Scope: Dietary advanced glycation products (dAGEs) have been reported to induce cognitive impairment while quercetin possesses potential neuroprotective effects. The aim is to explore whether dAGEs would induce similar cognitive impairment from both young and aged ICR mice, and the protective effects of quercetin. Methods and results: A total of 32 aged ICR mice (15-month-old) and 16 young ICR mice (3-month-old) are randomly assigned into the following six groups: Young mice control group, young mice fed with AGEs diet group, old mice control group, old mice fed with AGEs diet group, old mice with quercetin supplemented diet group, old mice fed with AGE diet supplemented with quercetin group. Dietary AGEs induced cognitive impairment only in aged, but not in young, ICR mice, while quercetin intervention is capable of reversing dAGEs-induced cognitive dysfunction. This may be since quercetin 1) increased miR-219, miR-15a, and miR-132 expression, inhibited p-ERK1/2, and tau phosphorylation; and 2) improved gut microbiota richness and diversity, inhibited phylum Tenericutes and Proteobacteria, and elevated butyric acid from cecum. Conclusion: Prolonged application of quercetin may be beneficial in the elderly, especially for those with high consumption of dAGEs.

Scope To explore how quercetin will affect memory impairments in APP/PS1 mice under different vitamin D status. Methods and results APP/PS1 mice are divided into four groups, i.e., control (CON), low (LVD), medium, and high vitamin D supplemented with quercetin. During Morris Water Maze test, mice of the LVD group function best for improving cognitive function demonstrated by reduced latency to platform, and increased number of crossing and swimming distance in the target quadrant. Compared to the CON group, in both hippocampus and cortex, the LVD group has significant reduction in Aβ plaques, p‐Tau at Ser396&Ser404, and neuroinflammation. In the hippocampus, BDNF is elevated, miR‐26a and miR‐125b is decreased, while miR‐132 is increased in the LVD group. The LVD group demonstrates increased gut microbial diversity and elevated relative abundance of Glutamicibacter, Facklamia and Aerocorrus. In the hippocampus, p‐Tau at ser396&404, GFAP, Ibα1, miR‐26a, and miR‐132 are negatively correlated with Aerococcus; and p‐Tau at ser404 and Ibα1 are negatively correlated with Facklamia. Conclusion Quercetin is more efficacious for improving cognitive function under low vitamin D status. This might be owing to that interventions reduce Aβ plaques, tau phosphorylation, and neuroinflammation, upregulate BDNF, reduce miR‐26a and miR‐125b, increase miR‐132, and elevate gut microbial diversity including Facklamia and Aerococcus.

Dietary advanced glycation end products (dAGEs) might be potential toxins involved in the pathogenesis of Alzheimer’s disease (AD). Quercetin is a flavonoid possessing neuroprotective effects. We aimed to explore whether a 21 days of dAGEs intake would result in cognitive dysfunction in aged ICR mice, and the protective effects of quercetin, with potential mechanisms explored. Fourteen‐month old ICR mice were randomly assigned into four groups, that is, Control, AGEs, quercetin, and AGE diet supplemented with quercetin. Key markers involved in Aβ, tau, and neuroinflammation from hippocampus and cortex were measured via western blot. Gut microbiota and short chain fatty acids profiles from intestinal contents were measured via 16S rRNA gene sequencing and gas chromatography (GC), respectively. Quercetin alleviated cognitive impairment induced by dAGEs in aged mice. This might be associated with that quercetin reduced cathepsin B, tau phosphorylation, and neuroinflammation, and elevated α‐diversity index (ACE, Chao1, and Shannon index), and reduced phylum Verrucomicrobia of gut microbiota. Practical applications Alzheimer’s disease (AD) has been regarded as the commonest cause of progressive dementia for the elderly. This study is the very first to demonstrate that even a short‐term dietary advanced glycation end product (dAGEs) intake induced impaired cognitive function in aged ICR mice, and querectin is capable of reversing dAGEs‐induced cognitive dysfunction. Reduced tau phosphorylation, neuroinflammation, and altered gut microbiota profiles may be involved in querectin’s protective effects against dAGEs‐induced cognitive impairment. Our study suggested that quercetin supplementation might be beneficial for improving cognitive function in elderly subjects with high consumption of dAGEs such as grilling, frying, and broiling of food.

Objectives To investigate the pooled prevalence of cerebral palsy in China, analyse the differences between different subgroups, and explore the trend over the 32-year period from 1988 to 2020. Methods All potential studies related to the prevalence of cerebral palsy among children and adolescents in China were identified from 3 English-language databases and 4 Chinese-language databases. Pooled prevalence was calculated to estimate the prevalence of cerebral palsy among 0-18 years old and different geographical regions in China, using a random-effects meta-analysis model. Continuous fractional polynomial regression modelling was used to estimate the trend in prevalence of cerebral palsy over time. Subgroup analysis and meta-regression were conducted to investigate heterogeneity. Funnel plots and Egger’s test were used to explore potential publication bias. Results The pooled prevalence of cerebral palsy over the study period among 0–18 years old and different geographical regions in China was 2.07‰ (95% confidence interval (95% CI) 1.66–2.47‰), and the prevalence of cerebral palsy was higher in males compared with females (2.25‰ vs 1.59‰), and in rural residents compared with urban residents (2.75‰ vs 1.90‰), respectively. The prevalence of cerebral palsy varied significantly between different geographical regions. In subjects with birthweights < 2.5 and > 4 kg, the prevalence of cerebral palsy was significantly higher than in subjects with birthweights between 2.5 and 4 kg. The trend in pooled prevalence of cerebral palsy increased continuously over the period studied, and could be divided into 3 stages; the mean annual increase in prevalence from 1988 to 1996 and from 2008 to 2019 was more rapid. Multivariate meta-regression found that the year of study was one of the sources of heterogeneity among overall prevalence. ( p -value = 0.006). Conclusion The pooled prevalence of cerebral palsy over the 32-year period from 1988 to 2020 was 2.07‰. There was an increasing trend in prevalence of cerebral palsy among children and adolescents in China over this period. LAY ABSTRACT There are few reports regarding trends in childhood cerebral palsy in China over the past 30 years. This study searched and statistically analysed all potentially relevant studies regarding cerebral palsy. The trend in childhood cerebral palsy in China increased continuously over the period studied, and could be subdivided into 3 stages. From 1988 to 1996, and from 2008 to 2019, the mean annual increase in prevalence was more rapid than for the other years studied. Counter-measures, such as health monitoring and management of infants and young children, are recommended to reduce the prevalence of childhood cerebral palsy in China.

Although observational studies have shown positive associations between body mass index (BMI) and the risk of atrial fibrillation (AF), the causal relationship is still uncertain owing to the susceptibility to confounding and reverse causation. This study aimed to examine the potential causality of BMI on AF by conducting a two-sample Mendelian randomization (TSMR) study. Methods: The independent genetic variants associated with BMI (n = 303) at the genome-wide significant level were derived as instrumental variables (IV) from the Genetic Investigation of Anthropometric Traits (GIANT) consortium consisting of 681,275 individuals of European ancestry. We then derived the outcome data from a GWAS meta-analysis comprised of 60,620 cases and 970,216 controls of European ancestry. The TSMR analyses were performed in five methods, namely inverse variance weighted (IVW) method, MR-Egger regression, the weighted median estimator (WME), the generalized summary data-based Mendelian randomization (GSMR), and the robust adjusted profile score (RAPS), to investigate whether BMI was causally associated with the risk of AF. Results: We found a genetically determined 1–standard deviation (SD) increment of BMI causally increased a 42.5% risk of AF (OR = 1.425; 95% CI, 1.346 to 1.509) based on the IVW method, which was consistent with the results of MR-Egger regression, WME, GSMR, as well as RAPS. The Mendelian randomization assumptions did not seem to be violated. Conclusion: This study provides evidence that higher BMI causally increased the risk of AF, suggesting control of BMI and obesity for prevention of AF.

We performed univariable and multivariable Mendelian randomization (MR) analysis to evaluate the association between blood lipids and risk of atrial fibrillation (AF), including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), Apolipoprotein A1, and Apolipoprotein B. Methods: Data on the single nucleotide polymorphisms (SNPs) related to blood lipids were obtained from the UK Biobank study with more than 300,000 subjects of White British European ancestry, and data for AF were from the latest meta-analysis of Genome-wide association study (GWASs) with six independent cohorts with more than 1,000,000 subjects of European ancestry. The univariable MR analysis was conducted to explore whether genetic evidence of individual lipid-related traits was significantly associated with AF risks and multivariable MR analysis with three models was performed to assess the independent effects of lipid-related traits. Results: The IVW estimate showed that genetically predicted LDL-C (OR: 1.016, 95% CI: 0.962–1.073, p = 0.560), HDL-C (OR: 0.951, 95% CI: 0.895–1.010, p = 0.102), TG (OR: 0.961, 95% CI: 0.889–1.038, p = 0.313), Apolipoprotein A1 (OR: 0.978, 95% CI: 0.933–1.025, p = 0.356), and Apolipoprotein B (OR: 1.008, 95% CI: 0.959–1.070, p = 0.794) were not causally associated with the risk of AF. Sample mode (OR: 0.852, 95% CI: 0.731–0.993, p = 0.043) and weighted mode (OR: 0.907, 95% CI: 0.841–0.979, p = 0.013) showed that a 1-unit increase in TG (mmol/L) was causally associated with a 14.8% and 9.3% relative decrease in AF risk, respectively. The multivariable MR analysis with model 1, 2, and 3 indicated that TG, LDL-C, HDL-C, Apolipoprotein A1, and Apolipoprotein B were not associated with the lower risk for AF. Conclusions: Our multivariable Mendelian randomization analysis (MVMR) finding suggested no genetic evidence of lipid traits was significantly associated with AF risk. Furthermore, more work is warranted to confirm the potential association between lipid traits and AF risks.

BACKGROUND The increased stroke risk associated with atrial fibrillation (AF) burden exceeding 5 min is a matter of debate. In addition, the potential linear or nonlinear relationship between AF burden and stroke risk has been largely unexplored. AIM To determine the association between AF burden > 5 min and the increased risk of stroke and explore the potential dose-response relationship between these two factors. METHODS Sixteen studies from six databases with 53141 subjects (mean age 65 years) were included. Fifteen studies were observational studies, and one was a randomized controlled trial study. The potential nonlinear dose-response association was characterized using a restricted cubic splines regression model. AF burden for each 1 h and 2 h was associated with an increased risk of stroke. Trial sequential analysis with a random-effect model was used to evaluate the robustness of the evidence from the included 16 studies. RESULTS AF burden > 5 min was associated with an increased risk of clinical AF [adjusted risk ratio (RR) = 4.18, 95% confidence interval (CI): 2.26-7.74]. However, no association was found with an increased risk of all-cause mortality (adjusted RR = 1.55, 95%CI: 0.87-2.75). Patients with AF burden > 5 min had an increased risk of stroke (adjusted RR = 2.49, 95%CI: 1.79-3.47). Moreover, a dose-response analysis showed that the increased stroke risk was paralleled by an increase in AF burden at a rate of 2.0% per hour ( P nonlinear = 0.656, RR = 1.02, 95%CI: 1.01-1.03). Trial sequential analysis provided robust evidence of the association between AF burden > 5 min and an increased risk of stroke. CONCLUSION AF burden was a significant risk factor for clinical AF and future stroke. A significant linear association was documented between increased AF burden and risk of future stroke.

Adipose tissue is a key organ with substantial senescent cell accumulation under both obesity and aging conditions. Chia seed is an ancient seed and is the richest plant source of α-linolenic acid. We aimed to determine how cellular senescence markers will be altered in adipose tissue of senescence-accelerated mouse-prone 8 (SAMP8) mice fed with high-fat diets (HFDs); and how chia seed can affect the above markers. SAMP8 mice and their control senescence-accelerated mouse-resistant 1 (SAMR1) were divided into four groups, that is, SAMR1 low-fat diet group (R1LF), SAMP8LF group (P8LF), SAMP8 high-fat group (P8HF), and SAMP8HF group supplemented with 10% chia seed (P8HC). At the end of the intervention, body composition was measured through T-weighted magnetic resonance imaging, and epididymal (EPI) and subcutaneous (SC) adipose tissues were dissected for further analysis. Compared with the R1LF group, the P8HF and P8HC groups had significantly increased body fat mass. In EPI fat, p16, CD68 and PAI-1 mRNA expression from P8HF group were significantly increased; chia seed partially reduced p16 and CD68 mRNA expression. The P8LF group has increased p16 and CD68, and the P8HF group has increased p16, p21, and CD68; and P8HC group has increased p16 mRNA expression. The protein expression of p-AMPK in EPI and SC fat from the P8HF group was reduced. In conclusion, reductions in AMPK activity might be partially responsible for elevation in HFD-induced senescence markers in both EPI and SC fat, and chia seed supplementation is able to reduce senescence-associated markers at least in EPI adipose tissue.