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CN113270140A - Clinical accurate application virtual simulation experiment system of fluvoxamine based on CYP2D6 genotype - Google Patents

Clinical accurate application virtual simulation experiment system of fluvoxamine based on CYP2D6 genotype Download PDF

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CN113270140A
CN113270140A CN202110462167.XA CN202110462167A CN113270140A CN 113270140 A CN113270140 A CN 113270140A CN 202110462167 A CN202110462167 A CN 202110462167A CN 113270140 A CN113270140 A CN 113270140A
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钱建畅
胡国新
蔡剑平
陈冰冰
高楠勇
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Wenzhou Medical University
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Abstract

本发明公开了一种以CYP2D6基因型为依据的氟伏沙明临床精准应用虚拟仿真实验平台,该平台以临床问题为导向,搭建实验室研究和药学服务的完整知识体系,培养学生对精准用药的理解,具体的,该项目按照特殊人群用药监护、药酶基因检测、代谢型判定、寻找指南、制定个体化给药方案的思路来指导学生理解掌握基因测序和分析。The invention discloses a virtual simulation experiment platform for the precise clinical application of fluvoxamine based on CYP2D6 genotype. The platform is guided by clinical problems, builds a complete knowledge system for laboratory research and pharmaceutical services, and cultivates students' understanding of precise drug use. Specifically, this project guides students to understand and master gene sequencing and analysis according to the ideas of drug monitoring for special populations, drug enzyme gene detection, metabolotype determination, finding guidelines, and formulating individualized drug regimens.

Description

Clinical accurate application virtual simulation experiment system of fluvoxamine based on CYP2D6 genotype
Technical Field
The invention belongs to the field of medical education, and particularly relates to a virtual simulation experiment system for accurately applying a compound (fluvoxamine) shown in a formula (I) to clinic based on CYP2D6 genotype.
Figure BDA0003042760170000011
Background
Cytochrome P450(CYP) is an important enzyme system for human body to metabolize exogenous substances (such as medicines, poisons and the like), and mainly catalyzes the oxidation reaction of a substrate. Among them, CYP2D6 accounts for only 2% of liver microsomes, but participates in metabolizing 20% of clinical drugs, and is a major metabolizing enzyme of fluvoxamine. However, CYP2D6 has gene polymorphism, so that the activity difference is obvious, the metabolism of fluvoxamine is also different, and different clinical drug curative effects can be caused. Therefore, the genotype of the patient is detected, and the possible drug metabolism types of the drug user are prompted according to the association between the CYP2D6 genotype and the metabolism types, so that the clinical significance for guiding the accurate and reasonable drug use is achieved.
The precise fluvoxamine administration has a wide knowledge range, comprises clinical medicine, genetics, molecular biology, pharmacology and the like, and the integrated teaching difficulty of the project is high when the series of problems that the practical teaching cannot directly aim at the class time required by a whole set of teaching of patient research development, laboratory gene detection development and clinical pharmaceutical service development, and a teacher with a precise administration knowledge system is scarce are considered. Therefore, the applicant breaks through the limitations of traditional experimental space, time and conditions, introduces a virtual simulation technology, develops the virtual teaching to guide students to know the related contents of medication education, deepens the understanding of the students on pharmacogenomics and pharmacokinetic theories and develops a formulation strategy for mastering an individualized administration scheme. Not only solves the difficult problems of some teaching levels, but also cultivates the comprehensive ability of students.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a clinical accurate application virtual simulation experiment system of fluvoxamine based on CYP2D6 genotype, the virtual simulation experiment system can provide an experiment condition capable of carrying out virtual simulation anytime and anywhere, and the requirement of students for acquiring knowledge is met to the greatest extent under the condition that the experiment is carried out without any line, so that the students can understand theoretical knowledge more thoroughly.
In order to solve the technical problems, the invention provides the following scheme:
a clinical accurate application virtual simulation experiment system of fluvoxamine based on CYP2D6 genotype comprises:
the device comprises an experiment target module, an experiment principle module, a laboratory and instrument display module, a drug-induced liver injury differential diagnosis module and a CYP2D6 gene sequencing and genotyping module;
the drug-induced liver damage differential diagnosis module is used for guiding students to learn the basic concept and diagnosis and treatment process of drug-induced liver damage caused by fluvoxamine, and checking the learning content in the form of practice problems;
the CYP2D6 gene sequencing and genotyping module is used for guiding students to learn the basic principle and the operation flow of CYP2D6 gene sequencing and genotyping, and checking the learning content in the form of practice problems;
the clinical administration module of the fluvoxamine is used for guiding students to learn the adjustment of the administration dosage of the fluvoxamine.
According to the invention, a virtual simulation experiment system is applied to the clinical precision of fluvoxamine based on the CYP2D6 genotype, a real case of drug-induced liver injury caused by the fluvoxamine is taken as a background, a virtual scene of a consulting room is established, the fact that the virtual patient has adverse reactions during drug treatment is found through simulation, a peripheral blood sample is collected, a human body data display result is fitted, and the whole scene of a precise drug administration scheme is implemented. The virtual simulation experiment system uses the technologies of virtual reality, multimedia, man-machine interaction and the like, according to the principles of 'virtual-real combination' and 'virtual-auxiliary-real', virtual simulation software is constructed, a cloud platform is constructed, the consulting room scene and the laboratory research are simulated and connected in series, and clear story guidance and problems are constructed.
Preferably, the learning of the diagnosis and treatment process of the drug-induced liver injury is realized by clinical diagnosis and detection of a virtual patient.
Preferably, the diagnosis and treatment process of the drug-induced liver injury comprises online inquiry of a virtual patient, presentation of a clinical diagnostic book and a detection report to simulate a real scene, provision of corresponding examination items according to the guidelines of the drug-induced liver injury by a virtual experiment system, and interpretation of the corresponding report.
The CYP2D6 gene sequencing and genotyping module simulates an experimental operation part of a student, informs the student of the specific content related to the part in a flow chart form, decomposes and explains each step in a video or other form before operation, strengthens operation principles and reagents for the student to ensure that the operation process is clear, and is assisted with practice questions to examine corresponding experimental content.
Preferably, the CYP2D6 gene sequencing and genotyping module comprises: the procedures of DNA extraction, CYP2D6 amplification, PCR purification, gene sequencing and the like are carried out in an on-line experimental manner.
Preferably, all steps of the online experiment are performed under the guidance of an operation chart and animation, so that the online operation steps are virtually restored as far as possible.
Preferably, in the case of performing the on-line test, the explanation and interpretation of the experimental principle, the experimental result, and the like are performed with animation and video.
Preferably, the dose of fluvoxamine administered is related to the patient's metabolic enzyme CYP2D6 genotype.
Preferably, the virtual simulation experiment system further comprises an experiment purpose module, an experiment principle module and a laboratory and instrument display module;
the experiment objective module provides the students with the three aspects of knowledge, emotion, ability and the like of the learning experiment, and clearly informs the students of the key points and difficult points of learning;
the experiment principle module provides core knowledge for students to learn the virtual project;
the laboratory and instrument display module enables students to observe laboratory instruments and various reagents at a first visual angle, and corresponding detailed information is acquired by moving and suspending a mouse on the instruments or the reagents.
The invention has the advantages that: the virtual simulation system takes a clinical example as a primer, takes a patient who has severe adverse reactions after taking fluvoxamine, then performs inquiry examination to adjust the drug dosage, vividly presents the process in front of the student in the form of animation, and is assisted with animation images such as experimental operation, experimental principles and the like, so that field experimental teaching is expanded and extended, and the student can more easily understand corresponding knowledge points. The virtual platform uses online-offline combination teaching as a principle to detect the key steps of the experiment through corresponding practice problems, so that students can know the learning effect of the students in time, and meanwhile, teachers can find the weak points of student learning through the platform, and can help the students to consolidate related knowledge better.
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Fig. 1 is a schematic diagram of "clinical precise application of fluvoxamine in virtual simulation experiment based on CYP2D6 genotype" combining online virtual simulation and offline experiment operation in a virtual-real combined manner.
FIG. 2 is a technical construction diagram of experimental teaching project of "clinical accurate application of virtual simulation experiment of fluvoxamine based on CYP2D6 genotype".
Detailed Description
The principles and features of the present invention are described below in conjunction with the following drawings, which are set forth to illustrate, but are not to be construed as limiting the present invention.
As shown in figure 1, the invention combines online virtual simulation with offline experimental operation, and takes clinical cases as background, patients have serious liver injury after taking fluvoxamine, and the problem of how to adjust the dose of the adverse reaction drug is derived, students are guided to discover the main metabolic enzyme CYP2D6 of the drug from the perspective of pharmacokinetics, and then the steps of blood sampling, DNA extraction, PCR, sequencing and the like are carried out in an online virtual experiment mode, and meanwhile, the online operation PCR method is assisted to detect the experiment of CYP2D6 gene, so that the cases are analyzed and a solution is given. In the on-line operation process, practice problems are set to carry out testing to detect the learning effect and provide reference for off-line explanation, the on-line experiment indicates off-line operation, and the off-line operation consolidates the on-line experiment to realize mutual promotion of teaching and learning.
As shown in fig. 2, the platform for supporting project operation and the framework for project operation are divided into 5 layers, which are a data layer, a support layer, a general service layer, a simulation layer and an application layer from bottom to top, each layer providing services for the upper layer until the construction of a specific virtual experiment teaching environment is completed, and finally, an experiment teaching application is developed.
The data layer relates to various types of virtual experiment components and data, and therefore a basic component library, an experiment course library, a typical experiment library, a standard answer library, a rule library, experiment data, user information and the like of a virtual experiment are respectively arranged to store and manage corresponding data.
The supporting layer is a core framework of the virtual experiment platform and a foundation for normal operation of projects and is responsible for operation, maintenance and management of the whole basic system. The system comprises several functional subsystems such as security management, service container, data management, resource management and monitoring, domain management, inter-domain information service and the like.
The universal service layer can provide some universal supporting components for providing a virtual experiment teaching environment, so that a user can complete a virtual simulation experiment in the virtual experiment environment quickly, the universal service comprises experiment teaching affair management, experiment teaching management, theoretical knowledge learning, experiment resource management, intelligent guidance, interactive communication, automatic correction of experiment results, experiment report management, teaching effect evaluation, project opening and sharing and the like, and meanwhile, a corresponding integrated interface tool is provided, so that the platform can conveniently integrate virtual experiment software of a third party into unified management.
The simulation layer mainly carries out corresponding equipment modeling, experiment scene construction, virtual instrument development and universal simulator aiming at the project, and finally provides formatted output of experiment result data for the upper layer.
The application layer finally realizes project teaching and open sharing based on all the service functions of the bottom layer, designs various typical experiment examples by utilizing various tools provided by the service layer and corresponding equipment models provided by the simulation layer, and finally realizes development and sharing of a 'Fluvoxamine clinical accurate application virtual simulation experiment' project based on the CYP2D6 genotype.

Claims (8)

1.一种以CYP2D6基因型为依据的氟伏沙明临床精准应用虚拟仿真实验系统,其特征在于,包括:1. a kind of fluvoxamine clinical accurate application virtual simulation experiment system based on CYP2D6 genotype, is characterized in that, comprises: 实验目的模块、实验原理模块、实验室与仪器展示模块、药物性肝损的鉴别诊断模块、CYP2D6基因测序与基因分型模块;Experimental purpose module, experimental principle module, laboratory and instrument display module, differential diagnosis module of drug-induced liver injury, CYP2D6 gene sequencing and genotyping module; 所述实验目的模块用于明确学习该虚拟实验系统后,所要达到的学习目的;The experimental purpose module is used to specify the learning purpose to be achieved after learning the virtual experiment system; 所述实验原理模块用于介绍该虚拟实验系统中涉及的核心技术原理,包括CYP2D6的功能、CYP2D6遗传多态性与临床意义、基因测序的基本原理、根据基因型指导临床用药的方法等;The experimental principle module is used to introduce the core technical principles involved in the virtual experimental system, including the function of CYP2D6, the genetic polymorphism and clinical significance of CYP2D6, the basic principle of gene sequencing, and the method of guiding clinical medication according to genotype, etc.; 所述药物性肝损的鉴别诊断模块用于引导学生学习氟伏沙明引起的药物性肝损的基本概念和诊治流程,并通过练习题的形式对学习内容进行考核;The differential diagnosis module for drug-induced liver damage is used to guide students to learn the basic concepts and procedures of diagnosis and treatment of drug-induced liver damage caused by fluvoxamine, and to assess the learning content in the form of practice questions; 所述的CYP2D6基因测序与基因分型模块用于引导学生学习CYP2D6基因测序和基因分型的操作流程,并通过练习题的形式对学习内容进行考核;最终应用基因测序结果获得基因分型,引导学生学习如何根据基因型指导氟伏沙明给药剂量的调整。The CYP2D6 gene sequencing and genotyping module is used to guide students to learn the operation process of CYP2D6 gene sequencing and genotyping, and to assess the learning content in the form of practice questions; finally, the gene sequencing results are used to obtain genotyping and guide Students learn how to guide fluvoxamine dose adjustment based on genotype. 2.根据权利要求1所述的以CYP2D6基因型为依据的氟伏沙明临床精准应用虚拟仿真实验系统,其特征在于,所述药物性肝损伤的诊治流程的学习通过对虚拟患者进行的临床诊断和检测来实现。2. the clinical accurate application virtual simulation experiment system of fluvoxamine based on CYP2D6 genotype according to claim 1, it is characterized in that, the study of the diagnosis and treatment process of described drug-induced liver injury is carried out by the clinical practice that virtual patient is carried out. Diagnosis and detection are implemented. 3.根据权利要求1所述的以CYP2D6基因型为依据的氟伏沙明临床精准应用虚拟仿真实验系统,其特征在于,所述药物性肝损伤的诊治流程包括对虚拟患者进行问诊,并出示临床诊断书与检测报告模拟真实场景,通过虚拟实验系统根据药物性肝损的指南开具相应的检查项目,并给出相应的报告进行解读。3. the clinical accurate application virtual simulation experiment system of fluvoxamine based on CYP2D6 genotype according to claim 1, is characterized in that, the diagnosis and treatment process of described drug-induced liver injury comprises that virtual patient is consulted, and Present the clinical diagnosis certificate and test report to simulate the real scene, and issue the corresponding inspection items according to the guidelines of drug-induced liver damage through the virtual experiment system, and give the corresponding report for interpretation. 4.根据权利要求1所述的以CYP2D6基因型为依据的氟伏沙明临床精准应用虚拟仿真实验系统,其特征在于,所述的CYP2D6基因测序与基因分型模块包括:以线上实验的方式对DNA提取、CYP2D6扩增、PCR纯化、测序等步骤进行操作。4. the virtual simulation experiment system of fluvoxamine clinical accurate application based on CYP2D6 genotype according to claim 1, is characterized in that, described CYP2D6 gene sequencing and genotyping module comprises: The steps of DNA extraction, CYP2D6 amplification, PCR purification, and sequencing were carried out. 5.根据权利要求4所述的以CYP2D6基因型为依据的氟伏沙明临床精准应用虚拟仿真实验系统,其特征在于,所述线上实验的所有步骤均在操作图、动画引导下进行,以线上虚拟尽可能还原线下操作步骤。5. the clinical accurate application virtual simulation experiment system of fluvoxamine based on CYP2D6 genotype according to claim 4, is characterized in that, all steps of described online experiment are all carried out under the guidance of operation diagram, animation, Virtually restore offline operation steps as much as possible. 6.根据权利要求4所述的以CYP2D6基因型为依据的氟伏沙明临床精准应用虚拟仿真实验系统,其特征在于,在进行线上试验时,辅以动画及视频对实验原理、实验结果等进行说明解读。6. the virtual simulation experiment system of fluvoxamine clinical accurate application based on CYP2D6 genotype according to claim 4, is characterized in that, when carrying out on-line test, is supplemented with animation and video to experiment principle, experiment result etc. to explain the interpretation. 7.根据权利要求1所述的以CYP2D6基因型为依据的氟伏沙明临床精准应用虚拟仿真实验系统,其特征在于,氟伏沙明给药剂量可由患者代谢酶CYP2D6基因型指导。7. The virtual simulation experiment system of fluvoxamine clinical precise application based on CYP2D6 genotype according to claim 1, is characterized in that, the dosage of fluvoxamine can be guided by the patient's metabolic enzyme CYP2D6 genotype. 8.根据权利要求1所述的以CYP2D6基因型为依据的氟伏沙明临床精准应用虚拟仿真实验系统,其特征在于,还包括实验目的模块、实验原理模块和实验室与仪器展示模块;8. the virtual simulation experiment system of fluvoxamine clinical accurate application based on CYP2D6 genotype according to claim 1, is characterized in that, also comprises experiment purpose module, experiment principle module and laboratory and instrument display module; 所述实验目的模块向学生提供学习本实验在知识、情感、能力等三个方面的目标,明确告知学生学习的重点与难点;The experimental objective module provides students with the objectives of the experiment in terms of knowledge, emotion, and ability, and clearly informs students of the key points and difficulties of learning; 所述实验原理模块向学生提供学习该虚拟项目所涉及的核心知识;The experimental principle module provides students with the core knowledge involved in learning the virtual project; 所述实验室与仪器展示模块使学生能以第一视角观察实验室仪器与各类试剂,通过鼠标移动和悬浮于仪器或试剂上来获取对应的详细信息。The laboratory and instrument display module enables students to observe laboratory instruments and various reagents from a first perspective, and obtain corresponding detailed information by moving and suspending the mouse on the instruments or reagents.
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