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.

Lymph node metastasis (LNM) is a crucial risk factor influencing an unfavorable prognosis in specific cancers. Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets. Nevertheless, the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments. Preclinical models, in this context, serve as the conduit connecting fundamental theories to clinical outcomes. In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms. Using various experimental animals, including mice, diverse methods, such as carcinogen-induced tumorigenesis, tumor cell line or human tumor transplantation, genetic engineering, and humanization, have been used effectively to construct numerous models for tumor LNM. Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis. Transplantation models, using human tumor cell lines or patient-derived tumors, offer a research platform closely mirroring the histology and clinical behavior of human tumors. Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment. Humanized models are used to overcome barriers between human and murine immune systems. Beyond mouse models, various other animal models have unique advantages and limitations, all contributing to exploring LNM. This review summarizes existing in vitro and animal preclinical models, identifies current bottlenecks in preclinical research, and offers an outlook on forthcoming preclinical models.
Animals ; Humans ; Mice ; Lymphatic Metastasis/pathology* ; Disease Models, Animal ; Cell Line, Tumor

Objective:To introduce the clinical application of three-dimensional(3D) printed titanium alloy prosthesis in the reconstruction of mandibular defects.Methods:Three patients with extensive mandibular defects, who were either ineligible for or refused autologous bone transplantation were selected from the Oral and Maxillofacial-Head and Neck Oncology Department at School & Hospital of Stomatology, Wuhan University between April 2019 and December 2021. Preoperative oral and maxillofacial CT scanning was performed, followed by a virtual surgical plan and the design and manufacture of titanium mandibular prosthesis as well as the surgery guide-plate. Repair of mandibular defects using 3D printed titanium mandibular prosthesis. Follow-up after surgery to evaluate the patient’s functional and cosmetic recovery.Results:The study included three male patients aged 27, 10 years and 8 months, and 74 years, respectively. Two cases involved recurrent mandibular tumors postoperatively, and one case involved mandibular defects following gingival tumor surgery that affected the patient’s facial appearance and eating. All surgeries were successfully completed, with postoperative outpatient follow-ups at 36, 32, and 6 months, respectively. Follow-up indicated that the facial contours were basically symmetrical, the degree of mouth opening was normal, and the occlusion on the healthy side was essentially normal. No exposure, loosening, or fracturing of the prostheses was observed.Conclusion:3D printed titanium mandibular prosthesis can effectively restore the facial contour and mandibular function of patients.

Objective:To introduce the clinical application of three-dimensional(3D) printed titanium alloy prosthesis in the reconstruction of mandibular defects.Methods:Three patients with extensive mandibular defects, who were either ineligible for or refused autologous bone transplantation were selected from the Oral and Maxillofacial-Head and Neck Oncology Department at School & Hospital of Stomatology, Wuhan University between April 2019 and December 2021. Preoperative oral and maxillofacial CT scanning was performed, followed by a virtual surgical plan and the design and manufacture of titanium mandibular prosthesis as well as the surgery guide-plate. Repair of mandibular defects using 3D printed titanium mandibular prosthesis. Follow-up after surgery to evaluate the patient’s functional and cosmetic recovery.Results:The study included three male patients aged 27, 10 years and 8 months, and 74 years, respectively. Two cases involved recurrent mandibular tumors postoperatively, and one case involved mandibular defects following gingival tumor surgery that affected the patient’s facial appearance and eating. All surgeries were successfully completed, with postoperative outpatient follow-ups at 36, 32, and 6 months, respectively. Follow-up indicated that the facial contours were basically symmetrical, the degree of mouth opening was normal, and the occlusion on the healthy side was essentially normal. No exposure, loosening, or fracturing of the prostheses was observed.Conclusion:3D printed titanium mandibular prosthesis can effectively restore the facial contour and mandibular function of patients.

Objective To assess the association between rs7969300 polymorphism of ATXN2 gene and schizophrenia.Methods Totally 1 207 schizophrenia patients diagnosed in accordance with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition(DSM-Ⅳ) and 1 120 healthy controls were involved.The rs7969300 gene SNP locus of ATXN2 gene was detected by ligase detection reaction polymerase chain reaction (PCR).PLINK software was used for statistical analysis.Results The results showed that there were no significantly different genotype frequencies(Schizophrenia patients(C/C:240,C/T:537,T/T:394),health controls (C/C:208,C/T:521,T/T:368),x2 =1.001,P=0.606) and allele frequencies (Schizophrenia patients (C 1017,T1325),health controls (C937,T1257),x2 =0.238,P=0.626) of rs7969300 polymorphism between schizophrenia patients and healthy controls.Conclusion This study does not support that ATXN2 rs7969300 is a susceptibility locus for schizophrenia.

Objective To determine the expression of TM4SF1 mRNA in 5 human pancreatic cancer cell lines,and investigate its effect on the proliferation,migration and invasion of pancreatic cancer cells.Methods The expression of TM4SF1 mRNA in MPanc96,MiaPaCa-2,PANC1,AsPC-1,HPAC cells was determined by qRT-PCR,and the results were compared with that of human pancreatic ductal epithelial (HPDE) cells.RNA interference method was used to transiently transfect siRNA targeting at TM4SF1 and negative control siRNA into MPanc96,MiaPaCa-2 cells.The proliferation of cells were measured by MTS method,and migration and invasion of cells were determined by Transwell.Results The expression levels of TM4SF1 mRNA in pancreatic cancer cell lines MPanc96,MiaPaCa-2,PANC1,AsPC-1 and HPAC were 1.205 ± 0.073,1.096 ± 0.260,1.382 ± 0.075,1.374 ± 0.363 and 0.744 ± 0.096,which were significantly highly than that in HPDE (0.020 ± 0.003,P ＜ 0.01).Compared with cells transfected with negative control siRNA,the proliferation of MPanc96 and MiaPaCa-2 cells transfected with siRNA targeting at TM4SF1 was not significantly changed,but the migration abilitiy was decreased by (62.5 ± 7.6) ％ and (72.8 ± 4.0) ％,and invasion abilitiy was decreased by (69.5 ± 5.7) ％ and (78.6 ± 6.3) ％.Conclusions TM4SF1 is highly expressed in pancreatic cancer cells and appears to promote the migration and invasion abilities of the cancer cells.

Objective To establish a rabbit model of radiation-induced skeletal muscle injury in order to study the ultrastructural pathological changes and underlying mechanism.Methods 28 New Zealand rabbits were randomly divided into 2 groups with 16 rabbits in experimental group and 12 rabbits in control group.The experimental rabbits were irradiated on hip with a single dose of 80 Gy of 9 MeV electrons from a linear accelerator.1 month and 6 months after irradiation the pathological changes were respectively observed under light microscope and electron microscope.Results One month after irradiation,the morphologic changes including degeneration,necrosis of muscle cells,and hemorrhage between the muscle cells were observed under light microscope and the swelling of myofibrillae,blurring of light and shade band,vacuolar degeneration of mitochondria and amorphous areas of necrosis were observed under electron microscope.Six months after irradiation,the morphologic changes of nucleolus chips,fibrous connective tissue,thickening of vascular wall and vascular congestion between the muscle cells and the amorphous areas of necrosis in the experimental group were much more serious than those of 1 month after irradiation.In addition,the myofilaments were lost in degeneration areas and the sarcomere became shorten.Observation with electron microscope showed that the mitochondrial size and its morphological changes were varied and the amounts of collagen between myofibrillaes were increased 6 months after irradiation.Conclusions A rabbit model of high-dose irradiated skeleton muscle injury was successfully established with a single dose of 80 Gy of 9 MeV electrons from a linear accelerator.The degeneration and necrosis of muscle cells may be promoted by mitochondrial and vascular injury,degeneration of vessel and nerve fiber.

Objective To investigate the effects of (?)doxazosin [(?)DOX] and its enantiomers on the myocardial morphology,cell cycle and cell apoptosis in rabbits fed with high fat diet. Methods Male New Zealand white rabbits were fed with high fat diet for 4 weeks. Forty such rabbits with hyperlipemia were then divided into atherogenic diet group (model),model + (-)doxazosin [(-)DOX] group,model + (+)doxazosin [(+)DOX] group and model + (?)DOX group (10 each). Another 10 rabbits were included as normal control group. In those drug-treated groups,1.0mg/kg of doxazosin or its enantiomers were intraperitoneally administered for 9 weeks; rabbits in normal control group and atherogenic diet group were given sterile distilled water. Percentages of myocardial cells in G0/G1 phase and in S phase,proliferation index (PI) and apoptotic rate of myocardial cells were compared among the groups,and the effects of doxazosin and its enantiomers were evaluated. Results Of the animals in atherogenic diet group,the proportion of myocardial cells in G0/G1 phase increased significantly (P0.05). No histomorphological alterations were observed in myocardial cells of the rabbits in normal control group. Pathological changes in myocardial cells were observed in the rabbits of atherogenic diet group,such as vacuolar degeneration,fatty degeneration,focal myocardial necrosis,myocardial fibrosis and focal lymphocyte infiltration. The pathological changes in myocardial cells were significantly ameliorated in the animals in (-)DOX and (?)DOX group,but aggravated in the rabbits of (+)DOX group. Conclusions A long term treatment with (-)DOX in the rabbits may improve the histopathological changes in myocardial cells caused by high fat diet. (-)DOX and (+)DOX may have a optical selective effect.