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.

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.

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 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

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.

Objective:To discuss the influence and curative effect of intensive lipid-lowering with atorvastatin on blood fat and ser-um inflammatory factors levels in the patients with acute cerebral infarction. Methods:Totally 94 cases of patients with acute cerebral infarction were divided into the intensive group(n=47) and the ordinary group (n=47). The patients in the two groups were given the basic medical treatment, such as reducing intracranial pressure and dehydration, controlling blood pressure and blood sugar, anti-platelet aggregation, neural protection and etc. The patients in the ordinary group were orally given 20mg atorvastatin calcium tablets, once a day, while the patients in the intensive group were additionally given 40mg atorvastatin calcium tablets, once a day, and the treatment course was 8 weeks. The changes of blood fat index and serum inflammatory factors of hs-CRP, TNF-αand IL-10 in the two groups before and after the medical treatment were detected, and the clinical curative effect was compared as well. Results:After the 8-week medical treatment, TC, TG and LDL-C levels in the two groups were declined at different degree, while HDL-C levels were in-creased at different degree (P<0. 05 or P<0. 01), and the changes in the intensive group was more notable than those in the ordinary group (P<0. 05). After the treatment, the serum hs-CRP and TNF-αlevels in the two groups were declined at different degree, while serum IL-10 levels were increased at different degree (P<0. 05 or P<0. 01), and the changes in the intensive group was more signifi-cant than those in the ordinary group (P<0. 05). Meanwhile, the total clinical efficiency in the intensive group (95. 74%) was much higher than that in the ordinary group (80. 85%, P<0. 05). Respectively 2 and 4 cases of untoward effect were appeared in the ordi-nary group and the intensive group without statistical difference between the two groups(P>0. 05). Conclusion:Intensive lipid-lower-ing with atorvastatin has significant curative effect with favorable security on acute cerebral infarction, which can obviously improve the degree of neural function defect, and the mechanism may related with reducing blood fat, serum hs-CRP and TNF-αlevels, increasing serum IL-10 levels and inhibiting topical inflammatory reactions.