BACKGROUND:Budd-Chiari syndrome (BCS) is caused by obstruction of the hepatic veins or suprahepatic inferior vena cava, leading to portal hypertension and the development of gastroesophageal varices (GEVs), which are associated with an increased risk of bleeding. Existing risk models for variceal bleeding in cirrhotic patients have limited applicability to BCS due to differences in pathophysiology. Radiomics, as a noninvasive technique, holds promise as a tool for more accurate prediction of bleeding risk in BCS-related GEVs. AIM:To develop and validate a personalized risk model for predicting variceal bleeding in BCS patients with GEVs. METHODS:We retrospectively analyzed clinical data from 444 BCS patients with GEVs in two centers. Radiomic features were extracted from portal venous phase computed tomography (CT) scans. A training cohort of 334 patients was used to develop the model, with 110 patients serving as an external validation cohort. LASSO Cox regression was used to select radiomic features for constructing a radiomics score (Radscore). Univariate and multivariate Cox regression identified independent clinical predictors. A combined radiomics + clinical (R + C) model was developed using stepwise regression. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA), with external validation to evaluate generalizability. RESULTS:The Radscore comprised four hepatic and six splenic CT features, which predicted the risk of variceal bleeding. Multivariate analysis identified invasive treatment to relieve hepatic venous outflow obstruction, anticoagulant therapy, and hemoglobin levels as independent clinical predictors. The R + C model achieved C-indices of 0.906 (training) and 0.859 (validation), outperforming the radiomics and clinical models alone (AUC: training 0.936 vs 0.845 vs 0.823; validation 0.876 vs 0.712 vs 0.713). DCA showed higher clinical net benefit across the thresholds. The model stratified patients into low-, medium- and high-risk groups with significant differences in bleeding rates (P < 0.001). An online tool is available at https://bcsvh.shinyapps.io/BCS_Variceal_Bleeding_Risk_Tool/. CONCLUSION:We developed and validated a novel radiomics-based model that noninvasively and conveniently predicted risk of variceal bleeding in BCS patients with GEVs, aiding early identification and management of high-risk patients.

Ferroptosis is an emerging therapeutic strategy in pancreatic cancer (PC) therapy. However, existing ferroptosis often concentrate on the generation of lipid peroxide (LPO), ignoring the negative feedback from intracellular anomalous metabolism, such as lactic acid accumulation. Herein, an "AND" logic gate functional nanoreactor is constructed with a combination of curcumin and glucose oxidase (Gox) (NRs@Cur@Gox) for metabolic remodeling-mediated starvation, ferroptosis, and immunotherapy. In acidic tumor cells, NRs@Cur@Gox is specifically activated to improve the permeability of the membranes, resulting in increased hydrogen peroxide (H2O2) production via the catalysis of Gox. High H2O2 subsequently induces self-destruction of the nanoreactor, releasing Cur and quinone methides to inhibit the expression of glucose transporter protein 1, generate lactate and deplete glutathione (GSH), respectively. Exhausted intracellular glucose and blockage of extracellular glucose transport interdict tumor cells from the root. Moreover, decreased lactate, increased H2O2, and GSH depletion synergistically activate ferroptosis. Starvation therapy combined with ferroptosis induces significant immunogenic cell death (ICD), promotes cytotoxic T lymphocyte proliferation, and inhibit PC regression. Importantly, the decreased lactate in the tumor microenvironment reverses immunosuppressive tumors into "hot" tumors, reinforcing the immunotherapeutic efficiency of NRs@Cur@Gox. Overall, this study provides a versatile metabolic intervention strategy for PC-ferroptosis immunotherapy.

Background: This study aimed to investigate the impact of circ_0046599 on hepatocellular carcinoma (HCC). Methods: Analysis of the GEO dataset identified circ_0046599 as significantly upregulated in HCC, and its impact on cell proliferation, apoptosis, migration, and invasion was assessed. Bioinformatics and dual-luciferase assays identified miR-1322 as a target of circ_0046599, which in turn regulates NT5DC2 expression. In vitro and in vivo experiments confirmed the ceRNA mechanism of circ_0046599 in HCC. Results: circ_0046599 was significantly upregulated in HCC, and predicts a worse survival in HCC patients. Increased expression of circ_0046599 promoted HCC cell proliferation, migration, invasion, and inhibited apoptosis. circ_0046599 bound to miR-1322, which exerted a tumor-suppressive effect in HCC cells. miR-1322 targeted NT5DC2, and circ_0046599 regulated the expression of NT5DC2 by competitively binding to miR-1322. Modulation of NT5DC2 expression affected the oncogenic role of circ_0046599. In in vivo experiments, inhibition of circ_0046599 suppressed the growth of xenograft tumors by upregulating miR-1322 expression and suppressing NT5DC2. Conclusion: circ_0046599 promoted the progression of HCC by competitively binding to miR-1322 and regulating the expression of NT5DC2.

Objective: The F-box protein (FBXO) family plays a key role in the malignant progression of tumors. However, the biological functions and clinical value of the FBXO family in liver cancer remain unclear. Our study comprehensively assessed the clinical value of the FBXO family in hepatocellular carcinoma (HCC) and constructed a novel signature based on the FBXO family to predict prognosis and guide precision immunotherapy. Methods: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the expression characteristics and prognostic value of the FBXO family in HCC. A predictive model based on the FBXO family using TCGA database; and its predictive ability was validated using the ICGC database. Further analyses revealed that this predictive model can independently predict the overall survival (OS) rate of patients with HCC. We further analyzed the association of this predictive model with signaling pathways, clinical pathological features, somatic mutations, and immune therapy responses. Finally, we validated the biological functions of cyclin F (CCNF) through in vitro experiments. Results: A predictive model involving three genes (CCNF, FBXO43, and FBXO45) was constructed, effectively identifying high and low-risk patients with differences in OS, clinicopathological characteristics, somatic mutations, and immune cell infiltration status. Additionally, knock-down of CCNF in HCC cell lines reduced cell proliferation in vitro, suggesting that CCNF may be a potential therapeutic target for HCC. Conclusions: The predictive model based on the FBXO family can effectively predict OS and the immune therapy response in HCC. Additionally, CCNF is a potential therapeutic target for HCC.

Background Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world. Lamin B1 (LMNB1) is a key component of the nuclear skeleton structure. Recent studies have found that LMNB1 is overexpressed in tumor tissues and is associated with the prognosis of patients. However, the underlying mechanism remains unclear in HCC.Objective This study aims to explore the clinical significance and molecular mechanisms of LMNB1 in HCC.Methods The expression level of LMNB1 and its clinical values were analyzed with public databases, and the level of LMNB1 in HCC tissues and adjacent normal tissues was confirmed by qRT-PCR and IHC. Functional assays were conducted to explore the impact of LMNB1 knockdown on cell proliferation both in vivo and in vitro. Additionally, Genes and Genomes enrichment analysis, recovery analysis, and ChIP assays were employed to investigate its underlying molecular mechanisms. Finally, we carried out an analysis of the relationship between LMNB1 and immune cell infiltration in HCC.Results LMNB1 was found to be overexpressed in HCC and correlated with the pathological stage and unfavorable prognosis. Functional assays demonstrated that LMNB1 promotes HCC proliferation both in vitro and in vivo. Further analysis revealed that LMNB1 promotes the progression of HCC by regulating CDKN1A expression. Furthermore, the infiltration of immune cells in HCC tissues suggests a potential correlation between immune infiltration cell markers and the expression of LMNB1.Conclusions LMNB1 emerged as a promising therapeutic target and prognostic biomarker for HCC, with its expression showing a correlation with several immune infiltration cell markers.

Background: Hepatocellular carcinoma (HCC) is a serious complication of hepatic vena cava Budd-Chiari syndrome (HVC-BCS) that significantly reduces the survival time of patients. Our study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring system. Methods: The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively analyzed. Kaplan -Meier curves and log -rank tests were used to analyze the survival curve of patients and the difference in prognoses between the groups. Univariate and multivariate Cox regression analyses were performed to analyze the influence of biochemical, tumor, and etiological characteristics on the total survival time of patients, and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical model. The prediction efficiency was evaluated using the time -dependent receiver operating characteristics curve and concordance index. Results: Multivariate analysis showed that serum albumin level < 34 g/L [hazard ratio (HR) = 4.207, 95% confidence interval (CI): 1.816-8.932, P = 0.001], maximum tumor diameter > 7 cm (HR = 8.623, 95% CI: 3.771-19.715, P < 0.001), and inferior vena cava stenosis (HR = 3.612, 95% CI: 1.646-7.928, P = 0.001) were independent predictors of survival. A prognostic scoring system was developed according to the above -mentioned independent predictors, and patients were classified into grades A, B, C and D. Significant differences in survival were found among the four groups. Conclusions: This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC, which is helpful for clinical evaluation of patient prognosis. (c) 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.

Objective: To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value. Methods: This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group (n=38) and the survival group (n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model's differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results: Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors (P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions: The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.

Objective:To investigate the predictive value of controlled nutritional status (CONUT) score for overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosys-temic stent-shunt (TIPSS) in Budd-Chiari syndrome patients.Method:The retrospective case-control study was conducted. The clinicopathological data of 48 Budd-Chiari syndrome patients who underwent TIPSS in the First Affiliated Hospital of Zhengzhou University from August 2014 to March 2021 were collected. There were 26 males and 22 females, aged (46±13)years. Observation indicators: (1) surgical situations and follow-up; (2) analysis of influencing factors of OHE after TIPSS; (3) predic-tion of OHE after TIPSS. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was performed using the t test. Measurement data with skewed distribution were represented by M( Q1, Q3), and comparison between groups was performed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Multivariate analysis was performed using the Logistic regression model with forward method. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate the efficacy. Comparison among AUC was performed using the Delong test. Results:(1) Surgical situations and follow-up. All 48 patients underwent TIPSS successfully, and the operation time of the 48 patients was (131±29)minutes. All patients were implanted with 8 mm covered stent. All 48 patients were followed up for 46(25,71)months, and there were 14 cases with OHE and 34 cases without OHE after TIPSS. Of the 14 cases with OHE, 12 cases were evaluated as West-Haven Ⅱ grade and 2 cases were evaluated as West-Haven Ⅲ grade. (2) Analysis of influencing factors of OHE after TIPSS. Results of multivariate analysis showed that history of hepatic encephalo-pathy and CONUT score were independent factors influencing the incidence of OHE of Budd-Chiari syndrome patients who underwent TIPSS ( odds ratio=8.36, 1.74, 95% confidence interval as 1.02?68.75, 1.12?2.69, P<0.05). (3) Prediction of OHE after TIPSS. Results of ROC curve showed that the AUC of the CONUT score, the Child-Pugh score of liver function and the integrated model of end-stage liver disease (iMELD) score in predicting the incidence of OHE after TIPSS was 0.77(95% confidence interval as 0.64?0.91, P<0.05), 0.71(95% confidence interval as 0.56?0.87, P<0.05) and 0.71(95% confidence interval as 0.53?0.88, P<0.05), respectively, and there was no significant difference between the AUC of the CONUT score and the Child-Pugh score of liver function or the iMELD score ( Z=0.84, 0.59, P>0.05). The optimal cutoff value of CONUT score in predicting the incidence of OHE after TIPSS was 7, with the sensitivity, specificity and Yodon index as 78.6%, 61.8% and 0.40, respectively. Conclusion:The CONUT score can be used to predict the incidence of OHE in Budd-Chiari syndrome patients who underwent TIPSS, and the discrimination of CONUT score is equivalent to the Child-Pugh score of liver function and the iMELD score.

INTRODUCTION AND OBJECTIVES:Congestive hepatopathy (CH) is a hepatic vascular disease that results in chronic liver congestion, which can lead to liver fibrosis. New uses of metformin have been discovered over the years. However, the function of metformin in congestive liver fibrosis is not yet fully understood. This study aimed to investigate the effect of metformin on liver fibrosis in a mouse model of CH. MATERIALS AND METHODS:Partial ligation of the inferior vena cava (pIVCL) was used to establish a mouse model of liver congestion. Metformin (0.1%) was added to the daily drinking water of the animals, and the effect of metformin on liver tissue was studied after 6 weeks. Hepatic stellate cells (HSCs) were also stimulated with CoCl2 to investigate the inhibitory impact of metformin on the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) pathway. RESULTS:Metformin attenuated liver congestion; decreased the expression of collagen, fibronectin, α-smooth muscle actin (α-SMA), and HIF-1α; and ameliorated liver fibrosis in pIVCL mice. The proliferation and migration of HSCs were inhibited by metformin in vitro, which prevented α-SMA expression and restrained HSC activation. The expression levels of phosphorylated-mTOR, HIF-1α, and vascular endothelial growth factor were also decreased. CONCLUSIONS:Metformin inhibits CH-induced liver fibrosis. Functionally, this beneficial effect may be the result of inhibition of HSC activation and of the mTOR/HIF-1α signaling pathway.

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignant tumors in the world. In recent years, more and more inhibitors against gene targets have been found to be beneficial to survival. However, the function of homo-sapiens histone H3 associated protein kinase (GSG2) in HCC has not been completely understood. METHODS The expression of GSG2 in HCC tissues was detected by immunohistochemical staining. The lentivirus-mediated short hairpin RNA (shRNA) was used to knockdown GSG2 expression in HCC cell lines Hep3B2.1-7 and SK-HEP-1. Cell proliferation and colony formation were detected by MTT assay and colony formation assay, respectively, and flow cytometry assay was used to investigate the cell apoptosis in vitro. Mice xenograft model was constructed to detect the functions of GSG2 on tumor growth in vivo. Human Apoptosis Antibody Array was conducted to find the possible mechanism. RESULTS GSG2 was overexpressed in HCC tissues compared with adjacent normal tissues. The knockdown of GSG2 had the functions of inhibiting the progression of HCC, including inhibiting cell proliferation and colony formation and promoting cell apoptosis. Compared with shCtrl group, the shGSG2 group expressed higher apoptotic genes such as caspase 3, caspase 8, Fas and FasL, while lower IGF1, Bcl2 and Bcl-w. CONCLUSIONS Our study showed that knockdown of GSG2 suppresses the tumor growth in vitro and vivo. Therefore, GSG2 might play an oncogenic role in HCC.

Objective:To explore the mechanism of mTOR/HIF-1α signaling pathway in Budd-Chiari syndrome (B-CS) liver fibrosis.Methods:Twenty male C57 mice were randomly divided into Sham operation group (Sham), sham operation+ rapamycin (Sham+ Ra) group, B-CS group, B-CS+ rapamycin (B-CS+ Ra) Group, 5 in each group. The B-CS mouse model was constructed by partial ligation of the inferior vena cava(IVC) at the posterior segment of the liver; IVC was not ligated in the Sham group. Mice in Sham+ Ra and B-CS+ Ra groups were intraperitoneally injected with rapamycin (2 mg/kg, 5% DMSO solution preparation) every other day, Sham group and B-CS group were injected with the same dose of 5% DMSO solution.After 6 weeks, samples were taken, and part of the liver tissue was used to make paraffin sections for hematoxylin-eosin (HE) and Sirus Red staining to observe the pathological changes, and immunohistochemical staining to detect the expression of α-SMA and Fibrinogen in liver tissues; Protein and RNA were extracted from fresh liver tissue, and Western-blot was used to detect α-SMA, Fibrinogen, p-mTOR, mTOR, HIF-1α, Collagen I, and VEGF protein levels. Real-time fluorescent quantitative PCR was used to detect mTOR, HIF-1α, CollagenⅠ, VEGF mRNA levels.Measurement data were expressed as mean±standard deviation ( ± s), and the comparison between groups was performed by one-way ANOVA test. Results:The results of pathological staining showed that in the B-CS group, there was severe congestion around the central vein of the liver and sinusoids, widening of the sinus space, and increased collagen deposition, indicating that this study successfully established a mouse B-CS liver fibrosis model. The expression levels of fibrosis indicators α-SMA and Collagen I protein, mTOR pathway related indicators p-mTOR and HIF-1α protein, and microthrombus indicator Fibrinogen protein in the Sham group were 0.027±0.012, 0.337±0.008, 0.138±0.024, 0.296±0.113, 0.733±0.192; B-CS group were 0.986±0.001, 0.927±0.055, 0.936±0.044, 1.693±0.443, 1.612±0.068, and the differences were statistically significant ( P<0.05). The expression levels of B-CS+ Ra group were 0.707±0.078, 0.311±0.024, 0.332±0.094, 0.254±0.117, 0.569±0.075, which were statistically significant compared with B-CS group ( P<0.05). Conclusions:The mTOR/HIF-1α signaling pathway is significantly activated in mouse B-CS liver fibrosis. This pathway may participate in the development of liver fibrosis by regulating microthrombosis.

Objective:To study the factors influencing short-term prognosis of patients with Budd-Chiari syndrome (B-CS) presenting with upper gastrointestinal bleeding and to assess the predictive value of platelet-albumin-bilirubin score (PALBI) on death within 30 d in these patients.Methods:A retrospective study was conducted on 74 patients with B-CS who presented with upper gastrointestinal bleeding and were treated at the First Affiliated Hospital of Zhengzhou University from January 2014 to February 2020. There were 51 males and 23 females, with age of (46.5±11.1) years old. These patients were divided into the survival group ( n=58) and the death group ( n=16) according to the disease outcomes up to 30 d of follow-up. Factors influencing short-term deaths of these patients were analyzed, and the predictive values of PALBI, ALBI, CTP and MELD scores on short-term prognosis of the patients were assessed. The receiver operating characteristic (ROC) curves were plotted, and the areas under the curve (AUC) were calculated and compared. Results:The differences between patients in the survival and death groups for white blood cell, platelet, PALBI score, PALBI classification, ALBI score, CTP score, MELD score, and presence or absence of hepatic encephalopathy were significantly different (all P<0.05). Multivariate logistic regression analysis showed that CTP score≥10 or CTP grade C ( OR=1.669, 95% CI: 1.048-2.661), and PALBI score >-2.09 or PALBI grade 3 ( OR=5.245, 95% CI: 2.128-12.924) were independent risk factors for predicting death within 30 days. The areas under the ROC curves for PALBI, ALBI, CTP and MELD score were 0.89, 0.72, 0.77 and 0.76, with the cut-off values of -1.92, -1.60, 8.50 and 13.60, respectively. The differences between the PALBI score and ALBI, CTP scores were significantly different ( P<0.05). Conclusion:The PALBI score showed a positive predictive value on short-term prognostic assessment of patients with B-CS presenting with upper gastrointestinal bleeding. It was comparable to the effect of the MELD score but was significantly better than the ALBI and CTP scores.

Objective:To investigate the clinical treatment options for cavernous transformation of portal vein (CTPV).Methods:Data of 65 CTPV patients receiving invasive treatment and followed up at the First Affiliated Hospital of Zhengzhou University between Apr 2011 and Apr 2021 were collected. Patients were divided into four groups based on different treatment option, 24 patients were treated with transjugular intrahepatic portosystemic stent-shunt (TIPS) and 11 patients with splenopneumopexy, while 22 patients underwent splenectomy and devascularization , 8 were treated by endoscopic variceal ligation . The difference of postoperative upper gastrointestinal bleeding and hepatic encephalopathy between the four groups were analyzed,Results:There were no difference between four groups in sex, age, preoperative serum aspartate aminotransferase, total bilirubin, albuminand Child-Turcotte-Pugh grade. The incidence of hepatic encephalopathy in the TIPS group was 33.3%±9.6%、46.5%±10.3% and 64.4%±13.1% in half year, 1 year, and 3 years , respectively. Postoperative hepatic encephalopathy rate was higher in TIPS group( χ2=31.191, P=0.000). Three patients in the TIPS group developed upper gastrointestinal hemorrhage within 6 months after the operation, and postoperative upper gastrointestinal bleeding rate was higher in splenopneumopexy group( χ2=7.542, P=0.006), Conclusion:The clinical treatment options for CTPV patients are complicated ,we should make individual treatment options depend on the etiology, clinical symptoms and site of blood flow obstruction.

ObjectiveTo investigate the effect of metformin on liver fibrosis in a mouse model of Budd-Chiari syndrome and its mechanism. MethodsA total of 30 male C57 mice were randomly divided into sham-operation group (SHAM group) with 6 mice, sham operation+metformin group (SHAM+M group) with 5 mice, Budd-Chiari model group (BCS group) with 10 mice, and Budd-Chiari model+metformin group (BCS+M group) with 9 mice. The mice in the model group were treated with partial ligation of the inferior vena cava, those in the SHAM group were not treated with ligation, and those in the metformin group were given 0.1% metformin in drinking water besides modeling. The mice were sacrificed after 6 weeks. HE staining and picrosirius red staining were used to observe liver histopathology and collagen deposition; immunohistochemistry was used to measure the expressions of α-smooth muscle actin (α-SMA) and fibrinogen; quantitative real-time PCR was used to measure the mRNA expression of hypoxia-inducible factor 1α (HIF-1α) and type Ⅰ collagen (collagen 1), and Western blot was used to measure the relative protein expression levels of HIF-1α, vascular endothelial growth factor (VEGF), fibrinogen, α-SMA, and collagen 1. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsPathological staining showed that compared with the SHAM group, the BCS group had significant liver fibrosis, disordered arrangement of hepatocytes near the central vein, sinusoidal expansion with red blood cell deposition and a small amount of inflammatory cell infiltration, and collagen deposition. The BCS group had significant increases in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P＜0.05); compared with the BCS group, the BCS+M group had significant alleviation of liver fibrosis, red blood cell deposition, and collagen deposition and significant reductions in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P＜0.05). ConclusionMetformin can improve congestive liver fibrosis caused by Budd-Chiari syndrome, possibly by reducing microthrombus in hepatic sinusoid and inhibiting the HIF-1α/VEGF pathway.

Background Ferroptosis is one of the main mechanisms of sorafenib against hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) plays an important role in the heterogeneity, tumor metastasis, immunosuppressive microenvironment, and drug resistance of HCC. However, there are few studies looking into the relationship between ferroptosis and EMT and how they may affect the prognosis of HCC collectively. Methods We downloaded gene expression and clinical data of HCC patients from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases for prognostic model construction and validation respectively. The Least absolute shrinkage and selection operator (LASSO) Cox regression was used for model construction. The predictive ability of the model was assessed by Kaplan–Meier survival analysis and receiver operating characteristic (ROC) curve. We performed the expression profiles analysis to evaluate the ferroptosis and EMT state. CIBERSORT and single-sample Gene Set Enrichment Analysis (ssGSEA) methods were used for immune infiltration analysis. Results A total of thirteen crucial genes were identified for ferroptosis-related and EMT-related prognostic model (FEPM) stratifying patients into two risk groups. The high-FEPM group had shorter overall survivals than the low-FEPM group (p<0.0001 in the TCGA cohort and p<0.05 in the ICGC cohort). The FEPM score was proved to be an independent prognostic risk factor (HR>1, p<0.01). Furthermore, the expression profiles analysis suggested that the high-FEPM group appeared to have a more suppressive ferroptosis status and a more active EMT status than the low- FEPM group. Immune infiltration analysis showed that the myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) were highly enriched in the high-FEPM group. Finally, a nomogram enrolling FEPM score and TNM stage was constructed showing outstanding predictive capacity for the prognosis of patients in the two cohorts. Conclusion In conclusion, we developed a ferroptosis-related and EMT-related prognostic model, which could help predict overall survival for HCC patients. It might provide a new idea for predicting the response to targeted therapies and immunotherapies in HCC patients.

目的 分析布-加综合征(Budd-Chiari Syndrome,BCS)及BCS合并肝癌患者血清中血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达水平及临床特征,探究影响BCS患者血清VEGF表达的相关因素.方法 收集59例BCS患者(其中下腔静脉型BCS患者12例,肝静脉型BCS患者12例,混合型BCS患者35例)、13例BCS合并肝癌患者和34例健康体检者外周血血清和临床资料,应用ELISA法检测研究对象血清VEGF表达水平并分析VEGF与临床各指标的关系.结果 BCS组血清VEGF表达水平高于健康组(P＜0.001),BCS合并肝癌组血清VEGF表达水平高于BCS组(P＜0.001);与BCS组相比,BCS合并肝癌组病程较长、副肝静脉(accessory hepatic vein,AHV)内径增宽(P＜0.05).BCS患者中,与肝静脉型相比,下腔静脉型及混合型BCS患者血清VEGF表达水平升高(P＜0.05);病程与VEGF表达呈中等强度正相关(ρ=0.558),AHV内径与VEGF表达呈较高强度正相关(ρ =0.646).结论 BCS患者血清VEGF表达水平与病程时长呈正相关关系,并与BCS类型有关.

目的 分析布-加综合征(B-CS)合并下腔静脉(IVC)血栓病人介入开通后的复发情况,并探讨其危险因素.方法 回顾性分析2015年10月至2020年10月在郑州大学第一附属医院接受介入治疗的79例B-CS合并IVC血栓病人临床资料并进行随访,使用Kaplan-Meier法计算术后复发率并绘制复发曲线,对影响复发的危险因素进行Cox回归分析.结果 42例病人于首次术后出现复发,6个月、1年、2年、3年、5年的累积复发率分别为24.3％、32.5％、51.0％、56.5％、69.7％.36例复发病人再次接受了介入治疗,其中14例IVC阻塞病人二次术后6个月、1年、2年的累积复发率分别为7.1％、15.6％、26.1％;另外22例合并血栓形成的病人二次术后累计复发率为14.3％、33.3％、38.9％.多因素Cox回归分析显示IVC阻塞段长度、A类副肝静脉数目、口服抗凝药类别、血小板计数、血清白蛋白、New Clichy指数是病人复发的独立危险因素(P值均＜0.01).结论 B-CS合并IVC血栓的介入术后复发率较高并受多种因素影响,定期复查、尽早干预能够改善病人预后.

Objective: To examine the effect of thrombolytic therapy of Budd-Chiari syndrome (B-CS) with inferior vena cava (IVC) thrombosis, and the prognosis factors of it. Methods: The clinical data of 67 patients of B-CS with IVC thrombosis treated in the Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2020 were analyzed retrospectively. There were 30 males and 37 females. The age was (47.7±11.1) years(range: 18 to 72 years). All patients received catheter directed thrombolysis, and the thrombolysis process, complications and outcomes were analyzed. All patients received IVC balloon angioplasty after thrombolytic therapy. The t test, χ2 test, Mann-Whitney U test were used for univariate analysis of the prognosis factors of thrombolysis effects, while unconditional Logistic regression model were used for multivariate analysis. Results: In the 67 patients, 47 cases succerssed in thrombolytic therapy. The successful rates of thrombolysis at 1-, 2-, 3- and 4-week were 9.0%, 29.9%, 64.2% and 70.1%, respectively. The rates of thrombolytic catheter-related infection at 1-, 2-, 3- and 4-week were 1.5%, 4.5%, 14.9% and 31.3%, respectively. No serious complications such as symptomatic and acute pulmonary embolism occurred during perioperative period of IVC balloon angioplasty. Univariate analysis showed that differences in thrombus length ((36.7±18.1) mm vs. (52.0±16.4) mm, t=-3.234, P=0.002), Child-Pugh classification (class A/B/C: 37/8/2 vs. 10/8/2, Z=-2.310, P=0.021) and pre-opening IVC proportion (68.1% (32/47) vs. 35.0% (7/20), χ²=6.313, P=0.012) were statistically significant. The thrombus length (OR=0.948, 95%CI: 0.913 to 0.984, P=0.005), pre-opening IVC (OR=5.451, 95%CI: 1.469 to 20.228, P=0.011) were independent prognosis factors of thrombolytic effect. Conclusions: Thrombolytic therapy for B-CS with IVC thrombosis were satisfactory, and the thrombolysis duration should be confined within 3 weeks. IVC balloon angioplasty is safe and effective for patients failing in thrombolysis, and pre-opening IVC is an important method to improve the thrombolytic effect.

The difference of splenic pathologic alterations and immune function changes in portal hypertension (PHT) with different etiology is unclear. We aimed to investigate the differences between the hypersplenic patients with hepatitis B virus (HBV)-related PHT and Budd-Chiari syndrome (B-CS). A total of 93 patients with hypersplenism due to Chinese primary B-CS (B-CS group), 105 patients with hypersplenism due to HBV-related cirrhosis (HBV/PHT group), and 31 healthy people (control group) were included in this study retrospectively. The peripheral bloods and paraffin sections of the spleen from part of patients were analyzed by flow cytometry and immunohistochemistry. Hypersplenism and PHT were more serious in HBV/PHT group than in B-CS group. In the peripheral blood, the percentages of regulatory T cell (15.1% vs. 8.1% vs. 2.2%, p = 0.0021) and myeloid-derived suppressive cells (2.8% vs. 0.8% vs. 0.9%, p = 0.009) were higher, but CD4+ T and CD8+ T cells were lower in HBV/PHT group compared with B-CS and control groups. In spleen, the percentages of CD4+ T and CD8+ T cells were lower, but CD68+ macrophages were higher in HBV/PHT group than in B-CS group. Moreover, CD86, inducible nitric oxide synthase, Toll-like receptor 4, and tumor necrosis factor-alpha expression in the spleen, as well as the plasma lipopolysaccharide (LPS) level (677.7 vs. 311.1 vs. 222.1 ng/mL, p = 0.0022), were significantly higher in HBV/PHT group than in B-CS and control groups. The HBV/PHT group showed more severe immunosuppression and immune dysfunction and more substantial hypersplenism and splenic phagocytosis than B-CS group.

肝硬化门静脉高压症所致静脉曲张多见于食管、胃底,十二指肠静脉曲张(duodenal varices,DV)破裂出血非常罕见,国内外鲜有报道.我们介入治疗 1 例十二指肠降部静脉曲张破裂出血患者,取得良好疗效,现报告如下.