Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
Humans ; RNA, Long Noncoding/genetics* ; Liver Cirrhosis/genetics* ; Liver/metabolism* ; Hepatic Stellate Cells/pathology* ; MicroRNAs/metabolism* ; Extracellular Matrix/metabolism* ; Drugs, Chinese Herbal

BACKGROUND: Current guidelines recommend hepatocellular carcinoma (HCC) screening in high-risk populations. However, the ideal HCC screening interval and screening modality have not been determined. This study aimed to compare the screening efficacy among different modalities with various intervals. METHODS: PubMed and other nine databases were searched through June 30, 2021. Binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs). Survival rates were also pooled using RR with 95% CIs because most eligible studies only provided the number of survival patients instead of hazard ratio. RESULTS: In all, 13 studies were included. Two random controlled trials (RCTs) and six cohort studies compared screening intervals for ultrasonography (US) screening and found no significant differences between shorter (3- or 4-month) and longer (6- or 12-month) screening intervals in terms of early HCC proportion, HCC significant mortality, 1-year survival rate; screening at 6-month interval significantly increased the proportion of early HCC (RR = 1.17, 95% confidence interval [CI]: 1.08-1.26) and prolonged the 5-year survival rate (RR = 1.39, 95% CI: 1.07-1.82) relative to the 12-month interval results. Three other RCTs and two cohort studies compared different screening modalities in cirrhosis or chronic hepatitis B, which indicated no statistical differences in the proportion of early HCC (RR = 0.89, 95% CI: 0.40-1.96) and HCC mortality (RR = 0.69, 95% CI: 0.23-2.09) between the biannual US and annual computed tomography (CT screening). Biannual US screening showed a lower proportion of early HCC than biannual magnetic resonance imaging (MRI) (RR = 0.60, 95% CI: 0.37-0.97) and biannual US combined with annual CT (RR = 1.31, 95% CI: 1.13-1.51) screening. The proportion of early HCC in the contrast-enhanced US group was slightly higher than that in the B-mode US (RR = 1.08, 95% CI: 1.00-1.23) group. CONCLUSIONS: The evidence suggests that 6 months may be the best HCC screening interval for US screening. The effectiveness of CT and MRI is better than US during same screening intervals. However, MRI and CT are more expensive than US, and CT also can increase the risk of radiation exposure. The selection of CT or MRI instead of US should be carefully considered. REGISTRATION No. CRD42020148258 at PROSPERO website ( https://www.crd.york.ac.uk/PROSPERO/ ).
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Liver Cirrhosis/complications* ; Risk Factors ; Cohort Studies

Hepatocellular carcinoma (HCC) is the most common type of primary hepatocellular carcinoma (PHC). Early diagnosis of HCC remains the key to improve the prognosis. In recent years, with the promotion of the concept of precision medicine and more in-depth analysis of the biological mechanism underlying HCC, new diagnostic methods, including emerging serum markers, liquid biopsies, molecular diagnosis, and advances in imaging (novel contrast agents and radiomics), have emerged one after another. Herein, we reviewed and analyzed scientific advances in the early diagnosis of HCC and discussed their application and shortcomings. This review aimed to provide a reference for scientific research and clinical practice of HCC.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Prognosis ; Early Diagnosis ; Precision Medicine

The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the "mucus layer-soil" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between "mucus layer-soil" and "gut bacteria-seed" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the "gut bacteria-seed". However, a lack of effective repair and management of the "mucus layer-soil" may be a reason why "seeds" cannot be well colonized and grow in the host gut, as the thinning and destruction of the "mucus layer-soil" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that "mucus layer-soil" restoration combined with "gut bacteria-seed" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.
Humans ; Non-alcoholic Fatty Liver Disease/therapy* ; Gastrointestinal Microbiome ; Probiotics ; Prebiotics ; Fecal Microbiota Transplantation ; Bacteria ; Liver/pathology*

Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Hypoglycemic Agents/therapeutic use* ; Liver Cirrhosis/pathology* ; Biopsy ; Patients ; Liver/pathology* ; Fibrosis

Transarterial interventional therapy is one of the most widely used treatment methods in patients with primary hepatocellular carcinoma. With the progress in interventional technology and the use of new drugs, transarterial interventional therapy has achieved favorable results in the treatment of primary hepatocellular carcinoma and has become the first choice non-surgical treatment for advanced liver cancer. However, at present, there are great differences in the drugs used in transarterial interventional treatment and the combined application of other drugs among centers, and there is no uniform consensus or guideline. Based on the latest research data and clinical practice experience, as well as the characteristics of Chinese patients, the Specialist Group of Interventional Drugs, Interventionalists Branch of the Chinese Medical Doctor Association was organized to formulate the Chinese expert consensus on intra-arterial drug and combined drug administration for primary hepatocellular carcinoma. The purpose of this consensus is to explore the efficacy and safety of drugs and drug combinations related to intra-arterial interventional therapy, the use of drugs in special populations, the management of adverse reactions, and adjuvant drugs to provide a reference for clinical practice.
Humans ; Carcinoma, Hepatocellular/pathology* ; Consensus ; East Asian People ; Liver Neoplasms/pathology* ; Pharmaceutical Preparations ; Infusions, Intra-Arterial/methods* ; Antineoplastic Agents/therapeutic use* ; Drug Therapy, Combination/methods*

Lamin B1 (LMNB1) is highly expressed in liver cancer tissues, and its influence and mechanism on the proliferation of hepatocellular carcinoma cells were explored by knocking down the expression of the protein. In liver cancer cells, siRNAs were used to knock down LMNB1. Knockdown effects were detected by Western blotting. Changes in telomerase activity were detected by telomeric repeat amplification protocol assay (TRAP) experiments. Telomere length changes were detected by quantitative real-time polymerase chain reaction (qPCR). CCK8, cloning formation, transwell and wound healing were performed to detect changes in its growth, invasion and migration capabilities. The lentiviral system was used to construct HepG2 cells that steadily knocked down LMNB1. Then the changes of telomere length and telomerase activity were detected, and the cell aging status was detected by SA-β-gal senescence staining. The effects of tumorigenesis were detected by nude mouse subcutaneous tumorigenesis experiments, subsequent histification staining of tumors, SA-β-gal senescence staining, fluorescence in situ hybridization (FISH) for telomere analysis and other experiments. Finally, the method of biogenesis analysis was used to find the expression of LMNB1 in clinical liver cancer tissues, and its relationship with clinical stages and patient survival. Knockdown of LMNB1 in HepG2 and Hep3B cells significantly reduced telomerase activity, cell proliferation, migration and invasion abilities. Experiments in cells and tumor formation in nude mice had demonstrated that stable knockdown of LMNB1 reduced telomerase activity, shortened telomere length, senesced cells, reduced cell tumorigenicity and KI-67 expression. Bioinformatics analysis showed that LMNB1 was highly expressed in liver cancer tissues and correlated with tumor stage and patient survival. In conclusion, LMNB1 is overexpressed in liver cancer cells, and it is expected to become an indicator for evaluating the clinical prognosis of liver cancer patients and a target for precise treatment.
Animals ; Mice ; Telomerase/metabolism* ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Telomere Shortening ; In Situ Hybridization, Fluorescence ; Mice, Nude ; Telomere/pathology* ; Carcinogenesis

Objective To study the effect and mechanism of pearl hydrolysate on hepatic sinusoidal capillarization in liver fibrosis. Methods Hepatic sinusoidal endothelial cells (HSEC) and hepatic stellate cells (HSC-LX2) were incubated with Hepu pearl hydrolysate.The proliferation of HSEC and HSC-LX2 was examined by MTT colorimetry.The cell cycle and apoptosis of HSC-LX2 were measured by flow cytometry.The changes of the microstructures such as fenestra and basement membrane of HSEC were observed by transmission electron microscopy. Results The intervention with leptin increased the viability of HSC-LX2 (P=0.041),decreased the viability of HSEC (P=0.004),and caused capillarization signs such as decreased number and diameter of fenestrae and formation of continuous basement membrane.The treatment with pearl hydrolysate at different doses increased and expanded the fenestrae of HSEC (low dose:P=0.020;medium dose:P=0.028;high dose:P=0.032),disintegrated the extracellular basement membrane of HSEC (low dose:P=0.020;medium dose:P=0.028;high dose:P=0.032),decreased the viability of HSC-LX2 (low dose:P=0.018;medium dose:P=0.013;high dose:P=0.009),and induced the apoptosis of HSC-LX2 (low dose:P=0.012;medium dose:P=0.006;high dose:P=0.005).Pearl hydrolysate exerted therapeutic effect on capillarization in a dose-dependent manner (low dose:P=0.020;medium dose:P=0.028;high dose:P=0.032).Moreover,high-dose pearl hydrolysate showed stronger effect on capillarization of hepatic sinuses than colchicine (P=0.034) and salvianolic acid B (P=0.038). Conclusion Hepu pearl hydrolysate can increase the viability of HSEC,restore the area of fenestrae,disintegrate the basement membrane,and decrease the viability and induce the apoptosis of HSC-LX2,demonstrating significant pharmacological effects on the capillarization of HSEC and HSC-LX2.
Humans ; Endothelial Cells/metabolism* ; Liver Cirrhosis ; Liver/pathology*

Primary myelofibrosis (PMF) is easily confused with cirrhosis, due to its main clinical manifestations of splenomegaly and the blood cytopenia. This review focuses on clinical studies to identify primary myelofibrosis and cirrhosis related portal hypertension, to analyze the differences between the two diseases, in order to distinguish PMF and cirrhosis from the pathogenesis, clinical manifestations, laboratory examinations and treatment principles, and simultaneously improve clinicians' understanding of PMF, which is a reference for exploring the early screening or diagnostic indicators of PMF, also provides a clinical basis for the application of new targeted drugs such as ruxolitinib.
Humans ; Primary Myelofibrosis/drug therapy* ; Hypertension, Portal/complications* ; Liver Cirrhosis/pathology* ; Splenomegaly/pathology* ; Anemia

Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology*