In terms of ERL, Simone et al recently reported that ERL and particularly good renal function. However, in another study, the use of combination CsA and mTORis leaded to potential 
longterm CNI nephrotoxicity. Since the number of SRL-based and ERL-based RCTs included in this meta-analysis is small, more high-quality RCTs based on SRL and ERL should be conducted to draw a clear conclusion on whether mTORis-based CNI minimization protocols are effective and safe in patients with impaired renal function. However, according to the results from the meta-analysis of observational trials and considering their well known anti-tumor effects, mTORis may be a good alternative for MMF to reduce or replace CNI in liver transplant recipients with a pre-transplant diagnosis of hepatocellular carcinomaand post-transplant renal dysfunction. However, clinicians should pay attention to the increased risks of infections when SRL is used. Undoubtedly, there are some limitations in the current metaanalysis as others. Firstly, we included studies using different regimens without comparing between themselves, it make us difficult to figure out which combination is the best one although the current data show that the MMF-based CNI minimization protocol received the greatest supports. Secondly, most of the studies we included didn’t undertake follow-ups longer than 12 months, giving us insufficient data on how CNI minimization would affect long-term graft or patient survival. Finally, as shown in Table 2, the risk of bias of the included randomized trials was relatively high, since no study was double blind designed and only 3 of 10 studies conducted intention-to-treat analysis, which may attenuate the power of the current study. In conclusion, this meta-analysis included all current relevant studies from various countries covering different populations. It can make up to the shortage of small sample size and limited population of individual studies, providing stronger evidence on the clinical Enzalutamide application of CNI minimization protocols. It is convincing that CNI minimization can improve renal function in liver transplant patients with CNI-related renal impairment, while has an equal or similar effect on acute rejection and patient survival as routine CNI regimen. However, it should be cautious to use SRL-based minimization regimens in patients with high risks of infections. Studies in the future should try to figure out whether this improved renal function can prolong long-term patient or graft survival, and which minimization protocol is the standard one in various Z-VAD-FMK combinations. The development and clinical use of HIV protease inhibitors has greatly contributed to the transition of HIV infection from a once fatal disease to its current status as a chronic condition. Tempering enthusiasm for this major advance in HIV treatment is the growing realization that patients treated with combined antiretroviral treatment regimens are at increased risk for the development of pro-atherogenic metabolic side effects including dyslipidemia and insulin resistance. A direct contribution of HIV protease inhibitors to altered glucose homeostasis has been established from several clinical studies. Despite growing awareness of these treatment-related side effects, understanding the mechanisms leading to the development of insulin resistance in treated HIV infection remains incomplete. The ability of PIs to induce insulin resistance in treated patients is not shared by all agents within this drug class. Indinavir and ritonavir appear to have the greatest effect on glucose transport both in vitro and in vivo whereas newer PIs such atazanavir and tipranavir have minimal to no effect on insulin sensitivity.