Hypoferraemia (i.e. iron deficiency) was initially reported among obese individuals several decades ago; however, whether obesity and iron deficiency are correlated remains unclear. Here, we evaluated the putative association between obesity and iron deficiency by assessing the concentration of haematological iron markers and the risks associated with iron deficiency in both obese (including overweight) subjects and non-overweight participants. We performed a systematic search in the databases PubMed and Embase for relevant research articles published through December 2014. A total of 26 cross-sectional and case-control studies were analysed, comprising 13,393 overweight/obese individuals and 26,621 non-overweight participants. Weighted or standardized mean differences of blood iron markers and odds ratio (OR) of iron deficiency were compared between the overweight/obese participants and the non-overweight participants using a random-effects model. Compared with the non-overweight participants, the overweight/obese participants had lower serum iron concentrations (weighted mean difference [WMD]: -8.37 μg dL(-1) ; 95% confidence interval [CI]: -11.38 to -5.36 μg dL(-1) ) and lower transferrin saturation percentages (WMD: 2.34%, 95% CI: -3.29% to -1.40%). Consistent with this finding, the overweight/obese participants had a significantly increased risk of iron deficiency (OR: 1.31; 95% CI: 1.01-1.68). Moreover, subgroup analyses revealed that the method used to diagnose iron deficiency can have a critical effect on the results of the association test; specifically, we found a significant correlation between iron deficiency and obesity in studies without a ferritin-based diagnosis, but not in studies that used a ferritin-based diagnosis. Based upon these findings, we concluded that obesity is significantly associated with iron deficiency, and we recommend early monitoring and treatment of iron deficiency in overweight and obese individuals. Future longitudinal studies will help to test whether causal relationship exists between obesity and iron deficiency.

NCT01613079.

Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.

BackgroundAlthough studies have examined the association between dietary magnesium intake and health outcome, the results are inconclusive. Here, we conducted a dose–response meta-analysis of prospective cohort studies in order to investigate the correlation between magnesium intake and the risk of cardiovascular disease (CVD), type 2 diabetes (T2D), and all-cause mortality.MethodsPubMed, EMBASE, and Web of Science were searched for articles that contained risk estimates for the outcomes of interest and were published through May 31, 2016. The pooled results were analyzed using a random-effects model.ResultsForty prospective cohort studies totaling more than 1 million participants were included in the analysis. During the follow-up periods (ranging from 4 to 30 years), 7678 cases of CVD, 6845 cases of coronary heart disease (CHD), 701 cases of heart failure, 14,755 cases of stroke, 26,299 cases of T2D, and 10,983 deaths were reported. No significant association was observed between increasing dietary magnesium intake (per 100 mg/day increment) and the risk of total CVD (RR: 0.99; 95% CI, 0.88–1.10) or CHD (RR: 0.92; 95% CI, 0.85–1.01). However, the same incremental increase in magnesium intake was associated with a 22% reduction in the risk of heart failure (RR: 0.78; 95% CI, 0.69–0.89) and a 7% reduction in the risk of stroke (RR: 0.93; 95% CI, 0.89–0.97). Moreover, the summary relative risks of T2D and mortality per 100 mg/day increment in magnesium intake were 0.81 (95% CI, 0.77–0.86) and 0.90 (95% CI, 0.81–0.99), respectively.ConclusionsIncreasing dietary magnesium intake is associated with a reduced risk of stroke, heart failure, diabetes, and all-cause mortality, but not CHD or total CVD. These findings support the notion that increasing dietary magnesium might provide health benefits.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0742-z) contains supplementary material, which is available to authorized users.

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Background The use and effectiveness of hematopoietic stem cell transplantation (HSCT) are limited by lethal complications, i.e., acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively), in which immune cells from the donor attack healthy recipient tissues. GVHD presents both prophylactic and therapeutic challenges, and overall survival is poor. Mesenchymal stem cells (MSCs) show considerable promise in the treatment of GVHD because of their potential immunomodulatory activity. Multiple studies have been performed to explore the possible benefit of MSCs in GVHD, but the results of these studies are sometimes conflicting. Therefore, we performed a systematic review and meta-analysis to estimate the effect of MSC infusion on GVHD treatment and prevention. Methods We systematically searched the MEDLINE (PubMed), Cochrane Library, EMBASE, ClinicalTrials.gov, and SinoMed CBM databases to identify studies published before February 2018 involving patients with hematologic malignancies undergoing HSCT and receiving MSC-based or conventional therapy. We included studies if they reported on the outcomes of interest. Results Ultimately, 10 studies were selected from among 413 candidates. According to our meta-analyses, compared with conventional treatment, MSC therapy demonstrated substantial improvements in terms of complete response (CR) and overall survival for cGVHD. However, MSC therapy did not show substantial improvements in terms of engraftment, the incidence of aGVHD, relapse, death, death due to relapse, or death due to infection. Subgroup analyses showed that MSCs derived from the umbilical cord (U-MSCs) and MSC infusion after HSCT substantially improved engraftment and cGVHD incidence, whereas MSCs derived from bone marrow (B-MSCs) and MSC infusion before HSCT shows no improvement. In addition, B-MSCs and MSC infusion before HSCT tend to prolong engraftment time, as well as increase the rates of relapse and death. Conclusions MSC infusion can reduce cGVHD but not aGVHD incidence and showed a positive effect in patients who already had aGVHD. For GVHD prevention, the use of U-MSCs and MSC infusion after HSCT were optimal for reducing cGVHD incidence and promoting engraftment, and might help decrease the incidence rate of relapse and death. However, B-MSCs and MSC infusion before HSCT may be harmful to patients and thus require serious consideration. A lack of robust evidence, owing to the small number of studies and small sample sizes, indicates a need for further high-quality clinical trials including large numbers of patients to validate our findings. Electronic supplementary material The online version of this article (10.1186/s13287-019-1287-9) contains supplementary material, which is available to authorized users.

The presence or absence of anti-citrullinated peptide antibodies (ACPA) and associated disparities in patients with rheumatoid arthritis (RA) implies disease heterogeneity with unknown diverse immunopathological mechanisms. Here we profile CD45+ hematopoietic cells from peripheral blood or synovial tissues from both ACPA+ and ACPA- RA patients by single-cell RNA sequencing and identify subsets of immune cells that contribute to the pathogenesis of RA subtypes. We find several synovial immune cell abnormalities, including up-regulation of CCL13, CCL18 and MMP3 in myeloid cell subsets of ACPA- RA compared with ACPA+ RA. Also evident is a lack of HLA-DRB5 expression and lower expression of cytotoxic and exhaustion related genes in the synovial tissues of patients with ACPA- RA. Furthermore, the HLA-DR15 haplotype (DRB1/DRB5) conveys an increased risk of developing active disease in ACPA+ RA in a large cohort of patients with treatment-naive RA. Immunohistochemical staining shows increased infiltration of CCL13 and CCL18-expressing immune cells in synovial tissues of ACPA- RA. Collectively, our data provide evidence of the differential involvement of cellular and molecular pathways involved in the pathogenesis of seropositive and seronegative RA subtypes and reveal the importance of precision therapy based on ACPA status.

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