Objective To study the effects of tyrosine kinase receptor B-brain-derived neurotrophic factor (TrkB-BDNF) signal pathway on the secretion of vascular endothelial growth factor (VEGF) and matrix metalloproteinases-9(MMP-9) of neuroblastoma.Methods We used all-trans retinoic acid (ATRA) to induce the high expression of TrkB in the SH-SY5Y cell line,and then added the ectogenid BDNF to activate the TrkB-BDNF and its three downstream signal pathways.TrkB-BDNF signal pathway was inhibited by specific tyrosine kinase inhibitor K252a.The three downstream signal pathway was respectively inhibited by LY294002 (the phosphatidylinositol 3-hydroxy kinase (PI3 K) pathway inhibitor)、U73122 (the phospholipase C pathway inhibitor) 、U0126(the mitogen activated protein kinase pathway inhibitor).Enzyme linked immunosorbent assay was used to detect the concentration of VEGF and MMP-9 protein in the SY5Y cell culture supernatants.Results VEGF [(485.89 ± 109.99) pg/ml] and MMP-9 [(15.73 ± 1.72) pg/ml] protein levels in neuroblastoma cells cultured in serum-free media in the group of ATRA + BDNF were significantly higher than that of the control group and ATRA alone group(P ＜0.05).VEGF [(272.42 ±86.33) pg/ml]and MMP-9 [(5.25 ± 1.44) pg/ml] protein levels in the group of ATRA + BDNF + K252a were significantly lower than those of the ATRA + BDNF group(P ＜ 0.05) and had no significant difference compared with the control group and the ATRA alone group(P ＞0.05).VEGF [(314.12 ±24.68) pg/ml] and MMP-9 [(4.91 ± 1.08) pg/ml] protein levels in the group of ATRA + BDNF + LY294002 were significantly lower than those of the ATRA + BDNF group(P ＜ 0.05) and had no significant difference compared with the control group and the ATRA alone group(P ＞0.05).VEGF [(444.08 ±64.49) pg/ml] and MMP-9 [(13.28 ±3.38) pg/ml] protein levels in neuroblastoma cells cultured in serum-free media in the group of ATRA +BDNF + U73122 had no significant difference compared with the ATRA + BDNF group(P ＞ 0.05).VEGF [(429.97 ± 19.95) pg/ml] and MMP-9 [(13.96 ± 4.45) pg/ml] protein levels in neuroblastoma cells cultured in serum-free media in the group of ATRA + BDNF + U0126 had no significant difference compared with the ATRA + BDNF group(P ＞ 0.05).Conclusion Activation of TrkB-BDNF signal pathway can increase the synthesis and secretion of VEGF and MMP-9 in human neuroblastoma cells.TrkB-BDNF signal pathway may be through activating its downstream PI3K pathway to increase the synthesis and secretion of VEGF and MMP-9 in human neuroblastoma cells.The synthesis and secretion of VEGF and MMP-9 can be inhibited by blocking the TrkB-BDNF signal pathway with K252a or blocking its downstream signal pathway PI3 K with LY294002.

BACKGROUND:There is often space between implant and bone during immediate implantation.Whether biological membrane is needed to guide bone regeneration remains poorly understood.OBJECTIVE:To createdifferent sizes of space between femurand implantsindogs and to observe the effects of biological membrane on bone regeneration capacity of bone defects surrounding implants.DESIGN,TIME AND SETTING:A self-control animal experiment was performed at the Laboratory Animal Center,Norman Bethune College of Medicine,Jilin University and School of Stomatology,Jilin University between March and December 2005.MATERIALS:BLB hydroxyapatite-coated implant was provided by Beijing Leiden Biomaterial Co.,Ltd.,China;BME-10X collagen membrane was purchased from Fujian Better Biotechnology Co..Ltd.,China.METHODS:BLB implants were installed in the bilateral proximal femoral bone to create standard gradient bone defects with horizontal width 3 mm.vertical depth 5 mm,and horizontal lengths of 0,1,2,3,and 4 mm Bone defects on the left femur were sutured directly and those on the right femur were covered with biological membrane prior to suture.All animals were sacrificed at 3 months after surgery.Specimens containing implants were harvested to prepare tissue blocks for radiological observation.MAIN OUTCOME MEASURES:The quantity,color,and texture of newly formed bone surrounding implants were observed from the surface and profile levels.The implant-bone integration and new bone formation were also examined by soft X-ray photography.RESULTS:Grossobservation results revealed that when the horizontal length of bone defect was 3 mm or less,there was no significant differenee in bone density between the newly formed bone and the host bone no matter whether biological membrane existed or not;when the horizontal length of bone defect was 4 mm the bone density was better when biological membranes were used than not.Soft X-ray photography results revealed that when the horizontal length ofbone defect was 3 mm or less.no significant difference in bone density and bone trabecular morphology and orientating was found between newly formed bone and host bone no matter whether biological membrane was used or not;in the 4-mm-length bone defect areas.implants contacted with newly formed bone directly,but the calcified degree ofnewly formed bone was poor,bone trabecula was thin,and bone trabecular course was irregular,nevertheless,the calcified degree of newly formed bone was better under the condition of being with biological membrane than without biological membrane.CONCLUSION:Biological membrane exhibits strong capacity to promote the regeneration and repair of bone defect tissue with a horizontal length of 3 mm or less,and plays an important role in repatr of large sizes of bone detect

Objective To investigate the relationship between acute biliary pancreatitis (ABP) and anomalous pancreaticobiliary duetal union (APBDU). Methods 131 patients with ABP were enrolled to test the serum total bilirubin (TB), alanine amintransferase (ALT), aspartate amintransferase (AST), alkaline phosphates (ALP), γ-glutamyl transferase (γ-GT). All the patients received medical treatment, and then these tests were performed again. Thereafter, all the patients underwent selective surgery and intra-operative cholangiography was performed to observe the pancreaticobiliary duetal union. Results 27 patients (20.6%) with APBDU were found in 131 patients. Among them, 8 cases (29.6%) was B-P subtype (TypeⅠ), 16 cases (59.3%) was P-B subtype (TypeⅡ) , and the remaining 3 cases was mixed subtype (TypeⅢ). A significant decrease of ALT, AST, ALP, γ-GT after non-surgical treatment in both group of APBDU and NAPBDU was noted (P＜0.05). The serum levels of ALT, AST,γ-GT in APBDU patients were (71.81± 23.19) U/L, (47.85±27.87) U/L, (52.86±31.49) U/L, respectively; and in NAPBDU patients were (51.96±15.40) U/L, (40.77±16.58) U/L, (34.86±26.47) U/L. The difference was statistically significant (P＜0.05). Condusions APBDU is an important etiology of ABP.

Objective:To compare the effect of three different titanium alloy surface topographies on the biological character fibro-blasts.Methods:Three different titanium alloy Ti6Al4V surface topographies were created by machining(M),direct current electro-chemical etching(DC)and alternating current electrochemical etching(AC)respectively,and standard sized samples were prepared. The surface topographies were observed field emission scanning electron microscopy(FE-SEM).Mouse L929 fibroblasts were cultured on different surfaces.The attachment of cells was examined by acridine orange staining and observed under fluorescent microscope.The proliferation of cells was measured using MTT assay.Results:Tubles with the diamete of 5 -20 μm were observed on the surface of the sample of group DC,and more evenly distributed tubles on that of group AC.Micro-sulci were observed and no microtuble was found on the sample surface of group M.L929 cells were attached on the surface of all the samples in the 3 groups.More adhered and better strached cells were observed on AC treated surface.The proliferation of fibroblasts on AC and DC surfaces was superior to that on M treated surface and at the 3 -5 day the proliferation of fibroblasts on the AC surface was higher than that on DC treated surface.Con-clusion:AC treated surface with the micro-submicro-nano hierarchical topography of titanium alloy has a superior biocompatibility and can promote the early attachment and proliferation of the fibroblasts.

Objective To investigate the changes and the role of plasma thrombomodulin(TM),von willebrand factor (vWF) ,and coagulation status indicators in children with Henoch-Schonlein purpura(HSP).Methods The plasma concentrations of TM,vWF were measured by ELISA method and the levels of D-dimer,PT,APTT,palatelet count were measured in 56 acute SHP patients,50 recovery patients and 40 healthy controls. Results The plasma levels of TM、vWF、D-dimer、palatelet count in acute group were significantly higher than those in healthy controls group and those of recovery group ( P = 0. 000). The plasma levels of PT、APTT showed no significant difference among three groups( P ＞ 0. 05 ). The plasma levels of TM、vWF in recovery group were significantly higher than those in healthy controls group ( P ＜ 0. 05, P ＜ 0. 01 ), while the levels of D-dimer、palatelet count reduced to nomal levels(P ＞0. 05). As compared to non-renal damage group, The plasma levels of TM、vWF、 D-dimer were higher in renal damage group ( P ＜ 0. 05, P ＜ 0. 01 ), the levels of PT 、APTT、palatelet count showed no significant difference ( P ＞ 0. 05 ). Conclusion The damage of vascular endothelium and hypercoagulability play an important role in the pathogenesis of HSP. Changes of plasma TM、 vWF、palatelet count can be used as an indicator of the early lesion of renal function.

Objective:To determin the effect of PLGA microspheres loading with PTH(1 34)[PTH(1 34)/PLGA]on the differentiation of MC3T3E1 cells.Methods:MC3T3E1 cells were divided into control group,continuous or intermittent PTH(1 34)adminstration groups,PLGA microsphere group and PTH(1 34)/PLGA group.Osteogenesis differentiation was observed by alkaline phosphatase activity(ALP),alizarin red staining and RTPCR.Results:The PTH(1 34)/PLGA with 1 0 -9 mol/L final release concentration enhanced ALP activity and mineralization,increased the mRNA expression of RUNX2,ALP and VEGF.Conclusion:Controlledrelease of PTH(1 34)from PLGA microspheres can promote the osteogenesis differentiation of MC3T3E1 cells.

Neurodegenerative diseases are threating our health seriously.Inflammation plays an important role in the initiation and development of neurodegenerative diseases, and its primary characteristics are the activation of microglia and the increasing level of inflammation cytokines.This review describes the relationship between neuroinflammation and several neurodegenerative diseases, and the models in vivo and in vitro.In addition, combining with traditional Chinese medicines knowledge of encephalopathy, we summarizes pharmacological effects and mechanisms of multiple herb extracts and monomer compounds in preventing the activation of microglia and inhibiting neuroinflammation, thus, to provide the basis for gradually revealing the related rules and characteristics of treating encephalopathy by traditional Chinese medicine, and improving the accuracy of the clinical drugs, as well as developing new drugs for the prevention and control of encephalopathy.

The proliferation of tumor cells is regulated by a complex array of signaling pathways, among these signaling pathways,the programmed cell death. Autophagy and apoptosis are two types of programmed death. There are significant differences in their morphological and functional features, but they also have many links. Both apoptosis and autophagy are involved in activation,expression and regulation of a series of genes. By reviewing the research progress in recent years, this article will discuss the cellular regulation and molecular mechanisms of their related genes. Through summarizing the relationship between autophagy and apoptosis,it aims to get a better understanding of the mechanisms of autophagy and apoptosis in tumor progression,and looking at the perspectives for studies on the autophagy and apoptosis in tumor treatment.

Objective To evaluate the effect of parathyroid hormone(1-34) [PTH(1-34)] and coralline hydroxyapatite(CHA) on bone regeneration of peri-implant bone defects.Methods Two implant sites were prepared on both sides of tibia in 8 mongrel dogs.The bone defect was created along one bone wall of each implant site.Implants were implanted into the implant sites,then CHA was grafted into the bone defects.After surgery,the animals were randomly divided into two groups.PTH(1-34) (40 μg/kg) was used for subcutaneous injection to the experimental group for three consecutive days,meanwhile the same amount of saline was given to the control group.Half of the animals of each group were sacrificed after 4 weeks and 8 weeks respectively.Specimens were subjected to implant pull-out strength tests,X-ray picture and histological observation.Results The bone density of bone defects in the experimental group were higher than that in the control group.No low-density images was observed between the implants and bone at 4 weeks and 8 weeks.The maximum pull-out force value of the experimental group(199.8 N,411.5 N) was higher at 4 weeks and 8 weeks than that of the control group(100.1 N,184.5 N) (P＜0.05).The pull-out force value of the experimental group at 4 weeks and the pull-out force value of the control group at 8 weeks were similar.The new bone trabecular around CHA of experimental group was thicker at 4 weeks.Implant surface contacted to the new bone directly without fiber.CHA granules of the experimental group at 8 weeks were fewer than that of the control group.New bone tissue of the experimental group was denser.The contact area between implant surface and new bone was wider in experimental group than in the control group.Conclusions PTH(1-34) and CHA can promote bone regeneration of peri-implant bone defects,shorten the implants and bone healing cycle and improve the implants osseointegration.

Objective To explore the biological indicators of diagnosis and treatment of irritable bowel syndrome (IBS), and to explore the mechanism of action of a Chinese medicine Wuji Pill (WJW) on irritable bowel syndrome (IBS). Methods (1) Postinflammatory irritable bowel syndrome (PI-IBS) rat model was established by acetic acid plus restraint stress method . (2) The colonic motor ability of rats was evaluated by colon motility index (MI), the number of fecal particles discharged within 2 h, and the time of glass pellet discharge. (3) The formation of PI-IBS model rats and the therapeutic effect of WJW were observed. (4) The levels of calcitonin gene-related peptide (CGRP), motilin (MTL), neuropeptide Y (NPY), substance P (SP), somatostatin (SS), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK) in the brain and colon tissues of PI-IBS rats were measured by ELISA. Results (1) The rat PI-IBS model was successfully established. Compared with the normal group, the body weight of the model rats was decreased, the food intake decreased, the amount of feces increased, loose stools and amorphous soft stools appeared, voluntary movements decreased, colon motility index ( MI) significantly increased ( P ＜ 0. 05 ), the number of fecal particles discharged significantly increased ( P＜ 0. 05), and the glass pellet discharge time was significantly shortened ( P ＜ 0. 05). (2) WJW treatment for 7 days significantly improved a variety of symptoms. Compared with the normal control, the levels of CGRP, SS and VIP in the brain tissue of PI-IBS rats were significantly increased (P＜ 0. 05), and the NPY concentration was significantly decreased ( P ＜ 0. 05). However, the treatment with WJW significantly reduced CGRP, SS and VIP levels (P＜ 0. 05), and significantly increased the NPY concentration level (P ＜ 0. 05). (3) Compared with the normal control group, the levels of CCK, NPY, MTL, SS and VIP in colonic tissues of PI-IBS rats were significantly decreased (P＜ 0. 05), while WJW significantly increased the CCK and VIP levels. Conclusions WJW can be used to treat IBS by regulating the levels of various brain-gut peptides in the brain and colon tissues of IBS rats. These anomalous and adjustable brain-gut peptides may become a potential biomarker for the diagnosis and treatment of IBS.