Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective To measure the related anatomical parameters of lumbosacral nerve root and adjacent structures by magnetic resonance neurography,and to analyze operative safety of transforaminal lumbar interbody fusion in Chinese people.Methods A total of 12 healthy volunteers,including 6 males and 6 females,underwent magnetic resonance neurography of lumbosacral nerve root using a Siemens 3.0T MRI machine.The Osirix software was used to reconstruct the three-dimensional imaging and measure the following anatomic parameters: 1) the distance between the nerve root and the superior pedicle; 2) the distance between the nerve root and the inferior pedicle; 3) the angle between the nerve root and the sagittal plane; 4) the distance between the superior and inferior nerve roots; 5) the distance between the superior and inferior pedicles.Results L1-L5 nerve roots got a good imaging by magnetic resonance neurography in all 12 volunteers.The distance between the nerve root and the superior pedicle and the angle between the nerve root and the sagittal plane gradually became smaller from L1 to L5.But the variation in the distance between the nerve root and the inferior pedicle and the distance between the superior and inferior pedicles was not obvious.The distance between the nerve root and the inferior pedicles,which was closely related to the operating space of TLIF,ranged from (8.99±0.88) mm to (10.72±1.01) mm for males and from (7.76±0.46) mm to (8.54±0.65) mm for females; it was less than 10 mm in each segments in the majority of subjects,and the data of females was significantly smaller than that of males.No significant differences were found in parameters between the left and right sides in the same segment.Conclusion Based on the above anatomical study and measurement analysis,we believe that there is some harassment to the upper nerve root in TLIF for Chinese patients,and for some patients there is a certain injury risk.