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ObjectiveThere is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need.Design and resultsA total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI −12.59 to −2.50; p=0.0018), respectively.ConclusionsThis is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group.Trial registrationNCT01770431; Post-results.

The aberrantly expressed microRNAs (miRNAs) including miR-200a-3p have been reported in the brains of Alzheimer’s disease (AD) patients in recent researches. Nevertheless, the role of miR-200a-3p in AD has not been characterized. The purpose of this study was to examine whether miR-200a-3p regulated β-Ameyloid (Aβ)-induced neuronal apoptosis by targeting SIRT1, a known anti-apoptotic protein. An increased level of miR-200a-3p and a decreased level of SIRT1 in the hippocampus of APPswe/PSΔE9 mice (a model for AD) were observed. To construct an in vitro cell model of AD, PC12 cells were cultured in presence of Aβ25-35. The results of flow cytometry analysis showed that the apoptosis rate and cleaved-caspase-3 expression in PC12 cells exposed to Aβ25-35 were remarkably increased, but the apoptosis rate and cleaved-caspase-3 activity were decreased when cells were transfected with anti-miR-200a-3p. On the other hand, MTT assay showed that the cell survival rate was increased in the Aβ25-35 + anti-miR-200a-3p group compared with the Aβ25-35 + anti-miR-NC group. Dual-luciferase reporter gene assay validated the predicted miR-200a-3p binding sites in the 3′-UTR of SIRT1 mRNA. In addition, downregulation of SIRT1 promoted Aβ25-35-induced neuronal apoptosis and cleaved-caspase-3 level in PC12 cells, whereas anti-miR-200a-3p reversed these effects. Knockdown of SIRT1 decreased the inhibitory effect of Aβ25-35 on cell viability, while anti-miR-200a-3p attenuated this effect. Overall, the results suggest that suppression of miR-200a-3p attenuates Aβ25-35-induced apoptosis in PC12 cells by targeting SIRT1. Thus, miR-200a-3p may be a potential therapeutic target for treatment of AD.

Background and aim Long non-coding RNAs have been confirmed to play a critical role in various cancers. In the present study, the effect of long non-coding RNA (lncRNA) CCAT1 on glioma cell proliferation and its potential mechanism were investigated. Methods and results Real-time PCR results showed that lncRNA-CCAT1 expression was significantly upregulated in glioma cancer tissues and cell lines compared with controls. After inhibiting CCAT1 expression in glioma cell line U251 with siRNA-CCAT1 (si-CCAT1), the cell viability and cell colony formation were decreased, the cell cycle was arrested in G1 phase, and the cell apoptosis was increased. As reported in bioinformatics software starbase2.0, a total of 22 microRNAs were potentially targeted by CCAT1. It was confirmed that miR-410 was altered most by si-CCAT1. After up-regulating CCAT1 expression in U251 cells, miR-410 level was decreased. Luciferase reporter assay confirmed that CCAT1 targeted miR-410. Correlation analysis showed that CCAT1 expression was negatively related to miR-410 expression in glioma cancer tissues. In addition, down-regulation of miR-410 reversed the inhibitory effect of si-CCAT1 on glioma proliferation. Conclusion These data demonstrated that lncRNA-CCAT1 promoted glioma cell proliferation via inhibiting miR-410, providing a new insight about the pathogenesis of glioma proliferation.

Objective Numerous long non-coding RNAs (lncRNA) have been identified in neurodegenerative disorders including Parkinson’s disease (PD). Emerging evidence demonstrates that β-asarone functions as neuroprotective effects in both in vitro and in vivo models. However, the role of β-asarone and its potential mechanism in PD remain not completely clear. Methods MPTP-induced PD mouse model and SH-SY5Y cells subjected to MPP+ as its in vitro model were used to evaluate the effects of β-asarone on PD. LncRNA MALAT1 and α-synuclein expression were determined by real-time PCR and western blot methods. Results β-Asarone significantly increased the TH+ cells number and decreased the expression levels of MALAT1 and α-synuclein in midbrain tissue of PD mice. RNA pull-down and immunoprecipitation assays confirmed that MALAT1 associated with α-synuclein, leading to the increased stability of α-synuclein and its expression in SH-SY5Y cells. β-asarone elevated the viability of cells exposed to MPP+. Either overexpressed MALAT1 or α-synuclein could canceled the protective effect of β-asarone on cell viability. In PD mice, pcDNA-MALAT1 also decreased the TH+ cells number and increased the α-synuclein expression in PD mice with treatment of β-asarone. Conclusion β-Asarone functions as a neuroprotective effect in both in vivo and in vitro models of PD via regulating MALAT1 and α-synuclein expression.

Official guidelines group together all cases of solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion, regardless of tumor size. Here, we examined whether this is justified based on overall survival (OS) after hepatic resection (HR). Patients with newly diagnosed solitary HCC treated by initial HR from January 2004 to October 2013 were classified into six groups based on tumor size (in 2-cm increments). Combining adjacent categories with similar OS led to three groups: ≤5 cm (n = 426),5 and ≤8 cm (n = 229), and8 cm (n = 202). Among all patients, median survival time was 62 months, and OS was 95 % at 1 year, 73 % at 3 years, and 54 % at 5 years. Patients in the ≤5 cm group showed significantly higher OS (P 0.001) and lower tumor recurrence (P = 0.004) than those in the5 and ≤8 cm group, who in turn showed significantly higher OS (P = 0.003) and lower tumor recurrence (P = 0.021) than those in the8 cm group. Our results suggest that patients with solitary HCC should be subclassified based on tumor size for more accurate prognosis. We propose defining solitary HCC tumors5 and ≤8 cm as "large" and tumors8 cm as "huge".