Ras/Raf/MEK/ERK singal transduction plays an important role in cell proliferation, differentiation, apoptosis, metastasis and metabolism. This investigation focused on this signal pathway and chose farnesyl transferase (FTase) as the main target and Raf-1 kinase as the second target. A lot of compounds were selected to construct the pharmacophore models of farnesyl transferase inhibitors (FTIs) and Raf-1 kinase inhibitors by using computer-aided drug design (CADD). The pharmacophore of FTIs is constituted by a hydrogen bonding acceptor, an aromatic ring, a positive ionizable and two hydrophobic regions; the pharmacophore of Raf-1 kinase is constituted by a hydrogen donor, a hydrogen acceptor, a hydrophobic regions and an aromatic ring. There are some similarities between the two pharmacophores. After analysis of the constructions of these two pharmacophores, some new aminomethylbenzoic acid derivatives with good forecasting activity against both of FTase and Raf-1 kinase were designed with these new pharmacophore models.

Objective To investigate and compare the clinical effects of intraarticular injection of sodium hyaluronate and diprospan on knee osteoarthritis. Methods 94 patients with knee osteoarthritis were divided into two groups, the HA group and Cortieosteroid group. Each patient in the HA group was treated with intra-articular injection of sodium hyaluronate at 2.5 ml every week for 5 weeks, and each patient in the Corticosteroid group was treated with intra-articular injection of diprospan at 1ml on the first and fourth week. The clinical assessments included pain,joint effusion,and Lequesne Index. Assessments were done at baseline, at week 4, and week 12. Results 88 cases were followed up for 3 months. A significant decrease in VAS scores for pain and in Lequesne Index was found in both groups at week 4 when compared to baseline and there were no significant differences between the two groups. However,at 12 week improvement in pain score and Lequesne Index was found in favour of hyaluronic acid. In addition,diprospan seemed to have preferable short-term effect on patient with joint effusion. Conclusion Both intra-articular injection of sodium hyaluronate and diprospan provided clinically significant improvement in short-term and demonstrated that hyaluronic acid had a more long-term beneficial effect in patients with knee osteoarthritis.

The effect of triptolide on proliferation and apoptosis of human multiple myeloma RPMI-8226 cells in vitro, as well as the roles of nuclear factor-kappa B (NF-κB) and IκBα was investigated. The effect of tritptolide on the growth of RPMI-8226 cells was studied by MTT assay. Apoptosis was detected by Hoechest 33258 staining and Annexin V/PI double staining assay. The expression of NF-κB and IκBα was observed by Western blot and confocal microscopy. The results showed that triptolide inactivated NF-κB apoptotic pathway in human multiple myeloma RPMI-8226 cells. Triptolide at nM range induced proliferation inhibition in a dose- and time-dependent manner and apoptosis in a dose-dependent fashion in RPMI-8226 cells. Besides, we observed the inhibition of NF-κB /p65 in the nuclear fraction was correlated with the increase in the protein expression of IκBα in the cytosol. These results suggested that triptolide might exhibit its strong anti-tumor effects via inactivation of NF-κB/p65 and IκBα.

Objective To evaluate the conditions and risk factors of esophageal stent dys-seal phenomenon (ESDP) .Methods Ninety-eight patients with malignant esophageal obstruction underwent metallic stent placement and 7 patients with ESDP were analyzed.The possible contributing factors,including age,gender,obstruction segment,esophagorespiratory fistula,surgical intervention,radiotherapy,the degree of upper obstruction segment expansion,stent with bellmouth,application of covered stent were investigated.All factors mentioned above were analyzed with Logistic regression analysis.Results ESDP was observed in 7 patients (7/98,7.14%) and defined as a space between the esophageal wall and the proximal part of stent without contrast agent obstruction within stent.The clinical situations of patients with ESDP included dysphagia,bucking and constantly chest pain,especially at foodintake.The results of Logistic regression analysis indicated radiotherapy (P=0.005) and the degree of upper obstruction segment expansion (P=0.017) were significantly correlated with ESDP.Conclusion ESDP is one of the complications after esophageal stent placement.It is prudent to implant esophageal stent for those patients with radiotherapy and significant upper obstruction segment expansion.

Objective To understand the clinical characteristics of pediatric patients who developed H1N1 influenza A virus-associated pneumonia during the outbreak of H1N1 influenza A in Shanghai. MethodsA dcscriptivc study was done to analyze the clinical and epidemiologic characteristics of 30 hospitalized children who developed complicated pneumonia caused by H1N1 influenza A virus infection in 2009 in Shanghai. The comparison of medians was done using rank sum test and comparison of rates was done using exact chi-square test. Results Among thirty pediatric patients with H1N1 influenza A virus-associated pneumonia, the median age was 5.9 years old, five cases (16.7 %) had pre-existing medical conditions. Twenty cases (66.7 % ) had been exposed to the classmates or family membcrs with fever. All cases had fever and cough. Eleven cases (36.7 %00 ) had tachypnca and ten (33.3%) had wheeze. Eleven cases (36.7%) showed white blood cell (WBC)＜4.0 × 109/L and 2 (6. 7%) had thrombocytopenia. All patients had bilateral or unilatcral patchy infiltrates in the lung indicated by chest X-ray and four (13. 3%) had extensive infiltrates with the evidence of pulmonary edema. One (3. 3%) critically ill child with pneumonia, chest computed tomography scan revealed lung fibrosis 3 months and 9 months after illness onset. Three(10. 0%) cases had pneumomediastinum and subcutaneous emphysema. Six cases (20. 0%) were complicated with acute respiratory failure, three (10. 0%) with acute asthmatic attack and one (3. 3%) with encephalitis. All patients were treated with oseltamivir plus antibiotics and four required mechanical ventilation. All patients survived. The median duration of fever in group with oseltamivir given within 2 days of fever onset was statistically shorter than that in group with oseltamivir given 2 days after fever onset (2 days vs 5 days, Z= -8. 015, P<0. 01). Conclusions Both pre-school age and schoolage children may develop complicated severe respiratory diseases after H1N1 influenza A virus infection. Early initiation of oseltamivir may shorten the duration of fever and reduce the occurrence of severe complications.

Objective To evaluate the efficacy of Fluency stent-graft (Bard Corp) in transjugular intrahcpatic portosystemic shunt (TIPS).Methods The clinical data of 21 consecutive patients treated by TIPS using Fluency stent-grafts were retrospectively reviewed.All of them were recurrent variceal bleeding secondary to portal vein hypertension,1 was bleeding secondary to primary hepatic carcinoma with port vein thrombns,and 1 was Budd-Chiari syndrome.They were followed-up after (10.1 ± 4.6) months (2.0 to 24.0 months).Stent-grafts patancy,portal vein pressure and liver function were recorded and compared.Results Twenty-five stent-grafts were successfully implanted in 21 patients,23 stent grafts were 8 mm 2 were 10 mm in diameter.The covered length of the stents varied from 6 to 8 cm.The bleeding was stopped and the portal vein pressure decreased significantly from (25.4 ± 3.5) mm Hg to (15.4 ± 2.8) mm Hg (t = 12.495,P < 0.01).During the follow-up period,The patient with primary HCC and portal vein thrombosis died 4 months after the procedure. One case had a new primary HCC during the follow-up and died 24 months after the procedure.One ease with variceal bleeding secondary to portal vein hypertension died of muhisystem organ failure.One case occluded in the hepatic vein and had another stcnt graft implanation.The other 17 cases had no stenosis after 7 to 17 months follow-up.Ultrasound showed that the stents were patent 1 week before the patients died.Three cases had transient symptoms of hepatic encephalopathy and recovered after treatment.The Child scores of the 19 patients survived more than 6 months were 6.3 ±1.4 before and 6.4 ± 1.9 after the procedure without significant difference (t = 0.645,P > 0.05).Conclusion The Fluency stent-grafts could increase the patency of the TIPS,but its efficacy on the long-term effect and hepatic encephalopathy need further investigation.

Objective To determine the clinical significance of pulmonary function test(PFT)in evaluating the features and severity of lung impairments associated with connective tissue diseases(CTD)by comparing the differences of pulmonary function test parameters among groups of CTD associated pulmonary disorders.Methods Cases of CTD associated pulmonary disorders were prospectively enrolled and assigned into 3 groups according to their lung impairments:CTD associated pulmonary arterial hypertension group (CTD-PAH,n=29),CTD associated interstitial lung disease group(CTD-ILD,n=35),CTD associated PAH plus ILD group(CTD-PAH+ILD,n=16)and CTD control group(n=34).Pulmonary function test parameters,including total lung capacity(TLC % predicted),forced vital capacity(FVC % predicted),forced expiratory volume in the first second(FEV_(1.0)% predicted),FE_(1.0)%/FVC and diffusing capacity of the lung for carbon monoxide(DLco,% predicted)were measured and compared among the four groups.Results One hundred and forteen eases were included and predominantly female with average onset age of 35～39 years old.CTDs that were predisposed to lung diseases were mixed connective disease(MCTD),systemic sclerosis(SSc),systemic lupus erythematosus(SLE)and primary Sj(o)ren syndrome(pSS),in order.There were 10,29 and 46 percent of patients presented with decreased TLC% in CTD-PAH,CTD-ILD and CTD-PAH+ILD group respectively,50,36 and 71 percent of patients with decreased FVC% respectively,54,47 and 71 percent of patients with decreased FEV_(1.0)% respectively,and 100,82 and 100 percent with decreased DLco% respectively.ANOVA analysis demonstrated that TLC%,FVC%,FEV_(1.0)%,DLco% had significant differences between CTD control group and each of the CTD associated lung disease group(P＜0.05),although none of them was lack of difference between the PAH and ILD groups.TLC% was significantly higher in CTD-PAH group than CTD-PAH+ILD group[(89±15)% vs(79±12)%,P＜0.05],while FVC% was significantly lower in CTDPAH+ILD group either than CTD-PAH group or than CTD-ILD group[(81±13)%,(80±16)% vs(65±22)%,P＜0.05].ConclusionPulmonary function test may be valuable in early screening for CTD associated lung disorders than distinguishing CTD-PAH from ILD,which usually reveal restrictive ventilation dysfunction and/or diffusing capacity dysfunction.

Forest musk deer (Moschus berezovskii), a rare wild medicinal animal, is listed under the category of the state key protected wildlife list of China. Musk, secreted by the musk glands, is with high economic and medicinal value and used as precious traditional medicine in China. In order to meet the needs of musk in Chinese traditional medicine, forest musk deer farming was conducted in 1950s, but the research progress on musk secretion mechanism was slow. Therefore, by reviewing the histological and anatomical structure of forest musk deer musk gland, the relationship between sex hormones and the musk secretion process, and the molecular mechanism of the musk secretion, the existing problems in investigating the musk secretion mechanism were analyzed and the development trends in this field were also discussed, in order to provide a reference for further studies on the musk secretion mechanism and improve musk production of forest musk deer.
Animals ; Deer ; metabolism ; Exocrine Glands ; anatomy & histology ; chemistry ; secretion ; Fatty Acids, Monounsaturated ; chemistry ; metabolism ; Male

Objective To investigate the causes and managements of dys-seal syndrome (DSS) developed after esophageal stent placement. Methods From June 2001 to June 2008, esophageal stenting was performed in 98 consecutive patients with malignant esophageal obstruction. A total of 99 metallic stents were used. Of 98 patients. gastroesophageal anastomosis stricture was seen in 19, preoperative radiotherapy history in 26 and tracheoesophageal fistula in 34. Results DSS occurred in 7 patients, with an occurrence rate of 7.14% ,which was significant higher than that in patients with preoperative radiotherapy history and in patients showing marked dilated esophagus proximal to the obstructed site (X~2=0.017, 0.005, P=0.036, 0.013, respectively). After treatment, such as fasting, IPN or nasogastric feeding,only 1 case retumed to semi-liquid diet. Among the rest 6 cases of DSS, an additional stent was employed in one (but in vain), nasogastric feeding tube was used in 2, and removal of the stent under endoscopic guidance was carried out in 3. Conclusion DSS is one of the complications developed after esophageal stent placement, its prognosis is rather poor. Removal of the inserted stent may be the optimal treatment. The prevention of DSS includes proper pre-operation evaluation, selection of suitable stent, enhancement of perioperative nutritional support, etc.

The killing effects of herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) approach by the addition of several commonly clinical chemotherapeutic agents on hormone refractory prostate cancer (HRPC) cells PC-3m were investigated. After transferring of the HSV-tk gene into PC-3m cells, mRNA and protein expression of HSV-tk was detected by reverse-transcript polymerase chain reaction (RT-PCR) and strept avidin-biotin complex (SABC) immunohistochemical method. The killing effect of GCV, cisplatin (CDDP), etoposide (VP-16), vincristine (VCR), methotrexate (MTX), 5-fluorouracil (5-Fu), and suramin on PC-3m cells was evaluated by morphological assessment analysis, trypan blue exclusion assay and MTT assay respectively. Additionally, the cooperative effect of HSV-tk/GCV system combined with the above agents on the target cancer cells was determined by MTT. Furthermore, apoptosis and necrosis induced by GCV plus 5-Fu or suramin was analyzed by flow cytometry (FCM). The results showed that that there was HSV-tk mRNA and protein expression in pDR2-tk plasmid transduced PC-3m cell. Combination of GCV with VP-16, VCR, 5-Fu or suramin led to an enhanced cellular killing effect, but with CDDP resulted in a reduced one and with MTX in an approximate one. FCM revealed that synergistic use of GCV and 5-fu or suramin resulted in a rather large proportion of apoptosis and necrosis with the apoptosis index being 36.38% and 35.51%, and the proportion of necrosis being 33.05% and 28.87%, respectively. In conclusion, HSV-tk/CGV approach by addition of certain clinical available chemotherapeutic drugs brings on statistically significant enhanced cell killing over single-agent treatment. Our results highlight the potential for such new combination therapies for future treatments of HRPC.