Objective To understand employment status of the eight-year program medical graduates from different medical colleges and put forward reasonable proposals on the current prob-lems. Method Through questionnaire, we conducted research among eight-year program medical graduates of three different grades (Grade 04,05,06) on the general condition of employment, research level, actual working time, expectations and actual salary, satisfaction with jobs and so on. Data statis-tics was done by Excel 2007. Totally, our research involved 11 medical colleges and 389 questionnaires. Results 94.34% (367/389) of the eight-year program medical graduates work in top three hospitals. The top five factors affecting the employment were reputation of the school 86.38%(336/389), reputation of the Principal Investigator 66.83% (260/389), social relations 60.15% (234/389), scientific research level 52.96% (206/389) and gender 46.79% (182/389). The amount of published papers from those graduates and their satisfaction with jobs vary greatly. Conclusion Eight-year program medical grad-uates employment faces both opportunities and challenges, and a clear training objective and improve-ment of continuing medical education system for the eight-year program medical graduates will have great significance on the promotion of their employment.

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 investigate the methods of reducing radiation dose in CT coronary angiography through optimizing individualized scan dosage protocol.Methods Two hundred patients (group A)underwent coronary CTA examination which was performed with fixed 120 kV and variable mA according to their BMI.The mA was set as 150-300 mA(BMI ＜ 18.5 kg/m2),300-500 mA (18.5 kg/m2 ≤ BMI ＜ 25.0 kg/m2),and 500-800 mA(BMI ≥ 25.0 kg/m2).When all examinations were finished,a linear regression was employed to analyze the correlation between mA and BMI,body surface(Suf),image noise(SD)respectively.The results of the analysis were used to formulate a regression equation,which was further used to establish a table list for quick search on how much mA that individualized coronary CTA scan would need.Another 200 patients(group B)enrolled for the individualized scan were scanned under new protocol that previous study established.The tube voltage was 100 and 120 kV.The tube current was variable according to the data in the table list.One-way ANOVA and Kruskal-wallis H test were used for statistics.Results Regression equation between mA and BMI,Suf,SD was:mA =17.984 × BMI + 169.149 × Suf-2.282 × SD-361.039.The SD(group A:32.08 ± 5.80,group B:28.60±4.47),dose index volume(CTDIvol)[group A:(41.97 ± 11.37)mGy,group B:(33.18±10.07)mGy],effective dose(ED)[group A:(10.91 ±3.07)mSy,group B:(8.83 ±2.72)mSv]had significant differences between the two groups(F =43.45,63.71,49.07 respectively,P ＜0.01 for all).The SD and ED results obtained in group B were better than those in group A.Conclusion Better performances were obtained when BMI combined Suf was used as a new individualized protocol than when BMI was used only,which means good image quality and lower radiation dosage in coronary CTA examination.

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.

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.

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.

AIM To determine the contents of arillanin A,tenuifoliside A and tenuifoliside C in raw Polygalae Radix (root barks),Polygalae Radix duramen,Glycyrrhizae Radix et Rhizoma-processed Polygalae Radix,waterboiling Polygalae Radix and honey-processed Polygalae Radix.METHODS The analyses of 50％ methanol extracts from samples were performed on a 30 ℃ thermostatic Kromasil C18 column (250 mm ×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％ formic acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 330 nm.RESULTS The contents of three oligosaccharide esters were the highest in raw Polygalae Radix,followed by those in honey-processed Polygalae Radix,and those in water-boiling Polygalae Radix were the lowest.These constituents also existed in Polygalae Radix duramen,but their contents were lower than those in root barks.CONCLUSION The ester bonds of oligosaccharide esters in Polygalae Radix may be hydrolyzed during processing,followed by the generation of small molecular organic acids.The medication of whole Polygalae Radix (root barks and duramen) can be taken into consideration in clinical practice to reduce toxicity and enhance efficacy.

Objective To analyze mutations in the ATP2A2 gene in a Kazakh family with Darier's disease.Methods Clinical data were collected from 49 members from a family with Darier's disease,and peripheral blood samples were obtained from 44 family members and 100 unrelated healthy people.Genomic DNA was extracted from these blood samples.PCR and DNA sequencing were performed to detect mutations in the ATP2A2 gene.Results Darier's disease was inherited in an autosomal dominant manner in this family.A G→A heterozygous mutation (1288-1G→A) was identified at position 1288-1 at the splice site in exon 12 of the ATP2A2 gene in 11 patients in this family,but not in 33 healthy members or 100 healthy controls.Conclusion Darier's disease in this family may be caused by the heterozygous mutation (1288-1G→A)at the splice site in exon 12 of the ATP2A2 gene.