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The dynamic coupling of stent degradation and vessel remodeling can influence not only the structural morphology and material property of stent and vessel, but also the development of in-stent restenosis. The research achievements of biomechanical modelling and analysis of stent degradation and vessel remodeling were reviewed; several noteworthy research perspectives were addressed, a stent-vessel coupling model was developed based on stent damage function and vessel growth function, and then concepts of matching ratio and risk factor were established so as to evaluate the treatment effect of stent intervention, which may lay the scientific foundation for the structure design, mechanical analysis and clinical application of biodegradable stent.
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Humans , Biomechanical Phenomena , Constriction, Pathologic , StentsABSTRACT
Objective:To establish a method based on the iPLEX analysis of MassARRAY mass spectrometry platform to detect multiplex genetic mutations among Chinese lung cancer patients. Methods:We reviewed the related literature and data of lung cancer treatments. We also determined 99 mutation hot spots in 13 target genes, namely, EGFR, KRAS, ALK, FGFR1, FGFR2, FGFR3, PIK3CA, BRAF, PTEN, MET, ERBB2, AKT1, and STK11, which are closely related to the pathogenesis, drug resistance, and metastasis of lung cancer and are associated with relevant transduction pathways. A total of 297 primers comprising 99 paired forward and reverse amplification primers and 99 matched extension primers were designed by using Assay Design in accordance with the mutation label and format requirements of the MassARRAY platform. The detection method was established by analyzing eight cell lines and six lung cancer specimens;the proposed method was then validated through comparisons with a LungCarta kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases. Results:The proposed method could detect multiplex genetic mutations in the lung cancer cell lines, and this finding is consistent with that observed using previously reported methods. The proposed method could also detect such mutations in clinical lung cancer specimens;this result is also consistent with that observed by using the LungCarta kit. However, an FGFR2 mutation was detected only by using the proposed method. The measured sensitivity and specificity were 100%and 96.3%, respectively. Conclusion:The proposed MassARRAY technology-based method could detect multiplex genetic mutations among Chinese lung cancer patients. Indeed, the proposed method can be potentially applied to detect mutations in cancer cells.
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AIM:To explore the effect of extracellular signal-regulated kinase 1/2 ( ERK1/2) on the vascular adventitial remodeling in a hypertension rat model .METHODS:The rats were randomly divided into control group , mini-pump infusion of saline group and mini-pump infusion of angiotensin II ( Ang II) group as the hypertension model .The sys-tolic pressure and vascular morphology of the rats were examined .Adventitial fibroblasts were treated with Ang II , PD98059 ( ERK1/2 inhibitor) and Ang II+PD98059.The catalase ( CAT) expression in the cells was detected by Western blotting . RESULTS:Compared with control group and mini-pump infusion of saline group , the systolic pressure and carotid media thickness (stained by HE) in mini-pump infusion of Ang II group were significantly increased (P<0.01).Meanwhile, ar-tery morphology in mini-pump infusion of Ang II group had obviously changed with a significant occurrence of pathological vascular remodeling .The result of Western blotting showed that the expression of CAT in the adventitial fibroblasts treated with Ang II+PD98059 was much higher than that in the cells treated with Ang II alone (P<0.05), indicating that down-regulation of CAT induced by Ang II was restored by ERK 1/2 signaling pathway .CONCLUSION:Ang II down-regulates CAT through ERK1/2 pathway and promotes cell phenotype transformation , which lead to pathological vascular remodeling .
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Objective To investigate the relationship between angiotensin Ⅱ ( AngⅡ) and transformation of vascular fibroblasts phenotype .Methods Eighteen rats were randomly assigned into the untreated group , mini-pump infusion of saline group and mini-pump infusion of AngⅡgroup which was used as the hypertension model .Their systolic pressure and vascular morphology were examined .The expression of catalase ( CAT ) and 4HNE was examined by immunohistochemistry .Western blotting was used to examine the expression of CAT of adventitial fibroblasts which were cultured by different incubation times and concentrations of Ang Ⅱ.Results Compared with untreated and mini-pump infusion of saline groups , the systolic pressure and carotid media thickness stained by HE of mini-pump infusion of AngⅡgroup were significantly higher (P<0.01).The results of immunohistochemistry showed that the expression of CAT ofAngⅡgroup was significantly lower than that of untreated group , however the expression of 4HNE of AngⅡgroupwas higher than that of untreated group (P<0.05).Furthermore, the results of Western blotting indicated that the effect of Ang Ⅱ on down-regulation of CAT function was in a dose and incubation time dependent manner .Conclusion AngⅡdown-regulates adventitial CAT expression and promotes fibroblasts phenotypic transformation which leads to pathological arterial vascular remodeling .
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Objective To investigate the expressions of transforming growth factor beta-1 (TGF-β1) and nuclear factor kappa B (NF-κB) in patients with chronic obstructive pulmonary disease (COPD),and to explore the mechanism of pathogenesis in COPD.Methods A total of 40 patients undergoing lung resections for pulmonary tumor were selected.Patients were divided into 2 groups according to COPD diagnostic criteria:the control group [patients without COPD,13 males,7 females,with an average age of (61.7±8.8) years] and the COPD group [patients with COPD,15 males,5 females,with an average age of (60.5 ± 9.4) years].Peripheral lung tissues from tumor lesions were detected in this study.The qualitative and quantitative expressions of NF-κB were determined by immunohistochemistry and Western blot,respectively.TGF-β31 mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR).Results The levels of TGF β1 mRNA and NF-κB protein and the NF-κB nucleus positive rate were significantly higher in the COPDgroup than in the control group [(0.42±0.11) vs.(0.34±0.13),(0.24±0.08) vs.(0.12±0.04),57.9% vs.26.7%,respectively,all P<0.05].The TGF-β31 mRNA level was positively correlated with the NF-κB protein expression in the 2 groups (r=0.497,0.618,both P<0.01).The ratio of 1 second forced expiratory volume/forced vital capacity (FEV1/ FVC) was negatively correlated with TGF-β1 mRNA level and NF-κB protein expression (r=-0.624,r=-0.659,both P <0.01) in the COPD group.Conclusions The expression levels of NF-κB and TGF-β1 are significantly increased in patients with COPD,and there is a positive correlation between TGF-β1mRNA level and NF-κB protein expression.NF-κB may participate in regulating TGF-β1 mRNA expression and in contributing to the airway remodeling,thereby in effecting pulmonary function.
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ObjectiveTo investigate the fusion sequence complexity of EML4-ALK in non-small cell lung cancer (NSCLC) patients,and the potential mutation in tyrosine kinase ( TK ) domain of ALK gene.MethodsIn routine practice,a novel echinoderm microtubule-associated protein-like4 and anaplastic lymphoma kinase (EML4-ALK) V3c variant was detected by rapid amplification of cDNA ends-polymerase chain reaction ( RACE-PCR )-sequencing technology in a patient with NSCLC.The further consecutive 39 cases( total of 40 cases)were screened by use of reverse transcription (RT)-PCR for EML4-ALK fusion.Positive PCR products were purified and cloned into T vectors,transformed into DH5a germ cells and colony picked up and sequenced for sequence complexity analysis.Tyrosine kinase domain of ALK was amplified by RT-PCR and sequenced.ResultsThree out of 40 cases had EML4-ALK fusion.One case had six novel variants of EML4-ALK co-existing,termed as V3c ( 64.6% ),V3d ( 25.0% ),V3e ( 2.1% ),V3f (4.2% ),V3g(2.1% )and V3h(2.1% ) variants,whereas without common V3a and V3b variants.In other two positive cases,one was V1 variant,another was concurrent V2,V3a and V3b variants.No mutations were detected in the TK domain of EML4-ALK in any case.ConclusionsSeveral EML-ALK variants could co-exist in a given lung cancer tissue,which suggest that the diversity and sequence complexity of EML4-ALK fusion are exist.Attentions should be paid to screen all the variants in clinic to improve the pick-up rate.
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Objective To establish a HRM assay to screen for KRAS mutations in clinical colorectal cancer patients.Methods The sensitivity of HRM was analyzed by detecting somatic mutations in exon 2,notably codons 12 and 13 of the KRAS gene in the serial plasmid mixture samples which were mixed using the different proportions mutation plasmid and wide type plasmid of KRAS.HRM analysis was performed for KRAS on DNA insolated from a panel of 60 colorectal cancer samples derived from fresh tissues.The results were compared with the direct sequencing data.Results After the PCR amplification,the mutation results could be available by performing HRM analysis in the same tube on a real time PCR machine with HRM capability.HRM detection could identify KRAS mutation in a proportion of 10% of mutation plasmid DNA.All 60 samples identified the KRAS mutation by HRM and sequencing.17 samples were positive(28.3%) by HRM for KRAS exon 2 mutations,and 15 samples were confirmed the presence of codon 12 or 13 mutations(25.0%) and the other 2 samples were wild type by sequencing.The 60 samples detected by HRM were given 100% sensitivity with 96% specificity.Conclusions HRM is a sensitive intube methodology to screen for mutations in clinical samples.HRM will enable high-throughput screening to gene mutations to allow appropriate therapeutic choices for patients and accelerate research aimed at identifying novel mutations in human cancer.
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Biochemistry is one of the major courses in basic medical science.All through the construction of the course in recent years,several teaching reforms have been taken in optimizing the content,improving teaching methods,enhancing education technique and intensifying teaching group,which contributed a lot to good teaching effect.As a result,the course of biochemistry was appraised as State-class Quality Course in 2005.
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Objectives:To observe the influence of glutamine supplemented TPN on surgical patients. Methods:Thirty cases were randomly divided into two groups.One was glutamine supplemented TPN group(Gln TPN) and another group was standard TPN group (S TPN). Results:①Total lymphocyte count(TLC) was raised significantly in Gln TPN than in S TPN.②There were no differences in hepatic function,Hb and ALB between two groups.③There was no difference in recorery of intestinal function between two groups.④The patients recovered more rapidly from POF in Gln TPN group than in S TPN group. Conclusions:Glutamine supplemented TPN could increase TLC of surgical patients and remit POF more rapidly.
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To comparet the role of nitrogly-cerin with nicorandil in relieving myocardial ischemia, a critical stenosis of the left anterior descending coronary artery was produced by an ex-ternal micrometer constrictor in 18 open chest dogs. Intracoronary infusion of nitroglycerin ( 1 ?g ? kg-1 ? min-1) had two effects: decreasing large coronary artery resistance (RL) and small coronary artery resistance (Rs) and increasing coronary blood flow (CBF) in first 5 min so as to relieve myocardial ischemia; then increasing RL, decreasing CBF and increasing whole blood viscosity (?o) and hematocrit (Hct) in coronary vein after 10 min so as to worsen myocardia ischemia. However, intracoronary infusion ofnicorandil(l ?g ? kg-1 ? min-1) increased CBF and decreased Rs and reduced ?o and Hct in coronary vein. The vasodilatory effect of nico-randil was moderate but long-lasting and it improved blood supply to the ischemic region in coronary circulation.
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It is general belied that myocardial ischemia caused an increase of plasma fibrinogen(Fg),but the changes of Fg in ischemic region is not clear.In 17 open chest dogs, an external stenosis or infarction was produced by a micro-meter constrictor on left circumflex coronary artery. The changes of Fg and platelet count(PC) in coronary sinus were observed for 60 min. The results showed that acute myocardial ischemia produed a decrease in Fg when coronary artery stenosis was more than 75%; there was also a decrease in PC when stenosis was more than 90%. The reduced amplitude of PC was more than that of Fg. Histopathologic examination confirmed the presence of damanged endothelial cell, platelet adhesion and aggregation coronary thrombosis and microemboli in ischemic region It is suggested that acute myocardial ischemia lead to a decrease of Fg in the ischemic myocardium, which was associated with platelet aggregation and coronary thrombosis.