ObjectiveTo investigate the effect of SU056， an azo-podophyllotoxin derivative， on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group， model group （CCl₄+normal saline）， and treatment group （CCl₄+SU056）， with 4 mice in each group. Mice were given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and during the middle stage of modeling， the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury， collagen deposition， and liver function were assessed based on HE staining， Masson staining， Sirius Red staining， the content of hydroxyproline in liver tissue， and the serum levels of alanine aminotransferase and aspartate aminotransferase， and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α （α-SMA）， collagen type Ⅰ， and Y-box binding protein 1 （YB1）. The human hepatic stellate cell （HSC） line LX-2 and primary mouse HSC were used， and CCK-8 assay was used to measure cell proliferation； Transwell assay was used to observe cell migration； quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ， collagen type Ⅲ， YB1， phosphorylated mammalian target of rapamycin （mTOR）， and phosphorylated S6K， so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-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. ResultsIn the mouse model of liver fibrosis induced by CCl₄， compared with the model group， the treatment group had significant alleviation of inflammatory cell infiltration， collagen deposition， and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue （all P<0.01）. Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA， collagen type I， and YB1 in liver tissue （all P<0.01）. In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells （P<0.01）， the migration of LX-2 cells （P<0.05）， and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ （all P<0.05） in a dose-dependent manner， and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1， phosphorylated mTOR， and phosphorylated S6K in LX-2 cells， and treatment with SU056 （10 and 20 µmol/L） could downregulate the protein expression levels of collagen type I， YB1， phosphorylated mTOR， and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice （P<0.01）. ConclusionSU056 can effectively inhibit HSC activation， proliferation， migration， and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis， by disrupting the YB1/mTOR positive feedback signaling axis.

Liver cirrhosis as the terminal stage of chronic liver disease has seen many new insights and advances in its treatment strategies and perspectives in recent years. However, there are still many controversies about cirrhotic portal hypertension management, prevention, therapy, and complications. This article summarizes the main key controversial points in the current treatment of liver cirrhosis from an evidence-based medicine perspective, including the use of non-selective β-blockers during decompensated stages, exploration of precise strategies for albumin, re-evaluation of the risks of statins, weighing the pros and cons of proton pump inhibitors, new understandings of anticoagulation therapy, breakthroughs in targeting gut microbiota, and nutritional support management. In addition, it combines the latest research data and guideline recommendations to explore future development directions so as to provide clinical practice reference.

Liver fibrosis is a common pathological process in various chronic liver diseases. Early-stage and accurate diagnosis, as well as assessment of the degree of liver fibrosis, is crucial for the management of chronic liver diseases. Conventional imaging techniques for liver fibrosis (elastography and magnetic resonance elastography) still have the drawback of low sensitivity in detecting early-stage fibrosis. In recent years, emerging imaging omics based on ultrasound and magnetic resonance have improved the diagnostic accuracy and visualization stage of liver fibrosis. The emergence of artificial intelligence technology has also provided more options for the technological advancement of liver fibrosis imaging. This article aims to review the emerging liver fibrosis imaging technologies in recent years and compare their diagnostic performance with ultrasound elastography, shear wave elastography, and magnetic resonance elastography recommended by the current domestic and international guidelines and to pinpoint simultaneously the limitations and challenges that still exist in liver fibrosis imaging while reflecting the technological advances.

Liver cirrhosis as the terminal stage of chronic liver disease has seen many new insights and advances in its treatment strategies and perspectives in recent years. However, there are still many controversies about cirrhotic portal hypertension management, prevention, therapy, and complications. This article summarizes the main key controversial points in the current treatment of liver cirrhosis from an evidence-based medicine perspective, including the use of non-selective β-blockers during decompensated stages, exploration of precise strategies for albumin, re-evaluation of the risks of statins, weighing the pros and cons of proton pump inhibitors, new understandings of anticoagulation therapy, breakthroughs in targeting gut microbiota, and nutritional support management. In addition, it combines the latest research data and guideline recommendations to explore future development directions so as to provide clinical practice reference.

Liver fibrosis is a common pathological process in various chronic liver diseases. Early-stage and accurate diagnosis, as well as assessment of the degree of liver fibrosis, is crucial for the management of chronic liver diseases. Conventional imaging techniques for liver fibrosis (elastography and magnetic resonance elastography) still have the drawback of low sensitivity in detecting early-stage fibrosis. In recent years, emerging imaging omics based on ultrasound and magnetic resonance have improved the diagnostic accuracy and visualization stage of liver fibrosis. The emergence of artificial intelligence technology has also provided more options for the technological advancement of liver fibrosis imaging. This article aims to review the emerging liver fibrosis imaging technologies in recent years and compare their diagnostic performance with ultrasound elastography, shear wave elastography, and magnetic resonance elastography recommended by the current domestic and international guidelines and to pinpoint simultaneously the limitations and challenges that still exist in liver fibrosis imaging while reflecting the technological advances.

Non-alcoholic fatty liver disease(NAFLD)constitutes a series of histological lesions characterized by varying degrees of hepatocyte damage,fat accumulation,inflammation,and fibrosis.Currently,liver biopsy is considered the"gold standard"for evaluating the degree of hepatic steatosis,inflammation,and fibrosis,and it also serves as the cornerstone for accurate grading of NAFLD.This article reviews the value and application of liver biopsy in the clinical diagnosis,staging,and clinical trials of NAFLD.

Objective:To investigate the factors associated with delay in anticoagulant therapy in patients with cerebral venous sinus thrombosis (CVST) and its effect on outcome.Methods:Patients with CVST admitted to Changhai Hospital, Naval Medical University from January 2010 to August 2021 were retrospectively enrolled. Patients were divided into early anticoagulation group and late anticoagulation group by the median time interval from first symptom to initiation of anticoagulation. The modified Rankin Scale was used for outcome assessment at 90 d after onset. 0-2 scores were defined as good outcome and 3-6 were defined as poor outcome. Demographic and clinical data were compared for the early versus late anticoagulation group and for the good versus poor outcome groups. Multivariable logistic regression was used to identify independent influencing factors of delay in anticoagulation and the correlation of delay in anticoagulation with poor outcome. Results:A total of 131 patients were included, their age was 40.07±15.11 years old, and 68 (51.91%) were male. Of these, 65 patients (49.62%) were in the early anticoagulation group and 14 (10.69%) were in the poor outcome group. Compared with the late anticoagulation group, the early anticoagulation group had a significantly higher proportion of patients with seizures and brain parenchymal damage as well as higher D-dimer levels on admission, while the proportion of patients with visual impairment/papilloedema was significantly lower (all P<0.05). Compared with the good outcome group, the poor outcome group had significantly higher proportions of patients with seizures, dyskinesia, impaired consciousness, low Glasgow Coma Scale score, and brain parenchymal damage as well as higher D-dimer, total cholesterol and low density lipoprotein cholesterol levels, sites of thrombus involvement were more common in the superior sagittal and straight sinuses, and significantly lower proportions of patients with headache and lower albumin levels on admission (all P<0.05). Multivariate logistic regression analysis showed that visual impairment/papilloedema (odds ratio [ OR] 0.119, 95% confidence interval [ CI] 0.030-0.473; P=0.002) and brain parenchymal damage ( OR 1.341, 95% CI 1.042-1.727; P=0.023) were independently associated with a delay in anticoagulation treatment, and a delay in anticoagulation treatment ( OR 6.102, 95% CI 1.185-30.504; P=0.030) and D-dimer level on admission ( OR 1.299, 95% CI 1.141-1.480; P<0.001) were the independent predictors of poor outcome in patients with CVST. Conclusions:Visual impairment/papilloedema and absence of brain parenchymal damage on cranial imaging are the independent risk factors for delay in anticoagulation in patients with CVST. The delay in anticoagulation is strongly associated with the poor outcome in patients with CVST.

ObjectiveTo study the mechanism of myocardial dielectric property changes in radio frequency during hypothermic preservation and explore myocardial viability evaluative method. Methods Hybrid young pigs (20-30 kg) were used in the experiment. Heart arrest was induced with GIK solution. According to preservative temperature, the animals were divided into three groups: group A (4 ℃),group B (15 ℃) and group C (25 C). The heart was preserved in saline for 12,6 and 4 h respectively. Myocardial dielectric properties and ATP content were tested every 5 and 30 min during hypothermic preservation respectively. The relationship between tanoδm and ATP content was analyzed. ResultsTanδm of three groups was decreased significantly at the beginning, most slightly in group A and most obviously in group C. There was no significant difference in Tanδm between group B and group C with group A at 1 h,but there was obvious difference at 2,3 and 4 h (P＜0. 05,P＜0. 05,P＜0. 01 ). There was correlation between tanδm and ATP in the three groups. ConclusionTanδm in three groups is dropped with preservation time and temperature, and tanδm had a correlation with ATP content. Detection of myocardial dielectric property in radio frequency is a kind of quick, accurate and noninvasive method.