Hangzhou Sixth Peoples Hospital

Hangzhou, China

Hangzhou Sixth Peoples Hospital

Hangzhou, China
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Xu H.Y.,Zhejiang University | Yu X.P.,Zhejiang Chinese Medical University | Feng R.,Hangzhou Sixth Peoples Hospital | Hu H.J.,Zhejiang University | Xiao W.W.,Zhejiang University
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2017

目的: 探讨肝癌患者肝动脉化疗栓塞术(TACE) 后相关性胆管损伤与血管栓塞位置的关系及临床预后。 方法: 回顾性分析2012年1月18日至2014年12月18日间21例肝癌TACE治疗患者的临床病理资料,探讨其发生胆管损伤的可能因素及临床转归。 结果: 21例患者总共行TACE 48次,其中肝固有动脉14次,左肝动脉3次,右肝动脉10次,左右肝动脉9次,肿瘤动脉供血分支12次。21例患者发生胆管损伤数目35个,其中靠近肿瘤位置7个,非靠近肿瘤位置2个,右肝7个,左肝2个,左右肝11个,肝门部6个。21例患者中,有10例患者经内科保守治疗及胆管内、外引流术后,肝功能好转;有4例肝门部胆管狭窄及胆汁瘤患者,胆管外引流效果不明显,后期出现胆管感染、胆囊结石及肝内胆管结石等并发症;有3例患者因肝功能衰竭,出现肝硬化失代偿并发症,其中1例患者因肝性脑病死亡;有4例患者随访期间肝癌复发。 结论: TACE相关性胆管损伤部位与栓塞肝动脉位置具有高度吻合性,可能存在某种血管参与胆管供血,如果给予完全栓塞,易造成胆管损伤。肝门部胆管狭窄的肝癌患者,胆管引流效果不佳,且后期易出现胆管相关的严重并发症。.Objective: To evaluate the correlation between bile duct injury after transcatheter arterial chemoembolization and the level of hepatic arterial embolization, and to analyze the clinical prognosis of hepatocellular carcinoma patients. Methods: From January18, 2012 to December18, 2014, 21 patients underwent TACE for HCC were retrospectively reviewed, including patients' clinical and pathological data. The clinical outcome and relevant factors for bile duct injury were analyzed. Results: A total of 21 patients were identified with bile duct injury at our single institution. All patients received 48 TACE treatments, including proper hepatic artery (14), left hepatic artery (3), the right hepatic artery (10), left and right hepatic artery (9) and tumor artery branches (12). Thirty-five bile duct injury occurred in 21 patients: 7 cases was close to the tumor, 2 distant to the tumor, 7 at right liver, 2 left liver, 11 both lobes of liver and 6 hepatic hilar. After medical conservative treatment and biliary tract inside and outside drainage, liver function of 10 cases were improved. In four patients with hepatic bile duct stricture and biloma, the effect of drainage was not obvious, which subsequently caused biliary complications such as infection, gallbladder and common bile duct stones. Three patients with liver cirrhosis at decompensation stage developed complications, and one of them died of hepatic encephalopathy. Four patients experienced tumor recurrence during the follow-up period. Conclusions: The location of bile duct injury after transcatheter arterial chemoembolization is quite consistent with the level of hepatic arterial embolization. There may be some blood vessels mainly involved in blood supply of biliary duct. Complete embolism of these vessels may lead to bile duct injuries. Biliary drainage is ineffective in patients with hilar bile duct stricture, and can lead to complications of biliary tract later on.


Shao P.,Zhejiang University | Wu X.,Zhejiang University | Li H.,Hangzhou Sixth Peoples Hospital | Wu Z.,Zhejiang University | And 2 more authors.
Molecular Medicine Reports | Year: 2017

The present study examined the relationship between cytokine and chemokine expression and the clinical presentation of hand, foot and mouth disease (HFMD), which is currently unclear. The present study involved 28 patients with mild HFMD, 44 patients with severe HFMD and 26 healthy children. Venous blood was tested for cytokine [interleukin (IL)-4, IL-12, IL-18, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ)] and chemokine expression [IL-8, regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1) and IFN-γ-inducible protein-10 (IP-10)]. Stool samples from the patients were tested for enterovirus 71 (EV71) RNA using reverse transcription-polymerase chain reaction. The results indicated that all cytokine/chemokine levels were increased in patients with severe HFMD compared with in patients with mild HFMD or control subjects. In addition, RANTES, MCP-1, IL-4, IL-12 and IL-18 levels were higher in mild HFMD patients than in the controls. In patients with severe HFMD, all expression levels (with the exception of IL-8 and IL-4) were increased in patients with encephalitis plus pulmonary edema compared with those with encephalitis alone. Furthermore, all levels (with the exception of IL-8) were increased in EV71-positive patients compared with EV71-negative patients. In mild HFMD, all levels (with the exception of IL-8 and IL-4) were increased in EV71-positive patients compared with EV71-negative patients. However, in severe HFMD, only RANTES, IP-10 and IFN-γ levels were increased in EV71-positive patients compared with EV71-negative patients. In the EV71-negative group, all levels were increased in severe HFMD compared with mild HFMD. In the EV71-positive group, all levels (with the exception of IL-8) were increased in severe HFMD compared with mild HFMD. These results indicated that cytokines and chemokines participate in HFMD pathogenesis, and may be useful to monitor disease progression and predict prognosis.


Xu D.-Z.,Capital Medical University | Wang X.-Y.,Fudan University | Shen X.-L.,National Vaccine and Serum Institute | Gong G.-Z.,Central South University | And 25 more authors.
Journal of Hepatology | Year: 2013

Background & Aims Even though various experimental therapeutic approaches for chronic hepatitis B infection have been reported, few of them have been verified by clinical trials. We have developed an antigen-antibody (HBsAg-HBIG) immunogenic complex therapeutic vaccine candidate with alum as adjuvant (YIC), aimed at breaking immune tolerance to HBV by modulating viral antigen processing and presentation. A double-blind, placebo-controlled, phase II B clinical trial of YIC has been reported previously, and herein we present the results of the phase III clinical trial of 450 patients. Methods Twelve doses of either YIC or alum alone as placebo were administered randomly to 450 CHB patients and they were followed for 24 weeks after the completion of immunization. The primary end point was HBeAg seroconversion, and the secondary end points were decrease in viral load, improvement of liver function, and histology. Results In contrast to the previous phase II B trial using six doses of YIC and alum as placebo, six more injections of YIC or alum resulted in a decrease of the HBeAg seroconversion rate from 21.8% to 14.0% in the YIC group, but an increase from 9% to 21.9% in the alum group. Decrease in serum HBV DNA and normalization of liver function were similar in both groups (p >0.05). Conclusions Overstimulation with YIC did not increase but decreased its efficacy due to immune fatigue in hosts. An appropriate immunization protocol should be explored and is crucial for therapeutic vaccination. Multiple injections of alum alone could have stimulated potent inflammatory and innate immune responses contributing to its therapeutic efficacy, and needs further investigation. © 2013 European Association for the Study of the Liver.


PubMed | Centers for Disease Control and Prevention, Wenzhou University, First Municipal Hospital of Hangzhou, Hangzhou Sixth Peoples Hospital and Zhejiang University
Type: Journal Article | Journal: PloS one | Year: 2015

Neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading cause of death in young children infected by Enterovirus 71 (EV71). However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models. Development of a suitable animal model is important for studying EV71 pathogenesis and assessing effect of therapeutic approaches. We had found neurological disorders in EV71-induced young gerbils previously. Here, we report severe pulmonary lesions characterized with pulmonary congestion and hemorrhage in a gerbil model for EV71 infection. In the EV71-infected gerbils, six 21-day-old or younger gerbils presented with a sudden onset of symptoms and rapid illness progression after inoculation with 1105.5 TCID50 of EV71 via intraperitoneal (IP) or intramuscular (IM) route. Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination. EV71 viral titer was found to be peak at late stages of infection. EV71-induced pulmonary lesions, together with severe neurological disorders were also observed in gerbils, accurately mimicking the disease process in EV71-infected patients. Passive transfer with immune sera from EV71 infected adult gerbils with a neutralizing antibody (GMT=89) prevented severe pulmonary lesion formation after lethal EV71 challenge. These results establish this gerbil model as a useful platform for studying the pathogenesis of EV71-induced pulmonary lesions, immunotherapy and antiviral drugs.


Xu F.,Centers for Disease Control and Prevention | Yao P.-P.,Centers for Disease Control and Prevention | Xia Y.,Centers for Disease Control and Prevention | Qian L.,Centers for Disease Control and Prevention | And 20 more authors.
PLoS ONE | Year: 2015

Neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading cause of death in young children infected by Enterovirus 71 (EV71). However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models. Development of a suitable animal model is important for studying EV71 pathogenesis and assessing effect of therapeutic approaches. We had found neurological disorders in EV71-induced young gerbils previously. Here, we report severe pulmonary lesions characterized with pulmonary congestion and hemorrhage in a gerbil model for EV71 infection. In the EV71-infected gerbils, six 21-day-old or younger gerbils presented with a sudden onset of symptoms and rapid illness progression after inoculation with 1×105.5 TCID50 of EV71 via intraperitoneal (IP) or intramuscular (IM) route. Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination. EV71 viral titer was found to be peak at late stages of infection. EV71-induced pulmonary lesions, together with severe neurological disorders were also observed in gerbils, accurately mimicking the disease process in EV71-infected patients. Passive transfer with immune sera from EV71 infected adult gerbils with a neutralizing antibody (GMT=89) prevented severe pulmonary lesion formation after lethal EV71 challenge. These results establish this gerbil model as a useful platform for studying the pathogenesis of EV71-induced pulmonary lesions, immunotherapy and antiviral drugs. © 2015 Xu et al.


Yao P.-P.,Centers for Disease Control and Prevention | Qian L.,Centers for Disease Control and Prevention | Xia Y.,Centers for Disease Control and Prevention | Xu F.,Centers for Disease Control and Prevention | And 7 more authors.
PLoS ONE | Year: 2012

A reliable disease model mimicking Enterovirus 71 (EV71) infection in humans is essential for understanding pathogenesis and for developing a safe and effective vaccine. Commonly used rodent models including mouse or rat models are not suitable for vaccine evaluation because the rodents are resistant to EV71 infection after they reach the age of 6 days. In this study, 21-day-old gerbils inoculated intraperitoneally (IP) with a non mouse-adapted EV71 strain developed neurological lesion-related signs including hind limb paralysis, slowness, ataxia and lethargy similar to those of central nervous system (CNS) infection of EV71 in humans. The infected gerbils eventually died of the neurological lesions and EV71 could be isolated from lung, liver, spleen, kidney, heart, spinal cord, brain cortex, brainstem and skeletal muscle. Significantly high virus replication was detected in spinal cord, brainstem and skeletal muscle by cellular analysis, real-time quantitative PCR (RT-PCR) and immunohistochemical staining. Histopathologic changes such as neuronal degeneration, neuronal loss and neuronophagia were observed in spinal cord, brain cortex, brainstem, and skeletal muscle along with necrotizing myositis and splenic atrophy. Gerbils that received two doses of inactive whole-virus vaccine showed no EV71-specific symptoms after challenged with EV71. In contrast, gerbils that received mock vaccination died of EV71-induced neuropathology after challenged with EV71. The result indicates that gerbils can serve as a reliable disease model for evaluating safety and efficacy of EV71 vaccine. © 2012 Yao et al.


Huang W.,Hangzhou First Peoples Hospital | Zhu G.,Hangzhou Sixth Peoples Hospital | Huang M.,Hangzhou First Peoples Hospital | Lou G.,Hangzhou Sixth Peoples Hospital | And 2 more authors.
Clinica Chimica Acta | Year: 2010

Background: The association between OPN level and the histological severity of hepatic fibrosis and inflammation in hepatitis C virus (HCV) induced liver fibrosis remains unknown. Methods: 120 chronic HCV-infected subjects and 75 controls were enrolled in this study. Assessment of liver histology was performed based on liver biopsy. Plasma OPN levels were determined. Results: Significant differences were noted in the mean plasma OPN levels between subjects with extensive fibrosis and those with mild fibrosis (4.29 ± 1.01. ng/ml vs. 2.15 ± 0.63. ng/ml, respectively; p<0.001). Similarly, the subjects with higher histological activity index (HAI) score had elevated OPN levels than those with mild HAI score (4.41 ± 1.11. ng/ml vs. 2.25 ± 0.94. ng/ml, respectively; p<0.001). The correlation between the plasma OPN levels and the severity of liver fibrosis degree and HAI score were noted (r=0.945, and r=0.788, respectively both p<0.001). Logistic regression analysis showed that serum OPN was an independent risk factor contributing to extensive liver fibrosis and inflammation (p=0.0018 and p<0.001, respectively) in patients with HCV subjects. Conclusion: The plasma OPN level is correlated with the severity of liver fibrosis and inflammation, suggesting OPN could be used as a biomarker to evaluate the severity of liver damages in HCV subjects. © 2010 Elsevier B.V.


Zhuang R.X.,Hangzhou Sixth Peoples Hospital
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology | Year: 2012

To study the effects of acetylcysteine magnesium on the vasoactive substances and hepatic fibrosis indexes in liver cirrhosis and portal hypertension of rats. The rat liver cirrhosis model was made with 12 microg/kg dimethylnitrosamines. Then acetylcysteine magnesium was injected respectively with 25, 50, and 100 mg x kg(-1) dose daily into abdominal cavity. After 8 weeks treatment, pathological section, TGF-beta1, NO, TNOS and iNOS of hepatic tissue were detected to assess the effect of acetylcysteine magnesium against cirrhosis portal hypertension. After the DMNA modeling was completed, the HE and Sweet reticulocyte staining of liver pathological section showed that cirrhosis of the liver was in the III-IV phase, the infiltration of lymphocytes and formation of pseudolobuli in liver were alleviated in three acetylcysteine magnesium treatment groups (low, medium, and high dose), and the degree of liver fiber sclerosis in three groups was significantly lower than control group. Compared with control group, TGF-beta1, NO, TNOS and iNOS were significantly reduced in all treatment groups (P < 0.05). Acetylcysteine magnesium is probably a distinctive antioxidant which can remove various free radical in body and modulate ligand-dependent signal transduction and the growth of cell. It also have protection in the liver cirrhosis and portal hypertension of rats induced by dimethylnitrosamine.


Liu S.R.,Hangzhou Sixth Peoples Hospital
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology | Year: 2011

To investigate the influence of the individual genotype differences of DC-SIGN and DC-SIGNR on the mother-to-neonate intrauterine infection of HBV. The genotypes of the gene DC-SIGN and DC-SIGNR in the pregnant women with HBV positive were detected by PCR and agarose gel electrophoresis. The significant difference of gene diversity of DC-SIGN and DC-SIGNR was analyzed by chi-square test. (1) All of 29 cases in intrauterine infection group were 7/7 DC-SIGN genotype. In the non-intrauterine infection group, 7/5 genotype were observed in 2 of 54 cases, and the other 52 cases were 7/7 genotype. The two groups was no significant difference (P = 0.54). (2) 29 cases of intrauterine infection group was observed 4 genotypes of DC-SIGNR such as 7/7, 7/5, 9/7 and 6/5, the genotype frequencies were 0.3793, 0.3448, 0.2414 and 0.0345 respectively. 54 cases of non-intrauterine infection group was found 6 genotypes such as 7/7, 7/5, 9/5, 9/7, 7/6 and 6/5, genotype frequencies were 0.5186, 0.1481, 0.0926, 0.1852, 0.0370 and 0.0185 respectively. The distribution of 7/5 genotype in the intrauterine infection group (29 cases) and the non-intrauterine infection group (54 cases) was statistically significant (P = 0.038) , and no significant difference was found in other genotypes between the two groups (P > 0.05). The gene DC-SIGN showed relatively little variation in the pregnant women infected with HBV. On the countrary, there were multiple genotypes of the gene DC-SIGNR in these women, and the genotype "7/5" of DC-SIGNR might be one of the susceptibility genes associated with intrauterine infection.

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