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.

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 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.

目的 探讨紫草素对肝癌Huh-7细胞增殖、迁移和侵袭的影响及其可能的分子机制.方法 实时荧光定量聚合酶链反应(FQ-PCR)检测微小RNA(miR)-637的表达水平;噻唑蓝(MTT)检测Huh-7细胞增殖;Transwell实验检测Huh-7细胞的迁移和侵袭;蛋白质印迹法检测Huh-7细胞中增殖、迁移和侵袭相关蛋白的表达.两组间比较采用t检验,多组件比较采用单因素方差分析,组内间比较采用SNK-q检验.结果 肝癌组织中miR-637表达水平低于癌旁组织(0.43±0.05比1.00±0.11,t=25.840,P＜0.05);1、2、3、4 μg/ml 紫草素组 Huh-7 细胞存活率低于对照组(82.24±7.82、54.15±6.16、43.34±6.35、38.68±5.24 比 100.00±9.69,t=4.279、11.980、14.670、16.700,P＜0.05);2μg/ml 紫草素处理组 Huh-7 细胞的增殖(0.81±0.07 比 1.46±0.18,t=10.097,P＜0.05)、迁移(79.28±8.12 比 137.19±14.36,t=10.531,P＜0.05)和侵袭(48.67±5.32 比102.52±11.25,t=12.982,P＜0.05)能力低于对照组.过表达miR-637组Huh-7细胞的增殖(0.78±0.08 比 1.52±0.13,F=96.865,P＜0.05)、迁移(74.12±8.16 比 134.26±15.69,F=77.227,P＜0.05)和侵袭(74.12±8.16 比 134.26±15.69,F=131.214,P＜0.05)能力低于 miR-NC组.2 μg/ml 紫草素+抗 miR-637 组 Huh-7 细胞增殖(1.27±0.15 比 0.75±0.08,F=65.743,P＜0.05)、迁移(116.28±12.53 比 71.45±7.82,F=58.264,P＜0.05)和侵袭(86.41±9.23 比46.32±4.92,F=113.920,P＜0.05)能力高于2μg/ml紫草素+抗miR-NC组.结论 紫草素可通过上调miR-637抑制Huh-7细胞的增殖、迁移和侵袭.

目的 分析基于案例学习(CBL)教学法联合模拟诊疗以及"WWWWTP"六步问答法在肝胆胰外科临床思维能力教学实践中的应用效果.方法 选取2021年8月至2022年1月在郑州大学第一附属医院实习的50名临床医学本科学生作为研究对象,以随机的方式将其分为实验组和对照组,每组25名.对照组学生采用传统教学方法,实验组学生在传统教学方法的基础上加入CBL联合模拟诊疗以及"WWWWTP"六步问答法.本科室实习期结束后,观察2组学生的临床思维考核评分、实践技能考核评分以及理论知识考核评分.结果 实验组学生的临床思维考核评分、实践技能考核评分以及理论知识考核评分均高于对照组,差异均有统计学意义(t=5.095,P＜0.001;t=5.146,P＜0.001;t=7.115,P＜0.001).结论 CBL教学法联合模拟诊疗以及"WWWWTP"六步问答法可有效提升肝胆胰外科实习学生的临床思维能力.

Selective separation and enrichment of phosphoproteins are essential for understanding their important functions in almost all cellular processes. Here, taking advantage of the feature that cadmium ion (Cd2+ ) has an overwhelming preference for phosphates, we developed a robust and simple Cd2+ co-precipitation strategy for the selective isolation of intact phosphoproteins. After evaluating the feasibility of Cd2+ in phosphoprotein precipitation, we compared the washing protocols for the removal of non-specific binding proteins and then used the best-performing protocol for the isolation of phosphoproteins from different complex samples. It was found that phosphoproteins can be specifically enriched from artificial protein mixtures containing α-casein, β-casein, and bovine serum albumin or plasma, in which bovine serum albumin or plasma were served as interferences with very high molar ratios. Applying this method to enrich phosphoproteins from complex cell lysates, a high specificity was confirmed by western blotting analysis with a phosphoprotein-specific kit. Finally, we successfully applied this method to the purification of caseins from drinking milk, highlighting its potential application in the studies where purified phosphoproteins were required. In a word, this Cd2+ co-precipitation method enables universal and effective capture, enrichment, and detection of intact phosphoproteins, making it a powerful tool for the comprehensive analysis of the phosphoproteome.

Hepatocellular carcinoma (HCC) remains one of the most fatal malignancies with high morbidity and mortality rates in the world, whose molecular pathogenesis is incompletely understood. As an RNA-binding protein participating in the processing and modification of RNA, KIAA1429 has been proved to be implicated in the pathogenesis of multiple cancers. However, how KIAA1429 functions in alternative splicing is not fully reported. In the current study, multi-omics sequencing data were used to analyze and decipher the molecular functions and the underlying mechanisms of KIAA1429 in HCC samples. RNA sequencing data (RNA-seq) analysis demonstrated that in HCCLM3 cells, alternative splicing (AS) profiles were mediated by KIAA1429. Regulated AS genes (RASGs) by KIAA1429 were enriched in cell cycle and apoptosis-associated pathways. Furthermore, by integrating the RNA immunoprecipitation and sequencing data (RIP-seq) of KIAA1429, we found that KIAA1429-bound transcripts were highly overlapping with RASGs, indicating that KIAA1429 could globally regulate the alternative splicing perhaps by binding to their transcripts in HCCLM3 cells. The overlapping RASGs were also clustered in cell cycle and apoptosis-associated pathways. In particular, we validated the regulated AS events of three genes using clinical specimens from HCC patients, including the exon 6 of BPTF gene and a marker gene of HCC. In summary, our results shed light on the regulatory functions of KIAA1429 in the splicing process of pre-mRNA and provide theoretical basis for the targeted therapy of HCC.

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.

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(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 investigate the effect of circular RNA 0007841 (circ_0007841) targeting microRNA (miR)-557 on the biological behavior of liver cancer cells MHCC97H.Methods:Liver cancer tissues and paracancerous tissues were collected from 47 patients with liver cancer who underwent surgical treatment in our hospital from January 2017 to December 2018. The relative levels of circ_0007841 and miR-557 were detected using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). According to different transfectants, MHCC97H cells were divided into si-NC group, si-circ_0007841 group, pcDNA group, pcDNA-circ_0007841 group, miR-NC group, miR-557 group, si-circ_0007841 + anti-miR-NC group, si-circ_0007841+ anti-miR-557 group. Cell counting kit-8 (CCK-8) assay, clone formation experiment, scratch healing experiment and Transwell experiment were applied to detect the absorbance ( A) value, clonal formation number, scratch healing rate and number of invasive MHCC97H cells. The dual luciferase report experiment verified the targeting relationship between circ_0007841 and miR-557. The independent-sample t test was used for comparison between the two groups, and the One-Way ANOVA and LSD- t test were used for the comparison between multiple groups. Results:The relative level of circ_0007841 (3.87±0.30 vs. 1.00±0.07, t=63.873, P<0.05) was increased, and that of miR-557 (0.34±0.04 vs. 1.00±0.09, P<0.05) was decreased in liver cancer tissues as compared with that in the adjacent tissues. As compared with the si-NC group, the A value (0.59±0.05 vs. 1.08±0.08, t=15.582, P<0.05), clonal formation number [(38.94±3.77) vs. (87.24±6.77, t=18.699, P<0.05), scratch healing rate [(25.21±2.51)% vs. (65.36±5.08)%, t=21.257, P<0.05] and the number of invasive cells [(47.97±4.82) vs. (111.04±9.84), t=17.268, P<0.05] in the si-circ_0007841 group were decreased, and the relative level of miR-557 (2.82±0.21 vs. 10.97±0.06, t=25.412, P<0.05) increased. As compared with the miR-NC group, the A value [(0.66±0.05) vs. (1.06±0.09), t=11.655, P<0.05)], clonal formation number [(46.17±4.02) vs. (46.17±4.02), t=15.098, P<0.05], scratch healing rate [(34.58±3.16)% vs. (68.56±5.81)%, t=15.413, P<0.05] and the number of invasive cells [55.12±5.58) vs. (109.94±11.52), t=12.848, P<0.05] in miR-557 group were decreased. As compared with the pcDNA group, the relative level of miR-557 [(0.36±0.04) vs. (1.00±0.00), t=48.000, P<0.05] in the pcDNA-circ_0007841 group was decreased. The circ_0007841 was directly bound with miR-557. As compared with the si-circ_0007841+ anti-miR-NC group, the A value [(0.89±0.06) vs. (0.56±0.05), t=12.676, P<0.05), clonal formation number [(76.01±6.35) vs. (36.94±3.93), t=15.695, P<0.05], scratch healing rate [(55.63±5.17)% vs. (23.54±2.92)%, t=16.214, P<0.05] and the number of invasive cells [(90.88±7.71) vs. (44.87±4.68), t=15.304, P<0.05] in the si-circ_0007841+ anti-miR-557 group were increased. Conclusion:Circ_0007841 may promote the proliferation, migration and invasion of liver cancer cells by targeting miR-557.

Objective:To explore the effect of phillyrin on the proliferation, migration, invasion and apoptosis of hepatoma cells and its regulatory effect on circ_0054537/miR-409-3p.Methods:Hep3B liver cancer cells were cultured in vitro, and Hep3B cells were treated with phillyrin at different doses (5, 10, 20 μmol/L). Cell counting kit-8 (CCK-8) method was used to detect cell proliferation. Flow cytometry was used to detect the apoptosis rate. Transwell cell test was used to detect cell migration and invasion ability. The expression levels of circ_0054537 and miR-409-3p were detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) method. The dual luciferase report experiment detected the targeting relationship of circ_0054537 and miR-409-3p. Hep3B cells were transfected with si-circ_0054537, pcDNA-circ_0054537, respectively, and cell proliferation, apoptosis, migration and invasion were detected by the above methods. SPSS 21.0 statistical software was used to analyze the data. The measurement data were expressed as ( Mean± SD) and all accorded with normal distribution. The comparison between the two groups was performed by independent sample t test. The comparison between groups was performed by one-way analysis of variance, with P<0.05 The difference was statistically significant. Results:Phillyrin could significantly reduce cell viability [(1.276±0.110) vs. (1.031±0.090), (0.637±0.050), (0.507±0.040), F=244.841, P<0.05], increased apoptosis rate [(7.34±0.62)% vs. (12.44±1.03)%, (22.86±2.12)%, (28.16±2.71)%, F=244.841, P<0.05], reduce the number of migrating cells [(154.15±12.76) vs. (124.06±10.04), (78.05±7.25), (61.13±5.83)] and the number of invasive cells [(112.04±10.08) vs. (89.43±8.13), (57.11±5.12), (43.08±4.05), F=186.018, 166.514, P<0.05], inhibit the expression of circ_0054537 [(1.00±0.10) vs. (0.40±0.04), t=16.713, P<0.05], promote the expression of miR-409-3p [(1.02±0.11) vs. (3.42±0.31), t=21.889, P<0.05]. Transfection of si-circ_0054537 could significantly inhibit cell viability [(1.264±0.10) vs. (0.686±0.06)], migration [(151.96±11.17) vs. (79.03±7.21)] and invasion ability[(115.28±11.05) vs. (68.14±6.43), t=14.869, 16.457, 11.062, P<0.05], increase the apoptosis rate [(7.26±0.71)% vs. (23.79±2.06)%, t=22.759, P<0.05]. The dual luciferase report experiment confirmed that circ_0054537 could target and bind to miR-409-3p. Transfection of pcDNA-circ_0054537 could significantly reverse the regulatory effect of phillyrin on proliferation, apoptosis, migration, invasion of Hep3B cells. Conclusion:Phillyrin could down-regulate the expression of circ_0054537 and up-regulate the expression of miR-409-3p to inhibit hepatocellular carcinoma cell proliferation, migration, invasion and promote apoptosis.

BACKGROUND Primary hepatic neuroendocrine tumors (PHNETs), a group of neuroendocrine neoplasms, are extremely rare. There are only few case reports about PHNETs in the literature. The lack of large samples and multicenter research results in poor diagnostic and therapeutic approaches. AIM To discuss the clinical characteristics, diagnosis, and treatment of PHNETs and risk factors related to survival. METHODS We retrospectively analyzed the clinical data, imaging features, immunohistochemistry data, and treatment efficacy of 40 patients who were pathologically diagnosed with PHNETs and admitted to The First Affiliated Hospital of Zhengzhou University from January 1, 2014 to November 15, 2019. Finally, survival analysis was performed to identify the risk factors for survival. RESULTS The main symptoms and signs included intermittent abdominal pain (19 patients, 47.5%) and bloating (8 patients, 20.0%). The positive rates of tested tumor markers were recorded as follows: Carbohydrate antigen 19-9 (CA19-9) (6 patients, 15.0%), CA72-4 (3 patients, 7.5%), carcinoembryonic antigen (7 patients, 17.5%), and alpha-fetoprotein (6 patients, 15.0%). Immunohistochemical staining results showed positivity for Syn in 38 (97.4%) of 39 patients, for chromogranin A in 17 (65.4%) of 26 patients, for CD56 in 35 (94.6%) of 37 patients, for AE1/AE3 in 28 (87.5%) of 32 patients, and for Ki-67 in all 40 (100.0%) patients. The overall survival rate was significantly related to the tumor grade, AE1/AE3, and Ki-67. No significant correlation was found between other parameters (age, gender, tumor number, tumor size, metastasis, and treatment) and overall survival. CONCLUSION Higher grade, negative AE1/AE3, and higher Ki-67 are associated with a worse survival rate. Kinds of treatment and other parameters have no significant influence on overall survival.

It has been found that the circular RNA (circRNA) CDR1as is upregulated in cholangiocarcinoma (CCA) tissues. In this study, we tried to explore the roles of CDR1as in CCA. CDR1as was overexpressed or knocked down in human CCA cells to assess the effects of CDR1as on cell behaviors and tumor xenograft growth. In vitro, the CDR1as level was significantly increased in CCA cell lines. The results showed that CDR1as promoted the cell proliferation, migration, invasion, and activation of the AKT3/mTOR pathway in CCA cells. Moreover, miR-641, a predicted target microRNA (miRNA) of CDR1as, could partially reverse the effects of CDR1as on cell behaviors in CCA cells. Furthermore, CDR1as improved tumor xenograft growth, and it could be attenuated by miR-641 in vivo Additionally, CDR1as expression was inversely correlated with miR-641 in CCA cells, and miR-641 could directly bind with CDR1as and its target genes, the AKT3 and mTOR genes. Mechanistically, CDR1as could bind with miR-641 and accelerate miR-641 degradation, which possibly leads to the upregulation of the relative mRNA levels of AKT3 and mTOR in RBE cells. In conclusion, our findings indicated that CDR1as might exert oncogenic properties, at least partially, by regulating miR-641 in CCA. CDR1as and miR-641 could be considered therapeutic targets for CCA.

WHAT IS KNOWN AND OBJECTIVE:Terlipressin has been shown to be effective in controlling variceal bleeding and decreasing associated mortality. Terlipressin is a synthetic analogue of vasopressin and is safer than arginine vasopressin; it induces selective vasoconstriction by stimulating the vasopressin V1 receptors that are predominantly located in the splanchnic tissues. However, severe hyponatraemia may occur during terlipressin treatment, resulting in neurological manifestations.CASE SUMMARY:We describe two patients who presented a marked decrease in serum sodium levels and developed obvious neurological manifestations after receiving terlipressin therapy. Although the two patients were given sodium supplementation, their serum sodium levels continually declined. After the discontinuation of terlipressin, their serum sodium levels rapidly recovered to normal limits, and the neurological manifestations subsequently disappeared in both patients.WHAT IS NEW AND CONCLUSION:Some studies have reported hyponatraemia as a side effect of terlipressin; however, severe hyponatraemia with neurological manifestations has rarely been reported. We presented the cases of 2 patients with obvious neurological manifestations after receiving terlipressin therapy. Severe hyponatraemia may develop in patients treated with terlipressin, resulting in associated neurological symptoms. Therefore, the close monitoring of serum sodium is necessary.