ObjectiveTo systematically evaluate the value of contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMRI) in the diagnosis of residual or recurrent lesion after transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). MethodsPubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang Data were searched for studies on CECT and/or CEMRI in the diagnosis of residual or recurrent lesion after TACE published up to April 2019. After two reviewers independently performed literature screening, data extraction, and assessment of the risk of bias using the QUADAS-2 tool, Stata 12.0 and RevMan 5.3 were used to analyze pooled sensitivity, specificity, and area under the receiver operator characteristic curve (AUC). ResultsA total of 13 studies on CECT and 13 studies on CEMRI in the diagnosis of residual or recurrent HCC lesion after TACE were included, with 934 lesions from 748 patients and 847 lesions from 557 patients, respectively. High heterogeneity was observed in the 13 studies on CECT in the diagnosis of residual or recurrent HCC lesion after TACE (P=0.001, Q=12.56, I2=84.08%), while no significant heterogeneity was observed in the 13 studies on CEMRI (P=0.473, Q=0.11, I2=0). In the diagnosis of residual or recurrent HCC lesion after TACE, CECT had a sensitivity of 72% (95% confidence interval ［CI］: 66%-78%), a specificity of 99% (95% CI: 93%-100%), and an AUC of 0.87 (95% CI: 0.83-0.89), and CEMRI had a sensitivity of 88% (95% CI: 82%-93%), a specificity of 96% (95% CI: 91%-98%), and an AUC of 0.98 (95% CI: 0.96-0.99). CECT had a significantly lower sensitivity than CEMRI in the diagnosis of residual or recurrent HCC lesion after TACE (Z=2.12, P=0.03). ConclusionIn comparison with CECT, CEMRI has an extremely higher diagnostic efficiency in the diagnosis of residual or recurrent HCC lesion after TACE and is thus an effective method for diagnosis.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*