Dongdong Zhang

Alzheimer’s disease (AD) is characterized by the deposition of senile plaques (SPs) and the formation of neurofibrillary tangles (NTFs), as well as neuronal dysfunctions in the brain, but in fact, patients have shown a sustained disease progression for at least 10 to 15 years before these pathologic biomarkers can be detected. Consequently, as the most common chronic neurological disease in the elderly, the challenge of AD treatment is that it is short of effective biomarkers for early diagnosis. The protein quality control system is a collection of cellular pathways that can recognize damaged proteins and thereby modulate their turnover. Abundant evidence indicates that the accumulation of abnormal proteins in AD is closely related to the dysfunction of the protein quality control system. In particular, it is the synthesis, degradation, and removal of essential biological components that have already changed in the early stage of AD, which further encourages us to pay more attention to the protein quality control system. The review mainly focuses on the endoplasmic reticulum system (ERS), autophagy–lysosome system (ALS) and the ubiquitin–proteasome system (UPS), and deeply discusses the relationship between the protein quality control system and the abnormal proteins of AD, which can not only help us to understand how and why the complex regulatory system becomes malfunctional during AD progression, but also provide more novel therapeutic strategies to prevent the development of AD.

Clinical research results of vitamin D supplementation in the improvement of prediabetes remain controversial. Accordingly, a literature search was conducted of PubMed, Embase (Ovid), and Web of Science prior to 9 November 2021. Randomized controlled studies reported that the following indicators were included: body mass index (BMI), fasting blood glucose (FBG), 2 h oral glucose tolerance test plasma glucose (2h-PG), hemoglobin A1c (HbA1c), insulin resistance by homeostasis model assessment (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-B), and fasting insulin (FINS). Twenty-nine articles (N = 3792) were included in the present meta-analysis. Intriguingly, vitamin D supplementation resulted in a vast improvement in FBG (standardized mean difference (SMD) = −0.38; 95%CI: −0.59, −0.16), HbA1c (SMD = −0.14; 95%CI: −0.22, −0.06) and FINS (SMD = 0.18; 95%CI: −0.26, −0.09), but not in other outcomes. However, preferred changes were observed in subgroups, as follows: Asia (SMD_2h-PG = −0.25, 95%CI: −0.45, −0.04), study duration ≥1 year (SMD_HOMA-IR = −0.44, 95%CI: −0.81, −0.06) (SMD_HOMA-B = 0.34, 95%CI: 0.01, 0.66), baseline 25(OH)D < 50 nmol/L (SMD_2h-PG = −0.23, 95%CI: −0.39, −0.06), and baseline 25(OH)D ≥ 50 nmol/L (SMD_HOMA-IR = −0.50, 95%CI: −0.96, −0.03). In conclusion, oral supplementation of vitamin D has shown better effects in improving FBG, HbA1c, and FINS compared with controls among prediabetics; long-term vitamin D supplementation could have additional effects in participants with vitamin D deficiency for 2h-PG, HOMA-IR, and HOMA-B.

The present study aimed to explore the association between dietary patterns in abdominal obesity obtained by reduced-rank regression (RRR) with visceral fat index (VFI) as a dependent variable and dyslipidemia in rural adults in Henan, China. A total of 29538 people aged 18–79 were selected from the Henan Rural Cohort Study. RRR analysis was used to identify dietary patterns; logistic regression analysis and restricted cubic spline regression models were applied to analyze the association between dietary patterns in abdominal obesity and dyslipidemia. VFI was used as a mediator to estimate the mediation effect. The dietary pattern in abdominal obesity was characterized by high carbohydrate and red meat intake and low consumption of fresh fruits, vegetables, milk, etc. After full adjustment, the highest quartile of dietary pattern scores was significantly associated with an increased risk of dyslipidemia (OR: 1·33, 95 % CI 1·23–1·44, P_trend < 0·001), there was a non-linear dose–response relationship between them (P_{overall-association} < 0·001, P_{non-lin-association} = 0·022). The result was similar in dose-response between the dietary pattern scores and VFI. The indirect effect partially mediated by VFI was significant (OR: 1·07, 95 % CI 1·06–1·08). VIF explained approximately 53·3 % of odds of dyslipidemia related to the dietary pattern. Abdominal obesity dietary pattern scores positively affected VFI and dyslipidemia; there was a dose-response in both relationships. Dyslipidemia progression increased with higher abdominal obesity dietary pattern scores. In addition, VFI played a partial mediating role in relationship between abdominal obesity dietary pattern and dyslipidemia.

Evidence shows that low serum vitamin D concentrations account for an increased risk of obesity by inducing vitamin D receptor (VDR) hypofunction. Although the correlation between single nucleotide polymorphisms (SNPs) of VDR gene and obesity-related anthropometric measures (such as body mass index [BMI] and waist circumference[WC]) has already been tested, there are only few studies on the association between direct measures of body fat percentage (BFP) and triceps skinfold thickness and the SNPs of VDR. The aim of the present study was to evaluate the effect of VDR gene polymorphism on multiple obesity indexes in Han Chinese, including BMI, WC, BFP and triceps skinfold thickness. In this cross-sectional study, five hundred and seventeen healthy Chinese adults were enrolled in the trial. Four loci in VDR gene (rs2228570 [FokI], rs2189480, rs2239179 and rs7975232[ApaI]) were genotyped by TaqMan probe assays. Obesity indexes including BMI, WC, BFP and triceps skinfold thickness were used to evaluate the relationship to the VDR SNPs. Multiple logistic regression, linear regression and general multifactor dimensionality reduction (GMDR) were performed to analyze the correlation of VDR gene and obesity indexes. None of the VDR SNPs were associated with BMI and WC, the C allele of FokI and the T allele of ApaI were associated with an increase in BFP (β = 0.069,P = 0.007; β = 0.087, P = 0.022 respectively); the G allele of rs2239179 and the T allele of ApaI were associated with an increase in triceps skin fold thickness (β = 0.074, P = 0.001; β = 0.122, P < 0.001 respectively). In regards to adiposity-related metabolic parameters, we found that the GT genotype of ApaI was associated with higher level of total cholesterol (TC) (P = 0.013) and Low-density lipoprotein cholesterol (LDL-C) (P = 0.001). Though we failed to prove that VDR SNPs were in correlation with BMI and WC, we did establish the association between VDR variants and BFP, as well as triceps skinfold thickness. Data obtained suggested that the VDR variants play an important role in regulating adipose tissue activity and adiposity among Han Chinese.

To compare the accuracy of different obesity indexes, including waist circumference (WC), weight-to-height ratio (WHtR), body mass index (BMI), and lipid accumulation product (LAP), in predicting metabolic syndrome (MetS) and to estimate the optimal cutoffs of these indexes in a rural Chinese adult population. This prospective cohort involved 8468 participants who were followed up for 6 years. MetS was defined by the International Diabetes Federation, American Heart Association, and National Heart, Lung, and Blood Institute criteria. The power of the 4 indexes for predicting MetS was estimated by receiver operating characteristic (ROC) curve analysis and optimal cutoffs were determined by the maximum of Youden’s index. As compared with WHtR, BMI, and LAP, WC had the largest area under the ROC curve (AUC) for predicting MetS after adjusting for age, smoking, drinking, physical activity, and education level. The AUCs (95% CIs) for WC, WHtR, BMI, and LAP for men and women were 0.862 (0.851–0.873) and 0.806 (0.794–0.817), 0.832 (0.820–0.843) and 0.789 (0.777–0.801), 0.824 (0.812–0.835) and 0.790 (0.778–0.802), and 0.798 (0.785–0.810) and 0.771 (0.759–0.784), respectively. The optimal cutoffs of WC for men and women were 83.30 and 76.80 cm. Those of WHtR, BMI, and LAP were approximately 0.51 and 0.50, 23.90 and 23.00 kg/m2, and 19.23 and 20.48 cm.mmol/L, respectively. WC as a preferred index over WHtR, BMI, and LAP for predicting MetS in rural Chinese adults of both genders; the optimal cutoffs for men and women were 83.30 and 76.80 cm.

The magnitude of the risk of metabolic syndrome (MetS) with increased resting heart rate (RHR) has been inconsistently reported in some observational studies, and whether a dose–response relationship exists between RHR and MetS is unclear. We performed a meta-analysis including dose–response analysis to quantitatively evaluate this association in adults. We searched PubMed, Web of Knowledge, China National Knowledge Infrastructure, and WanFang databases for articles published up to April 2, 2016. A random-effects model was used to pool relative risks (RRs) and 95% confidence intervals (CIs); restricted cubic spline function was used to assess the dose–response relationship. Seven prospective cohort studies and 10 cross-sectional studies with a total of 169,786 participants were included. The pooled RR was 2.10 (95% CI 1.80–2.46, I ² = 79.8%, n = 13) for the highest versus reference RHR category and 1.28 (95% CI 1.23–1.34, I ² = 87.7%, n = 15) for each 10 beats per minute (bpm) increment in RHR. We found no evidence of a nonlinear dose–response association between RHR and MetS (P _nonlinearity = 0.201). The relationship was consistent in most subgroup analyses and robust on sensitivity analysis. No significant publication bias was observed. This meta-analysis suggests that risk of MetS may be increased with elevated RHR.