1. 毕业设计（论文）的内容和要求

论文内容 替比夫定（sebivo）是治疗慢性乙型肝炎的核苷类似物药物，是临床使用广泛。

虽然起效快，但是存在较强的毒副作用，如可能引起罕见的不良反应#8212;横纹肌溶解症。

本课题利用自行开发的半乳糖苷酶结构修饰替比夫定，肝细胞的特异性识别半乳糖基提高抗肝病毒的靶向性，前药设计降低药物的毒副作用。

2. 参考文献

1]Tian Y, Ni D, Yang W, et al. Telbivudine treatment corrects HBV-induced epigenetic alterations in liver cells of patients with chronic hepatitis B[J]. Carcinogenesis, 2014, 35(1):53. [2]Hsu Y C, Ho H J, Lee T Y, et al. Temporal Trend and Risk Determinants of Hepatocellular Carcinoma in Chronic Hepatitis B Patients on Entecavir or Tenofovir[J]. J Viral Hepat, 2017.. [3]Hsu C W, Chen Y C, Chang M L, et al. Durability of Telbivudine-Associated Improvement of Renal Function Following Withdrawal or Switching of Antivirals in Chronic Hepatitis B Patients:[J]. Open Forum Infectious Diseases, 2018, 5(1).. [4]Chen Z X, Gu G F, Bian Z L, et al. Clinical course and perinatal transmission of chronic hepatitis B during pregnancy in a real-life setting: A prospective cohort study.[J]. Journal of Infection, 2017, 75(2):146-154. [5]Tenggara I R, Lesmana C R, Gani R A. Treatment Response Monitoring of Chronic Hepatitis B Patients using Transient Elastography and Aspartate Aminotransferase-to-Platelet Ratio Index (APRI)[J]. Acta Medica Indonesiana, 2017, 49(3):220. [6].Cai S, Cao J, Yu T, et al. Effectiveness of entecavir or telbivudine therapy in patients with chronic hepatitis B virus infection pre-treated with interferon compared with de novo therapy with entecavir and telbivudine[J]. Medicine, 2017, 96(22):e7021. [7]Cuomo G, Borghi V, Giuberti T, et al. What to start with in first line treatment of chronic hepatitis B patients: an Italian multicentre observational cohort, HBV-RER study group.[J]. Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive, 2017, 25(2):150. [8]Zhang C, Chen Y, Liang X, et al. Detection of Hepatitis B Virus M204I Mutation by Quantum Dot-Labeled DNA Probe:[J]. Sensors, 2017, 17(5):961. [9].Sun W, Zhao S, Lei M, et al. Telbivudine treatment started in early and middle pregnancy completely blocks HBV vertical transmission[J]. Bmc Gastroenterology, 2017, 17(1):51.Sun W, Zhao S, Lei M, et al. Telbivudine treatment started in early and middle pregnancy completely blocks HBV vertical transmission[J]. Bmc Gastroenterology, 2017, 17(1):51. [10]Lin S, Ye Q, Wang M, et al. Antiviral Therapy in Chronic Hepatitis B With Mild Acute Exacerbation:[J]. Gastroenterology Research, 2017, 10(1):6-14.

3. 毕业设计（论文）进程安排

2017.12.26- 2018.1.10 文献资料查阅、标准检索 2018.02.27- 2018.3.20 完成开题报告、熟悉实验方案 2018.03.21- 2018.3.30 酶制备，半乳糖基替比夫定酶法合成反应条件优化 2018.04.01- 2018.05.20 实验结果检测与分析，半乳糖基替比夫定酶法合成工艺构建 2018.05.21- 2018.6.15 数据整理、撰写论文、答辩