Heavy metals may play an important role as environmental risk factors in diabetes mellitus. This study aimed to explore the association of HbA1c with As, Cd, Cu, Ni, Pb, and Zn in single-metal exposure and multi-metal co-exposure models. A cross-sectional study involving 3472 participants was conducted. Plasma concentrations of heavy metals were determined by inductively coupled plasma mass spectrometry. We estimated the association of each metal with HbA1c by linear regression. Potential heterogeneities by sex, age, and smoking were investigated, and metal mixtures and interactions were assessed by the Bayesian kernel machine regression (BKMR). In linear regression, Cu (β = 0.324, p < 0.05) and Ni (β = -0.19, p < 0.05) showed significant association with HbA1c in all participants. In BKMR analyses, all exposure-response relationships were approximately linear. Cu was significantly and positively associated with HbA1c levels in overall participants, women, participants aged 60 years old and above, and nonsmokers. Ni was significantly and negatively associated with HbA1c levels in overall participants. We did not observe the overall effect of plasma metal mixtures on HbA1c or the interaction effect of the metals on HbA1c. Cu was positively correlated with HbA1c, whereas Ni was negatively correlated with HbA1c, when evaluated individually or in a metal mixture. Additional studies are necessary to confirm these correlations and to control for exposure to different metals in the general population.

The resurgence of mumps around the world occurs frequently in recent years. As the country with the largest number of cases in the world, the status of mumps epidemics in China is not yet clear. This study, taking the relatively serious epidemic province of Guangxi as the example, aimed to examine the spatiotemporal pattern and epidemiological characteristics of mumps, and provide a scientific basis for the effective control of this disease and formulation of related health policies. Geographic information system (GIS)-based spatiotemporal analyses, including spatial autocorrelation analysis, Kulldorff’s purely spatial and space-time scan statistics, were applied to detect the location and extent of mumps high-risk areas. Spatial empirical Bayesian (SEB) was performed to smoothen the rate for eliminating the instability of small-area data. A total of 208,470 cases were reported during 2005 and 2016 in Guangxi. Despite the fluctuations in 2006 and 2011, the overall mumps epidemic continued to decline. Bimodal seasonal distribution (mainly from April to July) were found and students aged 5–9 years were high-incidence groups. Though results of the global spatial autocorrelation based on the annual incidence largely varied, the spatial distribution of the average annual incidence of mumps was nonrandom with the significant Moran’s I. Spatial cluster analysis detected high-value clusters, mainly located in the western, northern and central parts of Guangxi. Spatiotemporal scan statistics identified almost the same high-risk areas, and the aggregation time was mainly concentrated in 2009–2012. The incidence of mumps in Guangxi exhibited spatial heterogeneity in 2005–2016. Several spatial and spatiotemporal clusters were identified in this study, which might assist the local government to develop targeted health strategies, allocate health resources reasonably and increase the efficiency of disease prevention.

Osteoarthritis (OA), the commonest arthritis type, features irreversible cartilage loss and synovitis. It was reported that macrophages have an important function in synovial inflammation, and our team revealed that the amounts of Sirt6, a nicotinamide adenine dinucleotide (NAD)⁺-dependent histone deacetylase, decrease during synovial inflammation and osteoarthritis. This work aimed to examine the anti-inflammatory properties of Sirt6 in synovial inflammation. Firstly, we compared Sirt6 amounts in acute meniscus injury and OA human knee synovial tissue samples by immunofluorescence and immunoblot. Secondly, Sirt6ʹs suppressive effects on inflammatory markers and macrophage polarization were evaluated. Finally, OA mice were histologically evaluated, and serum inflammatory factors were detected for assessing the impact of Sirt6 overexpression on the mouse synovium. We found significantly lower interleukin-4 (IL-4) amounts and M2 polarization in OA patients compared with control individuals. The expression of Sirt6 was lower in RAW264.7 cells of the lipopolysaccharides (LPS) + interferon-gamma (IFN-γ) group compared with the phosphate buffer saline (PBS) group, but higher than in the IL-4 group. The polarization of macrophages affected Sirt6 expression, which was reduced and elevated in M1 and M2 macrophages, respectively. Sirt6 inhibition could promote the release of proinflammatory cytokines by macrophages in the synovial membrane, induce M1 polarization in macrophages and inhibit M2 polarization in vitro, and Sirt6 overexpression alleviated osteoarthritis in vivo. These data strongly suggested that Sirt6 could inhibit synovial inflammation. Thus, this study provides a novel therapeutic target in osteoarthritis. Graphical abstract

Exposure to the heavy metal cadmium has adverse effects on human health, including DNA methylation. This study aimed to investigate the effects of cadmium on liver and kidney functions and Klotho gene methylation and to explore the relationship of methylation level with indicators of liver and kidney functions. Graphite furnace atomic absorption spectrometry was conducted to determine urinary cadmium, and an automatic biochemical analyzer was used to detect indices of liver and kidney functions. PCR pyrosequencing was performed to detect the methylation rate of Klotho. One-way ANOVA was adopted to compare the differences between groups, and the linear correlation to variables was analyzed. Cadmium exposure was negatively correlated with albumin level (r=-0.143, p=0.021) and positively correlated with urinary β₂-microglobulin level (r=0.229, p<0.001). However, the methylation levels of Klotho gene was decreased and increased by low and high doses of cadmium exposure, respectively. And Klothomethylation levels were negatively correlated with albumin levels and positively correlated with β₂-microglobulin levels.In this study, cadmium exposure affects liver and kidney functions as well as Klotho methylation levels, but the effect on Klotho methylation levels is not linear. Klotho methylation levels also influence liver and kidney functions.