Associations between insufficient sleep, skipping breakfast and depressive symptoms in children and adolescents: A school-based cross-sectional study in China.

OBJECTIVE: Insufficient sleep and skipping breakfast are increasingly prevalent among children and adolescents. Both behaviors are associated with the onset of depression. This study aims to examine the independent and joint associations of these two behaviors with depressive symptoms, and investigate whether these associations varied by age or sex. METHODS: The Center for Epidemiological Studies Depression Scale (CES-D) was used to evaluate the depressive symptoms. This cross-sectional study including 11,887 students aged 11-19 years using a stratified cluster, multistage sampling method in Ningbo, China. Multiple logistic regressions were conducted to evaluate the independent and joint association between insufficient sleep, skipping breakfast and depressive symptoms. Sensitivity analyses and stratified analyses by age and sex were performed using the same modelling strategies. RESULTS: The overall prevalence of depressive symptoms was 15.27%. Skipping breakfast (Odds Ratio (OR) = 2.557, 95% Confidence Interval (CI) = 2.236-2.925) and insufficient sleep (OR = 1.547, 95%CI = 1.390-1.723) was independently associated with depressive symptoms. Compared to students with "sufficient sleep and breakfast every day", the OR was 4.385 (95%CI = 3.649-5.271) for those with "insufficient sleep and skipping breakfast". Meanwhile, the joint association was moderated by age group, with a more apparent association observed in the 11-15-year-old group compared to the 16-19-year-old group. CONCLUSIONS: These findings indicated that insufficient sleep and skipping breakfast were independently and jointly associated with depressive symptoms. Insufficient sleep and skipping breakfast could be considered as two of the predictors of depression.

PAX6 gene promoter methylation is correlated with myopia in Chinese adolescents: a pilot sutdy.

PURPOSE: A large number of epidemiological studies have shown that myopia is a complex disease involving genetic, environmental, and behavioral factors. The purpose of this study was to explore the role of PAX6 gene methylation in myopia in Chinese adolescents. METHODS: Eighty junior high school students were divided into four groups based on their vision test results: mild myopia, moderate myopia, severe myopia, and non-myopia control. The methylation level of PAX6 gene promoter was detected by bisulfate pyrosequencing. RESULTS: The methylation level of PAX6 gene in myopia group (8.06% ± 1.43%) was slightly but significantly higher than that in non-myopia controls (7.26% ± 1.17%). In addition, PAX6 gene methylation levels presented a decreasing pattern along with the aggravation of myopia. Post-hoc analysis indicated significant inter-group differences for the mild myopia group and other groups (All p < .05). In the subgroup analysis by gender, the methylation level of PAX6 gene promoter in girls was higher than that in boys (p = .023). The ROC curves showed a high accuracy of PAX6 gene methylation to predict mild myopia (AUC (95% CI) = 0.828 (0.709-0.947), p < .001). CONCLUSIONS: The methylation of PAX6 gene might play a role in the onset and progression of myopia in Chinese adolescents. And this could potentially explore the potential molecular mechanisms of juvenile myopia in the future.

Chronotype is associated with eating behaviors, physical activity and overweight in school-aged children.

BACKGROUND: A later chronotype has been found to be associated with unhealthy habits and diseases, such as an unhealthy diet and metabolic syndrome in adults. Little is known about the association between chronotype, eating habits, physical activity and obesity. Thus, this study aimed to explore the relationships between chronotype, eating behaviors, physical activity, and overweight in Chinese school-aged children. METHODS: Data from this study was based on 952 schoolchildren (10-12 y) from six primary schools that participated in China. Anthropometric measurements of height and body weight were performed. Information about sleeping habits, dietary behaviors, and other lifestyle behaviors was gathered using a self-administered questionnaire. Multiple linear regression analysis or multivariable logistic regression model was performed to assess the associations between chronotype, eating behaviors, physical activity, and overweight. RESULTS: Nearly 70% (69.9%) of the participants had a self-reported morning chronotype. Multiple linear regression analysis revealed chronotype score was positively associated with physical activities (all P values < 0.001) and sleep duration (all P values < 0.001) and negatively associated with BMI, meal time, eating jet lag and social jet lag (all P values < 0.001). Multivariable logistic regression analysis showed that compared to morning types, non-morning types individuals were more likely to be overweight (OR = 1.593, P value < 0.05), and had more frequent consumption of fast food (OR = 1.616, P value < 0.05), but less frequent consumption of milk (OR = 0.716, P value < 0.05), less time taking part in moderate (OR = 1.356, P value < 0.05) or muscle strengthening (OR = 1.393, 1.877, P value < 0.05) physical activity. CONCLUSIONS: This study indicates that early chronotype children are more active, have healthier dietary habits, get more sleep, have shorter social jet lag, and are less likely to be overweight than non-early chronotype children. Our findings suggest that later chronotype may be a potential indicator in the early detection of overweight, unhealthy eating, and physical inactivity behaviors. Chronotype has been found to have an important impact on individual's health. In the present study, we conducted a cross-sectional study to investigate the association between chronotype, eating behaviors, physical activity, and overweight in school-aged children. The findings showed that children with early chronotype is associated with more active, healthier dietary behaviors, longer sleep duration, short social jet lag, and a lower risk of overweight.

Association between Dietary Behavior and Overweight and Obesity among Chinese Students: A Cross-Sectional Study.

OBJECTIVES: To investigate the prevalence of overweight and obesity among Ningbo students and explore the association between students' dietary behavior and overweight and obesity. MATERIALS AND METHODS: A total of 7299 students were recruited, including 3755 males and 3544 females. A questionnaire on student health status and influencing factors was used to investigate dietary behavior. Logistic regression analysis investigated the relationship between dietary behavior and overweight and obesity. Age, gender, area, grade, sleep duration, and physical activity were adjusted in the multivariate regression models. RESULTS: This study revealed that the prevalence of overweight and obesity in Ningbo students was 16.14% and 9.88%, respectively. The logistic regression analysis results showed that regular consumption of sugary beverages was associated with a higher risk of being overweight (OR = 1.256, 95% CI: 1.023-1.542, p = 0.029). The research indicated that skipping breakfast was considered a risk factor for obesity (OR = 2.102, 95% CI: 1.087-4.065, p = 0.027). After adjusting for age, gender, area, and grade and continuing to adjust for sleep duration and physical activity, the results showed that consuming fried food at least once a day increased the risk of obesity (OR = 1.494, 95% CI: 1.050-2.125, p = 0.026; OR = 1.516, 95% CI: 1.065-2.158, p = 0.021, respectively). This study found that the frequency of breakfast and the consumption of fried food, fresh vegetables, and fruits were not significantly associated with being overweight (p > 0.05). CONCLUSIONS: This study indicated that dietary behavior was related to overweight and obesity among Ningbo students. Further studies and more government support are required to confirm this study's findings and address the current overweight/obesity problems.

Sleep duration is associated with depressive symptoms in Chinese adolescents.

BACKGROUND: Depressive symptoms have become one of the most common mental health problems in adolescents. Identifying potential factors associated with adolescent depressive symptoms could be practical and essential for early intervention programs. The association between sleep duration and depressive symptoms in adolescents is inconsistent and needs further exploration. METHODS: A total of 7330 participants aged 10-19 years were included in this study. Sleep duration was categorized into <7 h, 7-8 h, 8-9 h, and ≥ 9 h per day. The Chinese version of the Center for Epidemiology Scale for Depression was used to assess depressive symptoms. Binary logistic regression analysis was performed to evaluate the association between sleep duration and the risk of depressive symptoms. Restrictive cubic spline analyses were conducted to evaluate the dose-response relationship between sleep duration and depressive symptoms. RESULTS: Thirty-four percent of the participants suffered from depressive symptoms. The prevalence of depressive symptoms in adolescents with sleep durations of <7 h, 7-8 h, 8-9 h, and ≥9 h per day was 52.66 %, 37.80 %, 27.55 %, and 20.49 %, respectively. After adjusting for potential covariates, long sleep duration was significantly associated with a decreased risk of depressive symptoms in adolescents. A nonlinear relationship between sleep duration and depressive symptoms was identified. CONCLUSIONS: Long sleep duration is independently associated with a decreased risk of depressive symptoms in Chinese adolescents.

The association between sleep duration and risk of myopia in Chinese school-aged children: a cross-sectional study.

BACKGROUND: Myopia is one of the most commonly diagnosed refractive disorders worldwide. Identifying risk factors for myopia at an early age may help to characterize children who would benefit most from individualized lifestyle advice and early interventions. The influence of sleep duration on myopia risk remains controversial and thus needs to be evaluated. METHODS: A population-based cross-sectional study of Chinese school-aged children was conducted. Information on sleep duration was derived. The association between sleep duration and myopia risk was investigated by logistic regression analysis. RESULTS: Myopia prevalence among 9530 Chinese school-aged children was 75.4% and decreased from 84.9%, 76.5%, 65.8%, to 61.3% along with the extension of sleep duration. Univariate logistic regression found longer sleep duration of 8-9 h (OR = 0.58, 95% CI: 0.51-0.66), 9-10 h (OR = 0.34, 95% CI: 0.30-0.39), and ≥ 10 h (OR = 0.28, 95% CI: 0.24-0.33) were protective factors for myopia in all participants (P for trend < 0.001). In the multivariate analyses, sleep duration was inversely associated with the risk of myopia, and a dose-effect relationship was observed when the analysis was split by age category. CONCLUSIONS: Long sleep duration was associated with decreased risk of myopia in Chinese school-aged children.

School lunch leftovers of primary and middle school students and its influencing factors in Ningbo / 中国学校卫生

Objective@#To analyze the situation and associated factors of school lunch leftovers of primary and middle school students in Ningbo, so as to provide a basis for formulating policies to improve the quality of nutritious meals and reduce the leftover meal rates.@*Methods@#During March to May of 2022, 20 primary and middle schools were selected from 10 districts in Ningbo, and 4 443 students were selected from grade 4 to 6 of primary school and grade 1 to 3 of middle school. A questionnaire was conducted among them for the students general situation and remaining meal situation.@*Results@#The total leftover rate was 62.4%, 7.9% of the students left rice every day, and 18.3% of the students left vegetables every day. The frequency of primary school students leftover food was lower than that of junior high school students ( χ 2=-2.18, P <0.05). Most of the students (68.3%) had only a little leftover food, half of the students (49.4%) had less than half leftovers, and the proportion of primary school students with large leftover food and leftovers was smaller than that of junior high school students ( χ 2=-2.05, -2.36, P <0.05). The main reason for students leftover food was "too much to eat" (accounting for 30.6%), and there was a statistical difference between primary school students and junior high school students in the composition of leftover food and leftovers ( χ 2=16.94, 14.28, P <0.05). The leftover rate of vegetables was the highest (54.5%) and the leftover rate of milk was the lowest (2.5%). Multivariate Logistic regression model showed that nutrition and food related courses during recent year, being aware the Chinese residents dietary guidelines, statisfaction with canteen food (general, more satisfied, very satisfied), reckoning school canteen food better than home food (almost, better than home) were less possibility to have leftover meals ( OR=0.79, 0.73, 0.57, 0.41, 0.26, 0.69, 0.82, P <0.05). Students chosed the meal after the teacher served the meal, the teacher divided meals and students who ate more frequently (4-6 times/week, 1 time/d, 2 times/d, ≥3 times/d) were more likely to have leftover meals ( OR=1.64, 2.23, 1.27, 1.21, 1.52, 1.44 , P < 0.05).@*Conclusion@#More than half of the students have leftovers. It should optimize the configuration of nutrition lunch, strengthen the education of nutrition knowledge and reduce the leftovers rate.

Associations between reading and writing postures and myopia among school students in Ningbo, China.

Background: We conducted this study to investigate the prevalence of myopia among school students in Ningbo and to explore the associations between reading and writing postures and myopia. Methods: A population-based and cross-sectional study was conducted, and 3,256 school students aged 8-19 years were recruited. Each enrolled subject was assessed for uncorrected distance visual acuity (UDVA) using a standard logarithmic visual acuity E-chart and a non-cycloplegic autorefraction examination. Self-administered questionnaires were used to investigate myopia-related reading and writing postures and behavioral habits among school students. Results: The prevalence of myopia among primary school, middle school, and high school students was 61.49, 81.43, and 89.72%, respectively. Regarding the associations between reading and writing postures and myopia, we identified that a reading distance >33 cm is a protective factor for myopia in female students [odds ratio (OR) = 0.31, 95% confidence interval (CI) = 0.15-0.64], in both primary school (OR = 0.55, 95% CI = 0.30-0.99) and middle school (OR = 0.37, 95% CI = 0.15-0.90). Conclusions: A reading distance >33 cm can be used as an additional measure to prevent and control myopia. Proper postural measures for reading and writing may have educational and public health benefits.

Association of the Expression Level of miR-16 with Prognosis of Solid Cancer Patients: A Meta-Analysis and Bioinformatic Analysis.

OBJECTIVE: To assess the association between the expression level of miR-16 and prognosis of solid cancer patients by meta-analysis and bioinformatic analysis. METHODS: PubMed, Web of Science, and Embase databases were searched until October 31, 2019, to identify eligible studies reporting the association of the miR-16 status with the prognosis of solid cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled, and a heterogeneity test was conducted. Sensitivity analysis and a publication bias test were also carried out. Furthermore, the miRpower database was used to validate the association. RESULTS: Thirteen articles with 2303 solid cancer patients were included in the meta-analysis. Solid cancer patients with low expression level of miR-16 had shorter survival time (I 2 = 84.0%, HR = 1.47, 95% CI: 1.13-1.91, P = 0.004). In the subgroup analyses of cancer sites, low miR-16 expression level was associated with poor prognosis in the reproductive system cancers (I 2 = 33.3%, HR = 1.24, 95% CI: 1.06-1.45, P = 0.008). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Begg's test and Egger's test revealed no publication bias in the meta-analysis. In bioinformatic analysis, the significant association between miR-16 level and prognosis of patients with reproductive system cancers was further confirmed (HR = 1.21, 95% CI: 1.03-1.42, P = 0.017). CONCLUSION: Low expression level of miR-16 is an indicator for poor prognosis of solid cancer patients, particularly in reproductive system cancers.

Impact of Individual and Combined Lifestyle Factors on Mortality in China: A Cohort Study.

INTRODUCTION: Although numerous studies have suggested that lifestyle-related factors are associated with chronic diseases and preventable deaths, limited evidence is available for the Chinese population. METHODS: This study established a prospective cohort of >360,000 residents on the basis of the Yinzhou Health Information System in China during 2004-2017 and calculated the combined effects of lifestyle-related factors, including BMI, smoking, alcohol consumption, and physical activity, using a points system. A Cox regression model estimated the combined effects of lifestyle-related factors on total mortality, and a competing risk model estimated the combined effects on cancer and cardiovascular disease mortality. All data analyses were conducted in 2018‒2019. RESULTS: During 3,755,879 person-years of follow-up, 11,791 deaths were identified, including 4,983 from cancer and 3,143 from cardiovascular disease. Having a standard BMI, never smoking, never drinking, and engaging in physical activity more than 4 times per week had protective effects on total mortality. Overall, the risk of total and cause-specific mortality increased with the increment of risk score. Compared with subjects in the lowest quartile, the risk of total and cause-specific mortality peaked among individuals in the fourth quartile (total mortality: hazard ratio=1.87, 95% CI=1.77, 1.98; cancer mortality: hazard ratio=2.05, 95% CI=1.87, 2.25; cardiovascular disease mortality: hazard ratio=1.51, 95% CI=1.35, 1.68). Sensitivity analyses excluding individuals with follow-up <3 years did not materially change the results. CONCLUSIONS: The combined effects of lifestyle-related factors, including BMI, smoking, alcohol drinking, and physical activity, are associated with total, cancer, and cardiovascular disease mortality among the Chinese population.

Alu Methylation and Risk of Cancer: A Meta-analysis.

BACKGROUND: The association between Alu methylation and risk of cancer remains uncertain. This meta-analysis was conducted to elucidate this issue. MATERIALS AND METHODS: PubMed and Web of Science up to December 31, 2018, and the reference lists of studies, as well as those presented in relevant meta-analyses and reviews were systematically searched. Standardized mean difference (SMD) in Alu methylation level between cases and controls were pooled using random effects model and assessed heterogeneity between strata by stratified factors using meta-regression model. Sensitivity analysis and publication bias test were also conducted. RESULTS: Twenty-five articles, including 2719 cases and 3018 controls were included in the meta-analysis. The significant difference in Alu methylation level between cancer cases and controls was greater in tissue (SMD = -1.89, 95% CI: -2.72, -1.05) than blood (SMD = -0.46, 95% CI: -0.82, -0.09), and heterogeneity was found in materials (P = 0.038). In tissue samples, Alu hypomethylation was found in carcinoma (SMD = -2.50, 95% CI: -3.51, -1.48), while not in non-carcinoma. The inverse associations were consistently found in subgroups stratified by data sources and quality score in tissue samples, and publication year was considered to be the potential source of between-study heterogeneity. Moreover, reduced Alu methylation level was found in the European subgroup, detection method of SIRPH and COBRA, and original data source in blood samples. CONCLUSIONS: Alu hypomethylation was associated with increased risk of cancer, which could be a potential biomarker for cancer.

Regression-based normative data for social health scale for the elderly (short version) in eastern China.

BACKGROUNDS: Social Health Scale for the Elderly short version (SHSE-S) is a psychometrically sound instrument that comprehensively assesses the social health status of older adults in China. The aim of the present study was to establish continuous normative data of SHSE-S. METHODS: We conducted a multicenter cross-sectional study among 31 communities in eastern China. Older adults aged 60 years and above were invited to participate in the study. Each participant was interviewed in-person to finish a structured questionnaire. The SHES-S score was calculated and standardized for each participant. We split the sample into generation and validation datasets and compared the distribution of SHSE-S score between two datasets. Multivariable linear regression was used to assess the SHSE-S score and demographic variables. Regression-based norms were built using a four-step process. RESULTS: A total of 6089 participants (51.2% females) aged 60 years old and above (mean age = 71.3, SD = 8.0) were enrolled as the normative sample. No significant difference was found between the distribution of SHSE-S standardized score in the generation (N = 2392) and validation (N = 3697) datasets. Multivariable linear regression showed that females, higher education levels were positive indicators while aging, living alone, divorced or never married, multimorbidity were negative factors. The regression-based norm which taking demographic factors into account was established and a user-friendly worksheet was also provided to facilitate the scoring and norming of the SHSE-S. CONCLUSIONS: The population-based regression norm of SHSE-S can be a useful tool for assessing the social health status of the Chinese elderly population.

Evaluating the predictive value of genetic risk score in colorectal cancer among Chinese Han population.

Increasing single nucleotide polymorphisms (SNPs) have been identified to be associated with colorectal cancer (CRC). We aimed to investigate whether genetic risk scores (GRS) that aggregate information from multiple genetic variants can predict the risk of CRC in a Chinese population. Fifty candidate SNPs were selected to explore the associations with CRC in a discovery sample with 1002 CRC cases and 999 healthy controls. We modeled the significant SNPs identified by the case-control study as a multilocus weighted GRS and estimated the association of GRS with CRC. Furthermore, 300 pairs of cases and controls were included as a validation sample to confirm the finding. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive power of GRS in CRC. A total of seven SNPs were found to increase the risk of CRC, and two SNPs were found to be negatively associated with CRC in the discovery sample. Relative to participants with the lowest quartile of GRS, those with the highest quartile had a 2.64-fold (95% CI: 1.99-3.51) higher risk for CRC. For every 0.1 point of GRS increase, the risk of CRC increase by 11% (95% CI: 8-14%). AUROC for GRS alone were 0.59 (95% CI: 0.57-0.62) and 0.52 (95% CI: 0.46-0.58) in the discovery and validation sample, respectively. AUROC increased to 0.62 (95% CI: 0.59-0.64) and 0.71 (95% CI: 0.65-0.76) by combining environmental risk factors. Our findings support an association between GRS and risk of CRC, which provides evidence of improved prediction model for CRC in China.

Polymorphisms of a novel long non-coding RNA RP11-108K3.2 with colorectal cancer susceptibility and their effects on its expression.

BACKGROUND: RP11-108K3.2 was recently identified as a novel long non-coding RNA (lncRNA) transcript, and several single nucleotide polymorphisms (SNPs) have been identified in its coding region. This study aimed to explore the associations of tagSNPs in RP11-108K3.2 with the risk of colorectal cancer and their effects on its expression. METHODS: A total of 821 colorectal cancer cases and 857 healthy controls were enrolled into this two-stage case-control study. Demographic characteristics and lifestyle information were collected by a validated questionnaire. Six tagSNPs were genotyped by using Sequenom MassARRAY platform. A total of 71 additional colorectal cancer cases were recruited, of which the genotypes of potential polymorphisms and the RP11-108K3.2 expression levels were determined. RESULTS: In the discovery set, only the rs2470151 C/T polymorphism was found to have a promising association with the risk of colorectal cancer, and this polymorphism was further replicated in the validation set with a significantly decreased risk of colorectal cancer (adjusted odds ratio 0.73; 95% confidence interval 0.55, 0.97). Combined discovery set and validation set together, this negative association was found both in the heterozygote codominant model and the dominant model. Furthermore, colorectal cancer patients carrying rs2470151 CT/TT genotypes had a marginally lower RNA expression of RP11-108K3.2 than those carrying the CC genotype. Stratified analyses showed the association between rs2470151 and the risk of colorectal cancer were influenced by family history of cancer, smoking, alcohol consumption, and tea drinking. CONCLUSIONS: These findings suggest that RP11-108K3.2 rs2470151 had a significant association with the risk of colorectal cancer; this may help to predict the susceptibility of colorectal cancer in Chinese populations.

Association between social health status and depressive symptoms among community-dwelling elderly adults in Zhejiang Province, China.

OBJECTIVE: Mental disorders of the elderly population in China deserve attention. Social health is significantly associated with depression. This study aimed to evaluate the rate of depressive symptoms and to test the relationships between social health and depressive symptoms among a large sample of community-dwelling elderly adults. METHODS: We conducted a cross-sectional study among community-dwelling adults aged 60 years or above in Zhejiang Province, China. Face-to-face interviews were used to complete a structured questionnaire for all participants. We used the Social Health Scale for the Elderly (SHSE) to evaluate social health status and used the short form of the Geriatric Depression Scale to evaluate depressive symptoms. Multivariate logistic regression was used to evaluate the association between social health status and depressive symptoms. RESULTS: Of the total of 3757 participants included, 1887 (50.23%) were female, and the mean±standard deviation (SD) age was (70.0±8.3) years. The rate of depressive symptoms was 25.92%. The social health score was higher in non-depressed participants than in depressed participants (raw score 50.7 vs. 48.3, P<0.001). Participants with "moderate" or "good" social health had a significantly lower risk of depressive symptoms than those with "poor" social health (odds ratio (OR)=0.55, 95% confidence interval (CI): 0.46-0.66 for moderate social health; OR=0.45, 95% CI: 0.35-0.60 for good social health). The association between social health and depressive symptoms was consistent across several subgroups. CONCLUSIONS: Social health is significantly inversely associated with depressive symptoms. The SHSE may serve as an efficient screener to identify those elderly adults with social health deficits, but systematic assessment to guide intervention merits further investigation.

Genome-wide methylation profiling identified novel differentially hypermethylated biomarker MPPED2 in colorectal cancer.

BACKGROUND: Epigenetic alternation is a common contributing factor to neoplastic transformation. Although previous studies have reported a cluster of aberrant promoter methylation changes associated with silencing of tumor suppressor genes, little is known concerning their sequential DNA methylation changes during the carcinogenetic process. The aim of the present study was to address a genome-wide search for identifying potentially important methylated changes and investigate the onset and pattern of methylation changes during the progression of colorectal neoplasia. METHODS: A three-phase design was employed in this study. In the screening phase, DNA methylation profile of 12 pairs of colorectal cancer (CRC) and adjacent normal tissues was analyzed by using the Illumina MethylationEPIC BeadChip. Significant CpG sites were selected based on a cross-validation analysis from The Cancer Genome Atlas (TCGA) database. Methylation levels of candidate CpGs were assessed using pyrosequencing in the training dataset (tumor lesions and adjacent normal tissues from 46 CRCs) and the validation dataset (tumor lesions and paired normal tissues from 13 hyperplastic polyps, 129 adenomas, and 256 CRCs). A linear mixed-effects model was used to examine the incremental changes of DNA methylation during the progression of colorectal neoplasia. RESULTS: The comparisons between normal and tumor samples in the screening phase revealed an extensive CRC-specific methylomic pattern with 174,006 (21%) methylated CpG sites, of which 22,232 (13%) were hyermethylated and 151,774 (87%) were hypomethylated. Hypermethylation mostly occurred in CpG islands with an overlap of gene promoters, while hypomethylation tended to be mapped far away from functional regions. Further cross validation analysis from TCGA dataset confirmed 265 hypermethylated promoters coupling with downregulated gene expression. Among which, hypermethylated changes in MEEPD2 promoter was successfully replicated in both training and validation phase. Significant hypermethylation appeared since precursor lesions with an extensive modification in CRCs. The linear mixed-effects modeling analysis found that a cumulative pattern of MPPED2 methylation changes from normal mucosa to hyperplastic polyp to adenoma, and to carcinoma (P < 0.001). CONCLUSIONS: Our findings indicate that epigenetic alterations of MPPED2 promoter region appear sequentially during the colorectal neoplastic progression. It might be able to serve as a promising biomarker for early diagnosis and stage surveillance of colorectal tumorigenesis.

Elevated methylation of cyclin dependent kinase inhibitor 2B contributes to the risk of coronary heart disease in women.

Cyclin dependent kinase inhibitor 2B (CDKN2B) encodes a cyclin-dependent kinase inhibitor that may enhance the formation of atherosclerotic plaques. The aim of the present study was to investigate the contribution of CDKN2B promoter methylation on the risk of coronary heart disease (CHD). The present results indicated a significant association between increased CDKN2B methylation and the risk of CHD (adjusted P=0.043). A breakdown analysis according to sex demonstrated that CDKN2B methylation was significantly associated with the risk of CHD in women (adjusted P=0.010), but not in men. A further breakdown analysis by age indicated a significant association of CHD in the women >60 years (P=0.024). Luciferase reporter gene assay results indicated that the CDKN2B promoter fragment significantly enhanced luciferase activity (P<0.001). In addition, CDKN2B transcription was significantly enhanced following treatment with 5-aza-2'-deoxycytidine methylation inhibitor in human aortic endothelial cells (HAEC) and human primary coronary artery smooth muscle cells (HPCASMC; P<0.05 and P<0.01), but not in 293 cells. Notably, estrogen treatment reduced CDKN2B methylation of several CpGs and significantly increased CDKN2B gene expression levels in HAEC, HPCASMC and 293 cells (P<0.05 and P<0.01). Additionally, treatment of HAEC and HPCASMC with simvastatin and γ-carboxy-L-glutamic acid reduced CDKN2B promoter methylation and increased CDKN2B transcription concomitantly. The present study suggests that CDKN2B promoter methylation may be associated with sex dimorphism in the pathogenesis of CHD.

Clinically useful flow cytometry approach to identify immunophenotype in acute leukemia.

OBJECTIVES: Acute leukemia (AL) is a highly heterogeneous malignant disease caused by hematopoietic cell abnormalities. Our study investigated the potential for immunophenotyping of leukemic cells via flow cytometry and the clinical usefulness of this approach in treatment of AL. METHODS: Bone marrow (BM) specimens were collected to detect antigen expression on hematopoietic cells in pre-treatment samples from patients with AL. In addition, fraction survival curves were calculated using the Kaplan-Meier method to explore the effect of markers on prognosis in AL. RESULTS: Expression levels of immunophenotypic markers in patients with acute lymphoblastic leukemia (ALL) were significantly different from those in patients with acute myeloid leukemia (AML). In addition, there was a potential association between the surface marker, cluster of differentiation 2 (CD2), and fraction survival in AML. However, no similar result was found in ALL. Moreover, genetic tests showed greater positive variation of the break point cluster-Abelson tyrosine kinase ( BCR-ABL) fusion gene in samples from patients with ALL than in samples from patients with AML. CONCLUSIONS: We have shown a rapid and effective flow cytometry method that enables the identification of immunophenotype in AL. Moreover, CD2 may constitute a predictive marker for prognosis in patients with AML.