Role of the portal system in liver regeneration:From molecular mechanisms to clinical management

The liver has a strong regenerative capacity that ensures patient recovery after hepatectomy and liver transplantation.The portal system plays a crucial role in the dual blood supply to the liver,making it a significant factor in hepatic function.Several surgical strategies,such as portal vein ligation,associating liver partition and portal vein ligation for staged hepatectomy,and dual vein embolization,have high-lighted the portal system's importance in liver regeneration.Following hepatectomy or liver trans-plantation,the hemodynamic properties of the portal system change dramatically,triggering regeneration via shear stress and the induction of hypoxia.However,excessive portal hyperperfusion can harm the liver and negatively affect patient outcomes.Furthermore,as the importance of the gut-liver axis has gradually been revealed,the effect of metabolites and cytokines from gut microbes carried by portal blood on liver regeneration has been acknowledged.From these perspectives,this review outlines the molecular mechanisms of the portal system's role in liver regeneration and summarizes therapeutic strategies based on the portal system intervention to promote liver regeneration.

Fibroblast growth factor 21(FGF21) attenuates tacrolimus-induced hepatic lipid accumulation through transcription factor EB(TFEB)-regulated lipophagy

Tacrolimus(TAC),also called FK506,is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation.However,it has been proved to be associated with post-transplant hyperlipemia.The mechanism behind this is unknown,and it is urgent to explore preventive strategies for hyperlipemia after transplantation.Therefore,we established a hyperlipemia mouse model to investigate the mechanism,by injecting TAC intraperitoneally for eight weeks.After TAC treatment,the mice developed hyperlipemia(manifested as elevated triglyceride(TG)and low-density lipoprotein cholesterol(LDL-c),as well as decreased high-density lipoprotein cholesterol(HDL-c)).Accumulation of lipid droplets was observed in the liver.In addition to lipid accumulation,TAC induced inhibition of the autophagy-lysosome pathway(microtubule-associated protein 1light chain 3β(LC3B)II/I and LC3B II/actin ratios,transcription factor EB(TFEB),protein 62(P62),and lysosomal-associated membrane protein 1(LAMP1))and downregulation of fibroblast growth factor 21(FGF21)in vivo.Overexpression of FGF21may reverse TAC-induced TG accumulation.In this mouse model,the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway.We conclude that TAC downregulates FGF21and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway.Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.

A novel nomogram for prognosis stratification in salvage liver transplantation:a national-wide study with propensity score matching analysis in China

Background:Salvage liver transplantation(SLT)has been reported to be an efficient treatment option for patients with recurrent hepatocellular carcinoma(HCC)after liver resection(LR).However,for recipients who underwent liver transplantation(LT)due to recurrent HCC after LR in China,the selection criteria are not well established.Methods:In this study,data from the China Liver Transplant Registry(CLTR)of 4,244 LT performed from January 2015 to December 2019 were examined,including 3,498 primary liver transplantation(PLT)and 746 SLT recipients.Propensity score matching(PSM)analysis was used to minimize between-group imbalances.The overall survival(OS)and disease-free survival(DFS)between PLT and SLT in recipients fulfilling the Milan or Hangzhou criteria were compared based on the multivariate analysis,nomograms were plotted to further classify the SLT group into low-and high-risk groups.Results:In this study,the 1-,3-and 5-year OS and DFS of SLT recipients fulfilling Milan criteria(OS,P=0.01;DFS,P<0.001)or Hangzhou criteria(OS,P=0.03;DFS,P=0.003)were significantly reduced when compared to that of PLT group after PSM analysis.Independent risk factors,including preoperative transarterial chemoembolization(TACE),alpha fetoprotein(AFP)level,tumor maximum size and tumor total diameter were selected to draw a prognostic nomogram.The low-risk SLT recipients(1-year,95.34%;3-year,84.26%;5-year,77.20%)showed a comparable OS with PLT recipients fulfilling Hangzhou criteria (P=0.107). Conclusions: An optimal nomogram model for prognosis stratification and clinical decision guidance of SLT was established. The low-risk SLT recipients based on the nomograms showed comparable survival with those fulfilling Hangzhou criteria in PLT group.

Nodeless superconducting gaps in Ca10(Pt(4-δ)As8)((Fe(1-x)Ptx)2As2)5 probed by quasiparticle heat transport

The in-plane thermal conductivity of the iron-based superconductor Ca10(Pt_(4-δ)As_8)((Fe_(1-x)Pt_x)_2As_2)_5 single crystal("10-4-8", T c= 22 K) was measured down to 80 m K. In a zero field, the residual linear term κ_0/T is negligible, suggesting the nodeless superconducting gaps in this multiband compound. In the magnetic fields, κ_0/T increases rapidly, which mimics the multiband superconductor Nb Se_2 and Lu Ni_2B_2 C with highly anisotropic gap. Such a field dependence of κ_0/T is an evidence for the multiple superconducting gaps with quite different magnitudes or highly anisotropic gap. Compared with the London penetration depth results of the Ca10(Pt_(4-δ)As_8)((Fe_(1-x)Pt_x)_2As_2)_5("10-3-8") compound, the 10-4-8 and 10-3-8 compounds may have a similar superconducting gap structure.

Aspirin in hepatocellular carcinoma:Is it an out-of-date or promising treatment?

Hepatocellular carcinoma(HCC)is one of the most aggressive human malignancies with a dismal survival rate.Few strategies can effectively prevent the occurrence of HCC.Although immunotherapy has significantly improved HCC-related survival in recent years,this systemic therapy is very expensive and lays a heavy burden on most HCC patients.Aspirin,which is currently one of the most widely used medications in analgesic and cardiovascular diseases,is reported to have anti-tumor effects on HCC.Most importantly,long-term administration of low-dose aspirin does not significantly increase the risk of gastrointestinal bleeding.Owing to its costeffectiveness and wide use,aspirin can be easily applied as an HCC treatment and is affordable for a wide range of patients.Therefore,deeper understanding and more attention are needed to extend the frontline of aspirin's preventive and therapeutic potential into cancer research and management.In this review,we discuss the preventive effect of aspirin on HCC in the context of different etiological factors,including hepatitis B or hepatitis C virus infection,non-alcoholic fatty liver disease,and alcohol-associated liver disease.The therapeutic role of aspirin in resectable or unresectable HCC management is also discussed.Furthermore,the mechanisms underlying the anti-cancer effects of aspirin on HCC are fully reviewed and discussed in the following two aspects:the effect of aspirin on multi-oncogenic signaling pathways in HCC(e.g.,AMPK,Wnt/β-catenin,NF-κB)and aspirinmediated immunometabolic responses in liver diseases.These findings indicate aspirin is a promising agent for populations at risk and HCC patients to prevent or treat HCC.