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.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Depressive disorder is a kind of mental disorder characterized by persistent and significant depressed mood, with complex etiology and high recurrence rate. At present, more precise and effective diagnostic and therapeutic approaches are still required. Increasing evidence suggests that hypoxia inducible factor-1 (HIF-1) and related pathways are involved in regulating the development and recovery of depression. HIF-1 enhances neuroplasticity, mitigates neuroinflammatory responses, alleviates oxidative stress, and modulates brain energy metabolism by influencing specific molecules associated with depression. This paper reviews pertinent domestic and international studies, examine the potential mechanisms of HIF-1 in the pathogenesis and progression of depression, and explore antidepressant treatment strategies targeting the HIF-1 signaling pathway. This article provides novel insights into elucidating the pathogenesis of depression and developing innovative therapeutic approaches.

Objective:To explore the predictive value of electrocardiogram repolarization related parameters combined with serum brain natriuretic peptide(BNP)and 25 hydroxyvitamin D3[25-(OH)-D3]for malignant arrhythmia(MA)after percutaneous coronary intervention(PCI)in patients with acute myocardial infarction.Methods:This study was a prospective single-center study,120 patients with acute myocardial infarction who underwent PCI in our hospital from June 2022 to June 2024 were selected,they were divided into combined group(n=25)and non combined group(n=95)based on whether MA occurred within 72 h after PCI.All patients underwent routine electrocardiogram examination,the mean R wave to R wave(RR)interval,QRS start to T end(QT)interval,T wave time,corrected QT(QTc)interval,T wave peak to T wave end(Tp-e)interval,T wave amplitude,and other electrocardiogram repolarization related parameters between two groups were measuredand compared.The serum BNP and 25-(OH)-D3 levels between two groups were detected and compared.Influencing factors were analyzed by single and multiple logistic regression analysis.Predict value was analyzed by receiver operating characteristic(ROC)curve.Results:The mean QT interval and QTc interval in the combined group were significantly lower than those in the non combined group(P＜0.05).The serum BNP levels in the combined group was significantly higher than that in the non combined group,and the serum 25-(OH)-D3 level was significantly lower than that in the non combined group(both P＜0.05).Univariate analysis showed that there were statistically significant differences in terms of age,number of vascular lesions,cardiac troponin I(cTnI),and creatine kinase MB(CK-MB)(P＜0.05).Multiple logistic regression analysis showed that serum CK-MB and BNP were independent risk factors for MA after PCI in patients with acute myocardial infarction,while mean QT interval,mean QTc interval,and elevated 25-(OH)-D3 were independent protective factors(P＜0.05).Draw ROC curves,and the results show that the mean QT interval,mean QTc interval,serum BNP,and 25-(OH)-D3 levels alone predict the area under curve(AUC)for postoperative MA after PCI was 0.762(0.706-0.817),0.822(0.772-0.871),0.809(0.757-0.862),and 0.709(0.642-0.775),respectively,the AUC for combined prediction was 0.882(0.843-0.920).Conclusion:Electrocardiogram repolarization related parameters such as mean QT interval and QTc interval for MA after PCI in patients with acute myocardial infarction were lower,serum BNP is increased,and 25-(OH)-D3 is decreased,the combined detection of these indicators has high predictive value for postoperative MA after PCI.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Depressive disorder is a kind of mental disorder characterized by persistent and significant depressed mood, with complex etiology and high recurrence rate. At present, more precise and effective diagnostic and therapeutic approaches are still required. Increasing evidence suggests that hypoxia inducible factor-1 (HIF-1) and related pathways are involved in regulating the development and recovery of depression. HIF-1 enhances neuroplasticity, mitigates neuroinflammatory responses, alleviates oxidative stress, and modulates brain energy metabolism by influencing specific molecules associated with depression. This paper reviews pertinent domestic and international studies, examine the potential mechanisms of HIF-1 in the pathogenesis and progression of depression, and explore antidepressant treatment strategies targeting the HIF-1 signaling pathway. This article provides novel insights into elucidating the pathogenesis of depression and developing innovative therapeutic approaches.

Major depressive disorder (MDD) is a common mental disorder characterized by long-term low mood, anhedonia, and may even lead to suicidal behavior. The development and progression of MDD involves a range of pathological alterations in the central nervous system, including dysfunction of synaptic transmission, hyper-activation of neuroinflammation, and diminished neurogenesis. The transient receptor potential vanilloid 1 (TRPV1) channel is highly expressed in brain regions associated with depression, and can regulate physiological activities such as neuroinflammation, neurogenesis, and synaptic transmission efficacy. Hence, the TRPV1 channel should be implicated in the pathogenesis of depression and be considered as a promising candidate for antidepressant treatment. This paper provides an overview of the structure and function of TRPV1 channel, with a focus on elucidating the potential mechanism of action of TRPV1 channel in depression, and explores its research trajectory and development prospects in the context of depression therapy.

Objective:To explore the predictive value of electrocardiogram repolarization related parameters combined with serum brain natriuretic peptide(BNP)and 25 hydroxyvitamin D3[25-(OH)-D3]for malignant arrhythmia(MA)after percutaneous coronary intervention(PCI)in patients with acute myocardial infarction.Methods:This study was a prospective single-center study,120 patients with acute myocardial infarction who underwent PCI in our hospital from June 2022 to June 2024 were selected,they were divided into combined group(n=25)and non combined group(n=95)based on whether MA occurred within 72 h after PCI.All patients underwent routine electrocardiogram examination,the mean R wave to R wave(RR)interval,QRS start to T end(QT)interval,T wave time,corrected QT(QTc)interval,T wave peak to T wave end(Tp-e)interval,T wave amplitude,and other electrocardiogram repolarization related parameters between two groups were measuredand compared.The serum BNP and 25-(OH)-D3 levels between two groups were detected and compared.Influencing factors were analyzed by single and multiple logistic regression analysis.Predict value was analyzed by receiver operating characteristic(ROC)curve.Results:The mean QT interval and QTc interval in the combined group were significantly lower than those in the non combined group(P＜0.05).The serum BNP levels in the combined group was significantly higher than that in the non combined group,and the serum 25-(OH)-D3 level was significantly lower than that in the non combined group(both P＜0.05).Univariate analysis showed that there were statistically significant differences in terms of age,number of vascular lesions,cardiac troponin I(cTnI),and creatine kinase MB(CK-MB)(P＜0.05).Multiple logistic regression analysis showed that serum CK-MB and BNP were independent risk factors for MA after PCI in patients with acute myocardial infarction,while mean QT interval,mean QTc interval,and elevated 25-(OH)-D3 were independent protective factors(P＜0.05).Draw ROC curves,and the results show that the mean QT interval,mean QTc interval,serum BNP,and 25-(OH)-D3 levels alone predict the area under curve(AUC)for postoperative MA after PCI was 0.762(0.706-0.817),0.822(0.772-0.871),0.809(0.757-0.862),and 0.709(0.642-0.775),respectively,the AUC for combined prediction was 0.882(0.843-0.920).Conclusion:Electrocardiogram repolarization related parameters such as mean QT interval and QTc interval for MA after PCI in patients with acute myocardial infarction were lower,serum BNP is increased,and 25-(OH)-D3 is decreased,the combined detection of these indicators has high predictive value for postoperative MA after PCI.

AIM To investigate the effects of Shuyu Pills combined with evolimus on the epithelial mesenchymal transformation of triple negative breast cancer cells 4T1 and MDA-MB-231 induced by TGF-β1.METHODS The 4T1 and MDA-MB-231 cells were divided into the blank group and the induction group to induce the epithelial mesenchymal transformation with TGF-β1 cytokine treatment,followed by the assignment into the model group,the Shuyu Pills group,the everolimus group and the Shuyu Pills combined with everolimus group.CCK8 method,plate cloning method,cell scratch test and Transewll test were used to detect the proliferation,cloning formation,migration and invasion ability of the cells whose expressions of E-cadherin,N-cadherin,Vimentin,MMP9,MMP2 and pathway proteins PTEN,PI3K,Akt and mTOR were detected by Western blot.RESULTS Compared with the blank group,the induction group displayed a cell morphological change from epithelioid to stromal,decreased expression of E-cadherin protein(P＜0.01);and increased protein expressions of N-cadherin and Vimentin(P＜0.05).Compared with the model group,each group intervened with the medicine displayed decreased proliferation,clone formation,migration and invasion ability of both kinds of cells(P＜0.01);increased protein expressions of PTEN and E-cadherin(P＜0.05,P＜0.01);and decreased protein expressions of PI3K,Akt,mTOR,N-cadherin,Vimentin,MMP9 and MMP2(P＜0.05,P＜0.01);and more significantly in the Shuyu Pills combined with evolimus group(P＜0.05,P＜0.01).CONCLUSION With a more ideal effect than the single uses in inhibiting the TGF-β1-induced epithelial mesenchymal transformation of triple-negative breast cancer cells,the combination use of Shuyu Pills and everolimus may work through the regulation of PI3K/Akt/mTOR signaling pathway.