Background Nonpharmacologic interventions that modify lifestyle can lower blood pressure (BP) and have been assessed in numerous randomized controlled trials and pairwise meta‐analyses. It is still unclear which intervention would be most efficacious. Methods and Results Bayesian network meta‐analyses were performed to estimate the comparative effectiveness of different interventions for lowering BP. From 60 166 potentially relevant articles, 120 eligible articles (14 923 participants) with a median follow‐up of 12 weeks, assessing 22 nonpharmacologic interventions, were included. According to the surface under the cumulative ranking probabilities and Grading of Recommendations Assessment, Development and Evaluation (GRADE) quality of evidence, for adults with prehypertension to established hypertension, high‐quality evidence indicated that the Dietary Approach to Stop Hypertension (DASH) was superior to usual care and all other nonpharmacologic interventions in lowering systolic BP (weighted mean difference, 6.97 mm Hg; 95% credible interval, 4.50–9.47) and diastolic BP (weighted mean difference, 3.54 mm Hg; 95% credible interval, 1.80–5.28). Compared with usual care, moderate‐ to high‐quality evidence indicated that aerobic exercise, isometric training, low‐sodium and high‐potassium salt, comprehensive lifestyle modification, breathing‐control, and meditation could lower systolic BP and diastolic BP. For patients with hypertension, moderate‐ to high‐quality evidence suggested that the interventions listed (except comprehensive lifestyle modification) were associated with greater systolic BP and diastolic BP reduction than usual care; salt restriction was also effective in lowering both systolic BP and diastolic BP. Among overweight and obese participants, low‐calorie diet and low‐calorie diet plus exercise could lower more BP than exercise. Conclusions DASH might be the most effective intervention in lowering BP for adults with prehypertension to established hypertension. Aerobic exercise, isometric training, low‐sodium and high‐potassium salt, comprehensive lifestyle modification, salt restriction, breathing‐control, meditation and low‐calorie diet also have obvious effects on BP reduction.

BackgroundAs biomarkers, DNA methylation is used to detect colorectal cancer (CRC) and make assessment of CRC prognosis. The published findings showed the association between the methylation of SFRP1, SFRP2, and WIF1, located in the Wnt signaling pathway, and the prognosis of CRC were not consistent. Our study aimed to explore the potential possibility of SFRP1, SFRP2, and WIF1 concomitant promoter methylation as prognostic biomarkers of postoperative CRC patients.MethodsAs a total of 307 sporadic postoperative CRC patients were followed up, we detected SFRP1, SFRP2, and WIF1 methylation obtained from tumor tissues and adjacent non-tumor tissues respectively on the basis of methylation-sensitive high resolution melting analysis. Univariate and multivariate Cox regressions were carried out so as to assess the potential possibility of SFRP1, SFRP2, and WIF1 promoter methylation as predictors of prognosis. Confounders in our study were controlled by Propensity Score (PS) analysis.ResultsThe SFRP1, SFRP2, and WIF1 methylation levels in tumor tissues were significantly higher than that in adjacent non-tumor tissues (P < 0.001). SFRP2 hypermethylation was significantly associated with a favorable clinical outcome at the hazard ratio (HR) of 0.343 [95% confidence intervals (CI): 0.164–0.718, P = 0.005] and 0.410 (95% CI: 0.200–0.842, P = 0.015) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1 and SFRP2 was significantly associated with a favorable clinical outcome at the HR of 0.333 (95% CI: 0.159–0.694, P = 0.003) and 0.398 (95% CI: 0.192–0.821, P = 0.013) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1, SFRP2 and WIF1 was significantly associated with a favorable clinical outcome at the HR of 0.326 (95% CI: 0.117–0.908, P = 0.032) and 0.401 (95% CI: 0.146–1.106, P = 0.077) in multivariate Cox regression and PS analysis, respectively.ConclusionsSFRP1, SFRP2, and WIF1 were frequently hypermethylated in CRC tumor tissues. It was apparent that the promoter hypermethylation of SFRP2 and co-hypermethylation of SFRP1 and SFRP2 might be considered as independent prognostic predictors for survival advantage of postoperative CRC patients.

Background: Migraine is a common neurological disorder and is affected by nutrients. Calcium and magnesium are essential minerals that play an important role in nerve function. So we investigated the association between dietary calcium and magnesium and migraine.Methods: We extracted 10,798 adults from the National Health and Nutrition Examination Surveys (NHANES) of America in 1999 to 2004. We classified patients who reported having severe headache or migraine as having possible migraine. Multivariable logistic regression and restricted cubic spline regression were conducted to determine the association between dietary calcium and magnesium and migraine.Results: We found that the adjusted ORs of the association between dietary calcium and magnesium and migraine for comparing the highest quintile intake with the lowest quintile intake were 0.77 (95% CI: 0.63–0.93, P = 0.008) and 0.69 (95% CI: 0.55–0.86, P = 0.001), respectively. For women, the adjusted ORs of dietary calcium and magnesium were 0.72 (95% CI: 0.56–0.93, P = 0.009) and 0.62 (95% CI: 0.47–0.83, P = 0.001), respectively. For men, the adjusted OR was 0.71 (95% CI: 0.52–0.97, P = 0.028) comparing the highest and the lowest quintile of calcium intake, but there was no statistically significant association between dietary magnesium intake and migraine. Joint analyses showed that the OR in the high-calcium and high-magnesium group was 0.74 (95% CI: 0.60–0.92, P = 0.006) compared with the low-calcium and low-magnesium group in women.Conclusions: High dietary intake of calcium and magnesium, independently or in combination, were inversely associated with migraine in women. For men, high dietary calcium was negatively related to migraine, but magnesium was not associated with migraine.

Background: Dietary iron intake and serum ferritin in relation to severe headache or migraine remain largely unknown. Therefore, we investigated the associations between dietary iron intake and serum ferritin with severe headache or migraine among American adults.Methods: This cross-sectional study included 7,880 adults (≥20 years) from the National Health and Nutrition Examination Surveys (NHANES) of America from 1999 to 2004. We performed multivariable logistic regression and restricted cubic spline (RCS) regression to assess the association of dietary iron and serum ferritin with severe headache or migraine.Results: Most women aged 20–50 years consumed less dietary iron than their recommended dietary allowances. Dietary iron intake was inversely associated with severe headache or migraine in women aged 20–50 years. For women over 50 years, serum ferritin was negatively associated with severe headache or migraine. For men, there was no significant relationship between dietary iron and serum ferritin, and severe headache or migraine.Conclusions: Dietary iron intake has different effects on migraine in women of different ages, and this different effect may be due to age-related menstrual changes. Women aged 20–50 years should have a higher awareness of RDA and increase their dietary iron intake if needed, which may play an important role in preventing severe headache or migraine. Higher serum ferritin levels in women aged 50 and above may have a protective effect against migraine.

Abnormal DNA methylation is considered a vital hallmark to regulate gene expression and influence the development and progression of colorectal cancer (CRC). Although CRC‐related methylation prognostic models have been developed, their clinical application is limited due to the lack of external validation and extension to other survival evaluation indicators. Therefore, this study aimed to develop and validate novel methylation prognostic models correlated with different survival indicators for individualized prognosis prediction for CRC patients. The prognostic‐related CpG sites of methylation‐driven genes screened by the MethylMix algorithm were identified and validated in The Cancer Genome Atlas (TCGA) CRC methylation data and our methylation data. The prognostic models correlated with different survival evaluation indicators (overall survival [OS] and disease‐free survival [DFS]) were developed and validated in the TCGA CRC dataset (N = 376) and our independent CRC dataset (N = 227). We utilized the combination of selected 3‐CpG methylation sites in three genes (DAPP1, FAM3D, and PIGR) to construct a prognostic risk‐score model. In the training dataset, Kaplan–Meier survival analysis demonstrated that high‐risk patients had significantly poorer survival than low‐risk patients (pOS = .0014; pDFS < .001). Then, the 3‐CpG methylation signature was successfully validated as an independent predictor in the testing data set (pOS = .016; pDFS = .016). A prognostic nomogram was constructed and validated. Additionally, mediation analysis revealed the direct effect of the methylation signature on CRC prognosis (pOS = 9.149e−06; pDFS = .001). In summary, our study revealed that the 3‐CpG methylation signature might be a potential prognostic indicator to facilitate individualized survival prediction for CRC patients.

Diagnostic markers for both colorectal cancer (CRC) and its precursor lesions are lacking. Although aberrant methylation of the secretin receptor (SCTR) gene was observed in CRC, the diagnostic performance has not been evaluated. Therefore, this study aimed to assess and verify the diagnostic value of SCTR methylation of CRC and its precursor lesions through integrating the largest methylation data. The diagnostic performance of SCTR methylation was analyzed in the discovery set from The Cancer Genome Atlas (TCGA) CRC methylation data (N = 440), and verified in a large‐scale test set (N = 938) from the Gene Expression Omnibus (GEO). Targeted bisulfite sequencing analysis was developed and applied to detect the methylation status of SCTR in our independent validation set (N = 374). Our findings revealed that the SCTR gene was frequently hypermethylated at its CpG islands in CRC. In the TCGA discovery set, the diagnostic score was constructed using 4 CpG sites (cg01013590, cg20505223, cg07176264, and cg26009192) and achieved high diagnostic performance (area under the ROC curve [AUC] = 0.964). In the GEO test set, the diagnostic score had robust diagnostic ability to distinguish CRC (AUC = 0.948) and its precursor lesions (AUC = 0.954) from normal samples. Moreover, hypermethylation of the SCTR gene was also found in cell‐free DNA samples collected from CRC patients, but not in those from healthy controls. In the validation set, consistent results were observed using the targeted bisulfite sequencing array. Our study highlights that hypermethylation at CpG islands of the SCTR gene is a potential diagnostic biomarker in CRCs and its precursor lesions.

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A recent study has reported that tsukushi ( TSKU ) may be related to the development of lung cancer. However, few studies focused on if TSKU associated with the prognosis and immune infiltration cells in non-small cell lung cancer (NSCLC). The effect of TSKU expression on prognosis with NSCLC was analyzed in the PrognoScan database and validated in The Cancer Genome Atlas. The composition of tumor infiltrating cells was quantified by methylation and expression data. We combined levels of tumor infiltrating cells with TSKU to evaluate the survival of patients. The analysis of a cohort (GSE31210, N=204) of lung cancer patients demonstrated that high TSKU expression was strongly associated with poor overall survival ( P =1.90E-05). The combination of high TSKU expression and low infiltration B cells identified a subtype of patients with poor survival in NSCLC. Besides, the proportion of B cells in NSCLC patients with TSKU hypermethylation were higher than those patients with TSKU hypomethylation ( P <0.001). Overall, high TSKU expression combined with low infiltration of B cells may associate with a poor prognosis of NSCLC patients. TSKU might be a potential prognostic biomarker involved in tumor immune infiltration in NSCLC.