A new orally active non-glycosidic, non-adrenergic cardiotonic agent, 2-[(2-me-thoxy-4-methysulfinyl) phenyl]-1 H-imidazo[4, 5-b]-pyridine, AR-L115BS, has been synthesized.The two key intermediates, 2, 3-diaminopyridine and 2-methoxy-4-methylmercap-tobenzoic acid were prepared according to the routes submitted by Fox and Zipp, respectively. The approaches were improved to adapt large scale laboratory preparation. The structure of the end product was proved by elemental analysis,mass spectra, 1H nuclear magnetic resonance spectra and infrared spectra.

Objective To investigate the association of HLA DRB1 alleles with gastric carcinoma and H. pylori infection. Methods HLA DRB1 alleles polymorphism in 63 patients with gastric adenocarcinoma and 136 normal controls were tested with the polymerase chain reaction/sequence specific primer(PCR/SSP) technique. The status of H. pylori infection was determined by histology of gastric biopsy specimens and /or by ELISA. Results Both HLA DRB1 0901 and HLA DRB1 12 were positively associated, and HLA DRB1 15 was negatively associated with gastric adenocarcinoma, but no significant associations were found between patients with and without above HLA DRB1 alleles with regard to patients' age at presentation, sex ratio, tumor site (distal vs proximal), TNM staging, histological grading of tumor or status of H. pylori infection. Conclusions Our results suggest that HLA DRB1 0901, DRB1 12 and DRB1 15 are associated with gastric adenocarcinoma, but are not associated with the clinical features of gastric adenocarcinoma and the status of H. pylori infection.

Objective To explore human cytomegalovirus UL97 mutations related to ganciclovir resistance in hematopoietic stem cell transplant (HSCT) recipients.Methods A total of 43 patients,including 24 males and 19 females,with an average age of 21 years old,who had HCMV DNAemia for more than two weeks after HSCT between 2008 and 2010 in Peking University People's Hospital,were included in this prospective study.UL97 GCV resistance mutations were investigated in 49 plasma specimens collected from those patients.GCV resistance mutations such as UL97 M460V/I,H520Q,A591V,A594V,L595S/F,and C603W,were analyzed by modified PCR-RFLP methods.UL97 mutations related to GCV resistance were assayed by the method of PCR-direct sequencing (PCR-DS).An amplified refractory mutation system real-time PCR (ARMS RT-PCR) was developed for the detection of UL97 A594V mutation.Results Eight known UL97 ganciclovir resistance mutations were not detected by PCR-RFLP and PCR-DS.Four new UL97 mutations like UL97 R494P,T502A,N558D,and G561S,were detected by PCR-DS.The ARMS RT-PCR for detecting of UL97 A594V was established successfully.The lower limit of detection of the method was at least 7.5 × 102 copies/ml combined with the use of nucleic acid extraction reagent.UL97 A594V resistance mutation was identified by the method of ARMS RT-PCR in two HSCT recipients.The rate of UL97 A594V mutation was 4.7％ (2/43) in HSCT recipients.Conclusion The ARMS RT-PCR assay represented a sensitive method for the identification of UL97 A594V mutation.

Objective To study the protective effect of octreotide on myocardial injury after hepatic ischemia-reperfusion in rabbit. Methods Pringle's maneuver rabbit hepatic ischemia-reperfusion model was established. 24 adult New Zealand rabbits were random divided into equal 3 groups: sham operative group ( group A) , ischemia-reperfusion group( group B) and octreotide preconditioning group ( group C ). The levels of CK-MB( MB isoenzyme of creatine kinase) and LDH ( 1actate dehydrogenase), superoxide dismutase (SOD) and malondialdehyde (MDA) of each group were measured at the time before ischemia (T1) , after ischemia for 30 mins ( T2 ) and after reperfusion for 60 mins ( T3 ), 120mins ( T4 ), 240 mins ( T5 ). The SOD and MDA in myocardial tissue of each group were measured after reperfusion for 240 mins. The changes of ultrastructure in the myocardial cell were observed by transmission electron microscopy after reperfusion for 240 mins. Results There was no significant difference in the levels of CK-MB and LDH in serum of each group before ischemia ( P ＞0. 05). The CK-MB and LDH of group B and C were higher than that of group A ( P ＜0.05) after ischemia for30 mins. The CK-MB and LDH of group C were lower than that of group B in this period( P ＜0. 05 ). The highest time point of LDH and CK-MB were after reperfusion for 120 mins and 240 mins. The contents of MDA in group B and group C were higher than that in group A from after ischemia for 30 mins in plasma and after reperfusion for 240 mins in myocardial tissue ( P ＜ 0. 05 ),and it in group C were lower than that in group B( P ＜0.05) .The contents of SOD in group B and group C were lower than that in group A from after ischemia for 30 mins in blood plasma and after reperfusion for 240 mins in myocardial tissue ( P ＜0. 05), and in group C were higher than that in group B( P ＜0. 05).The electromicroscope showed that the pathological change of myocardial ultrastructure of group C was slighter than that of group B. Conclusion Octreotide can stabilize myocardial cell membrane and reduce release of oxygen free radical and significantly relieve the injury of myocardial ultrastructure after hepatic ischemiareperfusion in rabbit. Octreotide preconditioning can relieve myocardial injury after hepatic ischemia-reperfusion in rabbit.

In this work, blank polylactic acid (PLA) nanoparticles with unstained surface were prepared by the nano-deposition method. On the basis of the preparation, the effect of surface modification on brain microvascular endothelial cells (BMECs) targeting was examined by in vivo experiments and fluorescence microscopy. The results showed that PLA nanoparticles are less toxic than PACA nanoparticles but their BMECs targeting is similar to PACA nanoparticles. The experiments suggest that drugs can be loaded onto the particles and become more stable through adsorption on the surface of PLA nanoparticles with high surface activity. The surface of PLA nanoparticles was obviously modified and the hydrophilicity was increased as well in the presence of non-ionic surfactants on PLA nanoparticles. As a targeting moiety, polysobate 80 (T-80) can facilitate BMECs targeting of PLA nanoparticles.
Brain/*blood supply ; Brain/drug effects ; Capillaries/cytology ; Capillary Permeability/drug effects ; Drug Delivery Systems ; Endothelium, Vascular/*cytology ; Lactic Acid/*pharmacology ; Mice, Inbred Strains ; Microscopy, Fluorescence ; Nanoparticles ; Polymers/*pharmacology

Objective To evaluate the effects of sulforaphane preconditioning on cognitive dysfunction induced by sevoflurane anesthesia in aged rats.Methods Thirty Sprague-Dawley rats,aged 22 months,weighing 380-560 g,were randomly divided into 3 groups (n =10 each) using a random number table:control group,sevoflurane group (Sev group),and sulforaphane group (Sul group).In group Sul,sulforaphane25 mg/kg was administered by oral gavage once a day for 7 consecutive days,while the equal volume of distilled water was given instead of sulforaphane in Sev and C groups.Groups Sev and Sul inhaled 3％ sevoflurane in oxygen (2.5 L/min) and group C inhaled air (100 min/d) for 5 consecutive days starting from the end of gavage.At 24 h after sevoflurane inhalation,cognitive function was detected using Morris water maze and open field tests.The escape latency,frequency of crossing the original platform,the number of crossing the grid,the number of standing on the back legs and the time the animals spent in the central square were recorded.Results Compared with group C,the frequency of crossing the original platform,the number of crossing the grid,and the number of standing on the back legs were significantly reduced,the time the animals spent in the central square and escape latency on 1st day were prolonged and no significant changes were found in the escape latency on 2nd-4th days in group Sev.Compared with group Sev,the frequency of crossing the original platform,the number of crossing the grid,and the number of standing on the back legs were significantly increased,and the time the animals spent in the central square and escape latency on 1st day were shortened.Conclusion Sulforaphane preconditioning can improve the cognitive dysfunction induced by sevoflurane anesthesia in aged rats.

Objective To compare the dosimetric difference of RapidArc and fixed gantry IMRT for liver carcinoma.Methods The CT data of 10 liver cancer patients were used to design 3 groups of treatment plan:IMRT plan,single arc RapidArc plan(RA1) ,and dual arc RapidArc plan(RA2).The planning target volume (PTV) dosimetric distrubition,the organs at risk (OAR) dose,the normal tissue dose,mornitor units(MU) and treatment time were compared.Results The maximum dose of PTV in RA1 and RA2 plans were lower than that of IMRT(Z = -2.090,-2.666,P ＜ 0.05).RapidArc groups had an improved 90% prescription dose conformity index than IMRT(Z = -2.805,-2.809 ,P ＜ 0.05).For organs at risk,RapidArc group plan had a significantly lower dose in V40 of stomach and small bowel than I MRT plan,but higher in mean dose of left kidney (Z = -1.988,-2.191,P ＜ 0.05).The values of V5,V10 and V15 of healthy tissue in RapidArc plan groups were higher than those in IMRT plan,while the values of V20 ,V25 and V30 of healthy tissue in RapidArc plan groups were lower than those in IMRT plan.The number of computed MU/fraction of Rapid Arc plan was 40% or 46% of IMRT plan and the treatment time was 30% and 40% of IMRT.Conclusion RapidArc showed improvements in conformity index and healthy tissue sparing with uncompromised target coverage.RapidArc could lead to the less MU and shorter delivery time compared to IMRT.

Objective To investigate the correlation between functional lung dose-volume histogram (f-DVH) parameters and radiation-induced lung toxicity (RILT) in patients of locally advanced non-small cell lung cancer (NSCLC) treated with late-course accelerated hyperfractionated radiotherapy and chemotherapy,and to identify the excellent predictors of f-DVH and their reference thresholds.Methods A total of 51 patients of NSCLC at stage Ⅲ underwent PET/CT/SPECT coregistered image guided radiotherapy.Philips Pinnacle3 planning system was used for delineation of the target volume and organs at risk so as to establish the three dimensional conformal radiotherapy or intensity-modulated radiotherapy treatment plans.The version 3.0 of the NCI Common Terminology Criteria for Adverse Events was used to evaluate the grade of RILT,and analyze the correlation of the DVH parameters of the total lung (TL),ipsilateral lung (IL),and functional lung (FL) and RILT,and to identify the excellent predictors.The median follow-up was 15 months.Results During the follow-up,10 cases of RILT (19.6%) ≥grade 2 were observed.Single factor analysis showed that the V5-V40 of TL,V5-V/20 of IL,and V5-V50 of FL were all related to the occurrence of RILT,and multiple factor analysis showed that TL-V15 and FL-V20remained associated with RILT (P = 0.005 and P = 0.016).According to ROC analysis,the V10 (45.38%) of FL was the most sensitive predictor with a sensitivity rate of 90.0% and 1/25 (27.78%) of FL was the most specific predictor with a specificity rate of 90.24%.The sensitivity,specificity and accuracy of V20 of FL were 70.00%,73.17%,and 74.90%,respectively.Conclusions The occurrence of RILT is closely associated with multiple f-DVH parameters of FL,and f-DVH has good sensitivity and specificity for prediction.

Objective To investigate the effect of sevoflurane anesthesia on the cognitive function and phosphorylation of tau in hippocampal neurons in amyloid precursor protein (APP) transgenic mice.Methods Male APP gene mutation mice,weighing 18-22 g,aged 8-12 weeks,were used in the study.Forty-four APP positive mice were randomly divided into 2 groups (n =10 each):sevoflurane group (group AS,n =28) and control group (group AC,n =16).Forty-four APP negative mice were randomly divided into 2 groups:sevoflurane group (group S,n =28) and control group (group C,n =16).Animals in groups S and AS inhaled 3％ sevoflurane for 4 h.While in groups C and AC,animals inhaled pure oxygen for 4 h.Morris water maze was performed 24 h after sevoflurane or pure oxygen inhalation.The phosphorylation of tau at Ser262 and Ser396 was detected by Western blot on 1 day after pure oxygen inhalation (T1) in groups AC and C,and on 1,3 and 7 days after sevoflurane inhalation in groups AS and S.Results Compared with group C,the escape latency was significantly prolonged and the duration of staying at the original platform quadrant was shortened in groups S and AC,and the phosphorylation of tau at Ser262 in group S and phosphorylation of tau at Ser262 and Ser396 in group AS were increased (P ＜0.05).Compared with group S,the escape latency was significantly prolonged,the duration of staying at the original platform quadrant was shortened and the phosphorylation of tau at Ser262 and Ser396 was increased in group AS (P ＜ 0.05).Compared with group AC,the escape latency was significantly prolonged,the duration of staying at the original platform quadrant was shortened and the phosphorylation of tau at Ser262 and Ser396 was increased in group AS (P ＜ 0.05).Conclusion Sevoflurane anesthesia can aggravate the impairment of cognitive function in APP positive mice and the increase in the phosphorylation of tau at Ser262 and Ser396 is involved in the mechanism.

Objective To compare and analyze the characteristics of intensity-modulated arc therapy (IMAT) versus fixed-gantry intensity-modulated radiotherapy (IMRT) in the treatment of cervical esophageal cancer.Methods Ten patients treated in our radiotherapy center were selected for this study.Based on the identical CT and planning target volume (PTV), two IMAT plans were generated with Eclipse ver8.6 planning system.IMAT1 consisting of a single 359.8° rotation, and IMAT2 consisting of two coplanar 359.8° rotations.PTV were prescribed to 60 Gy in 30 fractions.Planning objectives for PTV,corresponding with the IMRT plans, were V98 larger than 97% and V110 no more than 15%.The maximum dose of spinal-cord was constrained below 45 Gy.One-way ANOVA were applied to dose-volume values for PTV and OAR from DVH.Results There were no significant differences between IMRT and IMAT in PTV D98, V98, CI or total-lung V5, V10, V30, V40, V50 and mean lung dose (all P > 0.05).However, the differences were significant in terms of D2, V110 and HI of PTV, V20 of the total-lung (all P<0.05).On the MU,IMRT = 1174.8 MU,IMAT1 =709.7 MU,and IMAT2 =803.8 MU (F =39.25,P =0.000).On the treatment time,IMRT= 14.9 min,IMAT1 = 1.9 min, and IMAT2 =2.66 min (F=45.14,P=0.000).Conclusions IMAT is equal to IMRT in dosimetric evaluation.Due to much less MU and delivery time,IMAT is an ideal technique in treating patients by reducing the uncomfortable influences which could effect the treatment.However, IMAT1 is slightly inferior to IMAT2.