Metabolic Signature of Healthy Lifestyle and Risk of Rheumatoid Arthritis: Observational and Mendelian Randomization Study.

BACKGROUND: Although substantial evidence reveals that healthy lifestyle behaviors are associated with a lower risk of rheumatoid arthritis (RA), the underlying metabolic mechanisms remain unclear. OBJECTIVES: This study aimed to identify the metabolic signature reflecting a healthy lifestyle and investigate its observational and genetic linkage with RA risk. METHODS: This study included 87,258 UK Biobank participants (557 cases with incident RA) aged 37-73 y with complete lifestyle, genotyping, and nuclear magnetic resonance (NMR) metabolomics data. A healthy lifestyle was assessed based on 5 factors: healthy diet, regular exercise, not smoking, moderate alcohol consumption, and normal body mass index. The metabolic signature was developed by summing the selected metabolites' concentrations weighted by the coefficients using elastic net regression. We used the multivariate Cox model to assess the associations between metabolic signatures and RA risk, and examined the mediating role of the metabolic signature in the impact of a healthy lifestyle on RA. We performed genome-wide association analysis (GWAS) to obtain genetic variants associated with the metabolic signature and then conducted Mendelian randomization (MR) analyses to detect causality. RESULTS: The metabolic signature comprised 81 metabolites, robustly correlated with a healthy lifestyle (r = 0.45, P = 4.2 × 10-15). The metabolic signature was inversely associated with RA risk (HR per standard deviation (SD) increment: 0.76; 95% CI: 0.70-0.83), and largely explained the protective effects of healthy lifestyle on RA with 64% (95% CI: 50.4-83.3) mediation proportion. 1- and 2-sample MR analyses also consistently showed the associations of genetically inferred per SD increment in metabolic signature with a reduction in RA risk (HR: 0.84; 95% CI: 0.75-0.94; and P = 0.002 and OR: 0.84; 95% CI: 0.73-0.97; and P = 0.02, respectively). CONCLUSIONS: Our findings implicate that the metabolic signature reflecting healthy lifestyle is a potential causal mediator in the development of RA, highlighting the importance of early lifestyle intervention and metabolic status tracking for precise prevention of RA.

Short-term effect of ambient temperature and ambient temperature changes on the risk of warts outpatient visits in Hefei, China: a retrospective time-series study.

Concerns are growing about the adverse health effects of ambient temperature and ambient temperature changes. However, the association between ambient temperature and ambient temperature changes on the risk of warts outpatient visits is poorly understood. Our study used the distributed lag non-linear model (DLNM) aimed to evaluate the association between ambient temperature, ambient temperature changes (including temperature change between neighboring days (TCN) and diurnal temperature range (DTR)), and warts outpatient visits. We also performed subgroup analyses in order to find susceptible populations by gender and age groups. The maximum relative risk (RR) of low ambient temperature (0 °C) for warts outpatient visits was 1.117 (95% CI: 1.041-1.198, lag 04 days), and the maximum RR of high ambient temperature (32 °C) for warts outpatient visits was 1.318 (95% CI: 1.083-1.605, lag 07 days). The large temperature drop (TCN = - 3 °C) decreased the risk of warts visits, with the lowest RR value at the cumulative exposure of lag 7 days (RR = 0.888, 95% CI: 0.822-0.959), and the large temperature rise (TCN = 2 °C) increased the risk of warts visits, with the highest RR value at the cumulative exposure of lag 7 days (RR = 1.080, 95% CI: 1.022-1.142). Overall, both low and high ambient temperatures and large temperature rise can increase the risk of warts visits, while large temperature drop is a protective factor for warts visits. However, we did not find any association between DTR and warts visits. Furthermore, subgroup analyses showed that males and the young (0-17 years old) were more sensitive to low and high ambient temperatures, and the elderly (≥ 65 years old) were more susceptible to TCN. The results may provide valuable evidence for reducing the disease burden of warts in the future.

[The relationship between the level of circulating endothelial progenitor cells CD34+; and carotid artery arteriosclerosis in youth and middle aged patients with essential hypertension].

OBJECTIVE: To explore the relationship between the level of circulating endothelial progenitor cells (EPCs) CD34+ with the Framingham cardiovascular risk factors, or with the carotid artery intima-media thickness (IMT), and to evaluate the value of circulating EPCs CD34+ level as a cytological marker of early vascular lesion in youth and middle aged essential hypertension (EH) patients. METHODS: A total of 62 patients with EH aged between 25 to 45 were enrolled as study group and 20 healthy people were enrolled as control group. EH patients were stratified with cardiovascular risk factors according to Framingham risk factors score into low-risk group with 18 cases, mid-risk group with 14 cases, high-risk group with 17 cases, and extremely high-risk group with 13 cases. The level of circulating EPCs CD34+, carotid artery IMT were respectively measured. The relationship between the level of circulating EPCs CD34+ and Framingham cardiovascular risk factors score, carotid artery IMT was analyzed. RESULTS: The level of circulating EPCs CD34+ was gradually decreased with an increase of the Framingham risk factors score in each hypertensive subgroup [low-risk group: (0.12+/-0.02)%, mid-risk group: (0.07+/-0.03)%, high-risk group: (0.04+/-0.03)%, extremely high-risk group: (0.01+/-0.01)%], and they were significantly lower than that in control group [(0.15+/-0.03)%], and there was a significant difference among hypertensive subgroups (P<0.05 or P<0.01). Carotid artery IMT was significantly thicker among hypertensive subgroups [low- risk group: (0.80+/-0.07) mm, mid-risk group: (1.11+/-0.08) mm, high-risk group: (1.26+/-0.10) mm, extremely high-risk group: (1.45+/-0.09) mm], and there was a significant difference between each hypertensive group and that of control group [(0.73+/-0.08) mm, all P<0.01]. There was also statistical significance among hypertensive subgroups (P<0.05 or P<0.01). There was a negative correlation between the level of circulating EPCs CD34+ and Framingham risk factors score (r=-0.875, P<0.01), and also a negative correlation with carotid artery IMT (r=-0.852, P<0.01). CONCLUSION: There was a significant correlation between the level of circulating EPCs CD34+ with Framingham risk factors score and also carotid artery IMT in EH patients. Circulating EPCs CD34+ could be a cytological marker of early vascular lesion in hypertension patients.