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.

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: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 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.

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: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 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.

Purpose To investigate the clinical pathology of SMARCB1/INI1-deficient poorly differentiated chordoma.Methods Ten patients with poorly differentiated chordoma were collected.The expression of CK,vimentin,INI1,and Brachyu-ry was detected using EnVision immunohistochemistry.Clinical characteristics,histopathological features,as well as related prognosis were analyzed and the literature was reviewed.Results Among the 10 cases,including 5 males and 5 females,the mean age of onset was 4 years.10 cases were located in the cliv-us and had bone invasion,3 involved the cervical spine(18.2％).In morphology,tumor cells showed sheet or nest mass growth,with epithelioid tumor cells.The nucleus was round or oval,with obvious atypia and visible nucleoli.Mitotic figures were active.Lymphocytic infiltration was noted in the stroma.Tumor cells in 10 cases were positive for CK,Vimen-tin,EMA and Brachyury with loss of SMARCB1/INI1 expres-sion.Ten patients were followed-up postoperatively.5 patients had tumor recurrence(median progression-free survival was 4 months)and 7 died(median overall survival was 5 months).Conclusion SMARCB1/INI1-deficient poorly-differentiated chordoma is a relatively rare bone tumor with poor prognosis and challenging diagnosis.Understanding the clinical pathological characteristics of this tumor has great significance for diagnosis and treatment.

Objective:To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

Objective:To evaluate clinical efficacy of adjuvant radiotherapy (RT) for central neurocytoma (CN) after surgical resection.Methods:Clinical data of 136 CN patients admitted to Beijing Tiantan Hospital and Xuanwu Hospital from January 2001 to December 2020 were retrospectively analyzed. Preliminary interventions consisted of craniotomy (gross total resection, subtotal resection and partial resection, the latter two belonging to incomplete resection) and postoperative radiotherapy. Three-dimensional conformal or intensity-modulated radiotherapy was adopted, with a median radiotherapy dose of 54 Gy. Post-recurrence treatment included salvage surgery and radiotherapy. The overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Univariate analysis was performed by log-rank test to evaluate the effect of each prognostic factor on OS and PFS. The effects of multiple prognostic factors on PFS and OS were assessed by Cox regression model.Results:The median age was 28 years (range: 6-66 years). The median follow-up was 94.5 months (12-237 months). Among all patients, 79 cases underwent total resection, and 68 of them received adjuvant radiotherapy. Thirty-eight patients underwent subtotal resection, and 37 of them were treated with adjuvant radiotherapy. Sixteen patients received partial resection and adjuvant radiotherapy. Three cases received biopsy and postoperative radiotherapy. Among all patients, 3 cases died, including 2 from tumor recurrence and 1 from postoperative complication. Eight patients had recurrences during follow-up. Among them, 7 patients had recurrences at the primary site,1 had tumor dissemination to the spinal cord. The 5- and 10-year OS rates were 98.5% and 96.8%, and the 5- and 10-year PFS rates were 95.3% and 91.6% for the in the entire cohort. In the gross total resection without radiotherapy group, the 5- and 10-year PFS rates were 90.9% and 90.9%, and 96.6% and 96.6% in the gross total resection + radiotherapy group ( P=0.338). The 5- and 10-year OS rates were 100% and 100% in the gross total resection without radiotherapy group, and 98.5% and 98.5% in the gross total resection + radiotherapy group ( P=0.693). The 10-year PFS rates between the gross total resection±radiotherapy group and the incomplete resection+radiotherapy group was 95.8% vs. 90.3% ( P=0.368), and the 10-year OS rate was 98.6% vs. 94.7% ( P=0.436). Multivariate analysis showed that tumor site, degree of surgical resection, adjuvant radiotherapy and age exerted no significant effects on PFS and OS. A total of 81 patients had late neurotoxicities, including 69 cases at grade 1, 9 cases at grade 2, and 3 cases at grade 3. And 64.2% (52/81 cases) of patients suffered from short-term memory impairment. Conclusions:Gross total resection alone yields high efficacy for CN. Postoperative radiotherapy is not required. Incomplete resection combined with postoperative adjuvant radiotherapy can achieve equivalent clinical efficacy to gross total resection.