Depression is a severe and recurrent mental disease and contributes to the global disease burden. However, there are limited effective treatments for depression. This study evaluated the effect of a compound Gaoziban tablet (CGZBT) on depression and explored its potential mechanisms that underlie its action in rats.

CGZBT was analyzed by high-performance liquid chromatography. Sprague-Dawley rats were randomized into the control, chronic unpredictable mild stress (CUMS), CUMS + 0.4 g/kg CGZBT, CUMS + 0.8 g/kg CGZBT, CUMS + 1.6 g/kg CGZBT, and CUMS + 10 mg/kg fluoxetine (Flu) groups. CGZBT was administered once a day for 14 days, which started on day 28 after the induction of CUMS. Animal behaviors were assessed using the sucrose preference test, forced swimming test, and open field test weekly. The levels of neurotransmitters were identified by liquid chromatography-mass spectrometry, cytokines were quantified by enzyme-linked immunosorbent assay, and CA1 cells were counted after hematoxylin-eosin staining. The expression levels of the proteins of interest were assessed using immunohistochemistry and western blotting.

Compared with the controls, the administration of CGZBT significantly increased the levels of norepinephrine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid and serum interleukin (IL) 4 and IL10, but decreased tumor necrosis factor-alpha (TNF-α), IL1β, and IL6 in rats. The number of cells in the hippocampal CA1 area increased. In addition, CGZBT reduced the levels of Axin and adenomatous polyposis coli expression in the hippocampus and significantly upregulated the levels of Wnt1, β-catenin expression, and glycogen synthase kinase-3β (GSK-3β) phosphorylation in the brains of rats.

Our results demonstrated that CGZBT significantly ameliorated depression by promoting GSK-3β phosphorylation to enhance Wnt/β-catenin activation. Our findings might provide a basis for the clinical application of CGZBT.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is currently the most common chronic liver disease and affects at least a quarter of the global adult population. It has rapidly become one of the leading causes of hepatocellular carcinoma and cirrhosis in Western countries. In this review, we discuss the nomenclature and definition of MAFLD as well as its prevalence and incidence in different geographical regions. Although cardiovascular disease remains the leading cause of death in MAFLD patients, the proportion of patients dying from hepatic complications increases sharply as the disease progresses to advanced liver fibrosis and cirrhosis. In addition, patients with MAFLD are at increased risk of various extrahepatic cancers. Although a causal relationship between MAFLD and extrahepatic cancers has not been established, clinicians should recognize the association and consider cancer screening (e.g., for colorectal cancer) as appropriate.

With the global popularization of vaccination against coronavirus disease 2019 (COVID-19), the reports of cases of vaccine-related adverse events are gradually increasing. The most common events are local pain at the injection site and atypical symptoms, such as fever, headache, myalgia, and general discomfort. However, a few people might develop serious cardiovascular complications, such as myocarditis, coronary spasm, and thrombosis. Elderly people and adolescents should be more alert to vaccine-related cardiovascular adverse events due to their underlying chronic comorbidities or compromised immune systems.

CorMatrix acts as a tissue scaffold and is intended to promote the proliferation of small vessels and tissue remodeling to replicate normal tissue function.

At Temple University Hospital, Philadelphia, PA, USA from 2013 to 2016, CorMatrix material was utilized during mitral valve anterior leaflet augmentation repair in 25 adult patients, and four patients required repeat interventions at 4–12 months (8.25 ± 4.35 months) after the initial repair. This study evaluated the pathological changes in four patients.

Histological examination of the CorMatrix showed matrix degradation in all cases. At 4 months after repair, mixed acute and chronic inflammatory cells that included eosinophils were visible within the matrix, which was more severe around the suture material. Later, the extent of inflammation abated and became more chronic with macrophage dominance. Some macrophages and multinucleated cells were visible deep in the matrix. The neovascularization was limited to the tissue–matrix boundary at early time points; the more mature vessels with dilated lumens extended deeper into the matrix as time increased, combined with some elongated fibroblast-like cells. In addition, marked acute and chronic inflammation with neutrophil and eosinophil infiltrate was identified in the surrounding native tissue at 4 months, especially around the suture material. Marked granulomatous inflammation was identified in all cases, with prominent multinucleated giant cells present at later time points (50%). Immunohistochemical staining for CD68 and CD163 showed prominent M2 macrophages in the CorMatrix and surrounding tissue.

Our results demonstrated time-dependent changes in failed CorMatrix repaired valves after mitral valve repair, with macrophages and neovascularization in the matrix 12 months after the initial repair.

Nonalcoholic fatty liver disease (NAFLD) affects about a quarter of the world’s population and poses a major health and economic burden globally. Recently, there have been hasty attempts to rename NAFLD to metabolic-associated fatty liver disease (MAFLD) despite the fact that there is no scientific rationale for this. Quest for a “positive criterion” to diagnose the disease and destigmatizing the disease have been the main reasons put forth for the name change. A close scrutiny of the pathogenesis of NAFLD would make it clear that NAFLD is a heterogeneous disorder, involving different pathogenic mechanisms of which metabolic dysfunction-driven hepatic steatosis is only one. Replacing NAFLD with MAFLD would neither enhance the legitimacy of clinical practice and clinical trials, nor improve clinical care or move NAFLD research forward. Rather than changing the nomenclature without a strong scientific backing to support such a change, efforts should be directed at understanding NAFLD pathogenesis across diverse populations and ethnicities which could potentially help develop newer therapeutic options.

With high rates of recurrence post-treatment, hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and the major cause of cancer death. To improve the overall survival of HCC patients, identification of a reliable biomarker and precise early diagnosis of HCC remain major unsolved problems.

We initially screened data from the Cancer Genome Atlas liver cancer cohort to identify potential prognosis-related genes. Then, a meta-analysis of five international HCC cohorts was implemented to validate such genes. Subsequently, artificial intelligence models (random forest and neural network) were trained to predict prognosis accurately, and a log-rank test was performed for validation. Finally, the correlation between the molecular hepatocellular carcinoma prognostic score (mHPS) and the stromal and immune scoring in HCC were explored.

A comprehensive list of 65 prognosis-related genes was obtained, most of which have been not extensively studied thus far. A universal HCC mHPS system depending on the expression pattern of only 23 genes was established. The mHPS system had general applicability to HCC patients (log-rank p<0.05) in a platform-independent manner (RNA sequencing or microarray). The mHPS was also correlated with the stromal and immune scoring in HCC, reflecting the status of the tumor immune microenvironment.

Overall, the mHPS is an easy and cost-effective prognosis predicting system, which can disclose previously uncovered heterogeneity among patient subpopulations. The mHPS system can further stratify patients who are at the same clinical stage and should be valuable for precise treatment. Moreover, the prognosis-related genes recognized in this study have potential in targeted and immune therapy.

The effect of ginsenoside Rb1 on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury (ALI) is unknown. The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms.

Mice were pretreated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment, to induce ALI. The survival rate was monitored every hour for 24 h, and serum biochemical parameters, hepatic index and histopathological analysis were evaluated to measure the degree of liver injury. ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum. Immunohistochemistry staining, RT-PCR and western blotting were performed to evaluate the expression of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), and NLR family, pyrin domain-containing 3 protein (NLRP3) in liver tissue and Kupffer cells (KCs).

Ginsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%, significantly ameliorated the increased alanine and aspartate transaminase, restored the hepatic pathological changes and reduced the levels of oxidative stress and inflammatory cytokines altered by D-GalN/LPS. Compared to the control group, the KCs were increased in the D-GalN/LPS groups but did not increase significantly with Rb1 pretreatment. D-GalN/LPS could upregulate while Rb1 pretreatment could downregulate the expression of interleukin (IL)-1β, IL-18, NLRP3, apoptosis associated speck-like protein containing CARD (ASC) and caspase-1 in isolated KCs. Furthermore, ginsenoside Rb1 inhibited activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome induced by D-GalN/LPS administration.

Ginsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.

The immune system plays vital roles in hepatocellular carcinoma (HCC) initiation and progression. The present study aimed to construct an immune-gene related prognostic signature (IRPS) for predicting the prognosis of HCC patients.

Gene expression data were retrieved from The Cancer Genome Atlas database. The IRPS was established via least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. The prognostic values of the IRPS were further validated using the International Cancer Genome Consortium (ICGC) dataset.

A total of 62 genes were identified as candidate immune-related prognostic genes. According to the results of Lasso and multivariate Cox regression analysis, we established an IRPS and confirmed its stability and reliability in the ICGC dataset. The IRPS was significantly associated with advanced clinicopathological characteristics. Both Cox regression analyses revealed that the IRPS could be independent risk factors influencing prognosis of HCC patients. The relationships between the IRPS and infiltration of immune cells demonstrated that the IRPS was associated with immune cell infiltration. Furthermore, a nomogram was constructed to estimate the survival probability of HCC patients.

The IRPS was effective for predicting prognosis of HCC patients, which might serve as novel prognostic and therapeutic biomarkers for HCC.

Ewing’s sarcoma (ES) is a tumor that often occurs in the long bones and rarely arises from visceral organs primarily. Here, we report a case of primary hepatic ES, discuss its computed tomography (CT) and gadobenate dimeglumine-enhanced magnetic resonance (MRI) features. This is the first Chinese and fifth primary hepatic ES case reported, based on a literature review. Imaging examinations showed that the tumor was solid, with necrosis and hemorrhage. Contrast-enhanced images showed that the tumor was hypervascular and especially had heterogeneous signal intensity on hepatobiliary phase MRI images. Intratumoral vessels and vascular invasion were also present.

Vibration-controlled transient elastography (VCTE) is a noninvasive tool that uses liver stiffness measurement (LSM) to assess fibrosis. Since real-life data during everyday clinical practice in the USA are lacking, we describe the patterns of use and diagnostic performance of VCTE in patients at an academic medical center in New York City.

Patients who received VCTE scans were included if liver biopsy was performed within 1 year. Diagnostic performance of VCTE in differentiating dichotomized fibrosis stages was assessed via area under the receiver operating characteristics (AUROC). Fibrosis stage determined from VCTE LSM was compared to liver biopsy.

Of 109 patients, 49 had nonalcoholic fatty liver disease, 16 chronic hepatitis C, 15 congestive hepatopathy, and 22 at least two etiologies. AUROC was 0.90 for differentiating cirrhosis (stage 4) with a positive predictive value (PPV) range of 0.28 to 0.45 and negative predictive value range of 0.96 to 0.98. For 31 (32%) patients, VCTE fibrosis stage was at least two stages higher than liver biopsy fibrosis stage. Thirteen of thirty-five patients considered to have cirrhosis by VCTE had stage 0 to 2 and 12 stage 3 fibrosis on liver biopsy.

VCTE has reasonable diagnostic accuracy and is reliable at ruling out cirrhosis. However, because of its low PPV, caution must be exercised when used to diagnose cirrhosis, as misdiagnosis can lead to unnecessary health care interventions. In routine practice, VTCE is also sometimes performed for disease etiologies for which it has not been robustly validated.

The incidence of hepatocellular carcinoma (HCC) is significantly lower in women than men, implying that estrogen receptors (ERs) may play an important role in this sex dimorphism. Recently, considerable progress has been made in expanding our understanding of the mechanisms of ERs in HCC. As one of the most important ERs, ERα functions as a tumor suppressor in the progression of HCC through various pathways, such as STAT3 signaling pathways, lipid metabolism-related signaling pathways, and non-coding RNAs. However, the function of ERα was reduced with the changes of some molecules in the liver, which may develop further into HCC and make it difficult to achieve an effective hormone treatment effect. Intriguingly, there are signs that individualized hormone therapy according to the activity of ERα will overcome this challenge. Based on these observations, it is particularly imperative to reassess and extend the function of ERα. In this review, we mainly elucidated molecular mechanisms associated with ERα in HCC and investigated the individualized hormone therapy based on these mechanisms, with the aim of providing new insights for HCC treatment.

The proportions of patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) varies greatly in different countries or regions, ranging from 13% to 45%. The treatment regimens for PVTT recommended by HCC guidelines in different countries or regions also vary greatly. In recent years, with the progress and development of surgical concepts, radiotherapy techniques, systematic therapies (for example, VEGF inhibitors, tyrosine kinase inhibitors and immune checkpoint inhibitors), patients with HCC involving PVTT have more treatment options and their prognoses have been significantly improved. To achieve the maximum benefit, both clinicians and patients need to think rationally about the indications of treatment modalities, the occurrence of severe adverse events, and the optimal fit for the population. In this review, we provide an update on the treatment modalities available for patients with HCC involving PVTT. Trials with large sample size for patients with advanced or unresectable HCC are also reviewed.

Irreversible electroporation (IRE) is an emerging local ablation therapy which may be effective for unresectable tumors. This study aimed to evaluate the safety and efficacy of percutaneous IRE in the treatment of hepatocellular carcinoma (HCC) abutting the diaphragm.

A total of 26 participants with 39 tumors abutting the diaphragm were prospectively evaluated between July 2015 and September 2018. Complications associated with IRE were recorded, and the survival benefit of IRE was analyzed. The factors associated with time to local tumor progression (LTP) were analyzed using univariate and multivariate Cox regression models.

No major complications or treatment-related deaths occurred. The technical success rate was 96.2% (25/26) and complete ablation rate was 92.3% (36/39). The median follow-up period was 16.7 months (range: 3.0–43.0 months), the LTP occurred in 15.2% of tumors and median time to LTP was 20.4 months. Overall, tumor size (hazard ratio: 1.24 [95% confidence interval: 0.38, 3.81], p=0.03) was the only factor associated with time to LTP.

This study shows for the first time that percutaneous IRE is a safe and effective ablation technology for HCC abutting the diaphragm.

QingFeiPaiDu decoction (QFPDD) treatment benefits patients with coronavirus disease 2019 (COVID-19). This study aims to elucidate the mechanisms that underlie the anti-inflammatory effects of QFPDD.

Based on the clinical symptoms of COVID-19 patients, a component-target-disease network was constructed using the network pharmacology method, and the potential active components, targets, and molecular mechanisms of QFPDD for the treatment of COVID-19 were screened using topology parameter analysis. The best molecules that were affected by QFPDD were validated using Real-Time quantitative polymerase chain reaction (RT-qPCR) in a cellular inflammation model.

In total, 376 active ingredients were identified in QFPDD, and 18,833 potential anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets. The principal targets included PIK3CA, PIK3R1, APP, SRC, MAPK1, MAPK3, AKT1, HSP90AA1, EP300, and CDK1. Overall, 574 gene oncology entries and 214 signal pathways were identified. QFPDD affected the cellular response to nitrogen compounds, protein kinase activity, and membrane rafts. QFPDD modulated pathways that are associated with cancer, endocrine resistance, PI3K-Akt signaling, and proteoglycans in cancer. Molecular docking indicated that the core ingredients of QFPDD had a strong binding affinity for SARS-CoV-2 3-chymotrypsin-like cysteine protease (3CLpro) and angiotensin-converting enzyme 2 (ACE2). QFPDD treatment significantly mitigated the lipopolysaccharides-induced five targeted gene transcription in A549 cells.

Our findings preliminarily elucidated that through its active ingredients QFPDD targeted 3CLpro and ACE2 to modulate many factors and pathways that are associated with the pathogenesis of COVID-19. The identified potential molecular mechanism, relevant factors, and key genes QFPDD targeted might help in the design of new and specific antiviral drugs.

Previous studies have reported that the single nucleotide polymorphisms (SNPs) of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease (NAFLD). However, no studies have examined the effect of interactions between these three genotypes to affect liver disease severity. We assessed the effect of these three SNPs on nonalcoholic steatohepatitis (NASH) and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD.

We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD. Multivariable logistic regression analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409. Gene-gene interactions were analyzed by performing a generalized multifactor dimensionality reduction (GMDR) analysis.

The mean ± standard deviation age of these 415 patients was 41.3±12.5 years, and 75.9% were men. Patients with SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH, even after adjustment for age, sex and body mass index. GMDR analysis showed that the combination of all three SNPs was the best model for predicting NASH. Additionally, the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C.

NAFLD patients carrying the SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH. These three SNPs may synergistically interact to increase susceptibility to NASH.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term from nonalcoholic fatty liver disease (NAFLD) and is a positive diagnosis based on histopathology, imaging, or blood biomarkers. MAFLD is one of the common causes of liver dysfunction worldwide, likely due to the increase in metabolic syndrome as well as the high burden of disease and its relationship to other extrahepatic conditions. However, effective pharmacological therapeutic agents are still lacking; current management largely focuses on weight reduction and lifestyle modification. The purpose of this review was to summarize the updated evidence of novel therapies targeting different pathogenetic pathways in MAFLD.

Chronic kidney disease (CKD) usually occurs during the chronic infection of hepatitis B virus (HBV). However, the risk factors of CKD in an HBV population have not been completely demonstrated. Our present study aimed to investigate the risk factors of CKD in chronic HBV infection using a hospital based cross-sectional study in the northern area of China.

During January 2013 to December 2017, a total of 94 patients with CKD complicated by chronic HBV infection were consecutively enrolled in the study, as well as 548 age- and sex-matched hepatitis B patients without CKD who were enrolled as controls. Univariate and multivariate regression analyses were used to determine the effects of each variable after adjusting for cofounding factors.

Multivariate analysis showed that HBeAg-positive status (odds ratio [OR]=2.099, 95% CI 1.128–3.907), dyslipidemia (OR: 3.025, 95% CI 1.747–5.239), and hypertension (OR: 12.523, 95% CI 6.283–24.958) were independently associated with the incidence of CKD, while duration of HBV infection (≥240 months) (OR: 0.401, 95% CI 0.179–0.894), Log10 HBsAg (OR: 0.514, 95% CI 0.336–0.786), and coronary heart disease (OR: 0.078, 95% CI 0.008–0.768) were protective factors for the incidence of CKD. Duration of HBV infection, Log10 HBsAg, HBeAg-positive status and dyslipidemia remained the risk factors for CKD after adjusting for diabetes mellitus, hypertension, and coronary heart disease.

Duration of HBV infection, Log10 HBsAg, HBeAg-positive status and dyslipidemia contributed to the incidence of CKD during chronic HBV infection in a Chinese population.

AT-rich interactive domain-containing protein 1A (ARID1A) is frequently mutated or deficient in hepatocellular carcinoma (HCC). However, the role of ARID1A in HCC remains unclear. Therefore, the biological role of ARID1A in HCC was evaluated and a potential mechanism was investigated.

Arid1a was knocked out in the livers of mice using the CRISPR/Cas9 system delivered by hydrodynamic tail vein injection. The development of HCC was observed in different mouse models. The correlation of ARID1A and prognosis in patients with HCC was analyzed using cBioPortal. The effect of ARID1A on cell proliferation was assessed by MTT assay following the manipulation of candidate genes.

ARID1A deficiency alone did not cause HCC in mice, but knockout of ARID1A accelerated liver tumorigenesis in response to diethylnitrosamine (DEN) or when a combination knockout of phosphatase and tensin homolog (Pten) plus tumor protein P53 (p53) was introduced. ARID1A mutations were associated with a poorer prognosis in HCC patients. The mRNA level of MYC was significantly higher in patients with an ARID1A mutation compared to those without a mutation. Ectopic expression of ARID1A inhibited HCC cell proliferation. ARID1A knockout increased HCC cell growth and resulted in disruptions to DNA damage repair and apoptosis following radiation stress. Furthermore, mechanistic studies revealed that ARID1A inhibited the proliferation of HCC cells via transcriptional down-regulation of MYC.

These results describe ARID1A as a tumor suppressor in the liver. A deficiency in ARID1A predicts worse survival in HCC patients and promotes HCC progression via up-regulation of MYC transcription.