OBJECTIVE To evaluate the anti-tumor activities of WX-127-07,a new microtubule-tar-geting agent invitroand probe its molecular mechanism. METHODS The well-known microtubule-targe-ting anti-tumor drugs taxol,vincristine and anti-gout drug colchicine were used as positive controls. The anti-proliferation activity was examined in five different cell lines after treatment with WX-127-07(0.3 -300 nmol·L-1 )for 72 h by SRB assay. The cell cycle arrest profile was assayed by flow cytometry. The multiparameters of cytotoxicity,cell morphology,apoptosis and different signaling pathways related to tumorigenesis and inflammation were analyzed using the high content analysis platform. Tubulin tryptic digestion and competition inhibition assay for colchicine or vinblastine site were used to confirm the bind-ing site in microtubules at a molecular level. RESULTS All the tested compounds obviously inhibited the growth of A549,HepG2,HeLa,HLF and HUVEC cells. The lC50 values of WX-127-07 were 4.47±0.05, 5.18±0.08,4.90±0.19,4.10±0.16 and(5.04±0.08)nmol·L-1 respectively,lower than those of colchicine〔the lC50 values were 21. 17 ± 1. 22,14. 19 ± 0. 53,43. 80 ± 1. 64,145. 89 ± 10. 97 and( 27. 67 ± 1.79)nmol·L-1 ,respectively〕and those of vincristine〔the lC50 values were 16.51±0.36,16.76±0.33, 27.80±2.75,43.80±1.48 and(9.15±0.78)nmol·L-1 ,respectively〕,but were similar to or lower than those of taxol〔the lC50 values were 10. 68 ± 0. 61,12. 86 ± 0. 25,4. 81 ± 0. 61,102. 07 ± 15. 17 and( 3. 04 ± 0.12)nmol·L-1 ,respectively〕. High content multi-parameter analysis revealed that WX-127-07 induced a concentration-dependent microtubular depolymerization(P=0.0075)with the same pattern as colchicine and vincristine,but at a lower concentration. Both WX-127-07 and positive drugs could induce cell cycle arrest in A549 cells,increase nuclear membrane permeability and early signs of apoptosis in HepG2 cells,but neither cancer related pathways nor inflammation related pathways were affected. Microtubular competition inhibition assay showed that WX-127-07 inhibited the binding of colchicine with tubulin(P =0.0259). Tryptic digestion of tubulin-WX-127-07 premixture showed a similar electrophoretic band to that of tubulin-colchicine premixture. CONCLUSION WX-127-07 is a novel microtubule-depolymerizing agent with anti-proliferation activity and acting on the colchicine binding site.

Objective To identify the impact factors for community doctors with the essential medicine system in place,in support of mobilizing them and successful implementation of the essential medicine system in the community.Methods Based on the theory of ERG hierarchy of needs,the pathway analysis method was called into play to identify the three factors affecting community doctors,namely personal survival,interpersonal relations and self-development.Results Major factor of which is the interpersonal factor,with a score of 0.549,while the latter two factors do not directly affect the survival and development.The two however work on each other,and work on the interpersonal factor as well,with the impact coefficients of 0.320 and 0.402 respectively.Conclusion With the essential medicine system in place,the largest impact factor for community doctors'enthusiasm is the interpersonal one,involving the doctor-patient communications among others.This serving as the breakthrough point may improve the enthusiasm of the community doctors,paving the way for the system in the communities.

Objective To investigate the effect of Case Based Learning (CBL) method in clinical practice of internal medicine. Methods 88 clinical medicine students were divided into CBL teaching group and traditional teaching group. Traditional teaching method was introduced to traditional teaching group while CBL teaching method was carried out in the other. The test papers and questionnaires were analyzed in both groups. Result The students in CBL teaching group mastered internal medicine knowledge better than the other group. Conclusion CBL teaching mode helps improve the overall teaching quality of internal medical in clinical practice,and the interns' interest in learning and their clinical practice ability can be greatly enhanced.

Abstract： Objective To evaluate the filtration effects of various nanofiltration systems on intravenous human immunog⁃ lobulin（IVIG）in order to screen the optimal nanofiltration system. Methods Various nanofilters were used for IVIG filtration to determine the best one and then various prefilters were selected to combine with the optimal nanofilter for IVIG filtration to determine the optimal nanofiltration system. Results The tangential flow（cross flow）nanofilter showed better filtering effect than dead end（direct current）nanofilter，and nanofilter C was the best one. The effect of deep filtration prefilter was better than that of absolute filtration prefilter，and prefilter Y1 in series with nanofilter C was the optimal nanofiltration system. Conclusion The optimal nanofiltration system was determined through the effect evaluation of various nanofiltration systems filtering for IVIG.

Amyloid Neuropathies, Familial ; genetics ; Cardiomyopathies ; Humans ; Mutation

Objective To explore the chronic effects of mild and moderate iodine excess and iodine restriction on apoptosis of thyrocytes. Methods Wistar rats were exposed to 4 different doses of iodine: 4 μg/d (control), 6 μg/d (1.5 fold iodine excess), 12 μg/d (3 fold iodine excess), and 24 μg/d (6 fold iodine excess) for 1, 2, 4 and 8 months. Some rats treated for 8 months were fed with 4 μg/d iodine for another 3 months. Urinary iodine concentration was monitored by arscnic/cerium catalyzing spectrophotography. Apoptosis was determined by flow cytometry after Annexin V-FTTC staining and uhrastructure assessment under electronic microscope. Cell cycle kinetics was analyzed by flow eytometry after propidium iodine staining. Fluorescent measurement by DCFH-DA probe was used to determine the intracellular reactive oxygen species (ROS) level. Expressions of apoptic proteins were analyzed by flow cytometry and immunohistochemistry. Results Apoptotosis rate and ROS production in thyrocytes were significantly increased in 3 and 6 fold iodine excess groups after 4 months and 8 months (all P < 0.05), which was reversed with iodine restriction. 6 fold iodine exposure was proved to cause a reduction of cells in GOG1-phase (64% and 67% vs 80%, both P < 0. 05) and a concomitant accumulation in S-phase (5% and 6% vs 3%, both P <0.05) after 4 months and 8 months. Expressions of Fas, FasL and TRAIL proteins in 3 and 6 fold iodine excess groups after 8 months were increased by 2 to 4 times compared with control group and did not return to normal after iodine restriction. Bcl-2 and Bax remained constant. Positive correlations were observed among iodine amount, apoptosis rate and ROS level in 6 fold iodine excess group after 8 months (r = 0. 637-0.790, P < 0.01). Conclusion Chronic iodine excess results in thyrocyte apoptosis due probably to generation of ROS.

SAαt2,6 and SAα2,3 linked sialic acid molecules on epithelial cell membrane served as receptors for influenza virus, which axe specifically recognized by human and avian influenza viruses, respectively. The distribution of these two species of sialic acids in human respiratory tract from different anatomical sites and different age groups was investigated. The results showed that SAα2,3Gal species was prevalent in respiratory bronchiole and lung alveolar epithelium, but was infiequent in trachea, bronchus and bronchiole. On the contrary, the SAα2,6Gal species was more common in the trachea and bronchus and to a lesser degree in the alveolar epithelium. When compared the expression levels of SAα2,6Gal and α2,3Gal in the respiratory tract among different age groups, no significant difference was found. In the ex vivo H5N1 virus infection study, alveolus epithelium were found to be more susceptible to avian influenza than trachea and bronchus epithelial cells. These results suggest that the human respiratory tract, to some extent, is permissive for avian influenza viruses. The currently-observed limited human to human transmission of H5N1 virus may be associated with the different abundance of SAα2,3Gal linkages in human upper respiratory tract among individuals.

Objective To explore the effects of acupuncture and individualized occupational therapy on the rehabilitation of patients with unilateral spatial neglect ( USN ) after stroke.Methods Stroke patients with hemiplegia were evaluated by neuropsychological tests,including line bisection,a cancellation test,clock drawing,and figure and shape copying.Sixty-nine right hemispheric stroke patients identified with USN were randomly assigned to 3 groups:20 patients as a control group received conventional rehabilitation therapy ; another 22 patients as an occupational group received type-specific individualized occupational therapy combined with conventional rehabilitation therapy; the remaining 23 patients as an acupuncture combined with occupational therapy group received acupuncture in addition to both conventional rehabilitation therapy and occupational therapy.These three groups were evaluated with neuropsychological tests and the modified Barthel index (MBI) before and after treatment.Results ①MBI scores in the occupational therapy group and the combined group were significantly higher after treatment,but no significant difference was observed in the control group.②The increased MBI scores in the combined and occupational groups were higher than those in the control group.At the same time the increase in MBI scores in the combined group was significantly greater than in the occupational therapy group.③The assessment results with both line bisection and cancellation tests in all three groups were significantly different after treatment.The line bisection results in the occupational therapy group and the combined group were significantly better than in the control group.The cancellation test results in the combined group were significantly better than in the control group.Conclusion These findings show that acupuncture combined with occupational therapy can have a positive effect on neglect recovery and greatly improve the daily life of USN patients.

Objective To explore the best operation method in the patients with papillary thyroid microcarcinoma.Methods A total of 139 patients with papillary thjroid microcarcinoma were treated at our institute between Jan.2000 and Jan.2010.The data on the clinicopathological characteristics of patients and treatment were collected.Results The mean tumor size was (0.45 ± 0.24) cm.Of the 139 patients,30.2％ had multifocal tumors,19.4％ had bilateral tumors,42.4％ neck lymph node metastases.The number of eases of lymph node metastasis in level Ⅵ,Ⅱa,Ⅲ and Ⅳ was 58(41.7％),3(2.2％),10(7.9％),5(3.6％),respectively.Only one had lymph node metastasis in Level Ⅲ Microscopic extrathyroid extension was associated with neck lymph node metastases in papillary thyroid microcareinoma patients (x2 =38.39,P ＜0.001).No one developed permanent hypoparathyroidism.The median follow-up time was 103 (range,30-154) months,and local recurrence in the thyoid was diagnosed in 2 patients who underwent hemi-or subtotal thyroidectomy.Follow-up of 10 years was done in 16 cases,and the survival rate of 139 patients for 10-year was 100％.Conclusions It suggested that patients with papillary thyroid microcarcinoma has uniform clinicopathologic characteristics and the pattern of lymph node metastasis from those with papillary thyroid carcinoma.Total thyroidectomy plus level Ⅵ dissection is the optimal surgical treatment of papillary thyroid microcarcinoma.

Objective To study the value of the intervention of Nitroglycerin(NTG) on ~(99m)Tc-MIBI myocardial tomography imaging in the estimation of myocardial viability.Method According to the analysis of autologous electrocardiogram(ECG),a total of 66 patients with unstable angina(UA) was divided into group A and group B.The patients in group A were without old myocardial infarction and those of group B were with old myocardial infarction.The patients in the two groups were respectively underwent the resting ~(99m)Tc-MIBI myocardial tomography imaging and the NTG administration intervened the next day.The imaging was collected and tested by the computer.Results Of 594 myocardial segments in the 66 cases,242 segments(40.7%) in testing myocardial imaging were proved to be perfusion abnormal,while after the intervention of NTG administration,the perfusion of 114 segments(47.1%) had been improved according to the imaging.Conclusion The intervention of NTG administration on ~(99m)Tc-MIBI myocardial tomography imaging for myocardial viability is simple,safe,objective and accurate,which provides a forceful means for the post-operative evaluation and the selection of indication before the rebuilding of coronary artery of the UA patients.