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Occupational exposure is a significant source of metal contact; previous studies have been limited regarding the effect of occupational metal exposure on the development of hypertension. This study was conducted to assess the levels of exposure of certain metals (chromium (Cr), iron (Fe), manganese (Mn), and nickel (Ni)) in hypertensive and non-hypertensive workers and to assess the relationship between the risk of hypertension and metal exposure level. Our study included 138 hypertensive patients as case groups and 138 non-hypertensive participants as controls. The exposure risk level was divided according to the limit value after collecting and testing the metal dust in the workshop. Considering the influence of single- and poly-metal, single factor analysis and conditional logistic regression analysis of poly-metal were carried out. The results of the model indicated that the incidence of hypertension increased with an increase in Cr exposure level, and the risk of hypertension was 1.85 times higher in the highest exposure than in the lowest exposure (95% CI: 1.20–2.86, p < 0.05). Mn has the same effect as Cr. There was no significant correlation between Fe or Ni and hypertension. Our findings suggested that Cr and Mn exposure in the work environment might increase the risk of hypertension, while no effect of Fe and Ni on blood pressure was found. Prospective study designs in larger populations are needed to confirm our findings.

BackgroundWelding fumes are a risk factor for welder pneumoconiosis. However, there is a lack of population information on the occurrence of welding fume-induced lung cancer, and little is known about the welding fume pathogenesis.MethodsWelding fume and metal ion concentrations were assessed in a vehicle factory in Wuhan. A Cox regression model estimated lung-related disease risk in workers by independent and combined factors.ResultsWorkers' exposures were divided into four grades; the highest exposure was among the welders in the maintenance workshop, the highest Mn and Fe exposure was 4 grades, and the highest Cr exposure was 3 grades. Subgroup analysis found that the risk of lung-related disease was 2.17 (95% CI: 1.31–3.57, p < 0.05) in welders compared with non-welders, and the risk of pulmonary disease in male welders was 2.24 (95% CI: 1.34–3.73, p < 0.05) compared to non-welders. Smoking welders had a 2.44 (95% CI: 1.32–4.51, p < 0.01) higher incidence of lung-related diseases than non-welders. Total years of work as an independent protective factor for lung-related disease risk was 0.72 (95% CI: 0.66–0.78, p < 0.01). As an independent risk factor, high-high and high-low exposure had a 5.39 (95% CI: 2.52–11.52, p < 0.001) and 2.17 (95% CI: 1.07–4.41, p < 0.05) higher risk for lung-related diseases, respectively.ConclusionsHigh welding fume exposure is a significant risk factor for lung-related disease in workers.

BackgroundNon-coding RNAs (ncRNAs), including small nucleolar RNAs (snoRNAs), are widely involved in the physiological and pathological processes of human beings. While up to date, although considerable progress has been achieved in ncRNA-related pathogenesis of non-small cell lung cancer (NSCLC), the underlying mechanisms and biological significance of snoRNAs in NSCLC still need to be further clarified.MethodsQuantitative real-time polymerase chain reaction or RNAscope was performed to verify the expression of Small Nucleolar RNA, H/ACA Box 38B (SNORA38B) in NSCLC cell lines or clinical samples. BALB/c nude mice xenograft model or C57BL/6J mice syngeneic tumor model were estimated to detect the effects of SNORA38B in tumor growth or tumor immune microenvironment in vivo. Cytometry by time of flight, enzyme-linked immunosorbent assay and flow cytometry assay were conducted to clarify the effects and mechanisms of SNORA38B-mediated tumor immunosuppressive microenvironment. The binding activity between SNORA38B and E2F transcription factor 1(E2F1) was detected by RNA immunoprecipitation and RNA pull-down assays. Then, bioinformatics analysis and chromatin immunoprecipitation were utilized to demonstrate the regulation of GRB2-associated-binding protein 2 (GAB2) by E2F1. Moreover, the combinatorial treatment of SNORA38B locked nucleic acid (LNA) and immune checkpoint blockade (ICB) was used to treat murine Lewis lung carcinoma-derived tumor burden C57BL/6J mice to clarify the effectiveness of targeting SNORA38B in NSCLC immunotherapy.ResultsSNORA38B was found highly expressed in NSCLC tissues and cell lines, and associated with worse prognosis. Further results showed that SNORA38B functioned as an oncogene via facilitating cell proliferation, migration, invasion, and inhibiting cell apoptosis in vitro and promoting tumorigenesis of NSCLC cells in vivo. SNORA38B could also recruit the CD4+FOXP3+ regulatory T cells by triggering tumor cells to secrete interleukin 10, which in turn reduced the infiltration of CD3+CD8+ T cells in NSCLC tumor microenvironment (TME), favoring tumor progression and poorer immune efficacy. Mechanistically, SNORA38B mainly distributed in the nucleus, and promoted NSCLC progression by regulating GAB2 transcription to activate protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway through directly binding with E2F1. Moreover, we found that SNORA38B LNAs were able to ameliorate CD3+CD8+ T cell infiltration in TME, which sensitized NSCLC to the treatment of ICB.ConclusionsIn conclusion, our data demonstrated that SNORA38B functioned as an oncogene in NSCLC both in vitro and in vivo at least in part by regulating the GAB2/AKT/mTOR pathway via directly binding to E2F1. SNORA38B could also sensitize NSCLC to immunotherapy, which may be a critical therapeutic target for NSCLC.

Objective: To evaluate efficacy and safety of intra-articular therapy with methotrexate (MTX) in large volume of 10% glucose injection (GS) in ankylosing spondylitis (AS) patients with knee synovitis. Methods: As patients with knee synovitis (n=90) were randomly divided into three groups. 50 patients in MTX/GS group were treated with intra-articular injection of MTX (15 mg)in 10% GS (20 ml) every week for 8 times, while 20 patients in GS group with intra-articular injection of 10% GS (20 ml) every week for 8 times, and 20 patients in control group without injection. All the patients received ibuprofen sustained release tablets 0.3 twice daily and Sulphasalazine 1 g twice daily. Same dose of MTX (15 mg once weekly) were given orally to the patients in GS group and control group. At the beginning of the treatment and after 4, 8 and 24 weeks, all the patients underwent a clinical evaluation, measuring maximum flexion-extension angle, knee pain with visual analog scale (VAS), swelling with joint circumference, global assessment (ASA20, PGA, BASMI,BASDAI, BASFI). Erythrocyte sedimentation rate (ESR) and C-reactive protein were tested. Results: Joint pain, range of joint movement, circumference of swollen joint, ESR, CRP, patient’s global assessment(PGA) in MTX/GS group are significantly improved after 4 weeks of treatment in comparison with baseline and other groups at same time point (P