Yingzi Ming

Glycyrrhizin protects mice against renal ischemia‑reperfusion injury through inhibition of apoptosis and inflammation by downregulating p38 mitogen‑activated protein kinase signaling

Ischemia-reperfusion (I/R) often leads to acute kidney injury, chronic renal failure and kidney transplantation failure. Glycyrrhizin is extracted from Glycyrrhiza glabra roots and is the predominant active component, which exhibits anti-inflammatory effects. However, to the best of our knowledge, the effect of glycyrrhizin on I/R-induced renal injury has not been investigated. In the present study, glycyrrhizin was demonstrated to attenuate renal I/R injury in mice via administration of glycyrrhizin, which suppressed the serum levels of creatinine and blood urea nitrogen 6 h following reperfusion; furthermore, the superoxide anions as well as the activity of superoxide dismutase within renal tissues was reduced by glycyrrhizin pretreatment. Moreover, the protein level of cleaved caspase-3, as well as its activity in renal tissue, was suppressed as a result of the glycyrrhizin pretreatment, indicating that glycyrrhizin inhibits I/R-induced renal cell apoptosis. In addition, glycyrrhizin pretreatment appeared to ameliorate I/R-induced renal injury via inhibition of inflammatory cell infiltration, as well as the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β and IL-6. The underlying molecular mechanism was investigated and it was shown that the activity of p38 mitogen-activated protein kinase signaling was downregulated as a result of glycyrrhizin administration. In conclusion, the present study indicated that glycyrrhizin provided significant protection against I/R-induced renal injury in mice by inhibiting inflammatory responses and renal cell apoptosis. Therefore, glycyrrhizin may be used in abdominal surgery and kidney transplantation for the prevention of renal I/R damage.

Long-Term Outcomes of Ante-Situm Resection and Auto-Transplantation in Conventionally Unresectable Hepatocellular Carcinoma: A Single-Center Experience

Background Ante-situm resection and auto-transplantation (ante-situm for short) provides a more aggressive approach to conventionally unresectable hepatocellular carcinoma (HCC). We described the long-term outcomes of patients with HCCs who underwent this technique. Material/Methods Between October 2005 and December 2016, we performed 23 ante-situm liver resections. We evaluated postoperative complications, 90-day mortality, recurrence, and long-term survival rates, and reviewed the literature on this topic. Results Five types of complications associated with six patients were observed.: 1) primary nonfunctioning liver, thus receiving a liver transplantation; 2) initial poor liver function with recovery two weeks after treatment; 3) diagnoses of portal vein tumor thrombosis, biliary fistula, and small-for-size syndrome, respectively. The median follow-up was 3.6 years; 12 out of 23 patients were alive at the end of the study. One patient who had hepatic recurrence was lost to follow-up after three months. One patient died of multiple organ dysfunction syndrome after the operation, nine patients died due to hepatic recurrence and/or extrahepatic metastasis of HCC. The one-year, three-year, five-year, and 10-year survival rates were 65.2%, 56.5%, 50.9%, and 20.3%, respectively. The one-year, three-year, five-year, and 10-year recurrence rates were 60.9%, 50.7%, 50.7%, and 50.7%, respectively. The chi-square test revealed the patients with recurrence after ante-situm technique were more likely to have poor prognosis (mortality of patients with recurrence versus no-recurrence: 88.9% versus 14.3%, p<0.05) and a strong association was evidenced by Cramer’s V statistic (Cramer’s V=0.734). Conclusions Ante-situm procedure showed benefits in select patients with HCCs who had contraindications for conventional resection operations. In our case series, the ante-situm technique resulted in lower mortality compared to other ex-vivo hepatic resection techniques reported in the literature and similar long-term efficacy compared to cases of HCCs suitable for conventional resections. HCCs recurrence was a major risk factor associated with the survival rate of ante-situm technique.

Comparative efficacy and safety of antibody induction therapy for the treatment of kidney: a network meta-analysis

To evaluate the efficacy and safety of antibody induction therapies in kidney transplantation. Systematic literature searches were undertaken using MEDLINE, Embase, and Cochrane Library database from 1980 to 2016. Randomized controlled trials (RCTs) comparing three antibody induction therapies (alemtuzumab, interleukin-2 receptor antibodies and antithymocyte globulin) between each other were identified. Bayesian network meta-analysis was used to combine both the direct and indirect evidence on treatment efficacy and its safety. Antibody induction therapy studies, comprising of 18 RCTs (3444 kidney transplant recipients), were included. Overall, alemtuzumab treatment was superior to the ATG group (OR: 0.49, 95% CI: 0.32 to 0.71) and IL-2RAs group (OR: 0.36, 95% CI: 0.25 to 0.52) for reducing the 1-year acute rejection in kidney transplant recipients. Although alemtuzumab treatment was nearly same with ATG group and IL-2RAs group in improving patient survival and renal function, it can reduce the adverse effects of cytomegalovirus infection more efficiently than ATG group (OR: 0.59, 95% CI: 0.32 to 0.95) and IL-2RAs group (OR: 1.08, 95% CI: 0.61 to 1.73). Alemtuzumab was not associated with increased other adverse effects. Alemtuzumab treatment is safe and effective for kidney transplant recipients. No serious adverse effects were observed in trials or in general populations.