In 2025，Severe Liver Disease and Artificial Liver Group and Nutrition and Regeneration in End-Stage Liver Disease Group of Chinese Society of Hepatology，Chinese Medical Association，convened a panel of national experts to jointly develop China’s first guideline for the diagnosis and treatment of acute-on-chronic liver failure （ACLF）. Based on the latest research findings and clinical practice in China and globally，this guideline establishes a standardized definition of ACLF and provide recommendations for its diagnosis，treatment，and clinical management. This article gives an interpretation of the key points in the guideline，in order to provide a reference for standardized diagnosis and treatment of ACLF.

Objective To investigate the features and mechanism of action of intestinal flora in patients with nonalcoholic fatty liver disease （NAFLD） and Helicobacter pylori （HP） infection by comparing the changes in intestinal flora between the healthy population，the patients with HP infection，the patients with NAFLD，and the patients with NAFLD and HP infection. Methods This study was conducted among the 19 patients with NAFLD （NAFLD group），19 patients with HP infection （HP group），and 19 patients with NAFLD and HP infection （NAFLD+HP group） who were admitted to The Second Affiliated Hospital of Henan University of Science and Technology from March 1，2023 to April 30，2024，and 20 individuals undergoing physical examination were enrolled as control group. Fecal samples were collected，total DNA was extracted for PCR amplification，and 16S rDNA sequencing was performed to compare the features of intestinal flora between the four groups. An analysis of variance was used for comparison of continuous data between multiple groups，and the chi-square test was used for comparison of categorical data between multiple groups. The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of the species in intestinal flora. Results The NAFLD+HP group showed a tendency of reduction in flora abundance compared with the other three groups. There was a significant difference in flora distribution between the NAFLD+HP group and the NAFLD group and between the NAFLD group and the control group （P<0.05）. At the phylum level，the top three species in the NAFLD+HP group were Firmicutes （59.94%），Proteobacteria （17.00%），and Actinobacteria （14.75%），with an increase in the proportion of Proteobacteria and a reduction in the proportion of Actinobacteria compared with the other three groups. At the genus level，the top five dominant bacteria in the NAFLD+HP group were Bifidobacterium，Streptococcus，Escherichia-Shigella，Agathobacter，and Ruminococcus gnavus_group. Compared with the NAFLD group，the NAFLD+HP group had increases in the abundance of Streptococcus，Veillonella，and Rothia and reductions in the abundance of Dialister and Ruminococcus toraues_group. Compared with the HP group，the NAFLD+HP group had reductions in the abundance of Collinsella，Subdoligranulum，Catenibacterium，and Porphyromonas and increases in the abundance of Citrobacter and Olsenella （all P<0.05）. Conclusion Patients with NAFLD and HP infection have changed in intestinal flora. These flora may be the intestinal microecological factors for HP infection in promoting the development and progression of NAFLD.

Cirrhotic ascites is a highly prevalent and recurrent clinical condition. This consensus integrates the understanding of traditional Chinese and Western medicine on ascites caused by liver cirrhosis，comprehensively reviews the etiology，pathology，diagnostic techniques，and treatment strategies，presents the latest research progress in this field. Moreover，it emphasizes the advantages of combining traditional Chinese and Western medicine in relieving symptoms，controlling disease progression，and improving patients’ quality of life，and highlights the clinical practical orientation.

In April 2025，the European Association for the Study of the Liver （EASL） released an updated edition of clinical practice guidelines on Wilson’s disease，and compared with the 2012 edition，the updated guidelines perform detailed elaboration and updates on clinical manifestations，diagnostic algorithms，treatment strategies，and monitoring protocols，emphasize the role of serum exchangeable copper in the diagnosis and monitoring of Wilson’s disease，and provide the reference ranges for clinical application. The updated guidelines also recommend and summarize the drugs for symptomatic treatment of neuropsychiatric symptoms，add a dedicated section on transitioning pediatric patients to adult care，and discuss the optimal timing，multidisciplinary team composition，and implementation frameworks of the transition plan. These updates fully reflect the latest evidence and the development of clinical needs in the diagnosis and treatment of Wilson’s disease. This article gives an excerpt of the recommendations in the guidelines.

In February 2025，the American Association for the Study of Liver Diseases （AASLD） published online “Critical Update：AASLD Practice Guidance on Prevention，Diagnosis，and Treatment of Hepatocellular Carcinoma”. This update mainly focuses on the latest analysis results of the IMbrave050 study and performs corresponding updates and adjustments to recommendations based on the issues in clinical practice. As for the postoperative adjuvant therapeutic strategies for hepatocellular carcinoma （HCC） based on immune checkpoint inhibitors，the AASLD has re-evaluated and updated the practice guidance. The update revises related texts and recommendations for adjuvant therapy and the management algorithms for HCC recurrence during or after adjuvant therapy. Furthermore，the AASLD emphasizes that even for HCC patients at a high risk of recurrence after resection or local ablation，close monitoring for recurrence remains the current standard treatment regimen. Our team makes an excerpt of the update，systematically introduces the background and specific contents of the update，and discuss the adjuvant therapy for HCC，in order to provide a reference for readers.

Rheumatic diseases are a group of chronic disorders characterized by abnormalities in the immune system，while portal hypertension occurs due to increased blood flow or heightened resistance in the portal venous system or obstruction of hepatic venous outflow. Both rheumatic diseases and their medications can lead to noncirrhotic portal hypertension. The hypercoagulable state associated with rheumatic diseases can result in thrombosis within the portal and hepatic venous systems，and damage to the intrahepatic portal system and hepatic sinusoidal endothelial system can lead to porto-sinusoidal vascular disease and hepatic sinusoidal obstruction syndrome. Moreover，drugs used for the treatment of rheumatic diseases may cause liver parenchymal injury，which further leads to liver fibrosis and cirrhosis，or they may damage the hepatic vascular endothelium and thus cause noncirrhotic portal hypertension. This article elaborates on the mechanisms and characteristics by which common rheumatic diseases and their therapeutic agents lead to portal hypertension，in order to provide insights and assistance for clinical diagnosis，treatment，and follow-up monitoring.

Objective To investigate the association of alpha-fetoprotein （AFP） and prealbumin （PAB） with the 90-day prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF），as well as the difference in 90-day prognosis between the patients with different levels of AFP and PAB. Methods A total of 371 HBV-ACLF patients who were hospitalized in The General Hospital of Western Theater Command from January 2018 to January 2023 were enrolled，and according to the follow-up results on day 90 after discharge，they were divided into survival group with 216 patients and death group with 155 patients. The medical record system was used to collect general data，AFP，PAB，and other related laboratory markers. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups，and the least significant difference t-test was used for comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups，and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. The multivariate logistic regression analysis was used to identify the influencing factors for the prognosis of HBV-ACLF patients. The receiver operating characteristic （ROC） curve was plotted for AFP and PAB to determine their cut-off values. The Kaplan-Meier method was used to plot survival curves，and the Log-rank test was used for comparison. Results Compared with the death group，the survival group had significantly higher levels of hemoglobin （Hb），PAB，AFP，and platelet count （PLT）（all P<0.05） and significantly lower age，total bilirubin （TBil），white blood cell count （WBC），cystatin，creatinine，urea，international normalized ratio （INR），Model for End-Stage Liver Disease （MELD） score，proportion of patients with Child-Pugh class C，and incidence rates of ascites and hepatic encephalopathy （all P<0.05）. The multivariate logistic regression analysis showed that PAB （odds ratio ［OR］=0.985，95% confidence interval ［CI］：0.972‍ ‍—‍ ‍0.998，P=0.024），AFP （OR=0.998，95%CI：0.996‍ ‍—‍ ‍1.000，P=0.028），PLT （OR=0.989，95%CI：0.982‍ ‍—‍ ‍0.996，P=0.003），age （OR=1.046，95%CI：1.018‍ ‍—‍ ‍1.075，P=0.001），TBil （OR=1.004，95%CI：1.002‍ ‍—‍ ‍1.006，P<0.001），and WBC （OR=1.237，95%CI：1.110‍ ‍—‍ ‍1.379，P<0.001） were independent influencing factors for 90-day prognosis in HBV-ACLF patients. According to the cut-off values of AFP and PAB on ROC curves，the patients were divided into group A with 102 patients （AFP≥73.19 ng/mL and PAB≥22.55 mg/L），group B with 170 patients （AFP≥73.19 ng/mL and PAB<22.55 mg/L； AFP<73.19 ng/mL and PAB≥22.55 mg/L），and group C with 99 patients （AFP<73.19 ng/mL and PAB<22.55 mg/L）. There were significant differences between these three groups in age，Hb，INR，MELD score，and Child-Pugh class （all P<0.05）. The Kaplan-Meier survival analysis showed that group A had a significantly higher 90-day cumulative survival rate than groups B and C （χ²=19.825，P<0.001）. Conclusion AFP combined with PAB can better predict the 90-day prognosis of HBV-ACLF patients，and patients with high levels of AFP and PAB tend to have a lower mortality rate on day 90.

Pediatric rheumatic diseases are a group of complex chronic inflammatory disorders，mainly including juvenile idiopathic arthritis，diffuse connective tissue diseases，systemic vasculitis，and autoinflammatory diseases. Liver involvement is quite common in pediatric rheumatic diseases. In most cases，pediatric rheumatic diseases with liver involvement manifest as varying degrees of abnormal liver enzymes or hepatomegaly and may not have significant liver parenchyma lesions，and such diseases rarely progress to liver decompensation. Only a few children with rheumatic diseases may develop severe liver lesions. Liver involvement in children with rheumatic diseases may be caused by the primary disease itself or concurrent autoimmune liver diseases，but secondary factors are more common，including drug-induced liver damage caused by drugs used to treat rheumatic diseases，viral hepatitis，and fatty liver disease. This article summarizes liver involvement in pediatric rheumatic diseases，in order to provide a reference for the etiological analysis，diagnosis，and treatment strategies of liver involvement in pediatric rheumatic diseases.

Rheumatic diseases are chronic inflammatory autoimmune diseases that can affect multiple organs and systems. In clinical practice，most patients with rheumatic diseases present with asymptomatic liver function abnormalities during the course of the disease，and the etiology of such diseases may be associated with the rheumatic disease itself，medications，metabolism，viruses，or the presence of other chronic liver diseases. Immune-mediated inflammatory responses play a significant role in liver involvement （including hepatocyte injury，intrahepatic vascular lesions，and hepatic fibrosis） in rheumatic diseases. This article discusses the clinical features and management of liver involvement secondary to rheumatic diseases，in order to enhance the understanding of this condition among specialists in related fields.

Tumor budding is a distinct pathomorphological feature observed in various types of solid tumor. In recent years，tumor budding has been recognized as an important biological feature associated with tumor invasion and metastasis，and it has become a new focus in the research on tumor progression. Although studies have explored the role of tumor budding in different types of tumor，there are studies in the field of hepatocellular carcinoma （HCC）. This article systematically reviews the research advances in tumor budding in HCC，with a focus on the mechanism of tumor budding，the association between tumor budding and tumor progression，and the potential application of tumor budding in prognostic assessment，in order to provide new insights and strategies for the early diagnosis and treatment of HCC.

The liver is one of the organs most commonly affected by rheumatic diseases. Hepatic abnormalities in patients with rheumatic diseases can result from a variety of factors，including direct liver involvement by the disease itself，coexistence with primary liver disease，and drug-induced liver injury. When liver indicators are abnormal，a thorough differential diagnosis is required. For unexplained liver dysfunction，routine testing for autoantibodies should be performed to facilitate early identification of underlying autoimmune liver disease. If the etiology remains unclear，a liver biopsy is recommended for a final diagnosis if feasible. Alongside active management of rheumatic diseases，it is necessary to closely monitor liver function，avoid the use of agents that may exacerbate hepatic damage，particularly anti-rheumatic drugs with strong hepatotoxicity，and tailor treatment strategies according to personal specific conditions，so as to minimize liver damage and improve long-term outcome.

<正>根据中医的五行学说，自古就有五味入五脏之说，即“肺味辛，辛入肺；心味苦，苦入心；肝味酸，酸入肝；脾味甘，甘入脾；肾味咸，咸入肾”。大量研究表明，山楂各种提取物能调节肝脏的生理和病理稳态，减轻肝损伤。然而，尚不清楚“酸入肝”理论到底是部分特殊类型的酸味物质能保护肝损伤，还是酸味本身能减轻肝损伤。肝脏作为高度神经支配的器官，其功能受自主神经系统（交感与副交感神经）及中枢神经系统的精密调控。近年研究发现，肝内神经可通过释放神经递质（如乙酰胆碱）与免疫细胞（如巨噬细胞）相互作用，形成“脑-肝轴”调控网络。例如，迷走神经刺激可通过抑制Kupffer细胞活化减轻炎症，而交感神经过度激活可能加剧损伤。然而，神经信号如何动态调节缺血-再灌注损伤（IRI）中的免疫应答仍未完全阐明。

Objective To construct a circRNA-miRNA-mRNA competitive endogenous RNA （ceRNA） network，to investigate its potential regulatory mechanism in a mouse model of autoimmune hepatitis （AIH） induced by concanavalin A （ConA），and to verify the association between the expression of key genes and liver injury. Methods High-throughput data were used to identify differentially expressed circRNAs，miRNAs，and mRNAs，and the Pearson correlation analysis and the Miranda program were used to predict the pairing relationships between miRNAs and mRNAs/circRNAs and construct a ceRNA network. The gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for the differentially expressed genes in the network. A total of 12 specific pathogen-free male C57BL/6 mice were divided into control group and model group using a random number table，with 6 mice in each group. The mice in the model group were given injection of ConA via the caudal vein to establish a mouse model of AIH，and those in the control group were given injection of normal saline. The methods of qRT-PCR and Western blot were used to validate the expression levels of circ_0001577，miR-7055-3p，and Akt3. The serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured，as well as the content of malondialdehyde （MDA） and nitric oxide （NO） in liver tissue，and their correlation with gene expression was analyzed. The independent-samples t test was used for comparison of continuous data between two groups，and the Spearman correlation analysis was used to investigate the correlation between gene expression levels and liver injury indicators. Results A ceRNA network containing 5 795 circRNA-miRNA-mRNA pairings was constructed，and circ_0001577 was identified as the central gene. Compared with the control group，the model group had significant increases in the expression levels of circ_0001577 and Akt3 and a significant reduction in the expression of miR-7055-3p （all P<0.05），and circ_0001577 was positively correlated with Akt3 （r=0.861，P<0.001），while miR-7055-3p was negatively correlated with circ_0001577 and Akt3 （r=-0.644 and -0.855，both P<0.05）. Compared with the control group，the model group had a significantly higher protein expression level of Akt3 in the liver （1.04±0.10 vs 0.72±0.06，t=-6.49，P=0.001），which was positively correlated with circ_0001577 （r=0.579，P=0.048） and was negatively correlated with miR-7055-3p （r=-0.891，P<0.001）. Compared with the control group，the model group had significant increases in the serum levels of ALT and AST and the content of MDA and NO in liver tissue （all P<0.05），and these liver injury indicators were positively correlated with circ_0001577 and Akt3 （r=0.849，0.865，0.811，0.801； 0.889，0.954，0.938，and 0.961，all P<0.05） and were negatively correlated with miR-7055-3p （r=-0.687，-0.818，-0.833，and -0.870，all P<0.05）； in addition，they were positively correlated with the protein expression level of Akt3 （r=0.648，0.796，0.848，and 0.860，all P<0.05）. Conclusion This study shows that circ_0001577 promotes the expression of Akt3 by competitively adsorbing miR-7055-3p and relieving the inhibition of Akt3，thereby participating in the development and progression of AIH.

Objective To investigate the association of serum exosomal microRNAs （miRNAs） with hepatic inflammatory injury and histological outcomes in patients with chronic hepatitis B （CHB）. Methods Peripheral serum samples were collected from six healthy adults and six patients with CHB，and size exclusion chromatography was used to extract exosomes. Small RNA sequencing and transcriptomic analysis were used to identify the serum exosomal miRNAs associated with liver inflammatory injury and fibrosis，and quantitative real-time PCR was used for validation in a mouse model of acute liver injury induced by lipopolysaccharide/D-galactosamine，a rat model of liver fibrosis induced by carbon tetrachloride，and 84 CHB patients undergoing liver biopsy twice before and after treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； an analysis of variance was used for comparison between multiple groups，and the Tukey test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups，and the Dunn test was used for further comparison between two groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to investigate influencing factors. Results Abnormal expression of serum exosomal miR-122-5p was observed in patients with CHB，and it was downregulated in patients with confluent necrosis and advanced fibrosis. In the mouse model of acute liver injury and the rat model of liver fibrosis，compared with the control group，the model group had a significant reduction in the expression level of miR-122-5p in the liver （P=0.048 and 0.014），and compared with the patients with mild liver injury，the patients with severe confluent necrosis and advanced fibrosis showed a significant reduction in the expression level of miR-122-5p in liver tissue （P<0.05）. Among the 84 CHB patients，the patients with severe hepatic confluent necrosis or advanced liver fibrosis had a significantly lower expression level of serum exosomal miR-122-5p than those with mild liver injury （P<0.001 and P=0.003）. The multivariate Logistic regression analysis showed that the expression level of miR-122-5p was an independent influencing factor for confluent necrosis （odds ratio ［OR］=0.001，95% confidence interval ［CI］：0.000‍ ‍—‍ ‍0.037，P=0.005） and liver fibrosis degree （OR=0.568，95%CI：0.331‍ ‍—‍ ‍0.856，P=0.019）. In addition，compared with the patients with low expression of miR-122-5p，the patients with high expression of miR-122-5p before treatment had a significantly higher reversal rate of liver fibrosis after 72 weeks of antiviral therapy （64.3% vs 38.1%，P=0.029）. Conclusion Serum exosomal miR-122-5p in CHB patients is closely associated with the progression of hepatic confluent necrosis and fibrosis，and the reduction in the expression level of miR-122-5p may aggravate hepatic confluent necrosis，promote the progression of fibrosis，and affect the histological outcome of CHB patients after antiviral therapy.

Bile acids （BAs） are the main components of bile and serve as complex metabolic regulators and important signaling molecules，and they play a crucial role in fat metabolism. Hyperbileacidemia （HBA） is relatively common in clinical practice，but sometimes it is difficult to clarify its etiology. This article reviews the common diseases that cause HBA and the changes in the composition of the bile acid pool，so as to provide clear insights for the diagnosis of HBA.

Objective To compare the therapeutic effects of carvedilol alone and carvedilol combined with endoscopic variceal ligation （EVL） in the prevention of re-bleeding from gastroesophageal varices，and to provide strategies for clinical treatment. Methods We retrospectively included 178 patients who had received carvedilol alone or carvedilol plus EVL to prevent gastroesophageal variceal re-hemorrhage from October 2010 to June 2023. They were divided into carvedilol alone group （47 cases） and carvedilol+EVL group （131 cases）. Between-group comparisons were conducted using the paired t test for normally distributed continuous data，the Mann-Whitney U test for non-normally distributed continuous data，and the chi-square test for categorical data. A Cox proportional hazards model was employed for univariable and multi-variable analyses. The cumulative incidence rates of re-bleeding and mortality were estimated using the Kaplan-Meier method. The baseline characteristics of the two groups were matched through propensity score matching （PSM） to reduce selection bias and enhance the credibility of causal inference. Results The re-bleeding rate of the carvedilol+EVL group was significantly lower than that of the carvedilol alone group （10-year cumulative incidence：29.8% vs 36.2%，hazard ratio ［HR］=0.505，95% confidence interval ［CI］：0.292‍ ‍—‍ ‍0.847，P=0.015）. There was no significant difference in liver-related mortality （10-year cumulative incidence：21.3% vs 21.4%，HR=0.799，95%CI：0.406‍ ‍—‍ ‍1.578，P=0.518）. The results were stable with PSM analysis. The Cox regression analysis revealed that creatinine was an independent risk factor affecting re-bleeding （HR=1.004，95%CI：1.001‍ ‍—‍ ‍1.008，P=0.011） and liver-related mortality （HR=1.004，95%CI：1.001‍ ‍—‍ ‍1.007，P=0.019）. Conclusion Carvedilol combined with EVL is better than carvedilol alone in the prevention of gastroesophageal variceal re-bleeding.

Objective To investigate the changes in coagulation system in acute decompensated cirrhosis （ADC） patients with or without sepsis and the association of these changes with short-term prognosis. Methods A prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023，among whom there were 86 patients with sepsis and 30 patients without sepsis，and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography （TEG） and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected，and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups，and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. Results For the ADC patients with sepsis，the lungs and bloodstream were the main infection sites，and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone，the patients with ADC and sepsis had a significant reduction in median maximum amplitude （MA），a significant increase in coagulation time （K time），and a significant reduction in α angle （all P<0.05）； the patients with ADC and sepsis had a significantly longer reaction time （R time） than those with ADC alone （P=0.02），and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis （P=0.04）. There was no correlation between MA and platelet count in the patients with ADC and sepsis （r=-0.133，P=0.057），while there was a significant correlation between MA and platelet count in the patients with sepsis alone （r=0.595，P=0.001）. SOFA score was negatively correlated with MA in sepsis patients with or without ADC （r=-0.503 and -0.561，both P<0.001），and for the patients with ADC and sepsis，R time，K time，and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT （all P<0.05）. The patients with ADC alone all survived within 90 days，and compared with the death group，the patients with sepsis alone who survived had significantly higher values of MA and α angle （all P<0.05）； there was a significant difference in α angle on day 90 between the survival group and the death group，no matter whether the patients were comorbid with ADC or not （both P<0.01），while for the patients with ADC and sepsis，there was no significant difference in MA value on day 90 between the survival group and the death group （P>0.05）. Conclusion For ADC patients comorbid with sepsis，coagulation function assessment and monitoring should be taken seriously in clinical practice，and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.

Hepatic encephalopathy （HE） is a common complication of severe liver disease in the end stage，and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation，and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora，short-chain fatty acids （SCFAs） play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways，thereby playing an important role in the diagnosis，treatment，and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs，this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE，in order to provide new ideas for optimizing clinical prevention and treatment strategies.

胰腺癌作为恶性程度最高的实体肿瘤之一，其5年生存率长期维持在约13%，且80%的患者在确诊时已失去手术机会。此外，传统放化疗及靶向治疗因肿瘤异质性高、免疫抑制微环境复杂而效果有限。近年来，mRNA疫苗凭借其独特的技术优势，成为肿瘤免疫治疗的新焦点。基于非整合性mRNA模板，mRNA疫苗可精准编码肿瘤新抗原，在宿主体内高效表达并诱导多维度免疫应答。针对胰腺癌，研究热点集中在肿瘤相关抗原疫苗及肿瘤特异性抗原疫苗的研发与优化。当前研究主要关注基于测序的新抗原表位优化、靶向递送技术和人工智能驱动的免疫应答预测模型，以期推动mRNA疫苗在胰腺癌精准治疗中的应用。未来研究需进一步突破肿瘤微环境中关键免疫抑制分子的靶向阻断，精准识别肿瘤特异性抗原表位，开发高效新型疫苗，为胰腺癌患者带来新的治疗希望。

Primary biliary cholangitis （PBC） is a chronic progressive autoimmune liver disease that is often comorbid with other connective tissue diseases （CTDs），and such comorbidity can significantly alter the natural course or clinical phenotype of PBC or CTDs，limiting available therapeutic drugs and complicating clinical decision-making. Due to the involvement of the interdisciplinary subjects of hepatology，rheumatology，and clinical immunology and a paucity of large-scale cohort data and in-depth basic research，there is a limited understanding of such comorbidity in clinical practice，which increases the complexity of clinical diagnosis and treatment. This article summarizes the comorbidity of PBC with common CTDs such as Sjögren’‍s syndrome，systemic sclerosis，systemic lupus erythematosus，and idiopathic inflammatory myopathies，and analyzes related immune mechanisms，clinical manifestations，diagnostic challenges，treatment strategies，and prognosis. It is expected to establish PBC-CTD comorbidity cohorts through future multidisciplinary collaborations，focus on genetic background，immune mechanisms，and multi-omics approaches，elucidate pathogenesis and novel therapeutic targets，and improve the prognosis of patients by optimizing treatment strategies through precision medicine and artificial intelligence.

Nonalcoholic steatohepatitis （NASH） is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration，and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 （Th17） and regulatory T （Treg） cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 （TGF-β1） is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells，and TGF-β1 binds to its receptor and activates the Smad signaling pathway，thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells，in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation，and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis，uptake，secretion，and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important，and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis，3-hydroxy-3-methylglutaryl-coenzyme A reductase （HMGCR） has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism，the degradation and regulatory mechanisms of HMGCR，and the application of inhibitors，as well as the role of HMGCR in liver diseases，in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.

目的 探讨第三腰椎骨骼肌质量指数（L3-SMI）对慢加急性肝衰竭（ACLF）患者长期预后的预测价值，为ACLF患者的预后评分提供实用的工具。方法 回顾性纳入2017年12月—2021年12月在山西白求恩医院接受腹部CT检查并确诊为ACLF的126例患者，收集患者临床、生化指标以及计算终末期肝病模型（MELD）评分等指标，计算L3-SMI。符合正态分布的计量资料两组间比较采用成组t检验；不符合正态分布的计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ²检验。应用受试者操作特征曲线（ROC曲线）评估L3-SMI和其他变量如MELD评分和Child-Pugh评分的诊断价值，ROC曲线下面积（AUC）的比较使用Delong检验。结果 126例ACLF患者中有44例（35%）在2年内死亡，82例（65%）存活。死亡组患者年龄、腹水发生率、国际标准化比值、MELD评分、Child-Pugh评分均显著高于存活组（P值均<0.05）,L3-SMI显著低于存活组[38.40（35.95～46.29） cm²/m² vs 44.19（40.20～48.58） cm²/m²,Z=-2.855,P=0.004]。L3-SMI预测ACLF患者2年病死率的AUC为0.720，敏感度为63.6%，特异度为80.5%;L3-SMI+MELD评分+Child-Pugh评分联合预测的AUC优于MELD评分+Child-Pugh评分二者联合预测的AUC（0.809 vs 0.757,Z=2.015,P<0.05）。结论 L3-SMI对ACLF患者的预后有一定的预测作用，且L3-SMI+MELD评分+Child-Pugh评分联合预测ACLF患者预后的价值更高，将L3-SMI或肌肉减少症包括在ACLF患者常规预后的评分中，可能会提高预测疾病进展的能力。

Objective To investigate the impact of anticentromere antibody （ACA） on the clinical features and prognosis of patients with primary biliary cholangitis （PBC） by comparing clinical classification，ursodeoxycholic acid （UDCA） response，GLOBE score，and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients. Methods A total of 749 patients who were admitted to Beijing Ditan Hospital，Capital Medical University，from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients. According to their conditions on admission，the two groups were compared in terms of the distribution of clinical types，i.e.，chronic progression-type PBC，portal hypertension-type PBC，and standard jaundice/liver failure-type PBC. There were 261 patients with complete data after 1-year follow-up，among whom there were 53 patients with positive ACA and 208 with negative ACA. A statistical analysis was performed，and propensity score matching was performed based on sex and age at a ratio of 1∶2. The two groups were compared in terms of 1-year UDCA response rate，GLOBE score，and UK-PBC score before and after matching. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups，and the chi-square test was used for comparison of categorical data between two groups. Results Compared with the ACA-negative group，the ACA-positive group had a significantly higher age （61.28±10.35 years vs 56.74±12.17 years，t=4.164，P<0.001），a significantly higher proportion of female patients （93.9% vs 77.6%，χ²=20.221，P<0.001），a significantly higher proportion of patients with portal hypertension （48.3% vs 27.6%，χ²=23.289，P<0.001），and a significantly lower proportion of patients with jaundice/liver failure （24.5% vs 38.5%，χ²=10.205，P<0.001）. After 1-year follow-up，for the 261 PBC patients with complete data，there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group （41.5% vs 41.8%，P>0.05），and there was a significant difference in the proportion of patients with a GLOBE score of >0.3 between the ACA-positive group and the ACA-negative group （92.5% vs 80.3%，χ²=3.935，P=0.047）. There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching，and there were no significant differences between the two groups in UDCA response rate，GLOBE score，and UK-PBC score （all P>0.05）. Conclusion ACA-positive patients tend to have an older age，with a higher proportion of female patients or patients with portal hypertension，while there is a relatively low proportion of patients with jaundice/liver failure. Positive ACA has no significant impact on UDCA response rate，GLOBE score，and UK-PBC score.

This article systematically reviews the role and relationship of heme oxygenase （HO） in the pathogenesis of metabolic associated fatty liver disease （MAFLD） and discusses the biological function of HO，its expression in the liver，its association with lipid metabolism，and its regulatory role in inflammatory reaction and oxidative stress，in order to reveal the potential therapeutic targets and mechanism of HO in MAFLD and provide new perspectives and directions for future treatment strategies.

Hepatocellular carcinoma （HCC） is a common primary malignant tumor. In recent years，the role of ubiquitin-specific proteases （USPs） in HCC has attracted widespread attention. USPs are a class of key deubiquitinating enzymes that affect a variety of biological processes by regulating the ubiquitination status of proteins. Studies have shown that USPs participate in the regulation of cell proliferation，apoptosis，migration，and invasion by deubiquitinating various tumor-related proteins. In addition，the abnormal expression of USPs is closely associated with the prognosis of HCC patients and may thus be used as potential biomarkers and therapeutic targets. This article reviews the research advances in USPs in HCC and explores their key roles in the development，progression，and metastasis of HCC. A deep understanding of the mechanism of action of USPs in HCC not only helps to reveal the pathogenesis of HCC，but also provides a scientific basis for developing new diagnostic tools and treatment strategies. Future research should further explore the regulatory effect of USPs in HCC，in order to provide more effective means for the clinical treatment of HCC.

本文阐述了用于胰腺癌临床前肿瘤研究的各类模型的特点及应用进展，分析并探讨了人源性组织异种移植、条件重编程、患者来源的类器官等模型的历史发展、研究现状和优缺点，并在此基础上梳理了从临床前模型实现临床转化的研究，指出未来可能的研究前景。

Tissue-resident memory T cells （T_RM cells） are a subset of memory T cells that reside in tissues，exhibit tissue specificity，and do not recirculate. When potential hazards threaten the liver，such as pathogen invasion （bacteria，viruses，etc.） and excessive autoimmune responses，T_RM cells are essential as the first line of immune defense，playing an important role in viral hepatitis，autoimmune liver disease，metabolic dysfunction-associated fatty liver disease，liver cirrhosis，and liver transplantation. Here，we present the immunophenotypes of T_RM cells in the liver and their surface markers and transcriptional profiles，aiming to clarify the role of T_RM cells in chronic liver diseases and explore their potential function as therapeutic targets in immunotherapy.

Endoscopic retrograde cholangiopancreatography （ERCP），as an advanced endoscopic diagnostic and therapeutic technique，plays an important role in clinical practice. However，due to its complex operation and high technical requirements，it may lead to a series of severe complications，among which perforation is an important issue of concern. Perforation not only increases pain and treatment difficulty，but also threatens the life of patients. In order to guarantee good clinical outcomes，it is necessary to further improve the standard processes for the prediction，diagnosis，and management of perforation due to ERCP. This article discusses the risk factors，diagnostic methods，preventive measures，and treatment strategies for ERCP-related gastrointestinal perforation，in order to provide a reference for identifying high-risk populations and developing individualized treatment regimens in clinical practice.

Objective To analyze the expression level of triggering receptor expressed on myeloid cells-1 （TREM-1） in serum and ascites of patients with cirrhotic ascites，and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation. Methods A total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled，and according to the presence or absence of intra-abdominal infection，they were divided into infection group with 72 patients and non-infection group with 38 patients. The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients. Clinical data and laboratory markers were collected from all patients. Serum and ascites samples were collected，and ELISA was used to measure the level of TREM-1. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups，and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between indicators. A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection. The receiver operating characteristic （ROC） curve was used to evaluate the diagnostic and prognostic efficacy of each indicator，and the Delong test was used for comparison of the area under the ROC curve （AUC）. Results The level of TREM-1 in ascites was significantly positively correlated with that in serum （r=0.50，P<0.001）. Compared with the improvement group，the non-improvement group had a significantly higher level of TREM-1 in ascites （Z=-2.391，P=0.017） and serum （Z=-2.544，P=0.011），and compared with the non-infection group，the infection group had a significantly higher level of TREM-1 in ascites （Z=-3.420，P<0.001），while there was no significant difference in the level of TREM-1 in serum between the two groups （P>0.05）. The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein （CRP），procalcitonin （PCT），white blood cell count，and neutrophil-lymphocyte ratio （r=0.288，0.344，0.530，0.510，0.534，0.454，0.330，and 0.404，all P<0.05）. The ROC curve analysis showed that when PCT，CRP，and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection，the AUCs were 0.715 and 0.740，respectively. The multivariate Logistic regression analysis showed that CRP （odds ratio ［OR］=1.019，95% confidence interval ［CI］： 1.001‍ ‍—‍ ‍1.038，P=0.043） and serum TREM-1 （OR=1.002，95%CI： 1.000‍ ‍—‍ ‍1.003，P=0.016） were independent risk factors for the prognosis of patients with cirrhotic ascites and infection，and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis. Conclusion The level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites，and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.

Objective To investigate the expression of C1q tumor necrosis factor-related protein 3 （C1QTNF3） in liver cancer tissue，its association with the clinicopathological features of patients，and its potential value in predicting the prognosis of liver cancer. Methods Related data were collected from TIMER，UALCAN，TNMplot，and GEO databases，and the bioinformatics methods were used to measure the expression level of C1QTNF3 in pan-cancer，normal tissue/liver cancer tissue，and cancerous tissue/paracancerous tissue. Cancerous and paracancerous tissue samples were collected from 90 patients with liver cancer，and related clinical data were collected，including age，sex，tumor diameter，and tumor number. The independent-samples t test or the paired t-test was used for comparison of continuous data between groups，and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves，and the Log-rank test was used to investigate the association between the expression level of C1QTNF3 and the survival of patients with liver cancer. The Cox regression model was used to identify the risk factors for the prognosis of patients with liver cancer，and the receiver operating characteristic （ROC） curve was used to analyze the ability of C1QTNF3 expression at different time points for predicting the prognosis of patients with liver cancer. Results The bioinformatics analysis showed that the expression of C1QTNF3 was upregulated in various malignant tumors，especially in liver cancer tissue （P<0.001），and the expression level of C1QTNF3 in liver cancer tissue was significantly higher than that in normal tissue and paracancerous tissues （all P<0.01）. The immunohistochemical staining results of 90 patients with liver cancer showed that C1QTNF3 was mainly expressed in cytoplasm，with a small amount in nucleus，and it had negative expression in paracancerous tissue and positive expression in liver cancer tissue. The positive expression rate and strong positive expression rate of C1QTNF3 protein in liver cancer tissue were significantly higher than those in paracancerous tissue （positive expression rate： 76.67% vs 33.33%，χ²=34.141，P<0.01； strong positive expression rate： 54.44% vs 5.56%，χ²=51.217，P<0.01）. The liver cancer patients with a tumor diameter of ≥5 cm，an advanced stage，the presence of liver cirrhosis，negative HBsAg，and gamma-glutamyl transpeptidase （GGT）≥50 U/L had a significantly higher strong positive expression rate of C1QTNF3 protein than those with a tumor diameter of <5 cm，an early stage，the absence of liver cirrhosis，positive HBsAg，and GGT<50 U/L （all P<0.05）. The univariate Cox regression analysis showed that tumor diameter，recurrence，and C1QTNF3 expression were influencing factors for the prognosis of patients with liver cancer （all P<0.05），and the multivariate Cox regression analysis showed that the expression level of C1QTNF3 and recurrence were independent risk factors for the survival of patients with liver cancer （both P<0.05）. The survival curve analysis showed that for all patients with liver cancer，the patients with high （strong positive） expression of C1QTNF3 had significantly lower overall survival rate and disease-free survival rate than those with low expression （χ²=17.010 and 13.647，both P<0.001）； for liver cancer patients with a tumor diameter of ≥5 cm，an early/advanced stage，recurrence，the presence of liver cirrhosis，positive HBsAg，alanine aminotransferase （ALT） <40 U/L，ALT≥40 U/L，and GGT≥50 U/L，the patients with high expression of C1QTNF3 had a significant reduction in overall survival rate （χ²=11.086，5.578，5.295，19.159，16.391，13.774，10.119，8.152，and 12.035，all P<0.05）. The ROC curve analysis showed that C1QTNF3 expression had the strongest predictive potential at 5 years，with an area under the ROC curve of 0.77. Conclusion C1QTNF3 is highly expressed in liver cancer tissue，and the expression level of C1QTNF3 and recurrence are closely associated with the survival of patients with liver cancer. Patients with high expression of C1QTNF3 protein tend to have a lower survival rate.

目的 观察经聚乙二醇干扰素-α-2b（PEG-IFN-α-2b）治疗后，HBeAg阴性慢性HBV感染者HBV特异性CD8⁺T淋巴细胞活性的变化。方法 纳入2020年4月—2022年6月于新乡医学院第一附属医院、空军军医大学唐都医院就诊的HBe Ag阴性慢性HBV感染者53例，予以PEG-IFN-α-2b（180μg/周，皮下注射）抗病毒治疗，研究终点为HBsAg阴转（疗程<48周）或48周（疗程≥48周），分别选取基线和研究终点外周血单个核细胞，检测外周血T淋巴细胞计数，酶联免疫斑点试验检测分泌穿孔素、颗粒酶B、IFN-γ的HBV特异性CD8⁺T淋巴细胞频数。选择HLA-A^*02限制性患者17例，纯化CD8⁺T淋巴细胞，建立HBV特异性CD8⁺T淋巴细胞与Hep G2.2.15细胞直接接触和间接接触共培养系统，通过检测上清中乳酸脱氢酶水平计算Hep G2.2.15细胞死亡率，检测上清中HBV DNA水平、毒性分子和细胞因子分泌，流式细胞术检测凋亡配体表达，评估HBV特异性CD8⁺T淋巴细胞的杀伤功能。符合正态分布的计量资料2组间比较采用成组t检验或配对t检验，不符合正态分布的计量资料2组间比较采用Mann-Whitney U检验或Wilcoxon秩和检验。结果 研究终点时，HBsAg阴转率为30.19%（16/53）。外周血T淋巴细胞计数（CD3⁺、CD4⁺、CD8⁺T淋巴细胞）在基线和研究终点时的差异均无统计学意义（P值均>0.05）。研究终点时，患者分泌穿孔素、颗粒酶B、IFN-γ的HBV特异性CD8⁺T淋巴细胞频数较基线显著升高（U=177.50,t=11.90,U=186.50,P值均<0.001），发生HBsAg阴转的患者分泌穿孔素、颗粒酶B、IFN-γ的HBV特异性CD8⁺T淋巴细胞频数亦显著高于未发生HBsAg阴转的患者（U=120.50,t=2.73,U=121.50,P值均<0.01）。在直接接触和间接接触共培养系统中，研究终点时HBV特异性CD8⁺T淋巴细胞均可诱导Hep G2.2.15细胞上清中HBV DNA显著下降（P值均<0.001）,IFN-γ和TNF-α分泌水平显著升高（P值均<0.05），但仅在直接接触共培养系统中HBV特异性CD8⁺T淋巴细胞诱导Hep G2.2.15细胞死亡比例升高（13.62%±3.27%vs 11.39%±2.40%,t=2.27,P=0.030），穿孔素和颗粒酶B分泌水平亦升高（t=72.50,U=52.50,P值均<0.05）。在直接接触和间接接触共培养系统中，发生HBsAg阴转的患者HBV特异性CD8⁺T淋巴细胞较未发生HBsAg阴转的患者诱导HBV DNA下降水平均更显著（P值均<0.05）,IFN-γ和TNF-α分泌水平均升高（P值均<0.05）。结论 PEG-IFN-α-2b治疗HBe Ag阴性慢性HBV感染者可获得较高的HBsAg阴转率，HBV特异性CD8⁺T淋巴细胞活性显著增强，且与HBsAg阴转密切相关。

目的 比较高脂高糖高胆固醇联合腹腔注射10%四氯化碳（CCl4）诱导的代谢相关脂肪性肝炎（MASH）小鼠模型的肝脏胆汁酸谱与临床MASH胆汁酸谱的相似性，探究该模型用于药物干预MASH胆汁酸谱的可行性。方法 30只C57BL/6J雄性小鼠随机分为对照组和模型组，每组各15只。对照组：正常饲料饮食，正常饮水，每周注射橄榄油；模型组：高脂高糖高胆固醇饮食，高糖溶液饮水，每周注射CCl4+橄榄油。第8、12、16周末从每组中各取5只小鼠处理、取材。评估小鼠行为学、称取体质量、肝湿重；通过肝组织HE染色、SAF评分、油红O染色及染色面积半定量分析、血清ALT与AST水平及肝脏TG检测，评价肝脏病变和脂质沉积；通过肝组织天狼星红染色，评价肝脏纤维化；采用超高效液相色谱-串联质谱靶向代谢组学法检测肝脏胆汁酸谱，包括胆酸（CA）、甘氨胆酸（GCA）、鹅去氧胆酸（CDCA）、甘氨鹅去氧胆酸（GCDCA）、熊去氧胆酸（UDCA）、牛磺熊去氧胆酸（TUDCA）、猪去氧胆酸（HDCA）和甘氨去氧胆酸（GDCA）。符合正态分布的计量资料两组间比较采用成组t检验；不符合正态分布计量资料组间比较使用Wilcox秩和检验。结果 与同期对照组比较，第8、12、16周模型组小鼠毛发杂乱、无光泽，活动减弱，反应较迟缓；肝脏湿重均显著增加（P值均<0.05）；血清ALT水平及肝脏TG水平显著升高（P值均<0.05）,SAF评分显著升高（P值均<0.05）。肝组织中差异胆汁酸：第8周时，模型组中CA、CDCA显著高于对照组，UDCA、TUDCA、HDCA及GDCA低于对照组（P值均<0.05）；第12周时，模型组CA、GCA、CDCA、GCDCA均显著高于对照组，UDCA、HDCA低于对照组（P值均<0.05）；第16周时，模型组CA、GCA、CDCA、GCDCA、TUDCA均显著高于对照组，UDCA、HDCA、GDCA均低于对照组（P值均<0.05）。肝组织胆汁酸池中差异胆汁酸占比：第8周时，肝组织胆汁酸池差异胆汁酸中模型组CA、CDCA显著高于对照组，UDCA、TUDCA、GDCA、HDCA显著低于对照组（P值均<0.05）；第12、16周时，模型组GCA、GCDCA显著高于对照组，UDCA、GDCA、HDCA显著低于对照组（P值均<0.05）。结论 高脂高糖高胆固醇饮食联合CCl4诱导的MASH小鼠模型肝脏胆汁酸谱发生显著变化，与临床MASH胆汁酸变化具有较好的相似性，提示该模型可用于探究药物对MASH胆汁酸谱的干预作用。

<正>在2024年“不忘初心助力基层”主题实践系列公益活动中，《临床肝胆病杂志》响应号召，积极参与面向岷县人民医院、井陉县中医院的期刊捐赠活动，并获中国期刊协会医药卫生期刊分会、中国高校科技期刊研究会医学期刊专委会表彰。未来，《临床肝胆病杂志》将继续积极支援基层医疗卫生事业建设，助力基层医疗水平提升。

<正>酒精性肝病（ALD）作为全球范围内由过量饮酒引发的重大公共卫生问题，在肝病相关死亡中占据重要比例。长期酒精暴露可导致肝脏从单纯性脂肪肝发展到酒精性肝炎、肝纤维化、肝硬化及肝细胞癌。尽管ALD发病机制研究已取得显著进展，但现有临床治疗手段仍存在局限性，迫切需要开发新型治疗策略。成纤维细胞生长因子4(FGF4)属于旁分泌型FGF家族。前期研究揭示，FGF4在肝脏糖脂代谢调控中发挥关键作用，并具有抗凋亡、炎症反应调节及改善饮食诱导肝纤维化等多重功能。鉴于炎症和肝细胞凋亡是酒精性肝损伤的核心病理机制，FGF4可能通过多重机制参与酒精相关代谢紊乱的调控。然而，FGF4在酒精性肝损伤中的具体作用仍存在研究空白。2025年2月，温州医科大学李校堃院士团队宋林涛/黄志锋课题组在Hepatology发表的研究通过临床样本分析首次证实，ALD患者肝组织中FGF4 mRNA和蛋白水平显著上调，且与疾病严重程度呈正相关。在Lieber-DeCarli液体饮食诱导的小鼠模型中观察到一致现象，进一步验证了FGF4在ALD病理进程中的表达特征。肝细胞特异性敲除Fgf4后酒精诱导的肝脏氧化应激、炎症反应和细胞凋亡，以及肝损伤显著加剧。另外，肝细胞特异性敲除Fgf4的小鼠对乙醇联合CCl4诱导肝脏纤维化和损伤表现出更高易感性。然而，使用ERRγ反向激动剂GSK5182和CYP2E1抑制剂氯甲噻唑（CMZ）可缓解Fgf4缺失导致的肝损伤加剧。机制研究表明，FGF4通过激活FGFR4，进而磷酸化修饰ERRγ，促进其在肝细胞中的泛素化降解。肝脏特异性敲除Fgfr4加剧酒精性肝损伤，并完全阻断了重组FGF4△NT的药理保护作用。

目的 研究咖啡酸（CA）对雨蛙素联合脂多糖诱导的重症急性胰腺炎的影响及潜在机制，以期为重症急性胰腺炎治疗提供潜在新型药物的研究基础。方法 将6周龄C57BL/6J小鼠分为4组：对照组、模型组、CA组及醋酸奥曲肽（OA）组，每组6只。除对照组注射生理盐水外，其余各组通过腹腔注射雨蛙素联合脂多糖构建重症急性胰腺炎小鼠模型，在初次注射雨蛙素1 h后，CA组及OA组小鼠分别给予CA腹腔注射或OA皮下注射3次，每次间隔8 h。造模24 h后观察小鼠一般情况，收集血清和胰腺、肺、结肠组织。通过HE染色观察胰腺、肺组织病理变化。检测小鼠血清α-淀粉酶、脂肪酶、TNF-α、IL-6、ALT、AST和Cr水平。RT-PCR检测胰腺、肺组织促炎因子表达，通过髓过氧化物酶（MPO）免疫组化观察中性粒细胞浸润程度，Western Blot检测胰腺和肺组织核因子-κB(NF-κB)活化，中性粒细胞胞外陷阱（NET）形成标志物瓜氨酸化组蛋白H3(Cit H3)水平，以及结肠组织ZO-1表达水平。计量资料多组间数据比较采用单因素方差分析，进一步两两比较采用Dunnett’s t检验。结果 与对照组比较，模型组小鼠胰腺及肺组织损伤严重，血清α-淀粉酶、脂肪酶活性，以及血清、肺组织中促炎因子IL-6、IL-1β和TNF-α水平均显著升高（P值均<0.05），胰腺及肺组织中NF-κB活化、中性粒细胞浸润及NET形成均显著增加（P值均<0.05）。与模型组相比，CA组小鼠胰腺及肺组织病理损伤减轻，血清α-淀粉酶活性以及血清、肺组织中促炎因子IL-6、IL-1β和TNF-α水平均下调（P值均<0.05），胰腺及肺组织NF-κB活化、中性粒细胞浸润及NET形成均减少（P值均<0.05）。结论 CA可减轻雨蛙素联合脂多糖诱导的SAP小鼠模型的症状，抑制中性粒细胞募集及NET形成可能是其部分作用机制。

酒精性肝硬化患者多合并不同程度的营养不良，营养不良的患者更易出现感染、腹水等并发症，预后不佳。在临床工作中，对患者进行营养风险筛查尤为重要，使用合理的营养评估工具评定营养状态，制订个体化的营养补充方案，从而促进疾病恢复，改善患者预后及提高生活质量。本文阐述了酒精性肝硬化患者的营养筛查、评估及管理的具体方法，通过系统化的营养筛查和评估，可以早期识别出营养不良的患者，从而及时进行干预。个体化的营养补充方案需根据患者的情况进行调整，以满足其营养需求，促进肝功能的恢复和整体健康状况的改善，提升长期生活质量。

近年来，胰腺癌的规范化诊治已经在我国取得了长足的进步和发展。从最初的治疗手段匮乏，药物效果不佳，到如今手术、化疗、放疗、免疫与靶向治疗齐头并进，多学科共同决策的综合治疗模式，胰腺癌诊治逐步走向个体化、精细化与精准化。本文就胰腺癌诊治中的热点话题，结合最新的循证医学证据，探讨胰腺癌诊治的未来发展方向。

IARS1基因变异罕见，经检索，仅有10例详尽临床及遗传数据的病例被文献报道。本文报道了1例IARS1单杂合变异相关的生长迟缓和肝病，并总结IARS1变异导致生长迟缓、智力障碍、肌张力低下和肝病的临床及遗传学特点，扩展了生长迟缓、智力障碍、肌张力低下和肝病的遗传谱。

目的 通过分析血清醛酮还原酶家族1成员B10（AKR1B10）在肝细胞癌（HCC）患者中的表达情况，为HCC的临床诊断提供新的有价值的血清学标志物。方法 选取2020年5月—2024年5月承德医学院附属医院就诊的102例HCC患者、119例肝脏良性疾病患者、132例其他恶性肿瘤患者和148例健康体检者为研究对象。通过酶联免疫吸附法和化学发光法分别检测血清AKR1B10和AFP水平。非正态分布的计量资料两组间比较采用Mann-Whitney U检验，Kruskal-Wallis H检验用于多组间的比较和进一步两两比较，计数资料组间比较采用χ²检验，利用受试者操作特征曲线（ROC曲线）下面积（AUC）评估检验效能。结果 四组间AKR1B10表达差异有统计学意义[HCC组：3 053.79（1 475.67～4 605.86） pg/mL，肝脏良性疾病组：1 324.42（659.68～2 023.88） pg/m L，其他恶性肿瘤组：660.68（377.56～2 087.77） pg/m L，健康组：318.30（82.73～478.82） pg/m L,H=240.86,P<0.001)。进一步两两比较，HCC组明显高于肝脏良性疾病组、其他恶性肿瘤组和健康组（P值均<0.001）。HCC组与其他三组的ROC曲线结果显示，诊断HCC的最佳血清AKR1B10浓度界值为1 584.97 pg/mL,AUC为0.86,95%CI:0.82～0.90，敏感度为74.3%，特异度为85.2%。相较于单一指标，AKR1B10与AFP联合应用，可以提高HCC诊断的敏感度（81.8%）和特异度（91.4%）。AKR1B10诊断早中期HCC患者的AUC为0.84,95%CI:0.78～0.90，敏感度为76.2%，特异度为81.2%。AKR1B10诊断AFP阴性HCC患者的AUC为0.85,95%CI:0.77～0.92，敏感度为81.6%，特异度为79.9%。结论 AKR1B10是一种有潜力的诊断HCC的新型血清学标志物，与AFP联合使用，可能提高HCC（尤其是早中期HCC和AFP阴性HCC）患者的检出率。