Hepatitis C virus (HCV) genome is of high variation,which results in persistent infection of HCV and increases the incidence of liver cirrhosis and hepatocellular carcinoma.Following the successful paradigm established for HIV protease inhibitors,HCV NS3-4A serine protease has been selected as the main target for the development of small molecule antiviral agents.In this article,we review recent progress in the discovery and development of HCV NS3-4A protease inhibitors,and discuss their antiviral activities,pharmacokinetic properties,side effects and resistance profiles.

【Objective】To observe the anti-depression effect of Shugan Hewei Granules(SHG) on mice with behavioral despair.【Methods】Kunming mice were randomized into 5 groups: model group,low-,moderate-and high-dose SHG groups(in the dosages of 0.25,0.5 and 1.0 g?kg-1?d-1respectively) and chloropromazine(CP) group.Tail suspension test and forced swimming test were used to investigate immobility time of mice.【Results】Moderate-and high-dose SHG shortened the immobility time obviously during tail suspension test and forced swimming test(P

Objective: To investigate applicability for Boston naming test (30 items) (BNT) in Chinese elderly and identify effect for mild cognitive impairment (MCI) and Alzheimer's dementia(AD) using BNT. Methods:100 normal elderly, 38 amnesic MCI, 34 mild AD and 38 moderate AD were evaluated by neuropsychological tests (include BNT, mini mental state examination and auditory verbal memory test, etc). MMSE total score of 4 groups were 28.4?1.5, 26.1?2.6, 20.7?1.7, and 15.6?3.3, respectively. Results: Age, sex, level of education were found to be significant factors affecting overall scores of spontaneous naming in normal elderly group. Spontaneous naming score for participants of elementary, high school and college groups were 22.2?3.3, 25.5?2.5 and 26.3?1.8, respectively. Scoring of male participants higher than that of females. Spontaneous naming score of 4 groups were 24.9?3.0, 20.9?3.6, 18.7?4.0 and 15.7?4.2, respectively. As cut-off ≤22 score of spontaneous naming of BNT, the sensitivities for MCI, mild AD and moderate AD were 61%, 79% and 95% respectively; the specificities were all around 81%. Selective impairment of unfamiliar items occurred MCI and mild AD and hold of familiar item across diagnostic groups. Semantic cue naming and recognition ability by BNT showed there was progressive damage in AD patients, but less than that of spontaneous naming of BNT. Conclusion: The ability of naming is influenced by age, gender and educational level. Patients with MCI or mild AD have impairment in naming.

Objective To investigate surgical technique and clinical efficacy of Sky bone ex- pander kyphoplasty in the treatment of osteoporotic vertebral body compression fractures.Methods Eighteen cases with osteoporotic vertebral body compression fractures were treated with Sky bone expander kyphoplasty from August 2004 to November 2005.Under the local anesthesia,3.5-5ml of bone cements were injected into each pathologic vertebral body through unipedicle approach after reduction procedure was done with Sky bone expander.Results The postoperative follow-up ranged from 3 to 11 months, with an average of 4.5 months.Back pain was effectively relieved after the operation in all cases.No complications occurred.Conclusion The Sky bone expander kyphoplasty has the advantages of safe- ty,easy operation,minimal invasion,effective restoration of the vertebral body height and fast relief of pain.

Objective To evaluate early results of Endurant stent-graft in the treatment of abdominal aortic aneurysms (AAAs).Methods From July 2010 to June 2011,68 patients (57 men,11 women; mean age 74.3 years) were treated with Endurant stent-graft at our center.26 cases had hostile proximal neck in the anatomy.According to ASA classification,15 cases were class Ⅱ ; 32 cases were class Ⅲ and 21 cases were class Ⅳ.Results Intraoperative immediate technical success was achieved in all cases.At completion angiography,a type Ⅱ endoleak was detected in 18 (26％) of the 68 patients.The mean operation time was (96 ± 29) min,the mean blood loss was (99 ± 68 ) ml,and the mean contrast usage was (122 ± 65) ml.No intraoperative conversion to open surgery,stent migration,types Ⅰ/Ⅲ endoleak,other major complications,or death was encountered.49 patients (72％) had a postimplantation syndrome with fever,leukocytosis,and increase of C-reactive protein levels,which completely resolved within two weeks.The mean follow-up time was (8 ± 5) months.Conclusions Endurant stent-graft seems to be safe and effective in endovascular aneurysm repair,even in patients with hostile aortoiliac anatomy.

Objective To control residual DNA by optimizing methodology during the production of rabies vaccine using Vero cells as a vector .Methods The antigen recovery rate was assessed by linked immunosorbent assay-sandwich technique while the residual DNA was detected by DNA probe hybridization method .Antigen recovery and removal of DNA were the main indexes for evaluateing ultrafiltration , the vital part of rabies vaccine production .Three key factors in ultrafiltration were assessed: selection of membrane packages , ultrafiltration pressure and the concentration ratio .Then protamine was used to pretreat ultrafiltrates .Based on the two indicators mentioned above , the effect of protamine pretreat-ment on the ultrafiltrate was evaluated .Results and Conclusion The optimum condition of ultrafiltration was obtained on the basis of the general antigen recovery rate , DNA removal rate and actual production .The primary parameters of ultrafil-tration were as follows:7.5 ×105 ultrafiltration membrane packages, 20 times concentrated, 15 psi ultrafiltration pressure. After pretreatment with protamine , ultrafiltration has proved to be a molecular sieve in intercepting DNA ,while protamine can tangle the fragmented DNA and form a larger molecular segment , which is believed to be more conducive to ultrafiltra-tion interception .

Aim To investigate the effect of Ginsen-oside Rh2 on apoptosis in human colorectal cancer cell SW480,and to explore the possible mechanism of it. Methods The proliferation activity of SW480 treated with Ginsenoside Rh2 was measured CCK-8 assay.Ap-optosis rates were evaluated by FCM.Hoechst 33258 staining was used to observe cell nucleus morphologi-cal;change SW480 cells were treated with Ginsenoside Rh2,and the protein expressions of Bcl-2,Bax,p53, cleaved caspase-3 ,PI3 K,AKT,P-AKT,GSK-3β,P-GSK-3βwere detected by Western blot;SW480 cells were treated with LY294002,Rh2,LY294002+Rh2, the expressions of PI3 K,AKT,P-AKT,GSK-3β,P-GSK-3βwere detected by Western blot.Results The proliferation of SW480 cells was significantly inhibited by Ginsenoside Rh2 in dose-dependent and time-de-pendent manner.FCM showed the inducing apoptosis effect of Ginsenoside Rh2 was significantly different from that of control group.Hoechst 33258 staining in-dicated clearly cell apoptosis in Ginsenoside Rh2 treat-ment groups.Western blot showed Ginsenoside Rh2 decreased expression of Bcl-2,increased expression of Bax,p53 and cleaved caspase-3,PI3K/AKT/GSK-3βpathway proteins PI3 K,P-AKT,P-GSK-3βdecreased obviously,AKT and GSK-3βwere not changed signifi-cantly in SW480.SW480 cells were separately treated with LY294002,Rh2,LY294002 +Rh2,there were no significant difference in AKT and GSK-3βprotein a-mong all groups,and the expression of PI3 K,P-AKT, P-GSK-3βdecreased more obviously in LY294002 +Rh2 group compared with LY294002 and Rh2 alone. Conclusion Rh2 induces colorectal cancer cell apop-tosis through PI3 K/AKT/GSK-3βpathway,which ac-tivates p53 and cleaved caspase-3,and destroys the balance of Bcl-2/Bax.

Some studies indicate that adipose derived stem cells (ADSCs) can differentiate into adipogenic, chondrogenic, myogenic, and osteogenic cells in vitro. However, whether ADSCs can be induced to differentiate into neural cells in vitro has not been clearly demonstrated. In this study, the ADSCs isolated from the murine adipose tissue were cultured and transfected with the EGFP gene, and then the cells were induced for neural differentiation. The morphology of those ADSCs began to change within two days which developed into characteristics of round cell bodies with several branching extensions, concomitantly expressing EGFP fluorescence. Approximately 60% of the total cell populations were bipolar or multipolar in shape. Some of them appeared to make contact with their neighboring cells. RT-PCR, Western blot and Immunocytochemistry revealed that the expression levels of the markers of neurons and oligodendrocytes such as MAP2, NF-70, Neu N and RIP upon neural induction were increased, but the expression of the special marker of astrocytes, GFAP, was undetectable until 96 h after induction when a small signal was observed. It was concluded that the ADSCs transfected with EGFP possessed the ability to undergo morphologic and phenotypic changes consistent with neural differentiation in vitro. It suggests that these cells might provide an ideal source for further stem cell research with possible therapeutic application for spinal cord injury.

Microvesicles (MVs) are the heterogeneous mixtures of vesicles. MVs released by leukemia cells constitute an important part of the leukemia microenvironment. MVs might act as important reservoirs of microRNAs (miRNAs). It is worth evaluating whether MVs possess some unique miRNA contents that are valuable in understanding the pathogenesis. In this study, we investigated the miRNA expression patterns of Nalm-6-derived MVs, Jurkat-derived MVs and normal cell-derived MVs using miRNA microarrays. The potential target genes regulated by differentially expressed miRNAs were also predicted and analyzed. Results demonstrated that 182 miRNAs and 166 miRNAs were differentially expressed in Nalm-6-MVs and Jurkat-MVs, respectively. Many oncogenes, tumor suppressors and signal pathway genes were targeted by these aberrantly expressed miRNAs, which might contribute to the development of B-ALL or T-ALL. Our findings expanded the potential diagnostic markers of ALL and provided useful information for ALL pathogenesis.

Objective To identify differently expressed genes and pathways between Kashin-Beck disease (KBD) cartilage and healthy cartilage,and to explore the mechanism of articular cartilage lesions of KBD.Methods Cartilage specimens were collected from 9 patients with KBD and 9 healthy controls.Total RNA was extracted from cartilage specimens,and transcribed into cDNA.KBD and control groups were labeled by Cy3 and Cy5,respectively.Agilent genome-wide microarray was applied to compare the expression profile of KBD cartilage and healthy cartilage.The microarray data was analyzed by single gene and pathway expression analysis to identify differently expressed genes and pathways between KBD and healthy controls.Results ①Tweenty nine genes were significantly up-regulated in KBD group (averaged ratio =6.68 + 1.98,P ＜ 0.05),mainly involved in apoptosis,metabolism,extracellular matrix,cytoskeleton and cell movement.Additionally,extracellular matrix-related FBLN1 gene was down-regulated in KBD group(ratio =0.14 + 0.06,P ＜ 0.05).②Five apoptosis and 6 hypoxia-related pathways presented higher expression levels in KBD compared to healthy controls(all P＜ 0.05).Conclusions We find significant expression differences of apoptosis and hypoxia-related genes and pathways between KBD cartilages and healthy cartilages,suggesting that hypoxia might contribute to chondrocytes apoptosis of KBD.Further studies may be needed to investigate the relationship between hypoxia and articular cartilage lesions of KBD.