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ObjectivesThe prevalence of childhood hypertension is rising in parallel with the increasing prevalence of overweight and obesity in children. How growth trajectories from childhood to puberty relate to high blood pressure (HBP) is not well defined. We aimed to characterise potential body mass index (BMI) dynamic changing trajectories from childhood to puberty and investigate their association with HBP.DesignA dynamic prospective cohort.SettingChina Health and Nutrition Survey 1991–2015.ParticipantsThere were 1907 participants (1027 men and 880 women) in this study.OutcomesThe primary outcome was HBP defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) exceeding the standards or diagnosis by medical records or taking antihypertensive medication.ResultsA model of cubic parameters with three groups was chosen, labelled as normal increasing group (85.16%, n=1624), high increasing group (9.81%, n=187) and resolving group (5.03%, n=96). Compared with the normal increasing group, the unadjusted HRs (95% CIs) for the resolving and high increasing groups were 0.91 (0.45 to 1.86) and 1.88 (1.26 to 2.81), respectively. After adjusting for baseline age, region, sex, baseline BMI z-score, baseline SBP and baseline DBP in model 3, the HRs (95% CIs) for the resolving and high increasing groups were 0.66 (0.30 to 1.45) and 1.56 (1.02 to 2.38).ConclusionsThese results indicate that the BMI trajectories from childhood to puberty have significant impact on HBP risk. Puberty is a crucial period for the development of HBP.

ObjectiveThe important contribution of dietary triggers to migraine pathogenesis has been recognized. However, the potential causal roles of many dietary habits on the risk of migraine in the whole population are still under debate. The objective of this study was to determine the potential causal association between dietary habits and the risk of migraine (and its subtypes) development, as well as the possible mediator roles of migraine risk factors.MethodsBased on summary statistics from large-scale genome-wide association studies, we conducted two-sample Mendelian randomization (MR) and bidirectional MR to investigate the potential causal associations between 83 dietary habits and migraine and its subtypes, and network MR was performed to explore the possible mediator roles of 8 migraine risk factors.ResultsAfter correcting for multiple testing, we found evidence for associations of genetically predicted coffee, cheese, oily fish, alcohol (red wine), raw vegetables, muesli, and wholemeal/wholegrain bread intake with decreased risk of migraine, those odds ratios ranged from 0.78 (95% CI: 0.63–0.95) for overall cheese intake to 0.61 (95% CI: 0.47–0.80) for drinks usually with meals among current drinkers (yes + it varies vs. no); while white bread, cornflakes/frosties, and poultry intake were positively associated with the risk of migraine. Additionally, genetic liability to white bread, wholemeal/wholegrain bread, muesli, alcohol (red wine), cheese, and oily fish intake were associated with a higher risk of insomnia and (or) major depression disorder (MDD), each of them may act as a mediator in the pathway from several dietary habits to migraine. Finally, we found evidence of a negative association between genetically predicted migraine and drinking types, and positive association between migraine and cups of tea per day.SignificanceOur study provides evidence about association between dietary habits and the risk of migraine and demonstrates that some associations are partly mediated through one or both insomnia and MDD. These results provide new insights for further nutritional interventions for migraine prevention.

Background Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear. Method We searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al. Results Thirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy. Conclusions The findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations.

Purpose We aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them. Methods The main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses. Results Results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64–0.84; p -value < 0.001). This finding was consistent with the results of the sensitivity analyses. Physical activities can help improve the protective effect of education against breast cancer, with relatively large mediation proportions. Education increases the risk of ER-positive breast cancer due to alterations in high-density lipoprotein level, triglyceride level, height, waist-to-hip ratio, body mass index, and smoking status, with relative medium mediation proportions. Other mediators including low-density lipoprotein, hip circumference, number of cigarettes smoked per day, time spent performing light physical activity, and performing vigorous physical activity for > 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%. Conclusion A low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.

Background: Dietary habit plays an important role in the composition and function of gut microbiota which possibly manipulates host eating behavior. Gut microflora and nutritional imbalance are associated with telomere length (TL). However, the causality among them remains unclear. Methods: Firstly, we calculate the significance threshold based on genetic correlations. Then we perform bi-directional Mendelian Randomization (MR) analyses among 82 food intakes (FIs) (UK Biobank, N=455,146), 95 gut microbial traits (Flemish Gut Flora Project, N=2,223) and TL (genome-wide meta-analysis from 15 cohorts, N=37,684) using summary-level data from large genome-wide association studies. Fixed-effect inverse variance weighting is the main analysis method and the other eight two-sample MR methods and three sensitivity analyses are performed. Finally, GO enrichment analyses are used to investigate the bio-function. Results: Several bi-directional causal relationships among gut microbiota, FIs and TL are obtained by two-sample MR. Overall, we find suggestive evidence of three main causal pathways among them. Drinking more glasses of water per day is able to affect the habit of eating dried fruit through the host gut microbiota (Barnesiella). The change of one gut microbiota taxon (Collinsella) in the host causally influences another gut microbiota taxon (Lactonccus) through the diet habits (intake of oil-based spread). Additionally, the TL alters the habits of drinking ground coffee and further affects the gut microbiota (Acidaminococcaceae). GO enrichment analysis further confirmed the MR results. Conclusion: TL has an impact on diet habits and gut microbiota and there are bi-directional relationships between diet habits and gut microbiota.

Background: Dietary habit plays an important role in the composition and function of gut microbiota which possibly manipulates host eating behavior. Gut microflora and nutritional imbalance are associated with telomere length (TL). However, the causality among them remains unclear. We aim to explore the causal pathways among gut microbiota, food intake (FI) and TL. Results: Firstly, we calculate the significance threshold based on genetic correlations.Then we perform bi-directional Mendelian Randomization (MR) analyses among 82 FIs (UK Biobank, N=455,146), 95 gut microbial traits (Flemish Gut Flora Project, N=2,223) and TL (genome-wide meta-analysis from 15 cohorts, N=37,684) using summary-level data from large genome-wide association studies. Fixed-effect inverse variance weighting is the main analysis method and the other eight two-sample MR methods and three sensitivity analyses are performed. Several bi-directional causal relationships among gut microbiota, FIs and TL are obtained by two-sample MR. Overall, we find suggestive evidence of three main causal pathways among them. Drinking more glasses of water per day is able to affect the habit of eating dried fruit through the host gut microbiota (Barnesiella). The change of one gut microbiota taxon (Collinsella) in the host causally influences another gut microbiota taxon (Lactonccus) through the diet habits (intake of oil-based spread). Additionally, the TL alters the habits of drinking ground coffee and further affects the gut microbiota (Acidaminococcaceae). Finally, GO enrichment analyses are used to investigate the bio-function and confirm the MR results. Conclusions: TL has an impact on diet habits and gut microbiota and there are bi-directional relationships between diet habits and gut microbiota.