Huang X.,The General Hospital of Jinan Command |
Qin Y.,Shanghai University |
Li W.,The General Hospital of Jinan Command |
Shi Q.,Jinan Infectious Disease Hospital |
And 5 more authors.
Journal of Medical Virology | Year: 2013
This study was designed to detect and analyze mutations that occur within the presurface and surface (pre-S/S) gene of HBV in patients with occult hepatitis B, and determine their relationship to that disorder. Among 254 HBsAg negative samples of blood collected in eastern China, 183 were positive for anti-HBc alone, 61 were positive for anti-HBe alone, and 10 samples were positive for HBeAg. Within this group, 15 samples were found to be HBV DNA positive by real-time PCR and were designated Group I. A control group of 28 HBsAg positive samples were chosen at random from patients with chronic hepatitis B and designated Group II. The HBV pre-S/S gene was amplified by PCR and subjected to sequencing analysis. Occult hepatitis B was found in 1.6% of the patients with anti-HBc alone and in 3.3% of those with anti-HBe alone. Occult hepatitis B also was found in all HBsAg negative but HBeAg positive samples. Sequencing analysis showed a significant correlation between point mutations within the "a" determinant and occult hepatitis B (P<0.0001), and a close relationship between pre-S deletion mutations and occult hepatitis B (P=0.06). There were unique amino acid mutations at the G145 position other than G145R. The HBV DNA levels in patients with occult hepatitis B were significantly lower than those found in the control group. The "a" determinant mutations and pre-S deletions may play important roles in occult hepatitis B by affecting the expression, synthesis and secretion of the S protein and by impeding viral release and replication. © 2013 Wiley Periodicals, Inc.
Wang L.,Shandong University |
Liu F.,Shanghai JiaoTong University |
Liu Y.-D.,Yantai Infectious Disease Hospital |
Li X.-Y.,Jinan Infectious Disease Hospital |
And 3 more authors.
Journal of Viral Hepatitis | Year: 2010
The cessation criteria for lamivudine treatment vary in published articles and their results are contradictory, especially factors predicting relapse. To clarify these contradictions, this long-term follow-up study of 125 Chinese hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients was designed with stringent cessation criterion. All patients received lamivudine and achieved HBeAg seroconversion (group A, n = 82) or loss (group B, n = 43) with undetectable hepatitis B virus (HBV) DNA by PCR assay during the treatment. Lamivudine was withdrawn ≥6 months after HBeAg seroconversion/loss occurred. The median treatment durations were 24 (12-54) months and 36 (18-89) months in group A and group B, respectively. Patients were followed up for median 24 (2-84) months. The cumulative relapse (defined as serum HBV DNA ≥10 4 copies/mL) rates in the two groups at months 12, 24, 36 and 48 were 23.4%vs 35.0%, 25.0%vs 37.7%, 25.0%vs 41.1% and 29.4%vs 41.1%, respectively (log-rank test, P = 0.119). For patients whose total treatment duration ≥18 months in group A, the cumulative relapse rates at months 12, 24, 36 and 48 were 18.3%, 20.1%, 20.1% and 25.1%, which was significantly lower than those with a shorter duration (log-rank test, P = 0.002). The mean age and median total duration were statistically different between relapsers and nonrelapsers in group A (33.9 ± 13.6 vs 23.1 ± 11.0 years, P < 0.001 and 24 vs 26 months, P = 0.003). Cox regression revealed that age was the only predictive factor for relapse (RR, 1.069; 95% CI, 1.032-1.106, P < 0.001). Patients aged <30 years relapsed less frequently in 5 years (12.3%vs 53.5%, P = 0.001). In conclusion, for patients who maintained HBeAg seroconversion for ≥6 months and total duration for ≥18 months, lamivudine withdrawal is a reasonable option. Prolonged treatment may be required for patients aged greater than 30 years to reduce relapse. © 2009 Blackwell Publishing Ltd.
Gao S.,Shandong University |
Sun F.-K.,Shandong University |
Fan Y.-C.,Shandong University |
Shi C.-H.,Qingdao Infectious Disease Hospital |
And 3 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2015
Background Glutathione-S-transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute-on-chronic hepatitis B liver failure (ACHBLF). Aim To evaluate the methylation level of GSTP1 promoter in acute-on-chronic hepatitis B liver failure and determine its predictive value for prognosis. Methods One hundred and five patients with acute-on-chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained. Results GSTP1 methylation levels were significantly higher in patients with acute-on-chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83-59.05%) than those with CHB (median 1.25%, interquartile range 0.48-2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67-1.27%; P < 0.01). In acute-on-chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = -0.24, P = 0.01) and model for end-stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1- or 2-month mortality of acute-on-chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut-off points showed significantly poorer survival than those below (P < 0.05). Conclusions Aberrant GSTP1 promoter methylation exists in acute-on-chronic hepatitis B liver failure and shows high predictive value for short-term mortality. It might serve as a potential prognostic marker for acute-on-chronic hepatitis B liver failure. © 2015 John Wiley & Sons Ltd.
Wang C.,Jinan Infectious Disease Hospital |
Su L.,Jinan Infectious Disease Hospital |
Wu C.,Taian TCM Hospital |
Wu J.,Shandong University of Traditional Chinese Medicine |
And 2 more authors.
Drug Development and Industrial Pharmacy | Year: 2016
Context: Combination therapies provide a potential solution to address the tumor heterogeneity and drug resistance issues by taking advantage of distinct mechanisms of action of the multiple therapeutics. Objective: To design arginine-glycineaspartic acid (RGD) modified lipid-coated nanoparticles (NPs) for the co-delivery of the hydrophobic drugs against hepatocellular carcinoma (HCC). Materials and methods: RGD modified lipid-coated PLGA NPs were developed for the targeted delivery of both sorafenib (SRF) and quercetin (QT) (RGD-SRF-QT NPs). Chemical–physical characteristics and release profiles were evaluated. In vitro cell viability assays were carried out on HCC cells. In vivo antitumor efficacies were evaluated in HCC animal model. Results and discussion: The combination of SRF and QT formulations was more effective than the single drug formulations in both NPs and solution groups. RGD-SRF-QT NPs achieved the most significant tumor growth inhibition effect in vitro and in vivo. Conclusion: The resulting NPs could provide a promising platform for co-delivery of multiple anticancer drugs for achievement of combinational therapy and could offer potential for enhancing the therapeutic efficacy on HCC. © 2016 Informa UK Limited, trading as Taylor & Francis Group
Chu H.-L.,Shandong Normal University |
Chu H.-L.,General Hospital |
Mao H.,General Hospital |
Feng W.,General Hospital |
And 2 more authors.
International Journal of Biological Macromolecules | Year: 2013
Aim: To explore the inhibitory effect of sulfated polysaccharide from Masson pine (Pinus massoniana) pollen (SPPM60) on G2/M phase of human liver cancer HepG2 cells and its mechanism. Methods: The proliferation rate of HepG2 cells was evaluated by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The cycles of HepG2 cells were measured by flow cytometry when 200 μg/ml concentration of SPPM60 was adopted, the expression of the genes related to cell cycle was detected by real-time PCR. Results: SPPM60 inhibited the proliferation of HepG2 cells and the inhibition rate was elevated with increase of SPPM60 concentration. After treatment with 200μg/ml of SPPM60, the percentage of S phase cells was decreased, but that of G2/M phase was significantly increased (72h vs control: 32.96±0.33% vs 18.59±0.04%, 3.44±0.05% vs 18.30±0.08%, P<0.01). The results of real-time PCR showed that SPPM60 could down-regulate the mRNA levels of CDK1 and CyclinB (P<0.01), and up-regulate the expression of p53 and p21 (P<0.05). Conclusion: SPPM60 causes arrest of HepG2 cells at G2/M phase, and the mechanism is related to the down-regulation of CDK1 and CyclinB and up-regulation of p53 and p21 expression. © 2012 Elsevier B.V.
PubMed | General Hospital of Jinan Command and Jinan Infectious Disease Hospital
Type: Journal Article | Journal: Pharmaceutical development and technology | Year: 2016
Nanostructured lipid carriers (NLC) are potentially good colloidal drug carriers for gene delivery. They are advised to be the second lifetime of lipid nanocarriers.The aim of this study is to develop novel modified NLC as nanomedicine for delivery of plasmid-containing enhanced green fluorescence protein (pEGFP). This system could target the lung cancer cells through receptor-mediated pathways to increase the nuclear uptake of genetic materials.In the present study, pEGFP-loaded NLC (NLC/pEGFP) were prepared. Transferrin (Tf) containing ligands were used for the surface coating of the vectors. In vitro transfection efficiency of the modified vectors was evaluated in human alveolar adenocarcinoma cell line (A549 cells) and in vivo transfection efficiency of the modified vectors was evaluated on mice bearing A549 cells model.Tf-modified NLC/pEGFP (Tf-NLC/pEGFP) has a particle size of 157 nm, and 82% of gene loading quantity. Tf-NLC/pEGFP displayed remarkably higher transfection efficiency than non-modified NLC/pEGFP both in vitro and in vivo.The results demonstrate that the novel NLC gene delivery system offers an effective strategy for lung cancer gene therapy.
Rai D.,Shandong University |
Wang L.,Shandong University |
Jiang X.,Jinan Infectious Disease Hospital |
Zhan P.,Shandong University |
And 3 more authors.
Current Medicinal Chemistry | Year: 2015
Current treatment for HCV infections consists of approved direct acting antivirals (DAAs), viz. the protease inhibitors (boceprevir, telaprevir, and simeprevir), NS5B polymerase inhibitors (sofosbuvir) and NS5A inhibitor (ledipasvir) in combination with pegylated interferon α and ribavirin). These treatments have made a great improvement in the treatment of chronic HCV infections in recent years, but their adverse side effects, emergence of resistant mutants, high cost, and increased pill burden have limited their clinical use. Recently, with the increasing knowledge in understanding the HCV life cycle, more targets have been recognized. NS5A protein plays a critical role in assembly of infectious HCV particles and offering potential for HCV therapies. Therefore, discovery and development of novel DAAs targeting NS5A with novel mechanisms of action, are of great necessity to improve the quality of existing HCV treatments. In the present review, we discuss recent advances with NS5A inhibitors with potent anti-HCV activity, and the potential for the development of HCV NS5A inhibitors to combat HCV infections. © 2015 Bentham Science Publishers.
PubMed | Jinan No 4 Peoples Hospital, Jinan Minzu Hospital and Jinan Infectious Disease Hospital
Type: Journal Article | Journal: Experimental and therapeutic medicine | Year: 2016
Heart failure (HF) is a common pathological condition affecting 4% of the worldwide population. However, approaches for predicting or treating nondiabetic HF (ND-HF) progression are insufficient. In the current study, the gene expression profile GSE26887 was analyzed, which contained samples from 5 healthy controls, 7 diabetes mellitus-HF patients and 12 ND-HF patients with dilated ischemic cardiomyopathy. The dataset of 5 healthy controls and 12 ND-HF patients was normalized with robust multichip average analysis and the differentially expressed genes (DEGs) were screened by unequal variance t-test and multiple-testing correction. In addition, the protein-protein interaction (PPI) network of the upregulated and downregulated genes was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database and the Cytoscape software platform. Subsequently, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A total of 122 upregulated and 133 downregulated genes were detected. The most significantly up- and downregulated genes were
Zhu C.-B.,Jinan Infectious Disease Hospital |
Wang C.-X.,Shandong University |
Zhang X.,Shandong University |
Zhang J.,Shandong University |
Li W.,Shandong University
International Journal of Cancer | Year: 2011
Soluble human leukocyte antigen-G (sHLA-G) has been reported in malignancies and is implicated in mediating immune surveillance of tumor. The aim of our study is to detect serum sHLA-G levels in colorectal cancer and to determine whether sHLA-G may be helpful in distinguishing colorectal cancer from benign colorectal diseases. Serum sHLA-G levels were determined using enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve was used to evaluate the feasibility of sHLA-G in differentiating colorectal cancer from benign colorectal diseases. Median sHLA-G concentrations were significantly higher in colorectal cancer compared to normal colorectum, hyperplastic polyp, inflammatory bowel disease and adenoma (all at p < 0.001, respectively). ROC curve for sHLA-G revealed an area under the curve of 84.2%, and when 88.6 U/mL was used as cutoff, a sensitivity of 72.2% and a specificity of 87.8% were achieved. Comparison of sHLA-G and carcinoembryogenic antigen ROC curves indicated that sHLA-G was superior to CEA in differentiating colorectal cancer from benign colorectal diseases (p < 0.001). ROC curves analysis of the combined sHLA-G and CEA showed a higher detection capacity (area under the ROC curve, 87.4%) than that of markers considered singly. These findings reveal that serum levels of sHLA-G are significantly increased in colorectal cancer which may serve as a potent mediator of immune escape in colorectal cancer, and sHLA-G may be a useful indicator in differentiating colorectal cancer from benign colorectal diseases. Copyright © 2010 UICC.
Sun H.Y.,Shandong University |
Yu C.,Jinan Infectious Disease Hospital
Applied Mechanics and Materials | Year: 2013
In the WEB2.0 environment, the report of public events will appear on the Internet as soon as they occur and attract a large number of people's attention in a very short time. It is believed that the Internet public opinion represents the social public opinion. Hence, it is very valuable to study the relationship between the Internet public opinion and mass emergencies. In this paper, we proposed an improved effect model of the Internet public opinion spreading on mass emergencies. Different from the original model, we use variables as the parameters of the equation instead of constants and the whole mass emergency is divided into five stages. In the first two stages, the new participants proportion u(t) and the new leavers proportion v(t) holds the inequality u(t)≥v(t), and in the other stages, they hold u(t)≤v(t). Simulations show that the design of our proposed model can well fit the mass emergency development process. © (2013) Trans Tech Publications, Switzerland.