Early cartilage lesion and 5-year incident joint surgery in knee osteoarthritis patients: a retrospective cohort study.

OBJECTIVE: to investigate the association between cartilage lesion-related features observed in knee osteoarthritis (OA) patients' first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of these features for the incident knee surgery. METHODS: We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine joint space narrowing grade, cartilage lesion size grade, cartilage full-thickness loss grade and cartilage lesion sum score for the medial and lateral compartments, respectively. Generalized linear regression models examined the association of these features with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined referring to 5-year incident knee surgery. RESULTS: Totally, 878 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 61 knees. None of the cartilage-related features had been found significantly associated with incident surgery. The results were similar for medial and lateral compartments. The PPVs were low for all the features. CONCLUSIONS: Among symptomatic clinically diagnosed OA knees, cartilage lesions observed in the first MRI examinations were not found to be associated with the occurrence of joint surgery within a 5-year period. All these cartilage-related features appear to have no additional value in predicting 5-year incident joint surgery.

IGFBP2 upregulates ZEB1 expression and promotes hepatocellular carcinoma progression through NF-κB signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers owing to the high metastasis rate. The molecular mechanism underlying HCC progression remains unclear. AIMS: We aimed to explore the function and mechanism of action of insulin-like growth factor binding protein 2 (IGFBP2) in HCC. METHODS: Expression of IGFBP2 was evaluated with western blotting and reverse transcription polymerase chain reaction (RT-PCR). Loss- and gain-function assays were conducted to evaluate the effects of IGFBP2 on HCC cell proliferation, migration, and invasion. Signaling pathways were screened with a dual-fluorescein reporting system, and levels of epithelial and mesenchymal markers were measured after altering IGFBP2 expression. Cell fractionation analysis was conducted to evaluate the nuclear translocation of p65. RESULTS: IGFBP2 expression was upregulated in HCC tissues, predicted worse prognosis, and was associated with strong metastatic potentials. IGFBP2 depletion significantly inhibited HCC cell proliferation, migration, and invasion, whereas IGFBP2 overexpression showed reverse phenotypes. The underlying mechanism involved IGFBP2-mediated nuclear localization of p65, which activated nuclear factor kappa B (NF-κB) and zinc finger E-Box binding homeobox 1 (ZEB1) transcription via binding to the gene promoter. CONCLUSION: This study for the first time identifies IGFBP2 as a novel therapeutic target in HCC that activates the NF-κB-ZEB1 signaling axis and promotes HCC tumorigenesis.