is involved in the behavior of TN-gene knockout mouse through striatal DA transmission.

Effects of sub-chronic ethanol treatment on the mRNA levels of muscarinc acetylcholine receptor (mAChR) subtypes were studied in two neurohybrid cell lines, NG108-15 and NCB-20. The former expresses only m4-mAChRs, while the latter expresses m1- and m4-mAChRs. Exposure to 200 mM ethanol for 1 to 3 days induced a time-dependent increase in the levels of m4-mAChR mRNA in NG108-15 and NCB-20 cells. In contrast, the levels of m1-mAChR mRNA and mAChR-mediated phosphoinositide hydrolysis in NCB-20 cells were unchanged. The ethanol-induced up-regulation of m4-mAChR mRNA was associated with a parallel increase in the levels of mAChR binding sites assessed by using [ 3 H]quinuclidinyl benzilate. The mRNA up-regulation was closely correlated with a decrease in intracellular cyclic AMP concentration and the ethanol up-regulation was blocked by 8-bromo-cyclic AMP and forskolin, suggesting that m4-mAChR mRNA is under negative regulation by cyclic AMP. Thus, neurally-related cell lines are useful models for studying molecular mechanisms underlying ethanol-induced alteration of mAChR expression and function in the nervous system.

Tenascin is a large extracellular matrix glycoprotein which is highly expressed in the developing nervous system. To examine the role of tenascin in vivo, we have produced mice in which the tenascin-gene is inactivated. These animals did not easily habituate to unfamiliar circumstances and displayed hyperlocomotion. A dopamine receptor agonist, apomorphine, reduced this hyperlocomotion dose dependently, but this phenomenon was not due to the appearance of apomorphine-induced stereotypic behavior, suggesting that tenascin-gene mutant mice have a paradoxical behavioral response to apomorphine compared to wild-type mice.

We have recently demonstrated that some tenascin (TN) gene-knockout mice display abnormal behaviors, and that these abnormal behaviors stem from a low level of dopamine transmission in the brain. In the present study, we elucidated that tyrosine hydroxylase (TH) activity in the frontal cortex, striatum, and hippocampus of TN-knockout mice which showed abnormal behavior was significantly decreased. Also, the TH mRNA level of the midbrain was decreased by 43% in these animals compared with values for wild-type mice. These results suggest that the low dopamine turnover rate in some areas of the brain of TN-knockout mice accompanied by motor defects is due, at least in part, to the reduction in TH activity caused by diminished TH mRNA expression, and that TN-knockout mice exhibit abnormal behaviors in the presence of low levels of TH-gene expression.

A critical temperature is found in the phase transition of blue phase liquid crystal (BPLC), which affects the electro-optical properties and polymer stabilization of polymer stabilized BPLCs (PSBPLCs). The relation between lattice formation process of BPLCs and the temperature is also demonstrated showing that the heterogeneous lattice generation and the homogeneous lattice growth dominate the different temperature ranges in phase transition process. With different cooling rates, the material properties of BPLCs change as the result of different stages of heterogeneous lattice generation and homogeneous lattice growth.

NCB-20 cells expressed m1- and m4-muscarinic acetylcholine receptor (mAChR) mRNAs, while NG108-15 cells expressed only m4-mAChR mRNA. Butyrate induced a time-dependent increase in the level of m1-mAChR mRNA with no change in the m4-mAChR mRNA level in NCB-20 cells. Similarly, butyrate did not affect the m4-mAChR mRNA level in NG108-15 cells. In contrast, dibutyryl cAMP caused a significant time-dependent decrease in the level of m4-mAChR mRNA in NCB-20 and NG108-15 cells as well as m1-mAChR mRNA in NCB-20 cells. Our results suggest that these two differentiating agents are important physiological regulators of the transcription and/or stability of the mRNA of certain mAChR subtypes expressed in these two neurohybrid cell lines.