ObjectiveTo evaluate the effect of using Schwann-like cells derived from human umbilical cord blood mesenchymal stem cells (hUCBMSCs) as the seed cells to repair large sciatic nerve defect in rats so as to provide the experimental evidence for clinical application of hUCBMSCs. MethodsFourty-five male Sprague Dawley (SD) rats in SPF grade, weighing 200-250 g, were selected. The hUCBMSCs were harvested and cultured from umbilical cord blood using lymphocyte separating and high molecular weight hydroxyethyl starch, and then was identified. The hUCBMSCs of 3rd generation were induced to Schwann-like cells, and then was identified by chemical derivatization combined with cytokine. The acellular nerve basal membrane conduit was prepared as scaffold material by the sciatic nerve of SD rats through repeated freezing, thawing, and washing. The tissue engineered nerve was prepared after 7 days of culturing Schwann-like cells (1×107 cells/mL) on the acellular nerve basal membrane conduit using the multi-point injection. The 15 mm sciatic nerve defect model was established in 30 male SD rats, which were randomly divided into 3 groups (10 rats each group). Defect was repaired with tissue engineered nerve in group A, with acellular nerve basal membrane conduit in group B, and with autologous sciatic nerve in group C. The nerve repair was evaluated through general observation, sciatic function index (SFI), nerve electrophysiology, weight of gastrocnemius muscle, and Masson staining after operation. ResultsThe hUCBMSCs showed higher expression of surface markers of mesenchymal stem cells, and Schwann-like cells showed positive expression of glia cell specific markers such as S100b, glial fibrillary acidic protein, and P75. At 8 weeks after operation, the acellular nerve basal membrane conduit had no necrosis and liquefaction, with mild adhesion, soft texture, and good continuity at nerve anastomosis site in group A; group B had similar appearance to group A; adhesion of group C was milder than that of groups A and B, with smooth anastomotic stoma and no enlargement, and the color was similar to that of normal nerve. SFI were gradually decreased, group C was significantly greater than groups A and B, group A was significantly greater than group B (P<0.05). The compound action potential could be detected in anastomotic site of 3 groups, group C was significantly greater than groups A and B, and group A was significantly greater than group B in amplitude and conduction velocity (P<0.05). Atrophy was observed in the gastrocnemius of 3 groups; wet weight's recovery rate of the gastrocnemius of group C was significantly greater than that of groups A and B, and group A was significantly greater than group B (P<0.05). Masson staining showed that large nerve fibers regeneration was found in group A, which had dense and neat arrangement with similar fiber diameter. The density and diameter of medullated fibers, thickness of myelinated axon, and axon diameter of group C were significantly greater than those of groups A and B, and group A was significantly greater than group B (P<0.05). ConclusionTissue engineered nerves from hUCBMSCs-derived Schwann-like cells can effectively repair large defects of the sciatic nerve. hUCBMSCs-derived Schwann-like cells can be used as a source of seed cells in nerve tissue engineering.
The resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been brought into focus. COX-2 signal pathway was found to be closely related to EGFR signal pathway by recent researches, and there has been a growing interest to focus the researches on whether COX-2 pathway inhibition improves the efficacy of EGFR-TKIs in treating advanced NSCLC. In this review, we will illustrate recent advances of combined inhibition of EGFR and COX-2 signal pathways in NSCLC therapy.
ObjectiveTo systemically evaluate the efficacy and safety of cyclooxygenase-2 (COX-2) signal pathway inhibition in treating advanced non-small cell lung cancer (NSCLC). MethodsA systematic literature search in PubMed, EMbase, Cochrane Library, ASCO databases, CNKI and Wanfang database was conducted to identify relevant randomized controlled trials (RCTs) from the time of database establishment to June 2015. RCTs of COX-2 inhibitors treating advanced NSCLC were included. We assessed the methodology quality of the included studies by using Jadad's scale, and performed this meta-analysis by using stata12.0 software. ResultsTwelve RCTs involving three different COX-2 inhibitors with a total of 1 828 patients were identified including 8 studies of high quality and 4 studies of low quality. We found that COX-2 signal pathway inhibition could significantly increase overall response rate at RR=1.27 with 95%CI1.10 to 1.46 (P=0.001). While our present data could not confirm the efficacy of COX-2 inhibitors in improving progression-free survival (PFS) at HR=0.93 with 95%CI0.81 to 1.08 (P=0.334), overall survival (OS) at HR=0.95 with 95%CI0.84 to 1.08 (P=0.461), or one-year survival rate at RR=1.08 with 95%CI0.90 to 1.24 (P=0.29). As for toxicities, only increased risk of thrombocytopenia at RR=1.28 with 95%CI 1.03 to 1.85 (P=0.03) was observed in the patients treated with COX-2 inhibitors. ConclusionCOX-2 signal pathway inhibition is effective in improving the overall response rate of the patients with advanced NSCLC, and is well tolerated. Whether COX-2 signal pathway inhibition is effective in improving long-term survival of the patients with advanced NSCLC still needs to be confirmed via further clinical trials.
【Abstract】Objective To explore the differential diagnostic value of major fibrinolytic parameters in pleural fluid. Methods Tissue-type plasminogen activator( t-PA) and plasminogen activator inhibitor-1( PAI-1) in pleural fluid at the first thoracentesis were measured with ELISA and D-dimer was measured with immunoturbidimetry. Results Eighty-four patients with pleural effusion were enrolled, among which 40 with malignant effusion, 33 with infectious effusion and 11 with transudative effusion. t-PA level was higher in malignant and transudative pleural fluid than that in infectious pleural fluid[ ( 52. 49 ±31. 46) ng /mL and ( 58. 12 ±23. 14) ng /mL vs ( 37. 39 ±22. 44) ng /mL, P lt; 0. 05] , but was not statistically different between malignant pleural fluid and transudative ( P gt; 0. 05) . PAI-1 level was higher in malignant and infectious pleural fluid than that in transudative [ ( 164. 86 ±150. 22) ng/mL and ( 232. 42 ±175. 77) ng/mL vs ( 46. 38 ±16. 13) ng/mL, P lt; 0. 01] , but was not statistically different between malignant and infectious pleural fluid( P gt;0. 05) . D-dimer levels in the three types of pleural fluid were significantly different, which was ( 23. 66 ±25. 18) mg/L, ( 6. 36 ±10. 87) mg/L and ( 66. 90 ±42. 17) mg/L in malignant, transudative and infectious pleural fluid, respectively. As single-item detection for malignant pleural fluid, the cutoff of t-PA was gt; 38. 7 ng/mL( area under ROC curve was 64. 0 ) , with sensitivity of 60. 0% , specificity of 63. 6%, positive predictive value of 66. 7%, negative predictive value of 56. 8% and accuracy of 61. 6% .The cutoff of D-dimer was lt; 27. 0 mg/L( area under ROC curve was 85. 5) , with sensitivity of 84. 8% ,specificity of 72. 5% , positive predictive value of 85. 3% , negative predictive value of 71. 8% and accuracy of78.1%. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of combined examination( t-PA + D-dimer) were 92. 5% , 60. 6% , 74. 0% , 87. 0% , 78. 1% , respectively.Conclusions The t-PA, PAI-1 and D-dimer levels are significantly different in the three types of pleural fluid. The detection of fibrinolytic parameters in pleural fluid, especially the value of D-dimer,may be helpful in the differential diagnosis of pleural effusion.
ObjectiveTo systematically assess the efficacy and safety of percutaneous access and surgical cutdown in transfemoral transcatheter aortic valve implantation (TF-TAVI).MethodsWe searched databases including the Cochrane Library, PubMed, OVID, Embase, China National Knowledge Internet and Wanfang Database to collect randomized or non-randomized controlled trials comparing percutaneous access (PC group, the trial/exposure group) with surgical cutdown (SC group, the control group) in TF-TAVI between January 2002 and October 2017. The quality evaluation and data extraction were carried out by 2 reviewers independently. The Meta-analysis was performed using RevMan 5.3.5 software.ResultsA total of 11 literatures involving 4 893 aortic valve stenosis patients treated by TF-TAVI (2 877 patients in PC group and 2 016 patients in SC group) were included in this Meta-analysis. There was no significant difference between PC and SC group in terms of major vascular complications [odds ratio (OR)=0.86, 95% confidence interval (CI) (0.70, 1.06), P=0.17], minor vascular complications [OR=1.43, 95%CI (0.87, 2.37), P=0.16], major bleeding [OR=1.02, 95%CI (0.55, 1.90), P=0.94], minor bleeding [OR=0.90, 95%CI (0.51, 1.61), P=0.73] and all-cause mortality within 30 days [OR=1.03, 95%CI (0.76, 1.40), P=0.85]. As for the length of stay after TAVI, there was significant difference between the two groups [standard mean difference=–0.32, 95%CI (–0.52, –0.12), P=0.002].ConclusionPercutaneous access is as effective and safe as surgical cutdown in TF-TAVI, meanwhile leading to shorter length of stay after TAVI.
ObjectiveTo compare the efficacy and safety of Venus A-Valve and other overseas devices in transcatheter aortic valve replacement (TAVR) for patients with severe aortic stenosis (AS).MethodsWe retrospectively analyzed the baseline characteristics, procedural details, and postprocedural outcomes of severe AS patients who underwent TAVR with Venus A-Valve or overseas devices between April 2012 and January 2019 in West China Hospital of Sichuan University.ResultsA total of 342 AS patients undergoing TAVR were finally included, 238 with Venus A-Valve and the other 104 with overseas devices (43 with CoreValve, 33 with Lotus, 21 with SAPIEN XT, and 7 with SAPIEN 3). Baseline characteristics were comparable between the two groups, and the proportion of patients with bicuspid aortic valve was around 50% in both groups. After successful valve implantation, all patients’ hemodynamics were significantly improved, with the median of maximum velocity decreased to 2.30 m/s (inter-quartile range: 0.60 m/s) and 2.50 m/s (inter-quartile range: 0.62 m/s), respectively (P=0.003). Postprocedural 30-day and 1-year all cause mortalities were similar (30-day: 5.9% vs. 1.9%, P=0.086; 1-year: 8.4% vs. 5.8%, P=0.307), while low incidence of procedure-related complications and improved life quality were achieved in both groups.ConclusionTAVR with the domestic Venus A-Valve is feasible, safe, and can produce favorable outcomes for AS patients, and especially for Chinese TAVR population with a high prevalence of bicuspid aortic valve.
This article described the clinical diagnosis and treatment of a patient with bicuspid aortic stenosis occurring severe mitral regurgitation during transcatheter aortic valve replacement. Before transcatheter aortic valve replacement, the patient’s information about medical history, signs, evaluation of CT and echocardiography were collected. After discussion by the heart team, the trans-femoral aortic valve replacement was performed. After the valve was placed during the procedure, a severe mitral regurgitation occurred. No clear causes were found, and the patient’s hemodynamics was stable. The patient recovered well during follow-up, so surgery and other treatments were not considered. This article discussed the possible mechanism and solutions of mitral regurgitation during transcatheter aortic valve replacement, and owned certain value for similar cases to refer to.
Due to the lack of calcification of the aortic valve, it is difficult to provide effective support for the fixation of artificial valve in aortic stenosis characterized by leaflet thickening. There is a risk of postoperative perivalvular leakage and secondary valve implantation, which is widely regarded as a relative contraindication for transcatheter aortic valve replacement (TAVR). But aortic valvuloplasty and self-expanding transcatheter aortic valve has showed its safety and efficacy. This paper reports a patient with bicuspid aortic valve characterized by leaflet thickening treated with TAVR. After the operation, the patient’s symptom of exertional dyspnea was significantly improved, New York Heart Association class increased to Ⅱ, no perivalvular leakage was found, and the mean transaortic pressure gradient and the maximum aortic valve velocity decreased significantly.
A 78-year-old female patient was admitted to West China Hospital of Sichuan University because of “amaurosis and polypnea for 4+ years”. The examination results before admission showed that severe stenosis of aortic valve, bicuspid aortic valve malformation, severe horizontal heart with 61.54° aortic angle. The preoperative evaluation of the patient indicated that the Society of Thoracic Surgeons score was 17.9%, which was high risk for surgery. After discussion by the heart team, the aortic stenosis was finally relieved by transcatheter aortic valve replacement. The operation was successfully completed by using the method of pulling and releasing the device with the same side basket. One month follow-up showed that the patient’s condition was stable and no complications occurred. This case aims to provide a reference for the treatment of horizontal heart with aortic stenosis. In the future, it is hoped that through continuous clinical practice, such patients will be provided with a safer and more efficient treatment plan.