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Objective@#To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control.@*Methods@#This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data.@*Results@#A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events.@*Conclusion@#In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.
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Objective The aim of this study was to investigate the effect of hepatitis C virus (HCV) replication on expression of silent information regulator 1 (SIRT1) and glucose metabolism of hepatocytes using Huh 7.5 cells harboring HCV replicon.Methods The level of reactive oxygen species (ROS),value of nicotinamide adenine dinucleotide (NAD+)/reduced form of nicotinamide adenine dinucleotide (NADH) was detected by flow cytometry and chromatometry.The activity,mRNA expression,and protein level of SIRT1 were detected by a scintillation counter,real-time fluorescence quantitative polymerase chain reaction (RT-PCR),and Western blot,respectively.Glucose uptake by hepatocytes and gluconeogenesis were detected using radioactive isotope method and glucose oxidase method.The mRNA levels of SIRT1 downstream glucose-metabolism genes were measured by RT-PCR.Measurement date were compared by t test.Results In replicon cells,the level of ROS (3.8±0.5 vs 1.0±0.2; t=12.736,P＜0.01) was increased and the value of NAD+/NADH (0.03±0.01 vs 0.12±0.03; t=6.971,P＜0.01) decreased compared with Huh 7.5 cells.The activity (0.3±0.1 vs 1.0±0.2; t=7.668,P＜0.01),mRNA expression(0.4±0.1 vs 1.0± 0.3; t=4.648,P＜0.01) and protein level(0.3±0.1 vs 0.8±0.2; t=5.941,P＜0.01) of SIRT1 were reduced.Inhibition of SIRT1 not only increased insulin receptor substrate-1 (IRS-1) phosphorylation (0.7±0.2 vs 0.4±0.1; t=3.286,P＜0.01),decreased protein kinase B (Akt) phosphorylation (0.3 ± 0.1 vs 0.6 ± 0.2; t=3.286,P＜0.01),down regulated cell surface expression of glucose transporler 2 (GLUT2,0.4±0.1 vs 1.0 ± 0.2; t =6.573,P＜0.01) and suppressed cellular glucose uptake (count per minute:4600±500 vs 21 000±4600; t=8.682,P＜0.01); but also decreased phosphorylation of forkhead box O1 (FoxO1,0.2＝0.1 vs 0.5±0.1; t=5.196,P＜ 0.01),up-regulated phosphoenolpyruvate carboxykinase (PEPCK,2.8±0.6 vs 1.0±0.3; t=6.573,P＜0.01) and glucose 6-phosphatase (2.6±0.5 vs 1.0±0.2; t=7.278,P＜0.01) genes,and promoted glucose production (2.5±0.5 vs 1.0±0.2; t=5.543,P＜0.01).Conclusions HCV replication decreases NAD+/NADH ratio,which might down-regulate the activity and the expression of SIRT1,leading to changes in the expression profile of glucose metabolism related genes and causing glucose metabolism disorders of hepatocytes by a decrease in glucose uptake and an increase in glucose production,and promotes HCV replication.
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ObjectiveTo investigate the effect of adding metformin to peginterferon alfa-2a and ribavirin on the efficacy in patients with genotype 1 chronic hepatitis C and insulin resistance.Methods Ninety-eight patients with genotype 1 chronic hepatitis C and insulin resistance were randomized into the treatment group (n=49) and the control group (n=49).The patients in the control group were treated with peginterferon alfa-2a and ribavirin,and those in the treatment group were treated with metformin in addition to peginterferon alfa-2a and ribavirin. The virologic response rate,the homeostasis model assessment for insulin resistence index (HOMA-IR) and incidence of side effects were compared between two groups.The related factors of sustained virological response (SVR) were studied by multivariate logistic regression analysis.ResultsThe SVR rate of the patients in the treatment group was significantly higher than that of the control group (59.2％ vs 38.8％; x2 =4.083,P=0.043).The HOMA-IR of patients in the treatment group at week 12,24,48 of treatment and week 24 of follow-up were 3.00±0.65,1.90±0.45,1.75±0.40 and 1.60±0.35,respectively,which were all lower than those in the control group (3.50±0.72,2.90±0.64,2.74± 0.48 and 2.60±0.55,respectively) (t=3.610,8.947,11.091 and 10.738,respectively; all P＜ 0.01).The incidence of diarrhea in the treatment group was higher than the control group (28.6％ vs 10.2％ ; x2 =5.288,P=0.021).In multivariate logistic regression analysis,the independent factors associated with SVR were metformin treatment (P =0.009) and HOMA-IR＜ 2 at week 24 of treatment (P=0.011 ). Conclusion The combination of metformin,peginterferon alfa-2a and ribavirin improves insulin sensitivity and increases SVR rate of patients with hepatitis C genotype 1 and insulin resistance with good safety profile.
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Objective To investigate the dynamic changes of serum high mobility group box-1 (HMGB1)and epithelial neutrophil-activing peptide-78(ENA-78)associated with secondary brain edema in patients following acute brain injury.Methods The serum HMGB1 and ENA-78 in 110 patients with acute brain injury were determined by using enzyme-linked immunosorbent assay(ELISA)12 hours,3 days and the 5 days after acute brain injury.The outcomes were analyzed by t-test and estimated well with clinical symptoms,imaging data and Glasgow Outcome Scale(GOS)in combination of.Results The levels of HMGB1 and ENA-78 increased significantly with lowering the score of GCS 12 hours after acute brain injury.The more severity of acute brain injury resulted in more production of HMGB1 and ENA-78 and longer period of persisted and peaked brain edema(all P ＜0.01).HMGB1 levels had positive correlation with severity and persistence of brain edema(r =0.69,P ＜0.01 and r =0.70,P ＜0.01).ENA-78 levels had positive correlation with severity and persistence of brain edema(r =0.62,P ＜ 0.01 and r =0.65,P ＜ 0.01).Furthermore,there were statistical differences in HMGB1 and ENA-78 levels between different GOS groups.Compared with good outcome group and normal control group,the HMGB1 and ENA-78 levels in poor outcome group persistently increased and were higher within 5 days after brain injury(P ＜ 0.01 or P ＜0.05).There was a correlation between serum HMGB1 and ENA-78 levels in patients with acute brain injuries(r =0.68,P ＜ 0.01).Conclusions The changes of serum HMGB1 and ENA-78 levels were closely associated with secondary brain edema in patients following acute brain injury.
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Objective To investigate the changes of epidemiological and clinical features of patients with hemmorrhagic fever renal syndrome (HFRS) over past 10 years in Harbin region. Methods The epidemiological, clinical and laboratory data of patients with HFRS in 1995 and 2005 in The Second Affiliated Hospital of Harbin Medical University were retrospectively analyzed. The genotypes of Hantaan virus of patients in 2005 having an onset within 5 days were examined by reverse transcriptase polymerase chain reaction (RT-PCR). Positive rates in different groups were compared using chi square test. Results One hundred and sixty-five cases were collected, including 78 in 1995 and 87 in 2005. There were significant differences in epidemiological area (X2=10. 483, P<0.05), clinical classification (X2=7. 907, P<0.05), clinical stage (X2=10.500, P<0.05), the variance of total white blood cells (X2=20. 315, P<0.01) and blood sugar changes (X2=9.958, P<0.01) between two groups of patients. Bases on clinical manifestations, there were significant differences in two groups (1995 and 2005): headache, 70.5% and 50.6% (X2=6.812, P<0.01); lumbago, 60.3% and 40.2% (X2=6.598, P<0.05); fossaorbitalis pain, 50.0% and 19.5% (X2=17.019, P<0.01); melena, 60.3% and 40.2% (X2=6.598, P<0.05); bleeding point and eeehymosis, 50.0% and 33.3% (X2=4.715, P<0.05) ; flush of faee, neck and upper chest, 59.0% and 40.2% (X2=5.782, P<0.05); membrane-like object in urine, 44.9 % and 29.9% (X2=3.964, P<0.05) rates of thrombocytopenia, 79.5% and 64.4% (X2=4.615, P<0.05) ; rates of liver dysfunction, 50.0% and 80.5% (X2=17.019, P<0.01); rates of cardiac muscle enzymoiogy dysfunction, 50.0% and 92.0% (X2=36.003, P<0.01). The genotypes of patients in 2005 were Hantaan virus (34.8%) and Seroul virus (65.2%). Conclusion The differences in epidemiological and clinical feature of patients with HFRS over past 10 years may be related with the change of virus genotypes, and further study should be done.
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Objective To study the epidemiological and clinical features of the patients with forest encephalitis. Methods The epidemiological, clinical and laboratory data and prognosis of forest encephalitis patients with forest encephalitis virus-specific antibody positive were retrospectively analyzed. Results The onsets of 79 patients with forest encephalitis were mainly in May to August. Fifty-six of them were forestry workers, 9 were forest beekeepers, 8 were inhabitants with experience of getting potherb and 6 were tourists. Of the 79 patients, cases with mild, moderate and severe type were 5, 35 and 39, respectively; 7 cases died and 13 presented sequelae, such as head drooping, paralysis of the upper extremities, epilepsy, trembling and psychonosema. All 79 patients presented fever, headache, nausea and vomiting; and some of them presented other symptoms including 32 (40.5%) conscious disturbance, 74 (93.7%) neck rigidity, 74 (93.7%) meningeal irritation sign positive, 20 (25.3%) convulsion, 38 (48.1%) complexion flush, conjunctiva and oral mucosa congestion, 19 (24.1%) neck, shoulder, upper extremity muscle and limbs paralyzed, 4 (5.1%) respiratory muscle paralysis and 3 (3.8%) dysphagia. The abnormal laboratory findings included that 60 (80.0%) elevated cerebrospinal fluid pressure, 66 (88.0%) increased cell counts, 65 (82.3%) diffused and scattered slow waves on electroencephalograms, 8 (10.1%) liver dysfuncted and 18 (22.8%) elevated cardiac muscle enzymes. Conclusions Forest encephalitis is characterized by hyperpyrexia and central nervous system damage. The morbidity of severe patients is high, and the sequelae are common as well, to which we should pay much attention.
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Objective To study the clinical features of patients with hemorrhagic fever with renal syndrome(HFRS)complicating hyponatremia encephaledema and therapeutic effect of manicol and high sodium hemodialysis.Methods Eighty-three patients with HFRS complicating hyponatremia encephaledema were randomly divided into high sodium hemodialysis treatment group(n=41)and control group(n=42).The serum levels of potassium,sodium,chlorine,creatinine,osmotic pressure,normalization rates and normalization time of serum sodium,mortality of patients in two groups post-treatment were compared.Statistical analysis was performed using t test or chi square test.Resalts The serum levels of sodium [(128.95±7.3)mmol/L],chlorine[(96.7±6.2)mmol/L],osmotic pressure[(253.1±7.5)mOsm/L]of patients post-treatment in high sodium hemodialysis treatment group were all significantly higher than those[(117.8±7.1)mmol/L],[(92.2±6.9)mmol/L],[(242.1±8.4)mOsm/L]of patients in control group (t=7.14,t=3.12,t=15.22,respectively;all P＜0.05).The serum sodium normalization number of patients(12/19 cases)with moderate encephaledema in high sodium hemodialysis treatment group was significantly higher than that(6/19 cases)in control group(X2=3.867,P=0.049).The serum sodium normalization time of patients with moderate encephaledema in high sodium hemodialysis treatment group WaS(4.9±1.3)d,which was significantly shorter than that[(8.3±1.9)d]in control group(t=6.438,P=0.001).The serum sodium normalization number of patients(7/14 cases)with severe encephaledema in high sodium hemodialysis treatment group was significantly higher than that(2/14 cases)in control group(X2=4.094,P=0.043).The serum sodium normalization time of patients with severe encephaledema in high sodium hemodialysis treatment group was(7.8±1.9)d,which was significantly shorter than that[(11.6±2.8)d]in control group(t=3.235.P=0.034).The mortality in high sodium hemodialysis treatment group was 36.6%(15/41 cases),which was significantly lower than that(61.9%,26/42 cases)in control group(X2=5.321,P=0.021).Conclusions The conditions of patients with HFRS complicating hyponatremia encephaledema tend to be severe.In patients with HFRS complicating moderate or severe encephaledema,manicol and high sodium hemodialysis can improve the normalization rate and normalization time of serum sodium,and reduce the mortality.
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Objective To establish high level expression system of exogenous hepatocyte growth factor(HGF) protein in mouse livers by in vivo gene transfection and to observe the inhibition effect of exogenous HGF on hepatocyte apoptosis in mice. Methods Mice were divided into four groups, with 10 mice in each arm, which were injected with control solution, empty pcDNA3 plasmids, pCMV-HGF plasmid or 0.9% sodium chloride solution by tail vein. Enzyme-linked immunosorbent assay(ELISA) was used to determine the peak level and the expression duration of HGF protein in the peripheral blood and liver tissue. Western blotting was performed to measure the Caspase-3, tBid, Bax and Cytochrom C in the hepatocyte homogenatea and mitochondrion. Results HGF protein was detected in the mice blood as early as 4 hours after single injection of pCMV-HGF plasmid. The peak level of HGF protein in liver and plasma was respectively achieved by 8 hours and 12 hours after first injection while HGF protein was still detectable in the blood 6 days after the initial injection. D-Galactosamine/lipopolysaeeharide (LPS) led to obvious hepatocyte apoptnsis and induced an increased concentration of tBid, Bax, Caspase-3 and Cytochrom C in the hepatocyte homogenates and mitochondrion. Compared to sodium chloride control group and empty pcDNA3 protected group, the expression of tBid, Bax, Caspase-3 and Cytochrom C decreased in pCMV-HGF plasmid protecting group. Conclusions Hepatocyte apoptosis can be inhibited by exogenous HGF protein expression in mouse livers, which is induced by in vivo gene transfection. Moreover, it may inhibit the activation of downstream apoptotic proteins by blocking the expression of tBid.
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Objective To investigate epidemiological and clinical features of patients with clonorchiasis sinensis infection. Methods The epidemiological, clinical, laboratory and treatment data of clonorchiasis patients in Department of Infectious Diseases, Second Affiliated Hospital, Harbin Medical University from 2002 to 2004 were retrospectively analyzed. Results Sixty-eight point two percent patients had a history of eating raw freshwater fish and shrimp. Patients with occupations as cook, fish stock man, fishing man and fishmonger accounted for 22.6%. The transmission route was not clear in 9.1% of patients. The common clinical manifestations were abdominal pain (60.3%), fatigue (52.3%), diarrhea (33.0%), anorexia (69.3%), jaundice (23.9%), hepatomegaly (59.1%), splenomegaly (8.0%), dizziness (20.9%), fever (5.7%) and biliary colic (14.8%). Twenty-eight point four percent were asymptomatic. Other findings included liver dysfunction (70.4 %) and eosinophile granulocyteosis(69.3 %). Negative rate of stool egg of clonorchis sinensis after treatment with praziquantel or albendazole was 91.9% or 86.5%, respectively. There was no significant difference between the two groups ( χ2 = 0.561, P = 0.454). Conclusions Clinical manifestations of patients with clonorchiasis sinensis are complicated and often accompanied with liver dysfunction. Clonorchiasis sinensis is often misdiagnosed and should be paid much attention.
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OBJECTIVE To evaluate the clinical efficacy of lamivudine on prevention of liver injury in HBV carriers complicating tuberculous exudative pleurisy after use of antituberculosis drugs.METHODS Totally 120 HBV carriers complicating tuberculous exadative pleurisy after use of antituberculosis drugs were randomly divided into lamivudine group and control group.RESULTS The incidence rate of liver injury was 10.0% in lamivudine group vs 1.7% in control group(P0.05).CONCLUSIONS Lamivudine may be good for reducing liver injury in HBV carriers complicating tuberculous exadative pleurisy after use of antituberculosis drugs.
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OBJECTIVE: To evaluate the efficacy of compound glycyrrhizin in preventing liver injury induced by antituberculosis drugs. METHODS: A total of 180 cases with pulmonary tuberculosis were randomly divided into control group and trial group: 90 cases in the control group were treated with antituberculosis drugs alone for 6～8 months,and another 90 cases in the trial group were treated concomitantly with antituberculosis drugs and compound glycyrrhizin,the incidences of liver injury between 2 groups were monitored. RESULTS: The incidences of liver injury of the control group and the trial group were 32.2% and 8.9%,respectively(P