[Analysis of rush poppers use and related factors in men who have sex with men in Jinan and Qingdao, 2016].

Objective: To understand the use of drug and its related factors among men who have sex with men, and to provide reference for the development of reasonable intervention measures. Methods: MSM was recruited from Jinan and Qingdao by means of on-site and internet recruiting from March to June in 2016. Anonymous questionnaires were conducted and HIV and syphilis serological tests were performed. The questionnaire included the general situation, sexual behavior, HIV related services and so on. Multi-factor unconditioned logistic regression model was used to explore related factors about rush poppers use. Results: The rush poppers use rate of 901 MSM was 30.1%（271/901）, the age was (29.3±8.1) years, the HIV infection rate was 4.6% (41/901) and the syphilis infection rate was 8.7% (78/901). Multivariate analysis showed that compared with those who were>25 years old, the OR (95%CI) of those who were ≤ 25 years old was 1.571 (1.110-2.224); compared with the number of anal sexual behavior was<2 times in the last week, the OR (95%CI) of those whose number of anal sexual behavior was ≥2 times was 2.991 (1.100-8.132); compared with those who had not received peer education services in the last year, the OR (95%CI) of those who received peer education services was 13.651 (7.239-25.742). Conclusion: Rush poppers are very popular in the MSM crowd, and those who aged less than 25 years old, who had anal sex more than twice in the past week, and who had received peer education services were more likely to use rush poppers. We should carry out targeted interventions according to the characteristics.

A new locus regulating MICALL2 expression was identified for association with executive inhibition in children with attention deficit hyperactivity disorder.

Impaired executive inhibition is a core deficit of attention deficit hyperactivity disorder (ADHD), which is a common childhood-onset psychiatric disorder with high heritability. In this study, we performed a two-stage genome-wide association study of executive inhibition in ADHD in Han Chinese. We used the Stroop color-word interference test to evaluate executive inhibition. After quality control, 780 samples with phenotype and covariate data were included in the discovery stage, whereas 922 samples were included in the replication stage. We identified one new significant locus at 7p22.3 for the Stroop word interference time (rs11514810, P=3.42E-09 for discovery, P=0.01176 for replication and combined P=5.249E-09). Regulatory feature analysis and expression quantitative trait loci (eQTL) data showed that this locus contributes to MICALL2 expression in the human brain. Most genes in the network interacting with MICALL2 were associated with psychiatric disorders. Furthermore, hyperactive-impulsive-like behavior was induced by reducing the expression of the zebrafish gene that is homologous to MICALL2, which could be rescued by tomoxetine (atomoxetine), a clinical medication for ADHD. Our results suggested that MICALL2 is a new susceptibility gene for executive inhibition deficiency related to hyperactive-impulsive behavior in ADHD, further emphasizing the possible role of neurodevelopmental genes in the pathogenic mechanism of ADHD.

A DNA methylation biomarker of alcohol consumption.

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

Grading meningiomas using mono-exponential, bi-exponential and stretched exponential model-based diffusion-weighted MR imaging.

AIM: To prospectively evaluate and compare the potential of various diffusion metrics obtained from mono-exponential model (MEM), bi-exponential model (BEM), and stretched exponential model (SEM)-based diffusion-weighted imaging (DWI) in the grading of meningiomas. MATERIAL AND METHODS: Consecutive 93 patients with histopathologically confirmed meningiomas received DWI of multiple b-values. Apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), water molecular diffusion heterogeneity index (alpha), and distributed diffusion coefficient (DDC) were calculated and compared between low-grade and high-grade meningiomas. Receiver operating characteristic and multivariable stepwise logistic regression analyses were performed to evaluate the diagnostic performance of different parameters. RESULTS: The mean and normalised ADC, D, f, and DDC values were significantly lower in high-grade meningiomas than those in low-grade meningiomas (all p<0.05). The AUCs of D and DDC were significantly higher than that of f in the differentiation (all p<0.05). D was the only variable that could be used to independently differentiate high-grade and low-grade meningiomas (p<0.001). CONCLUSION: Different models of DWI, including MEM, BEM, and SEM, are useful in the differentiating high-grade and low-grade meningiomas; however, D obtained from BEM is the most promising diffusion parameter for predicting the grade of meningiomas.

[Comparison of gemstone spectral curve and CT value of gastric cancer with different pathological types and differentiation degrees].

Objective: To investigate the differences of gemstone spectral curve and CT value of gastric cancer with different pathological types and differentiation degrees. Methods: 91 cases of preoperative gemstone CT images with gastric cancer were collected, including 24 cases of mucinous carcinoma, 67 cases of non-mucinous carcinoma, 16 cases of signet ring cell carcinoma, 8 cases of mucinous adenocarcinoma, 32 cases of moderately differentiated adenocarcinoma and 35 cases of poorly differentiated adenocarcinoma. Gemstone CT spectral imaging was performed preoperatively, and the spectral curve of the lesion in venous phase was obtained by using GSI Viewer software, the slope of the curve was calculated, and 11 monoenergetic CT values of 40~140 keV (10 keV interval) were measured. The gemstone spectral curves and CT values of gastric cancer with different pathological types and differentiation degrees are compared. Results: The curve slopes of non-mucinous carcinoma, signet ring cell carcinoma and poorly differentiated adenocarcinoma were -1.92±0.53, -1.73±0.37 and -2.14±0.54, respectively. The absolute values were higher than those of mucinous carcinoma (-1.45±0.54), mucinous adenocarcinoma (-0.90±0.34) and moderately differentiated adenocarcinoma (-1.67±0.41), and the differences were all statistically significant (P<0.05). There were significant differences in monoenergetic CT values between mucinous and non-mucinous carcinomas at 40-140 keV (all P<0.05). The former was lower than the latter in different degrees, and the lower the energy, the greater the difference was. There were significant differences in monoenergetic CT values between signet ring cell carcinoma and mucinous adenocarcinoma at 40-100 keV (all P<0.05); monoenergetic CT values between poorly differentiated adenocarcinoma and moderately differentiated adenocarcinoma at 40-90 keV showed statistically significant differences (P<0.05). Conclusions: Gastric cancer with different pathological types and differentiation degrees have their characteristic spectral curves in venous phase, and the monoenergetic CT values are significantly different at low energy. The spectral curve of gemstone CT may be helpful to evaluate the pathological type and differentiation degree of gastric cancer before operation.

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10-8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.

Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.

Association between water fluoride and the level of children's intelligence: a dose-response meta-analysis.

OBJECTIVES: Higher fluoride concentrations in water have inconsistently been associated with the levels of intelligence in children. The following study summarizes the available evidence regarding the strength of association between fluoridated water and children's intelligence. STUDY DESIGN: Meta-analysis. METHODS: PubMed, Embase, and Cochrane Library databases were systematically analyzed from November 2016. Observational studies that have reported on intelligence levels in relation to high and low water fluoride contents, with 95% confidence intervals (CIs) were included. Further, the results were pooled using inverse variance methods. The correlation between water fluoride concentration and intelligence level was assessed by a dose-response meta-analysis. RESULTS: Twenty-six studies reporting data on 7258 children were included. The summary results indicated that high water fluoride exposure was associated with lower intelligence levels (standardized mean difference : -0.52; 95% CI: -0.62 to -0.42; P < 0.001). The findings from subgroup analyses were consistent with those from overall analysis. The dose-response meta-analysis suggested a significant association between water fluoride dosage and intelligence (P < 0.001), while increased water fluoride exposure was associated with reduced intelligence levels. CONCLUSIONS: Greater exposure to high levels of fluoride in water was significantly associated with reduced levels of intelligence in children. Therefore, water quality and exposure to fluoride in water should be controlled in areas with high fluoride levels in water.

Age-Related Response of Rumen Microbiota to Mineral Salt and Effects of Their Interactions on Enteric Methane Emissions in Cattle.

Mineral salt bricks are often used in cow raising as compensation for mineral losses to improve milk yield, growth, and metabolic activity. Generally, effects of minerals are partially thought to result from improvement of microbial metabolism, but their influence on the rumen microbiota has rarely been documented to date. In this study, we investigated the response of microbiota to mineral salt in heifer and adult cows and evaluated ruminal fermentation and enteric methane emissions of cows fed mineral salts. Twelve lactating Holstein cows and twelve heifers fed a total mixed ration (TMR) diet were randomly allocated into two groups, respectively: a treatment group comprising half of the adults and heifers that were fed mineral salt and a control group containing the other half fed a diet with no mineral salt supplement. Enteric methane emissions were reduced by 9.6% (P < 0.05) in adults ingesting a mineral salt diet, while concentrations of ruminal ammonia, butyrate, and propionate were increased to a significant extent (P < 0.05). Enteric methane emissions were also reduced in heifers ingesting a mineral salt diet, but not to a significant extent (P > 0.05). Moreover, the concentrations of ammonia and volatile fatty acids (VFAs) were not significantly altered in heifers (P > 0.05). Based on these results, we performed high-throughput sequencing to explore the bacterial and archaeal communities of the rumen samples. Succiniclasticum and Prevotella, two propionate-producing bacteria, were predominant in samples of both adults and heifers. At the phylotype level, mineral salt intake led to a significant shift from Succiniclasticum to Prevotella and Prevotellaceae populations in adults. In contrast, reduced abundance of Succiniclasticum and Prevotella phylotypes was observed, with no marked shift in propionate-producing bacteria in heifers. Methanogenic archaea were not significantly abundant between groups, either in adult cows or heifers. The shift of Succiniclasticum to Prevotella and Prevotellaceae in adults suggests a response of microbiota to mineral salt that contributes to higher propionate production, which competes for hydrogen utilized by methanogens. Our data collectively indicate that a mineral salt diet can alter interactions of bacterial taxa that result in enteric methane reduction, and this effect is also influenced in an age-dependent manner.

[Relationship between glycemic control and visceral adiposity index among the patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients. METHODS: A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use. Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI. Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels. Logistic models were applied in multiple analysis adjusting for possible confounders. RESULTS: A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years. Among them, 78.3% were on hypoglycemic therapy. The cutoff points of quartiles of VAI were calculated for the males and females, respectively. According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e. Q1, Q2, Q3, and Q4. The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, P<0.001). After adjustment for age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-C, smoking, cardio-cerebral vascular disease (CVD) history, hypoglycemic therapy, T2DM duration, and family history of diabetes, the Logistic regression models showed that the glycemic control rate was significantly associated with VAI levels among the patients with T2DM. Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128 to 2.088), respectively (trend P=0.003). With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1.282). CONCLUSION: The glycemic control among the patients with T2DM is significantly associated with VAI. High level of VAI is an indicator of poor glycemic control.

RNA-Seq analysis for the potential targets and molecular mechanisms of 17 ß-estradiol in squamous cell lung carcinoma.

The efficacy of 17 ß-estradiol (E2) was valid in some cancers, while its effects on squamous cell lung carcinoma (SCLC) were still unclear. The aim of our study was to investigate the potential targets and molecular mechanisms of E2 in SCLC cells.Two RNA libraries from human lung carcinoma cells (SK-MES-1) with and without E2 treatment were constructed and sequenced. The differentially expressed genes (DEGs) between cells with or without E2 treatment were identified by cuffdiff software. Hierarchical Clustering Analysis (HCA) was performed for displaying gene expression changes and classification. Furthermore, enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology Biological Process (GO BP) terms were performed through DAVID. The protein-protein interaction (PPI) network was constructed through STRING. Additionally, differentially expressed lncRNAs were also selected by cuffdiff software.Total 129 DEGs including 58 up- and 71 down- regulated genes were obtained. Cancer-related pathways including small cell lung cancer, hypertrophic cardiomyopathy (HCM) and pathways in cancer and biological processes including regulation of phosphorus metabolic process, protein localization and nucleus organization were enriched. The PPI network with 113 nodes and 312 edges was constructed. CASP3, ITGA2, COL4A6, PML and CDC25B were identified as hub nodes which had more interactions with others in the PPI network. Furthermore, eight up-regulated and ten down-regulated lncRNAs were selected.CASP3, ITGA2 and Lnc-DLK1-4:31 (one of down-regulated lncRNAs) might play pivotal roles in E2 treated SCNC cells by influencing cell apoptosis, angiogenesis and cell invasion respectively.

Significance of TNF-α and IL-6 expression in invasive pituitary adenomas.

The aim of this study was to investigate expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in invasive pituitary adenomas (IPAs). The streptavidin peroxidase immunohistochemical method was employed to detect their expression in 40 cases of IPA and 40 of non-invasive pituitary adenoma (NIPA). TNF-α and IL-6 were found to be upregulated in IPA tissue compared with that of NIPA (P < 0.05). These proteins may therefore play important roles in the occurrence and progression of IPA.

A genome-wide association study of bronchodilator response in asthmatics.

Reversibility of airway obstruction in response to ß2-agonists is highly variable among asthmatics, which is partially attributed to genetic factors. In a genome-wide association study of acute bronchodilator response (BDR) to inhaled albuterol, 534 290 single-nucleotide polymorphisms (SNPs) were tested in 403 white trios from the Childhood Asthma Management Program using five statistical models to determine the most robust genetic associations. The primary replication phase included 1397 polymorphisms in three asthma trials (pooled n=764). The second replication phase tested 13 SNPs in three additional asthma populations (n=241, n=215 and n=592). An intergenic SNP on chromosome 10, rs11252394, proximal to several excellent biological candidates, significantly replicated (P=1.98 × 10(-7)) in the primary replication trials. An intronic SNP (rs6988229) in the collagen (COL22A1) locus also provided strong replication signals (P=8.51 × 10(-6)). This study applied a robust approach for testing the genetic basis of BDR and identified novel loci associated with this drug response in asthmatics.

Seasonality of reported tuberculosis cases from 2006 to 2010 in Wuhan, China.

We investigated the seasonality of tuberculosis (TB) in Wuhan, China, to evaluate the increased risk of disease transmission during each season and to develop an effective TB control strategy. We applied spectral analysis to the weekly prevalence data of sputum smear positive (SSP) and sputum smear negative (SSN) pulmonary TB reported from 2006 to 2010. Cases of both SSP and SSN feature 1·0- and 0·5-year periodic modes. The least squares method was used to fit curves to the two periodic modes for SSP and SSN data. The curves demonstrated dominant peaks in spring similar to cases reported previously for other locations. Notably for SSP, dominant peaks were also observed in summer. The spring peaks of SSP and SSN were explained in terms of poorly ventilated and humid rooms and vitamin D deficiency. For the summer peaks of SSP, summer influenza epidemics in Wuhan may contribute to the increase in TB prevalence.

Polymorphisms in calpastatin and mu-calpain genes are associated with beef iron content.

The objective of this study was to assess the association of markers in the calpastatin and mu-calpain loci with iron in beef cattle muscle. The population consisted of 259 cross-bred steers from Beefmaster, Brangus, Bonsmara, Romosinuano, Hereford and Angus sires. Total iron and heme iron concentrations were measured. Markers in the calpastatin (referred to as CAST) and mu-calpain (referred to as CAPN4751) genes were used to assess their association with iron levels. The mean and standard error for iron and heme iron content in the population was 35.6 ± 1.3 µg and 27.1 ± 1.4 µg respectively. Significant associations (P < 0.01) of markers were observed for both iron and heme iron content. For CAST, animals with the CC genotype had higher levels of iron and heme iron in longissimus dorsi muscle. For CAPN4751, individuals with the TT genotype had higher concentrations of iron and heme iron than did animals with the CC and CT genotypes. Genotypes known to be associated with tougher meat were associated with higher levels of iron concentration.

Analysis of genetic relationships and identification of lily cultivars based on inter-simple sequence repeat markers.

Inter-simple sequence repeat (ISSR) markers were used to discriminate 62 lily cultivars of 5 hybrid series. Eight ISSR primers generated 104 bands in total, which all showed 100% polymorphism, and an average of 13 bands were amplified by each primer. Two software packages, POPGENE 1.32 and NTSYSpc 2.1, were used to analyze the data matrix. Our results showed that the observed number of alleles (NA), effective number of alleles (NE), Nei's genetic diversity (H), and Shannon's information index (I) were 1.9630, 1.4179, 0.2606, and 0.4080, respectively. The highest genetic similarity (0.9601) was observed between the Oriental x Trumpet and Oriental lilies, which indicated that the two hybrids had a close genetic relationship. An unweighted pair-group method with arithmetic means dendrogram showed that the 62 lily cultivars clustered into two discrete groups. The first group included the Oriental and OT cultivars, while the Asiatic, LA, and Longiflorum lilies were placed in the second cluster. The distribution of individuals in the principal component analysis was consistent with the clustering of the dendrogram. Fingerprints of all lily cultivars built from 8 primers could be separated completely. This study confirmed the effect and efficiency of ISSR identification in lily cultivars.