Association between ideal cardiovascular health and abnormal glucose metabolism in the elderly: evidence based on real-world data.

BACKGROUND: Limited information is available on the effect of ideal cardiovascular health (CVH) and abnormal glucose metabolism in elderly people. We aimed to analyze the prevalence of CVH behaviors, abnormal glucose metabolism, and their correlation in 65 and older people. METHODS: In this study, randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used. Recruiting was carried out between January 2020 and December 2020, and 1984 participants aged 65 years or older completed the study. RESULTS: The prevalence of abnormal glucose metabolism in this group was 26.7% (n = 529), among which the prevalence of impaired fasting glucose (IFG) was 9.5% (male vs. female: 8.7% vs 10.1%, P = 0.338), and the prevalence of type 2 diabetes mellitus (T2DM) was 19.0% (male vs. female: 17.8 vs. 19.8%, P = 0.256). The ideal CVH rate (number of ideal CVH metrics ≥ 5) was only 21.0%. The risk of IFG and T2DM decreased by 23% and 20% with each increase in one ideal CVH metrics, with OR (95%CI) of 0.77(0.65-0.92) and 0.80(0.71-0.90), respectively (P -trend < 0.001). TyG fully mediated the ideal CVH and the incidence of T2DM, and its mediating effect OR (95%CI) was 0.88(0.84-0.91). CONCLUSIONS: Each increase in an ideal CVH measure may effectively reduce the risk of abnormal glucose metabolism by more than 20%.

Identification and precision therapy for three maturity-onset diabetes of the young (MODY) families caused by mutations in the HNF4A gene.

Background: Heterozygous pathogenic variants in HNF4A gene cause maturity-onset diabetes of the young type 1 (MODY1). The mutation carriers for MODY1 have been reported to be relatively rare, in contrast to the most frequently reported forms of MODY2 and MODY3. Methods: Whole exome sequencing (WES) and Sanger sequencing were performed for genetic analysis of MODY pedigrees. Tertiary structures of the mutated proteins were predicted using PyMOL software. Results: Three heterozygous missense mutations in the HNF4A gene, I159T, W179C, and D260N, were identified in the probands of three unrelated MODY families using WES, one of which (W179C) was novel. Cascade genetic screening revealed that the mutations co-segregated with hyperglycemic phenotypes in their families. The molecular diagnosis of MODY1 has partly transformed its management in clinical practice and improved glycemic control. The proband in family A successfully converted to sulfonylureas and achieved good glycemic control. Proband B responded well to metformin combined with diet therapy because of his higher body mass index (BMI). The proband in family C, with paternal-derived mutations, had markedly defective pancreatic ß-cell function due to the superposition effect of T2DM susceptibility genes from the maternal grandfather, and he is currently treated with insulin. In silico analysis using PyMOL showed that the I159T and D260N mutations altered polar interactions with the surrounding residues, and W179C resulted in a smaller side chain. Discussion: We identified three heterozygous missense mutations of HNF4A from Chinese MODY families. Structural alterations in these mutations may lead to defects in protein function, further contributing to the hyperglycemic phenotype of mutation carriers.

Age at first birth and risk of urinary incontinence after delivery: a dose-response meta-analysis.

Studies investigating the impact of age at first birth on urinary incontinence after delivery have reached inconsistent conclusions. We performed this systematic review and meta-analysis of studies assessing the risk of urinary incontinence after delivery, regardless of the type, with age at first birth. MEDLINE via PubMed and Web of science databases were searched up to March 13, 2021. Restricted cubic splines were used to model the dose-response association. Twelve publications were included in this meta-analysis. The summary odds ratio (OR) and 95% confidence interval (CI) per 1-year increase in age at first birth were 1.01 (95% CI (0.99, 1.02)) for urinary incontinence (America: 1.00 (0.99, 1.00); Europe: 1.03 (1.00, 1.06); Asian: 0.99 (0.89, 1.10)). A non-linear dose-response (Pnonlinearity < 0.01) indicated that age at first birth older than 32 (P < 0.05) increases the risk of urinary incontinence. First birth before age 32 make decrease the risk of urinary incontinence after delivery.

The top 5 causes of death in China from 2000 to 2017.

Limited information is available on the epidemiological characteristics of major causes of death in the last 18 years. In this study, we investigated the epidemiological characteristics of the top 5 causes of death in China from 2000 to 2017. Data were obtained from the 18-year reports of Ministry of Health and analyzed by Grid Search Method, Permutation test, and log-linear regression model. The top 5 consistent causes of death, malignant tumor, cerebrovascular disease, heart trouble, respiratory disease, trauma and toxicosis accounted for 82.6% in 2000, 86.49% in 2017 in urban areas and 83.31% in 2000, 88.34% in 2017 in rural areas. The increasing trends (P < 0.05) of proportions of death of malignant tumor, cerebrovascular disease, and heart trouble have average annual percent change (AAPC) = 0.5%, 0.3%, 2.4% in urban areas and 1.7%, 1.5%, 4.3% in rural areas. The AAPCs of respiratory disease are - 1.4% in urban areas and - 3.6% in rural areas. Cardio-cerebrovascular disease increased (Urban: 39.02% to 43.56%, AAPC = 1.3%, P < 0.05; Rural: 32.03% to 45.91%, AAPC = 2.7%, P < 0.05) steeply from 2000 to 2017 which are higher than that of malignant tumor (P < 0.05). The top 5 causes of death in China accounted for more than 85% of all deaths in 2017, in which cardio-cerebrovascular disease accounted for the largest proportion with the steepest increasing trend.

Identification of recombination in novel goose parvovirus isolated from domesticated Jing-Xi partridge ducks in South China.

Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. This rapidly spreading, infectious disease affects ducks in particular, with a high morbidity and low mortality rate, causing huge economic losses. This study analyzed the evolution of NGPV isolated from Jing-Xi partridge duck with SBDS in South China. Complete genome sequences of the NGPV strains GDQY1802 and GDSG1901 were homologous with other GPV/NGPV and Muscovy duck parvovirus (MDPV) strains. Phylogenetic analysis showed that the NGPV isolated from mainland China was related to the Taiwan 82-0321v strain of GPV. In contrast to 82-0321v and the SDLC01 strain, which was first isolated from China, the two isolates showed no deletions in the inverted terminal repeat (ITR) region. Further, in these isolates, 24 amino acid sites of the replication protein were different compared to that of GPV live vaccine strain 82-0321v, and 12 sites were unique across all NGPV isolates. These isolates also showed differences in 17 amino acid sites of the capsid protein from that of 82-0321v, two of which were the same as those in MDPV. Recombination analysis identified the major parents of GDSG1901 and GDQY1802 as the NGPV-GD and NGPV-Hun18 strains, and the minor parents as the classical GPV 06-0329 and GPV LH strains, respectively. GDQY1802 and GDSG1901 are recombinant GPV-related parvovirus isolated from domesticated partridge duck. Recombination is evident in the evolution of NGPV, and as such, the use of live attenuated vaccines for NGPV requires further study.

Relationship between age at menarche and risk of glucose metabolism disorder: a systematic review and dose-response meta-analysis.

OBJECTIVE: Studies investigating the impact of age at menarche on glucose metabolism disorder have reached inconsistent conclusions, and a quantitative comprehensive assessment of the dose-response association between age at menarche and glucose metabolism disorder has not been reported. We performed a systematic review and meta-analysis of studies assessing the risk of glucose metabolism disorder by age at menarche. METHODS: MEDLINE via PubMed and EMBASE databases were searched up to March 13, 2019. Restricted cubic splines were used to model the dose-response association. RESULTS: Twenty-five publications (including 34 studies) were included in the meta-analysis. The summary risk ratios (RRs) and 95% confidence limit (CL) per 1-year increase in age at menarche were 0.98 (95% CL 0.98, 0.99) for type 2 diabetes mellitus (T2DM), 0.97 (95% CL 0.96, 0.99) for impaired fasting glucose (IFG), and 0.98 (95% CL 0.97, 0.99) for gestational diabetes mellitus (GDM). We identified linear negative correlations between age at menarche and T2DM (Pnonlinearity = 0.052) and IFG (Pnonlinearity = 0.145), a nonlinear dose-response between age at menarche and GDM (Pnonlinearity = 0.038). CONCLUSIONS: Older age at menarche (range 8-18 years old) is associated with reduced risk of glucose metabolism disorder. The strongest reduction in risk of GDM is observed at menarche age of 14.5 years.

Thermodynamic Basis of Selectivity in the Interactions of Tissue Inhibitors of Metalloproteinases N-domains with Matrix Metalloproteinases-1, -3, and -14.

The four tissue inhibitors of metalloproteinases (TIMPs) are potent inhibitors of the many matrixins (MMPs), except that TIMP1 weakly inhibits some MMPs, including MMP14. The broad-spectrum inhibition of MMPs by TIMPs and their N-domains (NTIMPs) is consistent with the previous isothermal titration calorimetric finding that their interactions are entropy-driven but differ in contributions from solvent and conformational entropy (ΔSsolv, ΔSconf), estimated using heat capacity changes (ΔCp). Selective engineered NTIMPs have potential applications for treating MMP-related diseases, including cancer and cardiomyopathy. Here we report isothermal titration calorimetric studies of the effects of selectivity-modifying mutations in NTIMP1 and NTIMP2 on the thermodynamics of their interactions with MMP1, MMP3, and MMP14. The weak inhibition of MMP14 by NTIMP1 reflects a large conformational entropy penalty for binding. The T98L mutation, peripheral to the NTIMP1 reactive site, enhances binding by increasing ΔSsolv but also reduces ΔSconf However, the same mutation increases NTIMP1 binding to MMP3 in an interaction that has an unusual positive ΔCp This indicates a decrease in solvent entropy compensated by increased conformational entropy, possibly reflecting interactions involving alternative conformers. The NTIMP2 mutant, S2D/S4A is a selective MMP1 inhibitor through electrostatic effects of a unique MMP-1 arginine. Asp-2 increases reactive site polarity, reducing ΔCp, but increases conformational entropy to maintain strong binding to MMP1. There is a strong negative correlation between ΔSsolv and ΔSconf for all characterized interactions, but the data for each MMP have characteristic ranges, reflecting intrinsic differences in the structures and dynamics of their free and inhibitor-bound forms.