End-stage liver disease (ESLD) covers the end-stage of acute and chronic liver diseases, mainly involving decompensated cirrhosis, various types of liver failure, and advanced liver cancer. Hepatocyte transplantation has shown promise in treating ESLD, but its clinical application is hampered by the shortage of donor hepatocytes. Cell therapy, an emerging effective treatment for ESLD, faces the same limitation due to scarce hepatocyte availability. Hepatocyte-like cells (HLCs), which are terminally differentiated cells, can be induced from both stem cells and somatic cells. As HLCs exhibit the morphology and function of primary hepatocytes, they offer a promising supplementary source of hepatocytes for cell therapy. First, we provide a background for the differentiation and maturation of primary hepatocytes. Subsequently, based on the current insights into the molecular pathways that regulate hepatocyte differentiation in vivo, we describe a strategy for establishing HLC derived from either stem cells or somatic cells. The key characteristics of these HLCs are also detailed. Furthermore, HLC offers therapeutic potential for liver failure, and HLC-based liver organoids and bioartificial liver systems have demonstrated the ability to provide liver functions, offering an innovative approach to treating various types of ESLD. Despite their promise, challenges such as efficiency in differentiation and functional maturation need to be addressed to improve the clinical application of HLCs. This review discusses these advancements and outlines the therapeutic potential and current challenges of HLC therapy for ESLD.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

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.

OBJECTIVES: This study aimed to use modified articular disc anchorage in treating old irreducible temporomandibular joint (TMJ) disc displacement with perforation and rupture, as well as to explore its efficacy. METHODS: A total of 31 patients (34 sides) with 47 TMJ disc perforations who underwent surgical treatment in the Affiliated Stomatolo-gical Hospital of Nanchang University from January 2018 to December 2021 were selected. According to the location of disc perforation, it has five types: posterior disc perforation (typeⅠ), anterior disc perforation (typeⅡ), lateral disc perforation (type Ⅲ), composite disc perforation, and destruction disc perforation. The modified methods of disc anchoring were divided into two types according to the location of the perforation. TypesⅠandⅢ disc perforation were trea-ted by posterior anchoring method. For posterior ancho-ring, a screw was implanted into the posterolateral side of the condylar neck, and the disc was fixed on the screw by horizontal mattress suture. TypeⅡdisc perforation and compo-site disc perforation combined typeⅡperforation were treated by anterior and posterior double-anchoring method. For anterior anchoring, anchor screws or holes were placed at the anterior edge of the condylar neck, and horizontal mattress suture was performed at the posterior edge of the anterior perforation with an anchor wire. The articular disc was then fixed on the anchor screws or holes. For the posterior anchoring method, it was the same as the previous one. Paired t test was used to analyze the visual analog scale (VAS), maximum interincisal opening (MIO), and TMJ disorder index (CMI) of the patient before surgery and 1, 3, and 6 months after surgery. Disk-condyle position relationship by magnetic resonance imaging and postoperative quality of life in postoperative were analyzed. RESULTS: The incidence of perforation was 41.2% (14/34) in typeⅠ, 11.8% (4/34) in typeⅡ, 8.8% (3/34) in typeⅢ, 29.4% (10/34) in composite type, and 8.8% (3/34) in destruction type. The VAS, MIO, and CMI at 3, 6 months after operation significantly improved compared with those before operation (P<0.05). The effective reduction rate of disc was 96.77% (30/31). The quality of life at 6 months after surgery was 47.22±2.13, and the rate of excellent evaluation was 96.4% (27/28). CONCLUSIONS Modified articular disc anchorage achieves a good curative effect for treating temporomandibular joint disc perforation and rupture. Nevertheless, its long-term effect requires further observation.
Humans ; Temporomandibular Joint Disc/surgery* ; Quality of Life ; Joint Dislocations/surgery* ; Temporomandibular Joint Disorders/surgery* ; Magnetic Resonance Imaging/methods* ; Temporomandibular Joint/pathology* ; Mandibular Condyle

Liver transplantation (LT) is one of the most effective treatments for end-stage liver diseases. The number of LT in China currently ranks as the second worldwide. Extended criteria donor (ECD) reconditioning and functional improvement is an important research direction at present in order to address the bottleneck of donor graft shortage. In the future, it is pivotal to explore the original breakthroughs in basic theories of stem cell fates regulation, organ restoration and tissue regeneration, and to conduct national-wide, multicenter clinical investigations on the basis of innovative platform of medical, engineering and information technology. Therefore, the authors summarize evidence-based medical proof, latest research achievements and clinical experi-ences with novel concept of "machine perfusion plus" to explore the most updated mode that inte-grates traditional machine perfusion with cutting edge technologies such as multi-omics, molecular biology, information technology, automation technology and nanoparticle targeted delivery tech-nology. This aims to achieve real-time, non-invasive, intelligent quality assessment and monitoring of donor graft, and finally to establish a new technology system of ECD reconditioning and functional improvement, which can safely and effectively expand the donor pool, decrease the risk of post-transplant complications, and improve the prognosis of recipients, thus promoting the higher quality development of LT in China.