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Objectives The association of tea or coffee consumption with gout is inconsistently reported. Few prospective studies have explored their dose–response relationship. Therefore, we aimed to quantitatively investigate the association between tea, coffee and the risk of developing gout. Methods The study included 447 658 participants in the UK Biobank who were initially free of gout. Tea and coffee consumption were assessed at baseline. We used Cox proportional hazards models to estimate the associations between tea/coffee consumption and incident gout, with restricted cubic spline added to the Cox models to evaluate the dose–response relationships. Results During a median follow-up period of 13.42 years, we recorded 3,053 gout cases. The associations between tea, coffee and gout were nonlinear, with a significant reduction in the risk by ∼ six cups/day of tea and three cups/day of coffee. Compared with those who were not tea and coffee drinkers, those who consumed >6 cups/day of tea or coffee were associated with 23% (HR 0.77, 95% CI, 0.66, 0.91) and 40% (HR 0.60, 95% CI, 0.47, 0.77) lower risks of gout, respectively, and both caffeinated and decaffeinated coffee consumption were associated with a decreased risk. Moreover, hyperuricaemia may modify the association between coffee and gout. Compared with non-coffee consumers with hyperuricaemia, those with ≥4 cups/day coffee intake without hyperuricaemia had the lowest risk (HR 0.34, 95% CI, 0.28, 0.41). Conclusion Consumption of tea or coffee had a strong nonlinear association in gout risk reduction. Hyperuricaemia status had a potential effect modification on the association of coffee intake with gout.

DNA methylation plays an important role in the development and etiology of type 2 diabetes; however, few epigenomic studies have been conducted on twins. Herein, a two-stage study was performed to explore the associations between DNA methylation and type 2 diabetes, fasting plasma glucose, and HbA1c. DNA methylation in 316 twin pairs from the Chinese National Twin Registry (CNTR) was measured using Illumina Infinium BeadChips. In the discovery sample, the results revealed that 63 CpG sites and 6 CpG sites were significantly associated with fasting plasma glucose and HbA1c, respectively. In the replication sample, cg19690313 in TXNIP was associated with both fasting plasma glucose (P = 1.23 × 10-17, FDR < 0.001) and HbA1c (P = 2.29 × 10-18, FDR < 0.001). Furthermore, cg04816311, cg08309687, and cg09249494 may provide new insight in the metabolic mechanism of HbA1c. Our study provides solid evidence that cg19690313 on TXNIP correlates with HbA1c and fasting plasma glucose levels.

Background: Teaching assistants (TAs) play an important role in pedagogical practices, and teaching assistant (TA) training has become a critical measure to promote teaching quality and interaction. TAs’ confidence might significantly increase the performance of TAs’ work. However, little evidence paid attention to the TAs’ confidence changes after TA training. Methods: A self-control quasi-experiment was conducted to explore the TAs’ confidence changes before and after TA training. A qualified questionnaire was used to investigate the confidence of the graduate teaching assistants before and after the TA training. Results: A total of 372 TAs from school of basic medicine (N=173), school of pharmacy (N=112), school of public Health (N=69) and other schools (N=18) submitted complete questionnaires. They had a median total confidence score of 88 and 85 before and after the TA training. The total TA confidence score decreased after TA training (PConclusion: TA confidence decreased after TA training. Therefore, in addition to teaching skills training, it is necessary to establish and strengthen TAs’ confidence when designing TA training programs.

We investigated whether lifestyle influences epigenetic aging in 143 monozygotic twin pairs discordant for the combined healthy lifestyle score. Twins were scored for four lifestyle factors as unhealthy or healthy; non-smoker, moderate drinker, adequate fruit and vegetable intake, and sufficient physical activity. The combined healthy lifestyle score was calculated for each participant by summing the binary score for each factor. Individual and co-twin analyses were used to assess the relationship between single or combined lifestyle scores, along with DNA methylation age acceleration (AA) calculated using Horvath’s and Li’s epigenetic clocks, focusing on AA and intrinsic epigenetic age acceleration (IEAA) measures. Compared with the twins that scored no or one healthy lifestyle point, those who scored four healthy lifestyle points had lower Li_IEAA with similar results observed in the co-twin analysis. No significant relationships were found in analyses based on Horvath’s clock, although the direction of correlations was consistent with that determined using Li’s clock. Smoking and drinking did not significantly affect DNA methylation AA; however, physical activity and intake of vegetables and fruits did, although the influence varied depending on the epigenetic clock. Our findings suggest that a healthy lifestyle may be an important way to delay aging and prevent age-related diseases.

Accumulating evidence suggests that an instant exposure to particulate matter (PM) may elevate blood pressure (BP), where cell-adhesion regulatory genes may be involved in the interplay. However, few studies to date critically examined their interaction, and it remained unclear whether these genes modified the association. To assess the association between instant PM exposure and BP, and to examine whether single-nucleotide polymorphisms (SNPs) mapped in four cell adhesion regulatory genes modify the relationship, a cross-sectional study was performed, based on the baseline of an ongoing family-based cohort in Beijing, China. A total of 4418 persons from 2089 families in Northern China were included in the analysis. Four tagged SNPs in cell adhesion regulatory genes were selected among ZFHX3, CXCL12, RASGRP1 and MIR146A. A generalized additive model (GAM) with a Gaussian link was adopted to estimate the change in blood pressure after instant PM

Evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with cardiovascular diseases (CVDs). However, the results are inconsistent, and the causality remains to be established.We aimed to investigate the potential causal relationship between NAFLD and CVDs, including arterial stiffness, coronary artery disease, heart failure, stroke, ischemic stroke and its subtypes using two-sample Mendelian randomization (MR).Genetic instruments were used as proxies for NAFLD. Publicly available summary-level data were obtained from the UK Biobank, the CARDIoGRAMplusC4D Consortium, the MEGASTROKE Consortium, and other consortia. Six complementary MR methods were performed, including inverse variance weighted method (IVW), MR-Egger, weighted median, weighted mode, MR-PRESSO, and MR-RAPS.NAFLD was significantly associated with arterial stiffness (β = 0.04 [95%CI, 0.02-0.06], P = 5.53E-04). Moreover, the results remained consistent and robust in the sensitivity analysis. As for heart failure, the IVW method suggested that NAFLD was significantly associated with heart failure (OR = 1.08, 95%CI: 1.02-1.14, P = 0.005) in the absence of pleiotropy. However, there were no significant associations of NAFLD with coronary artery disease, stroke, ischemic stroke, or any ischemic stroke subtype.The MR study supported the causal effect of NAFLD on arterial stiffness. However, the study did not provide enough evidence suggesting the causal associations of NAFLD with heart failure, coronary artery disease, and any stroke subtypes.

Starting from the transfer characteristics of the DC voltage divider, an equivalent circuit model of each part of the DC voltage divider is constructed. The transfer function of the DC voltage divider is derived at first. Then, its step response dynamic performance is analyzed. Based on PSCAD/EMTDC platform, a UHVDC electromagnetic transient simulation model is constructed. Furthermore, the influence of the transmission characteristics of the DC voltage divider on voltage traveling wave protection is simulated. It shows that when an type I voltage divider is used, the amplitude of the traveling wave criterion of the secondary side of the voltage divider after a fault is reduced, but the protection can still operate correctly; When a type II voltage divider is used, the amplitude of the traveling wave criterion on the secondary side of the voltage divider increases after the fault, and the waveform distortion is severe. At the same time, traveling wave protection responds more faster than type I voltage divider.

Fabry disease (FD) was an X-linked lysosomal storage disorder resulting from a deficiency in glycosphingolipid catabolism caused by mutations in the α-galactosidase A gene GLA. Variant FD patients did not present with classical symptoms during childhood and were undiagnosed or misdiagnosed with other kidney diseases, such as chronic glomerulonephritis (CGN). In this study, we utilized exome sequencing and Sanger sequencing identified the variation p.E66Q of GLA completely co-segregated with the disease phenotype in a Chinese family, which previously been diagnosed as possible CGN. Female patients exhibited preferential X-chromosome inactivation (XCI) of the normal p.E66 allele, as indicated by XCI analysis. By measuring α-Gal A activity, we found that male patients in the pedigree had just little enzymatic activity while female patients had residual enzymatic activity. These patients were diagnosed with renal variant FD in subsequent clinical review. Our results directly implicated the GLA mutation p.E66Q as the genetic etiology of the Chinese renal variant FD pedigree.

AMPD1 is an adenosine monophosphate deaminase that catalyzes the deamination of AMP to IMP. To understand the physiological function of AMPD1, we obtained a strain of Ampd1 mutant mice from KOMP repository, which was generated by a knockout-first strategy. An elevated AMP level and almost complete lack of IMP was detected in the skeletal muscle of E18.5 Ampd1tm1a/tm1a mice. However, Ampd1tm1a/tm1a mice died in 2 days postnatally, which was contradicting to previous reports. After removal of the knockout-first cassette and critical exon, mice homozygous for the Ampd1tm1c/tm1c and Ampd1tm1d/tm1d alleles survived to adulthood. RNA-seq analysis indicated that the expression of two neighboring genes, Man1a2 and Nras, were disrupted in the Ampd1tm1a/tm1a mice, but normal in the Ampd1tm1c/tm1c and Ampd1tm1d/tm1d mice. The neonatal lethality phenotype in the Ampd1tm1a/tm1a mice was consistent with the Man1a2-deficient mice. Our results indicated the knockout-first cassette may cause off-target effect by influence the expression of neighboring genes. This study, together with other reports, strongly suggests that removal of targeting cassette by site-specific recombinases is very important for the accurate phenotypic interpretation on mice generated by target mutations.