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 analyze the predictive value of different obesity indicators on acute cerebral infarction in patients with transient ischemic attack (TIA). Methods A total of 310 patients with TIA admitted to Tangdu Hospital of Air Force Medical University from March 2022 to September 2025 were selected and classified into non-event group (276 cases) and cerebral infarction group (34 cases) based on acute cerebral infarction within 90 days. The basic data and obesity-related indicators [body mass index (BMI), waist-to-hip ratio, body adiposity index (BAI), conicity index (C-index) and a body shape index (ABSI were compared. Multivariate logistic regression analysis was utilized to screen the independent influencing factors. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive efficiency. Results The age, proportions of concurrent hypertension and concurrent diabetes mellitus, ABCD2 score, waist-to-hip ratio, ABSI, C-index, BMI and BAI in the cerebral infarction group were older or higher than those in the non-event group, and the symptoms duration was longer (P<0.05). The above indicators were all related factors for acute cerebral infarction in patients with TIA within 90 days (P<0.05), and ABSI and ABCD² score were independent influencing factors (P<0.05). The prediction model was manifested as Logit (P)=− 4.205 + 0.482 × ABCD² score + 1.120 × ABSI × 100. ABSI and ABCD2 score had predictive value on the occurrence of acute cerebral infarction (P<0.05), and the predictive efficiency of combined model was higher than that of single indicator (P<0.05). Conclusion Among different obesity indicators, ABSI has the highest value on predicting recent acute cerebral infarction in TIA. The prediction model based on ABSI and ABCD2 score exhibits the best predictive efficiency.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Objective:To investigate the role and underlying mechanism of protein arginine methyltransferase 1 (PRMT1) and its inhibitor in alkali burn-induced corneal neovascularization (CNV).Methods:Seventy-two SPF-grade C57BL/6 mice were randomly divided into a normal group and 1 day post-modeling, 4 days post-modeling, and 7 days post-modeling groups to establish an alkali burn-induced CNV model and determine the optimal time point for analysis.Another 90 mice were randomly assigned to five groups: alkali burn group, dimethyl sulfoxide (DMSO) group, PRMT1 inhibitor group, fibroblast growth factor 2 (FGF2) inhibitor group, and PRMT1 inhibitor combined with FGF2 group to evaluate the role of PRMT1 in CNV.Human umbilical vein endothelial cells (HUVECs) and murine macrophage-like RAW264.7 cells were used to establish a hypoxia/reoxygenation (H/R)-induced in vitro model to mimic the ischemic microenvironment.Cells were assigned to the following groups: control group, H/R group, H/R+ DMSO group, H/R+ si-NC group, H/R+ si-PRMT1 group, H/R+ si-FGF2 group, H/R+ PRMT1 inhibitor group, and H/R+ PRMT1 inhibitor+ FGF2 group.Corneal opacity and CNV areas were assessed by slit-lamp microscopy.Corneal structural changes and inflammatory cell count were determined by hematoxylin and eosin staining.PRMT1-positive cell count was determined by immunohistochemistry and the expression of PRMT1, CD31, vascular endothelial growth factor (VEGF), F4/80, CD206, and inducible nitric oxide synthase (iNOS) was assessed by immunofluorescence staining.The expression levels of macrophage markers, including F4/80, iNOS, CD206, interleukin-10 (IL-10), and arginase-1 (Arg-1), were quantified by real-time quantitative PCR and Western blot.Cell proliferation, migration, and angiogenic capacity were evaluated by functional assays including the CCK-8 assay, wound healing assay, Transwell migration assay, and tube formation assay.The research process followed the relevant regulations of the Visual and Ophthalmology Association, and the research plan was approved by the Laboratory Animal Committee of Wuhan University (No.20220504A). Results:Compared with the normal group, the 7 days post-modeling group showed significantly increased corneal opacity scores and CNV area, upregulated VEGF expression, and increased inflammatory cells (all P<0.05).The number of PRMT1-positive cells in the alkali burn group was (39.67±3.51) cells/visual field, which was significantly higher than (3.33±0.58) cells/visual field in the normal group ( t=17.68, P<0.01).Both mRNA and protein expression levels of PRMT1 and FGF2 were significantly elevated in the alkali burn group compared with the normal group (all P<0.01).Compared with the alkali burn group, the PRMT1 inhibitor group showed reduced corneal opacity scores, decreased CNV area, fewer inflammatory cells, and lower expression levels of PRMT1, FGF2, VEGF, Arg-1, IL-10 proteins, as well as CD206 mRNA (all P<0.05).Cell viability, migration distance, migration number, and tubes formed were significantly increased in the H/R group compared with the control group, significantly reduced in the H/R+ si-PRMT1 and H/R+ PRMT1 inhibitor groups compared with the H/R group and significantly increased in H/R+ PRMT1 inhibitor+ FGF2 group than in H/R+ PRMT1 inhibitor group (all P<0.05).Compared with the H/R group, the H/R+ PRMT1 inhibitor group exhibited reduced expression of FGF2, VEGFA, p-PI3K, and p-Akt, while those were upregulated in the H/R+ PRMT1 inhibitor+ FGF2 group compared with the H/R+ PRMT1 inhibitor group (all P<0.05).The proportions of CD206-positive cells in the H/R, H/R+ DMSO, H/R+ PRMT1 inhibitor, and H/R+ PRMT1 inhibitor+ FGF2 groups were all significantly higher than those in the control group, and significantly higher in the H/R, H/R+ DMSO, and H/R+ PRMT1 inhibitor+ FGF2 groups compared with the H/R+ PRMT1 inhibitor group (all P<0.05).Compared with the alkali burn group, the FGF2 inhibitor group, PRMT1 inhibitor group, and PRMT1 inhibitor+ FGF2 group all showed reduced corneal opacity scores, CNV area, and decreased number of VEGFA-, CD206-, and F4/80-positive cells, with the above indicators being lower in the PRMT1 inhibitor group compared with the FGF2 inhibitor and PRMT1 inhibitor+ FGF2 groups and higher in PRMT1 inhibitor+ FGF2 group than in the FGF2 inhibitor group (all P<0.05).Compared with the alkali burn group, the PRMT1 inhibitor group had decreased protein expression levels of FGF2, p-PI3K, p-Akt, CD31, VEGFA and Arg-1, with higher protein expression levels in the PRMT1 inhibitor+ FGF2 group than in the PRMT1 inhibitor group (all P<0.05). Conclusions:PRMT1 may regulate macrophage activation and anti-inflammatory polarization via the FGF2/PI3K/Akt signaling pathway, thereby promoting the occurrence and development of CNV.Targeted inhibition of PRMT1 may serve as an effective therapeutic strategy for CNV.

Objective To observe the complication incidences after percutaneous lung biopsy and sealed the tract with different sealants.Methods A total of 129 patients with solitary pulmonary nodule who underwent CT-guided percutaneous lung biopsy were retrospectively included and divided into group A(n=37),B(n=47)and C(n=45).The biopsy tract was sealed with sealant A(1 g gelatin sponge particles mixed with 10 ml 50％glucose solution)in group A,with sealant B(1 g gelatin sponge particles mixed with 10 ml normal saline)in group B,while with sealant C(1 g gelatin sponge particles mixed with the coagulant enzyme from Bothrops atrox venom and 10 ml normal saline)in group C.The incidence rate of complications such as pneumothorax and hemoptysis were comparatively observed among groups.Binary logistic regression was performed to screen the independent influencing factors associated with complications of percutaneous lung biopsy.Results No significant difference of gender,age,proportion of smoking history nor emphysema,diameter of pulmonary nodules,depth of puncture into lung parenchyma nor times of puncture was found among groups(all P＞0.05).Complications occurred in 43 cases(43/129,33.33％),i.e.27 cases in group B(27/47,57.45％),11 cases in group A(11/37,29.73％)and 5 cases in group C(5/45,11.11％),and the complication rates decreased order of group B,A and C(all P＜0.05).Compared with sealant A,sealant B was associated with increased risk(OR[95％CI]=3.190[1.183,8.598],P=0.022),whereas sealant C was associated with reduced risk(OR[95％CI]=0.266[0.079,0.889],P=0.031)of complications.Conclusion After percutaneous lung biopsy,the complication incidences decreased sequentially when the needle tract was sealed with saline B,A and C.

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.