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 explore the diagnosis and treatment strategies for elderly patients with ground-glass opacity (GGO). Methods The imaging features and postoperative pathological findings of the elderly patients with pulmonary GGO receiving surgery in our hospital from 2017 to 2019 were retrospectively analyzed. The patients were divided into an elderly patient group and a non-elderly patient group based on their age. Results Finally 575 patients were included in the study. There were 281 elderly patients, including 83 males and 198 females, with an average age of (67.0±5.3) years. There were 294 non-elderly patients, including 88 males and 206 females, with an average age of (49.1±7.3) years. Compared with the non-elderly patients, elderly GGO patients showed the following distinct clinical features: long observation time for lesions (P=0.001), high proportion of rough edges of GGO (P<0.001), significant pleural signs (P＜0.001) and bronchial signs (P＜0.001), and high proportion of type Ⅱ-Ⅳ GGO (P<0.001), lobectomy type (P=0.013), and invasive lesions reported in postoperative pathology (P<0.001). There was no statistical difference in the average hospital stay between the two groups (P=0.106). Multivariate logistic regression analysis showed that GGO diameter and GGO type were the main factors affecting the operation. Observation time, GGO diameter, GGO type and pleural signs were the main influencing factors for postoperative pathological infiltrative lesions. The cut-off value of GGO diameter in predicting infiltrating lesions was 10.5 mm in the elderly patients group. Conclusion The size and type of GGO are important factors in predicting invasive lesions and selecting surgical methods. Elderly patients with radiographic manifestations of type Ⅱ-Ⅳ GGO lesions with a diameter greater than 10.5 mm should be closely followed up.

Objective:This study aimed to assess the patch test positivity rate, allergen distribution, and their associations with demographic characteristics and immune indicators in patients with allergic contact dermatitis (ACD).Methods:A retrospective medical record analysis was conducted on 402 patients suspected of ACD (338 females, median age 38 years; 64 males, median age 43 years) seen at Xuanwu Hospital, Capital Medical University between June 2023 and June 2024. Standard patch tests (using 100 haptens from the Chinese baseline series) were administered, and serum total IgE and eosinophil levels were measured. Statistical analyses included chi-square tests, t-tests/Mann-Whitney U tests for group comparisons, and Spearman correlation for associations. Results:The overall patch test positivity rate among the 402 patients was 62.69% (252/402), with 85.71% (216/252) showing sensitivity to the top 21 allergens. Predominantly, the affected individuals were females (84.26%, 182/216) aged 19-35 years (36.57%, 79/216). The primary sensitizers were cobalt chloride (22.89%, 92/402) and nickel sulfate (19.90%, 80/402). The highest proportion of severe reactions (+++) was observed with thimerosal (10/16). Males exhibited significantly higher positive risks for carba mix ( OR=5.10, P=0.002) and octyl gallate ( OR=2.64, P=0.047) compared to females. The age-stratified results revealed that the cobalt chloride positive rate was abnormally increased to 76.72% (50/65) in the 36-50 years age group, a rate significantly higher than those observed in the ≤18 years group (20.00%), the 19-35 years group (21.51%), and the >50 years group (16.13%; all P<0.05). In contrast, the >50 years age group exhibited the highest positive rate for nickel sulfate among all age groups at 20.96% (13/62). No significant correlations were found between the number of positive patch tests, reaction intensity (average/maximum), and total IgE ( r=-0.075-0.063), absolute and percentage of eosinophils ( P>0.05). Clinically, eczema prevalence in the>50 age group was 22.58% (14/62), with ACD complicated by allergic dermatitis being the most common (16.67%, 36/216). Conclusion:Nickel sulfate and cobalt chloride are primary sensitizers for ACD. Sensitization patterns across age groups are similar and unrelated to IgE/EOS levels. The higher incidence of severe reactions to thimerosal may be linked to heightened sensitization to mercury-containing products like vaccine preservatives. The notably increased cobalt chloride positivity in the 36-50 age group suggests a unique exposure risk, while the higher prevalence in females may be associated with contact with nickel/cobalt-containing items such as jewelry and cosmetics.

Objective To explore the mechanism of Cistanche phenylethanoid glycosides(CPhGs)in treating osteoporosis by regu-lating osteogenic differentiation via SIRT2-C/EBPβ-AREG axis.Methods An osteoporosis mouse model was established using ova-riectomy.Trabecular number/thickness,bone formation rate,and tissue morphology were evaluated using micro-computed tomography,calcein double labeling,and hematoxylin and eosin staining,respectively.SIRT2,C/EBPβ,AREG,proteins related to the SIRT2-C/EBPβ-AREG axis,were analyzed by Western blotting and co-immunoprecipitation.The mRNA expression of osteogenic differentiation marker genes OCN,OPN,RUNX2,C/EBPβ,and AREG were detected by real-time quantitative PCR.Results CPhGs intervention significantly improved the trabecular microarchitecture and promoted bone formation in mice undergoing ovariectomy,and the mechanism involved the activation of SIRT2-mediated deacetylation of C/EBPβ,which in turn upregulated AREG expression.Cell experiments confirmed that CPhGs significantly increased the activity of alkaline phosphatase and the expression of osteogenic genes such as OCN,OPN,and RUNX2 in MC3T3-E1 cells by enhancing the interaction between SIRT2 and C/EBPβ.Notably,this effect could be reversed by SIRT2 knockdown.Conclusion CPhGs regulate the osteogenic differentiation process through the SIRT2-C/EBPβ-AREG axis,providing a new molecular target and theoretical basis for the treatment of osteoporosis with the active ingredients of traditional Chinese medicine.

Purpose To investigate the correlation between two autophagy-related proteins,JMY and WHAMM,and autophagic dysfunction and prognosis in gliomas.Methods A total of 113 cases of diffuse gliomas and 14 control brain tissues were collected.The expression of JMY,WHAMM,and autophagy-related markers were evaluated using the EnVision two-step method of immunohistochemistry.Correlations between the expression of JMY and WHAMM and clinicopathological features,prognosis,and autophagy markers were analyzed.Results The high expression rates of JMY and WHAMM in control brain tissue were significantly higher than those in diffuse gliomas.The expressions of JMY and WHAMM were associated with pathological grade and age.Compared with low-grade gliomas(LGG),high-grade gliomas(HGG)showed significantly lower high-expression rates of JMY and WHAMM.Patients with low expres-sion of JMY and WHAMM had shorter overall survival than those with high expression.Cox regression analysis indica-ted that the high pathological grade and low expression of JMY were independent prognostic risk factors.The expression profiles of autophagy markers suggested reduced autophagic activity in HGGs,and JMY expression was positively corre-lated with autophagy markers.Conclusion The high expression rates of JMY and WHAMM are significantly lower in HGGs compared to LGGs.JMY and WHAMM may serve as potential molecular markers for the prognostic evaluation of diffuse gliomas.

Purpose To investigate the correlation between two autophagy-related proteins,JMY and WHAMM,and autophagic dysfunction and prognosis in gliomas.Methods A total of 113 cases of diffuse gliomas and 14 control brain tissues were collected.The expression of JMY,WHAMM,and autophagy-related markers were evaluated using the EnVision two-step method of immunohistochemistry.Correlations between the expression of JMY and WHAMM and clinicopathological features,prognosis,and autophagy markers were analyzed.Results The high expression rates of JMY and WHAMM in control brain tissue were significantly higher than those in diffuse gliomas.The expressions of JMY and WHAMM were associated with pathological grade and age.Compared with low-grade gliomas(LGG),high-grade gliomas(HGG)showed significantly lower high-expression rates of JMY and WHAMM.Patients with low expres-sion of JMY and WHAMM had shorter overall survival than those with high expression.Cox regression analysis indica-ted that the high pathological grade and low expression of JMY were independent prognostic risk factors.The expression profiles of autophagy markers suggested reduced autophagic activity in HGGs,and JMY expression was positively corre-lated with autophagy markers.Conclusion The high expression rates of JMY and WHAMM are significantly lower in HGGs compared to LGGs.JMY and WHAMM may serve as potential molecular markers for the prognostic evaluation of diffuse gliomas.

Objective:To investigate the clinical, imaging and neuropathological characteristics of neuronal intranuclear inclusion disease (NIID) with symptoms of the central nervous system, and to improve the diagnosis and treatments of NIID.Methods:The clinical data of 7 patients with NIID diagnosed by brain biopsy in Xuanwu Hospital, Capital Medical University, Beijing, China from February 2009 to December 2024 were collected. The characteristics of clinical manifestations, imaging, and histology on brain biopsy were retrospectively analyzed.Results:Among the 7 patients, 5 were male and 2 were female. Their ages ranged from 44 to 70 years, median 56 (52, 65) years. Patients were classified into three types of tumor, stroke and encephalitis according to the onset symptoms, imaging manifestations and pathological changes. The chief complaint of the 5 patients was headache, while 4 patients had paroxysmal convulsions, 3 had speech disorders, 2 had abnormal mental behaviors, 2 had memory decline, and 1 had fever accompanied by consciousness disorders. Diffusion-weighted magnetic resonance imaging of the head showed the "ribbon sign" at the junction of the cortex and medulla in 2 cases. Most of the patients had white matter lesions, gyrus swelling and cerebral atrophy. Occasionally gyrus-like enhancement was observed. Brain biopsy reveals the histological changes that matched those on images and initial symptoms. There were proliferation of oligodendrocytes and astrocytes in the white matter, leukoaraiosis and edema, cortical disintegration and lamellar necrosis, as well as infiltration of lymphocytes and microglia, etc. However, the characteristic changes were eosinophilic hyaline inclusions in the nuclei of neurons and astrocytes. Immunohistochemical staining of p62 and ubiquitin showed homogeneous staining in round or ring-shaped nuclei.Conclusions:The clinical manifestations of NIID are highly variable, and a correct diagnosis of NIID requires careful integration of clinical, imaging and histopathologic data. For patients with a high suspicion of NIID, immunohistochemical staining of p62 and ubiquitin is diagnostically valuable.

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:This study aimed to assess the patch test positivity rate, allergen distribution, and their associations with demographic characteristics and immune indicators in patients with allergic contact dermatitis (ACD).Methods:A retrospective medical record analysis was conducted on 402 patients suspected of ACD (338 females, median age 38 years; 64 males, median age 43 years) seen at Xuanwu Hospital, Capital Medical University between June 2023 and June 2024. Standard patch tests (using 100 haptens from the Chinese baseline series) were administered, and serum total IgE and eosinophil levels were measured. Statistical analyses included chi-square tests, t-tests/Mann-Whitney U tests for group comparisons, and Spearman correlation for associations. Results:The overall patch test positivity rate among the 402 patients was 62.69% (252/402), with 85.71% (216/252) showing sensitivity to the top 21 allergens. Predominantly, the affected individuals were females (84.26%, 182/216) aged 19-35 years (36.57%, 79/216). The primary sensitizers were cobalt chloride (22.89%, 92/402) and nickel sulfate (19.90%, 80/402). The highest proportion of severe reactions (+++) was observed with thimerosal (10/16). Males exhibited significantly higher positive risks for carba mix ( OR=5.10, P=0.002) and octyl gallate ( OR=2.64, P=0.047) compared to females. The age-stratified results revealed that the cobalt chloride positive rate was abnormally increased to 76.72% (50/65) in the 36-50 years age group, a rate significantly higher than those observed in the ≤18 years group (20.00%), the 19-35 years group (21.51%), and the >50 years group (16.13%; all P<0.05). In contrast, the >50 years age group exhibited the highest positive rate for nickel sulfate among all age groups at 20.96% (13/62). No significant correlations were found between the number of positive patch tests, reaction intensity (average/maximum), and total IgE ( r=-0.075-0.063), absolute and percentage of eosinophils ( P>0.05). Clinically, eczema prevalence in the>50 age group was 22.58% (14/62), with ACD complicated by allergic dermatitis being the most common (16.67%, 36/216). Conclusion:Nickel sulfate and cobalt chloride are primary sensitizers for ACD. Sensitization patterns across age groups are similar and unrelated to IgE/EOS levels. The higher incidence of severe reactions to thimerosal may be linked to heightened sensitization to mercury-containing products like vaccine preservatives. The notably increased cobalt chloride positivity in the 36-50 age group suggests a unique exposure risk, while the higher prevalence in females may be associated with contact with nickel/cobalt-containing items such as jewelry and cosmetics.

Objective:To analyze the imaging features of primary leiomyosarcoma of the inferior vena cava (PLV).Methods:This study was a case series analysis. The clinical and imaging data of 17 patients with PLV confirmed by pathology who underwent CT, MRI and/or PET-CT examinations in the Second Affiliated Hospital of Zhejiang University School of Medicine from June 2012 to September 2022 were retrospectively collected. The CT or MRI findings, including the number, location, size, shape, margin, density (signal), enhancement characteristics, surrounding invasion, and metastasis of the lesion were analyzed.Results:Among the 17 cases there were 7 males and 10 females, aged 32 to 78 years. All patients had single tumors, the maximum diameter of the mass was 3.8 to 19.0 cm, and in 12 cases it was consistent with the inferior venacava.There were 11 cases of "petal-like" necrosis cystic lesion, and 6 cases of "fissure" necrosis cystic lesion. Collateral circulation was found around the mass in 15 cases. There were 3 cases of intraluminal type, 2 cases of extraluminal type, and 12 cases of junctional type. The tumors of intraluminal type presented as "worm-like" appearance, while the extraluminal and junctional type tumors presented as lobulated shape, with local "umbilical depression sign". The margins were clear in 3 cases and unclear in 14 cases. Vascular invasion by the mass was observed in 7 cases. On CT plain scan, the solid component of PLV presented as isodense or slightly hypodense. On MRI T1-weighted images, the solid component presented as isodense or slightly hypodense, and on fat-suppressed T2-weighted images, it presented as isodense or slightly hyperdense. On MRI diffusion-weighted imaging, 12 cases showed high signal intensity, and the corresponding apparent diffusion coefficient map showed low signal intensity. On CT enhanced scan, 8 cases showed mild to moderate enhancement of the solid part of PLV in the arterial phase and 9 cases showed obvious enhancement. In the venous phase and delayed phase, 10 cases showed continuous enhancement and 7 cases showed progressive enhancement. On MRI enhanced scan, 8 cases showed moderate enhancement and 6 cases showed obvious enhancement of the solid part of PLV in the arterial phase. In the venous phase and delayed phase, continuous progressive enhancement was observed; no enhancement was seen in the necrotic and cystic areas.Conclusion:The imaging characteristics of PLV show that the maximum diameter of the masses are consistent with the direction of inferior vena cava, most masses exhibit a "petal-like" necrotic cyst morphology with collateral circulation, and a localized "umbilical concave sign", and some cases possess hemophilic tube features.