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 investigate the diagnostic and prognostic value of serum leucine-rich alpha-2-glycoprotein 1(LRG1)and dipeptidyl peptidase 4(DPP4)levels in patients with acute cerebral watershed infarction(ACWI).Methods Selected 150 ACWI patients treated in the Baoding Second Central Hospital from January 2022 to December 2023 as the study subjects(ACWI group),and another 120 volunteers who underwent physical examinations were regarded as the control group.According to the prognosis of ACWI patients,they were separated into a good prognosis group(n=98)and a poor prognosis group(n=52).ELISA was used to detect serum LRG1,DPP4 and carcinoembryonic amtigen(CEA)levels,a biochemical analyzer was used to detect levels of albumin(ALB),adenosine deaminase(ADA),creatinine(Cre).Multivariate logistic regression was applied to analyze the influencing factors of poor prognosis in ACWI patients.Spearman correlation analysis of LRG1 and DPP4 levels with NIHSS and mRS scores in the ACWI group.The ROC curve was applied to analyze the diagnostic value of LRG1 and DPP4 levels for the occurrence of ACWI and prognosis,and Z-test was used to compare the differences in AUC.Results The serum LRG1(56.03±16.11pg/ml)and DPP4(9.90±3.25ng/L)levels in ACWI patients were higher than those in the control group(41.78±12.54pg/ml,7.34±2.32ng/L),the differences were statistically significant(t=7.951,7.272,all P＜0.001).ACWI patients with poor prognosis had higher National Institute of Health Stroke Scale NIHSS scores,mRS scores,larger infarct proportion,LRG1 and DPP4 levels than those with good prognosis(t/χ2=3.258～17.208),but had lower ALB levels than those with good prognosis(t=3.143),the differences were statistically significant(all P＜0.001).Multivariate logistic regression analysis showed that large area infarction,increased NIHSS score,mRS score,LRG1 and DPP4 levels were independent risk factors for poor prognosis in ACWI patients(Wald χ2=4.358～6.000,all P<0.05),while elevated ALB was an independent protective factor for poor prognosis in ACWI patients(Wald χ2=4.535,P<0.05).Spearman correlation analysis showed a positive correlation between serum LRG1 and DPP4 levels in ACWI patients(r=0.446,P<0.001).ROC curve analysis showed that the AUC(95%CI)for diagnosing ACWI with serum LRG1 and DPP4 were 0.788(0.734～0.835)and 0.790(0.736～0.837),respectively,while the AUC(95%CI)for combined diagnosis was 0.922(0.883～0.951),which was better than individual diagnosis(Z=5.798,5.612,all P<0.05).The AUC(95%CI)of LRG1 and DPP4 in diagnosing ACWI patients with poor prognosis was 0.796(0.722～0.857)and 0.800(0.727～0.861),respectively,and the AUC(95%CI)of combined diagnosis was 0.924(0.869～0.961),which was better than their respective individual diagnoses(Z=2.891,4.222,all P<0.05).Conclusion LRG1 and DPP4 levels are higher in the serum of ACWI patients and higher in patients with poor prognosis.The two levels are positively correlated,and the combination has a certain value in diagnosing the occurrence of ACWI and poor prognosis,which provides a theoretical basis for clinical diagnosis.

Objective To explore the factors affecting the occurrence of transient arrhythmia after percuta-neous coronary intervention(PCI)in patients with acute coronary syndromes(ACS),to establish a risk prediction model,and to test the prediction effect.Methods 480 ACS patients who underwent PCI in Western Theater Air Force Hospital of PLA from August 2022 to February 2024 were selected as study subjects and were divided into 336 cases in the construct group and 144 cases in the validation group according to the ratio of 7:3.The data of the construct group were used to construct the model,and the validation group was used to validate the model.The patients in the constructed group were divided into 84 cases in the occurrence group and 252 cases in the non-occurrence group according to whether they had experienced postoperative transient arrhythmia,and the validation group was divided into 36 cases in the occurrence group and 108 cases in the non-occurrence group.The baseline data of the study subjects in the two groups were observed,and the predictive value of continuous variables was analyzed using the ROC experiment;the influencing factors of the occurrence of transient arrhythmia after PCI in ACS patients were analyzed using multifactorial logistic regression;the Nomogram prediction model was constructed using the R language;and the model was evaluated and validated using calibration curves and decision curves.Results The results of a one-way analysis of the constructed group showed that older age,the presence of a history of diabetes mellitus,the time from onset to admission≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS(P<0.05),and the prediction model established accordingly had an AUC of 0.865 and a 95%CI of 0.804～0.927,which was effective in predicting the occurrence of transient arrhythmia after PCI in patients with ACS.The model performed well in predicting the occurrence of transient arrhythmia after PCI,with a C-index of 0.858(0.753～0.865),and provided a good stan-dardized net benefit when its risk threshold was between 0.10 to 0.96.The validation group ROC curve and calibra-tion curve results are good,with an AUC of 0.846 and a C-index of 0.840(0.737～0.851),suggesting that the model has a good external predictive efficacy.The results of the validation group decision curve analysis indicated that the model could provide better standardized net returns when the risk threshold was between 0.06 and 0.94.Conclusion The results of univariate analysis showed that older age,the presence of a history of diabetes melli-tus,onset-to-admission time≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS,and the Nomogram model constructed on the basis of these four influenc-ing factors could effectively predict the risk of transient arrhythmia after PCI in patients with ACS.

BACKGROUND:Stem cell therapy has broad prospects in improving cardiac remodeling after myocardial infarction;however,alteration in the myocardial microenvironment affects the therapeutic efficacy of stem cells.Exercise preconditioning is similar to ischemic preconditioning and can have a protective effect on the myocardium.However,little attention has been paid to the effects and mechanisms of the combined effects of exercise preconditioning and stem cell transplantation. OBJECTIVE:To observe the effect of exercise preconditioning on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction and to explore the mechanism of local inflammatory microenvironment. METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group,and combination group,with 20 rats in each group.The rat model of myocardial infarction was made by ligating the left anterior descending branch of coronary artery.The sham operation group was only threaded without ligature.The transplantation and combination groups were injected with bone marrow mesenchymal stem cells of male rats into the myocardium after modeling.In addition,the combination group also required 8 weeks of treadmill exercise(i.e.,exercise preconditioning)before modeling.Four weeks after stem cell transplantation,exercise performance was measured by incremental exercise exhaustion test;cardiac structure and function were measured by echocardiography;left ventricular hemodynamics was measured by pressure-volume catheterization,and myocardial histopathology was observed by in situ staining and myocardial collagen volume fraction was obtained.Quantitative reverse transcription polymerase chain reaction was used to detect left ventricular pro-inflammatory factor(interleukin-1β,interleukin-6,tumor necrosis factor-α),anti-inflammatory factor(interleukin-10),sex-determining region of Y chromosome,and fetal genes(atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain)mRNA expression level at 1,7 days and 4 weeks after stem cell transplantation. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:compared with sham operation group,exercise performance,and left ventricular ejection fraction were reduced(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were increased(P<0.05);the mRNA expression of fetal genes and pro-inflammatory factors were up-regulated(P<0.05),and the mRNA expression of interleukin-10 was down-regulated(P<0.05)in the model group.Compared with the model group,exercise performance and left ventricular ejection fraction were increased(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were decreased(P<0.05);mRNA expression of fetal genes and pro-inflammatory factors was down-regulated(P<0.05),and that of interleukin-10 had no significant change(P>0.05)in the transplantation group.Compared with the transplantation group,all the above indicators in the combination group were further improved(P<0.05).(2)One day and 7 days after stem cell transplantation,compared with the transplantation group,the mRNA expression of sex-determining region of Y chromosome in the combination group increased(P<0.05).(3)Correlation analysis showed that interleukin-1β,interleukin-6(except on the 1st day after transplantation),and tumor necrosis factor-α were negatively correlated with the mRNA expression of sex-determining region of Y chromosome(P<0.05),while interleukin-10 was positively correlated with that of sex-determining region of Y chromosome(P<0.05).These findings suggest that exercise preconditioning can enhance the effect of bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction,which is characterized by suppression of cardiac remodeling and further amelioration of cardiac function.The mechanism is related to the improvement of the myocardial inflammatory microenvironment to promote bone marrow mesenchymal stem cell retention and survival.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Objective To investigate the diagnostic and prognostic value of serum leucine-rich alpha-2-glycoprotein 1(LRG1)and dipeptidyl peptidase 4(DPP4)levels in patients with acute cerebral watershed infarction(ACWI).Methods Selected 150 ACWI patients treated in the Baoding Second Central Hospital from January 2022 to December 2023 as the study subjects(ACWI group),and another 120 volunteers who underwent physical examinations were regarded as the control group.According to the prognosis of ACWI patients,they were separated into a good prognosis group(n=98)and a poor prognosis group(n=52).ELISA was used to detect serum LRG1,DPP4 and carcinoembryonic amtigen(CEA)levels,a biochemical analyzer was used to detect levels of albumin(ALB),adenosine deaminase(ADA),creatinine(Cre).Multivariate logistic regression was applied to analyze the influencing factors of poor prognosis in ACWI patients.Spearman correlation analysis of LRG1 and DPP4 levels with NIHSS and mRS scores in the ACWI group.The ROC curve was applied to analyze the diagnostic value of LRG1 and DPP4 levels for the occurrence of ACWI and prognosis,and Z-test was used to compare the differences in AUC.Results The serum LRG1(56.03±16.11pg/ml)and DPP4(9.90±3.25ng/L)levels in ACWI patients were higher than those in the control group(41.78±12.54pg/ml,7.34±2.32ng/L),the differences were statistically significant(t=7.951,7.272,all P＜0.001).ACWI patients with poor prognosis had higher National Institute of Health Stroke Scale NIHSS scores,mRS scores,larger infarct proportion,LRG1 and DPP4 levels than those with good prognosis(t/χ2=3.258～17.208),but had lower ALB levels than those with good prognosis(t=3.143),the differences were statistically significant(all P＜0.001).Multivariate logistic regression analysis showed that large area infarction,increased NIHSS score,mRS score,LRG1 and DPP4 levels were independent risk factors for poor prognosis in ACWI patients(Wald χ2=4.358～6.000,all P<0.05),while elevated ALB was an independent protective factor for poor prognosis in ACWI patients(Wald χ2=4.535,P<0.05).Spearman correlation analysis showed a positive correlation between serum LRG1 and DPP4 levels in ACWI patients(r=0.446,P<0.001).ROC curve analysis showed that the AUC(95%CI)for diagnosing ACWI with serum LRG1 and DPP4 were 0.788(0.734～0.835)and 0.790(0.736～0.837),respectively,while the AUC(95%CI)for combined diagnosis was 0.922(0.883～0.951),which was better than individual diagnosis(Z=5.798,5.612,all P<0.05).The AUC(95%CI)of LRG1 and DPP4 in diagnosing ACWI patients with poor prognosis was 0.796(0.722～0.857)and 0.800(0.727～0.861),respectively,and the AUC(95%CI)of combined diagnosis was 0.924(0.869～0.961),which was better than their respective individual diagnoses(Z=2.891,4.222,all P<0.05).Conclusion LRG1 and DPP4 levels are higher in the serum of ACWI patients and higher in patients with poor prognosis.The two levels are positively correlated,and the combination has a certain value in diagnosing the occurrence of ACWI and poor prognosis,which provides a theoretical basis for clinical diagnosis.

Objective To explore the factors affecting the occurrence of transient arrhythmia after percuta-neous coronary intervention(PCI)in patients with acute coronary syndromes(ACS),to establish a risk prediction model,and to test the prediction effect.Methods 480 ACS patients who underwent PCI in Western Theater Air Force Hospital of PLA from August 2022 to February 2024 were selected as study subjects and were divided into 336 cases in the construct group and 144 cases in the validation group according to the ratio of 7:3.The data of the construct group were used to construct the model,and the validation group was used to validate the model.The patients in the constructed group were divided into 84 cases in the occurrence group and 252 cases in the non-occurrence group according to whether they had experienced postoperative transient arrhythmia,and the validation group was divided into 36 cases in the occurrence group and 108 cases in the non-occurrence group.The baseline data of the study subjects in the two groups were observed,and the predictive value of continuous variables was analyzed using the ROC experiment;the influencing factors of the occurrence of transient arrhythmia after PCI in ACS patients were analyzed using multifactorial logistic regression;the Nomogram prediction model was constructed using the R language;and the model was evaluated and validated using calibration curves and decision curves.Results The results of a one-way analysis of the constructed group showed that older age,the presence of a history of diabetes mellitus,the time from onset to admission≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS(P<0.05),and the prediction model established accordingly had an AUC of 0.865 and a 95%CI of 0.804～0.927,which was effective in predicting the occurrence of transient arrhythmia after PCI in patients with ACS.The model performed well in predicting the occurrence of transient arrhythmia after PCI,with a C-index of 0.858(0.753～0.865),and provided a good stan-dardized net benefit when its risk threshold was between 0.10 to 0.96.The validation group ROC curve and calibra-tion curve results are good,with an AUC of 0.846 and a C-index of 0.840(0.737～0.851),suggesting that the model has a good external predictive efficacy.The results of the validation group decision curve analysis indicated that the model could provide better standardized net returns when the risk threshold was between 0.06 and 0.94.Conclusion The results of univariate analysis showed that older age,the presence of a history of diabetes melli-tus,onset-to-admission time≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS,and the Nomogram model constructed on the basis of these four influenc-ing factors could effectively predict the risk of transient arrhythmia after PCI in patients with ACS.

Objective:To establish a classification system for the repair band in the subchondral bone origination point in MRI for traumatic osteonecrosis of the femoral head (ONFH) and preliminarily explore the correlation between this classification and the progression of femoral head collapse.Methods:A retrospective analysis was conducted on 73 cases of traumatic ON-FH treated at the Quanzhou Orthopedic-traumatological hospital from January 2000 to December 2019. Among them, there were 46 males and 27 females with an average age of 34.9±8.3 years (range 19-55 years). Clinical and radiological data such as age, gender, side, fracture classification, reduction quality, JIC classification, and bone repair band (BRB) classification were recorded. The progression of traumatic ONFH was assessed using the ARCO staging system, with stages IIIA and IIIB defined as mild collapse and progressive collapse, respectively. The BRB classification was established based on MRI findings, and the inter- and intra-observer consistency of the BRB classification was analyzed using Kappa test. The correlation between the BRB classification and progressive femoral head collapse was analyzed using the Kaplan-Meier survival curve and binary variable Cox regression analysis.Results:According to the BRB classification, 73 cases were divided into type 1 with superficial lesion in 38.4%, type 2 with uncertain lesion in 21.9%, and type 3 with extensive lesion in 39.7%. The inter-observer consistency Kappa value for the BRB classification was 0.798, and the intra-observer consistency Kappa value was 0.896, indicating a high level of consistency. A follow-up of 73 cases (54.8±34.9 months, range 24-165 months) showed a significant correlation between the BRB classification and ARCO staging at the last follow-up (χ 2=37.556, P<0.001), with progression to stages IIIA and IIIB as follows: type 1 had 3 and 1 cases, type 2 had 4 and 1 cases, and type 3 had 14 and 12 cases, respectively. Using the occurrence of progressive collapse (stage IIIB) as the endpoint, the risk of progression to stage IIIB for type 2 was not statistically different from type 1 [ HR=1.766, 95% CI (0.465, 6.702), P=0.403]; the risk of progression to stage IIIB for type 3 was significantly higher than for type 1 [ HR=15.126, 95% CI (4.708, 48.592), P<0.001]. Conclusion:The BRB classification is closely related to the progression of traumatic ONFH and is an independent risk factor for predicting the occurrence of progressive collapse; this classification is helpful for early diagnosis and predicting the progression of collapse and treatment plan decision-making.

OBJECTIVE To establish the specific chromatogram of Qianghuo Shengshi Tang(QHSS) reference sample, clarify the key quality attributes of QHSS, providing reference for the quality evaluation of QHSS reference sample. METHODS The SilGreen C18 column(4.6 mm×250 mm, 5 μm) was used. The mobile phase consisted acetonitrile and 0.2% formic acid aqueous solution. The detection wavelength was 328 nm. Established an HPLC characteristic spectrum analysis method for the reference sample of QHSS. A variety of chromatographic columns and different instruments were applied to investigate the adaptability of the system. HPLC-LTQ-Orbitrap MS was used to identify the specific peaks of the QHSS reference samples in positive ion mode. RESULTS There were 14 peaks in the specific chromatogram, which belonged to Notopterygii Rhizoma Et Radix, Angelicae Pubescentis Radix, Ligustici Rhizoma Et Radix, Chuanxiong Rhizome, Viticis Fructus, respectively. Ferulic acid(peak 3) was reference peak. A total of 22 compounds were identified by mass spectrometry, including coumarin and flavonoids. CONCLUSION The established specific chromatogram method of QHSS is simple, stable and reproducible. The material basis of QHSS reference sample is basically determined, providing a reference for the development and quality control of QHSS.