BACKGROUND & AIMS:Ribosomal protein L8 (RPL8) is up-regulated in hepatocellular carcinoma (HCC), yet its clinical value and microenvironment role remain unclear. METHODS:Multi-omics (TCGA, CPTAC), scRNA-seq (GSE146115) and spatial transcriptomics were integrated; function was tested by RPL8 knockdown, proliferation/migration assays and drug-sensitivity screens. RESULTS:RPL8 mRNA/protein were markedly elevated (p < 0.001) with AUC 0.95 for diagnosis. High RPL8 independently predicted shorter overall (HR 1.42) and disease-specific survival (HR 1.35). Mechanistically, RPL8 co-activated MYC/G2M signaling, rewired glutathione metabolism and correlated with cell-cycle/DNA-repair scores (p < 0.001). scRNA-seq showed selective RPL8 enrichment in malignant hepatocytes and exhausted CD8+T cells; spatial maps revealed tumor-confined expression inversely linked to immune infiltration (p < 0.01). Silencing RPL8 suppressed proliferation, migration and glutathione synthesis (p < 0.001), while sensitizing cells to sirolimus and sclareol (p < 0.05). CONCLUSIONS:RPL8 drives HCC progression and immune evasion, qualifying it as a diagnostic biomarker and therapeutic target.

OBJECTIVES:To identify molecular biomarkers associated with chronic liver failure (CLF) progression to acute-on-chronic liver failure (ACLF). METHODS:RNA-seq data from 8 CLF patients-stratified into high-severity (G, ACLF with total bilirubin ≥171 μmol/L) and low-severity (L, stable CLF with total bilirubin <171 μmol/L) groups-along with 4 healthy controls were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-associated gene modules. RESULTS:A total of 3112 differentially expressed genes (DEGs) were identified, with KEGG analysis showing enrichment in innate immune pathways. Metabolomic profiling revealed 63 differentially expressed metabolites (DEMs), with four bile acids-Glycochenodeoxycholic acid, Glycocholic acid, Glycodeoxycholic acid, and Lithocholic acid-identified as key metabolites in bile acid biosynthesis pathways. Strong negative correlations were observed between these hydrophobic bile acids and 33 hub genes. CONCLUSIONS:Bile acid metabolism dysregulation and associated hub genes may contribute to CLF severity progression, warranting validation in larger cohorts.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a pressing need for effective biomarkers and therapeutic targets. Despite the clinical use of alpha-fetoprotein (AFP) as a diagnostic biomarker, its limitations in sensitivity and specificity necessitate the identification of novel markers. In this study, we investigated the role of Protein Kinase, DNA-Activated, Catalytic Subunit (PRKDC) in HCC prognosis and its potential as a therapeutic target. Utilizing spatial transcriptomics and single-cell RNA sequencing (scRNA-seq), we dissected the cellular composition of PRKDC in HCC tissue samples, revealing its high expression in malignant cell subpopulations and its association with the tumor immune microenvironment. Through clinical signature analysis, we observed widespread PRKDC expression in HCC tissues, particularly in immune cells, highlighting its link to immune cell infiltration. Further analyses confirmed high PRKDC expression in malignant cells and its inhibitory effect on immune cell infiltration. Copy number variation (CNV) analysis revealed significant genomic instability, with PRKDC exhibiting both amplifications and deletions across chromosomal regions, underscoring its role in tumorigenesis. Functional overexpression of PRKDC in HCC cell lines enhanced cell proliferation, migration, and altered cell cycle dynamics, with a notable increase in the G2/S phase. Taken together, we first to integrate spatial transcriptomics and single-cell transcriptomics and bulk RNA-seq to reveal that PRKDC is a reliable prognostic biomarker and a potential therapeutic target. High PRKDC expression is associated with shorter survival times and an abnormal tumor microenvironment, highlighting its impact on immune cell infiltration and HCC prognosis. Targeting PRKDC could selectively inhibit its expression in tumor cells, providing new strategies for HCC treatment.

ETHNOPHARMACOLOGY RELEVANCE:Jiedu Huayu Granules (JDHY), a compound formula of six traditional Chinese herbal medicines, has been used for nearly twenty years to treat acute liver failure (ALF) with good clinical efficacy. Its underlying drug mechanisms warrant in-depth exploration. AIM OF THE STUDY:This study aims to investigate the inhibitory effects and mechanisms of JDHY on D-Galactosamine + Lipopolysaccharides (D-GalN + LPS)-induced ALF cell and animal models in mice. MATERIALS AND METHODS:The 10 mg/mL D-GalN+1 μg/mL LPS-induced ALF cell model in mice was established according to previous methods, and 15 % JDHY-containing serum was used for intervention. Transcriptomics and proteomics analyses were employed to explore the effective mechanism of JDHY in treating ALF, and verification was carried out at the cell and animal levels based on the omics results. RESULTS:Transcriptomics revealed JDHY anti-ALF mechanism involves ferroptosis. Proteomics suggested 5-lipoxygenase (5-LOX) mediates JDHY anti-ferroptotic effects. Crucially, 5-LOX subcellular localization influences its activity: cytoplasmic retention exacerbates ALF oxidative stress and ferroptosis, which ferroptosis inhibitor Fer-1 significantly attenuated. Mechanistically, cAMP-PKA pathway activation promotes 5-LOX nuclear-to-cytoplasmic translocation. Conversely, JDHY inhibited cAMP-PKA expression, facilitated 5-LOX nuclear reflux, and alleviated ferroptosis-mimicking PKA siRNA effects. In addition, JDHY inhibition of ALF ferroptosis might be multifaceted, as we also found that it promoted the expression levels of Slc7a11, GSH, and GPX4, indirectly improving the antioxidant capacity of cells. CONCLUSION:JDHY suppresses 5-LOX-catalyzed lipid peroxidation via negative feedback regulation of the cAMP-PKA pathway, mitigating ALF-associated ferroptosis. Moreover, the data provided in this paper suggest that 5-LOX can serve as a potential target for inhibiting ALF ferroptosis, providing a scientific basis for the clinical prevention and treatment of ALF.

BACKGROUND:Primary liver cancer (PLC) exhibits a high incidence and mortality rate. Early diagnosis and effective treatment are crucial for improving patient survival rates. This study aims to identify biomarkers of hepatitis B-related liver cancer and establish a new method for molecular subtype classification based on differential metabolite-related regulatory gene expression profiles. METHODS:This study collected sterile midstream urine samples from patients with hepatitis B-related liver cancer who had not received standardized systematic antiviral therapy or anticancer therapy, as well as from healthy controls. Potential biomarkers were identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis performed on the differential metabolites. Gene expression data of 371 hepatocellular carcinoma (HCC) samples in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database were clustered using gene annotations for differential metabolites derived from the Human Metabolome Database (HMDB). The Kaplan-Meier (KM) survival curve was employed to assess the prognosis of different HCC molecular subtypes. Expression differences of subtype-specific genes and their enrichment in Hallmark, KEGG and Gene Ontology (GO) pathways were analyzed. The Tumor Immune Dysfunction and Exclusion (TIDE) scoring tool was used to evaluate the subtypes' response to immunotherapy. Sensitivity to sorafenib was also compared across the different subtypes. RESULT:A total of 53 differential metabolites were identified (p < 0.01), which were significantly enriched in seven metabolic pathways (p < 0.05). Three potential biomarkers were discovered: Suberic acid, 2'-O-methylcytidine, and 3'-Sialyllactose. Regulatory genes associated with these differential metabolites clustered HCC samples from the TCGA-LIHC database into two molecular subtypes (C1 and C2). KM survival analysis indicated that patients in the C2 subtype exhibited higher overall survival compared to those in C1. Differential genes between the two subtypes were significantly enriched in Hallmark, KEGG and GO pathways. The TIDE scoring tool revealed a higher likelihood of immune escape in C1 subtype patients. Molecular targeted drug analysis suggested that sorafenib may be more effective in patients with the C1 subtype. CONCLUSIONS:Suberic acid, 2'-O-methylcytidine, and 3'-Sialyllactose hold promise as metabolic biomarkers for hepatitis B-related liver cancer. Understanding the diversity of the human liver cancer gene expression profile from a metabolomic perspective has potential applications for developing novel clinical treatment strategies.

Background:Hepatocellular carcinoma (HCC) is characterized by high incidence and mortality rates, with hypoxia and anoikis resistance playing crucial roles in its progression and metastasis. While long non-coding RNA (lncRNA) significantly influence tumor biology, their roles in hypoxia-anoikis-resistant HCC remain unclear. Methods:This study utilized RNA-seq data and clinical information from the TCGA and GEO databases to analyze 154 hypoxia- and anoikis-related lncRNAs and identify differentially expressed candidates. Cluster analysis with Consensus Cluster Plus revealed links to clinical outcomes and genomic features. Tumor immune microenvironment and pathway enrichment were assessed using CIBERSORT and ssGSEA. A nine-gene risk model was developed via LASSO Cox regression and internally validated. Preliminary experimental assays suggested that the identified lncRNAs may influence apoptosis under hypoxia and anoikis conditions. Results:HCC patients were classified into two molecular subtypes, C1 and C2, with distinct prognostic outcomes and clinical features. These subtypes showed distinct immune infiltration characteristics and differential immunotherapy response scores. A nine-lncRNA prognostic model effectively predicted overall survival (OS), with the high-risk group showing increased immunosuppressive elements, such as Tregs and inactivated M0 macrophages, suggesting limited immunotherapy efficacy. Chemotherapy sensitivity analysis revealed varying drug responses between risk groups, while hypoxia- and anoikis-related lncRNAs, including LINC01554, FIRRE, LINC01139, LINC01134 and NBAT1 were downregulated in this model. Conclusion:Research has demonstrated that hypoxia- and anoikis-related lncRNAs serve as reliable biomarkers for predicting liver cancer prognosis and immunotherapy response, offering potential for developing novel therapeutic targets and strategies to enhance treatment outcomes and patient prognosis.

Liver failure (LF) is prevalent in China and is characterized by complex pathogenesis, challenging clinical management, poor prognosis, and rising incidence and mortality rates. The immune status is an important factor affecting LF prognosis. Interleukins (Ils) are a type of cytokine that act and interact with multiple cells, including immune cells. These signaling molecules play important roles in intercellular information transmission, including the regulation of immune cells; mediation of the activation, proliferation, and differentiation of T and B cells; and orchestration of the inflammatory response. To date, many studies have explored the correlation between IL expression and liver disease prognosis, but few studies have evaluated Ils as the prognostic biomarkers of LF. This article reviews the potential use of Ils as the prognostic biomarkers of LF. Particularly, it evaluates the predictive values of IL-21, IL-22, and IL-31, the three often overlooked yet promising prognostic biomarkers, in predicting susceptibility to LF. Harnessing biomarkers for early prognostic insights can facilitate tailored treatment strategies and enhance patient survival. Thus, this article focuses on the identification of IL-21, IL-22, and IL-33 as biomarkers in preclinical and clinical studies on LF and reviews their role as biomarkers in the pathogenesis and diagnosis of LF.

Objective This study aims to explore the potential mechanisms of Jiedu Huayu granules (JDHY) mitigate D-galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced acute liver failure (ALF) in a cell damage model. Methods ALF was modeled using various concentrations of D-GalN + LPS. JDHY-medicated serum at different concentrations was then co-cultured with the cell model in proportion. The best concentration and time of JDHY-medicated serum intervention were determined by Cell Counting Kit-8, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST). Western blot was used to assess the expression of Ferritin Heavy Chain 1 (FTH1), Transferrin Receptor 1(TfR1), Glutathione Peroxidase 4 (GPX4), Lysyl Oxidase (LOX), Prostaglandin-Endoperoxide Synthase 2(PTGS2). Malondialdehyde was analyzed for cell lipid peroxidation, and enzyme-linked immunosorbent assay was used to detect glutathione, Tumor Necrosis Factor-alpha, Interleukin-10, Interleukin-6 expression, and liver function indicators (ALT, AST). Additionally, GPX4 was knocked down using cell transfection, and the molecular mechanisms of JDHY in treating ALF were explored through Western blot, PCR, and enzyme-linked immunosorbent assay. Results The appropriate dose and time of D-GalN/LPS-induced ALF (10 mg/mL D-GalN + 1 μg/mL LPS for 48 h) and the optimal intervention concentration of JDHY-medicated serum (15%) were determined through ALT, AST, and Cell Counting Kit-8 assays. JDHY treatment reduced ALT and AST levels, alleviated cell lipid peroxidation, and inhibited ferroptosis. The mechanism involves JDHY enhancing the antioxidant capacity in liver cells by increasing the expression of GPX4 and glutathione, regulating ferroptosis proteins (downregulating TfR1, upregulating FTH1), inhibiting LOX and PTGS2, and suppressing inflammation (downregulating Tumor Necrosis Factor-alpha and Interleukin-6, upregulating Interleukin-10). In addition, GPX4 knockdown experiments revealed that knocking down GPX4 worsened ALF, while JDHY can alleviate ALF by promoting GPX4 expression and enhancing the antioxidant capacity of liver cells. Conclusion JDHY enhance GPX4 expression and reduce lipid peroxidation in liver cells affected by ALF, protecting liver cell, alleviating inflammatory, and inhibiting ferroptosis.

It has been reported that plumbagin (PL) can inhibit tumor cell growth and induce apoptosis, but the underlying mechanisms remain unclear. In this study, plumbagin nanoliposomes were prepared, and Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays were performed to determine the effects of PL on HepG2 cell proliferation. Transwell and wound healing assays were also used to investigate the effects of PL on HepG2 cell motility. Additionally, quantitative real-time polymerase chain reaction (qRT–PCR) was carried out to confirm the expression of microRNAs (miRNAs) under PL treatment, in which miR-16-5p showed the most substantially elevated profile among all miRNAs. After transfection with mimics or inhibitors of miR-16-5p or treatment with PL alone, the efficiency of up- and downregulation of miR-16-5p was determined by qRT–PCR in HepG2 cells. Furthermore, EdU, Transwell, and wound healing assays were used to explore the effects of up- and downregulation of miR-16-5p in HepG2 cells. Next, bioinformatic analysis was used to predict the potential target genes of miR-16-5p, along with further validation by dual luciferase reporter assays, qRT–PCR, and western blotting. To investigate the roles of PL and miR-16-5p in vivo , HepG2 cells were infected with lentivirus of miR-16-5p mimics or inhibitor, or the negative control (NC), and stable expression tumor cell lines were established. Then, a tumor mouse model was constructed and PL nanoliposomes were administered to evaluate their therapeutic effect. The volume and weight of tumor were recorded and analyzed and immunohistochemical assays were applied to determine the tumor growth and motility changes. The results showed that PL nanoliposomes suppressed HepG2 cell proliferation and migration in a dose-dependent manner. Mechanistically, PL enhanced miR-16-5p expression and inhibited HepG2 cell growth and migration by targeting the VEGFA/EMT pathway both in vitro and in vivo . Our study demonstrated that PL can inhibit the malignant functions of HepG2 cells by enhancing miR-16-5p expression, which functions as a tumor suppressor gene through targeting the VEGFA/EMT pathway.

INTRODUCTION:The prevalence of chronic kidney disease (CKD) rises with age and co-morbid diseases such as liver diseases.OBJECTIVES:The main aim of the current meta-analysis is to assess the relationship between Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease incidence in both diabetic and non-diabetic subjects compared with control.MATERIAL AND METHODS:A systematic literature search of papers published from January 1, 2005, till April 30, 2022, found 19 studies including 1,111,046 subjects; 310,804 were diagnosed with NAFLD, and 800,242 were non-NAFLD. The measured outcome was the incidence of CKD among NAFLD subjects compared to non-NAFLD subjects in diabetic and non-diabetic subjects. Dichotomous analysis methods were used within the random effects model to calculate the odds ratio (OR) with 95% confidence intervals (95% CIs).RESULTS:The incidence of CKD is highly significant in NAFLD subjects compared with controls (OR: 1.95; 95% CI: 1.65-2.31). The diabetic non-NAFLD subjects showed a significantly increased incidence of CKD compared to the non-diabetic subjects with NAFLD (OR: 1.79; 95% CI: 1.35-2.38).. In addition, the incidence of CKD was significantly higher in the NAFLD group compared with the non-NAFLD non-diabetic subjects (OR: 2.52; 95% CI: 1.91-3.32). Diabetes acts as an independent risk factor for CKD, as proven by a significant increase in incidence of diabetic subjects compared to non-diabetic NAFLD subjects (OR: 1.82; 95% CI: 1.15-2.88).CONCLUSION:Non-alcoholic fatty liver disease is significantly related to an increased incidence of CKD, which is significantly higher in diabetic subjects.

To establish a high-quality, easy-to-use, and effective risk prediction model for hepatic encephalopathy, to help healthcare professionals with identifying people who are at high risk of getting hepatic encephalopathy, and to guide them to take early interventions to reduce the occurrence of hepatic encephalopathy. Patients (n = 1178) with decompensated cirrhosis who attended the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were selected for the establishment and validation of a nomogram model for risk prediction of hepatic encephalopathy. In this study, we screened the risk factors for the development of hepatic encephalopathy in patients with decompensated cirrhosis by univariate analysis, LASSO regression and multifactor analysis, then established a nomogram model for predicting the risk of getting hepatic encephalopathy for patients with decompensated cirrhosis, and finally performed differentiation analysis, calibration analysis, clinical decision curve analysis and validation of the established model. A total of 1178 patients with decompensated cirrhosis who were hospitalized and treated at the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were included for modeling and validation. Based on the results of univariate analysis, LASSO regression analysis and multifactor analysis, a final nomogram model with age, diabetes, ascites, spontaneous peritonitis, alanine transaminase, and blood potassium as predictors of hepatic encephalopathy risk prediction was created. The results of model differentiation analysis showed that the AUC of the model of the training set was 0.738 (95% CI 0.63–0.746), while the AUC of the model of the validation set was 0.667 (95% CI 0.541–0.706), and the two AUCs indicated a good discrimination of this nomogram model. According to the Cut-Off value determined by the Jorden index, when the Cut-Off value of the training set was set at 0.150, the sensitivity of the model was 72.8%, the specificity was 64.8%, the positive predictive value was 30.4%, and the negative predictive value was 91.9%; when the Cut-Off value of the validation set was set at 0.141, the sensitivity of the model was 69.7%, the specificity was 57.3%, the positive predictive value was 34.5%, and the negative predictive value was 84.7%. The calibration curve and the actual events curve largely overlap at the diagonal, indicating that the prediction with this model has less error. The Hosmer–Lemeshow test for goodness of fit was also applied, and the results showed that for the training set, χ 2 = 1.237587, P = 0.998, and for the validation set, χ 2 = 31.90904, P = 0.0202, indicating that there was no significant difference between the predicted and actual observed values. The results of the clinical decision curve analysis showed that the model had a good clinical benefit, compared with the two extreme clinical scenarios (all patients treated or none treated), and the model also had a good clinical benefit in the validation set. This study showed that aged over 55 years, complications of diabetes, ascites, and spontaneous bacterial peritonitis, abnormal glutamate aminotransferase and abnormal blood potassium are independent risks indicators for the development of hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model based on the indicators mentioned above can effectively and conveniently predict the risk of developing hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model established on this study can help clinical healthcare professionals to timely and early identify patients with high risk of developing hepatic encephalopathy.

肝硬化腹水常见于肝硬化失代偿期,是肝硬化的严重并发症之一,腹水一旦出现,提示病情进展迅速,治疗难度大,预后凶险.有研究显示肝硬化腹水患者1年病死率为15％,5年病死率可高达44％[1,2],严重威胁人民的身心健康.在中医学中无"肝硬化腹水"这一病名,根据其临床症状及体征,可归属于"鼓胀"范畴[3].肝硬化腹水的临床治疗较为棘手.现代医学主要治疗手段包括限钠、利尿、腹腔穿刺放液、补充白蛋白、经颈静脉肝内门体分流术、肝移植等[2],虽有一定疗效,但易诱发电解质紊乱、肝肾综合征、肝性脑病等严重并发症.近年来随着中医药的不断深入研究,中医外治法在该病治疗上取得了较大进展.本文对中医外治技术在肝硬化腹水的治疗进展进行综述.

目的 探讨大黄煎剂保留灌肠治疗慢性乙型肝炎重症化患者的临床疗效.方法 选取 2019 年6 月—2021 年6 月期间广西中医药大学第一附属医院收治的慢性乙型肝炎重症化患者 100 例,按随机数字表法分为对照组和治疗组,每组各50 例.两组患者均采用常规西医基础治疗,治疗组在对照组基础上加用大黄煎剂保留灌肠.治疗2 周后,观察比较两组患者治疗后临床疗效、肝衰竭发生率及治疗期间不良反应,治疗前后证候积分、肝功能指标[总胆红素(Total bilirubin,TBil)、丙氨酸氨基转移酶(Alanine amiotransferase,ALT)、天门冬氨酸氨基转移酶(Aspartate Transaminase,AST)]、凝血功能指标[凝血酶原时间(Prothrombin time,PT)、凝血酶原活动度(Prothrombin time activity,PTA)]、HBV-DNA 转阴例数.结果 治疗后治疗组临床疗效总有效率 94.00%(47/50)高于对照组 82.00%(41/50),差异有统计学意义(P＜0.05).经两个疗程治疗,并进行 4 周、12 周随访,治疗组肝衰竭发生率4.00%(2/50)低于对照组 10.00%(5/50),差异有统计学意义(P＜0.05).治疗后两组患者证候积分较治疗前降低,差异有统计学意义(P＜0.05);且治疗组低于对照组,差异有统计学意义(P＜0.05).治疗后两组患者肝功能指标TBIL、AST、ALT水平均较治疗前降低,差异有统计学意义(P＜0.05);且治疗组低于对照组,差异有统计学意义(P＜0.05).治疗后两组患者凝血功能改善PT较治疗前降低,PTA较治疗前升高,差异有统计学意义(P＜0.05);且治疗组PT低于对照组,PTA高于对照组,而两组患者间HBV-DNA转阴例数比较,差异无统计学意义(P＞0.05).两组患者治疗过程中均未见明显不良反应.结论 在慢性乙型肝炎重症化患者临床治疗中,联合应用大黄煎剂保留灌肠技术疗效优于单纯西医基础治疗,值得推广应用.

[提要] 代谢相关脂肪性肝病(MAFLD)是全球慢性肝脏疾病的主要类型,我国成人MAFLD的患病率呈快速增长趋势,现已成为仅次于病毒性肝炎的第二大肝病."二次打击"理论是MAFLD从肝细胞单纯性脂肪变性发展为脂肪性肝炎进而形成肝硬化的主要原因,这个过程包含多种与氧化应激及炎症因子相关的因素,如线粒体功能障碍、内质网应激、铁积聚、菌群失调等.本文对氧化应激及炎症因子在MAFLD中的作用机制进行综述,旨在为MAFLD的诊疗寻找新靶点.

Liver failure is a common clinical syndrome of severe liver diseases, which belongs to one of the critical medical conditions. Immune response plays a leading role in the pathogenesis of liver failure. Lactic acid as a target for the treatment and prediction of liver failure has not attracted enough attention. Since the emergence of the concept of "histone lactation," lactic acid has shown great promise in immune response and escape. Therefore, targeted lactic acid may be a reliable agent to solve immune and energy metabolism disorders in liver failure. Based on the relationship between lactic acid and immune response, the cross-talk between lactic acid metabolism, its compounds, and immune regulation and its significance in the diagnosis and treatment of liver failure were expounded in this article to provide new ideas for understanding and treating liver failure.

龙富立教授善于运用调肝理肺法治疗肝硬化,疗效显著.该文介绍龙富立教授基于"龙虎回环"理论运用调肝理肺法治疗肝硬化的经验,并分享两则验案.

Inflammation is closely associated with the development of cancer. Tumor-associated macrophages（TAM） actively participate in tumor-related inflammation and promote tumor growth and metastasis, while under certain conditions, TAM also show cytotoxicity and tumor killing activity and thus inhibit the progression of cancer. Crosstalk between TAM and neighboring cells is closely associated with the progression of hepatocellular carcinoma（HCC） and drug resistance during treatment. This article summarizes the role of macrophages in HCC and the crosstalk between macrophages and other cells, so as to provide new strategies for the clinical diagnosis and treatment of HCC.

铁死亡是由 Dixon于 2012 年发现的一种新型的细胞死亡形式,其有异于目前发现的其他细胞死亡方式,并犹如一把双刃剑在不同疾病层面发挥着不同的生物学效应.越来越多研究表明,铁死亡发生在各类急慢性肝病的发病、转归、预后等各个方面,所以了解铁死亡有利于明晰更多肝脏疾病的发病机制,而靶向调控铁死亡将有望成为治疗各类肝脏疾病的奠基石.我们通过查阅中外文献数据库,概述铁死亡独特的细胞死亡机制及其相关影响信号和通路,并介绍在各类急慢性肝病中铁死亡可能性的切入机制和靶点,为铁死亡在肝脏疾病中的应用和研究提供科学依据.

急性肝衰竭(acute liver failure,ALF)是一种严重的终末期肝病临床症候群,以肝细胞大量坏死为病理特征,目前认为其核心机制是过度的全身炎症反应和免疫失调.间充质干细胞(mesenchymal stem cells,MSC)作为干细胞疗法最常见的细胞来源,在先天性和适应性免疫应答的调节中起重要作用,并已被广泛应用于临床试验治疗自身免疫性和炎症性疾病.近年研究表明,MSC 能够抑制多种促炎细胞的活化和增殖,减少促炎细胞因子的分泌,同时促进抗炎细胞的激活,从而在免疫调节中发挥作用,增强肝细胞增殖能力,促进ALF中肝损伤的修复和再生,已成为ALF中的一种具有较大潜力的治疗方法.本文从MSC与肝再生之间的免疫调节关系出发,综述了其在 ALF治疗中的潜在意义.

目前全球医学界对慢加急性肝衰竭(ACLF) 的定义尚未完全统一. 《肝衰竭诊治指南(2018 年版)》指出,ACLF是由于各种因素所导致的慢性肝病患者肝功能水平急剧降低的急性肝衰竭综合征,可合并多种并发症如肝性脑病、腹水、感染、电解质紊乱、肝肾综合征等,甚至由此引发肝外器官功能衰竭.