建立基于粪便标本的幽门螺杆菌感染个体化药物根除治疗相关基因检测技术

Helicobacter pylori infection and its related diseases are very important public health issues endangering the people all over China. Due to the generally and remarkably increased antibiotic resistance to Helicobacter pylori, it becomes much more difficult to eradicate Helicobacter pylori infection by means of all kinds of empiric therapy regimens. So, the tailored therapy, which will be guided by the information from antibiotic resistance of Helicobacter pylori strains and characteristics of medicine metabolism in hosts, should be the most effective and long-lasting method to achieve excellent eradication efficacy. Depending on the gastric mucosal tissues sampling by upper endoscopy and antimicrobial sensitivity test (E test or agar dilution method) after Helicobacter pylori cultures, the traditional and classical individualized diagnosis and therapy are very hard and difficult to popularize in clinical settings. To make the tailored therapy to be widely and easily used, it is the key to establish a rapid, easy, accurate and cheap genes detection technique and to build a convenient, comfortable and non-invasive sampling method. To achieve this goal, Helicobacter pylori resistance-related genes chips based on PCR reverse dot blot hybridization technique and method of sampling from feces will be explored and used in this study. Based on new methods, the presence of Helicobacter pylori infection, the single nucleotide polymorphism information of cytochrome P450 isoenzyme 2C19 in hosts and of mutations in clarithromycin and levofloxacin resistance related genes of Helicobacter pylori strains will be simultaneously and rapidly collected and obtained, which are very helpful and important to guide the selection of antibiotics and proton pumper inhibitors to eradicate Helicobacter pylori infection appropriately. This new strategy and method will significantly improve the effectiveness of eradication therapy in contrast to conventional empiric therapy and markedly reduce the abuse of antibiotics. This study and project includes three key steps: establishment and development of microarray of related genes chip, verification and optimization of microarray and its initial application in clinical settings. Finally, the innovative procedures and kit will be established to obtain the therapy related genes information from feces samples, which will enable the tailored therapy for Helicobacter pylori infection truly, widely and easily used in clinical practice. The study has good scientific research and clinical significance and value.

幽门螺杆菌（Hp）感染及相关疾病是我国重大卫生健康问题。由于抗生素耐药率显著升高等原因，目前我国各种经验性Hp根除方案的疗效均欠佳。采用新的个体化根除治疗策略是解决这一核心问题最为有效的方法。传统的基于胃镜和Hp菌株培养的个体化诊治方法无法满足广泛临床实践的要求。建立快速、简便、准确、价廉、舒适、无侵入性的相关基因检测技术和粪便取样方法，是实现Hp感染个体化诊治在临床广泛应用的关键瓶颈问题和重要解决途径。本项目旨在利用PCR反向斑点杂交芯片技术，通过检测粪便标本，同时获得Hp现症感染、克拉霉素和左氧氟沙星耐药基因突变以及人宿主CYP2C19基因代谢型的多重信息，从而指导Hp感染个体化根除方案的药物合理选择，提高根除疗效，避免抗生素滥用，降低耐药率。本项目将从基因检测芯片的研制与开发、验证与优化、初步临床应用三个方面开展工作，最终建立基于粪便标本的Hp感染个体化药物根除治疗相关基因检测技术。

幽门螺杆菌感染及相关疾病是我国重大卫生健康问题。由于抗生素耐药率显著升高等原因，目前我国各种经验性Hp根除方案的疗效均欠佳。采用新的个体化根除治疗策略是解决这一核心问题最为有效的方法。传统的基于胃镜和幽门螺杆菌菌株培养的个体化诊治方法无法满足广泛临床实践的要求。建立快速、简便、准确、价廉、舒适、无侵入性的相关基因检测技术和粪便取样方法，是实现幽门螺杆菌感染个体化诊治在临床广泛应用的关键瓶颈问题和重要解决途径。本项目利用PCR反向斑点杂交芯片技术，通过检测粪便标本，同时获得幽门螺杆菌现症感染、克拉霉素和左氧氟沙星耐药基因突变以及人宿主CYP2C19基因代谢型的多重信息，从而指导幽门螺杆菌感染个体化根除方案的药物合理选择，提高根除疗效，避免抗生素滥用，降低耐药率。本项目从基因检测芯片的研制与开发、验证与优化、初步临床应用三个方面开展工作，建立了基于粪便标本的幽门螺杆菌感染个体化药物根除治疗相关基因检测技术。本研究取得了一系列研究成果，圆满完成了既定任务：建立了基于粪便标本的幽门螺杆菌感染个体化诊治相关基因检测技术和流程，开发了相应的检测试剂盒，发表研究论文5篇（其中2篇为SCI论文），获批国内发明专利1项，完成人才培养（科研骨干人员及博士和硕士研究生）。

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