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.

This study systematically dissects the core pathogenesis of chronic heart failure （CHF） featured by internal deficiency and external excess，imbalance of Qi，blood，Yin，and Yang，and intermingling of phlegm，blood stasis，and fluid retention. According to the traditional Chinese medicine （TCM） therapeutic principles of simultaneously treating root cause and symptoms，regulating Yin and Yang，replenishing Qi and activating blood，and promoting urination to relieve edema，this article deeply explores the formula-syndrome correspondence of Qili Qiangxin （QLQX） capsules in the treatment of CHF，providing a solid theoretical basis for the multi-effect characteristics of this drug. CHF is a common critical cardiovascular disease in clinical practice，and its pathological process involves multiple links including myocardial injury，neurohumoral disturbance，and ventricular remodeling. Its TCM pathogenesis is complex and involves multiple Zang-Fu organs，making it difficult for a single therapeutic method to achieve comprehensive coverage. QLQX capsules，formulated based on classical TCM theory，perfectly matches the pathogenic characteristics of CHF. Modern pharmacological studies have confirmed that QLQX capsules possess definite cardiotonic，diuretic，and vasodilatory effects. The active ingredients of QLQX capsules can rapidly and effectively alleviate the core clinical symptoms such as chest tightness，shortness of breath，decreased exercise tolerance，limb edema，palpitations，and fatigue of CHF patients by enhancing myocardial contractility and coronary blood flow，improving renal water excretion function，dilating peripheral blood vessels，and reducing cardiac load，thereby significantly improving patients' quality of life. On the basis of analyzing the symptomatic treatment of CHF with QLQX capsules，this study further expounds that the drug can intervene in ventricular remodeling through multiple pathways and targets，regulate the pathological mechanism of CHF，improve vascular endothelial function，mediate the activation of related signaling pathways，inhibit the transdifferentiation of cardiac fibroblasts，and regulate myocardial energy metabolism，thus delaying disease progression. QLQX capsules exert significant benefits in reducing composite cardiac events，improving New York Heart Association （NYHA） cardiac function classification，left ventricular ejection fraction （LVEF），6-minute walking distance （6MWD），and quality of life，demonstrating favorable clinical value. With the TCM pathogenesis of CHF as the guiding principle and modern pharmacology as the evidence，this study systematically clarifies the core advantage of QLQX capsules in treatment based on syndrome differentiation and multi-target synergy through the in-depth integration of TCM theory and modern pharmacology. It provides academic support with both theoretical depth and practical value for TCM intervention in CHF，and contributes TCM wisdom and schemes to the construction of a chronic disease management system with Chinese characteristics.

This study systematically dissects the core pathogenesis of chronic heart failure （CHF） featured by internal deficiency and external excess，imbalance of Qi，blood，Yin，and Yang，and intermingling of phlegm，blood stasis，and fluid retention. According to the traditional Chinese medicine （TCM） therapeutic principles of simultaneously treating root cause and symptoms，regulating Yin and Yang，replenishing Qi and activating blood，and promoting urination to relieve edema，this article deeply explores the formula-syndrome correspondence of Qili Qiangxin （QLQX） capsules in the treatment of CHF，providing a solid theoretical basis for the multi-effect characteristics of this drug. CHF is a common critical cardiovascular disease in clinical practice，and its pathological process involves multiple links including myocardial injury，neurohumoral disturbance，and ventricular remodeling. Its TCM pathogenesis is complex and involves multiple Zang-Fu organs，making it difficult for a single therapeutic method to achieve comprehensive coverage. QLQX capsules，formulated based on classical TCM theory，perfectly matches the pathogenic characteristics of CHF. Modern pharmacological studies have confirmed that QLQX capsules possess definite cardiotonic，diuretic，and vasodilatory effects. The active ingredients of QLQX capsules can rapidly and effectively alleviate the core clinical symptoms such as chest tightness，shortness of breath，decreased exercise tolerance，limb edema，palpitations，and fatigue of CHF patients by enhancing myocardial contractility and coronary blood flow，improving renal water excretion function，dilating peripheral blood vessels，and reducing cardiac load，thereby significantly improving patients' quality of life. On the basis of analyzing the symptomatic treatment of CHF with QLQX capsules，this study further expounds that the drug can intervene in ventricular remodeling through multiple pathways and targets，regulate the pathological mechanism of CHF，improve vascular endothelial function，mediate the activation of related signaling pathways，inhibit the transdifferentiation of cardiac fibroblasts，and regulate myocardial energy metabolism，thus delaying disease progression. QLQX capsules exert significant benefits in reducing composite cardiac events，improving New York Heart Association （NYHA） cardiac function classification，left ventricular ejection fraction （LVEF），6-minute walking distance （6MWD），and quality of life，demonstrating favorable clinical value. With the TCM pathogenesis of CHF as the guiding principle and modern pharmacology as the evidence，this study systematically clarifies the core advantage of QLQX capsules in treatment based on syndrome differentiation and multi-target synergy through the in-depth integration of TCM theory and modern pharmacology. It provides academic support with both theoretical depth and practical value for TCM intervention in CHF，and contributes TCM wisdom and schemes to the construction of a chronic disease management system with Chinese characteristics.

Blonanserin,a second-generation atypical antipsychotic agent,acts as an antagonist for dopamine D2,D3,and serotonin 5-HT2A receptors.Clinical studies have demonstrated that blonanserin is non-inferior to other antipsychotics,such as haloperidol and risperidone,in alleviating the symptoms of schizophrenia.Moreover,it exhib-its beneficial effects on cognitive symptoms and social functioning,with a favorable safety profile,making it one of the key treatment options for schizophrenia.With extensive clinical experience accumulated in China,this expert consensus aims to provide psychiatrists with updated and localized guidance on the optimal use of blonan-serin.Based on a systematic review of the latest evidence-particularly studies in Chinese population,this paper pres-ents the updated Chinese expert recommendations for the clinical use of blonanserin in 2024.

Soybean meal (SBM) prepared by soybean crushing is the most popular protein source in the poultry and livestock industries (Cai et al., 2015) due to its economic manufacture, high protein content, and good nutritional value. Despite these benefits, SBM contains various antigen proteins such as glycinin and β-conglycinin, which account for approximately 70% of the total proteins of the SBM and reduce digestibility and damage intestinal function (Peng et al., 2018). Treating SBM with proteases (neutrase, alcalase, and trypsin) or fermentation can eliminate these antigen proteins (Contesini et al., 2018). Because of its safety and rapid growth cycle, Bacillus strains are considered ideal for the fermentation industry (Yao et al., 2021). SBM fermented by Bacillus yields products with high nutritional value and low levels of antinutritional factors (ANFs), stimulating research in this area (Yuan et al., 2017). Kumari et al. (2023) demonstrated that fermentation with Bacillus species effectively degrades antigen proteins and increases crude protein content. The degradation of antigen proteins relies on protease hydrolysis. Low protease production is the major obstacle hindering the widespread use of microbial fermentation techniques.
Bacillus amyloliquefaciens/metabolism* ; Fermentation ; Glycine max/metabolism* ; Soybean Proteins/metabolism* ; Peptide Hydrolases/metabolism* ; Ribosomes/metabolism* ; Globulins ; Antigens, Plant ; Seed Storage Proteins

Objective To explore the longitudinal associations of body roundness index (BRI), visceral adiposity index (VAI), and metabolic score for visceral fat (METS-VF) with the risk of new-onset atrial fibrillation (AF). Methods This study included participants from the UK Biobank who were free of AF or pregnancy at baseline and completed the first and second assessments of BRI, VAI, and METS-VF. The changes in BRI, VAI, and METS-VF were classified using K-means clustering analyses, and the cumulative adiposity indices were also calculated. The primary outcome was new-onset AF. Three Cox regression models were employed to investigate the longitudinal associations of the BRI, VAI, and METS-VF changes with the risk of incident new-onset AF. The results were presented as hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Restricted cubic spline analyses were performed to explore potential non-linear associations between baseline or cumulative adiposity indices and the risk of new-onset AF. C-index analyses were conducted to evaluate the predictive value of BRI, VAI, and METS-VF for new-onset AF. Subgroup analyses were performed according to age, gender, race, smoking status, alcohol consumption, and physical activity. Polygenic risk scores were applied to account for genetic susceptibility and investigate potential interactions between adiposity indices and genetic risk. Univariate linear regression analyses were performed to evaluate the relationships of cumulative adiposity indices and magnetic resonance imaging and dual X-ray absorptiometry parameters, including visceral adipose tissue (VAT) volume, VAT mass, trunk fat volume, and trunk fat mass. We further applied the eXtreme Gradient Boosting (XGBoost) algorithm, with the feature importance being measured to evaluate the predictive value of each adiposity index for imaging parameters. Mendelian randomization analysis was further conducted to investigate the potential causal relationship between trunk fat mass and AF. Results A total of 12 776 participants were included. Over a median follow-up of 9.60 years, 761 (5.96%) new-onset AF events were recorded. Participants were divided into four classes based on the changes in adiposity indices. In the fully adjusted model, compared to participants in Class 1 of BRI, those in Class 3 (HR＝1.30, 95%CI 1.04-1.63, P＝0.023) and Class 4 (HR＝2.17, 95%CI 1.61-2.93, P＜0.001) were associated with significantly higher risks of new-onset AF. Regarding METS-VF, participants in Class 4 of METS-VF also demonstrated a significantly higher risk of new-onset AF compared to those in Class 1 (HR＝1.66, 95%CI 1.15-2.39, P＝0.007). However, no significant association was observed between different classes of VAI and the risk of new-onset AF. For every 1 standard deviation increase in cumulative BRI, VAI, and METS-VF, the fully adjusted HRs of new-onset AF were 1.23 (95%CI 1.13-1.35), 1.02 (95%CI 0.94-1.10), and 1.23 (95%CI 1.12-1.35), respectively. Cumulative adiposity indices (BRI, VAI, and METS-VF) were divided into quartiles. Using the first quartile as reference, participants in the highest quartiles of BRI (HR＝1.40, 95%CI 1.10-1.79, P＝0.007) and METS-VF (HR＝1.44, 95%CI 1.13-1.83, P＝0.003) both exerted a significantly higher risk of new-onset AF. Regarding VAI, no significant association was observed (HR＝1.00, 95%CI 0.81-1.23, P＝0.988). Restricted cubic spline analyses revealed non-linear relationships between cumulative BRI, baseline/cumulative VAI, and baseline/cumulative METS-VF with new-onset AF risk (all P_overall＜0.05, P_non-linear＜0.05). In the C-index analysis, BRI demonstrated the highest predictive performance for new-onset AF, followed by METS-VF and VAI. Subgroup analysis indicated a stronger association between METS-VF and the risk of new-onset AF amongst participants younger than 60 years (P_interaction＝0.008). Polygenic risk score analysis stratified by genetic risk demonstrated a synergistic effect between BRI and genetic risk with new-onset AF, with the overall risk of new-onset AF increasing as both BRI and genetic risk increased. Linear regression analysis revealed a positive correlation between cumulative BRI with VAT volume, VAT mass, trunk fat volume, and trunk fat mass. The feature importance plot derived from the XGBoost algorithm indicated that cumulative BRI had the greatest predictive value on VAT volume, VAT mass, trunk fat volume, and trunk fat mass. Mendelian randomization analysis confirmed a significant causal relationship between trunk fat mass and AF. Conclusions There are significant non-linear associations between BRI, METS-VF, and VAI with new-onset AF. Higher BRI and METS-VF are significantly associated with a higher risk of new-onset AF, whereas no significant association is observed for the VAI. BRI exhibits a positive correlation with VAT and trunk fat, and demonstrates superior performance in predicting new-onset AF compared to VAI and METS-VF. Monitoring and managing BRI may be important in the early detection and intervention of AF.

Objective To compare the value of three-dimensional tomography ultrasound imaging(3D-TUI)and MRI for diagnosng early cesarean scar pregnancy(CSP).Methods Seventy-six patients who had gestational week not more than 12 weeks and with clinically suspected CSP were retrospectively enrolled.According to surgical and postoperative pathological findings,the patients were categorized into CSP group(n=65)and non-CSP group(n=11).The diagnostic performance of 3D-TUI,MRI and the combination of these two for CSP,also the depiction of CSP characteristics of 3D-TUI and MRI were compared.Results The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of combination of 3D-TUI and MRI for diagnosing CSP was 96.92％,90.91％,96.05％,98.44％and 83.33％,respectively,with the accuracy higher than that of 3D-TUI alone(P＜0.05).No significant difference of diagnostic efficacy was found between 3D-TUI and MRI(all P＞0.05).3D-TUI showed a higher accuracy rate than MRI for displaying yolk sac,embryo,villi invasion into local scars and implantation of villi into muscle layer(all P＜0.05),whereas MRI was more accurate for diagnosing intrauterine bleeding(P＜0.05).Conclusion 3D-TUI could be used as the preferred initial imaging examination for early CSP.Combining with MRI could further improve its diagnostic accuracy.

Objective To compare the value of three-dimensional tomography ultrasound imaging(3D-TUI)and MRI for diagnosng early cesarean scar pregnancy(CSP).Methods Seventy-six patients who had gestational week not more than 12 weeks and with clinically suspected CSP were retrospectively enrolled.According to surgical and postoperative pathological findings,the patients were categorized into CSP group(n=65)and non-CSP group(n=11).The diagnostic performance of 3D-TUI,MRI and the combination of these two for CSP,also the depiction of CSP characteristics of 3D-TUI and MRI were compared.Results The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of combination of 3D-TUI and MRI for diagnosing CSP was 96.92％,90.91％,96.05％,98.44％and 83.33％,respectively,with the accuracy higher than that of 3D-TUI alone(P＜0.05).No significant difference of diagnostic efficacy was found between 3D-TUI and MRI(all P＞0.05).3D-TUI showed a higher accuracy rate than MRI for displaying yolk sac,embryo,villi invasion into local scars and implantation of villi into muscle layer(all P＜0.05),whereas MRI was more accurate for diagnosing intrauterine bleeding(P＜0.05).Conclusion 3D-TUI could be used as the preferred initial imaging examination for early CSP.Combining with MRI could further improve its diagnostic accuracy.

AIM:To investigate the effects of emo-din on autophagy and apoptosis in rats with severe pneumonia(KP)caused by K.pneumoniae and its possible mechanism.METHODS:The KP rat model was established by infecting K pneumonia was treat-ed with Emodin.The rats were grouped into Sham surgery group,KP group,low concentration Emodin group,medium concentration Emodin group,high concentration Emodin group,and Emodin+sirtinol(SIRT1 activity inhibitor)group;Arterial partial pres-sure of carbon dioxide(PaCO2),arterial partial pres-sure of oxygen(PaO2)and arterial oxygen saturation(SaO2)were measured by blood gas analyzer;the white blood cells and neutrophils in bronchoalveo-lar lavage fluid(BALF)were measured by Wright-Gi-emsa staining;HE staining was applied to detect pathological changes in lung tissue in each group;ELISA was applied to detect the expression of IL-6,TNF-α,and IL-1β in lung tissues of each group;elec-tron microscopy scanning was applied to observe the autophagy of cells in lung tissues of each group;the expression of LC3B in lung tissues was observed by immunofluorescence staining;TUNEL method was applied to detect changes in cell apoptosis in lung tissue of rats in each group;Western blot was applied to detect the expression of silent informa-tion regulatory factor(SIRT1),adenosine monophos-phate activated protein kinase(AMPK),LC3-Ⅱ,LC3-Ⅰ,c-caspase-3,and caspase-3 proteins in lung tissue.RESULTS:K.pneumoniae caused severe lung tissue damage in rats with pneumonia,increased inflam-matory infiltration and cytokine release in the lungs,arterial blood PaO2 and SaO2 levels de-creased,PaCO2 levels increased,white blood cells and neutrophils count increased in BALF,increased cell apoptosis rate and c-caspase-3/caspase-3 level,and the cell autophagy and the levels of autophagy related proteins LC3-Ⅱ/LC3-Ⅰ were decreased(all P＜0.05),after Emodin treatment,SIRT1/AMPK signal-ing pathway was activated,PaO2 and SaO2 levels in arterial blood were increased,PaCO2 levels was de-creased,inflammatory reaction was inhibited,cell apoptosis in lung tissue was inhibited(all P＜0.05),and cell autophagy level was restored,sirtinol,a SIRT1 inhibitor,partially reversed the therapeutic ef-fect of Emodin on KP rats after inhibiting SIRT1/AMPK signaling pathway(P＜0.05).CONCLUSION:Emodin may enhance autophagy of lung tissue cells and inhibit apoptosis of rat lung tissue cells by acti-vating SIRT1/AMPK pathway,which may provide po-tential therapeutic options for KP.

Objective To explore the longitudinal associations of body roundness index(BRI),visceral adiposity index(VAI),and metabolic score for visceral fat(METS-VF)with the risk of new-onset atrial fibrillation(AF).Methods This study included participants from the UK Biobank who were free of AF or pregnancy at baseline and completed the first and second assessments of BRI,VAI,and METS-VF.The changes in BRI,VAI,and METS-VF were classified using K-means clustering analyses,and the cumulative adiposity indices were also calculated.The primary outcome was new-onset AF.Three Cox regression models were employed to investigate the longitudinal associations of the BRI,VAI,and METS-VF changes with the risk of incident new-onset AF.The results were presented as hazard ratios(HRs)and the corresponding 95%confidence intervals(CIs).Restricted cubic spline analyses were performed to explore potential non-linear associations between baseline or cumulative adiposity indices and the risk of new-onset AF.C-index analyses were conducted to evaluate the predictive value of BRI,VAI,and METS-VF for new-onset AF.Subgroup analyses were performed according to age,gender,race,smoking status,alcohol consumption,and physical activity.Polygenic risk scores were applied to account for genetic susceptibility and investigate potential interactions between adiposity indices and genetic risk.Univariate linear regression analyses were performed to evaluate the relationships of cumulative adiposity indices and magnetic resonance imaging and dual X-ray absorptiometry parameters,including visceral adipose tissue(VAT)volume,VAT mass,trunk fat volume,and trunk fat mass.We further applied the eXtreme Gradient Boosting(XGBoost)algorithm,with the feature importance being measured to evaluate the predictive value of each adiposity index for imaging parameters.Mendelian randomization analysis was further conducted to investigate the potential causal relationship between trunk fat mass and AF.Results A total of 12 776 participants were included.Over a median follow-up of 9.60 years,761(5.96%)new-onset AF events were recorded.Participants were divided into four classes based on the changes in adiposity indices.In the fully adjusted model,compared to participants in Class 1 of BRI,those in Class 3(HR=1.30,95%CI 1.04-1.63,P=0.023)and Class 4(HR=2.17,95%CI 1.61-2.93,P＜0.001)were associated with significantly higher risks of new-onset AF.Regarding METS-VF,participants in Class 4 of METS-VF also demonstrated a significantly higher risk of new-onset AF compared to those in Class 1(HR=1.66,95%CI 1.15-2.39,P=0.007).However,no significant association was observed between different classes of VAI and the risk of new-onset AF.For every 1 standard deviation increase in cumulative BRI,VAI,and METS-VF,the fully adjusted HRs of new-onset AF were 1.23(95%CI 1.13-1.35),1.02(95%CI 0.94-1.10),and 1.23(95%CI 1.12-1.35),respectively.Cumulative adiposity indices(BRI,VAI,and METS-VF)were divided into quartiles.Using the first quartile as reference,participants in the highest quartiles of BRI(HR=1.40,95%CI 1.10-1.79,P=0.007)and METS-VF(HR=1.44,95%CI 1.13-1.83,P=0.003)both exerted a significantly higher risk of new-onset AF.Regarding VAI,no significant association was observed(HR=1.00,95%CI 0.81-1.23,P=0.988).Restricted cubic spline analyses revealed non-linear relationships between cumulative BRI,baseline/cumulative VAI,and baseline/cumulative METS-VF with new-onset AF risk(all Poverall＜0.05,Pnon-linear＜0.05).In the C-index analysis,BRI demonstrated the highest predictive performance for new-onset AF,followed by METS-VF and VAI.Subgroup analysis indicated a stronger association between METS-VF and the risk of new-onset AF amongst participants younger than 60 years(Pinteraction=0.008).Polygenic risk score analysis stratified by genetic risk demonstrated a synergistic effect between BRI and genetic risk with new-onset AF,with the overall risk of new-onset AF increasing as both BRI and genetic risk increased.Linear regression analysis revealed a positive correlation between cumulative BRI with VAT volume,VAT mass,trunk fat volume,and trunk fat mass.The feature importance plot derived from the XGBoost algorithm indicated that cumulative BRI had the greatest predictive value on VAT volume,VAT mass,trunk fat volume,and trunk fat mass.Mendelian randomization analysis confirmed a significant causal relationship between trunk fat mass and AF.Conclusions There are significant non-linear associations between BRI,METS-VF,and VAI with new-onset AF.Higher BRI and METS-VF are significantly associated with a higher risk of new-onset AF,whereas no significant association is observed for the VAI.BRI exhibits a positive correlation with VAT and trunk fat,and demonstrates superior performance in predicting new-onset AF compared to VAI and METS-VF.Monitoring and managing BRI may be important in the early detection and intervention of AF.