BackgroundPrimary mitochondrial disorders (PMDs) are a diagnostic challenge for paediatricians, and identification of reliable and easily measurable biomarkers has become a high priority. This study aimed to investigate the role of serum fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) in children with PMDs.MethodsWe analysed serum FGF21 and GDF15 concentrations by enzyme-linked immunosorbent assay (ELISA) in children with PMDs, patients with non-mitochondrial neuromuscular disorders (NMDs), and aged-matched healthy children, and compared them with serum lactate and ratio of lactate and pyruvate (L/P). We also evaluated correlations between these biomarkers and the phenotype, genotype, and severity of PMDs.ResultsThe median serum GDF15 and FGF21 concentrations were significantly elevated in fifty-one patients with PMDs (919.46 pg/ml and 281.3 pg/ml) compared with those of thirty patients with NMDs (294.86 pg/ml and 140.51 pg/ml, both P < 0.05) and fifty healthy controls (221.21 pg/ml and 85.02 pg/ml, both P < 0.05). The area under the curve of GDF15 for the diagnosis of PMDs was 0.891, which was higher than that of the other biomarkers, including FGF21 (0.814), lactate (0.863) and L/P ratio (0.671). Calculated by the maximum Youden index, the critical value of GDF15 was 606.369 pg/ml, and corresponding sensitivity and specificity were 74.5and 100%. In the PMD group, FGF21 was significantly correlated with International Paediatric Mitochondrial Disease Scale (IPMDS) score. The levels of GDF15 and FGF21 were positively correlated with age, critical illness condition, and multisystem involvement but were not correlated with syndromic/non-syndromic PMDs, different mitochondrial syndromes, nuclear DNA/mitochondrial DNA pathogenic variants, gene functions, or different organ/system involvement.ConclusionRegardless of clinical phenotype and genotype, circulating GDF15 and FGF21 are reliable biomarkers for children with PMDs. GDF15 can serve as a screening biomarker for diagnosis, and FGF21 can serve as a severity biomarker for monitoring.
Tangential ultrasonic vibration-assisted grinding (TUAG) has a wide prospect in machining difficult-to-machine materials. However, the surface generation mechanism in TUAG is not fully recovered. This study proposes an analytical model of the surface topography produced by TUAG. Based on the model, the surface topography and roughness are predicted and experimentally verified. In addition, the influence of the grinding parameters on the surface topography is analyzed. The predicted surface topography well coincides with experimental measurements, and the prediction error in surface roughness Ra by the proposed model is less than 5%. Compared with conventional grinding, TUAG produces a surface with more uniform scratches and surface roughness Ra was reduced by up to 27% with the proper parameters. However, the improvement of surface roughness in TUAG is weakened when grinding speed or depth of cut increases. Moreover, the influence of the ultrasonic vibration amplitude on the surface roughness is not monotonous. With the grinding parameters selected in this study, TUAG with an ultrasonic amplitude of 7.5 μm produces the minimum surface roughness.
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