Contact Analysis of Separation Between Concrete Slab and Cushion Layer in Tianshengqiao Concrete-Faced Rockfill Dam

Tianshengqiao concrete-faced rockfill dam (CFRD), with a maximum height of 178m, is the highest dam of the same kind in China and the second highest in the world. During the construction of the dam, some problems special for high CFRDs occurred, such as deficient of cushion layer and separation of concrete slab from cushion layer. In this paper, a finite element analysis is made to understand the deformation of the cushion layer and the separation between the slab and the cushion. Direct constraints method and Coulomb friction law are used to simulate the contact behavior between the deformable concrete slab and the cushion layer. The methods are shown to be effective through a comparison of the numerical results with in-situ measurements. The mechanism of occurrence of the separation between the slab and the cushion is discussed. Valuable suggestions are made for further design and construction of high concrete-faced rockfill dams

Association of promoter methylation with histologic type and pleural indentation in non-small cell lung cancer (NSCLC)

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a major cause of death worldwide. Gene promoter methylation is a major inactivation mechanism of tumor-related genes, some of which can be served as a biomarker for early diagnosis and prognosis evaluation of lung cancer.</p> <p>Methods</p> <p>We determined the promoter methylation of 6 genes using quantitative methylation-specific PCR (Q-MSP) technique in 96 clinically well-characterized non-small cell lung cancer (NSCLC).</p> <p>Results</p> <p>Highly frequent promoter methylation was found in NSCLC. With 100% diagnostic specificity, high sensitivity, ranging from 44.9 to 84.1%, was found for each of the 6 genes. Our data also showed that promoter methylation was closely associated with histologic type. Most of genes were more frequently methylated in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Moreover, promoter methylation significantly increased the risk of pleural indentation in NSCLC.</p> <p>Conclusion</p> <p>Our findings provided evidences that multiple genes were aberrantly methylated in lung tumorigenesis, and demonstrated the promoter methylation was closely associated with clinicopathologic characteristics of NSCLC. More importantly, we first revealed promoter methylation may be served as a potentially increased risk factor for pleural indentation of NSCLC patients.</p

Concomitant hypermethylation of multiple genes in non-small cell lung cancer (NSCLC)

Primary lung cancer remains the leading cause of cancer death worldwide. Promoter hypermethylation is a major inactivation mechanism of tumor-related genes, and increasingly appears to play an important role in carcinogenesis. In the present study, we used quantitative methylation-specific PCR (Q-MSP) assays to analyze promoter hypermethylation of nine genes in a large cohort of well-characterized non-small cell lung cancer (NSCLC) and explore their associations with the clinicopathological features of tumor. We found that there were significant differences in methylation levels for six of nine gene promoters between cancerous and noncancerous lung tissues. More importantly, with 100% diagnostic specificity, high sensitivity, ranging from 44.9% to 84.1%, was found for each of the nine genes. Interestingly, promoter hypermethylation of most genes was closely associated with histologic type, which was more frequent in squamous cell carcinomas (SCC) than in adenocarcinomas (ADC). In addition, highly frequent concomitant methylation of multiple genes was found in NSCLC, particularly in SCC. Our data showed that multiple genes were aberrantly methylated in lung tumorigenesis, and that they were closely associated with certain clinicopathological features of NSCLC, particularly of the histologic type, suggesting that these hypermethylated genes could be potential biomarkers in early detection of NSCLC in high-risk individuals, as well as in evaluating the prognosis of NSCLC patients. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 1, 132&#8211;141

Aberrant DNA methylation of drug metabolism and transport genes in nodular goiter

The genes encoding drug-metabolizing enzymes and transporters play an important role in maintaining the normal life processes of human body. Their disorder or defect will lead to the occurrence and development of various diseases. Currently, most of studies have focused on genetic variations in these genes, however, in the present study, we analyzed promoter methylation of 11 drug metabolism and transport genes in a cohort of nodular goiter and normal thyroid tissues using methylation-specific PCR (MSP). Our data first revealed a distinct methylation profiling in drug metabolism and transport genes between nodular goiter and normal thyroid tissues, particularly ABCB4, CYP1B1 and CYP24A1 and SLC1A2. Given these genes contribute to the development and progression of various diseases, such as multidrug resistance and tumorigenesis, these epigenetic events may thus play a critical role in the pathogenesis of nodular goiter

Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC)

<p>Abstract</p> <p>Background</p> <p>Lung cancer is the leading cause of cancer-related death worldwide. Genetic and epigenetic alterations have been identified frequently in lung cancer, such as promoter methylation, gene mutations and genomic amplification. However, the interaction between genetic and epigenetic events and their significance in lung tumorigenesis remains poorly understood.</p> <p>Methods</p> <p>We determined the promoter methylation of 6 genes and <it>PIK3CA </it>amplification using quantitative methylation-specific PCR (Q-MSP) and real-time quantitative PCR, respectively, and explore the association of promoter methylation with <it>PIK3CA </it>amplification in a large cohort of clinically well-characterized non-small cell lung cancer (NSCLC).</p> <p>Results</p> <p>Highly frequent promoter methylation was observed in NSCLC. With 100% diagnostic specificity, excellent sensitivity, ranging from 45.8 to 84.1%, was found for each of the 6 genes. The promoter methylation was associated with histologic type. Methylation of <it>CALCA, CDH1, DAPK1</it>, and <it>EVX2 </it>was more common in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Conversely, there was a trend toward a higher frequency of <it>RASSF1A </it>methylation in ADC than SCC. In addition, <it>PIK3CA </it>amplification was frequently found in NSCLC, and was associated with certain clinicopathologic features, such as smoking history, histologic type and pleural indentation. Importantly, aberrant promoter methylation of certain genes was significantly associated with <it>PIK3CA </it>amplification.</p> <p>Conclusions</p> <p>Our data showed highly frequent promoter methylation and <it>PIK3CA </it>amplification in Chinese NSCLC population, and first demonstrated the associations of gene methylation with <it>PIK3CA </it>amplification, suggesting that these epigenetic events may be a consequence of overactivation of PI3K/Akt pathway.</p

Advanced glycation end product (AGE) modified proteins in tears of diabetic patients

Purpose: High glucose level in diabetic patients may lead to advanced glycation end product (AGE) modified proteins. This study investigated AGE modified proteins in tears and compared their levels in diabetic patients (DM) with nondiabetic controls (CTL). Methods: Basal tears were collected from DM with (DR) or without (DNR) retinopathy and CTL. Total AGE modified proteins were detected quantitatively by a dot immunobinding assay. The AGE modified proteins were separated in 1Dand 2D-SDS gels and detected by western-blotting. The individual AGE modified proteins were also compared between groups using densitometry. Results: Compared with the CTL group, tear concentrations of AGE modified proteins were significantly elevated in DR and DNR groups. The concentration of AGE modified proteins in diabetic tears were positively correlated with AGE modified hemoglobin (HbA1c) and postprandial blood glucose level (PBG). Western blotting of AGE modified proteins from 1D-SDS gels showed several bands, the major one at around 60 kDa. The intensities of AGE modified protein bands were higher in DM tears than in CTL tears. Western blotting from 2D-SDS gels showed a strongly stained horizontal strip, which corresponded to the major band in 1D-SDS gels. Most of the other AGE modified protein species were within molecular weight of 30-60 kDa, PI 5.2-7.0. Densitometry analysis demonstrated several AGE modified proteins were elevated in DR or DNR tears. Conclusions: Total and some individual AGE modified proteins were elevated in DM tears. AGE modified proteins in tears may be used as biomarkers to diagnose diabetes and/or diabetic retinopathy.9 page(s

Changes to tear cytokines of type 2 diabetic patients with or without retinopathy

Purpose: To investigate changes in cytokine levels in tears of type 2 diabetics with or without retinopathy. Methods: Tears were collected from 15 type 2 diabetics without retinopathy (DNR), 15 patients with retinopathy (DR), and 15 age and gender matched non-diabetic controls. Tear concentrations of 27 cytokines were measured by multiplex bead immunoassay. Cytokine differences between groups, ratios of type-1 T helper (Th1)/type-2 T helper (Th2) cytokines and anti-angiogenic/pro-angiogenic cytokines were analyzed statistically. Results: The most abundant cytokine detected in tears was interferon-induced protein-10 (IP-10). In comparison with controls, IP-10 and monocyte chemoattracant protein-1 (MCP-1) levels were significantly elevated in DR (p=0.016 and 0.036, respectively) and DNR groups (p=0.021 and 0.026, respectively). Interleukin-1 (IL-1) receptor antagonist (IL-1ra) levels were significantly increased in DNR (p=0.016). Th1/Th2 cytokines interferon-gamma (IFN-γ)/IL-5 and IL-2/IL-5 ratios were significantly increased in DR compared to controls (p=0.037 and 0.031, respectively). Anti-angiogenic/angiogenic cytokines IFN-γ/MCP-1 and IL-4/MCP-1 ratios in DR and DNR were significantly decreased compared to controls (p<0.05). IL-4/IL-8 and IL-12p70/IL-8 ratios were also significantly decreased in DR compared to controls (p=0.02 and 0.045, respectively). No significant correlation was demonstrated between tear cytokine concentrations and glycosylated hemoglobin (HbA1c) or fasting plasma glucose (FPG). Conclusions: Diabetic tears exhibited elevated levels of IP-10 and MCP-1. The Th1/Th2 cytokine balance may shift to a predominantly Th1 state in DR patients. Pro-angiogenic cytokines are more highly represented than anti-angiogenic cytokines in the tears of diabetic patients.8 page(s

Gender-Specific Risk of Central Compartment Lymph Node Metastasis in Papillary Thyroid Carcinoma

Our aim was to evaluate the impact of gender on the predictive factors of central compartment lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC). A retrospective study of 590 patients treated for PTC was performed. Univariate and multivariate analyses showed that gender (female; P=0.001), age (≥45 y; P<0.001), tumor size (>1 cm; P<0.001), and multifocality (P=0.004) were independent predictive factors of CLNM in PTC patients. Patients were divided into male group (n=152) and female group (n=438). Age (≥45 y; P=0.001), T4 (P=0.006) and multifocality (P=0.024) were independent predictive risk factors of CLNM in male patients. As for female patients, age (≥45 y; P<0.001), tumor size (>1 cm; P<0.001), multifocality (P=0.002), and microcalcification (P=0.027) were independently correlated with CLNM. The sensitivity of the multivariate model for predicting CLNM in male patients was 64.9%, specificity was 82.9%, and area under the ROC curve (AUC) was 0.764. As for female patients, the sensitivity was 55.7%, specificity was 77.9%, and AUC was 0.73. This study showed that the predictive factors of CLNM indeed varied according to gender. To have a more accurate evaluation of CLNM, different predictive systems should be used for male and female patients

Lipid alternations in the plasma of COVID-19 patients with various clinical presentations.

BACKGROUND: COVID-19 is a highly infectious respiratory disease that can manifest in various clinical presentations. Although many studies have reported the lipidomic signature of COVID-19, the molecular changes in asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain elusive. METHODS: This study combined a comprehensive lipidomic analysis of 220 plasma samples from 166 subjects: 62 healthy controls, 16 asymptomatic infections, and 88 COVID-19 patients. We quantified 732 lipids separately in this cohort. We performed a difference analysis, validated with machine learning models, and also performed GO and KEGG pathway enrichment analysis using differential lipids from different control groups. RESULTS: We found 175 differentially expressed lipids associated with SASR-CoV-2 infection, disease severity, and viral persistence in patients with COVID-19. PC (O-20:1/20:1), PC (O-20:1/20:0), and PC (O-18:0/18:1) better distinguished asymptomatic infected individuals from normal individuals. Furthermore, some patients tested positive for SARS-CoV-2 nucleic acid by RT-PCR but did not become negative for a longer period of time (≥60 days, designated here as long-term nucleic acid test positive, LTNP), whereas other patients became negative for viral nucleic acid in a shorter period of time (≤45 days, designated as short-term nucleic acid test positive, STNP). We have found that TG (14:1/14:1/18:2) and FFA (4:0) were differentially expressed in LTNP and STNP. CONCLUSION: In summary, the integration of lipid information can help us discover novel biomarkers to identify asymptomatic individuals and further deepen our understanding of the molecular pathogenesis of COVID-19