BackgroundTumor suppressive let-7 miRNAs are universally down-regulated in human hepatocellular carcinoma (HCC) versus normal tissues; however, the roles and related molecular mechanisms of let-7 in HCC stem cells are poorly understood.MethodsWe examined the inhibitory effect of let-7 miRNAs on the proliferation of MHCC97-H and HCCLM3 hepatic cancer cells by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, which was further confirmed by apoptosis and cell cycle studies. The sphere-forming assay was used to study the effects of let-7a on stem like cells. Through western blot, immunofluorescence and the luciferase-reporter assay, we explored the activity of epithelial-mesenchymal transition (EMT) signaling factors in HCC cells. qRT-PCR was applied to detect miRNA expression levels in clinical tissues.ResultsLet-7a effectively repressed cell proliferation and viability, and in stem-like cells, also let-7a decreased the efficiency of sphere formation.in stem-like cells. The suppression of EMT signaling factors in HCC cells contributed to let-7’s induced tumor viability repression and Wnt activation repression. Besides, Wnt1 is critical and essential for let-7a functions, and the rescue with recombinant Wnt1 agent abolished the suppressive roles of let-7a on hepatospheres. In clinical HCC and normal tissues, let-7a expression was inversely correlated with Wnt1 expression.ConclusionsLet-7 miRNAs, especially let-7a, will be a promising therapeutic strategy in the treatment of HCC through eliminating HCC stem cells, which could be achieved by their inhibitory effect on the Wnt signaling pathway.

This study aimed to investigate the effect of miR-671-5p on metastasis of clear cell renal cell carcinoma (ccRCC) and underlying mechanism involved. The migration and invasion of ccRCC cells were determined by transwell and boyden assays in vitro and in vivo. Genes mRNA and protein expression were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The target gene of miRNA was confirmed by luciferase reporter assays. Transcriptional regulation of miRNA by transcription factor was detected by chromatin immunoprecipitation assay (ChIP). The expressions of miRNA in clinical specimens were detected by in situ hybridization (ISH). miR-671-5p promoted migration and invasion of ccRCC in vivo and in vitro. Moreover, miR-671-5p directly targeted APC to activate Wnt signaling, thus inducing the epithelial-mesenchymal transition (EMT) in ccRCC. Intriguingly, miR-671-5p expression was transcriptionally enhanced by HMGA1. Consistently, bioinformatics analysis suggested that HMGA1 was positively correlated with miR-671 expression; however, miR-671 was negatively correlated with APC. In situ hybridization analysis showed that miR-671-5p was upregulated in ccRCC compared with paracarcinoma and correlated with poor prognosis of ccRCC patients. In addition, univariate and multivariate analysis indicated that miR-671-5p expression was an independent prognostic factor for overall survival in ccRCC patients. Our data suggest that miR-671-5p is a tumor enhancer in regulating of ccRCC metastasis, and miR-671-5p may be utilized as a factor for the clinical diagnosis and prognosis of ccRCC.

BackgroundPatients on maintenance hemodialysis (MHD) frequently complain of insomnia. Poor sleep quality impairs their quality of life and adversely affects long-term outcome. Previously we applied auricular acupressure therapy (AAT) for MHD patients with insomnia and yielded favorable results. AAT probably improves sleep quality by stimulating the vagus nerve and inhibiting sympathetic overactivity. However, the efficacy of AAT for insomnia in this population is still lacking. The proposed randomized controlled trial (RCT) will evaluate the efficacy and safety of AAT for improvement of sleep quality in MHD patients with insomnia.Methods/designThe proposed study is a multi-center, double-blind (participants and assessors), parallel-group RCT. A total of 112 participants with insomnia will be recruited from six hemodialysis centers in Guangzhou, China, and randomly allocated in a 1:1 ratio to receive auricular acupressure on either active points (AA group) or control points (points irrelevant to insomnia management, SAA group). The treatment will last for 8 weeks prior to a follow-up period of 12 weeks. Evaluation by blinded assessors at baseline, at 8 weeks (end of treatment) as well as at 4-week, 8-week and 12-week follow-ups (after intervention) will include Pittsburgh Sleep Quality Index (PSQI) scores and average weekly dose of hypnotics. The primary endpoint is clinical response rate (percentage of participants who reach a reduction of PSQI global score ≥ 3 in each group) at 8 weeks from baseline. Secondary endpoints include the changes in PSQI scores over time from baseline, as well as the changes in weekly dose of hypnotics.DiscussionThis paper describes the rationale and design of a double-blind RCT that aims to determine the efficacy and safety of AAT for insomnia of hemodialysis patients. If successful, this project will provide evidence of the efficacy and safety of AAT for insomnia of hemodialysis patients.Trial registrationClinicalTrials.gov, Identifier: NCT03015766. Registered on 22 December 2016.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2546-2) contains supplementary material, which is available to authorized users.

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After following 141 children with likely asymptomatic congenital cytomegalovirus infection in a highly immune population in China, four children (2.8%) were found to have late-onset hearing loss. No maternal or childhood factors, except higher saliva cytomegalovirus viral load at birth (P = 0.03), were associated with increased risk of developing a hearing loss.