[Upregulation of PLOD2 promotes invasion and metastasis of osteosarcoma cells].

Objective: To investigate the relationship of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression and the clinical characteristics of osteosarcoma, and explore the potential mechanism of tumour metastasis promoted by PLOD2. Methods: The expression of PLOD2 in osteosarcoma tissues and paired adjacent tissues were detected by immunohistochemistry and qRT-PCR. Correlation of PLOD2 expression in osteosarcoma with the clinical pathologic features was analyzed by Chi square test and Kaplan-Meier analysis.Fibrillar collagen formation and collagen deposition in the tumor tissues were detected by picrosirius red staining. We transfected U-2OS cells with LV-vector, LV-over/PLOD2, sh-NC and sh-PLOD2. The expression of PLOD2 was detected by qRT-PCR. The impact of POLD2 on U-2OS cell invasion was determined by wound-healing assay and Transwell migration assay. The expressions of PLOD2/FAK/JAK2-STAT3 signal pathway related proteins were detected by western blotting. Results: The high expression level of PLOD2 in osteosarcoma tissues was 72.5%, significantly higher than 0% in paired adjacent noncancerous tissues (P<0.01), the expression of PLOD2 was positively correlated with lymph node metastasis, pulmonary metastasis and poor outcome (P<0.01). The same results were also observed in qRT-PCR assay. The median survival time of patients with high expression of PLOD2 protein was 13 months, significantly shorter than 32 months of patients with low expression of PLOD2 (P<0.05). The result of picrosirius red staining showed that the percentage of collagen fiber deposition in the osteosarcoma tissue with high level of PLOD2 was (74.43+ 9.63)%, significantly higher than (9.67±1.28)% in tissue with low expression of PLOD2 (P<0.001). The result of wound-healing and Transwell migration assay showed that over-expression of PLOD2 markedly promoted the invasion, however, knockdown of PLOD2 suppressed the invasion of U-2OS cells (both P<0.01). The result of western blotting showed that over-expression of PLOD2 significantly increased the expression levels of p-FAK, p-JAK2, p-STAT3, but knockdown PLOD2 decreased the levels of p-FAK, p-JAK2, p-STAT3 in U-2OS cells. Conclusions: Up-regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK/JAK2-STAT3 signal pathway.

Effects of Pretreatment, Specimen Thickness, and Artificial Aging on Biaxial Flexural Strength of Two Types of Y-TZP Ceramics.

OBJECTIVES: To evaluate the effects of surface treatment, specimen thickness, and aging on the biaxial flexural strength (BFS) of two types of yttria-stabilized, tetragonal zirconia polycrystal (Y-TZP) ceramics. METHODS AND MATERIALS: Disc-shaped specimens, 0.4 and 1.3 mm thick, made from hot isostatic pressed (Denzir) and non-hot isostatic pressed (ZirPlus) Y-TZP, were sandblasted, heat treated, and autoclaved. The surface topography was assessed in accordance with European Standard 623-624:2004 and the BFS tests in accordance with International Organization for Standardization Standard 6872:2008. For statistical analyses, one-way Shapiro-Wilk test, analysis of variance (post hoc: least significant differences), Mann-Whitney U-test, and Pearson correlation tests (p<0.05) were used. RESULTS: As delivered, the BFS of the 0.4-mm ZirPlus was >1.3-mm ZirPlus (p<0.01), and the BFS of the 0.4-mm Denzir was >1.3-mm Denzir (p<0.001). Sandblasting with 0.2 MPa reduced the BFS of the ZirPlus and Denzir discs (p<0.01), whereas sandblasting with 0.6 MPa increased the BFS of the 0.4-mm Denzir (p<0.001) and reduced the BFS of the 0.4-mm ZirPlus (p<0.05). Heat treatment significantly reduced the BFS of all the groups except for the 0.6 MPa sandblasted 0.4-mm ZirPlus. Autoclaving reduced the BFS of the as-delivered ZirPlus and Denzir specimens (p<0.001), whereas autoclaving the 0.6 MPa sandblasted and heat-treated specimens had no effect (p>0.05) on the BFS. The 0.6 MPa sandblasted, heat-treated, and autoclaved 0.4-mm Denzir exhibited higher BFS than the 0.6 MPa sandblasted, heat-treated, and autoclaved 0.4-mm ZirPlus (p<0.05). CONCLUSIONS: Thickness and surface treatment of Y-TZP-based ceramics should be considered since those factors could influence the BFS of the material.

[Mechanism of MALAT1 induced osimertinib resistance in HCC827 lung cancer cells].

Objective: To test the effect of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) and/or osimertinib on the proliferation and apoptosis of HCC827 cells, and explore the potential mechanism of MALAT1 induced resistance to osimertinib. Methods: We transfected HCC827 cells with LV-vector or LV-over/MALAT1. Stable transfected cells (HCC827/Vector, HCC827/MALAT1) were selected by adding puromycin. HCC827/MALAT1 cells were further transfected with the shRNA-negative control (NC) or shRNA-human epidermal growth factor receptor 3 (ERBB3) plasmid. The effects of overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib on the proliferation of HCC827 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. Cell apoptosis induced by MALAT1 overexpression, knockdown of ERBB3 and/or osimertinib treatment were analyzed by flow cytometry analysis. The expressions of EGFR and ERBB3 signal pathway related proteins in HCC827 cells treated with overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib treatment were detected by western blot. Results: The MTT assay showed that sensitivity to osimertinib of HCC827/MALAT1 cells were significantly repressed. The 50% inhibitive concentration (IC(50)) of osimertinib >4 000 nmol/L in HCC827/MALAT1 cells. However, knockdown of ERBB3 facilitated the anti-proliferation effect of osimertinib, and the IC(50) of osimertinib in shRNA-ERBB3 cells was (17.27±3.21) nmol/L. The results of flow cytometry analysis showed that the apoptotic rate of HCC827/MALAT1 cells induced by 10 nmol/L osimertinib was (8.38±0.92)%, significantly lower than (27.17±5.83)% of knockdown of ERBB3 (P<0.01). Western blotting showed that the expression of p-ERBB3, p-AKT and p-extracellular regulated protein kinases (ERK) in HCC827/MALAT1 cells was markedly up-regulated, while the expression of p-epithelial growth factor receptor (EGFR) was inhibited. The expressions of p-ERBB3, p-AKT and p-ERK were marginally affected by osimertinb. However, osimertinib downregulated the expressions of p-EGFR, p-ERBB3, p-AKT and p-ERK in ERBB3 deleted cells. Conclusions: MALAT1 confers resistance to osimertinb in HCC827 cells by activating of the ERBB3/PI3K/AKT and ERBB3/MAPK/ERK signaling pathways.

[Expression of PLOD2 in esophageal squamous cell carcinoma and its correlation with invasion and metastasis].

Objective: To investigate PLOD2 expression in esophageal squamous cell carcinoma, and to explore the potential mechanism by which PLOD2 promotes tumor metastasis. Methods: The expression of PLOD2 in 60 cases of esophageal squamous cell carcinoma (the patients were collected at the first Affiliated Hospital of Xinxiang Medical University, from January 2016 to December 2017) was investigated by immunohistochemistry. Fibrillar collagen formation and collagen deposition were detected by picrosirius red staining. Correlation of PLOD2 expression with clinical pathologic features of the patients was performed using χ(2) test and Kaplan-Meier analysis. After EC-109 cells were transfected with LV-vector and LV-over/PLOD2, the expression of PLOD2 was detected by real time PCR and the impact of POLD2 on invasion in EC-109 cells was determined by transwell migration and invasion assays. The expression of PLOD2/AKT epithelial-to-mesenchymal transition signal pathway related proteins was detected by Western blot. Results: The expression level of PLOD2 in esophageal squamous cell carcinoma was 81.7% (49/60 cases),higher than their paired noncancerous tissues(8.3%, 5/60; P<0.01), and correlated significantly with tumor depth of invasion and nodal metastasis (P<0.01). Picrosirius red staining showed that collagen deposition was increased and the degree of fibrillar organization was enhanced in carcinoma tissues that had higher PLOD2 expression. Transwell migration and invasion assays showed that PLOD2 significantly promoted the migration and invasion ability of EC-109 cells. Western blot showed that PLOD2 significantly increased the expression levels of p-FAK, p-AKT and vimentin in EC-109 cells. Conclusions: Esophageal squamous cell carcinoma has a high expression of PLOD2 that correlates with tumor invasion and lymph node metastasis. PLOD2 promotes invasion and metastasis of esophageal squamous cell carcinoma through epithelial-to-mesenchymal transition via FAK/AKT signal pathway.

[Mechanism of miR-221 contributes to gefitinib resistance in PC-9 cells].

Objective: To investigate the effect of microRNA-221 (miR-221) overexpression on gefitinib resistance in PC-9 cells and study its underlying mechanisms. Methods: PC-9 cells were transfected with LV-NC and LV-miR-221 to establish cell stabilizing strains (PC-9/NC and PC-9/miR-221), then they were used to detect the relative expression of miR-221 and apoptotic protease activating factor-1 (APAF-1) mRNA by real-time fluorescence quantitative PCR (qRT-PCR). The effects of gefitinib (0-4 µmol/L) on the growth and proliferation of cell stabilizing strains were detected by CCK-8 Assay. After gefitinib treatment, cell apoptosis was detected by Flow Cytometry Assays. The expression of epidermal growth factor receptor (EGFR), phosphorylated epidermal growth factor receptor (p-EGFR), APAF-1 and cleaved cysteinyl aspartate specific proteinase-3 (Cleaved-caspase-3) were detected by Western blot. Dual-Luciferase Reporter Assay was used to evaluate the relationship between APAF-1 and miR-221. Results: The relative expression of miR-221 in PC-9/NC cells was significantly lower than that in PC-9/miR-221 cells[(1.00±0.082) vs (40.24±0.017)](P<0.01). The half maximal inhibitory concentration (IC(50)) in PC-9/NC cells was significantly lower than that in PC-9/miR-221 cells[(IC(50)=0.1 µmol/L) vs (IC(50)>4 µmol/L)](P<0.05). Apoptosis rate of PC-9/NC cell was significantly higher than PC-9/miR-221[(33.42±4.28)% vs (10.27±1.12)%](P<0.05); APAF-1 mRNA expression was significantly higher in PC-9/NC cells than PC-9/miR-221[(1.000+ 0.069) vs (0.701±0.072)](P<0.05), and the expression of APAF-1 protein in PC-9/NC cells was significantly higher than that of PC-9/miR-221 cells. The dual luciferase reporter gene results showed that miR-221a inhibited luciferase activity significantly stronger than transfected miRNA negative control group after co-transfection of luciferase plasmids pmir-REPORT-APAF-1-wt and miR-221a mimics (P<0.01). p-EGFR was down-regulated in both PC-9/NC and PC-9/miR-221 cells after treatment with gefitinib. APAF-1 and Cleaved-caspase-3 proteins were significantly down-regulated in PC-9/miR-221 cells compared with PC-9/NC cells, while APAF-1 and Cleaved-caspase-3 proteins were up-regulated in PC-9/NC cells treated with gefitinib compared with PC-9/miR-221 cells (P<0.05). Conclusion: miR-221 induces resistance to gefitinib in PC-9 cells by downregulating APAF-1 expression.

Inter-rater agreement of novel high-resolution impedance manometry metrics: Bolus flow time and esophageal impedance integral ratio.

BACKGROUND: Novel high-resolution impedance manometry (HRIM) metrics of bolus flow time (BFT) and esophageal impedance integral (EII) ratio have demonstrated clinical utility, though the reliability of their analysis has not been assessed. We aimed to evaluate the inter-rater agreement of the BFT and EII ratio. METHODS: HRIM studies including five upright, liquid swallows from 40 adult patients were analyzed by two raters using a customized MATLAB program to generate the BFT and EII ratio. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC) for median values generated per patient and also for all 200 swallows. KEY RESULTS: The ICC (95% confidence interval, CI) for BFT was 0.873 (0.759-0.933) for median values and 0.838 (0.778-0.881) for all swallows. The ICC (95% CI) for EII ratio was 0.983 (0.968-0.991) for median values and 0.905 (0.875-0.928) for all swallows. Median values for both BFT and EII ratio were similar between the two raters (P-values .05). CONCLUSIONS AND INFERENCES: The BFT and EII ratio can be reliably calculated as supported by generally excellent inter-rater agreement. Thus, broader utilization of these measures appears feasible and would facilitate further evaluation of their clinical utility.

Association between polymorphisms in the APOB gene and hyperlipidemia in the Chinese Yugur population.

We investigated the influence of apolipoprotein B gene (APOB) variants on the risk of hyperlipidemia (HL) in 631 middle-aged and elderly members of the Chinese Yugur population (HL, n=336; normolipidemia, n=295). APOB polymorphisms were identified using mass spectrometry, and five single nucleotide polymorphisms (rs1042034, rs2163204, rs512535, rs676210, and rs679899) and serum lipids were further analyzed. rs1042034 and rs676210 were significantly associated with HL (P<0.05). Compared with the GG or AA genotype, individuals with AG and AG+AA in rs1042034 and with AG and AG+GG in rs676210 had a 1.67-fold (95%CI=1.20-2.33),1.63-fold (95%CI=1.19-2.24), 1.72-fold (95%CI=1.24-2.40), and 1.67-fold (95%CI=1.21-2.291) increased risk of high HL, respectively. rs2163204 was in strong linkage disequilibrium with rs1042034, rs676210, and rs679899, and strong disequilibrium was observed between rs1042034 and rs676210 (D'>0.9). Compared with the GTGAA haplotype, haplotypes ATGGA and ATAGG were more strongly associated with HL [odds ratio (OR)=1.46, 95%CI=0.02-2.11; OR=1.63, 95%CI=1.03-2.60, respectively]. The risk factors age (P=0.008), body mass index (P<0.0001), GA+GG genotype in rs676210 (P=0.009), and alcohol consumption (P=0.056) contributed strongly to HL development. The A allele of rs1042034 and the G allele of rs676210 may thus predispose middle-aged and elderly members of the Chinese Yugur population to HL in combination with other genetic or nutritional factors, and could be used as new genetic markers for HL screening.

[Mechanism of long non-coding RNA-metastasis associated lung adenocarcinoma transcript 1 induced invasion and metastasis of esophageal cancer cell EC-109].

Objective: To investigate the effect and mechanism of long non-coding RNA-metastasis associated lung adenocarcinoma transcript 1, (LncRNA-MALAT1) on invasion and metastasis of esophageal cancer cell EC-109. Methods: EC-109 cells were transfected with lentiviral vector carrying short hairpin RNA of MALAT1( shRNA-MALAT1) or a nonspecific shRNA control (shRNA-control). The expressions of MALAT1, microRNA-200a, ZEB1 and ZEB2 were detected by qRT-PCR. The effect of shRNA-MALAT1 on invasion of EC-109 cells was determined by transwell assay. The expressions of components of epithelial-msenchymal transition pathway in EC-109 cells were determined by immunofluorescence array and western blotting. The expression relationship between MALAT1 and miR-200a in EC-109 cells was detected by dual-luciferase reporter assay. Results: The result of qRT-PCR showed that the expressions levels of MALAT1, ZEB1 and ZEB2 in shRNA-MALAT1 group were 0.43±0.06, 0.64±0.04 and 0.51±0.04, respectively, significantly lower than 0.97±0.08, 1.06±0.07 and 0.98±0.05 in shRNA-control group and 1 in control group, respectively(all P<0.05). Transwell assay showed that the number of invaded cells in shRNA MALAT1 group was (96.81±10.43) per low-power field, markedly lower than that of (278.44±13.28) per low-power field in shRNA-control group (P<0.01). Immunofluorescence staining and Western blotting showed that MALAT1 downregulation significantly reduced the expressions of proteins related to EMT signal pathway in EC-109 cells.Dual luciferase reporter assay showed that compared to negative control, the activities of luciferase reporter in EC-109 cells co-transfected with pmirGLO-MALAT1-wt and miR-200a were significantly down-regulated. While co-transfected pmirGLO-MALAT1-mut with miR-200a mimics had no effect on the luciferase reporter activities of MALAT1. Conclusion: LncRNA MALAT1 functions as a competing endogenous RNA to regulate the expressions of ZEB1 and ZEB2 by sponging miR-200a and promotes invasion and migration of esophageal cancer cells through inducing epithelial-mesenchymal transition.

Could the peristaltic transition zone be caused by non-uniform esophageal muscle fiber architecture? A simulation study.

BACKGROUND: Based on a fully coupled computational model of esophageal transport, we analyzed how varied esophageal muscle fiber architecture and/or dual contraction waves (CWs) affect bolus transport. Specifically, we studied the luminal pressure profile in those cases to better understand possible origins of the peristaltic transition zone. METHODS: Two groups of studies were conducted using a computational model. The first studied esophageal transport with circumferential-longitudinal fiber architecture, helical fiber architecture and various combinations of the two. In the second group, cases with dual CWs and varied muscle fiber architecture were simulated. Overall transport characteristics were examined and the space-time profiles of luminal pressure were plotted and compared. KEY RESULTS: Helical muscle fiber architecture featured reduced circumferential wall stress, greater esophageal distensibility, and greater axial shortening. Non-uniform fiber architecture featured a peristaltic pressure trough between two high-pressure segments. The distal pressure segment showed greater amplitude than the proximal segment, consistent with experimental data. Dual CWs also featured a pressure trough between two high-pressure segments. However, the minimum pressure in the region of overlap was much lower, and the amplitudes of the two high-pressure segments were similar. CONCLUSIONS & INFERENCES: The efficacy of esophageal transport is greatly affected by muscle fiber architecture. The peristaltic transition zone may be attributable to non-uniform architecture of muscle fibers along the length of the esophagus and/or dual CWs. The difference in amplitude between the proximal and distal pressure segments may be attributable to non-uniform muscle fiber architecture.

[Prevalence and risk factors of allergic rhinitis: a Meta-analysis].

Objective:To clarify the morbidity and risk factors of allergic rhinitis (AR) in China so as to provide scientific basis for prevention of AR in the relevant populations.Method:Pubmed,Embase,Web of science,Cochrane Library,CNKI,VIP,Wanfang Data,CBM databases were searched for associated studies. The prevalence and risk factors of AR in China were retrieved from individual studies and the pooled estimates generated by R3.2.3 software.Result:Thirty-one cross-sectional studies were included in the Meta-analysis. The results indicated that the incidences of AR in Chinese children were 15.79%(95%CI 15.13-16.45).The highest prevalence is 17.20% in central China,the lowest is 13.94% in eastern China. The incidences of AR in Chinese adult were 13.26% (95%CI 12.05-14.47).The highest prevalence is 15.45% in southern China,the lowest is 10.93% in southwestern China. The pooled odds ratio (OR) values of family history (5.40),dust exposure history (2.04),drug allergy history (2.83),history of asthma(4.45),environmental tobacco smoking(ETS)(2.00),water damage (1.50),upholstering(1.41),pollen allergy(17.18),molds(1.31),keeping pets (1.29),cockroach (1.69).Conclusion:A study on the epidemic tendency of AR in China showed the morbidity of AR in Chinese children is higher than adult. Moreover,prevalence vary from region to region. Eleven kinds of risk factors mentioned above play imperative roles in the pathogenesis of AR. The early interventions which are associated with risk factors should be implemented in AR.

Association between polymorphisms in the APOB gene and hyperlipidemia in the Chinese Yugur population

We investigated the influence of apolipoprotein B gene (APOB) variants on the risk of hyperlipidemia (HL) in 631 middle-aged and elderly members of the Chinese Yugur population (HL, n=336; normolipidemia, n=295). APOB polymorphisms were identified using mass spectrometry, and five single nucleotide polymorphisms (rs1042034, rs2163204, rs512535, rs676210, and rs679899) and serum lipids were further analyzed. rs1042034 and rs676210 were significantly associated with HL (P<0.05). Compared with the GG or AA genotype, individuals with AG and AG+AA in rs1042034 and with AG and AG+GG in rs676210 had a 1.67-fold (95%CI=1.20-2.33),1.63-fold (95%CI=1.19-2.24), 1.72-fold (95%CI=1.24-2.40), and 1.67-fold (95%CI=1.21-2.291) increased risk of high HL, respectively. rs2163204 was in strong linkage disequilibrium with rs1042034, rs676210, and rs679899, and strong disequilibrium was observed between rs1042034 and rs676210 (D′>0.9). Compared with the GTGAA haplotype, haplotypes ATGGA and ATAGG were more strongly associated with HL [odds ratio (OR)=1.46, 95%CI=0.02-2.11; OR=1.63, 95%CI=1.03-2.60, respectively]. The risk factors age (P=0.008), body mass index (P<0.0001), GA+GG genotype in rs676210 (P=0.009), and alcohol consumption (P=0.056) contributed strongly to HL development. The A allele of rs1042034 and the G allele of rs676210 may thus predispose middle-aged and elderly members of the Chinese Yugur population to HL in combination with other genetic or nutritional factors, and could be used as new genetic markers for HL screening.

[Meta-analysis of the morbidity of asthma in children with allergic rhinitis].

Objective: Pathogenesis of allergic rhinitis(AR) is thought to be related with asthma in children. However, lager scaled reports concerned on the co-morbidity of this two diseases in children are rare. In this meta-analysis, we aim to clarify the morbidity of asthma in children with AR.Method:Pubmed, Science, Springer, Elsevier, Embase, BMJ Journals, Wanfang data, VIP, CBM and CNKI were searched for relevant studies．The prevalences of asthma in children with AR were retrieved from individual studies and the pooled estimates generated by R3.2.3.Result:Fifteen cross-sectional studies were included in the meta-analysis. The results showed that the incidences of asthma in AR children were 35.01%(95％CI32.32%-37.70%) in China and 31.59%(95％CI28.02%-35.16%) in foreign countries.Conclusion:Comorbidity of AR and asthma was high in children. The incidence of asthma is higher in children with AR in China than that in foreign countries.

Increased aryl hydrocarbon receptor expression in patients with allergic rhinitis.

BACKGROUND: A predominant Th17 population is a marker of allergic rhinitis (AR). As a ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR) plays a vital role in promoting or inhibiting the development of specific Th cells. However, its role in AR remains undefined. OBJECTIVE: To analyze the potential role of AhR in the pathogenesis of AR. METHODS: In total, 30 AR patients and 13 healthy controls were recruited for this study and AR patients had clinical features, as demonstrated by rhinoconjunctivitis quality of life questionnaires, total symptom scores and visual analog scale scores. The expression of AhR, IL-17 and IL-22 and the presence of Th17 cells in peripheral blood mononuclear cells were measured before and after treatment with the nontoxic AhR ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). RESULTS: Pretreatment ITE studies revealed that all AR patients had a significant increase in AhR expression compared with controls and AhR expression positively correlated with clinical parameters. After ITE intervention, a severe reduction in the differentiation of Th17 cells and the production of IL-17 and IL-22 was noted in both AR patients and normal subjects. Simultaneously, a dramatic enhancement of AhR expression was also observed in all healthy controls, but not in AR patients. CONCLUSION: The results suggested that the AhR may be one of the mechanisms underlying the Th17 response during the pathogenesis of AR and AhR levels were closely related to clinical severity in all AR patients. Additionally, ITE may represent a new drug candidate in the treatment of AR.

Impaired balance of Th17/Treg in patients with nasal polyposis.

Nasal polyposis (NP) is a chronic inflammatory disease of the nasal cavity and sinuses that is regulated by T lymphocyte subsets. Imbalance of Th17/Treg has been considered critical in the development of inflammation and atopic reactions. To assess whether the balance of Th17/Treg is disrupted in patients with NP, we evaluated the distribution of Th17 and Treg cells among peripheral blood mononuclear cells (PBMCs) in atopic patients with NP, non-atopic patients with NP and controls. We then determined mRNA levels of RORc and Foxp3 and protein levels of IL-17, TGF-ß and IL-10 in polyp tissue among the three groups. Finally, we investigated the correlation between Th17-, Treg- and Th1-, Th2-related cytokines (INF-γ, IL-4, IL-5). The results demonstrated that both atopic and non-atopic patients with NP revealed significantly increased Th17 proportion and decreased Treg proportion in PBMCs, as well as significantly increased RORc and IL-17 levels and decreased Foxp3 and TGF-ß levels in polyp tissue. Furthermore, these differences were significant between atopic and non-atopic groups. The frequency of Treg in PBMCs was found to be negatively correlated with Th1 and Th2 cytokines in polyps. These results indicated that an impaired balance of Th17/Treg existed in patients with NP and was more severe in atopic patients, suggesting that the imbalance of Treg/Th17 may play an important role in the development of NP and that atopy may aggravate NP by promoting the imbalance of Th17/Treg.

Fracture behaviour of zirconia FPDs substructures.

The purpose of this study was to evaluate the occurrence of superficial flaws after machining and to identify fracture initiation and propagation in three-unit heat-treated machined fixed partial dentures (FPDs) substructures made of hot isostatic pressed (HIPed) yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) after loaded to fracture. Four three-unit HIPed Y-TZP-based FPDs substructures were examined. To evaluate the occurrence of superficial flaws after machining, the surfaces were studied utilizing a fluorescent penetrant method. After static loading to fracture, characteristic fracture features on both mating halves of the fractured specimens were studied using a stereomicroscope and a scanning electron microscope. Grinding grooves were clearly visible on the surfaces of the machined FPDs substructures, but no other flaws could be seen with the fluorescent penetrant method. After loading to fracture, the characteristic fracture features of arrest lines, compression curl, fracture mirror, fracture origin, hackle and twist hackle were detected. These findings indicated that the decisive fracture was initiated at the gingival embrasure of the pontic in association with a grinding groove. Thus, in three-unit heat-treated machined HIPed Y-TZP FPDs substructures, with the shape studied in this study, the gingival embrasure of the pontic seems to be a weak area providing a location for tensile stresses when they are occlusally loaded. In this area, fracture initiation may be located to a grinding groove.

Surface roughness of five different dental ceramic core materials after grinding and polishing.

In clinical practice, core materials can be exposed after adjustments are made to previously-luted all-ceramic restorations. The purpose of this study was to evaluate the surface roughness of five different dental ceramic core materials after grinding and polishing. Five different ceramic core materials, Vita In-Ceram Alumina, Vita In-Ceram Zirconia, IPS Empress 2, Procera AllCeram, and Denzir were evaluated. Vita Mark II was used as a reference material. The surface roughness, Ra value (mum), was registered using a profilometer. The measurements were made before and after grinding with diamond rotary cutting instruments and after polishing with the Sof-Lex system. The surface of representative specimens was evaluated qualitatively using scanning electron microscopy (SEM). Results were statistically analysed using analysis of variance (anova) supplemented with Scheffè's and Bonferroni multiple-comparison tests. Before grinding, Procera AllCeram and Denzir had the smoothest surfaces, while IPS Empress 2 had the coarsest. After grinding, all materials except IPS Empress 2 became coarser. Polishing with Sof-Lex provided no significant (P > 0.05) differences between Denzir, Vita Mark II and IPS Empress 2 or between Procera AllCeram and In-Ceram Zirconia. There were no significant differences (P > 0.05) either between the ground and the polished Procera AllCeram or In-Ceram Alumina specimens. Polishing of Denzir, IPS Empress 2 and In-Ceram Zirconia made the surfaces smoother compared with the state after grinding, whereas the polishing effect on Procera AllCeram and In-Ceram Alumina was ineffective. The findings of the SEM evaluation were consistent with the profilometer readings.

Behavioural endocrine immune-conditioned response is induced by taste and superantigen pairing.

Administration of bacterial superantigen, such as staphylococcal enterotoxin B (SEB), induces in vivo stimulation of T cell proliferation and cytokine production such as interleukin-2 (IL-2). It has been previously reported that SEB administration induces fever, c-Fos expression in the brain, and hypothalamus-pituitary-adrenal axis activation, demonstrating that the brain is able to sense and respond to SEB. Previously it had been shown that immune functions can be behaviourally conditioned pairing a novel gustatory stimulus together with an immunomodulatory drug or an antigen. We designed an experimental protocol using Dark Agouti rats in which saccharin taste, as conditioned stimulus, was paired with an i.p. injection of SEB (2 mg/kg), as unconditioned stimulus. Six days later, when conditioned animals were re-exposed to the conditioned stimulus they displayed strong conditioned taste avoidance to the saccharin. More importantly, re-exposure to the conditioned stimulus significantly increased IL-2, interferon-gamma and corticosterone plasma levels, in comparison with conditioned animals which had not been re-exposed to saccharin taste. These results demonstrate a behavioural-immune-endocrine conditioned response using a superantigen as unconditioned stimulus. In addition, they illustrate the brain abilities to mimic the unconditioned effects of a superantigen by yet unknown mechanisms.

Antiarrhythmic drug therapy in the Multicenter UnSustained Tachycardia Trial (MUSTT): drug testing and as-treated analysis.

OBJECTIVES: Using data from the Multicenter UnSustained Tachycardia Trial (MUSTT), we examined the factors used to select antiarrhythmic drug therapy and their impact on outcomes. BACKGROUND: The MUSTT examined the use of programmed ventricular stimulation (PVS) to guide antiarrhythmic therapy in patients with coronary arteriosclerosis, left ventricular dysfunction and asymptomatic, unsustained ventricular tachycardia (VT). Trial outcomes may reflect factors used to select antiarrhythmic drug therapy. METHODS: We compared subgroups of patients with inducible sustained VT randomized to PVS-guided antiarrhythmic therapy (n = 351), in particular those receiving PVS-guided antiarrhythmic drug therapy (n = 142) versus no antiarrhythmic therapy (controls, n = 353). RESULTS: "Effective" antiarrhythmic drug therapy (i.e., the term "effective" was used to denote therapy that resulted in noninducible VT or hemodynamically stable induced VT) was found for 142 of the 351 patients (43%), most often at the first or second PVS session (125/142, 88%). Mortality among the 142 patients did not differ from that among control patients. Of these 142 patients, the PVS end point was noninducibility in 91 patients and stable VT in 51 patients. Mortality did not differ between these two groups either, but arrhythmia was numerically more frequent in the PVS-induced stable VT group. Mortality was greatest in the few patients receiving propafenone (unadjusted p = 0.07, adjusted p = 0.14 vs. controls), but mortality with all agents did not differ from that of controls, even after adjustment. CONCLUSIONS: Even when presenting the results as favorably as possible, we found no benefit with PVS-guided drug therapy in patients with clinical unsustained VT who had inducible sustained VT. These findings are unaltered by using different end points for PVS or considering the response to individual drugs.

[Changes in the activity of platelet L-arginine/nitric oxide pathway in hypercholesterolemia patients].

OBJECTIVE: To investigate the changes of the platelet L-arginine (L-Arg)/nitric oxide (NO) pathway in hypercholesterolemia patients. METHODS: The platelet NO production in 21 hypercholesterolemia (HC) patients and 26 normal individuals was assayed by spectrum, the NOS activity and the transportation of L-Arg were determined by (3)H-labelled L-Arg. RESULTS: The NO production in hypercholesterolemic platelets [(24.06 +/- 3.70) nmol/10(8) platelets] was decreased significantly as compared with normal controls [(28.39 +/- 4.45) nmol/10(8) platelets] (P < 0.01), and so did the NOS activity [(1.46 +/- 0.47) pmol/10(8) platelets] vs (1.81 +/- 0.50) pmol/10(8) platelets]. The transportation of L-Arg by hypercholesterolemia platelets also decreased significantly than that by normal controls. The Vmax in the former [(46.84 +/- 3.39) pmol x (10(7) platelets)(-1) x min(-1)] was significantly lower than that in the latter [(53.89 +/- 3.45) pmol x (10(7) platelets)(-1) x min(-1)]. There was no difference between the two groups in K(d) (P > 0.05). CONCLUSIONS: The activity of the L-arg/NO pathway in hypercholesterolemia platelets is decreased significantly as compared with normal controls, implying that it is probably one of the reasons for the hyperactivity of hypercholesterolemia platelets.

Outcome of men with ischemic cardiomyopathy, asymptomatic nonsustained ventricular tachycardia, and negative electrophysiologic studies.

The natural history of patients with ischemic cardiomyopathy, asymptomatic nonsustained ventricular tachycardia, and negative electrophysiologic studies was assessed in a retrospective analysis of 55 consecutive patients. The results suggest that the prognosis for arrhythmic death in these patients is not necessarily benign.