申请人致力于急性肾损伤发病机制及治疗探索研究，第一/通讯作者论文发表于Lancet，Nature Medicine，J Clin Invest等杂志。主要成绩如下：组织完成中国急性肾损伤流行病调查，揭示严重疾病负担和严峻诊疗现状；创建急性肾损伤预警系统，从根本上解决漏误诊难题。开展急性肾损伤机制研究探索新治疗靶点：揭示急性肾损伤时肾小管上皮细胞的天然自我防御机制--通过高表达肾损伤分子-1负向调控天然免疫反应并阐明调控机制；揭示肾小管上皮细胞在急性肾损伤后发生细胞周期G2/M阻滞，启动纤维化分泌表型引发慢性纤维化，并阐明相关机制。开创了肾脏保护和抗纤维化治疗的新研究领域。申请人在本领域发表SCI论文22篇（总影响因子161，SCI他引713次，单篇最高他引286次），获批/公示国家发明专利2项。2015年获“中国大挑战青年科学家奖”。拟开展的研究为急性肾损伤后纤维化发病机制及干预靶点探索。

The applicant performs basic and medical research to investigate the mechanism and the potential therapeutic targets of acute kidney injury (AKI), and has published research papers as first/corresponding author in top medical journals such as the Lancet, Nature Medicine, and J Clin Invest. We organized and accomplished the first nation-wide multi-center survey of AKI in China, and revealed the huge burden and big challenge of AKI across the country. We then designed and successfully built up an automatic AKI alert system which effectively avoids misdiagnosis of AKI in clinical practice and thus improves the outcome of patients. Meanwhile, in order to deplore novel therapeutic strategies targeting kidney protection and fibrosis prevention in AKI, we performed series of basic researches. We firstly discovered the natural self-protective mechanism of renal proximal tubular cells against AKI. Through overproduction of kidney injury molecule-1 (KIM-1), which mediates the phagocytosis of apoptotic cells and consequently induces trans-repression of pro-inflammatory NFB, the renal tubular cells act as negative modulators of innate immune response through paracrine signals, and thus limit the amplification of inflammatory injury in the acute phase of AKI. We next discovered that the renal tubular cells develop cell cycle G2/M arrest under acute severe injury and trigger the fibrotic process post AKI. The relevant molecular mechanism was elucidated and opened up a novel study field of anti-fibrotic therapies in AKI. To date, the applicant has published 22 peer-reviewed papers in the field of AKI with total impact factor of 161.231 and citation of 713 by others. The most cited paper was published in J Clin Invest with a citation of 286. Besides, the applicant has got two China invention patents with authorization or publicity, and was rewarded China Challenge Award for young scientists in 2015. Based on the previous work, we will further explore the therapeutic targets for treating chronic fibrosis post AKI.