1.Therapeutic effects of Fuzheng Huayu decoction in different pathological stages CCl4-induced liver cirrhosis rat model and on hepatic stellate cells activation
Wenhua YI ; Ye LI ; Shibin XIE
The Journal of Practical Medicine 2014;(9):1366-1369
Objective To evaluate the influence of Fuzheng Huayu decoction on different pathological stages fibrotic liver tissue and activated hepatic stellate cells (HSCs). Methods Use a carbon tetrachloride (CCl4)-induced liver cirrhosis rat model system. The drug intervention was administered via oral-gastric irrigation in building, the end of week 2 and 4. Rats were batch sacrificed at the end of week 2 , 4, and 6. Liver fibrosis was evaluated by histology, and expression of a-smooth muscle actin (α-SMA) was determined by immunohistochemistry. Between-group comparisons were made by completely random design and ANOVA with Bonferroni correction. Results At the end of weeks 2, 4 and 6, the model group and drug intervention groups had significantly higher area ratio of liver fibrosis and higher expression of α-SMA than the normal group, but the three drug intervention groups had significantly less area ratio of liver fibrosis and less expression of α-SMA than the model group and the drug intervention 1 group showed the most robust decrease (P<0.05). Conclusion The Fuzheng Huayu decoction leads to down-regulated α-SMA expression and reduced degree of liver fibrosis on different pathological stages of fibrotic liver tissue, and the earlier drug intervention, the better the results.
2.The impact of serum levels of immunoglobulin and complement during nucleoside antiviral treatment in chronic hepatitis B patients
Chan XIE ; Junqiang XIE ; Yufeng ZHANG ; Dongying XIE ; Shibin XIE ; Liang PENG ; Bingliang LIN ; Zhiliang GAO
Chinese Journal of Infectious Diseases 2012;30(2):100-104
Objective To evaluate the effects of nucleoside/nucleotide analogue treatment on immunoglobulin and complement in patients with chronic hepatitis B (CHB).MethodsA total of 157 CHB patients were recruited and divided into CHB group,liver cirrhosis (LC) group and severe hepatitis B (SHB) group.There were 50 patients who received oral antiviral treatment (lamivudine 100 mg/d,or entecavir 0.5 mg/d,or telbivudine 600 mg/d).Serum levels of complement 3 and 4 (C3,C4),C-reaction protein (CRP),hemolytic complement (CH50),immunoglobulin G,M,A (IgG,IgM,IgA),hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were detected by enzyme-linked immunosorbent assay (ELISA) or immunoturbidimetry.Hepatitis B virus (HBV) DNA was quantified by real-time polymerase chain reaction (RT-PCR) before and 1,2,3 and 4 weeks after nucleoside antiviral therapy.Comparison of means was done by t test and Mann-Whitney test.The correlation was analyzed by Pearson correlation coefficient test.ResultsSerum IgA and IgM levels of SHB and LC patients were significantly higher than those of CHB patients (P<0.01).Levels of C3,C4,CH50 and CRP were significantly different among three groups.Levels of C3,IgM,IgG and HBV DNA in HBeAg positive patients were significantly different from those in HBeAg negative patients.There was a statistically significant difference of IgA,IgM,C3 and CH50 levels between patients with high HBV DNA level and low HBV DNA level in HBeAg-positive patients.While in the HBeAg-negative patients,only the IgA level was significantly different with HBV DNA levels.After anti-viral treatment,immunoglobulin and HBV DNA levels were all decreased in three groups,while the serum complement level was increased compared to baseline,and the differences became significant at week 4 of treatment. HBV DNA level was negatively correlated with C3 (r=-0.78,P=0.021) and HBeAg titer was positively correlated with C3 (r=0.87,P=0.015).ConclusionsThe immunoglobulin,CRP,C3,C4,and C H50 could reflect the inflammatory activity in liver.The changes of C3 level can predict the efficacy of antiviral therapy.
3.Study on the role of asialoglycoprotein receptor for human bone marrow mesenchymal stem cells against hepatitis B virus infection
Chan XIE ; Shibin XIE ; Shaoquan ZHANG ; Junqiang XIE ; Bingliang LIN ; Zhiliang GAO
Chinese Journal of Infectious Diseases 2010;28(8):455-460
Objective To investigate the susceptibility of bone marrow mesenchymal stem cell (BMSC) to hepatitis B virus (HBV) infection during induction toward hepatocyte and the role of asialoglycoprotein receptor (ASGPR) in BMSC HBV infection. Methods BMSC obtained from hepatitis B patients were tested for HBV infection and then cultured with HBV infectious serum in vitro and induced to differentiate into hepatocyte through exposure to hepatocyte growth factor (HGF), fibroblast growth factor-4(FGF-4), and epidermal growth factor(EGF). Subsequently these cells were determined for the presence of hepatitis B virus e antigen( HBeAg), hepatitis B virus surface antigen(HBsAg) and ASGPR. All experiments were repeated for 3 times in 5 different samples. The results were analyzed by non-parametric test. Results After 6 days of exposure, BMSC-derived hepatocyte-like cells expressed hepatic special genes and proteins, including alpha fetoprotein(AFP),cytokeratin18 (CK18), albumin (Alb), and manifested hepatocyte functions, including glycogen synthesis, urea secretion and albumin synthesis. Expressions of CK18 and Alb were increased, and AFP was decreased with time of induction. The BMSC were resistant to HBV infection both in vitro and in vivo or after induction toward hepatocyte. ASGPR expression level was low in BMSC, which was increased in the induced BMSC but still lower than that of the control HepG2 cells. Conclusions BMSC are resistant to HBV infection both in vitro and in vivo. The low level expression of ASGPR may be a reason for this.
4.Application of a new scoring system for severity evaluation of acute-on-chronic liver failure induced by hepatitis B
Tianhuang LIU ; Jianyun ZHU ; Shaoquan ZHANG ; Shibin XIE ; Weimin KE ; Zhiliang GAO
Chinese Journal of Clinical Infectious Diseases 2013;6(6):321-324
Objective To assess the application of a new scoring system for severity evaluation of acute-on-chronic liver failure induced by hepatitis B.Methods A total of 399 patients (203 survivals and 196 deaths) with acute-on-chronic liver failure induced by hepatitis B were collected from the Third Affiliated Hospital of Sun Yat-sen University during January 2003 and June 2008.All patients were graded with the new scoring system and model for end-stage liver disease (MELD) at critical stage (survivals) or terminal stage (deaths).The survival rates and fatality rates of patients who were graded by two scoring systems were analyzed and compared.Results With MELD system,the fatality rate was 11.89% (17/143) in patients with scores of 15-26,64.68% (141/218) with scores of 27-48,and 100% (38/38) with scores of 49-69.No score range with fatality rate of 0 was found.While with the new scoring system,the survival rate was 99.2% (126/127) when the severity scores were between 2 to 8,and patients with scores 2,3,4,5,6 and 8 were all survived; the fatality rates were gradually raised from 4.2% (1/24) with scores of 9-17 to 100% (82/82) with scores of 18 and above.Conclusion The new scoring system is more objective,simple and sensitive than MELD system,which can be used for severity evaluation of acute-onchronic liver failure induced by hepatitis B.
5.The role of surgery in the management and prognosis of limited-stage Ⅱ small cell lung cancer
Mingran XIE ; Shibin XU ; Jin GAO ; Xinyu MEI ; Tian LI ; Xiaohui SUN ; Dongchun MA
Chinese Journal of Thoracic and Cardiovascular Surgery 2014;30(9):517-520
Objective The aim of this retrospective study was to analyze the role of surgery in the management of limited-stage-Ⅱ small cell lung cancer.Methods A retrospective review of 82 patients with limited-stage Ⅱ small cell lung cancer between January 2001 and December 2009 was performed.The prognostic impact of different therapy and the clinicopathologic factors were analyzed.Using SPSS 16.0 statistical software for data analysis.Log-rank test for the difference of survivale rate.Using the Cox model for muliti-factor survival analysis.Chi-square test for local recurrence and distant metastasis rate.Results The overall median survival time and the 1-,3-,and 5-year overall survival rates were 27.0 months,62.1%,35.9%,and 21.0%,respectively.Median survival was 34.0 months in surgical patients vs 16.0 months in nonsurgical patients (P =0.000).Median survival after lobectomy or pneumonectomy was significantly longer than after wedge resection (P =0.048).However,survival after wedge resection was still significantly longer than survival in nonsurgical patients(P =0.024).Survival analysis confirmed that the operation,chemotherapy and radiotherapy were showed to be independent prognostic factors.The local-regional recurrencer rates of lobectomy or pneumonectomy group was lower than wedge resection group(P =0.030).The distant metastasis rates of lobectomy or pneumonectomy group was lower than nonsurgical grou (P =0.021).Conclusion This study suggests that lobectomy or pneumonectomy combined with adjuvant radio-chemotherapy should be recommended for patients with limited-stage Ⅱ small cell lung cancer.
6.Alanine aminotransferase and aspartate aminotransferase levels are sensitive indicators for liver inflammation grading in HBeAg-negative chronic hepatitis B patients
Shaoquan ZHANG ; Jing LAI ; Shibin XIE ; Xiaohong ZHANG ; Ying ZHANG ; Zhixin ZHAO ; Weimin KE ; Zhiliang GAO
Chinese Journal of Infectious Diseases 2011;29(8):463-467
Objective To investigate the relationship between serum levels of alanine aminotransferase (ALT)or aspartate aminotransferase (AST)apportioned by the same hepatic parenchyma cell volume and liver histological necroinflammation grades in HBeAg-negative chronic hepatitis B (CHB)patients.Methods A total of 145 CHB patients were divided into four groups:Gl,G2,G3 and G4 based on the liver histological necroinflammation grade.The serum ALT and AST levels were determined by automatic biochemical instrument in these four groups.Furthermore,serum ALT and AST levels were then apportioned by the same hepatic parenchyma cell volume.The data were analyzed by ANOVA.Results Mean serum ALT levels in G1,G2,G3 and G4 groups were (35.3±29.1),(91.6±120.4),(111.6± 116.1)and (118.0±122.1)U/L,respectively,and the serum ALT levels apportioned by same hepatic parenchyma cell volume were ( 54.0 ± 45.1 ),( 144.2 ± 184.9 ),(191.3± 204.8)and (215.1 ± 226.5)U/L,respectively.The pairwise comparison between G1 and other three groups all showed statistically significant difference (P<0.05).Meanwhile,AST levels in G1 to G4 groups were (35.5± 29.0),(64.9±71.7),(96.0±81.9)and (102.8±77.0)U/L,respectively and the serum AST levels apportioned by the same hepatic parenchyma cell volume were (54.3±44.6),(102.3± 107.9),(165.2±148.7)and (189.4±145.4)U/L,respectively.The pairwise comparison between G1 and G3,G1 and G4,G2 and G3,G2 and G4 all showed statistically significant difference (P<0.05).Conclusion Both AST and ALT levels are sensitive indicators for liver inflammation grading in HBeAg-negative CHB patients during the natural history of the disease.
7.Long-term prognosis of patients with HBV-related decompensated cirrhosis treated by nucleos( t)ide analogues
Shibin XIE ; Lijiao ZENG ; Ying ZHANG ; Jianyun ZHU ; Chao MA ; Zhiliang GAO
Chinese Journal of Clinical Infectious Diseases 2009;2(4):201-204
Objective To evaluate the long-term prognosis of patients with HBV-related decompensated cirrhosis after treatment with nucleos (t) ide analogues. Methods Totally 94 patients with HBV-related decompensated cirrhosis were enrolled, 53 in nucleos(t) ide group, 41 in control group, and both received routine treatments. Patients in nucleos (t)ide analogue group also received lamivudine ( 100 mg/d), or adefovir ( 10 mg/d), or entecavir (0.5 rag/d). The follow-up was terminated for those who developed hepatocellular carcinoma, received liver transplantation, died or refused the treatment. Serum biochemical markers, Child-Pugh grades and clinical outcomes were compared between two groups at the end of following up. Results After nucleos (t) ide analogues therapy, ALT, AST, globulin ( Glb), and TBil decreased, while Alb and cholinesterase (CHE) increased in the nucleos(t)ide group, and Chiid-Pugh scores decreased in 43 (81.1%) patients. While in the control group, ALT, AST, Glb and TBil did not show significant changes, but the CHE was significantly lower than before ( t = 5. 225, P < 0. 01 ). More patients in nucleos (t)ide group showed improvements in Child-Pugh grades, and there was significant difference between the two groups (X2 = 52.16, P <0.01). The incidence of HCC is lower in nucleos(t) ide group (0%) than that in the control group ( 19.5% ) ( X2 = 23.07, P < 0.01 ). The incidence of death and liver transplantation between two groups did not show siguificant difference. Conclusions Nucleos(t) ide analogues therapy can significantly improve biochemical status of liver functions in patients with HBV-related decompensated cirrhosis. The incidence of hepatocellular carcinoma may decline and the long-term prognosis can be improved.
8.Establishment of a scoring system for evaluating the severity of hepatitis B patients with acute-on-chronic liver failure
Tianhuang LIU ; Jianyun ZHU ; Shaoquan ZHANG ; Shibin XIE ; Weimin KE ; Zhiliang GAO
Chinese Journal of Infectious Diseases 2010;28(5):293-296
Objective To establish a scoring system for evaluating the severity of hepatitis B patients with acute-on-chronic liver failure and to compare the validity of this system with model for end-stage liver disease (MELD). Methods MELD score was used in hepatitis B patients with acuteon-chronic liver failure who were divided into survival group (203 cases) and death group (196 cases).Seven clinical relative indices, including prothrombin activity, serum creatinine, hepatic encephalopathy, accompanying infections, serum total bilirubin, the dimension of liver, the amount of ascites, were selected for evaluating the severity. Each index was graded with 1 to 4 points based on the severity. Then the total score was counted by adding up scores of each index. T test and area under receiver operating characteristic (ROC) were used to evaluate the difference and similarity of the two systems. Results According to the new scoring system, the total score was 8. 07±3. 14 in the survival group and 16. 91 ±3. 54 in the death group. There was a statistically significant difference between these two groups (t = 26.125. P<0.01). In 81.32% of survival patients, their scores ranged from 3.91 to 12.23, while in 81.32% of dead patients, their scores ranged from 12.23 to 21.60. The two ranges overlapped at 12.23. According to the MELD system, the total score was 26. 43 ±5. 58 in the survival group and 40. 16 ±10. 22 in the death group. The difference between the two groups was statistically different (t = 16. 566, P<0. 01). In 61.02% of survival patients, the MELD scores ranged from 21. 49 to 31. 19, while in 61. 02% of the dead patients, the MELD scores ranged from 31. 19 to 48. 94. The two ranges overlapped at 31.19. The areas under ROC of the new scoring system and MELD system were 0.960 (95% CI: 0. 944-0. 977) and 0.886 (95% C/;0. 852 - 0. 920). No overlap was found in these two 95%CJ and there was a statistically significant difference. Conclusions The new scoring system is applicable for evaluating the severity and prognosis of acute-on-chronic liver failure in hepatitis B patients. The sensitivity of this new scoring system is approximate to the MELD system.
9.Risk factors of hepatitis B virus re-infection after orthotopic liver transplantation
Jianyun ZHU ; Ying ZHANG ; Shibin XIE ; Lijiao ZENG ; Chao MA ; Minqiang LU ; Zhiliang GAO
Chinese Journal of Clinical Infectious Diseases 2010;3(2):80-84
Objective To investigate the risk factors of hepatitis B virus(HBV) re-infection after orthotopic liver transplantation(OLT)and to evaluate the therapeutic efficacy of hepatitis B immunoglobulin(HBIG)combined with nucleos(t)ide analogues. Methods The study included 160 patients with HBVrelated liver diseases who underwent OLT in the Third Affiliated Hospital of Sun Yat-sen University from October 2003 to Augest 2007, 117 of whom were treated with nucleos(t)ide analogues before OLT;and all patients were received HBIG i. m and nucleos(t)ide analogues treatment after OLT. Preoperative data of the patients were retrospectively reviewed, and HBV re-infection was assessed prospectively. Independent t test was used to compare normally distributed data and Fisher's exact test was used for the comparison of rates among groups. Results HBV re-infection Was observed in 19 patients after OLT with a rate of 11. 88%(19/160), which was not correlated with HBV DNA loads, HBeAg and the duration of antiviral therapy before OLT(r=0.108, 0.127 and 0.033, P>0.05). Of 19 patients with HBV re-infection, 17 were treated with lamivudine after OLT, and HBV YMDD mutants were detected in 8. The YMDD positive group had a higher HBV DNA level than YMDD negative group(7.0 ± 2.0 log copies/mL vs 3.2 ± 2.5 log copies/mL, t = 3.531, P=0.003). Among above 17 patients, 12 received adefovir add-on treatment, and3 received entecavir instead of lamivadine; all achieved satisfactory responses. Conclusions Low dose of HBIG combined with long-term use of nucleos(t)ide analogues can effectively prevent HBV re-infection after OLT. HBV YMDD mutation may be the primary reason for HBV re-infection in the patients treated with lamivudine after OLT.
10.Prognostic value of the number of negative lymph nodes in non-small cell lung cancer without lymphatic metastasis after pulmonary resection
Mingran XIE ; Shibin XU ; Xinyu MEI ; Zhenghua ZHANG ; Jieyong TIAN ; Jun WANG ; Dongchun MA
Chinese Journal of Clinical Oncology 2014;(7):439-443
Objective:This study aims to investigate the correlation between the number of resected lymph nodes (LNs) and the prognosis of patients with node-negative non-small cell lung cancer (NSCLC). Methods:A retrospective review of 305 patients with NSCLC, who received curative resection between January 2004 and December 2009, was conducted. All patients were proved without lymph node involvement histopathologically. The prognostic impact of the number of negative LNs and the clinicopathologic factors were analyzed. Results:The overall median survival time and the 1-, 3-, and 5-year overall survival rates were 60.0 months, 76.1%, 59.3%, and 47.1%, respectively. Survival analysis confirmed that the number of negative LNs, T staging and the stations of the mediasti-nal lymph nodes dissected were showed to be independent prognostic factors. Patients with a high number of negative LNs had better overall survival than patients with a low number of negative LNs (P<0.05). The patients with dissected LNs counts of more than 11 for cases with pTl~2 tumor (P<0.05) and more than 16 for cases with pT3 tumor (P<0.05) had better long-term survival outcomes. The post-operative complication rate was 12.1%, which was not significantly correlated with the number of dissected lymph nodes (P>0.05). Conclusion:The number of negative lymph nodes is an independent prognostic predicting factor for node-negative NSCLC. Sufficient dissection of LNs is recommended to improve the survival of the patients with node-negative NSCLC.