The effect of reaction media cosolvent water activity, temperature and pH on Novozym 435-caulyzed enantioselective esterification of ketoprofen was systematically explored. Novozym 435 showed high catalytic activity and enantioselectivity in cyclohexane; E value increases markedly by addition of toluene to cyclohexane; the optimum temperature and the initial water activity were found to be 30℃ and 0.09 respectively; pH shows little effect on enzymatic reaction wilson the scope studied.

Aim To establish a LC-MS/MS method for the determination of pirfenidone(BT)and its major metabolite 5-carboxy-pirfenidone(SBT)in human plasma.Methods Human plasma samples containing BT and SBT,as well as their corresponding deuterium-labeled internal standards pirfenidone-d5(dBT)and 5-carboxy-pirfenidone-d5(dSBT),were precipitated using methanol.Chromatographic separation was carried out on an Agilent ZORBAX SB C18(3.0 mm×100 mm,3.5 μm)column with the mobile phase of water(0.5％formic acid)and acetonitrile(50/50).The detection of analytes was performed on a tandem mass system equipped with an electrospray ionization source in positive ion mode using multiple-reaction monitoring.The MS/MS ion transitions monitored were m/z 185.958→77.1 for BT,m/z 215.944→77.0 for SBT,m/z 190.965→81.1 for dBT and m/z 220.948→99.1 for dSBT.Results There was no remarkable interference in blank solvent,plasma,and there was no mutual interference between analytes or internal standards.The proposed method showed good linearity over the concentration range of 0.020 59～25.14 mg·L-1 for BT and 0.016 73～20.42 mg·L-1 for SBT.The intra-batch and inter-batch precision and accuracy were proved to be acceptable.Human samples kept stable after 4 h at room temperature,the three freeze-thaw cycles and 10,29 and 52 days at-70 ℃,and the processed samples remained stable after 24 h in the autosampler.The average extraction recovery and matrix effect were precise,reproducible and acceptable.Conclusion Our current LC-MS/MS method is proved to be sensitive,accurate and convenient,and could be suitable for the clinical pharmacokinetic studies of BT-related preparations.

OBJECTIVE:To provide reference for medical costs control in China. METHODS:Based on main characteristics of the United States health service system,information asymmetry,principal-agent theory and Freedman’s consumption theory were used to analyze the advantages of restrictive relationship among doctors,hospitals and health insurance institutions in control-ling medical costs and improving the quality of diagnosis and treatment. The growth rate of medical cost,the percentage of drug ex-penditure and other aspects were compared between China and the United States;the effect of restrictive relationship on medical cost control was demonstrated. RESULTS & CONCLUSIONS:In the United States,there are hierarchical medical system and two-way referral system;for-profit hospitals and non-profit hospitals are mutually complementary;different natures of health insur-ance system,different payment methods and strict“commercial bribe”monitoring system are carried out;doctors,hospitals and health insurance restrict each other. Not only there are many advantages in theory,but also in practice the growth rate of medical cost and the percentage of drug expenditure are superior to our country. Finally it controls the rapid growth of medical cost to a cer-tain extent. Combined with our national conditions,learning from the United States experience,restrictive relationship among doc-tors,hospitals and health insurance institutions is established to control the increase of medical cost in China through reducing infor-mation asymmetry and standardizing payment audit;establishing a scientific pattern of mixed payment;strengthening the indirect impact of the health insurance institutions on doctors and hospitals,etc.

Objective Laminectomy is destructive to bone structure in spine , which affect spinal stability .This article was to investigate the effect on spinal stability after laminectomy in different segments of vertebral plate in the treatment of lumbar intraspinal tumors. Methods Retrospective analysis were made on the data of 143 patients with lumbar intraspinal tumors from January 2009 to June 2012 in 6 hospitals.All the patients underwent laminectomy with no use of inner regular apparatus during the operation .JOA evalu-ation was applied to observe short-term efficacy , while ASIA scale for long-term efficacy .Comparison was made on lumbar spinal stability before operation and in the last visiting . Results From the observation of short-term efficacy, JOA evaluation score rised from (1.12 ± 0.65)to (1.97 ±0.71).Form the observation of long-term efficacy, ASIA scale classification was as follows:4 cases of Grade I, 6 cases of Grade II, 14 cases of Grade III, 53 cases of Grade IV and 66 cases of Grade V.In the following 12-30 months′visiting, all patients were covered.In the last postoperative visiting, patients suffering spinal instability after laminectomy were as follows:2 of 45(one seg-ment), 9 of 47(two segments), 5 of 27 (three segments) and 2 of 14 (four segments).From the observation on the postoperative spinal sta-bility and the segments in laminectomy , spinal stability of one-segment group was significantly higher than that of multi-segment group ( P=0.047).No significant difference exist between the groups of less than 2 segments and more than 3 segments as well as the groups of less than 3 segments and more than 4 segments. Conclusion A single seg-ment laminectomy on lumbar intraspinal tumors showed good postopera-tive spinal stability .But laminectomy in two or more segments implied greater risk of postoperative spinal instability .

Animals ; Atherosclerosis ; diet therapy ; physiopathology ; Humans ; Plaque, Atherosclerotic ; drug therapy

Objective To explore the optimal methods to detect helicobacter pylori(Hp)antigen in children.Methods 13C labeled urea breath test(13C-UBT)was performed on 937 children of alimentary department from Sep.2000 to Feb.2006.Gastric mucosa biopsy of 96 children was detected.Hp stool antigen(HpSA)status of the 557 children were evaluated.Both 13C-UBT and HpSA were assayed in 105 children from Apr.2003 to Apr.2004.Method of 13C-UBT was taken as the golden standard on diagnosis of Hp infection.Results Forty-one point seven percent children was positive for 13C-UBT.Forty point six percent children was positive for gastric mucosa biopsy.Thirty-eight point two percent was positive for HpSA.The difference was not significant.2.Among the 105 children performed by both 13C-UBT and HpSA,41.9% was positive for 13C-UBT and 39.0% for HpSA.Taking 13C-UBT as the golden standard,sensitivity of HpSA to diagnose Hp infection was 91.8%,and its specificity was 81.8%.Consistency Kappa coefficient was 0.743(P=0),which denoted that there was no significant difference on the positive detection rate between 13C-UBT and HpSA(P=0.388).Conclusions 13C-UBT and HpSA as non-invasive technique is effective to detect the Hp antigen.Compared to 13C-UBT,as a convenient,noninvasive,economical method,HpSA detection is much more acceptable to children and their patients.

Objective To investigate the effects and safety of sequential treatments with methotrexate and mifepristone for ectopic pregnancy with fetal cardiac activity.Methods 4 cases of ectopic pregnancy with fetal car- diac activity in our hospital were given by sequential therapy with methotrexate and mifepristone.Serum?-HCG,liv- er function and renal function,blood routine and gastrointestinal response were observed.Results 4 cases of ectopic pregnancy with fetal cardiac activity with 1～4 periods of sequential treatments were cured.Except light gastroin- testinal response,and one had slight rise of serum ALT level and AST level,no one had rnyelosuppression and heavy hepatic injury.Conclusion The sequential therapy with methotrexate and mifepristone is an effective and safe method for the treatment to ectopic pregnancy with fetal cardiac activity.

Objective To study the clinicopathological features of syringomatous adenoma of the nipple (SAN).Methods The clinical,histopathological and immunohistochemical findings of four cases of SAN were described,with a review of the literature.The diagnosis and differential diagnosis of SAN were also discussed.Results Among the four patients,three were female,and one was male.The mean age at onset was 42 years,and clinical course ranged from 3 months to 10 years.Clinically,SAN was manifested as an asymptomatic subcutaneous nodule,which was located in the areola of breast of female patients and in the right armpit of the male patient.Histopathologically,the tumor was located in the dermis and subcutaneous tissue,composed of nests and cords of epithelial cells forming tubular structures and infiltrating the indurated stroma between smooth muscle bundles.These tubules were lined by two layers of cells and displayed a comma or tadpole shape.Keratotic microcysts were seen.Immunohistochemically,the tumor cells stained positive for cytokeratin,cytokeratin 5/6,Ki67 (1％),but negative for estrogen receptor,progesterone receptor,CerbB2,cytokeratin 8/18,P53 and gross cystic disease fluid protein-15 (GCDFP-15).The peritubular myoepithelial cells expressed P63 and smooth muscle actin (SMA).Conclusions SAN is a rare benign tumor,which is often confused with some benign and malignant carcinomas of the breast.

ObjectiveTo investigate the effects of protein phosphatase 2A (PP2A) inhibitors on the viability of pancreatic cancer cell line PANC-1 and its mechanism.MethodsPANC-1 cells were treated with PP2A inhibitors Cantharidin or Okadiac acid.The activity degree of NF-κB pathway was tested by Western blot.NF-κB pathway was blocked from all sectors by PP2Acα plamid transfection,NF-κB inhibition of protein kinase α (IKKα) and NF-κB inhibitor α (IκBα) dominant negative mutant and p65 interfering plasmid.Cell viability was determined by MTT.ResultsPP2A inhibitors could induce phosphorylation of IKKα,further phosphorylation of IκBα and degradation and followed by the release of p65 into nucleus.When PP2Acα,IKKα dominant negative mutant and IκBα dominant negative mutant were overexpressed,or p65 was interfered,the inhibition rate of Cantharidin on cell viability decreased (31.85±13.37) ％,(23.48±8.98)％,(22.63±5.81)％ and (20.88±3.24)％respectively,and the inhibition rate of Okadiac acid on cell viability decreased (40.17 ± 11.65)％,(27.34±14.28)％,(24.85±3.39)％ and (27.08±3.81)％ respectively.ConclusionsPP2Ainhibitors play a role in preventing pancreatic cancer through PP2Acα/IKKα/IκBα/p65 pathway.

Objective To evaluate the clinical value of pro-gastrin-releasing peptide (ProGRP) for small cell lung cancer ( SCLC ).Methods Serum levels of ProGRP and neuron-specific enolase (NSE) were measured by both chemiluminescent immunoassay and electrochemiluminescent immunoassay in 46 patients with SCLC (26 patients with limited disease,20 patients with extensive disease ),51 patients with non-small cell lung cancer (NSCLC),45 patients with benign pulmonary diseases and 56 healthy subjects.Patients were recruited by the Affiliated Hospital of Medical College,Qingdao University,from September 2010 to April 2011.The receiver operating characteristic curves (ROC) was used to set the cutoff value of ProGRP and NSE and the areas under ROC ( ROC-AUC).The sensitivity and specificity of ProGRP and NSE were analyzed for diagnosing SCLC.Results Serum levels of ProGRP in healthy subjects,benign pulmonary diseases,NSCLC and SCLC groups were 22.9 ( 19.5 - 28.7 ),23.7 ( 20.0 - 27.8 ),28.9 (23.8-34.7) and 370.9( 129.4- 1951.6) ng/L respectively; the serum levels of NSE were 14.1 (12.5- 15.7),13.3(10.3- 15.3),16.8(11.7-22.1) and 39.9(16.1-93.9) μg/L,respectively.The Kruskal-Wallis H test showed significantly difference amoun groups of ProGRP and NSE (H =92.116 and 55.481,P ＜0.001 ).The serum levels of ProGRP in limited disease SCLC (LD-SCLC) group[ 156.2(65.4-547.5 ) ng/L]were also significantly higher than those in the healthy group,benign pulmonary diseases group and NSCLC group ( U =57,70 and 144,P ＜ 0.001 ).In extensive disease SCLC (ED-SCLC) group,the ProGRP and NSE results[ 1933.1 (325.9 -4512.1) ng/L and 61.0(35.4- 115.5 ) μg/L ]were higher than those in the LD-SCLC group ProGRP,NSE [ 24.3 ( 15.1 - 16.3 ) μg/L,U =119 and 153,P ＜ 0.05 ].Using healthy subjects group as control,the largest Youden index point of ROC was used to set the cut-off value of ProGRP and NSE (34.0 ng/L and 20.2 μg/L).The ROC-AUC of ProGRP (0.96 ) was statistically higher than that of NSE ( 0.86 ) in the SCLC group ( Z =2.57,P ＜0.05).The ROC-AUC results between combining detection of ProGRP and NSE (0.96 ) and ProGRP itself (0.96) were not significant difference ( Z =0.21,P ＞ 0.05 ).The sensitivity of ProGRP ( 89.1％ ) was statistically higher than that of NSE in the SCLC group (71.7％,x2 =4.90,P ＜0.05 ) ; the specificity of ProGRP (98.2％) compared with NSE did not have statistical significance (96.4％,x2 =0.00,P ＞0.05 ).The combining detection of ProGRP and NSE had no influence on the sensitivity and specificity compared with ProGRP itself (91.3％ vs 89.1％,94.6％ vs 98.2％,x2 were all 0.00,P ＞ 0.05 ).Using benign pulmonary diseases group as control,the largest Youden index point of ROC was used to set the cutoff value of ProGRP and NSE (49.5 ng/L and 23.1 μg/L).The ROC-AUC of ProGRP (0.95) was statistically higher than that of NSE (0.87) in the SCLC group (Z =1.99,P ＜0.05 ).The ROC-AUC of combining detection of ProGRP and NSE ( 0.95 ) and ProGRP itself ( 0.95 ) were not difference significantly ( Z =0.02,P ＞ 0.05 ).The sensitivity of ProGRP (84.8％ ) was statistically higher than that of NSE in the SCLC group (69.6％,x2 =4.00,P ＜0.05);the specificity of it (97.8％) was equal to that of NSE (97.8％,x2 =0.50,P ＞0.05 ).The combining detection of ProGRP and NSE had no obviously influence on the sensitivity and specificity compared with ProGRP itself ( 87.0％ vs 84.8％,95.6％ vs 97.8％,x2 were all 0.00,P ＞0.05 ).Using NSCLC group as control,the largest Youden index point of ROC was to set the cut-off value of ProGRP and NSE (49.1 ng/L and 23.0 μg/L).The ROC-AUC of ProGRP ( 0.90) was statistically higher than that of NSE (0.76) in the SCLC group (Z=2.90,P＜0.05).The ROC-AUC of combining detection of ProGRP and NSE (0.90 ) and ProGRP itself (0.90 ) were not difference significantly ( Z =0.00,P ＞ 0.05 ).The sensitivity of ProGRP ( 84.8％ ) was higher than that of NSE in the SCLC group ( 69.6％,x2 =4.00,P ＜ 0.05 ) ; the specificity of it ( 96.1％ ) was also higher than that of NSE (80.4％,x2 =6.13,P ＜ 0.05 ).The combining detection of ProGRP and NSE had no obviously influence on the sensitivity and specificity compared with ProGRP itself ( 87.0％ vs 84.8％,95.6％ vs 96.1％,x2 were all 0.00,P ＞ 0.05 ).Conclusion ProGRP has a higher diagnostic value than NSE in SCLC.