0.05). The median duration of survival was 11.5 months for TEP gr oup versus 8.5 months for EP group (P0.05,no statistical difference). The main toxicity wa s myelosuppression for the two groups.The incidence rate of Ⅲ～Ⅳ degree neutro p enia and thrombocytopenia was higher in the TEP group than that in the EP group( P

Objective To compare the therapeutic effects of cordyceps sinesis (CS) and reduced glutathione on experimental non-alcoholic fatty liver disease (NAFLD) rats and explore the possible molecular mechanisms. Methods After NAFLD rats were induced by high-fat diet and were treated by CS and reduced glutathione. The histopathologic changes of livers were evaluated. The levels of TG and FFA in serum and liver were measured. The levels of SOD and ATP in liver were measured too. Results (1)In the development of NAFLD, extensive adipose degeneration, inflammatory cell infiltration and necrosis, local fibrous tissue hyperplasia were found in the liver. The increase of TG, FFA in the serum and liver and decrease of SOD and ATP in the liver were seen. (2)In CS treated group, adipose degeneration had been alleviated with slightly inflammatory cells infiltration and no necrosis or fibrosis had been found. The concentrations of TG and FFA were decreased in the serum and liver, but SOD and ATP increased. (3)In glutathione treated group, adipose degeneration of liver and inflammatory cells infiltration remained obviously with focus or punctiform necrosis, but without fibrosis. The increase of SOD in liver was distinguished. No changes of TG, FFA, UCP-2 and ATP had been detected. Conclusion Both CS and reduced glutathione have therapeutic effects on NAFLD, by preventing the generation of liver fibrosis. CS has a better therapeutic effects on metabolic disturbance or accumulation of lipid and energy metabolic imbalance of liver cells.

Objective To evaluate the clinical value of Gli1 expression in breast cancer.Methods Immunohistochemistry was used to analyze the protein expression of Glil in breast cancer tissues,adjacent cancer tissues and metastatic lymph node.Results ①Breast cancer tissues expressed high levels of Gli1 compared to paracancerous tissues.Gli1 overexpression was found in 93.3％ of breast cancer tissues with recurrence and metastasis and 81.2％ in breast cancer tissues without metastasis.Gli1 expression could be detected either in interstitial tissues of cancer or in cancer tissues,or in both.The rate of Gli1 overexpression was 89.3％ in the inter stitial tissues of the primary cancer with recurrence and metastasis and 13.4％ in interstitial tissues of breast cancer tissues without metastasis.The difference had statistical significance(P ＜ 0.001).②High expression of Gli1 in breast cancer tissues was closely related to early recurrence and metastasis of breast cancer.Gli1 expression displayed a significant correlation with relapse-free survival (RFS) (P =0.046).The recurrence rate was 17.8％ in the high expression group in breast cancer tissue,whereas it was only 6.2％ in the low expression group(P =0.046),while the recurrence rate was 31.2％ in the high expression group in interstitial tissues,whereas it was only 11.1％ in the low expression group(P ＜ 0.001).Conclusion The high expression of Gli1 in breast primary cancer tissues,metastasis tissues and interstitial tissues is associated with recurrence and metastasis of breast cancer.

Objective To investigate the clinical efficacy and safety of lyophilized recombinant human brain natriuretic peptide(rhBNP) in the treatment of patients with congestive heart failure (CHF).Methods 120 CHF patients were randomly divided into two groups.58 cases in the observation group were given lyophilized rhBNP,and 62 patients in the control group were given sodium nitroprusside.The clinical effect,changes of echocardiographic indicators and hemodynamic parameters,adverse reactions were observed.Results After treatment,the total effective rate of the observation group was 91.37％,which was significantly higher than that of the control group(x2 =4.23,P ＜ 0.05).The LVEF and NT-proBNP levels in observation group were (59.0 ± 8.2)％ and (535.4 ± 123.8)ng/L,which had higher improvement than control group (P ＜ 0.05).The incidence rate of adverse reactions between the two groups had no significant difference (P＞ 0.05).Conclusion Lyophilized rhBNP in the treatment of CHF has significant effect,and it is worthy of clinical application and promotion.

ObjectiveTo investigate the clinical significance of determination of 20S proteasomal activities changes in circulating white blood cells (WBC) in patients with advanced gastric carcinoma.MethodsThe 20S proteasomal activities in circulating WBC separated from 80 patients with advanced gastric carcinoma were determined by 20S proteasome assay kit; the concentrations of interleukin-6(IL-6) in plasma were determined by radioimmunoassay method.The result was compared with that of 11 healthy volunteers.ResultsThe proteasomal activities in circulating WBC[(38.26 ±9.23),(101.85 ±27.63)pmol AMC/ ( s *mg pro) ] and concentrations of IL-6 [ (23.89 ± 6.76),(72.52 ± 20.71 ) ng/L ] of healthy volunteers and the patients with advanced gastric carcinoma had statistical significance (P ＜ 0.01 ).The proteasomal activities and the concentration of IL-6 were correlated with age,pathological type,weight changes,Karnofsky score and disease severe degree(P ＜ 0.01 );while they had no relationship with sex(P ＞ 0.05).Cox's proportional hazard regression model demonstrated that pathological type,Karnofsky score and proteasomal activities were the independent risk factors affecting the survival of patients with advanced gastric carcinoma (P ＜0.01 or ＜0.05).20S proteasomal activities and the concentration of IL-6 had positive correlation (r =0.691,P =0.000).ConclusionsThe proteasomal activites in circulating WBC and the concentration of IL-6 in plasma increase and are correlated with age,pathological type,weight changes,Karnofsky score and disease severe degree.Proteasomal activities in circulating WBC can be used as the prognostic reference factor of advanced gastric carcinoma.20S proteasomal activities and the concentration of IL-6 have positive correlation.

Objective To investigate the prevalence and risk factors of highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (LD) in patients with acquired immunodeficiency syndrome (AIDS) treated with HAART in China.Methods A total of 137 AIDS patients treated with HAART for more than 2 years were analyzed.Sixteen clinical parameters (including gender,age,baseline body mass index,baseline human immunodeficiency virus [HIV] viral load,stage of disease,routes of HIV transmission,baseline CD4+ T lymphocyte count,white blood cell count,fasting plasma glucose level,serum triglycerides level,serum cholesterol level and other laboratory results,and HAART regimens) that might be associated with HAART-LD occurrence were evaluated using Cox proportional hazards models.Results HAART regimens were significantly correlated with HAART-LD (P=0.031),while the remaining 15 factors were not associated with the risk of HAART-LD (all P＞0.05).Patients who received stavudine d4T)-containing regimen was 2.684 times more likely to develop HAART-LD than patients who received zidovudine (AZT)-containing regimen (95 ％ CI:1.302-5.531,P=0.007) ; HAART-LD prevalence rates were gradually increased with treatment duration in both groups.First HAART-LD was seen at 24 weeks in both d4T group and AZT group,and the prevalence rates were 2.7％,1.6％ at 24 weeks,27.0％,7.9％ at 48 weeks and 37.8％,15.9％ at 96 weeks respectively.The prevalence of HAART-LD in d4T group was much higher than that in AZT group and the difference was statistically significant (x2 =8.285,P=0.004).Conclusions HAART regimen is an independent predictor of HAART-LD.HAART-LD tend to occur more frequently in patients treated with d4T or AZT,especially d4T.Our study recommends to avoid the use of d4T-contained HAART regimen.

Objective To report the clinical and peripheral neuropathological findings in two patients with autosomal recessive Charcot-Marie-Tooth disease 2K(AR-CMT2K).Methods Case one was a nine year-old girl.She had distal weakness of lower limbs for six years, with calf atrophy and contracture of Achilles tendon for three years.Case two was an eight year-old boy.He had distal weakness of lower limbs with contracture of Achilles tendon and calf muscle atrophy for three years, and proximal weakness of low limbs for two years.The motor nerve conduction velocities in median nerves were 48.1 m/s in case one and 47.6 m/s in case two.The compound motor action potential amplitude of median nerves decreased by 46% in case one and 69% in case two.Sural nerve biopsies and gene targeted next-generation sequencing were performed in both patients.Results Density of myelinated fibers was 8 407/mm2 in case one and 7 714/mm2 in case two.The ratio of myelinated fibers with diameter over 8 μm was 2.6% in case one and 0 in case two.Both patients had small regenerating cluster of myelinated fibers.Thin myelinated fibers appeared in case one.In case two, atypical onion bulb formations with focal folded myelin appeared, and electromicroscopy revealed mitochondrial aggregate in axons.Compound heterozygous mutations of ganglioside-induced differentiation associated protein 1 gene were detected in both patients, including c.767A>G(p.H256R) and c.466G>A (p.A156T) in case one and c.767A>G and 845G>A(p.R282H) in case two.Conclusions Contracture of Achilles tendon may appear in early childhood of AR-CMT2K patients.The main pathological changes in sural nerve are loss of large myelinated fibers, mitochondrial aggregate in axons and myelin abnormalities.

Objective To explore whether the mitochondrial toxicity markers of peripheral blood mononuclear cells (PBMC)are of significance in monitoring mitochondrial toxicity during highly active antiretroviral therapy (HAART)in patients with acquired immune deficiency syndrome (AIDS).Methods Mitochondrial DNA (mtDNA),mitochondrial thymidine kinase (TK2 )and p53-inducible ribonucleotide reductase small subunit 2 (p53R2 )were selected as mitochondrial toxicity markers.The expression changes of theses markers of PBMC in 22 AIDS patients were detected by real time quantitative polymerase chain reaction (q-PCR)at baseline,48 weeks and 96 weeks after initiation of the treatment. All the patients received stavudine/zidovudine and lamivudine as the mainstay of the HAART regimen. Independent-samples t test was used.Results The relative expression level of mtDNA in patients before HAART was 3.27 ± 0.94,and decreased to 2.16±0.85 at week 48 and 1 .66±0.66 at week 96, respectively.The differences were both significant compared with the level prior to the treatment (t =-3.90,P <0.01 and t =-6.29,P <0.01 ,respectively).The relative expression level of TK2 before HAART was 0.37 ±0.13,and increased to 1 .01 ±0.25 at week 48 and 2.13 ±0.61 at week 96 of the treatment.After pairwise comparisons of the three pairs of data (pre-HAART vs week 48 of the treatment,pre-HAART vs week 96 of the treatment and week 48 vs week 96 of the treatment),the differences were all significant (t = 10.77,8.00 and 3.56,respectively;all P < 0.01 ).The relative expression level of p53R2 was 0.86±0.39 before HAART,but gradually increased to 2.36 ±1 .14 and 7.73±0.65 ,respectively,at week 48 and week 96 of the treatment.The differences in p53R2 levels among three groups after pairwise comparison were all significant (t=3.27,12.26 and 13.25,respectively;all P < 0.01 ).Conclusions The expression levels of mtDNA,TK2 and p53R2 in PBMC could change significantly during HAART in AIDS patients,which might be used as indexes for monitoring mitochondrial toxicity.

Objective To investigate hepatic expressions and significances of cannabinoid receptor 1 (CB1) and cannabinoid receptor 2(CB2) in C57 mice with experimental cirrhosis.Methods Thirty C57 mice were randomly divided into three groups,i.e.normal control group,model control group and model colchicine group.Hepatic fibrosis model was prepared by intraperitoneal injection of carbon tetrachloride.The expressions of CB1 and CB2 in liver tissue of mice were observed by immunohistochemistry.The scores of inflammation grade (G) and fibrosis stage (S) were simultaneously performed.Results The scores of G and S in model control group and model colchicine group were significantly higher than those in normal control group( F =125.41,P =0.00; F =99.18,P =0.00).The scores of G and S in model control group were significantly higher than those in model colchicine group(P ＜0.01 ).The scores of CB1 and CB2 expressions in model control group and model colchicine group were significantly higher than those in normal control group ( F =29.27,P =0.00; F =36.99,P =0.00).The scores of CB1 and CB2 in model control group were significantly higher than those in model colchicine group( P ＜ 0.05 or P ＜ 0.01 ).There were significant relationships among scores of CB1,CB2,G and S in model control group and model colchicine group(Ps ＜0.05).As the scores of G and S became higher,the expressions of CB1 and CB2 gradually became more intensive.Conclusion The hepatic expressions of CB1 and CB2 in C57 mice with experimental cirrhosis increased significantly and have significant relationship with the grades of liver tissue inflammation and fibrosis.

Objective To observe expression and location of cannabinoid receptor 1 (CB1) in liver tissue of patients with chronic hepatitis B (CHB) ,and analyze the relationship of it with the liver fibrosis score,the serum levels of TGF-β1 and Leptin. Methods Liver biopsies were performed in 118 patients with CHB.The expression of CB1 in liver tissue was observed by immune histochemical staining, and semi-quantitative analysis was carried out to devide the CB1 score into four grades: -, +, + +, + + +. Serum levels of TGF-β1 and Leptin were determined by ABC-ELISA double-antibody sandwich method. Results The expression of CB1 in liver tissue with CHB had significant relationship with the fibrosis score. As the expression of the CB1 increased, the fibrosis score became higher ( F = 23. 369,P = 0. 000). Moreover, the expression of CB1 in liver tissue with CHB had significant relationship with the serum levels of TGF-β1 and Leptin( F values were 8. 762 and 5. 749;P values were 0. 001 and 0. 027, respectively). Conclusion CB1 may play promotive role in the process of hepatic fibrosis through regulation of TGF-β1 and Leptin.