Tian-bing Wang

Currently, exosomes derived from Cancer-associated fibroblast (CAF) have reportedly been involved in regulating hepatocellular carcinoma (HCC) tumour microenvironment (TME). LIM domain and actin binding 1 (LIMA1) is an actin-binding protein that is involved in controlling the biological behaviour and progression of specific solid tumours. We aimed to determine the effect of LIMA1 and exosome-associated miR-20a-5p in HCC development. LIMA1 and miR-20a-5p expression levels were examined by real-time quantitative PCR (qRT-PCR), western blotting or immunohistochemistry (IHC). Functional experiments, including Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) assays, colony formation assays, wound healing assays, and Transwell invasion assays, were performed to investigate the effect of LIMA1 and miR-20a-5p. A dual-luciferase reporter gene assay was performed to confirm the interaction of miR-20a-5p and LIMA1. Exosomes were characterised by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. We noted that LIMA1 was downregulated in human HCC tissues and cells and remarkably correlated with overall survival (OS) and recurrence-free survival (RFS). LIMA1 overexpression suppressed HCC cell proliferation and metastasis in vitro and in vivo, while LIMA1 knockdown had the opposite effects. A mechanistic investigation showed that LIMA1 inhibited the Wnt/β-catenin signalling pathway by binding to BMI1 and inducing its destabilisation. Additionally, we found that LIMA1 expression in HCC cells could be suppressed by transferring CAF-derived exosomes harbouring oncogenic miR-20a-5p. In summary, LIMA1 is a tumour suppressor that inhibits the Wnt/β-catenin signalling pathway and is downregulated by CAF-derived exosomes carrying oncogenic miR-20a-5p in HCC.

BACKGROUND: Few data on ankle fractures in China from large multicenter epidemiological and clinical studies are available. The aim of this research was to evaluate the epidemiological features and surgical outcomes of ankle fractures by reviewing 235 patients who underwent ankle fracture surgery at five hospitals in China. METHODS: This study included patients who underwent ankle fracture surgery at five Chinese hospitals from January 2000 to July 2009. Age, gender, mechanism of injury, Arbeitsgemeinschaft für Osteosynthesefragen (AO) fracture type, fracture pattern, length of hospital stay and treatment outcome were recorded. Statistical analyses were conducted using SPSS software. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, visual analogue scale (VAS), and arthritis scale were used to evaluate outcome. RESULTS: Of 235 patients with ankle fractures, 105 were male with an average age of 37.8 years and 130 were female with an average age of 47.3 years. The average follow-up period was 55.7 months. There were significant differences in the ratios of patients in different age groups between males and females, and in mechanisms of injury among different age groups. There were also significant differences in the length of hospital stay among different fracture types and mechanisms of injury. In healed fractures, the average AOFAS ankle-hindfoot score was 95.5, with an excellence rate of 99.6%, the average VAS score was 0.17, and the average arthritis score was 0.18. Movement of the injured ankle was significantly different to that of the uninjured ankle. There were no significant differences between AO fracture types, fracture patterns or follow-up periods and AOFAS score, but there were some significant differences between these parameters and ankle joint movements, pain VAS score and arthritis score. CONCLUSIONS: Ankle fractures occur most commonly in middle-aged and young males aged 20 - 39 years and in elderly females aged 50 - 69 years. The most common mechanisms of injury are twisting injuries and falls from a standing height or less. The results of surgical treatment are satisfactory.

Tumor microenvironment (TME) is involved in the occurrence and development of hepatocellular carcinoma (HCC), and immune cells in the TME have been implicated in its progression and treatment. However, the association of genes involved in the TME with HCC prognosis remains unclear. Thus, in this study, we obtained transcriptomic and clinicopathological data of patients with HCC from The Cancer Genome Atlas to identify key genes in TME associated with HCC prognosis. Stromal and immune cell scores were calculated using the ESTIMATE method, and differentially expressed genes (DEGs) were determined. We identified 830 DEGs, which were further subjected to survival analyses and functional enrichment analysis. Next, we identified prognostic TME-associated DEGs, established a protein-protein interaction (PPI) network, and performed Cox analysis.Consequently, four key prognostic genes (CXCL5, CXCL8, IL18RAP, and TREM2) associated with TME, were identified, in which CXCL5 and IL18RAP may be potential independent prognostic factors. Age, clinical stage, N stage, and risk score were also determined as significant prognostic variables. CIBERSORT was used to predict the constitution and relative content of the immune cells, wherein M0 macrophages were the most closely related to the key genes. In conclusion, CXCL5, CXCL8, IL18RAP, and TREM2 were associated with HCC prognosis and were important for immune cell invasion into the TME. Additionally, IL18RAP expression may contribute toward favorable prognosis in patients with HCC. Consequently, these genes may serve as potential biomarkers and immunotherapeutic targets for HCC.