Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, and fibrosis. Importantly, growing evidence elucidates that the disruption of the gut–liver axis and microbe-derived metabolites drive the pathogenesis of NAFL/NASH. Extracellular vesicles (EVs) act as a signaling mediator, resulting in lipid accumulation, macrophage and hepatic stellate cell activation, further promoting inflammation and liver fibrosis progression during the development of NAFL/NASH. Targeting gut microbiota or EVs may serve as new strategies for the treatment of NAFL/NASH. Finally, other mechanisms, such as cell therapy and genetic approaches, also have enormous therapeutic potential. Incorporating drugs with different mechanisms and personalized medicine may improve the efficacy to better benefit patients with NAFL/NASH.

Objective To determine the value of an enhanced recovery after surgery (ERAS) protocol for prostate cancer patients undergoing laparoscopic radical prostatectomy (LRP). Methods We conducted a retrospective cohort study using clinical data for 288 patients who underwent LRP in our hospital from June 2010 to December 2016. A total of 124 patients underwent ERAS (ERAS group) and the remaining 164 patients were allocated to the control group. ERAS comprised prehabilitation exercise, carbohydrate fluid loading, targeted intraoperative fluid resuscitation and keeping the body warm, avoiding drain use, early mobilization, and early postoperative drinking and eating. Results The times from LRP to first water intake, first ambulation, first anal exhaust, first defecation, pelvic drainage-tube removal, and length of hospital stay (LOS) were all significantly shorter, and hospitalization costs and the incidence of postoperative complications were significantly lower in the ERAS group compared with the control group. No deaths or reoperations occurred in either group, and there were no readmissions in the ERAS group, within 90 days after surgery. Conclusion ERAS protocols may effectively accelerate patient rehabilitation and reduce LOS and hospitalization costs in patients undergoing LRP.

PTEN-Long is a translational variant of PTEN (Phosphatase and Tensin Homolog). Like PTEN, PTEN-Long is able to antagonize the PI3K-Akt pathway and inhibits tumor growth. In this study, we investigated the role PTEN-Long plays in the development and progression of clear cell renal cell carcinoma (ccRCC) and explored the therapeutic possibility using proteinaceous PTEN-Long to treat ccRCC. We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt). Gain of function experiments showed overexpression of PTEN-Long in the ccRCC cell line 786-0 suppressed PI3K-Akt signaling, inhibited cell proliferation, migration and invasion, and eventually induced cell death. When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage. Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model. Our results implicated that understanding the roles of PTEN-Long in renal cell carcinogenesis has therapeutic significance.