Mammalian topoisomerase 1 (TOP1) is an essential enzyme for normal development. TOP1 relaxes supercoiled DNA to remove helical constraints that can otherwise hinder DNA repli-cation and transcription and thus block cell growth. Unfortunately, this exact activity can covalently trap TOP1 on the DNA that could lead to cell death or mutagenesis, a precursor for tumorigenesis. It is therefore important for cells to find a proper balance between the utilization of the TOP1 cat-alytic activity to maintain DNA topology and the risk of accumulating the toxic DNA damages due to TOP1 trapping that prevents normal cell growth. In an apparent contradiction to the negative attribute of the TOP1 activity to genome stability, the detrimental effect of the TOP1-induced DNA lesions on cell survival has made this enzyme a prime target for cancer therapies to kill fast-growing cancer cells. In addition, cumulative evidence supports a direct role of TOP1 in pro-moting transcriptional progression independent of its topoisomerase activity. The involvement of TOP1 in transcriptional regulation has recently become a focus in developing potential new treat-ments for a subtype of autism spectrum disorders. Clearly, the impact of TOP1 on human health is multifold. In this review, we will summarize our current understandings on how TOP1 contributes to human diseases and how its activity is targeted for disease treatments.

Bilingual education is an important teaching reform in universities. Since 2006,our college has enacted the attempt for bilingual teaching of pathology,and accumulated abundant experiences during the conducting of the bilingual teaching of pathology.

At present, many weak points still exist in teaching practices of medical English in medical colleges, such as lack of clear learning goals and prospects for medical English among medi-cal students, as well as the absence of systematic and practical teaching materials, as well as inappro-priate construction of teacher team for teaching practice. Therefore, corresponding modifications on teaching objectives, construction of teacher team and implementation methods for medical English are urgently needed so as to achieve effective teaching and subsequently meet the new international stan-dards for medical education.

Objective To inVestigate the effect of emodin on hyPertroPhic scar fibroblasts ( HSFs ) and exPlore the underlying mechanism. Methods HSFs were treated by emodin at final concentrations of 0,20,40,and 80 μmol·L-1, resPectiVely,in the cultural media. Forty_eight hours later,the cells were subjected to MTS assay and flow cytometry assay with annexin V and ProPidium iodide as dyeing indicators. Whole cell lysates from the cells of eVery grouP were subjected to Western blotting to measure the Protein exPression leVels of ERK1∕2,Bcl_2,Mcl_1 and RIP1. Results The cell Viability of HSFs was inhibited by emodin in a dose dePendent manner. The mortality rate of HSFs treated with emodin for 48 h at the concentrations of 40 and 80 μmol·L-1 were 28. 6%and 68. 0%,resPectiVely,which was significantly higher than that of the control grouP ( P<0.01).Pretreatmentwith Z_VAD_FMK could Partially reduce the mortality caused by emodin (P<0.05).PhosPhorylation of ERK1∕2 and the exPression of RIP1 and Mcl_1 were inhibited by emodin. Conclusion Down regulation of ERK1∕2,RIP1 and Mcl_1 by emodin may account for the inhibited Proliferation and increased cell death of HSFs.

Hospital research mainly by high-level researcher to promote,and researcher of the research initiative will determine the contribution of their research.This initiative from the start of economic regulation researcher to explain the economics-based perspective that affect high-level researcher positive factors research and put forward relevant mathematical relationship between the influencing factors and mathematical models,and scientific researcher positive regulator of a number of ways.

Objective To elucidate the effect of bioimpedance ratio in the calf (calf-RBI) for volume evaluation on hypertension in hemodialysis (HD) patients. Methods Bioimpedance in the right calf was measured by bioimpedance spectroscopy (BIS). As an index of volume status, calf-RBI was calculated as follows: calf-RBI =impedance at 200 kHz / impedance at 5 kHz. The range of age-stratified 1SD from mean calf-RBI in the healthy control was assumed as the target range for the corresponding HD patients. The dry body weight (DBW) was stepwise decreased under the guidance of calf-RBI. The changes of calf-RBI, blood pressure and antihypertensive medications were recorded and correlation analysis among indexes was performed. Results The calf-RBI showed a normal distribution in both healthy subjects and HD patients. The calf-RBI was positively correlated with age, but not with gender or BMI. Forty-two patients with (35.9%) calf-RBI beyond target range were identified in 117 HD patients. The percentage of uncontrolled hypertensive individuals was significantly higher as compared to those with calf-RBI within or below target range (59.5% vs 33.3% and 16.7%, P＜0.01). The percentage of uncontrolled hypertensive individuals and the dose of antihypertensive medications was significant improved after decreasing the DBW in the patients with calf-RBI beyond target range (74.1% vs 33.3%, P＜0.01) and defined daily dose (2.00±2.28 vs 2.49±2.47, P＜0.05 ). Conclusions The age-stratified calf-RBI may be used as a useful index for estimation of volume status, and has a good association with clinical manifestations. Recognition and correction of chronic fluid overload based on age-stratified calf-RBI is helpful in hypertension control for hemodialysis patients.

AIM: To investigate the changes of the redox status and the antioxidative capability in the tissue of malignant tumors. METHODS: The carcinoma tissues collected from 42 patients with primary cancer in digestive tract (13 cases of esophageal cancer, 14 cases of gastric cancer and 15 cases of colorectal cancer),the corresponding paratumor mucosa tissues were taken as the control samples. The content of oxidized and reduced glutathion (GSSG and GSH), oxidized and reduced coenzyme II (NADP+ and NADPH) were measured, the GSH/GSSG, NADPH/NADP+ ratios, and the GSH/GSSG, NADPH/NADP+ redox potentials were calculated according to Nernst formula. RESULTS: The levels of GSH and NADPH in cancer tissues were significantly higher than those in corresponding paratumor tissues (P0.05). CONCLUSIONS: The significant increase in GSH and NADPH contents in cancer tissues indicates a notable enhancement of its antioxidative capability compared with the corresponding paratumor tissues. Based on this changes, the redox potential in the cancer tissues has only slightly reductive shift, which may suggest an apparent oxidative stress existed in the cancer tissues.

Objective To establish a patient-derived gastric cancer xenograft( PDX) model in nude mice and to in-vestigate the application of near infrared fluorescent ( NIRF) dye IR-783 in in vivo imaging of gastric cancer xenograft mod-els.Methods Fresh human gastric cancer tissue was taken and transplanted into the subrenal capsule of nude mice to es-tablish the xenograft model.When the transplanted tumors grew,took part of the tumor tissue to do HE staining and compare the structural characteristics with the primary tumor.Another portion of the tumor was xenografted into nude mice subcutane-ously.Twenty days later,the tumor-bearing mice were injected intraperitoneally with IR-783 dye (10μM) in a dose of 100 mg/20 g.The intensity of the tumor image was monitored by optical NIRF imaging.The correction between tumor volume and fluorescence intensity was analyzed.Finally,the expression of OATP1B3 and HIF1αin the xenografted tumor tissue was detected by immunohistochemistry.Results We successfully established three patient-derived xenograft ( PDH) models of human gastric cancer.The transplanted tumor tissues maintained the histological characteristics of the primary tumor well.NIRF signal can be detec ted in subrenal capsule of the xenografted nude mice.The correlation between tumor size and fluorescence intensity in the PDX models reached higher than 98%.Strong positive expressions of HIF1αand OATP1B3 in the tumor tissues were detected.Conclusions NIRF dye IR-783 can be specifically accumulated at the tumor site,therefore, can be used to detect PDX in vivo early.The tumor targeting property may be related to the expression of OATP1B3 and HIF1α.

Aim To investigate the role of K562 cells conditioned media on redox state of human umbilical vein endothelial cells (HUVECs) and the role of buthionine sulfoxine(BSO), a selective inhibitor of ?-glutamylcysteine synthetase, on HUVECs cultured with K562 cells conditioned media. Methods Glutathione(GSH)、oxidized glutathione (GSSG)、NADP~+、NADPH concentration and the viability of HUVECs under various conditions were determinated. Results GSSG、GSH、NADP~+、NADPH concentration of HUVECs increased when HUVECs were cultured with K562 cells conditioned media. The inhibition of HUVECs growth by Bso enhanced when K562 cells conditioned media were used at the same time. Conclusion Under the effection of chronic myelogenous leukemia cells conditioned media, endothelial cells may be more sensitive to BSO.

Objective: To investigate the effect of clopidogrel on antiplatelet therapy in patients with coronary artery disease (CAD) combining chronic kidney disease (CKD) in order to provide a medication reference in clinical practice. Methods: We retrospectively investigated 423 CAD patients with coronary angiography (CAG) conifrmed diagnosis in our hospital from 2014-01 to 2014-09. According to the value of eGFR, the patients were classiifed into 2 groups:CAD+ CKD- group,n=257 patients with eGFR ≥ 90 ml/(min?1.73 m2), including 182 male and 75 female at the mean age of (60.39 ± 11.09) years, and CAD+CKD+ group,n=166 patients with eGFR < 90 ml/(min?1.73 m2), including 107 male and 59 female at the mean age of (65.80 ± 10.84) years. The patients were treated either by aspirin 0.1 g/d with clopidogrel 75 mg/d for at least 7 days, or by PCI operation with the load of aspirin 0.3g and clopidogrel 300 mg. The thrombelastography was conducted to examine and compare the inhibitory rates of ADP receptor and arachidonic acid (AA) pathway in platelet between 2 groups. Results: The inhibitory rate of platelet ADP receptor in CAD+CKD- group (64.9 ± 27.2) % was higher than that in CAD+CKD+ group (56.6 ± 27.4) %,P=0.039. Based on clinical standard of platelet’s ADP and AA inhibitory rates, in CAD+CKD- group, there were 24/257 (9.4%) of patients only insensitive to clopidogrel, in comparison with 25 (9.7%) of patients only insensitive to aspirin,P=0.99. While in CAD+CKD+ group, there were 21/166 (12.7%) of patients only insensitive to clopidogrel, in comparison with 11 (6.6%) of patients only insensitive to aspirin,P= 0.045. Conclusion: Clopidogrel has decreased effect on anti-platelet therapy in CAD patients combining with CKD, such patients have reduced sensitivity to relevant medication.