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.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in adolescents, with potential causes etiologies associated with mesenchymal stem cells, genetic factors, histological features, and biomechanical aspects. Biomechanically, the pelvis, serving as the central and majort load-bearing structure, exhibits morphological and alignment abnormalities highly correlated with the development of AIS. Recent studies have extensively explored three-dimensional pelvic parameters and kinematics, demonstrating that abnormal pelvic characteristics may contribute to AIS onset and progression and are increasingly incorporated into clinical interventions. This review summarizes sagittal and coronal features of the spine-pelvis, as well as the influence of three-dimensional kinematic features on the pathogenesis of AIS, providing insights for advancing the study of spine-pelvis features related to AIS.
Humans ; Scoliosis/pathology* ; Adolescent ; Spine/pathology* ; Pelvis/pathology* ; Biomechanical Phenomena

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.
Lupus Erythematosus, Systemic/immunology* ; Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Animals

OBJECTIVES: Magnetic resonance imaging (MRI) was used to study the efficacy of modified anterior splint (MAS) combined with anterior repositioning splint (ARS) in maintaining the normal disk-condyle relationship. METHODS: We obtained clinical and imaging data of 10 patients with acute anterior disk displacement without reduction (ADDwoR) of the temporomandibular joint undergoing successful mandibular manipulation in the Affiliated Stomatological Hospital, Nanchang University from January to June 2024. The MAS and ARS were used for subsequent treatment. Maximum active mouth opening (MMO) and visual analogue score (VAS) were recorded before treatment and 2 weeks, 1 month, and 3 months after treatment. The changes in the disk-condyle relationship, disk-condyle angle, joint effusion, and double contour sign before and after treatment were analyzed through MRI. RESULTS: Three months after treatment, the MMO increased from 28.90 mm to 46.85 mm, VAS decreased from 4.68 to 0.61, and the disk-condyle angle decreased from 58.84° to 25.99°. MRI analysis found that 6 patients showed normal disk-condyle relationship, 2 patients exhibited displacement with reduction, and 2 patients exhibited ADDwoR. The disk-condyle angle was 58.84° before treatment and 25.99° after treatment. CONCLUSIONS The MAS combined with ARS could further stabilize the coordinated disk-condyle relationship and reduce the recurrence rate.
Humans ; Male ; Magnetic Resonance Imaging ; Female ; Adult ; Temporomandibular Joint Disorders/diagnostic imaging* ; Splints ; Middle Aged ; Mandible ; Temporomandibular Joint Disc ; Occlusal Splints ; Temporomandibular Joint ; Young Adult ; Joint Dislocations/therapy*

Family with sequence similarity 3 member A(FAM3A),a novel mitochondrial protein,plays a pivotal role in hepatic glucose and lipid metabolism by enhancing ATP synthesis and secretion and mod-ulating the ATP-P2 receptor-Akt signaling pathway.Dysregulation of FAM3A is closely associated with the pathogenesis of non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM).In this study,targeting FAM3A as a therapeutic candidate,we conducted virtual screening to identify 47 small-molecule compounds with potential binding activity.Surface plasmon resonance(SPR)analysis re-vealed three compounds exhibiting high binding affinity to FAM3 A.Further structural characterization of the FAM3A-compound complexes,combined with intermolecular interaction analysis,elucidated the binding mode of the lead compound Index 2(taxifolin)to FAM3A at atomic resolution.These findings provide critical insights into the molecular mechanisms underlying ligand-FAM3A interactions and deliver valuable chemical scaffolds for the development of therapeutics targeting NAFLD and T2DM.This work establishes a foundation for advancing drug discovery efforts focused on FAM3A-mediated metabolic disor-ders.

Objective:This study aimed to evaluate the value of CT-based radiomics machine learning models in predicting spread through air spaces(STAS)in lung adenocarcinoma(LUAD)and to determine the optimal peritumoral analysis region.Methods:Data from 378 pa-tients who underwent non-small cell lung cancer surgery at Zhejiang Cancer Hospital between January 2013 to January 2017 were retro-spectively analyzed.Logistic regression,random forest,and XGBoost models were constructed using regions extending 0,3,6,9,and 12 mm outward from the tumor margin.Results:The XGBoost model using the 6 mm peritumoral region performed best on the test set,with an AUC-ROC of 0.855(95%CI:0.756-0.950),followed by the XGBoost model using the 9 mm region.Decision curve analysis(DCA)indicated that the XGBoost models for the 6 mm and 9 mm regions had higher net clinical benefits.Feature analysis revealed that some wavelet trans-form features significantly contributed to STAS prediction.Conclusions:This preliminary study suggests that CT-based radiomics machine learning models have predictive value for STAS.The XGBoost model based on the 6 mm peritumoral region demonstrated the best perform-ance,and holds promise in assisting preoperative assessment.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Family with sequence similarity 3 member A(FAM3A),a novel mitochondrial protein,plays a pivotal role in hepatic glucose and lipid metabolism by enhancing ATP synthesis and secretion and mod-ulating the ATP-P2 receptor-Akt signaling pathway.Dysregulation of FAM3A is closely associated with the pathogenesis of non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM).In this study,targeting FAM3A as a therapeutic candidate,we conducted virtual screening to identify 47 small-molecule compounds with potential binding activity.Surface plasmon resonance(SPR)analysis re-vealed three compounds exhibiting high binding affinity to FAM3 A.Further structural characterization of the FAM3A-compound complexes,combined with intermolecular interaction analysis,elucidated the binding mode of the lead compound Index 2(taxifolin)to FAM3A at atomic resolution.These findings provide critical insights into the molecular mechanisms underlying ligand-FAM3A interactions and deliver valuable chemical scaffolds for the development of therapeutics targeting NAFLD and T2DM.This work establishes a foundation for advancing drug discovery efforts focused on FAM3A-mediated metabolic disor-ders.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:This study aimed to evaluate the value of CT-based radiomics machine learning models in predicting spread through air spaces(STAS)in lung adenocarcinoma(LUAD)and to determine the optimal peritumoral analysis region.Methods:Data from 378 pa-tients who underwent non-small cell lung cancer surgery at Zhejiang Cancer Hospital between January 2013 to January 2017 were retro-spectively analyzed.Logistic regression,random forest,and XGBoost models were constructed using regions extending 0,3,6,9,and 12 mm outward from the tumor margin.Results:The XGBoost model using the 6 mm peritumoral region performed best on the test set,with an AUC-ROC of 0.855(95%CI:0.756-0.950),followed by the XGBoost model using the 9 mm region.Decision curve analysis(DCA)indicated that the XGBoost models for the 6 mm and 9 mm regions had higher net clinical benefits.Feature analysis revealed that some wavelet trans-form features significantly contributed to STAS prediction.Conclusions:This preliminary study suggests that CT-based radiomics machine learning models have predictive value for STAS.The XGBoost model based on the 6 mm peritumoral region demonstrated the best perform-ance,and holds promise in assisting preoperative assessment.