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.

Objective To investigate the repair effects of co-expression of the VEGF and BMP genes via an adeno-as-sociated viral vector on early steroid-induced avascular necrosis of the femoral head in rabbits. Methords To construct ani-mal model of early SANFH and screen by MRI. The SANFH animal were divided into rAAV-IRES-hrGFP(AAV-GFP), rAAV-hVEGF165-IRES-hrGFP(AAV-VEGF), rAAV-hBMP-7-IRES-hrGFP(AAV-BMP)and rAAV-hVEGF165-IRES-hBMP-7(AAV-VEGF/BMP)groups. The four group virus vectors were injected into core decompression region at the dose of 25μl/site after core decompression operation directly. Repair effects of rAAV vector on early SANFH in rabbits were evaluated by Western blot assay, HE staining, immunohistochemical staining, MRI, radionuclide bone scan, blood vessel counting detected by ink perfusion and fro-zen section, Micro-CT and biomechanical strength detection on the 12th week post-injection. Results Model success ratio was 73.33%. rAAV-hVEGF165-IRES-hBMP-7 virus vector efficiently expressed hVEGF165 and hBMP-7 genes on the 12th week after rAAV injection. hVEGF165 protein secreted in vivo promoted metabolism in core decompression region by increasing the quantity of new vessels and improving the blood supply;hBMP-7 protein secreted in vivo promoted new bone formation in core decompres-sion region by increasing bone mineral density and improving bone biomechanical strength. The AAV-VEGF/BMP group can pro-mote repair effects more effectively than AAV-VEGF group or AAV-BMP group. Conclusion The adeno-associated viral vectors co-expressing hVEGF165 and hBMP-7 can promote repair effects on early SANFH in rabbits by increasing the blood supply and strengthening the bone quality of femoral head.

Objective We evaluate if supplementary grading system can refine patient selection and accurately predict neurological outcome in BAVM. Methods We retrospectively study 221 BAVM patients who were treated micro?surgically by our hospital. The score of pre and post operation mRS and relative clinical, radiology data were collected. Two different logistic models (Spetzler-Martin, Supplementary Spetzler-Martin grading model) were constructed to com?pare the area under ROC. Results Some factors are significant different between worse outcome patients and good out?come patients:Non-hemorrhagic presentations prior surgery, AVM bigger than 3cm, diffuse shape of AVM and the elder patients. Predictive accuracy was higher for the supplementary model (ROC area, 0.91), than the Spetzler-Martin model (ROC area, 0.774). So the predictive accuracy of supplementary model was significantly better than that of the Spet?zler-Martin model (P=0.0362). Conclusions Supplementary Spetzler-Martin model can improve preoperative risk pre?diction and subgroup the patients more efficiently. When the score less than 5(including 5) in supplementary Spet?zler-Martin patients seem to have lower risk relative to surgery.

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.

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.

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.

BACKGROUND:Symptomatic treatment is the main management strategy for patients with knee osteoarthritis at early metaphase. Some previous studies have demonstrated that neuromuscular electrical stimulation can al eviate pain in knee osteoarthritis patients. To date, this effectiveness, however, stil remains controversial.
OBJECTIVE:To assess the efficacy of neuromuscular electrical stimulation on pain in patients with knee osteoarthritis.
METHODRandomized control ed trials concerning the efficacy of neuromuscular electrical stimulation in the treatment of knee osteoarthritis were identified from the Medline database conducted up to July 3, 2014. These studies were selected independently by two reviewers according to the inclusion and exclusion criteria. Meta-analysis was performed using Revman5.2 software.
RESULTS AND CONCLUSION:A total of 5 randomized control ed trials consisting of 239 participants were included. The results of the meta-analysis indicate neuromuscular electrical stimulation has no significant impact on measure of pain in knee osteoarthritis patients in comparison to the blank control group [mean difference=-0.40, 95%confidence interval (-1.34-0.54), P=0.40]. Owing to the sample limitations of our study, it is hard for us to draw a conclusion that the application of neuromuscular electrical stimulation in managing pain in patients with knee osteoarthritis is of little significance. Further work based on large-sample and high-quality randomized control ed trials is needed to determine the role of neuromuscular electrical stimulation in pain in this population.

BACKGROUND:Reconstruction of the anterior cruciate ligament has become the gold-standard treatment for an anterior cruciate ligament rupture. Despite the popularity of the procedure, there remains a considerable amount of controversies over whether an autograft or anal ograft should be used for primary anterior cruciate ligament reconstruction. OBJECTIVE:To compare the clinical outcomes of al ograft and autograft in primary anterior cruciate ligament reconstruction. METHODS:Randomized control ed trials concerning autograft versus non-irradiated al ograft for anterior cruciate ligament reconstruction were identified from the PubMed/Medline database conducted up to July 12, 2014. These studies were selected independently by two reviewers according to the inclusion and exclusion criteria. Meta-analysis was performed using Revman5.2 software. RESULTS AND CONCLUSION:A total of 6 randomized control ed trials consisting of 858 cases were included, 441 cases in autograft group and 417 cases in non-irradiated al ograft. The results of the meta-analysis indicate no significant difference between autografts and non-irradiated al ografts in overal IKDC [relative risk (RR)=1.02, 95%confidence interval (CI) (0.99 to 1.06), P=0.21], degree of laxity [mean difference (MD)=-0.13, 95%CI (-0.29 to-0.02), P=0.09], Lachman test [RR=1.04, 95%CI (0.95 to 1.13), P=0.37], pivot shift test [RR=1.00, 95%CI (0.95 to 1.05), P=0.96], one-leg hop test [RR=1.01, 95%CI (0.96 to 1.06), P=0.77], Lysholm score [MD=-0.64, 95%CI (-1.45 to 0.17), P=0.12], Tegner score [MD=0.16, 95%CI (-0.16 to 0.47), P=0.34] and rate of postoperative complications [RR=1.42, 95%CI (0.67 to 3.04), P=0.36]. Therefore, in the meta-analysis, there is no significant difference between autograft and non-irradiated al ograft in clinical outcomes. However due to the limitations of our study, further work is needed to determine this conclusion.

This study in pursuit of the synthetic technologies and structure characterization of polyacrylamide-based matrices (PAM beads) for low density lipoprotein (LDL) adsorbent and their adsorbability for LDL was intended for an experimental evidence of developing advanced matrices for LDL adsorbent. PAM beads were synthesized by inverse suspension polymerization, and their structure characterization was characterized by SEM, image analyzer and small angle X-ray scattering. The tripeptide serine-aspartic-glutamic acid (SDE) was coupled on the PAM beads to prepare the LDL adsorbents whose adsorbability for LDL was determined in vitro. The results showed that the PAM beads with the average size diameter 142.1 microm and the average pore diameter 119.8 nm could act as the matrices in accordance with the requirement of adsorbent for LDL. When the amount of acrylamide and the crosslinking agent N,N'-methylene-bis(acrylamide) was fixed, the average pore diameter decreased with the increase of the crosslinking agent content. Although the nonspecific binding of PAM beads for LDL was low, they could selectively adsorb LDL after coupling the SDE on the PAM beads.
Acrylic Resins ; chemical synthesis ; Adsorption ; Blood Component Removal ; methods ; Cross-Linking Reagents ; Hemoperfusion ; instrumentation ; methods ; Humans ; Lipoproteins, LDL ; Microspheres

OBJECTIVETo investigate the relationship between heart rate variability (HRV) and prostaglandin E2 (PGE2) in patients with renal insufficiencies.

METHODSHRV blood and 24-hour urine prostaglandin E2 (PGE2) detection were detected in the following 4 groups of people: group A was a control group comprised of 20 normal individuals; group B had 20 patients with renal disease but exhibiting normal renal function; group C contained 20 patients with renal disease and compensatory renal function; group D had 20 patients demonstrating renal insufficiencies. The indices standard deviation of all NN intervals (SDNN), index of standard deviation of the averages of NN intervals (SDANN), mean of the standard deviation of all NN intervals performed on all 5-minute segments of the entire recording (SDNNindex), square root of the mean of the sum of the squares of differences between adjacent NN intervals (rMSSD) and NN50 count divided by the total number of all NN intervals (PNN50) were used to evaluate HRV, blood and 24-hour urine were determined by specific radioimmunoassay (RIA).

RESULTSPGE2 in blood and urine and HRV exactly within 24 hours in patients with renal insufficiencies, negatively correlated with worsening damage to renal function. There was a slight or moderate correlation between blood and urine PGE2 and the SDNNindex, SDANNindex, SDNN, rMSSD and PNN50 indices (P < 0.05).

CONCLUSIONSHRV and cardiac autonomic regulatory functions are decreased in the patients with renal insufficiencies, while lower levels of PGE2 may be a related factor.

Adolescent ; Adult ; Aged ; Dinoprostone ; physiology ; Female ; Heart Rate ; physiology ; Humans ; Male ; Middle Aged ; Renal Insufficiency ; physiopathology