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The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing globally, being the most widespread form of chronic liver disease in the west. NAFLD includes a variety of disease states, the mildest being non-alcoholic fatty liver that gradually progresses to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Small non-coding single-stranded microRNAs (miRNAs) regulate gene expression at the miRNA or translational level. Numerous miRNAs have been shown to promote NAFLD pathogenesis and progression through increasing lipid accumulation, oxidative stress, mitochondrial damage, and inflammation. The miR-23–27–24 clusters, composed of miR-23a–27a–24–2 and miR-23b–27b–24–1, have been implicated in various biological processes as well as many diseases. Herein, we review the current knowledge on miR-27, miR-24, and miR-23 in NAFLD pathogenesis and discuss their potential significance in NAFLD diagnosis and therapy.

OBJECTIVES To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to

Background and Aim In China, clinical experience with direct‐acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C‐CORAL is a phase 3, multinational, placebo‐controlled, double‐blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia‐Pacific region and Russia. Here, we report the data from participants enrolled in China. Methods Treatment‐naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate‐treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred‐treatment group, DTG). The primary efficacy end‐point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end‐point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN‐5172‐067). Results A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug‐related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug‐related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient‐reported outcomes indicate improved quality of life at follow‐up week 4 in participants receiving EBR/GZR compared to placebo. Conclusion EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection., A sustained virologic response was achieved by 96.7% (146/151) of treatment‐naive participants with hepatitis c virus infection receiving elbasvir/grazoprevir (50 mg/100 mg) for 12 weeks. Patient‐reported outcomes indicate improved quality of life following clearance of HCV.

Plant sugar transporters are key physiological elements in transporting sucrose and sensing specific sucrose signals. A knockoff of the novel sugar transporter gene (ScERD6) was developed by RACE-PCR from sugarcane, which incorporated an ORF of 1521 bp encoding a protein of 506 amino acids. The isolated ScERD6 gene was measured by 4722 bp DNA and containing 17 exons and 16 introns. It was found that the ScERD6 only had one transcript, and the ScERD6 protein consisted of potentially 12 transmembrane domains, belonging to sugar transporter protein. The promoter sequence was cloned by using genome walking, which included CAAT-boxes and TATA-boxes, as well as specific acting elements such as cis-regulatory elements involved in hormone response, seed development, environmental stresses, ACES, G-box, I-box, L-box, and rbcS-CMA7 light response element, etc. The treatments with 15% PEG and 6 °C stress can induce the expression of ScERD6 in the leaf, root, and stem. But ScERD6 expression in stem was different from that in leaf and root of sugarcane. Real-time PCR analysis uncovered the presence of ScERD6 in roots, stems, leaves, inflorescence, and buds, excessively, and the highest transcript level was observed in inflorescence, and the lowest in roots, while the average was detected in the stem. This finding predicted an important role of this gene in reproductive and floral development.

The protein arginine methyltransferase 5 (PRMT5), which is highly expressed in tumour tissues, plays a crucial role in cancer development. However, the mechanism by which PRMT5 promotes cancer growth is poorly understood. Here, we report that PRMT5 contributes to lipid metabolism reprogramming, tumour growth and metastasis depending on the SIRT7-mediated desuccinylation of PRMT5 K387 in tumours. Mass spectrometric analysis identified PRMT5 lysine 387 as its succinylation site. Moreover, the desuccinylation of PRMT5 K387 enhances the methyltransferase activity of PRMT5. SIRT7 catalyses the desuccinylation of PRMT5 in cells. The SIRT7-mediated dessuccinylation of PRMT5 lysine 387 fails to bind to STUB1, decreasing PRMT5 ubiquitination and increasing the interaction between PRMT5 and Mep50, which promotes the formation of the PRMT5-Mep50 octamer. The PRMT5-Mep50 octamer increases PRMT5 methyltransferase activity, leading to arginine methylation of SREBP1a. The symmetric dimethylation of SREBP1a increases the levels of cholesterol, fatty acid, and triglyceride biogenesis in the cells, escaping degradation through the ubiquitin-proteasome pathway. Functionally, the desuccinylation of PRMT5 K387 promotes lipid metabolism reprogramming, tumour growth and metastasis in vitro and in vivo in tumours.

Highbush blueberry is a small berry fruit tree belonging to the family Ericaceae and genus Vaccinium, which fruit has high nutritional value. High-throughput sequencing technology was applied in this study to sequence and assemble the whole chloroplast genome of the southern highbush blueberry variety sharpblue. The results of the study showed that the circular genome of sharpblue is 170,737 bp in length, and the GC content of the genome was 36.8%. The complete chloroplast genome of sharpblue has consisted of two inverted repeat regions (IRs), a large single-copy region (LSC, 31, 076 bp), and a small single-copy region (SSC, 3, 044 bp). The chloroplast genome contained a total of 144 functional genes, including 100 mRNA genes, eight rRNA genes, and 36 tRNA genes. In addition, V. corymbosum and V. oldhamii were clustered into one group in this phylogenetic analysis which indicated that they have a close evolutionary relationship. The findings of this investigation are a significant reference source for the phylogeny and evolutionary origin of the Ericaceae family.

Rationale: Hepatitis B virus (HBV) is a leading cause of liver diseases. HBV covalently closed circular DNA (cccDNA) is a critical obstacle of complete elimination by anti-HBV therapy. HBV cccDNA accumulates in nucleus as a chromatin-like cccDNA minichromosome assembled by histones and non-histones. However, the underlying mechanism of modulation of cccDNA minichromosome in hepatocytes is poorly understood. Methods: A human liver-chimeric mouse model was established. The cccDNA-ChIP, Southern blot analysis, confocal assays, RIP assays and RNA pull-down assays, et al. were performed to assess the mechanism of assembly and epigenetic regulation of cccDNA minichromosome in human liver-chimeric mouse model, human primary hepatocytes (PHH), dHepaRG, HepG2-NTCP cell lines and clinical liver tissues. Results: Importantly, the expression levels of HAT1, CAF-1 and lncRNA HULC were significantly elevated in the liver from HBV-infected human liver-chimeric mice. Strikingly, the depletion of HAT1 reduced HBV replication and cccDNA accumulation, and impaired the assembly of histone H3/H4 and the deposition of HBx and p300 onto cccDNA to form cccDNA minichromosome in the cells. Mechanically, chromatin assembly factor-1 (CAF-1) was involved in the events. Interestingly, HAT1 modified the acetylation of histone H3K27/H4K5/H4K12 on cccDNA minichromosome. Moreover, lncRNA HULC-scaffold HAT1/HULC/HBc complex was responsible for the modification on cccDNA minichromosome. Additionally, HBV activated HAT1 through HBx-co-activated transcriptional factor Sp1 in a positive feedback manner. Conclusion: HAT1 signaling contributes to assembly and epigenetic regulation of HBV cccDNA minichromosome.

Pueraria thomsonii is a leguminous plant with high root yield and starch content. It is also a medicinal material in the Chinese pharmacopeia. However, the raw materials of P. thomsonii are often confused with some non-medicinal Pueraria plants. To enrich the genetic resources of P. thomsonii and guide its molecular identification, the complete chloroplast genome was sequenced and reported. The total genome of P. thomsonii is 153,434 bp in length. consisting of two inverted repeat regions (IRS, 25,640 bp each) separated by a large single-copy (LSC, 84,155 bp) and a small single-copy region (SSC, 17,999 bp). The overall GC content is 35.41%. It contains 130 genes, including 85 protein coding genes, 8 rRNA genes and 37 tRNA genes. Phylogenetic analysis showed that P. thomsonii could be distinguished from other plants and closely related to the legume Pachyrhizus erosus. This study enriches the genetic information of P. thomsonii and contributes to the screening of excellent germplasm.

Five SUT genes, namely SoSUT1, SoSUT2, SoSUT3, SoSUT4, and SoSUT5, were cloned, and their expressions in roots, stems, leaves, inflorescence, and buds at physiological mature stage were analyzed by qRT-PCR. Major findings of the study were: (1) the molecular mass of deduced sugarcane sucrose transporter proteins was between 53.44 and 61.80 kDa, and the pIs were between 5.94 and 10.68; (2) all sugarcane sucrose transporter proteins had 12 typical transmembrane domains; (3) there were two DNA sequences encoding the SoSUT3 gene with six exons and five introns; (4) while SoSUT2, SoSUT4, and SoSUT5 belonged to Clades SUT2, SUT4, and SUT5, other SoSUT proteins belonged to Clade SUT3; (5) real-time PCR analyses results showed SoSUT1, SoSUT4, and SoSUT5 had highly abundant expression in the inflorescence, and SoSUT2 and SoSUT3 highly expressed in the buds and inflorescence at physiological maturity. These data may indicate that different SUT genes may be transcribed during the sucrose accumulation process in sugarcane stems and that the expressions of SoSUTs may play an important role in sugarcane inflorescence development.

BACKGROUND AND AIM Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6. METHODS Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12 or 24 weeks, respectively. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12). RESULTS Of 389 patients, 42% had genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male, 58% were treatment-naive, and 15% had cirrhosis. SVR12 rates for patients receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95% confidence interval [CI], 87-98%) for HCV genotype 1 and 97% (95% CI, 84-100%) for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24 weeks were 95% (95% CI, 87-99%) for genotype 1, 100% (95% CI, 40-100%) for genotype 6, and 95% (95% CI, 90-98%) for genotype 3. For genotype 2 patients receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83-97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events. Three (

OBJECTIVE To evaluate tolvaptan as a novel therapeutic option for Chinese patients with liver cirrhosis-associated ascites in a phase 2 clinical trial. METHODS This randomized, double-blind, placebo-controlled, multicenter trial was conducted in patients with insufficient responses to combination therapies of an oral loop diuretic and an aldosterone antagonist. Reduction in body weight and abdominal circumference, increase in 24-h cumulative urine volume and improvement in serum sodium level from baseline to the end of treatment in the tolvaptan groups (15 mg/day or 30 mg/day orally) were compared with those in the placebo group. Drug safety was also assessed. RESULTS Sixty-two patients were allocated to the placebo group, 56 to the tolvaptan 15-mg group and 63 to the tolvaptan 30-mg group. Their mean changes in body weight were -0.5 ± 1.6 kg, -2.1 ± 2.0 kg and -1.9 ± 2.0 kg, respectively. Body weight reductions in both tolvaptan groups were significantly greater than that in the placebo group (difference -1.6, 95% confidence interval [CI] -2.5 to -0.8, and difference -1.4, 95% CI, -2.2 to -0.7, both P

Pueraria thomsonii is a leguminous plant with high root yield and starch content. It is also a medicinal material in the Chinese pharmacopeia. However, the raw materials of P. thomsonii are often confused with some non-medicinal Pueraria plants. To enrich the genetic resources of P. thomsonii and guide its molecular identification, the complete chloroplast genome was sequenced and reported. The total genome of P. thomsonii is 153,434 bp in length. consisting of two inverted repeat regions (IRS, 25,640 bp each) separated by a large single-copy (LSC, 84,155 bp) and a small single-copy region (SSC, 17,999 bp). The overall GC content is 35.41%. It contains 130 genes, including 85 protein coding genes, 8 rRNA genes and 37 tRNA genes. Phylogenetic analysis showed that P. thomsonii could be distinguished from other plants and closely related to the legume Pachyrhizus erosus. This study enriches the genetic information of P. thomsonii and contributes to the screening of excellent germplasm.

Capparis versicolor Griff. is a rare and threatened medicinal plant in South China. Chloroplast (cp)-derived markers have been widely used to study evolutionary relationships of many species. In th...

Aberrant expression of miR-511 is involved in the development of cancer, but the role of miR-511 in hepatocellular carcinoma (HCC) is not well documented. In this study, we explored the molecular mechanisms of miR-511 in hepatocarcinogenesis. Our results of bioinformatics analysis suggested that B cell translocation gene 1 (BTG1), a member of anti-proliferative gene family, was one of the putative targets of miR-511. The expression levels of miR-511 were significantly higher in 30 clinical HCC tissues than in corresponding peritumor tissues, and were negatively correlated with those of BTG1 in the HCC tissues (r=-0.6105, P

This study aimed to explore and evaluate the tolerability and antiviral activity of pegylated recombinant human consensus interferon-α (PEG-CIFN) in adults with hepatitis C virus (HCV) infection. A total of 48 adult subjects chronically infected with HCV were divided into five groups, which were treated separately with PEG-CIFN 1.0 µg/kg (n=10), 1.5 µg/kg (n=10), 2.0 µg/kg (n=9) or 3.0 µg/kg (n=10), or pegylated IFN α-2a (Pegasys) 180 µg (n=9) as controls. Symptoms were observed and laboratory results collected to monitor adverse reactions, adjust drug dosage and evaluate tolerability. The thrombocytopenic effects in all PEG-CIFN dose groups were less than that of pegylated IFN α-2a (at week 14, P

BACKGROUND AND AIM Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.

Chitosan is a linear polysaccharide that is made by treating the chitin shells of shrimp and crustaceans with an alkaline substance, for example sodium hydroxide. Due to its unique physical and chemical properties, chitosan has a wide range of applications in the medical field. Currently, there are no effective treatments for liver fibrosis; therefore, the aim of the present study was to investigate the therapeutic effect of chitosan in a CCl4‑induced hepatic fibrosis (HF) rat model. The serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were measured by ELISA. Collagen (COL) 3 and α‑smooth muscle actin (SMA) expression levels in the rat liver were detected by reverse transcription‑semiquantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that treatment with chitosan significantly improved HF, by decreasing the serum levels of AST, ALT, and ALP; improving liver histology; and decreasing the expression levels of COL3 and α‑SMA. Chitosan may offer an alternative approach for the clinical treatment of HF.

AIM To assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection. METHODS Patients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebo-deferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in DUAL-treated patients compared with placebo patients during the first 12 wk (double-blind phase), and during 24 wk of DUAL in both arms combined. RESULTS In total, 207 patients were randomly assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them, 13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/mL. Among patients in the immediate treatment arm, SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ≥ 65 years (92%), male sex (90%), baseline HCV RNA ≥ 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistance-associated polymorphisms (at L31 or Y93H). During the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the most common adverse events (≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths. CONCLUSION DUAL was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%) exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.

To evaluate tolvaptan as a novel therapeutic option for Chinese patients with liver cirrhosis-associated ascites in a phase 2 clinical trial.This randomized, double-blind, placebo-controlled, multicenter trial was conducted in patients with insufficient responses to combination therapies of an oral loop diuretic and an aldosterone antagonist. Reduction in body weight and abdominal circumference, increase in 24-h cumulative urine volume and improvement in serum sodium level from baseline to the end of treatment in the tolvaptan groups (15 mg/day or 30 mg/day orally) were compared with those in the placebo group. Drug safety was also assessed.Sixty-two patients were allocated to the placebo group, 56 to the tolvaptan 15-mg group and 63 to the tolvaptan 30-mg group. Their mean changes in body weight were -0.5 ± 1.6 kg, -2.1 ± 2.0 kg and -1.9 ± 2.0 kg, respectively. Body weight reductions in both tolvaptan groups were significantly greater than that in the placebo group (difference -1.6, 95% confidence interval [CI] -2.5 to -0.8, and difference -1.4, 95% CI, -2.2 to -0.7, both P 0.0001). The administration of tolvaptan also significantly reduced the abdominal circumference, increased 24-h cumulative urine volume and serum sodium level compared with placebo. The most common adverse events in the tolvaptan groups were constipation, diarrhea, dry mouth and thirst, with no severe adverse events observed.Tolvaptan at 15 mg/day significantly reduced the body weight and abdominal circumference in patients with liver cirrhosis-associated ascites, which needs to be confirmed in a phase 3 trial.

Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6.Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12 or 24 weeks, respectively. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12).Of 389 patients, 42% had genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male, 58% were treatment-naïve, and 15% had cirrhosis. SVR12 rates for patients receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95% confidence interval [CI], 87-98%) for HCV genotype 1 and 97% (95% CI, 84-100%) for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24 weeks were 95% (95% CI, 87-99%) for genotype 1, 100% (95% CI, 40-100%) for genotype 6, and 95% (95% CI, 90-98%) for genotype 3. For genotype 2 patients receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83-97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events. Three ( 1%) discontinued treatment because of adverse events, of whom one died because of treatment-unrelated adverse events.Sofosbuvir-based regimens were highly effective and safe in Chinese patients with HCV genotype 1, 2, 3, or 6, suggesting sofosbuvir could serve as the backbone for HCV treatment in China irrespective of genotype.

Cell wall invertase (CIN) plays an important role in carbohydrate partitioning and regulation of sink-source interaction. In this study, a full length cDNA encoding CIN gene was cloned by RT-PCR and RACE-PCR from sugarcane. The open reading frame of 1731 bp encodes a protein of 577 amino acids with a predicted molecular mass of 141.04 kDa and theoretical PI of 4.67. A size of 4,537 bp DNA encoding SoCIN1 was isolated, which contains seven exons and six introns. Using genome walking approach, a promoter sequence of 974 bp of SoCIN1 was isolated, and prediction with PlantCARE and PLACE software revealed that it has several key cis-regulatory elements known to be involved in various biotic and abiotic plant stresses. Relative expression in specific tissues was done using qRT-PCR, and the results demonstrated that SoCIN1 expression level was higher in the immature leaves and maturing leaves than the matured leaves and internodes at elongation stage and processing maturing stage. The conditions of 15 % PEG and 6 °C could have a similar function for inducing the expression of SoCIN gene in leaves, while 15 % PEG, 100 mM NaCl and 6 °C could induce the expression of SoCIN gene in roots.

Ethylene receptor (ethylene response sensor, ERS) is the primary component involving in the ethylene biosynthesis and ethylene signal transduction pathway. In the present study, a GZ-ERS gene encoding ERS was cloned from a sugarcane cv. YL17 (Saccharum spp.) using RT-PCR and ligation-mediated PCR with primers designed based on conserved amino acid sequences of ERS from rice and corn. The GZ-ERS gene was 2,243 base pairs in length and coded for a polypeptide of 633 amino acid residues. The amino acid sequence of GZ-ERS encoded protein was 97, 96 and 91 % identical to OS-ERS (AAX95525) of rice, ZmERS25 (AAR25567) of corn, and Sc-ERS (ACF60981) of a sugarcane cv. ROC22, respectively. Genomic Southern analysis using a GZ-ERS cDNA insert as the probe indicated the presence of a single copy of GZ-ERS gene per haploid sugarcane genome. Real-time qPCR analysis showed that GZ-ERS was widely expressed in the vegetative tissues of sugarcane, and its expression in maturing internodes and leaf tissues was higher than in immature tissues. Furthermore, the expression level of GZ-ERS was the highest in maturing leaves, but very low in immature internodes. The GZ-ERS expression level in maturing leaves was enhanced by ethephon treatment, but was reduced under low temperature, drought, and dark conditions. The results from this study may help understand the regulation of gene expression in sugarcane and its responses to plant growth regulator ethephon and environmental stresses. As the sugarcane ERS family has multiple members, other members need to be isolated and characterized in future studies.

Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels. Following liquid chromatography-tandem mass analysis of the DIOB content of DB extract, male ICR mice were randomly orally administered DB or DIOB for 14days. Liver injury was assessed by histopathological and biochemical analysis of liver fuction. The levels of transporter protein and mRNA were determined by western blotting and real-time PCR. Liver function and histopathological analysis indicated that both DB and DIOB could induce liver injury in mice, and that DIOB might be the primary toxic compound in DB. Moreover, down-regulation of Mrp2 blocked the excretion of bilirubin, glutathione disulfide, and bile acids, leading to the accumulation of toxic substrates in the liver and a redox imbalance. We identified down-regulated expression of Mrp2 as potential factors linked to increased serum bilirubin levels and decreased levels of glutathione in the liver and increased liver injury severity. In summary, our study indicates that down-regulation of Mrp2 represents the primary mechanism of DB- and DIOB-induced hepatotoxicity, and provides insight into novel therapies that could be used to prevent DB- and DIOB-mediated liver injury.

Sucrose synthase (SS), sucrose phosphate synthase (SPS), soluble acid invertase (SAI) and neutral invertase (NI) are the key enzymes of sucrose metabolism, which activities play key role in sugar accumulation. In the present study, sugarcane variety GT28 was used as the plant material, effects of ethephon, an ethylene releasing agent, on the key enzymes of sucrose metabolism and ethylene production in relation to sucrose accumulation in sugarcane stalk and leaves were analyzed. The plants were treated by foliar spray of 400 mg/L ethephon at late growth stage. The results showed that ethylene production in leaves was positively while that in stalk internodes was negatively correlated with the maturity of leaves and stalks. The activities of SS, SPS and NI in stalk and leaves were positively while that of NI was negatively correlated with the maturity of stalks and leaves. High concentration of ethephon significantly inhibited the ethylene production and the activities of SS, SPS and NI but increased the activity of SAI enzyme in immature leaves, while promoted the ethylene production and the activities of SS, SPS and NI in maturing and matured leaves and the activity of SAI in maturing leaves but inhibited the activity of SAI in matured leaves. The active duration of ethylene releasing and the effects of ethephon on the key enzymes in leaves lasted for about 5–10 days. The ethylene production was much lower in internodes than in leaves. High concentrations of ethephon significantly increased the ethylene production in all the three different internodes in a short time but longer for immature internode, and it significantly improved the activities of SS, SPS in all the internodes and that of NI in immature and maturing internodes, but inhibited the activity of SAI in the three internodes and that of NI in matured internode. It is suggested that high concentration of ethephon may accelerate the leaf maturity and aging of the matured leaves by increasing ethylene production which could promote the activities of SS, SPS and NI in maturing and matured leaves, and the activity of SAI in immature and maturing leaves, speeding up the sucrose synthesis in maturing and matured leaf and the sucrose transportation from leaves to immature and maturing internodes, resulting in faster sugar accumulation in immature and maturing internodes of the stalks and higher sucrose content in whole cane.

Measurement for hemodynamic parameters has always been a hot spot of clinical research. Methods for measuring hemodynamic parameters clinically have the problems of invasiveness, complex operation and being unfit for repeated measurement. To solve the problems, an indicator densitometry analysis method is presented based on near-infrared spectroscopy (NIRS) and indicator dilution theory, which realizes the hemodynamic parameters measured noninvasively. While the indocyanine green (ICG) was injected into human body, circulation carried the indicator mixing and diluting with the bloodstream. Then the near-nfrared probe was used to emit near-infrared light at 735, 805 and 940 nm wavelengths through the sufferer's fingertip and synchronously capture the transmission light containing the information of arterial pulse wave. By uploading the measured data, the computer would calculate the ICG concentration, establish continuous concentration curve and compute some intermediate variables such as the mean transmission time (MTT) and the initial blood ICG concentration (c(t0)). Accordingly Cardiac Output (CO) and Circulating Blood Volume (CBV) could be calculated. Compared with the clinical "gold standard" methods of thermodilution and I-131 isotope-labelling method to measure the two parameters by clinical controlled trials, ten sets of data were obtained. The maximum relative errors of this method were 8.88% and 4.28% respectively, and both of the average relative errors were below 5%. The result indicates that this method can meet the clinical accuracy requirement and can be used as a noninvasive, repeatable and applied solution for clinical hemodynamnic parameters measurement.

Currently, functional near-infrared spectroscopy (fNIRS) is widely used in the field of Neuroimaging. To solve the signal-noise frequency spectrum aliasing in non-linear and non-stationary fNIRS characteristic signal extraction, a new joint multi-resolution algorithm, EEMD-ICA, is proposed based on combining Independent Component Analysis with Ensemble Empirical Mode Decomposing. After functional brain imaging instrument detected the multi-channel and multi-wavelength NIR optical density signals, EEMD was performed to decompose measurement signals into multiple intrinsic mode function according to the signal frequency component. Then ICA was applied to extract the interest data from IMFs into ICs. Finally, reconstructed signals were obtained by accumulating the ICs set. EEMD-ICA was applied in de-noising Valsalva test signals which were considered as original signals and compared with Empirical Mode Decomposing and Ensemble Empirical Mode Decomposing to illustrate validity of this algorithm. It is proved that useful information loss during de-noising and invalidity of noise elimination are completely solved by EEMD-ICA. This algorithm is more optimized than other two de-noising methods in error parameters and signal-noise-ratio analysis.

Dyslipidemia, is a major risk factor for premature coronary artery disease. Our aim was to estimate the prevalence of dyslipidemia (blood lipid abnormalities) and other risk factors associated with coronary artery diseases among an adult population in northeastern China. Throughout the months of September and October of 2007,a population-based cross-sectional study was conducted and a total of 3,815 individuals were included. Total cholesterol (TC), high-density cholesterol (HDL-C), low-density cholesterol (LDL-C), and triglycerides (TG) were measured. A binary logistic regression analysis was conducted to determine risk factors associated with dyslipidemia. The prevalence of hypercholesterolemia, high LDL-C, low HDL-C, and hypertriglyceridemia were 17.3%, 27.8%, 11.66% and 29.85%, respectively. The prevalence of hypertension, central obesity, alcoholic liver disease (ALD), non-ALD, diabetes and metabolic syndrome was higher in serum lipid abnormality groups than in the non-dyslipidemia group (p < 0.001). In a binary logistic regression, hyperlipidemia was positively correlated with age, male, hypertension, high body mass index, etc. There were negative correlations with being female and the level of education a subject had attained. Dyslipidemia is a major risk factor for premature coronary artery diseases and an important public health issue in the northeastern part of China. Dyslipidemia is more frequent than expected based on previous studies. To control dyslipidemia, routine evaluations in clinics and community centers are needed, as well as effective public health education.

Nucleoside/tide analogs are now widely used for treatment of chronic hepatitis B (CHB). However, available nucleoside/tide analogs for treatment of CHB usually have limited therapeutic effect and potential adverse effects on CHB patients. We evaluated the anti-HBV effects of three novel derivatives (compounds 1, 4, and 8) of adefovir on the replication of hepatitis B virus (HBV) and determined their cytotoxicity. The effects of those compounds on the replication of human HBV in the HepG2 2.2.15 cell line and duck HBV in infected ducks were characterized by measuring the extracellular and intracellular HBV DNA using the quantitative real-time PCR and Southern blot assays. Their cytotoxicities against HepG2 cells were evaluated by MTT and measuring the contents of mitochondrial DNA using the dot blot assay. We found that all of the compounds inhibited the production of HBV in a dose-dependent manner, similar to that of adefovir dipivoxil. Furthermore, treatment with any of the compounds reduced significantly the replication of DHBV in ducks, accompanied by a significant reduction of inflammation in the livers, and the compound 1 appeared to be a fast-acting and long-lasting anti-DHBV reagent. Importantly, all of the compounds showed little cytotoxicity against HepG2 cells, even at a concentration of 1 mM. Collectively, those novel derivatives of adefovir had potent anti-HBV activity with little adverse effect and may be therapeutic candidates for potential clinical studies.

Background: Serum biochemical liver tests (LTs) (alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase) and platelet counts are often used to screen for chronic liver disease. We determined the prevalence and etiologies of abnormal LTs in an adult population in Jilin, China. Methods: A total of 3791 individuals between the ages of 18 and 79 years were interviewed and then underwent ultrasonography and blood tests. Results: The prevalence of abnormal LTs was 14.77% (560 out of 3791 subjects). The risk factors for abnormal LTs were non-alcoholic fatty liver disease (NAFLD) alone, which accounted for 11.61%, metabolic syndrome alone for 25%, or both for 22.14%. Abnormal LTs were more common in male than in female subjects. The development of abnormal LTs was correlated with older age males, increased daily alcohol intake, poor quality of sleep, smoking, fasting plasma glucose, body mass index, triglyceridemia, and low-density lipoprotein. Abnormal LTs in patients with metabolic syndrome and NAFLD were associated with high fasting plasma glucose, triglycerides, body mass index, low density lipoprotein, male, young age, poor sleep quality, smoking, and alcohol intake. However, abnormal LTs in patients with hepatitis B virus were associated with gender and increased age. Conclusions: The results from the current study demonstrated that the prevalence of abnormal LTs is high in the population (14.77%). Metabolic syndrome, NAFLD, and alcohol intake appear to be potentially important causes of the observed abnormal LTs.

Background: Serum biochemical liver tests (LTs) (alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase) and platelet counts are often used to screen for chronic liver disease. We determined the prevalence and etiologies of abnormal LTs in an adult population in Jilin, China.Methods: A total of 3791 individuals between the ages of 18 and 79 years were interviewed and then underwent ultrasonography and blood tests.Results: The prevalence of abnormal LTs was 14.77% (560 out of 3791 subjects). The risk factors for abnormal LTs were non-alcoholic fatty liver disease (NAFLD) alone, which accounted for 11.61%, metabolic syndrome alone for 25%, or both for 22.14%. Abnormal LTs were more common in male than in female subjects. The development of abnormal LTs was correlated with older age males, increased daily alcohol intake, poor quality of sleep, smoking, fasting plasma glucose, body mass index, triglyceridemia, and low-density lipoprotein. Abnormal LTs in patients with metabolic syndrome and NAFLD were associated with high fasting plasma glucose, triglycerides, body mass index, low density lipoprotein, male, young age, poor sleep quality, smoking, and alcohol intake. However, abnormal LTs in patients with hepatitis B virus were associated with gender and increased age.Conclusions: The results from the current study demonstrated that the prevalence of abnormal LTs is high in the population (14.77%). Metabolic syndrome, NAFLD, and alcohol intake appear to be potentially important causes of the observed abnormal LTs.

The mutant of virus is a frequent event. Hepatitis B virus X protein (HBx) plays a vital role in the development of hepatocellular carcinoma (HCC). Therefore, the identification of potent mutant of HBx in hepatocarcinogenesis is significant. Previously, we identified a natural mutant of the HBx gene (termed HBxΔ127). Relative to wild type HBx, HBxΔ127 strongly enhanced cell proliferation and migration in HCC. In this study, we aim to explore the mechanism of HBxΔ127 in promotion of proliferation of hepatoma cells. Our data showed that both wild type HBx and HBxΔ127 could increase the expression of miR-215 in hepatoma HepG2 and H7402 cells. However, HBxΔ127 was able to significantly increase miR-215 expression relative to wild type HBx in the cells. We identified that protein tyrosine phosphatase, receptor type T (PTPRT) was one of the target genes of miR-215 through targeting 3'UTR of PTPRT mRNA. In function, miR-215 was able to promote the proliferation of hepatoma cells. Meanwhile anti-miR-215 could partially abolish the enhancement of cell proliferation mediated by HBxΔ127 in vitro. Knockdown of PTPRT by siRNA could distinctly suppress the decrease of cell proliferation mediated by anti-miR-215 in HepG2-XΔ127/H7402-XΔ127 cells. Moreover, we found that anti-miR-215 remarkably inhibited the tumor growth of hepatoma cells in nude mice. Collectively, relative to wild type HBx, HBxΔ127 strongly enhances proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT. Our finding provides new insights into the mechanism of HBx mutant HBxΔ127 in promotion of proliferation of hepatoma cells.

Chronic liver diseases are a major burden in China. Alanine aminotransferase (ALT) can be used as an indicator of hepatocyte damage. In this study, we determined the prevalence and etiologies of elevated ALT in an adult population in Jilin, China.A total of 4072 individuals aged between 18 and 79 years were first interviewed, and then underwent ultrasonography and blood tests.The prevalence of elevated ALT was 17.53%. The most noticeable risk factor for ALT elevation was non-alcoholic fatty liver disease (NAFLD) (accounting for 10.79%), metabolic syndrome (16.25%), or both (20.31%). The development of NAFLD occurred mostly in female peasants and small businessmen with increased income, age, fasting plasma glucose, body mass index, triglyceridemia, and low-density lipoprotein and decreased education level, high-density lipoprotein. Elevated ALT frequently occurred in low education level, male peasants and small businessmen with increased income, body mass index and triglyceride who had NAFLD and/or metabolic syndrome. However, elevated ALT with infection of hepatitis B or C virus was not associated with metabolic disorders, but rather with gender, occupation and increased age.The results from the current study demonstrate that elevated ALT is fairly high in the Northeast population (17.53%) and that the cause of its elevation is mostly due to NAFLD and metabolic syndrome.

The impact of adefovir dipivoxil (ADV) treatment on the immune system in patients with chronic hepatitis B (CHB) is unknown. The present study was designed to determine the expression of six cytokines, IL-2, IFN-γ, TNF-α, IL-4, IL-6 and IL-10, and their correlation with liver functions and clinical responses to ADV treatment. A total of 22 CHB patients were treated with ADV at a daily oral dose of 10 mg. Six cytokines, as well as AST, ALT and HBV DNA levels in blood samples were quantified prior to and following the treatment. A total of 10 healthy volunteers were enrolled as the control group. The six cytokines in CHB patients were significantly lower than in healthy individuals, and were increased significantly following 4, 12 and 24 weeks of ADV treatment. Although ALT, AST and HBV DNA were reduced following treatment, no correlation was found between these six cytokines and liver function or HBV DNA levels. The levels of the six cytokines in the group of patients with a complete clinical response were significantly higher than those in the group with a partial clinical response. ADV treatment increases the immunity of Th1/Th2 cells in CHB patients, and the increases in cytokines partly reflect the efficacy of the antiviral treatment.

To investigate the distribution of hepatitis B virus (HBV) genotypes in patients with chronic HBV infection among 11 cities of China.A total of 1214 serum samples from patients with chronic HBV infection were collected in 11 cities of China, including Beijing, Qingyuan, Shenzhen, Shijiazhuang, Hanchuan, Nanjing, Changchun, Liaocheng, Jinan, Ningbo and Wenzhou. Genotypes of the 1214 HBV strains were identified by PCR method with type specific primers. Parts of the results were confirmed by direct sequencing analysis of PCR products.Among the 1214 patients with chronic HBV infection, 0.7% (9/1214)were genotype A, 28.4% (345/1214)genotype B, 58.4% (709/1214) genotype C, and 12.4% (151/1214) genotype B and genotype C mixed infection. No other genotypes were found. Genotype C was predominant in the northern part of China, such as Changchun, Beijing, Shijiazhuang,while genotype B was more commonly seen in south of China. 71.4% (20/28) for patients from Qingyuan and 63.6% (70/110) from Shenzhen were infected with genotype B.HBV genotypes had distinct geographic distribution. Genotype B and C the predominant strains in patients with chronic HBV infection in China. Genotype C was predominantly identified in the northern part of China versus genotype B the south.