Phosphaturic mesenchymal tumours (PMTs) are uncommon soft tissue and bone tumours that typically cause hypophosphataemia and tumour-induced osteomalacia (TIO) through secretion of phosphatonins including fibroblast growth factor 23 (FGF23). PMT has recently been accepted by the World Health Organization as a formal tumour entity. The genetic basis and oncogenic pathways underlying its tumourigenesis remain obscure. In this study, we identified a novel FN1-FGFR1 fusion gene in three out of four PMTs by next-generation RNA sequencing. The fusion transcripts and proteins were subsequently confirmed with RT-PCR and western blotting. Fluorescence in situ hybridization analysis showed six cases with FN1-FGFR1 fusion out of an additional 11 PMTs. Overall, nine out of 15 PMTs (60%) harboured this fusion. The FN1 gene possibly provides its constitutively active promoter and the encoded protein's oligomerization domains to overexpress and facilitate the activation of the FGFR1 kinase domain. Interestingly, unlike the prototypical leukaemia-inducing FGFR1 fusion genes, which are ligand-independent, the FN1-FGFR1 chimeric protein was predicted to preserve its ligand-binding domains, suggesting an advantage of the presence of its ligands (such as FGF23 secreted at high levels by the tumour) in the activation of the chimeric receptor tyrosine kinase, thus effecting an autocrine or a paracrine mechanism of tumourigenesis.

Objective: This study was to investigate the effectiveness of action observation therapy on arm and hand motor function, walking ability, gait performance, and activities of daily living in stroke patients. Design: Systematic review and meta-analysis of randomized controlled trials. Data sources: Searches were completed in January 2019 from electronic databases, including PubMed, Scopus, the Cochrane Library, and OTseeker. Review methods: Two independent reviewers performed data extraction and evaluated the study quality by the PEDro scale. The pooled effect sizes on different aspects of outcome measures were calculated. Subgroup analyses were performed to examine the impact of stroke phases on treatment efficacy. Results: Included were 17 articles with 600 patients. Compared with control treatments, the action observation therapy had a moderate effect size on arm and hand motor outcomes (Hedge’s g = 0.564; P < 0.001), a moderate to large effect size on walking outcomes (Hedge’s g = 0.779; P < 0.001), a large effect size on gait velocity (Hedge’s g = 0.990; P < 0.001), and a moderate to large effect size on activities of daily function (Hedge’s g = 0. 728; P = 0.004). Based on subgroup analyses, the action observation therapy showed moderate to large effect sizes in the studies of patients with acute/subacute stroke or those with chronic stroke (Hedge’s g = 0.661 and 0.783). Conclusion: This review suggests that action observation therapy is an effective approach for stroke patients to improve arm and hand motor function, walking ability, gait velocity, and daily activity performance.

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