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.

BACKGROUND: There is no any mature and complete system to repair nerve tissue after segmental injury due to particularity of nerve tissue regeneration. Using tissue-engineering technique to solve this problem is difficult and challenged.OBJECTIVE: To research an artificial nerve bridging substance in application of repairing nerve injury on clinic and obverse its microcosmic spatial structure at the same time.DESIGN: Open experiment.SETTING: Orthopaedic Research Institute, Xijing Hospital of the Fourth Military Medical University of Chinese PLA.MATERTALS: The experiment was carried out in the Orthopaedic Research Institute, Xijing Hospital of the Fourth Military Medical University of Chinese PLA from November 2001 to January 2003. CollagenⅠ, collagen Ⅳ and gelatin were provided by Sigma-aldrich Company, USA.METHODS: Establishment of bridging substance: Collagen Ⅰ (65.53%) and collagen Ⅳ (32.77%) were added into 0.05 mol/L acetic acid solution, respectively; and then, two suspensions were mixed together and stirred at 4℃. The suspension of collagen and heparin sulfate was pumped, held still and poured into silica gel tube with bore of 3 mm.Continuously, two ends of tube were enclosed and suffered from cold drench and mold at five various speeds. General observation was done. Composites were intercepted cross section, vertical section and 45° section for observation by optic microscope at different speeds of 10×10-5 m/s, 5×10-5 m/s, 2.5×10-5 m/s, 1.0×10-5 m/s and 1.0×10-6 m/s; meanwhile, interior structure of microtubule was observed with scanning electron microscope. Interior diameter of microtubule was calculated as the following formula: actual aperture = (magnification × area of microtubule) ÷ (length of guage × perimeter of aperture).MAIN OUTCOME MEASURES: ① General observation; ② observation with microscope; ③ observation with scanning electron microscope and interior diameter of microtubule.RESULTS: ① General observation: Models were regular cylinders and had symmetrical features. Flexility was wonderful,texture was well-proportioned, and elasticity was strong. ② Results of optic microscope: Structure of external surface was completely blocking without any poricidal dehiscence. Surface was smooth and had good continuity. ③ Results of electron microscope: External surface shaped like terrace tile; asides, interior structure of microtubule was average and its courser was coincident and parallel to each other. Microtubules with longitudinal courser were independence on each other. The structure was blocking and did not connect to each other. This was as the same as courser of nerve fibrous bands of organis. Cross section of interior microtubule was general round and regular, and the diameter was average. Interior microtubule had groat continuity without breaks or transection. Trabeculae of microtubule also had groat continuity,and its surface was smooth. Interior diameter of microtubule ranged from 197.3 μm to 258.8 μm.CONCLUSION: Nerve bridging substance is made of collagen and gelatin which are characterized by groat compatibility and degradation after mixture, lysis and cold drench, It has singly longitudinal microtubule and microstructure of high imitation by normal nerves, so nerve bridging substance can be used in basic researches and repair nerve injury on clinic.

Objective: To explore the ethical and juristic signif-icance of hearing with living-related kidney transplantation. Methods: This study involved 18 donors and recipients who received medical e-valuating and informing the related medical risk between Jul.2006 and Jun.2007. Our experience of 18 hearings with living-related kidney transplantation, which comprised members of Human Organ Transplant Te-chnique and Ethics Committee,donors,recipients and their direct rela-tives,was analyzed. Results the 16 hearings were successful, one res-igned donation,and two were controvertible and succeeded after re-ev-aluating. Conclusion:The hearing should have known,voluntary,equitab-le, unclassified and no commercial principle,and endeavour to ensure the medical,ethical and juristic entirety and integrity of living-re-lated kidney transplantation.