Objective To study the impact of ribavirin cumulative dose on virological response rates in genotype 1 hepatitis C virus(HCV)infected patients.Methods The medical records of 225 genotype 1 chronic hepatitis C(CHC)patients treated with peginterferon α-2a plus ribavirin were retrospectively analyzed.These patients were divided into four groups according to ribavirin cumulative dose:>97%,80%-97%,60%-79%and<60%of standard cumulative dose.The relationship between ribavirin cumulative dose and virological response rates was studied.Data as analyzed by chisquare test or F test.Results The incidence of ribavirin cumulative dose<97%was 43.1%(97/225),which was higher than peginterferon alfa-2a(27.1%,61/225)(x2=12.641,P=0.001).The sustained virological response rate(SVR)was 27.8%(5/18)in group of ribavirin cumulative dose <60%,which was much lower than those in groups of ribavirin cumulative dose>97%(65.6%,84/128),80%-97%(60.5%,26/43),60%-79%(58.3%,21/36)(x2=9.538,P=0.023).The relapse rate was 61.5%(8/13)in group of ribavirin cumulative dose<60%,which was significantly higher than those in groups of ribavirin cumulative dose>97%(20.0%,21/105),80%-97%(23.5% ,8/34),60%-79%(27.6%,8/29)(x2=10.837,P-0.013).Among patients achieved rapid virological response(RVR),SVR in groups of ribavirin cumulative dose>97%,80%-97%,60%-79%and<60 % of standard dose were 92.0%(23/25),88.9%(8/9),85.7%(6/7)and 75.0%(3/4),respectively(x2=1.098,P=0.778).Conclusiom Mlid reduction of ribavirin dose not affect SVR of genotype 1 HCV infected patients.However,the relapse rate is high and SVR is low in patients treated with ribavirin cumulative dose<60% of standard dose.

Objective To investigate the corelation between neutropenia (ANC) incidence and infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C.Methods A retrospective cohort study of 399 patients treated with peginterferon and ribavirin derived from database of Department of Infectious Diseases, the Second Affiliated Hospital, Harbin Medical University was conducted.The incidence of infections and their relation with ANC were investigated.Potential risk factors for infection were identified by multivariate analysis.Results During treatment,neutropenia (ANC ＜ 1.50 ×109/L) occurred in 251 patients.Among which,mild neutropenia [ANC: ( ＞ 0.75-＜ 1.50) x 109/L],moderate neutropenia [ANC: ( 0.50-0.75 ) × 109/L]and severe neutropenia ( ANC ＜ 0.50 × 109/L)occurred in 132 patients,103 patients and 16 patients,respectively.A total of 80 infections (20.1％ )occurred,among which,14 infections were defined as severe.There was no significant difference in infection rate between patients with and without neutropenia ( 19.9％,50/251 vs 20.3％,50/251 ; x2 =0.007,P =0.933).There was no significant difference in infection rate between patients with and without peginterferon dose reduction ( 21.5％,31/144 vs 19.2％,49/255 ; x2 =0.307,P =0.580 ).In multivariate logistic regression analysis,the independent factors associated with infection were age (P =0.021),diabetes (P =0.004) and cirrhosis (P =0.012).Conclusions Infections during treatment with peginterferon alfa and ribavirin for chronic hepatitis C are irrelevant to neutropenia.The independent factors associated with infection are age,diabetes and cirrhosis.

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.

Objective To assess the effects of cyclic stretch on fibroblast orientation in order to find the appropriate cyclic stretch to cause maximum fibroblast orientation and to explore the mechanism of cell signalling since cells are known to orient in response to the application of mechanical forces. Methods Human forehead dermal fibroblasts were seeded onto collagen coated flexible membranes. Membranes were then deformed at 10 cycles per minute by the application of 135 mmHg subatmospheric pressure. This corresponded to strain levels of 0% to 24% from the center to extremity of the flexible membrane. Cells orientation angles were studied by inverted microscopy. Integrin ?1 distribution were studied with immunocytochemical staining and confocal microscopy. Integrin ?1 expression and focal adhesion kinase ( FAK) phosphorylation were analyzed with Western blot analysis. Results A minimum of 15% cell stretch was required to significantly stimulate the fibroblast orientation response. Cyclic stretch induced integrin ?1 redistribution and FAK phosphorylation. Incubation of cells with anti-integrin ?1 prior to the application of stretch abrogated fibroblast orientation and FAK phosphorylation. Conclusion Fibroblast orientation in response to cyclic stretch is mediated at least in part by integrin ?1 through phosphorylation of FAK.

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.

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.

Objective To study the role of silent mating type information regulation 2 homolog1 (SIRT1)-adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in hepatitis C virus core protein (HCV-core) induced energy metabolism disorders of hepatocytes.Methods HepG2 cells were transfected with recombined expressed plasmid pcDNA3.1-core.The level of reactive oxygen species (ROS),value of ATP/ADP and activity of AMPK α-2,and nicotinamide adenine dinucleotide (NAD)+/NADH in HepG2 cells expressing HCV-core were detected by flow cytometry,liquid scintillation counter and chromatometry,respectively.The activity of SIRT1 was detected with a fluorometric assay kit.Reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay were performed to examine the expression of SIRT1 and AMPK α-2.Quantitative data were analyzed by t-test.Results It was confirmed by Western blot assay that HepG2 cells expressed HCV-core with relative molecular weight of 22 000.Compared to HepG2 cells,the level of ROS in HepG2 cells expressing HCV-core was significantly increased (1.0 ±0.1 vs 4.0±0.5,t=14.411,P＜0.01),the values of ATP/ADP were similar (8.2±2.2 vs 9.3±2.8,t=0.757,P＞0.05),AMPK α-2 (0.8±0.2 vs 0.2±0,t=7.345,P＜0.01),the values of NAD+/NADH (0.08±0.02 vs 0.02±0,t=7.348,P＜0.01),the activity of SIRT1 [(0.30±0.05) pmol· μg-1 · min-1 vs (0.15±0.04) pmol · μg 1 · min 1,t=5.738,P＜0.01] and the mRNA levels of SIRT1 (0.8±0.2 vs 0.4±0.1,t=4.382,P＜0.01) and AMPK α-2 mRNA (0.9±0.3 vs 0.2±0,t=5.715,P＜0.01),and the expression of SIRT1 (0.8±0.2 vs 0.3±0,t=5.941,P＜0.01) and phosphorylated AMPK protein (0.5±0.1 vs 0.1±0,t=9.608,P＜0.01) were all significantly decreased.Conclusion HCV core protein induces energy metabolism disorders of hepatocytes by down-regulation of SIRT1-AMPK signaling pathway.

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.

ObjectiveTo investigate the impact of age and sex on virologic responses rates to peginterferon alfα-2a and ribavirin treatment in patients with chronic hepatitis C.MethodsThe medical records of 449 chronic hepatitis C patients,treated with peginterferon and ribavirin in Department of Infectious Diseases,the Second Affiliated Hospital,Harbin Medical University,were retrospectively analyzed.These patients were divided into three groups according to age:patients ＜40 years (n =131 ),patients 40-50 years ( n =131 ) and patients ＞ 50 years ( n =187 ).The virologic response rates,the incidences of side events,and the rates of patients receiving ≥ 80％ of planned peginterferon alfα-2a or ribavirin dose were compared between male and female patients in the three groups.The influential factors on sustained virologic response (SVR) of patients were studied by multivariate analysis.Results For genotype 1,in patients ＜ 40 years group,the SVR rate of female was significantly higher than that of male (75.0％,30/40 vs 54.0％,27/50; P ＜0.05 ) ; in patients 40-50 years group,there was no significant difference in the SVR rate between male and female (51.0％,25/49 vs 53.7％,22/41 ; P ＞ 0.05 ) ; in patients ＞50 years group,the SVR rate of female was significantly lower than that of male (31.1％,19/61 vs 50.7％,34/67; P ＜0.05).For genotype 2,there were no significant differences in virologic response rates between male and female in the three groups.The incidence of adverse events of patients aged ＜ 40 years group,40-50 years group,＞ 50 years group,were 51.1％ (67/131),51.1％ (67/131),and 70.6％ (132/187),respectively,and the incidence of adverse events of patients aged ＞ 50 years was significantly higher than those of other groups ( P ＜ 0.001 ).For genotype 1,in patients ＞ 50 years group,the rate of patients receiving ≥80％ of planned ribavirin dose of female was significantly lower than that of male (42.6％,26/61 vs 62.7％,42/67; P ＜ 0.05).In multivariate analysis,the independent factors associated with SVR of patients aged ＞ 50 years were sex ( P =0.013 ),genotypes ( P =0.002 ),cirrhosis ( P =0.004 ),≥ 80％ of planned ribavirin dose ( P =0.008 ) and presence of rapid virologic response (RVR) ( P =0.001 ).ConclusionsFor genotype 1 patients,in patients ＜ 40 years group the SVR rate of female is higher than that of male; in patients 40-50 years group,male and female share similar SVR rates;in patients ＞ 50 years group the SVR rate of female is lower than that of male.Age and sex has no impact on virologic responses rates for genotype 2 patients.

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.