Urate oxidase (Uox) plays a pivotal role in uric acid (UA) degradation, and it has been applied in controlling serum UA level in clinical treatment of hyperuricemia (HUA). However, because Uox is a heterogenous protein to the human body, the immune rejections typically occur after intravenous administration, which greatly hampers the application of Uox-based agents. In this study, we used Lactococcus lactis NZ9000, a food-grade bacterium, as a host to express exogenous Uox genes, to generate the Uox-expressing engineered strains to treat HUA. Aspergillus flavus-derived Uox (aUox) and the "resurrected" human-derived Uox (hUox) were cloned into vector and expressed in NZ9000, to generate engineered strains, respectively. The engineered NZ9000 strains were confirmed to express Uox and showed UA-lowering activity in a time-dependent manner in vitro. Next, in an HUA mice model established by oral gavage of yeast paste, the UA levels were increased by 85.4% and 106.2% at day 7 and day 14. By contrast, in mice fed with NZ9000-aUox, the UA levels were increased by 39.5% and 48.3% while in mice fed with NZ9000-hUox were increased by 57.0% and 82.9%, suggesting a UA-lowering activity of both engineered strains. Furthermore, compared with allopurinol, the first-line agent for HUA treatment, mice fed with NZ9000-aUox exhibited comparable liver safety but better kidney safety than allopurinol, indicating that the use of engineered NZ9000 strains not only alleviated kidney injury caused by HUA, but could also avoided the risk of kidney injury elicited by using allopurinol. Collectively, our study offers an effective and safe therapeutic approach for HUA long-term treatment and controlling.
Animals ; Lactococcus lactis/metabolism* ; Urate Oxidase/genetics* ; Mice ; Uric Acid/blood* ; Hyperuricemia ; Humans ; Administration, Oral ; Aspergillus flavus/genetics* ; Male

Objective To evaluate the clinical effect of ultrasound - guided sclerosing agent lauromacrogol injection in treating lymph leakage. Methods A total of 31 patients with postoperative lymph leakage were selected for this study. Of the 31 patients, successful conservative oppression treatment was accomplished in 16, and lauromacrogol injection had to be carried out in 15 as conservative oppression treatment failed. The patients were followed up and the results were analyzed. Results In 15 patients receiving lauromacrogol injection treatment, complete cure of lymph leak was obtained in 14 with a success rate of 93.33%. Among the 14 cases, the second lauromacrogol injection was employed in 3 at one week after the first injection. Infection occurred in another case one day after the injection , which was cured after dressing change for 15 days. Conclusion For the treatment of lymph leakage, ultrasound-guided sclerosing agent lauromacrogol injection is effective and safe.