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 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 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 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.

OBJECTIVETo investigate clinical outcomes of tendon allograft reconstruction with arthroscopy minimally invasive technique at stage I for the treatment of knee dislocation with multiple ligaments injury.

METHODSForty-eight patients with knee dislocation were reconstructed anterior and posterior ligament under arthroscopy at stage I from January 2008 to January 2012, and repaired ligaments injury of knee joint by minimally invasive technique. There were 38 males and 10 females aged from 20 to 59 years old with an average of 35.6 years old; 22 cases on the left side and 26 cases on the right side; the time from injury to operation ranged from 2 d to 2 weeks. Two cases combined with anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL) and posterolateral complex injuries, 36 cases combined with ACL, PCL, and MCL injuries, 10 cases combined with ACL, PCL and PLC injuries; 4 cases combined with peroneal nerve injury. Lysholm scoring were used to compared the cases before operation and final following-up to evaluate knee function.

RESULTSAll patients were followed up from 12 to 30 months with an average of (18.2 ± 6.3) months. Activity and stability of joint were obviously improved. Lysholm score were improved from 40.3 ± 4.1 before operation to 87.0 ± 6.4 at final following-up.

CONCLUSIONReconstruction with arthroscopy minimally invasive technique at stage I for the treatment of knee dislocation with multiple ligaments injury could recover stability of joint better,reserve joint function. Preoperative training and postoperative individualized rehabilitation treatment is the key point of recover knee joint function.

Adult ; Anterior Cruciate Ligament Injuries ; Arthroscopy ; Female ; Humans ; Knee Dislocation ; rehabilitation ; surgery ; Male ; Middle Aged ; Multiple Trauma ; surgery ; Posterior Cruciate Ligament ; injuries ; Reconstructive Surgical Procedures ; methods

Evaluation Studies as Topic ; Humans ; Medicine, Chinese Traditional ; Publishing ; standards ; Quality Control ; Randomized Controlled Trials as Topic ; standards

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 .

Objective To explore the value of diffusion tensor imaging (DTI) and diffusion tensor tracography (DTT) in assessment of Corticospinal tract (CST) and medial lemniscus (ML) in tumors involving brainstem.Methods A total of 35 cases with pathologically confirmed tumors involving brainstem were collected,and 35 volunteers matched with genders and ages were recruited as the normal group.DTI scanning was performed on all the patients and controls.The damage degrees of CST and ML were evaluated and graded by DTT,and the dysfunction degrees were evaluated for the patients.Spearman correlation was used to statistically analyze the relationships of limb movement,sensory dysfunction and CST and ML damage.Results According to the rating results,normal findings,shifting,edema or infiltration and damage of CST was found in 9,9,11,and 6 cases respectively.They were 8,9,15,3 cases for ML.Motor function was normal in 20 cases,slightly defective in 11 cases,and moderate defective in 4 cases.Sensory function was normal in 21 cases,slightly defective in 6 cases,and moderate defective in 8 cases.The patients' dyskinesia and CST damage degree,sensory dysfunction and ML damage degree were positively correlated (r was 0.786 and 0.686 respectively,P ＜ 0.01).The position relationship among tumor and CST and ML could be well displayed on images.None of the patients showed new symptoms of dysneuria after surgery.Conclusions DTI and DTT technology can be used to evaluate CST and ML damage degree in tumors involving brainstem.They can display the position relationship between tumor and the brainstem CST and ML,which is important in protecting the brainstem fiber tract during operation and evaluating the recovery after the operation.

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 investigate the role of negative-regulatory factors of toll-like receptors (TLRs)signal pathways in immunological pathogenesis of Kawasaki disease(KD).Methods Thirty-two chil- dren with Kawasaki disease and 16 age-matched healthy children were studied.Reverse-transcription PCR (RT-PCR)and real-time PCR were used to evaluate the mRNA expression levels of toll-like receptor 4(TLR4), MD-2,MyD88,IRAK-4,TRAF6,T1/ST2,IRAK-M,Triad 3A,and proinflammatory factors such as IL-1?, IL-6,IL-8 and TNF-?,in peripheral blood monocytes/macrophages(MC).The expression of TLR4 protein in MC was analyzed by flow cytometry.Results①Compared with the control group,the mRNA levels of TLR4, MD-2,MyD88,IRAK-4 and TRAF6 in KD group were up-regulated significantly(P＜0.01),and the expression level of TLR4 protein was also found to be up-regulated in KD group during acute phase.It was detected that expression levels of TLR4 protein in KD with coronary artery lesion(KD-CAL~+)was significantly higher than that of KD without coronary artery lesion(KD-CAL-)[flow cytometry:(6.5?1.7)% vs(11.9_+2.4)%,P＜0.01].②The expression level of negative-regulatory factors such as IRAK-M and Triad3A were significantly up-regulat- ed in acute phase of Kawasaki disease,while the mRNA levels of IRAK-M and Triad3A in KD-CAL~+ group was found to be significantly lower than those of KD-CAL~- group(P＜0.01).No difference of T1/ST2 mRNA expres sion level was detected among all groups(P＞0.05).③The expressions of proinflammatory eytokines such as IL-1?, IL-6,IL-8 and TNF-?in monoeytes/macrophages during acute phase of Kawasaki disease were higher than those of the control group(P＜0.01),and expression of proinflammatory cytokines in KD-CAL~+ group was significantly higher than that of KD-CAL~- group.Conclusion Relative insufficient expression of negative-regulatory factors, such as IRAK-M and Triad3A,maybe correlate with immunological pathogenesis of Kawasaki disease.