An epidemiologic study of hypertension in Newfoundland

The distribution of arterial blood pressure (BP) values of 1499 adult inhabitants of four Newfoundland communities was surveyed. Mean age- and sex-adjusted BP scores were found to be higher in each of three fishing villages than in the logging and mining community, Badger, in the central part of the province. It is postulated that the observed differences may be caused by environmental factors. The prevalence of individuals with probable essential hypertension (diastolic BP > 100 mm. Hg) in individuals over 50 years of age was found to be three times higher in the island community, Fogo, than in Badger. In both communities less than one third of those with probable hypertensive disease had received treatment.     

The remarkable geographical pattern of gastric cancer mortality in Ecuador

AimThis study was aimed to describe the gastric cancer mortality trend, and to analyze the spatial distribution of gastric cancer mortality in Ecuador, between 2004 and 2015.MethodsData were collected from the National Institute of Statistics and Census (INEC) database. Crude gastric cancer mortality rates, standardized mortality ratios (SMRs) and indirect standardized mortality rates (ISMRs) were calculated per 100,000 persons. For time trend analysis, joinpoint regression was used. The annual percentage rate change (APC) and the average annual percent change (AAPC) was computed for each province. Spatial age-adjusted analysis was used to detect high risk clusters of gastric cancer mortality, from 2010 to 2015, using Kulldorff spatial scan statistics.ResultsIn Ecuador, between 2004 and 2015, gastric cancer caused a total of 19,115 deaths: 10,679 in men and 8436 in women. When crude rates were analyzed, a significant decline was detected (AAPC: −1.8%; p < 0.001). ISMR also decreased, but this change was not statistically significant (APC: −0.53%; p = 0.36). From 2004 to 2007 and from 2008 to 2011 the province with the highest ISMR was Carchi; and, from 2012 to 2015, was Cotopaxi. The most likely high occurrence cluster included Bolívar, Los Ríos, Chimborazo, Tungurahua, and Cotopaxi provinces, with a relative risk of 1.34 (p < 0.001).ConclusionThere is a substantial geographic variation in gastric cancer mortality rates among Ecuadorian provinces. The spatial analysis indicates the presence of high occurrence clusters throughout the Andes Mountains.     

Trend analysis of cancer incidence and mortality in China

正The National Central Cancer Registry of China(NCCRC)updated their nationwide statistics of cancer incidence and mortality in China according to 2013 population-based cancer registration data(due to the time required for data collection,quality control and analysis,the latest cancer statistics available in China have a 3-year lag behind the current year).In this report,the NCCRC provides a comprehensive review of cancer incidence and mortality rates,as well as the statistics overall and by geographical area,cancer sites or age groups(Chen et al.,2017a).It shows that the burden of cancer in     

Relationship of drinking water quality (hardness-softness) to cardiovascular mortality in Newfoundland

The profile of mortality in Newfoundland was analysed for all deaths occurring in 1969 of persons 35 to 69 years of age, of whom the total was 1036. An exceptionally high cardiovascular mortality (793 deaths/100,000) was noted for St. John''s, the capital city of Newfoundland, a city which has an extremely soft drinking-water supply. This high rate corresponds to that observed in the “high mortality belt” reported for the east coast of the United States, and in conjunction with data from mainland Canada, extends the belt across the entire eastern aspect of North America. The proportion of cardiovascular deaths of men occurring outside the hospital was less within hard drinking-water areas in Newfoundland than in the soft water areas of the province. Thus, the statistics reported here of cardiovascular mortality confirm evidence reported elsewhere on “macro-geographic” variations in this disease(s) as well as “micro-geographic” regional variations which may be dependent upon local environmental factors.     

Flow cytometric analysis of paraffin-embedded material in human gastric cancer

Flow cytometric DNa analysis was performed on formalin-fixed, paraffin-embedded samples obtained by gastroscopic biopsy from 9 patients with histologically normal gastric mucosa (36 specimens) and by radical gastrectomy from 42 cases of human gastric cancer (120 specimens). Ploidy patterns and the distribution of cells in the different cell cycle phases were estimated, and the results were correlated with the histologic and clinical features. All samples of normal mucosa showed a diploid modal DNA content whereas DNA aneuploidy was encountered in 71.4% of the gastric tumors. The correlation between aneuploidy and histologic malignancy grading was statistically significant: aneuploidy was found in 36.4% of highly differentiated (grade 1 and grade 2) tumors and in 75.0% of poorly differentiated (grade 3) tumors (P less than .05). The percentage of cells in S-phase in normal gastric mucosa (median: 5.0%) was lower than that in the tumors (median: 11.3%) (P less than .05). There was a trend for grade 3 tumors to have higher median values (median: 13.4%) than grade 1 and 2 tumors (median: 9.3%); however, this was not statistically significant. An aneuploid DNA pattern was associated with a poorer prognosis, both in early and in advanced stages of gastric tumors, while proliferative activity did not correlate with postoperative survival.     

Comprehensive analysis of tumor mutation burden and immune microenvironment in gastric cancer

Tumor mutation burden (TMB) was a promising marker for immunotherapy. We aimed to investigate the prognostic role of TMB and its relationship with immune cells infiltration in gastric cancer (GC). We analyzed the mutation landscape of all GC cases and TMB of each GC patient was calculated and patients were divided into TMB-high and TMB-low group. Differentially expressed genes (DEGs) between the two groups were identified and pathway analysis was performed. The immune cells infiltration in each GC patient was evaluated and Kaplan–Meier analysis was performed to investigate the prognostic role of immune cells infiltration. At last, hub immune genes were identified and a TMB prognostic risk score (TMBPRS) was constructed to predict the survival outcome of GC patients. The relationships between mutants of hub immune genes and immune infiltration level in GC was investigated. We found higher TMB was correlated with better survival outcome and female patients, patients with T1-2 and N0 had higher TMB score. Altogether 816 DEGs were harvested and pathway analysis demonstrated that patients in TMB-high group were associated with neuroactive ligand–receptor interaction, cAMP signaling pathway, calcium signaling pathway. The infiltration of activated CD4⁺ memory T cells, follicular helper T cells, resting NK cells, M0 and M1 macrophages and neutrophils in TMB-high group were higher compared than that in TMB-low group and high macrophage infiltration was correlated with inferior survival outcome of GC patients. Lastly, the TMBPRS was constructed and GC patients with high TMBPRS had poor prognosis.     

Tea drinking and cancer risk: epidemiologic evidence

Tea and tea compounds have been shown to inhibit carcinogenic processes in experimental animals, raising the possibility that tea drinking may lower cancer risk in humans. However, epidemiologic studies have produced inconsistent evidence on the relation between tea drinking and cancer risk. Ecological data show considerable international variation in tea consumption but relatively small differences in cancer rates. Results from case-control and cohort studies also are inconclusive. Nevertheless, high consumption of tea has been linked to a reduced risk of digestive tract cancers in a number of epidemiologic studies. A lack of detailed information on duration and amount of tea drinking, a narrow range of tea intake in some study populations, inadequate control for confounding, and potential biases in recall and reporting of tea drinking patterns in case-control studies may have contributed to the diverse findings. Further research is needed before definitive conclusions on tea's impact upon cancer risk in humans can be reached.     

Overexpression of cathepsin B in gastric cancer identified by proteome analysis

We aimed to validate an analytical approach based on proteomics on gastric cancer specimens for the identification of new putative diagnostic or prognostic markers. Primary screening was performed on gastrectomy specimens obtained from ten consecutive patients with gastric cancer. Gastric epithelial cells were obtained with an epithelial cell enrichment technique, homogenized and then separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The differential protein expression pattern was verified stepwise by Western blotting and immunohistochemistry on samples from 28 and 46 cancer patients, respectively. The putative clinical applicability and prognostic use were tested by an enzyme-linked immunoabsorbent assay on serum samples obtained from 149 cancer patients. One hundred-ninety-one differentially expressed protein spots were found by 2-D PAGE and identified by mass spectrometry, including cathepsin B, which was over-expressed in six (60%) patients. Western blotting confirmed that the active form of cathepsin B is over-expressed, while immunohistochemistry showed strong cytoplasmic staining in cancer tissues of 45 (98%) patients. The serum level of cathepsin B was increased in patients with gastric cancer compared to healthy controls (P = 0.0026) and correlated with T-category and the presence of distant metastases (P < 0.05). Serum levels above 129 pmol x L(-1) were associated with a reduced survival rate (P = 0.0297). Proteome analysis is a valuable tool for the identification of prognostic markers in gastric cancer: Increased cathepsin B serum levels are associated with advanced tumor stages and progressive disease, which enables the classification of some gastric cancer patients into a subgroup that should undergo aggressive therapy.     

Integrative network analysis reveals active microRNAs and their functions in gastric cancer

Background

Ralstonia eutropha H16, found in both soil and water, is a Gram-negative lithoautotrophic bacterium that can utillize CO₂ and H₂ as its sources of carbon and energy in the absence of organic substrates. R. eutropha H16 can reach high cell densities either under lithoautotrophic or heterotrophic conditions, which makes it suitable for a number of biotechnological applications. It is the best known and most promising producer of polyhydroxyalkanoates (PHAs) from various carbon substrates and is an environmentally important bacterium that can degrade aromatic compounds. In order to make R. eutropha H16 a more efficient and robust biofactory, system-wide metabolic engineering to improve its metabolic performance is essential. Thus, it is necessary to analyze its metabolic characteristics systematically and optimize the entire metabolic network at systems level.

Results

We present the lithoautotrophic genome-scale metabolic model of R. eutropha H16 based on the annotated genome with biochemical and physiological information. The stoichiometic model, RehMBEL1391, is composed of 1391 reactions including 229 transport reactions and 1171 metabolites. Constraints-based flux analyses were performed to refine and validate the genome-scale metabolic model under environmental and genetic perturbations. First, the lithoautotrophic growth characteristics of R. eutropha H16 were investigated under varying feeding ratios of gas mixture. Second, the genome-scale metabolic model was used to design the strategies for the production of poly[R-(-)-3hydroxybutyrate] (PHB) under different pH values and carbon/nitrogen source uptake ratios. It was also used to analyze the metabolic characteristics of R. eutropha when the phosphofructokinase gene was expressed. Finally, in silico gene knockout simulations were performed to identify targets for metabolic engineering essential for the production of 2-methylcitric acid in R. eutropha H16.

Conclusion

The genome-scale metabolic model, RehMBEL1391, successfully represented metabolic characteristics of R. eutropha H16 at systems level. The reconstructed genome-scale metabolic model can be employed as an useful tool for understanding its metabolic capabilities, predicting its physiological consequences in response to various environmental and genetic changes, and developing strategies for systems metabolic engineering to improve its metabolic performance.