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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.

Backgrounds and aims MicroRNAs (miRNAs) have been reported to be involved in degenerative disorders including Parkinson’s disease (PD). α-synuclein expression is strong associated with the pathogenesis of PD. In the present study, we investigated whether the regulation of α-synuclein expression by miR-214 is the potential mechanism underlying the neuroprotective effect of Resveratrol. Methods The PD mouse model was established with the injection of MPTP (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and the human neuroblastoma cell line, SH-SY5Y, was administrated with MPP+. Results The midbrain of PD mice and MPP+ treated SH-SY5Y cells had the lower expression levels of miR-214 and higher mRNA and protein expression of α-synuclein, which were reversed by Resveratrol administration. MiR-214 mimic down-regulated expression of α-synuclein and its 3′-UTR activity, while the levels were up-regulated by miR-214 inhibitor. In addition, the cell viability, elevated by Resveratrol, was also decreased by miR-214 inhibitor or overexpressed α-synuclein. In vivo , miR-214 inhibitor down-regulated TH+ cells of ipsilateral and up-regulated α-synuclein expression compared with the group treated with Resveratrol. Conclusion The loss of miR-214 in PD resulted in the increase of α-synuclein expression, which was the potential mechanism underlying the neuroprotective effects of Resveratrol.

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.

The aim of this study was to investigate the differences in portal hemodynamics between whole liver transplantation and living donor liver transplantation (LDLT). Twenty patients who underwent LDLT (the L group) and 42 patients who underwent whole liver transplantation (the W group) were enrolled, and colored Doppler ultrasonography was performed preoperatively and on postoperative days (PODs) 1, 3, 5, 7, 30, and 90. The changes in the portal blood flow velocity (PBV) and portal blood flow volume (PBF) were monitored. The graft and spleen sizes were measured with angiographic computed tomography, and upper endoscopy was used to measure esophageal varices on PODs 14, 30, and 90. Although the portal venous pressure (PVP) decreased after graft implantation, it was higher in the L group with a smaller graft size ratio (25.7 ± 5.1 cm H2O for the L group and 18.5 ± 4.6 cm H2O for the W group, P < 0.05). PBF and PBV increased in both the W and L groups on POD 1 after transplantation; however, the PBF and PBV peaks were significantly higher in the W group. The postoperative PVP and graft volume were greatly related to PBF on POD 1. Grafts in the L group regenerated rapidly after the operation, and the volume increased from 704 ± 115 to 1524 ± 281 mL as early as 1 month after transplantation. A rapid improvement in splenomegaly was observed in both groups. An improvement in esophageal varices was observed in the W group on POD 14 after transplantation, whereas no change was observed in the L group. The portal venous flow in patients with portal hypertension showed a high perfusion state after LDLT, but in contrast to whole liver transplantation, the PVP elevation after LDLT postponed the closing time of the collateral circulation and affected the recovery from splenomegaly. Liver Transpl 16:1236-1241, 2010. © 2010 AASLD.

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".

Transforming growth factors β (TGF-β) pathway has been proven to play important roles in oncogenesis and angiogenesis of gliomas. MiR-132 might be related to TGF-β signaling pathway and high miR-132 expression was reported to be a biomarker of poor prognosis in patients diagnosed with glioma. However, the expression regulation way involved in TGF-β pathway and clinical significance of miR-132 have not been investigated in glioma cells. Here we reported that the mRNA level of miR-132 and TGF-β concentration were both increased in patients with brain glioma. Correlation analysis revealed that TGF-β concentration was positively correlated with mRNA level of miR-132. In addition, the mRNA level of miR-132 was up-regulated by TGF-β in a concentration-dependent and time-dependent manner. Furthermore, we found that miR-132 was involved in modulation of the TGF-β signaling pathway and down-regulation of SMAD7 expression by directly targeting the SMAD7 3'-UTR. MiR-132 was negatively correlated with SMAD7 in patients with brain glioma. Taken together, our results suggest that miR-132 could be stimulated by TGF-β and might enhance the activation of TGF-β signaling through inhibiting SMAD7 expression in glioma cells. These findings contribute to a better understanding of the mechanism of the activation of TGF-β signaling by miR-132.

It has been implicated that electroacupuncture can relieve the symptoms of sciatica with the increase of pain threshold in human, and arginine vasopressin (AVP) in the brain rather than the spinal cord and blood circulation participates in antinociception. Our previous study has proven that AVP in the brain played a role in the process of electroacupuncture analgesia in rat. The goal of the present study was to investigate the role of AVP in electroacupuncture in treating primary sciatica in human. The results showed that (1) AVP concentration of cerebrospinal fluid (CSF) (7.5 ± 2.5 pg/ml), not plasma (13.2 ± 4.2 pg/ml) in primary sciatica patients was lower than that in health volunteers (16.1 ± 3.8 pg/ml and 12.3 ± 3.4 pg/ml), although the osmotic pressure in CSF and plasma did not change; (2) electroacupuncture of the bilateral "Zusanli" points (St. 36) for 60 min relieved the pain sensation in primary sciatica patients; (3) electroacupuncture increased the AVP level of CSF, not plasma in primary sciatica patients; and (4) there was the positive correlation between the effect of electroacupuncture relieving the pain and the AVP level of CSF in the primary sciatica patients. The data suggested that central AVP, not peripheral AVP might improve the effect of electroacupuncture treatment of primary sciatica in human, i.e., central AVP might take part in the electroacupuncture relieving the pain sensation in primary sciatica patients.