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PubMed | Xixi Hospital of Hangzhou and Zhejiang University
Type: Journal Article | Journal: International journal of molecular medicine | Year: 2016

Retinoblastoma binding protein4(RbAp48) is a histone chaperone which has been suggested to play a role in gene silencing. However, the role of RbAp48 in human immunodeficiency virus type1(HIV-1) infection and gene replication has not been determined to date, to the best of our knowledge. For this purpose, we demonstrated in the present study that RbAp48 expression was upregulated by HIV-1 infection, whereas the knockdown of RbAp48 promoted HIV infection and the production of virus particles. The ectopic expression of RbAp48 inhibited HIV-1 expression, and this inhibition correlated with a marked decrease in the expression of HIV-1 genomic RNA and various RNA transcripts. Further experiments to determine the mechanism responsible for the inhibitory effects of RbAp48 revealed that the ectopic expression of RbAp48 repressed HIV-1 long terminal repeat(LTR)-mediated basal transcription as well as TNF-- and phorbol 12-myristate 13-acetate(PMA)activated transcription. Furthermore, the results of the electrophoretic mobility shift assay(EMSA) and chromatin immunoprecipitation(ChIP) analysisrevealed that RbAp48 binds to the HIV-1 LTR invitro. Taken together, these findings demonstrate that, as a transcriptional cofactor, RbAp48 is likely to act as a potent antiretroviral defense.

Chen G.,Hangzhou Normal University | Xu C.,Tongde Hospital of Zhejiang Province | Cen M.,Xixi Hospital of Hangzhou
Heart and Vessels | Year: 2016

The transforming growth factor (TGF-β)-inducible early gene (TIEG1) plays in regulatory role in cell apoptosis and proliferation, which are well known in cancer research, but have been only rarely reported in stem cell therapy. In our study, we first investigated the effects of TIEG1 on the cardioprotective properties of human adipose-derived mesenchymal stem cells (AdMSCs) in myocardial infarction (MI). In vitro, cell proliferation, apoptosis, angiogenic function, and paracrine potential of AdMSC were determined using a cell counting kit (CCK-8), terminal deoxynucleotidyl transferase-mediated dUPT nick end-labelling (TUNEL) assay, tube formation, ELISA, and qRT-PCR, respectively, after transduction with lentiviral TIEG1 encoding over-expressing, silencing, or nullifying a vector. In vivo, intramyocardial delivery of AdMSCs was implemented in a rat MI model, and then cardiac function, infarct size, and paracrine effect were measured. Deficiency of TIEG1 enhanced the anti-apoptotic and proliferative capacity of AdMSCs, meanwhile, conditioned medium from AdMSCsiTIEG1 preserved most cardiomyocytes (CMs) and capillary vessels of human umbilical vein endothelial cell (HUVEC). Furthermore, TIEG1 suppression stimulated expression of different cardioprotective cytokines, in AdMSCs, conditioned media, and cell-transplanted hearts. Lower apoptotic rate, higher capillary density, improved cardiac function, and smaller infarct size were observed in the hearts that received AdMSCsiTIEG. This study found for the first time that TIEG1 defects induced the enhancement of survival capacity and the cardioprotective paracrine function of AdMSCs and improved the therapeutic efficacy of AdMSCs for infarct injury by a cardioprotective cytokinal mechanism. © 2016 Springer Japan

Mi X.-X.,Hangzhou Normal University | Wang L.,Zhejiang Chinese Medical University | Xun Y.-H.,Xixi Hospital of Hangzhou | Shi J.-P.,Hangzhou Normal University
International Journal of Clinical and Experimental Medicine | Year: 2016

Nonalcoholic fatty liver disease (NAFLD) is emerging as one of the leading disorders of liver worldwide. NAFLD fibrosis score (NFS) is a noninvasive simple test for staging fibrosis in patients with NAFLD, with an acceptable diagnostic performance and extensively validated in various populations. In clinical practice, the suboptimal diagnostic accuracy however makes it clinically valuable only in excluding severe fibrosis, or in a combination with other complimentary approaches. Nevertheless, the NFS could be used as a helpful tool to monitor disease progression and to evaluate efficacy of potential therapies for NAFLD adults. This review describes the implementation of NFS in fibrosis staging and outcome predicting. The outcome prediction of NAFLD traditionally depends on baseline histology of biopsy specimen, and advanced fibrosis is best associated with overall and liver-related mortality among the individual pathologic features. Accordingly, NFS exhibits an intriguing ability for outcome prediction, including the long term mortality, hepatic and extra hepatic complications and whether liver related or not. Its merit in predication for long-term outcomes could derive substantially from its ability in fibrosis evaluation, as a moderately prognostic accuracy was replicated by FIB-4, another good noninvasive simple test for identifying liver fibrosis, in our study and others. In addition, this ability could be explained by the incorporated variables. In more detail, lower level of albumin, older age and the concomitant injury of glucometabolism, all suggest an overall poorer outcome in complications whether liver related or not for NAFLD patients. Here we propose to calculate NFS in newly diagnosed patients with NAFLD and recalculate annually to timely monitor disease progression. Nonetheless, the appropriate cutoff values of the NFS for different purposes remain to be determined. © 2016, E-Century Publishing Corporation. All rights reserved.

PubMed | University of Hong Kong, Zhejiang Chinese Medical University, Xixi Hospital of Hangzhou and Hangzhou Normal University
Type: Journal Article | Journal: Clinical and experimental pharmacology & physiology | Year: 2016

An imbalance between neutrophil elastase (NE) and its inhibitor 1-antitrypsin (A1 AT) is known to contribute to the development of obesity-related inflammation. This study aimed to investigate the role of the NE-A1 AT system in the histological progression of non-alcoholic fatty liver disease (NAFLD), and to evaluate the ability of it to predict nonalcoholic steatohepatitis (NASH). A total of 252 adults (NAFLD group, n=202; healthy group, n=50) were recruited. Clinical biochemical characteristics, NE and A1 AT concentrations were measured in all subjects. Among the NAFLD group, 86 patients had previously undergone liver biopsy and information on histological characteristics was consequently available. The area under the receiver operating characteristic curve (AUC) was used to determine the predictive accuracy of the NE-A1 AT system for NASH. NAFLD patients had an elevated serum NE concentration and a reduced A1 AT level with consequent NE/A1 AT imbalance. NE increased in the early stage of steatosis, preceding the decline in A1 AT, dating from the onset of NASH (NAS 3-4), and subsequently NE/A1 AT increased in the presence of NASH. Nonetheless, this increase began to resolve as the disease state progressed to advanced fibrosis. A1 AT had a sensitivity (SEN) of 83.8% and a specificity (SP) of 83.3% with the optimal cut-off of -1459.43, NE/A1 AT had a SEN of 88.8% and a SP of 83.3% with cut-off of 0.363 to predict NASH. An increased NE: A1 AT ratio is closely associated with liver Inflammation in patients with NASH and could serve as a novel marker to predict NASH in humans.

PubMed | Xixi Hospital of Hangzhou and Zhejiang Chinese Medical University
Type: Journal Article | Journal: Chinese journal of integrative medicine | Year: 2016

To investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia.There were two experiments. The experiment 1: 40 male Sprague-Dawley (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation (SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide (DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above.SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42 (P<0.01 or P<0.05).The central mechanism of EA-induced anti-hyperalgesia may be partially associated with the reduced expression of p-p38 MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain. Therefore, EA may be a new complementary and alternative therapy for neuropathic pain.

PubMed | University of Hong Kong, Dalian University, Zhejiang University, Xixi Hospital of Hangzhou and Hangzhou Normal University
Type: | Journal: Hepatology research : the official journal of the Japan Society of Hepatology | Year: 2016

This study aimed to evaluate the relationship between serum uric acid (SUA) level and non-alcoholic fatty liver disease (NAFLD) in non-obese adults.A cross-sectional study was carried out among 4098 adults, including 1936 non-obese and 2162 obese individuals. An additional 93 non-obese adults with biopsy-proven NAFLD were also included.The overall prevalence of NAFLD was 39.51% in the study group, and 14.88% in non-obese adults. The NAFLD patients had significantly higher SUA levels than controls in both men and women. The non-obese group had a higher NAFLD risk with increased SUA levels than the obese group, with odd ratios (95% confidence interval) of 2.559 (1.870-3.503) and 1.692 (1.371-2.087), respectively. In 93 non-obese adults with biopsy-proven NAFLD, SUA levels were significantly higher in those with non-alcoholic steatohepatitis. The prevalence of non-alcoholic steatohepatitis and lobule inflammation tended to increase to 57.58% and 66.67% as the SUA level increased to the fourth quartile. Subjects with hyperuricemia had significantly higher NAFLD activity scores and more serious lobule inflammation than the normal group.Non-obese adults have higher NAFLD risk with increased SUA levels than obese individuals, and the inflammation progression of NAFLD is associated with increased SUA level in non-obese subjects.

PubMed | Red Cross and XiXi Hospital of Hangzhou
Type: Journal Article | Journal: Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih | Year: 2017

Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion (URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials (RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions (thrombocytopenia ) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook (v5.1.0). Meta-analysis was conducted using RevMan (v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI (1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI (0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI (0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI (0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI (0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.

PubMed | Xixi Hospital of Hangzhou and Zhejiang University
Type: Journal Article | Journal: Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences | Year: 2015

To explore the clinical value of virtual touch tissue quantification (VTQ) technique and the PGA index [prothrombin time (P), -glutamyl transpeptadase (GG) and apolipoprotein A1 (ApoAl)] in evaluating the degree of liver fibrosis in alcoholic patients.A total of 64 patients with long-term alcohol history were enrolled for this study. The liver ultrasonography elasticity was examined by VTQ techniques, the VTQ value was assessed in the liver target region, and then the PGA index was calculated. According the liver biopsy biological results, a golden standard, the patients were divided into a non-fibrosis group (n=11), a fibrosis group (n=10), a significant fibrosis group (n=14) and a cirrhosis group (n=29). The diagnostic value of VTQ and PGA index were compared in alcoholic patients following the classification of liver fibrosis.The elastography VTQ values were (1.380.33), (1.490.30), (1.760.22) and (2.280.53) m/s; while the PGA indexes were 2.090.94, 2.301.06, 3.571.09, and 2.211.99 in the non-fibrosis group, the fibrosis group, the significant fibrosis group and the cirrhosis group, respectively. The VTQ value and PGA index were positively correlated with the classification of liver fibrosis (VTG: r=0.719, PGA: r=0.683; both P<0.01).The alcoholic liver fibrosis can be assessed by noninvasive VTQ technology and PGA index. As a real-time ultrasound elastography technique, VTQ is more accurate than the PGA index. Combination of the two methods is helpful for early diagnosis and treatment in the patients with alcoholic liver fibrosis.

PubMed | Zhejiang Agriculture And forestry University, Xixi Hospital of Hangzhou and Zhejiang University
Type: Journal Article | Journal: PloS one | Year: 2015

Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1 expression and prognosis of solid tumor is still in controversial. Here, we elicit a systematic review and meta-analysis to investigate the potential value of PD-L1 in the prognostic prediction in human solid tumors.Electronic databases were searched for studies evaluating the expression of PD-L1 and overall survival (OS) of patients with solid tumors. Odds ratios (ORs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed.A total of 3107 patients with solid tumor from 28 published studies were included in the meta-analysis. The median percentage of solid tumors with PD-L1 overexpression was 52.5%. PD-L1 overexpression was associated with worse OS at both 3 years (OR = 2.43, 95% confidence interval (CI) = 1.60 to 3.70, P < 0.0001) and 5 years (OR = 2.23, 95% CI = 1.40 to 3.55, P = 0.0008) of solid tumors. Among the tumor types, PD-L1 was associated with worse 3 year-OS of esophageal cancer, gastric cancer, hepatocellular carcinoma, and urothelial cancer, and 5 year-OS of esophageal cancer, gastric cancer and colorectal cancer.These results suggest that expression of PD-L1 is associated with worse survival in solid tumors. However, the correlations between PD-L1 and prognosis are variant among different tumor types. More studies are needed to investigate the clinical value of PD-L1 expression in prognostic prediction and treatment option.

PubMed | Hangzhou Normal University, Xixi Hospital of Hangzhou and Zhejiang University
Type: | Journal: Scientific reports | Year: 2015

Non-alcoholic fatty liver disease (NAFLD) is an important health issue worldwide. We aimed to develop a simple model to determine the presence of NAFLD in a Chinese population. A cross-sectional study with 9602 subjects was conducted. Potential predictors were entered into a stepwise logistic regression analysis to obtain the model. We used 148 patients with liver biopsy to validate this model. The model, named the ZJU index, was developed based on body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG), and the serum alanine aminotransferase (ALT) to serum aspartate transaminase (AST) ratio. The area under the receiver operating characteristic curve (AUROC) of the ZJU index to detect NAFLD was 0.822. At a value of <32.0, the ZJU index could rule out NAFLD with a sensitivity of 92.2%, and at a value of >38.0, the ZJU index could detect NAFLD with a specificity of 93.4%. In patients with liver biopsy, the ZJU index could detect steatosis with good accuracy, with an AUROC of 0.896. This study revealed that the ZJU index is a helpful model to detect NAFLD for community physicians in China. It was validated not only by a validation cohort but also by pathological data.

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