Over 170 million people worldwide are infected with hepatitis C virus (HCV), a major cause of liver diseases. Current interferon-based therapy is of limited efficacy and has significant side effects and more effective and better tolerated therapies are urgently needed. HCV is a positive, single-stranded RNA virus with a 9.6 kb genome that encodes ten viral proteins. Among them, the NS3 protease and the NSSB polymerase are essential for viral replication and have been the main focus of drug discovery efforts. Aided by structure-based drug design,potent and specific inhibitors of NS3 and NSSB have been identified, some of which are in late stage clinical trials and may significantly improve current HCV treatment. Inhibitors of other viral targets such as NSSA are also being pursued. However, HCV is an RNA virus characterized by high replication and mutation rates and consequently, resistance emerges quickly in patients treated with specific antivirals as monotherapy. A complementary approach is to target host factors such as cyclophilins that are also essential for viral replication and may present a higher genetic barrier to resistance. Combinations of these inhibitors of different mechanism are likely to become the essential components of future HCV therapies in order to maximize antiviral efficacy and prevent the emergence of resistance.

Objective To analyze the role of Clinical Pathway in controlling hospitalization cost and to provide the basis for reasonable control of medical cost.Methods The data of patients undergoing unilateral and bilateral total hip replacement in 2005 and 2010 in Arthritis Clinical and Research Center of Peking University People's Hospital were retrospectively analyzed.There were 70 unilateral and 14 bilateral total hip replacement cases in 2005,whereas the number of those in 2010 was 173 and 46 respectively.All charges were assigned to 1 of 9 categories:hospital room,nursing,radiology and laboratory,prosthesis,blood transfusion,surgery,pharmacy,treatment,diagnosis.We compared the total costs and cost of each category between 2005 and 2010.Results There was no statistical significant difference between 2005 and 2010 in terms of age,gender distribution,pri mary disease and type of prosthesis.The total costs for unilateral and bilatcral total hip replacement was 40 852.72 yuan and 73 020.28 yuan in 2010,respectively.They were both significantly lower than those of 2005 (49 371.35 yuan and 80 962.61 yuan respectively).The charge for each category of total hip replacement in 2010 was 585.88,145.38,2 885.47,3 222.32,1 776.15,3 805.29,132.79,4 100.88,and 3 0953.75 yuan.Compared with 2005,each category of charge dropped in 2010,especially the cost of surgery,treatment,diagnosis and hospital room,which decreased by 35.11％,31.76％,31.40％ and 30.67％ respectively.The tendency of each category change in charge of unilateral and bilateral total hip replacement was similar to the overall costs.Conclusion The total costs for total hip replacement (unilateral and bilateral total hip replacement) in 2010 were lower than those of 2005,which might be the result of adopting Clinical Pathway since 2010.Nevertheless,the prosthesis cost accounted for a large proportion in both years.Therefore,controlling the prosthesis cost might be an effective way to reduce medical costs for total hip replacement.

Arrhythmias, Cardiac ; etiology ; Birth Weight ; Electrocardiography ; Female ; Humans ; Hypocalcemia ; complications ; Infant, Newborn ; Male

Objective To compare the development of postoperative cognitive dysfunction ( POCD) under total inhalation anesthesia with sevoflurane versus total intravenous anesthesia with propofol in elderly patients. Methods Sixty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 65-77 yr, weighing 43-78 kg, with preoperative Mini?Mental State Examination ( MMSE) score≥25, scheduled for elective surgery for oral and maxillofacial carcinoma, were divided into 2 groups ( n=30 each) using a random number table: total inhalation anesthesia with sevoflurane group ( group S) and total intravenous anesthesia with propofol?based anesthesia group ( group P ) . The patients were tracheally intuba?ted under local infiltration anesthesia. In group S, anesthesia was induced with inhalation of 8% sevoflurane (oxygen flow rate 8 L∕min), rocuronium 0?9 mg∕kg was injected intravenously when the bispectral index ( BIS) value reached 45, and the patients were mechanically ventilated; anesthesia was maintained with inhalation of sevoflurane with the end?tidal concentration of 2%-3%. In group P , anesthesia was induced with iv propofol 2 mg∕kg and sufentanil 0?3μg∕kg, rocuronium 0?9 mg∕kg was injected intravenously when the BIS value reached 45, and the patients were mechanically ventilated; anesthesia was maintained with target?controlled infusion of propofol ( target plasma concentration 3-5μg∕ml) and remifentanil ( target plas?ma concentration 3-5 ng∕ml). In both groups, intermittent iv boluses of cisatracurium 0?04 mg∕kg were given to maintain muscle relaxation during operation, and BIS value was maintained at 40-60 during opera?tion. Before intubation ( T1 ) , immediately after onset of intubation ( T2 ) , at 10 min of intubation ( T3 ) , immediately after begninning of skin incision ( T4 ) , while operating on the base of tongue or sawing the low?er jaw ( T5 ) , at the end of operation ( T6 ) and on the morning of the postoperative day 1 ( T7 ) , blood sam?ples from the elbow vein were collected for determination of plasma norepinephrine and epinephrine concen?trations by high?performance liquid chromatography and electrochemistry. At T1?7 and on the morning of the postoperative day 3 ( T8 ) , blood samples from the elbow vein were collected for measurement of plasma cor?tisol concentrations by radioimmunoassay. MMSE was used to assess the cognitive function on the postopera?tive day 7. MMSE score< 24 was defined as POCD, and the occurrence of POCD was recorded. Results Compared with group S, the plasma concentrations of norepinephrine and epinephrine were significantly de?creased at T4 and T5 , the plasma cortisol concentration was significantly decreased at T4?7 ( P<0?05) , and no significant change was found in the incidence of POCD on the postoperative day 7 in group P ( P>0?05) . Conclusion Although the probability of the development of POCD is low when the two anesthetic methods are used, total intravenous anesthesia with propofol?based anesthesia induces a marked decrease in periop?erative stress responses when compared with total inhalation anesthesia with sevoflurane.

Adult ; Humans ; Laryngeal Neoplasms ; Male ; Neurofibroma ; Vocal Cords ; pathology

Objective:To evaluate the effect of concentrate growth factor extract(CGFe)on the proliferation and differentiation of MC3T3-E1 osteoblasts.Methods:MC3T3-1 cells were cultured with and without CGFe respectively.At 1 ,3,5 d of culture the pro-liferation of the cells was detected by MTT assay,the activity of alkaline phosphatase (ALP)of the cells was examined by ALP kit;at 1 4,21 d of culture the calcium nodus formation was observed by Alizarin red staining;RUNX2 and OSX expression was quantified by real-time PCR.Results:With the extension of culture time,the proliferation,ALP activity,the calcium nodus and the level of RUNX2 and OSX mRNA of the experimental group were increased more than those of the control group.Conclusion:CGFe may pro-mote the proliferation and differentiation of osteoblasts.

Objective To examine the effect of donepezil on cognitive function of Alzheimer's disease from a naturalistic observation in memory clinic.Methods From the subject pool in memory clinic,thirteen patients with mild to moderate Alzheimer's disease(meeting NINCDS-ADRDA criteria of probable AD)were enrolled in the naturalistic observation.Donepezil with dosage of 5 mg daily Was administered.Cognitive Ability Screening Instrument (CASI)Was used to assess the cognitive function,and was administered at baseline,3 and 6 months after treatment with donepezil.Resuits After 6-month treatment with donepezil,the change of score of verbal fluency from baseline Was significant[(4.3±3.1)vs(6.2±2.7),P＜0.05].There was a trend that constructional praxis was also improved after 6-month treatment(P=0.06).The change of scores of other cognitive domains remained the sanle(P＞0.05).Conclusion In the naturalistic observation at memory chnic,donepezil may improve verbal fluency of AD patients,and keep most cognitive function stable.

BACKGROUND: Many factors can lead to a large area of skin defects, and tissue-engineered artificial skil transplantation composed by seeding cel s and scaffold materials can be used for skin defect repair. OBJECTIVE: To construct the skin implantation scaffold based on human epidermal stem cel s combined with acel ular dermal matrix in nude mice. METHODS: Human epidermal stem cel s from children’s foreskin were isolated and cultured, and the skin of nude mice was obtained to prepare acel ular dermal matrix scaffold. Then, the human epidermal stem cel s were cultured on the acel ular dermal matrix scaffold to construct artificial skin. Ten Sprague-Dawley rats were equivalently randomly divided into two groups: rats treated by human epidermal stem cel s combined with acel ular dermal matrix scaffold as combined group, and those treated by simple acel ular dermal scaffold as acel ular dermal scaffold group after skin defect models were prepared. RESULTS AND CONCLUSION: The artificial skin was milky white, soft and elastic, not easy to break, and has good flexibility, and good plasticity, and could be processed into different shapes. No obvious exudation appeared in the rat wound of two groups after repair. At 2 weeks after modeling, the transplanted skin showed good growth and skin wound healed gradual y in the combined group. In contrast, scar healing and two animals with transplant failure occurred in the acel ular dermal scaffold group. These results show that human epidermal stem cel s combined with acel ular dermal materials in nude mice can construct the tissue-engineered skin, which exerts good repair effects for skin defects in animals.

Objective To investigate the formation mechanism of string beads sign in peripheral small cell lung cancer (SCLC) and evaluate the significance of it in differential diagnosis among SCLC,peripheral lung adenocarcinoma and peripheral lung squa-mous cell carcinoma.Methods 78 cases of SCLC,69 cases of peripheral lung adenocarcinoma and 33 cases of peripheral lung squa-mous cell carcinoma,confirmed pathologically were included in this study.The positive rates of string beads sign,mediastinal lymph node metastasis and mediastinal lymph nodes larger than primary lung lesions were calculated and analyzed in these three groups.Results 10 out of SCLC cases (12.8%)have string beads sign,in which all mediastinal lymph nodes were larger than lung lesions.Mediasti-nal lymph node metastases were observed in 63(80.8%)of 78 cases,and 42 (53.8%)cases had larger mediastinal lymph nodes than lung lesions.No string beads sign was observed in patients with peripheral solid lung adenocarcinomas,but 25 of 69 cases (36.2%) have mediastinal lymph node metastasis and 2 cases (2.9%)had larger mediastinal lymph nodes than lung lesions.13 cases(39.4%) of 33 patients with peripheral lung squamous cell carcinomas had mediastinal lymph node metastasis,and 6 cases (16.7%)had larger mediastinal lymph nodes than lung lesions.The statistical results showed the positive rate of string beads sign was not significantly different between peripheral SCLC group and peripheral lung squamous cell carcinoma group,but that of mediastinal lymph node and larger mediastinal lymph nodes than lung lesions were statistically different among these three groups.Conclusion To some extent, string beads sign on CT could reflect the biologic character of SCLC.It played an important role in differential diagnosis of peripheral SCLC,peripheral lung adenocarcinoma and periph-eral lung squamous cell carcinoma,but it should be combined with mediastinal lymph node size.

BACKGROUND:Basic fibroblast growth factor is a pluripotent cytokine that can promote the proliferation of mesodermal and neuroectodermal cells.
OBJECTIVE:To observe the effect of basic fibroblast growth factor in human periodontal ligament cells cultured in vitro.
METHODS:Human periodontal ligament cells at passage 5 were inoculated into the 96-wel plates at the density of 1×108/L, and were randomly divided into four groups. The cells were cultured inα-MEM containing 15%fetal bovine serum and 0, 1, 10, 100μg/L basic fibroblast growth factor, respectively. At 1, 3, 5, 7 days of the culture, the cellproliferation was determined, and the activity of alkaline phosphates was detected at 1 and 7 days.
RESULTS AND CONCLUSION:There were significant differences in the proliferation of human periodontal ligament cells among the four groups (F=6.586, P=0.024). As the increase of the basic fibroblast growth factor concentrations, the absorbance value was gradual y increased and reached the peak in 100μg/L basic fibroblast growth factor group (P<0.05). The alkaline phosphatase activity in basic fibroblast growth factor groups was lower than that of the control group (P=0.000), the higher the concentration was, the lower activity was (P<0.05). Results show that basic fibroblast growth factor can promote the proliferation of human periodontal ligament cells and inhibit the activity of alkaline phosphatase, and the effect is concentration-dependent.