Objective To establish the mice model of AHL, to investigate the relationship between AHL and the cytoactive factors of the cochlear hair cells in C57BL/6J mice, and to classify the presbycusis models of the C57BL/6J mice. Methods C57BL/6J mice were divided into 6 experimental groups by age (A: 3 months old(m), B: 8 m, C: 9 m, D: 10 m, F: 17 m, G: 18 m) . The auditory functions mice were measured by auditory brainstem response (ABR) with the stimulus click and toneburst at 6 kHz and 8 kHz. 3 months later, Groups C , G, E and H were tested again for ABR. After ABR testing, the cytoactive of the hair cells was detected by succinate dehydrogenase staining and surface preparation technique(two mice from each group except groups C and G). Results The ABR thresholds elevated with age, and the marked change of the cochlea was the degeneration of the cytoactive of the cochlear hair cells, especially those of the outer hair cells. In the beginning, the basement of the basal membrane suffered from the mitochondrion degeneration in the outer hair cells, then it spread to the top region. Subsequently, the inner hair cells were involved. Conclusion C57BL/6J mouse was a typical animal model for the AHL,and the main change of the cochlea was the degeneration of the hair cells, especially the outer hair cells. Thus, C57BL/6J mice can be used as a suitable animal model for the study of presbycusis.

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 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.

The up-to-date quantitative structure-antitumor activity relationship studies of taxol analogues based on molecular modeling techniques were reviewed in the present paper. Both the common understandings and the debates about the contributions of several key structural groups, including the C13 side chain, the substituents of C14, C2 and C10 as well as the oxtane ring to the biological activities of taxol derivatives were summerized. In addition, the studies about other factors influencing the activity except for the structure and the classification research of the molecules were also discussed.

Objective:To study the effects of Yiqi Huoxue Huayu Chinese medicine on neogenesis of blood vessels and basic fibroblast growth factor(bFGF)expression in benign prostatic hyperplasia(BPH)rats.Methods:7 days after being castrated,fifty SD rats were injected with testosterone(5 mg?kg-1?d-1),the decoction of Yiqi Huoxue Huayu and Zerguilongshuang were orally administrated respectively,after 30 days'treatment,the rats were sacrificed,the prostate volume were measured,and the prostate index(PI)were analyzed,the micro-vessels density(MVD)and level of bFGF were measured.Results:The prostate volume and index of rats in model group was obviously higher than those in normal group(P

OBJECTIVE: To evaluate the extent of endolymphatic hydrops as shown by three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D FLAIR MRI) performed 24 hours after bilateral intratympanic gadolinium administration and discuss the positive rate of endolymphatic hydrops in vestibule and cochlea. METHOD: Twenty-four hours after bilateral intra-tympanic 8 times diluted gadolinium administration, three-dimensional fluid-attenuated inversion recovery MRI, using a three-Tesla unit, was performed in 48 patients, and then assessed the extent of endolymphatic hydrops in the MRI images. RESULT: Forty-eight patients showed different levels of enhancement of perilymth in the inner ear. In these patients, obvious signs of endolymphatic hydrops were visualized in vestibule,including 8 slight hydrops, 17 mild hydrops and 23 severe hydrops with a diagnostic rate of 83.3%. There were almost no complications in all 48 patients after bilateral intra-tympanic injection except short vertigo in some of them. CONCLUSION 3D FLAIR MRI resonance imaging has a high positive diagnostic rate in assessing endolymphatic hydrops of Ménière's disease and provides direct imaging evidence for diagnosing Ménière's disease.
Cochlea ; Contrast Media ; Ear, Inner ; Ear, Middle ; Gadolinium DTPA ; Humans ; Imaging, Three-Dimensional ; Injections ; Magnetic Resonance Imaging ; Meniere Disease ; diagnosis ; Vestibule, Labyrinth

Objective: To establish p53 trancated muteins group and analyse their expression and effects on p53 related downstream genes in HeLa cells. Methods: Using PCR-based site-directed mutagenesis technique, a group of P53 muteins with the N- and/or C-terminals differently trancated were set up. The plasmids with p53 mutein genes were used to transfect HeLa cells, the p53 muteins and some p53 related downstream genes' expression were analyzed by RT-PCR. Results: The p53 muteins were expressed in HeLa cells and they had effects on some of p53 related downstream genes. Conclusion: The P53 muteins may be a good tool to analyze P53 function and has effects on p53 related downstream genes' expression model.

[Objective]This study was conducted to examine the effects of dexmedetomidine on the proliferation and angiogenesis of MHCC97H and SMCC7721 human hepatocellular carcinoma(HCC)cell lines cultured in hypoxia condition in vitro,and investigated the possible mechanism involved.[Methods]MHCC97H and SMCC7721 human HCC cell lines under hypoxia culture condition were treated with presence or absence of dexmedetomidine(100 μmol/L). Cell viability,colony formation,vasculogenic mimicry(VM) formation were assessed. The effects of dexmedetomidine on α-2A adrenergic receptor(α2A),hypoxia induced factor-1a(HIF-1a),and vascular endothelial growth factor(VEGF)protein expression were evaluated with Western blot analysis.[Results]Cell proliferation assay and colony formation assay indicated that hypoxia obviously promoted the proliferation of MHCC 97H and SMCC7721 cells(CoCl2 group vs corresponding control group,the proliferation rate of MHCC97H and SMCC7721:Day 3,142.2%and 133.8%;Day 4,134.7%and 131.0%;Day 5,133.5%and 136.2%;all P<0.05),and VM formation assay suggested that hypoxia increased angiogenesis of MHCC97H and SMCC7721 cells. Whereas dexmedetomidine significantly inhibited the proliferation(Dex+CoCl2 group vs CoCl2 group,the proliferation rate of MHCC97H and SMCC7721:Day 3,55.7%vs 60.7%;Day 4,46.9%vs 58.1%;Day 5,46.4%vs 57.0%,all P<0.05)and angiogenesis of MHCC97H,SMCC7721 cells induced by hypoxia. Dexmedetomidine may exert these functions by activating α-2A adrenergic receptor,causing an decrease in HIF-1a and VEGF protein,while hypoxia activated HIF-1a and VEGF protein to promote the growth and angiogenesis of cells.[Conclusion]The findings provide evidence that hypoxia could promote the proliferation and angiogenesis of MHCC97H and SMCC7721 cells,while dexmedetomidine might inhibit these effects by down-regulating HIF-1a and VEGF protein expression through activatingα-2A adrenergic receptor.

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 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.