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OBJECTIVE To determine the contents of N-nitroso impurities in raw materials/formulations of propranolol， metoprolol， atenolol， esmolol and bisoprolol， and clarify the attention threshold. METHODS Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q/Orbitrap HRMS）was adopted. An ACE Excel 3 C18-AR column was used for the separation and a mixture of 0.2% formic acid solution with 0.01 mol/L ammonium acetate and methanol was employed as the mobile phase by gradient elution， at a flow rate of 0.60 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The heated electrospray ionization source was employed in the positive full mass spectra-selected ion monitoring mode. The contents of N-nitroso impurities in raw materials/formulations of 15 batches of β-blockers from 10 manufacturers were determined by this method. Discovery Studio software was applied to predict the toxicity of the impurities and estimate the attention threshold. RESULTS Among 5 kinds of β-blockers， the linear ranges of N-nitroso propranolol， N-nitroso metoprolol， N-nitroso atenolol， N-nitroso esmolol and N-nitroso bisoprolol were 1.01-503.38， 1.02-508.38， 0.97-483.63， 1.11-554.27 and 1.05-523.92 ng/mL， respectively （r＞0.999）. The limits of quantitation were 1.04， 0.25， 0.05， 0.55 and 1.05 ng/mL， and the limits of detection were 0.52， 0.08， 0.02， 0.17 and 0.52 ng/mL， respectively. RSDs of precision， reproducibility， recovery， stability and durability tests were all lower than 7.5% （n＝6 or n＝5）. Among the 15 batches of samples， except for 1 batch， N-nitroso propranolol （1.07-8.91 ng/mg）， N-nitroso metoprolol （1.43-3.37 ng/mg）， N-nitroso atenolol （1.33 ng/mg）， N-nitroso esmolol （0.19 ng/mg） and N-nitroso bisoprolol （1.27 ng/mg） were detected in all other batches. According to predictions， the above 5 impurities had varying degrees of reproductive toxicity， mutagenicity and carcinogenicity， with attention thresholds of 1.0， 0.4， 4.3， 0.2 and 46.7 ng/mg， respectively. CONCLUSIONS The established method is simple， rapid， sensitive and specific， the estimated attention thresholds are clear， which can be used for the control of N-nitroso impurities in various β-blockers.
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A new system of blood flow block for control of bleeding in abdominal operation is composed of an abdominal magnetic blocking unit, an abdominal external electromagnet unit and other non-magnetic operation instrument. The abdominal external electromagnetic unit is placed in advance in the operation bed. The abdominal magnetic blocking unit can be placed directly on the ventral of the large vessels when need to blocking the abdominal large vessels during the operation. According to the non-contact suction characteristics of magnetic materials, the two magnetic units will attract each other and compression the vessels. Using this system for vascular occlusion does not need clear exposure and without separating vessel. There is the advantage of rapid, accurate and reliable for the system.
Subject(s)
Abdomen , Blood Loss, Surgical , Electromagnetic Phenomena , Equipment Design , Surgical EquipmentABSTRACT
BACKGROUND:In recent years, many manufacturing techniques have been recently developed for soft tissue engineering scaffolds. Especialy additive manufacturing with a unique material accumulated forming principle can be feasible and reliable to manufacture the highly precise scaffolds with gradient structures and multi-materials for large soft tissue defect repairing. OBJECTIVE:To summarize scaffolds manufacturing technologies in the soft tissue engineering applications developed in recent years and to predict the direction of development. METHODS: A retrieval was performed for the literature about the manufacturing methods of soft tissue scaffolds using key words of “additive manufacturing, microfabrication, vascular tissue engineering, muscle tissue engineering, cartilage tissue engineering, stereolithography, 3D printing, biodegradable hydrogel” in English and Chinese, which were published between January 2010 and September 2013 in PubMed Database and China National Knowledge Infrastructure (CNKI) Database. RESULTS AND CONCLUSION:For large soft tissue defects repairing, structure design of the scaffolds has been shifted from a simple planar structure to a more complex three-dimensional structure, and integration of scaffold structure, materials and cels, and growth factors during the manufacturing procedure can be used to obtain the resolution of vascularization. Additive manufacturings become one of the most promising approaches for the ideal soft tissue scaffolds with gradient and complex structure and multi-materials. In particular, the hydrogel/cellcomposite scaffolds fabrication, a hot but promising approach to develop the soft tissue engineering wil be made progress by the accurate principles and processes of the hydrogel additive manufacturing combined with the introduction of living cels and growth factors.
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Objective: To enable an artificial mandible substitute to be with individualized shape in the individual patient. Methods: Rapid prototyping and surface imitating were used as the primary technology in the individualized design and manufacturing of the artificial mandible substitute. Results: The shape and size of the manufactured artificial mandibe were almost the same to those of the original natural one. Conclusion: Rapid prototyping may be used in individualized bone substitute preparation.
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Objective: To enable an artificial mandible substitute to be mostly suitable for mandibular reconstructon in individual patients. Methods: Use rapid prototypinlg and surface imitating as the primary technology for individualized design and manufacturing of the artificial mandible substitute. Results: An individualized artificial mandible substitute was designed and prepared. Conclusion: Rapid prototyping is feasible in individualized bone substitute preparation.