Qiang Xia

Shanghai Cancer Institute, Shanghai, Shanghai Shi, China

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Publications (225)299.93 Total impact

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    ABSTRACT: Hepatoblastoma (HB) is the most common primary liver tumor in children. Mutations in the β-catenin gene that leads to constitutive activation of Wnt pathway have been detected in a large proportion of HB tumors. To identify novel mutations in HB, we performed whole-exome sequencing of 6 paired HB tumors and their corresponding lymphocytes. This identified 24 somatic non-synonymous mutations in 21 genes, many of which were novel, including three novel mutations targeting the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) genes in the Wnt pathway, and genes previously shown to be involved in the ubiquitin ligase complex (SPOP, KLHL22, TRPC4AP and RNF169). Functionally, both the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) were observed to be gain-of-functional mutations, and the CAPRIN2 (R968H/S969C) was also shown to activate the Wnt pathway in HB cells. These findings suggested the activation of the Wnt pathway in HB, which was confirmed by immunohistochemical staining of the β-catenin in 42 HB tumors. We further used shRNA-mediated interference to assess the effect of 21 mutated genes on HB cell survival. The results suggested that 1 novel oncogene (CAPRIN2) and 3 tumor suppressors (SPOP, OR5I1 and CDC20B) influence HB cell growth. Moreover, we found that SPOP S119N is a loss-of-function mutation in HB cells. We finally demonstrated that one of the mechanisms by which SPOP inhibits HB cell proliferation is through regulating CDKN2B expression. Conclusion: these results extend the landscape of genetic alterations in HB and highlight the dysregulation of Wnt and ubiquitin pathways in HB tumorigenesis. (Hepatology 2014;).
    Hepatology 06/2014; · 12.00 Impact Factor
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    ABSTRACT: To compare the surgical outcomes between living-donor and deceased-donor liver transplantation in patients with hepatic carcinoma. From January 2007 to December 2010, 257 patients with pathologically confirmed hepatic carcinoma met the eligibility criteria of the study. Forty patients who underwent living-donor liver transplantation (LDLT) constituted the LDLT group, and deceased-donor liver transplantation (DDLT) was performed in 217 patients. Patients in the LDLT group were randomly matched (1:2) to patients who underwent DDLT using a multivariate case-matched method, so 40 patients in the LDLT group and 80 patients in the DDLT group were enrolled into the study. We compared the two groups in terms of clinicopathological characteristics, postoperative complications, long-term cumulative survival and relapse-free survival outcomes. The modified Clavien-Dindo classification system of surgical complications was used to evaluate the severity of perioperative complications. Furthermore, we determined the difference in the overall biliary complication rates in the perioperative and follow-up periods between the LDLT and DDLT groups. The clinicopathological characteristics of the enrolled patients were comparable between the two groups. The duration of operation was significantly longer (553 min vs 445 min, P < 0.001) in the LDLT group than in the DDLT group. Estimated blood loss (1188 mL vs 1035 mL, P = 0.055) and the proportion of patients with intraoperative transfusion (60.0% vs 43.8%, P = 0.093) were slightly but not significantly greater in the LDLT group. In contrast to DDLT, LDLT was associated with a lower rate of perioperative grade II complications (45.0% vs 65.0%, P = 0.036) but a higher risk of overall biliary complications (27.5% vs 7.5%, P = 0.003). Nonetheless, 21 patients (52.5%) in the LDLT group and 46 patients (57.5%) in the DDLT group experienced perioperative complications, and overall perioperative complication rates were similar between the two groups (P = 0.603). No significant difference was observed in 5-year overall survival (74.1% vs 66.6%, P = 0.372) or relapse-free survival (72.9% vs 70.9%, P = 0.749) between the LDLT and DDLT groups. Although biliary complications were more common in the LDLT group, this group did not show any inferiority in long-term overall survival or relapse-free survival compared with DDLT.
    World Journal of Gastroenterology 04/2014; 20(15):4393-400. · 2.55 Impact Factor
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    ABSTRACT: The aim of this study was to assess serum levels of presurgical α-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9) as prognostic markers in patients with hepatic carcinoma after liver transplantation (LT). A total of 226 patients were recruited for the analysis of serum AFP and CA19-9 levels, on the basis of which the tumor marker type (TMT) was defined and evaluated for prognostic prediction. Overall survival (OS) and relapse-free survival (RFS) were analyzed using Kaplan-Meier curves, and univariate and multivariate Cox models. One-year and 5-year OS were 79.0 and 58.0%, respectively, whereas RFS were 70.3 and 62.2%, respectively, in this cohort of patients. There were six variables predicting both OS and RFS, including TMT, tumor size, number of tumor lesions, extrahepatic or vascular invasion, and histopathological grade. Among these, TMT, tumor size, and extrahepatic invasion were all independent predictors of OS and RFS among these patients. Further, on the basis of TMT, novel LT selection criteria for patients with hepatic carcinoma, which supplemented the Milan criteria, were adopted, because the patients within the Milan criteria (n=107) and those exceeding Milan but fulfilling the proposed criteria (n=30) had similar 5-year OS (77.8 vs. 79.3%, P=0.862) and RFS (85.5 vs. 75.1%, P=0.210) rates. The data from this study showed that serum levels of preoperative AFP and CA19-9 were able to predict survival of patients with hepatic carcinoma after LT. This study included novel criteria, adding serum AFP and CA19-9 levels to the selection criteria for LT eligibility of patients, in addition to the Milan criteria.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
    European journal of gastroenterology & hepatology 03/2014; · 1.66 Impact Factor
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    ABSTRACT: To investigate the influence of total flavonoids of Elsholtzia splendens (TFES) on isolated ischemia/reperfusion rat hearts and its underlying mechanisms.
    03/2014; 30(2):161-5.
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    ABSTRACT: Orthotopic liver transplantation is currently the best treatment option for selected patients with hepatocellular carcinoma (HCC). From 1980 to 2011, 8874 patients with HCC in China underwent liver transplantation. The organ donation classification criteria of China (China criteria), which are established by the Government of China, are divided into three parts: China criteria I, donation after brain death; China criteria II, donation after cardiac death and China criteria III, donation after dual brain-cardiac death. Data from the China Liver Transplant Registry(CLTR) System shows that patients within the Milan criteria have higher survival rates than those who are beyond these criteria. Based on CLTR data, altogether 416 patients received living-donor liver transplantation(LDLT) in China. Their 1-year and 3-year survival rates were significantly higher than those of the non-LDLT recipients. The most common early stage(<30 days after liver transplantation) complications include pleural effusion, diabetes, peritoneal effusion or abscess, postoperative infection, hypertension and intraperitoneal hemorrhage; while the most common late stage (≥ 30 days after liver transplantation) complications were diabetes, hypertension, biliary complications,postoperative infection, tacrolimus toxicity and chronic graft rejection. The incidence of vascular complication, which is the main reason for acute graft failure and re-transplantation, was 2.4%. Liver transplantation is an effective treatment for patients with HCC in China.
    Journal of Digestive Diseases 02/2014; 15(2):51-3. · 1.85 Impact Factor
  • Ping Wan, Xin Yu, Qiang Xia
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    ABSTRACT: Living donor liver transplantation (LDLT) has emerged as an alternative to deceased donor liver transplantation (DDLT) with the increasing number of patients waiting for a liver transplant. However, whether it can achieve similar operative outcomes compared with DDLT in adult patients remains controversial. We conducted this meta-analysis to compare the operative outcomes between LDLT and DDLT recipients. A literature search was performed to identify clinical controlled studies comparing LDLT with DDLT published before October 2013. Four perioperative outcomes (duration of recipient operation, red blood cell transfusion requirement, length of hospital stay and cold ischemia time) and five postoperative complication outcomes (biliary complications, vascular complications, intraabdominal bleeding, perioperative death and retransplantation) were the main outcomes assessed. Nineteen studies with a total of 5450 patients were included in the meta-analysis. Compared with DDLT, LDLT was associated with significantly longer duration of recipient operation, and shorter cold ischemia time. We found biliary complications (Weighted mean difference [WMD]: 3.08, 95% confidence interval [CI]: 1.97 to 4.81, P<0.001), vascular complications (WMD: 2.16, 95% CI: 1.32 to 3.54, P=0.002) and retransplantation (WMD: 1.76, 95% CI: 1.09 to 2.83, P= 0.02) occurred more frequently in LDLT recipients, and the subgroup analysis indicated biliary complication rate decreased dramatically with greater LDLT experience. No significant difference was observed in red blood cell transfusion requirement, length of hospital stay, intraabdominal bleeding rate and perioperative mortality between LDLT and DDLT recipients. In conclusion, LDLT was associated with a higher rate of surgical complications post-transplantation. Reduction of postoperative complication rate could be achieved as centers gained greater experience with LDLT. However, LDLT still offered an excellent alternative to DDLT because it facilitated access to a liver transplant. Liver Transpl , 2014. © 2014 AASLD.
    Liver Transplantation 01/2014; · 3.94 Impact Factor
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    ABSTRACT: Little information is available regarding the impact of cytochrome P450 (CYP) 3A5 on the metabolism of TAC in infant LTx. Therefore, the CYP3A5 genotype of Chinese pediatric recipients (intestine) as well as donors (graft liver) was performed for the purpose of establishing an optimal dosage regimen in children. Sixty-four patients were divided according to CYP3A5 genotype (expression of *1 allele: EX and NEX) for each recipient (R) and donor (D), EX-R/EX-D (n = 21), EX-R/NEX-D (n = 8), NEX-R/EX-D (n = 8) and NEX-R/NEX-D (n = 27). Results indicated that initial TAC daily dose requirement was higher among EX-R/EX-D children compared with those who did not express CYP3A5 (0.28 ± 0.10 vs. 0.19 ± 0.08 mg/kg/day, p < 0.01). CYP3A5 expression contributed an overall of 38.35% to its C/D ratios, and graft liver was a key determinant. Additionally, the EX-R/EX-D group showed significantly higher incidence of infectious complications, lower immune response and was an independent risk factor for the development of infections (odds ratio 3.86, p = 0.025). Donor CYP3A5 expression partially explains TAC dose requirement, the effect of CYP3A5 variation may influence clinical outcomes; therefore, monitoring immune response may be important for preventing risks associated with under- and over-immunosuppression.
    Pediatric Transplantation 01/2014; · 1.50 Impact Factor
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    ABSTRACT: Cbx4 is a polycomb group protein that is also a SUMO E3 ligase, but its potential roles in tumorigenesis remain to be explored. Here, we report that Cbx4, but not other members of the Cbx family, enhances hypoxia-induced vascular endothelial growth factor (VEGF) expression and angiogenesis in hepatocellular carcinoma (HCC) cells through enhancing HIF-1α sumoylations at K391 and K477 in its two SUMO-interacting motifs-dependent mechanisms and increasing transcriptional activity of HIF-1. The Cbx4 expression is significantly correlated with VEGF expression, angiogenesis, and the overall survival of HCC patients and also in subcutaneously and orthotopically transplanted mice HCC models. Collectively, our findings demonstrate that Cbx4 plays a critical role in tumor angiogenesis by governing HIF-1α protein.
    Cancer cell 01/2014; 25(1):118-31. · 25.29 Impact Factor
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    ABSTRACT: Objective The purpose of this meta-analysis was to compare outcomes of different techniques used for biliary reconstruction in adult donor liver transplantation. Methods We searched the literature via Pubmed, Embase, Ovid, the Cochrane Hepato-Biliary Group Controlled Trials Regsistry, the Cochrane Central Registry of Controlled Trials, the Cochrane Library database, and Web of Science. Then with the data extracted from the literature, the effects that biliary reconstruction techniques in living-donor liver transplantation (LDLT) had on the occurrence of biliary complications were compared. With the use of random-effects and fixed-effect models, the results were obtained and expressed as odds ratio. Results We found 16 eligible studies from various medical centers around the world. Duct-to-duct (DD) reconstruction was performed in the majority of patients (922/1,564). Multiple biliary ducts were encountered in 16.7%–60.4%, and ductoplasty was performed in 7.9%–74% of the patients. Both graft and posterior layer of bile duct anastomosis in DD reconstruction were studied, and no statistically differences in incidence of biliary complications were found between the Roux-en-Y hepaticojejunostomy (RYHJ) and DD groups. Nonsurgical management of biliary complications was the first choice of treatment. Conclusions Our study found that there is no clear evidence in favor of using DD or RYHJ during adult LDLT.
    Transplantation Proceedings 01/2014; 46(1):208–215. · 0.95 Impact Factor
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    ABSTRACT: MicroRNA-24 (miR-24) may be involved in neoplastic process; however, the role of this microRNA in the hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) has not been well elaborated. Here, we tested miR-24 expression in 207 pathology-diagnosed HCC cases from high AFB1 exposure areas and HCC cells. We found that miR-24 was upregulated in HCC tumor tissues relative to adjacent noncancerous tissue samples, and that the high expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation. Additionally, this microRNA overexpression modified the recurrence-free survival (relative hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.66-8.47) and overall survival (HR = 3.58, 95% CI = 2.34-5.46) of HCC patients. Furthermore, we observed some evidence of joint effects between miR-24 and AFB1 exposure on HCC prognosis. Functionally, miR-24 overexpression progressed tumor cells proliferation, inhibited cell apoptosis, and developed the formation of AFB1-DNA adducts. These results indicate for the first time that miR-24 may modify AFB1-related HCC prognosis and tumorigenesis.
    BioMed research international. 01/2014; 2014:482926.
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    ABSTRACT: To establish a prognostic prediction system for patients with hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation (LT). A total of 130 patients undergoing LT for HCC exceeding Milan criteria were enrolled into the study. Independent predictors for relapse-free survival (RFS) were adopted to establish a grading system to predict the risk of post-LT tumor recurrence. Multivariate Cox analysis revealed that tumor size >10 cm [vs. ≤5 cm: relative risk (RR) = 4.214, P < 0.001], preoperative alpha fetoprotein > 400 ng/ml (vs. ≤400 ng/ml: RR = 1.657, P < 0.001), extrahepatic invasion (RR = 2.407, P = 0.005) and vascular invasion (RR = 1.917, P = 0.013) were independent predictors for RFS. The risk index of each patient was defined as the sum of the RR obtained in the Cox analysis for RFS. The risk of tumor recurrence was classified into four grades: grade I-risk index equal to 0, grade II-risk index from 0 to 2, grade III-risk index from 2 to 6 and grade IV-risk index >6. RFS rates of patients with grade I-IV (n = 35, 46, 30 and 19) were 87.5, 57.8, 34.7 and 0 % in 1 year; and 74.4, 41.7, 14.4 and 0 % in 5 years. Both of overall survival (OS) and RFS correlated well with the risk index grade. Patients with grade I achieved comparable prognostic outcomes with the Milan group patients (n = 119) (5-year OS = 73.7 vs. 74.7 %, P = 0.748; 5-year RFS = 74.4 vs. 85.7 %, P = 0.148). The new grading system was proved to be a promising system in predicting the patient prognosis after LT for HCC exceeding Milan criteria.
    Journal of Cancer Research and Clinical Oncology 12/2013; · 2.91 Impact Factor
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    ABSTRACT: Although the protective effect of lipopolysaccharide (LPS) pretreatment on renal ischemia/reperfusion injury is known, a link to hypoxia-inducible factors (HIFs) has not been established. Here we show that LPS treatment led to HIF-2α accumulation in mouse kidneys and endothelial cells, a result of nuclear factor-κB activation. Inactivation of HIF-2α, rather than HIF-1α, completely negated LPS-mediated protection against renal ischemia/reperfusion injury. LPS-stimulated renoprotection was related to inducible/endothelial nitric oxide synthase (iNOS/eNOS) expression, increased production of nitric oxide, and enhanced postischemic microcirculatory recovery. All these effects were lost in HIF-2α knockout mice. Preischemic administration of a nitric oxide donor, rather than erythropoietin, restored the lost preconditioning effect of LPS in HIF-2α knockout mice. In vitro and in vivo studies demonstrated that HIF-2α in endothelial cells, rather than myeloid cells or hepatocytes, was responsible for the LPS-mediated effects. Thus, our results demonstrated that LPS preconditioning protected against renal ischemia/reperfusion injury by HIF-2α activation in endothelial cells that subsequently improved renal microvascular perfusion and reduced ischemic tubular damage.Kidney International advance online publication, 11 September 2013; doi:10.1038/ki.2013.342.
    Kidney International 09/2013; · 7.92 Impact Factor
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    ABSTRACT: A multilocular cystic hepatic lesion detected at computed tomography (CT) and magnetic resonance (MR) imaging is a common but nonspecific radiologic finding that can cause potential challenges for differential diagnosis. This imaging pattern may be observed in a wide spectrum of common and uncommon neoplastic or nonneoplastic entities. Neoplastic lesions include cystadenoma, cystadenocarcinoma, hepatocellular carcinoma (HCC), metastases, mesenchymal hamartoma, and inflammatory myofibroblastic tumor. Nonneoplastic lesions include hepatic abscess, echinococcal cyst, intrahepatic hematoma, and biloma. The multiple coalescent cysts seen in polycystic liver disease may exhibit an imaging pattern similar to that of a multilocular cystic lesion. Mural nodularity, irregular thickness of the septa, ragged inner surface, and typical enhancement pattern in the solid portion of the lesion are often indicative of malignancy, although multilocular primary or secondary malignant tumors are uncommon. Recognition of the more common necrosis or cystic change of HCC and metastases induced by locoregional or systemic treatment also is important. The nonenhanced cystic component may be composed of different types of fluids (eg, serous, mucinous, proteinaceous, hemorrhagic, bilious, or mixed) or spontaneous or treatment-related necrosis, whereas the septa may be formed by a wide range of tissues depending on the lesion type. An understanding of the CT and MR imaging findings of these lesions and their respective pathologic correlation aids in accurate diagnosis.
    Radiographics 09/2013; 33(5):1419-33. · 2.79 Impact Factor
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    ABSTRACT: OBJECTIVES: To assess the performance of the Milan, Shanghai Fudan and Hangzhou Criteria based on preoperative evaluation in patients undergoing liver transplantation (LT) for hepatitis B-related hepatocellular carcinoma (HCC). METHODS: Using a prospectively collected database, data of consecutive patients with hepatitis B-related HCC undergoing LT from January 2005 to December 2009 were reviewed. Overall survival and tumor recurrence rates of patients fulfilled Milan, Shanghai Fudan and Hangzhou Criteria were compared using the log-rank test. RESULTS: Altogether 148 patients were enrolled in the study, in which 88 fulfilled the Milan criteria, 24 and 39 were beyond Milan but within Shanghai Fudan or Hangzhou criteria, respectively. After followed up for a median period of 44 months, survival rates did not differ among the three groups (P = 0.8780). Recurrence rates was significantly lower for newly eligible patients by Shanghai Fudan or Hangzhou Criteria compared with those within the Milan Criteria. CONCLUSIONS: The Milan criteria should be applied as the preferred criteria of hepatitis B-related HCC. Moderate expansion of Milan criteria must be performed cautiously considering high tumor recurrence rates and donor scarcity until high quality clinical trials are conducted.
    Journal of Digestive Diseases 06/2013; · 1.85 Impact Factor
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    ABSTRACT: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity and may play an important role in carcinogenesis. We investigated the role of genetic polymorphisms at XRCC4 codon 247 (rs3734091, XRCC4P) and XRCC5 codon 180 (rs80309960, XRCC5P) in liver cancer (hepatocellular carcinoma) caused by aflatoxin B1 (AFB1). A hospital-based case-control study, including 1499 liver cancer cases and 2045 controls without any liver disease, was conducted in a high aflatoxin exposure area in the Guangxi region of China to assess the relationship between these two polymorphisms and aflatoxin-related liver cancer risk and prognosis. Genotypes, mRNA levels, and the hot-spot mutation of TP53 gene (TP53M) related to AFB1 exposure was tested using TaqMan-PCR technique. XRCC4 protein level was analyzed by immunohistochemistry. For XRCC4P and XRCC5P, only XRCC4P modified liver cancer risk. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased liver cancer risk (odds ratio [OR] = 1.35 and 2.02, respectively). Significant interactive effects between risk genotypes (OR > 1) and aflatoxin exposure status were also observed in the joint effects analysis. Moreover, this polymorphism was associated not only with lower XRCC4 expression levels but also with higher AFB1-DNA adduct levels and increasing TP53M and portal vein tumor risk. Additionally, XRCC4P modified the recurrence-free survival and overall survival of cases, especially under conditions of high aflatoxin exposure. XRCC4P may be a genetic modifier for the risk and outcome of hepatocellular carcinoma induced by AFB1 exposure.
    Epidemiology (Cambridge, Mass.) 06/2013; · 5.51 Impact Factor
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    ABSTRACT: WSB-1 is involved in DNA damage response by targeting homeodomain-interacting protein kinase 2 (HIPK2) for ubiquitination and degradation. Here, we report that hypoxia significantly up-regulates the expression of WSB-1 in human hepatocellular carcinoma (HCC) cells. We also provide evidence that WSB-1 is a target of hypoxia-inducible factor 1 (HIF-1). Silencing the expression of HIF-1α in HCC cells by RNA interference abolishes hypoxia-induced WSB-1 expression. Using chromatin immunoprecipitation and luciferase reporter assays, we identified a HRE of the WSB-1 gene. Moreover, silencing the expression of WSB-1 by RNA interference rescues HIPK2 expression in hypoxic HCC cells and promotes etoposide-induced cell death in hypoxic HCC cells. Taken together, these data shed light on the mechanisms underlying hypoxia-induced chemoresistance in HCC cells.
    FEBS letters 06/2013; · 3.54 Impact Factor
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    ABSTRACT: Objective: To investigate the beneficial effect of bicyclol on rat hearts subjected to ischemia-reperfusion (IR) injuries and its possible mechanism. Methods: Male Sprague-Dawley rats were intragastrically administered with bicyclol (25, 50 or 100 mg/(kg∙d)) for 3 d. Myocardial IR was produced by occlusion of the coronary artery for 1 h and reperfusion for 3 h. Left ventricular hemodynamics was continuously monitored. At the end of reperfusion, myocardial infarct was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and serum lactate dehydrogenase (LDH) level and myocardial superoxide dismutase (SOD) activity were determined by spectrophotometry. Isolated ventricular myocytes from adult rats were exposed to 60 min anoxia and 30 min reoxygenation to simulate IR injuries. After reperfusion, cell viability was determined with trypan blue; reactive oxygen species (ROS) and mitochondrial membrane potential of the cardiomyocytes were measured with the fluorescent probe. The mitochondrial permeability transition pore (mPTP) opening induced by Ca(2+) (200 μmol/L) was measured with the absorbance at 520 nm in the isolated myocardial mitochondria. Results: Low dose of bicyclol (25 mg/(kg∙d)) had no significant improving effect on all cardiac parameters, whereas pretreatment with high bicyclol markedly reduced the myocardial infarct and improved the left ventricular contractility in the myocardium exposed to IR (P<0.05). Medium dose of bicyclol (50 mg/(kg∙d)) markedly improved the myocardial contractility, left ventricular myocyte viability, and SOD activity, as well decreased infarct size, serum LDH level, ROS production, and mitochondrial membrane potential in rat myocardium exposed to IR. The reduction of ventricular myocyte viability in IR group was inhibited by pretreatment with 50 and 100 mg/(kg∙d) bicyclol (P<0.05 vs. IR), but not by 25 mg/(kg∙d) bicyclol. The opening of mPTP evoked by Ca(2+) was significantly inhibited by medium bicyclol. Conclusions: Bicyclol exerts cardioprotection against IR injury, at least, via reducing oxidative stress and its subsequent mPTP opening.
    Journal of Zhejiang University SCIENCE B 06/2013; 14(6):487-95. · 1.11 Impact Factor
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    ABSTRACT: Continuous hyperglycemia is considered to be the most significant pathogenesis of diabetic cardiomyopathy, which manifests as cardiac hypertrophy and subsequent heart failure. O-GlcNAcylation has attracted attention as a post-translational protein modification in the past decade. The role of O-GlcNAcylation in high glucose-induced cardiomyocyte hypertrophy remains unclear. We studied the effect of O-GlcNAcylation on neonatal rat cardiomyocytes that were exposed to high glucose and myocardium in diabetic rats induced by streptozocin. High glucose (30 mM) incubation induced a greater than twofold increase in cell size and increased hypertrophy marker gene expression accompanied by elevated O-GlcNAcylation protein levels. High glucose increased ERK1/2 but not p38 MAPK or JNK activity, and cyclin D2 expression was also increased. PUGNAc, an inhibitor of β-N-acetylglucosaminidase, enhanced O-GlcNAcylation and imitated the effects of high glucose. OGT siRNA and ERK1/2 inhibition with PD98059 treatment blunted the hypertrophic response and cyclin D2 upregulation. OGT inhibition also prevented ERK1/2 activation. We also observed concentric hypertrophy and similar changes of O-GlcNAcylation level, ERK1/2 activation and cyclin D2 expression in myocardium of diabetic rats induced by streptozocin. In conclusion, O-GlcNAcylation plays a role in high glucose-induced cardiac hypertrophy via ERK1/2 and cyclin D2.
    Amino Acids 05/2013; · 3.91 Impact Factor
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    ABSTRACT: OBJECTIVE: The aim of this study was to analyze the incidence and risk factors of de novo hepatitis B infection from HBcAb positive donors in pediatric living donor liver transplantation (LDLT). METHODS: We retrospectively analyzed 46 recipients without pretransplantation hepatitis B infection evidence who undergone LDLT from October 2006 to May 2011 in our center. Hepatitis B virus (HBV) markers including HBsAg, HBsAb, HBcAb, HBeAg and HBeAb were determined in both donors and recipients before transplantation. HBV DNA was measured if the donors or recipients were highly suspected of de novo hepatitis B infection. RESULTS: Without prophylaxis, de novo hepatitis B infection after liver transplantation occurred in 11 of 46 recipients (23.9%) 6 to 36 months after transplantation. All 11 patients received grafts from HBcAb positive donors. Donor's basic status and the variables of recipients at the time of transplantation were not associated with acquisition of de novo hepatitis B infection. The overall survival rate of patients from HBcAb-positive donors at 2 year was 84.2%. Two de novo HBV infected patients who had YMDD mutation administrated adefovir combined with lamivudine, and their liver function gradually improved during follow-up time. CONCLUSIONS: HBcAb-postive donor can significantly increase the incidence of de novo HBV infection in HBsAg-negative recipients. Adding adefovir to patients who were resistant to lamivudine seems to be effective and safe to control de novo hepatitis B infection.
    Journal of Digestive Diseases 05/2013; · 1.85 Impact Factor
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    ABSTRACT: X-ray repair complementing group 4 (XRCC4) is very important in maintaining the overall genome stability and may play an important role in carcinogenesis. We aimed to investigate the role of polymorphisms in the coding region of this gene in hepatocellular carcinoma (HCC) caused by aflatoxin B1 (AFB1). A hospital-based case-control study, including 1499 HCC cases and 2045 controls without any liver diseases or tumors, was conducted in a high AFB1 exposure area Guangxi region to assess the relationship between 21 polymorphisms in the coding region of XRCC4 and AFB1-related HCC risk and prognosis. Among these 21 polymorphisms, only rs28383151 modified HCC risk. These individuals with the genotypes of rs28383151 A alleles (rs28383151-GA/AA), compared the homozygote of rs28383151 G alleles (rs28383151-GG), faced increasing risk of HCC (odds ratio (OR), 2.17; 95% confidence interval (CI), 1.77-2.67). Significant interactive effects between risk genotypes (OR > 1) and AFB1 exposure status were also observed in the joint-effects analysis. Furthermore, this polymorphism was correlated not only with lower XRCC4-expressing levels, but with higher AFB1-DNA adducts levels and increasing TP53M and portal vein tumor risk. Rs28383151 polymorphism modified the recurrence-free survival and overall survival of HCC patients, especially under high AFB1 exposure conditions. Additionally, this polymorphism multiplicatively interacted with the glutathione-S-transferase M1 polymorphism with respect to HCC risk (OR(interaction) = 2.13). Conclusion: Our data indicated, for the first time, that genetic polymorphisms in the coding region of XRCC4 may be risk and prognostic biomarkers of AFB1-related HCC, and rs28383151 is such a potential candidate. (HEPATOLOGY 2013.).
    Hepatology 02/2013; · 12.00 Impact Factor

Publication Stats

982 Citations
299.93 Total Impact Points

Institutions

  • 2014
    • Shanghai Cancer Institute
      Shanghai, Shanghai Shi, China
  • 2009–2014
    • Shanghai Jiao Tong University
      • • Shanghai Chest Hospital
      • • School of Medicine
      Shanghai, Shanghai Shi, China
    • China Three Gorges University
      Tung-hu, Hubei, China
  • 2013
    • Xuzhou Medical College
      Hang-hsien, Zhejiang Sheng, China
    • Youjiang Medical College For Nationalities
      T’ien-yüan-shih, Zhejiang Sheng, China
  • 2009–2013
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
  • 2008–2011
    • Renji Hospital
      Shanghai, Shanghai Shi, China
  • 2001–2011
    • Zhejiang University
      • • Department of Physiology
      • • School of Medicine
      • • Department of Physics
      Hangzhou, Zhejiang Sheng, China
  • 2010
    • Jiaxing University
      Kashing, Zhejiang Sheng, China
    • Sir Run Run Shaw Hospital
      Hang-hsien, Zhejiang Sheng, China
  • 2009–2010
    • Hangzhou Normal University
      Hang-hsien, Zhejiang Sheng, China
  • 2005–2010
    • Shaoxing University
      Shao-hsing, Zhejiang Sheng, China
  • 1997–2005
    • The University of Hong Kong
      • • Department of Physiology
      • • Department of Medicine
      Hong Kong, Hong Kong
  • 2004
    • Lands Department of The Government of the Hong Kong Special Administrative Region
      Hong Kong, Hong Kong
  • 1998
    • Zhejiang Medical University
      Hang-hsien, Zhejiang Sheng, China