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Objective To explore the cooperative effect from β-propensity of amyloidogenic peptides on amyloid nucleation and its related products. Methods Based on a coarse-grained model for amyloidogenic peptides containing two states ( a soluble state and a β-sheet-forming state), with the consideration of two kinds of cooperative effects on β-propensity of peptides ( inhibiting and promoting the conformational conversion of peptides), the regulation of cooperative effects from amyloidogenic peptides on amyloid nucleation was analyzed through Monte Carlo simulations. Results In the case of the cooperative effect inhibiting the conformational conversion of peptides, amyloid nucleation occurred only within a certain interval of the peptide concentration, as well as inside the oligomers with certain sizes. Besides, the coexistence of on-pathway and off-pathway oligomers was observed. In the case of the cooperative effect promoting the conformational conversion of peptides, the β-sheet protofibril could be observed at physiological concentration as low as 4 μmol / L. Conclusions In this study, a more realistic coarse-grained model for amyloidogenic peptides was developed by introducing the cooperative effects of local concentration on β-propensity of amyloidogenic peptides, with observation of some intriguing phenomena not reported in previous simulations. The research findings not only improve current understandings about the mechanism of amyloid formation, but also provide theoretic references for the therapeutic strategies for curing neurodegenerative diseases
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Objectives To assess the clinical outcomes,the technical characteristics of percutaneus endoscopic interlaminar decompression for lumbar lateral recess stenosis in elderly patients.Methods From May 2014 to June 2015,76 elderly patients with lumber lateral recess stenosis were accepted percutaneus endoscopic interlaminar decompression,including 48 males and 28 females aged from 60-91 years old (average,71.7:8.8 years).There were 40 patients with stenosis in L45,29 patients with stenosis in L5S1 and 7 patients with stenosis in L4.5 and L5S1.Back and leg pain were assessed by visual analogue scale (VAS).The influence of pain was evaluated by Oswestry disability index (ODI).The change of spinal canal was assessed by lateral recess angle.The MacNab criteria was evaluated at last follow-up.Results All of the 76 operations had been completed successfully with an average operation time of 64.3±23.9 min (range,56-98 min).An average follow-up time was 31.5 months (range,24-36months).There was no operative segment errors and nerve root tear during operation.Dural sac tear in 1 case,2 cases of nerve root injury and 1 case of postoperative kakesthesia,transient seizures after anesthesia occurred in 1 case and 1 case had postoperative delirium.There were significances in lumbocrural pain scores,leg pain scores and ODI scores between preoperation and postoperative 1,3,6,12 month and last follow-up (P＜0.05).In the MacNab last follow-up,the fineness rate was 92.1％,including 52 cases of excellence,18 cases of good,and 6 cases of fair.The latera recess angle between preoperation and postoperation was significantly different.During follow-up period,there were 3 cases developed into lumbar instability.No recurrence,discitis and leakage of cerebrospinal fluid were found,delayed incision healing was found in 1 case.Conclusions Percutaneus endoscopic interlaminar decompression for lumbar lateral recess stenosis in elderly patients is a safe,effective and minimally invasive method of operation with the characteristics of precise decompression of bone stenosis,sufficient resection of ligamentum flavum to decompress soft stenosis,small effect on spinal stability and low complications.
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Objective To evaluate the clinical efficacy of anterior single segmental decompression and instrumentation through Endoring self-support retractor-assisted minimally invasive small incision approach in the treatment of Denis type B thoracolumbar burst fractures.Methods A retrospective case series study was made on 26 cases (14 males and 12 females,mean age of 48.5 years) of Denis type B thoracolumbar burst fractures treated by anterior single segmental decompression and instrumentation through Endoring self-support retractor-assisted minimally invasive small incision approach from January 2007 to June 2009.Age was 18-68 years (mean,48.5 years).The fractured vertebrae included T1 in three cases,L1 in 18 and L2 in five.The neurological status was Grade C in eight cases,Grade D in 12 cases and Grade E in six cases according to American Spinal Injury Association (ASIA) classification.The operation duration,blood loss and incision length were recorded.The neurological function,lower back pain were evaluated by visual analogue score (VAS),correction of kyphosis and restoration of the fractured vertebral body height followed and documented at 3,6 and 9 months and annually after surgery.The healing of the graft was assessed using Brantigan method based on 3-dimensional computed tomography at final follow-up.Results All patients were successfully managed with this approach.The operation duration was (214.6 ± 30.5)min,and the intraoperative blood loss was (389.7 ± 57.1) ml.The length of incision was (8.5 ± 1.3) cm.All patients were followed up for (6.3 ± 0.4) years.At final follow-up,the neurological functions of all patients with incomplete neurological deficit were improved for at least one grade.The VAS of lower back pain was improved from preoperative (7.8-± 1.6) points to (2.1 ± 0.8) points at final follow-up (P ＜ 0.05).The height of the intervertebral body was restored from preoperative (29.8 ± 5.3) mm to (35.2 ± 2.4) mm at final follow-up (P ＜ 0.05).The kyphosis was corrected from preoperative (20.4 ± 11.7) ° to (11.3 ± 5.5) ° at final follow-up (P ＜ 0.05).Bone fusion was achieved in all patients,with no looseness,breakage or displacement of internal fixation at follow-up.Conclusions Anterior single segmental decompression and instrumentation through Endoring self-support retractor-assisted minimally invasive small incision approach can reduce the surgical trauma,achieve complete spinal canal decompression,adjust kyphosis,fix segment,obtain high rate of bone graft fusion and hence is a safe and effective method with minimal invasion for Denis type B thoracolumbar burst fractures.
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Objective:To investigate the influence and related mechanisms of T7 peptide derived from tumstatin on angiogenesis in vitro.Methods:HUVECs were incubated in hypoxia chamber(37℃,1％ O2,5％ CO2,94％ N2) to simulate the hypoxic microenvironment in tumors,and grouped into:hypoxia group,hypoxia+T7 peptide (1.0 μ mol/L) group,and hypoxia+T7 peptide(2.0μ mol/L) group.The tube formation assay was applied to analyze the influence of T7 peptide on angiogenesis under hypoxia.Cell Counting Kit-8 was applied to observe the cell viability.The apoptosis rate was detected with Annexin V-FITC,and the expression levels of pro-apoptotic protein BAX and anti-apoptotic protein Bcl-2 were observed with western blot.Immunofluorescence and western blot were used to detect the expression of VE-cadherin.Results:Under hypoxic condition,T7 peptide significantly inhibited capillary-like tube formation (P＜0.05),inhibited ECs viability(P＜0.05),and increased the ECs apoptosis rate in vitro;T7 peptide resulted in the downregulation of anti-apoptotic protein Bcl-2 (P＜0.01)and upregulation of pro-apoptotic protein BAX(P＜0.05);the expression of VE-cadherin was downregulated by T7 peptide significantly(P＜0.05).Conclusions:T7 peptide could execute its anti-angiogenic activity via inhibition of ECs viability,induction of ECs apoptosis rate,and downregulation of VE-cadherin expression.
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Objective:The aim of this study was to detect the P2X7 receptor (P2X7R) protein expression in pancreatic carcinoma and to analyze its association with clinicopathology features of pancreatic carcinoma.And furtherly to explore the effects and underlying mechanisms of P2X7R on invasion and migration of PANC-1 cell line.Methods:P2X7R expression was determined by immunohistochemistry in specimens of primary cancer and adjacent noncancerous tissues respectively,and analyzed the relationship between P2X7R expression and clinicopathology features of pancreatic carcinoma.The transwell assay and wound healing assay were used for investigating cell invasion and migration ability of PANC-1,and western blotting was performed to measure the expresions of MMP2 and MMP9.Results:P2X7R protein was highly expressed in both PANC-1 cell line and tumor tissue,and associated positively with the histological differentiation and lymph node staging.The active P2X7R could increase the cell migration and invasion ability of PANC-1 cell line through up-regulated MMP2 and MMP9.Conclusions:The overexpression of P2X7R plays crucial roles in the migration and invasion of pancreatic carcinoma,and may represent a novel molecular target in pancreatic carcinoma therapy.