Xiaojun Wang

Introduction: Chronic hepatitis B virus (HBV) infection is the leading cause of primary liver cancer (PLC), notably hepatocellular carcinoma. G-protein coupled receptor-associated sorting protein 1 (GPRASP1), a G protein-coupled receptor-associated protein, has been implicated in multiple malignancies. However, its role in PLC, particularly in hepatitis B surface antigen (HBsAg)-positive patients, remains unclear. Objective: To explore the GPRASP1 expression pattern and its clinical significance in PLC, with a focus on HBsAg-positive cases, and to evaluate its potential as a candidate biomarker. Methods: Tumor center tissues and paired adjacent non-tumor liver tissues were collected from 12 pathologically confirmed PLC patients, including seven with active HBV infection or chronic carrier status. GPRASP1 mRNA expression levels were quantified using reverse-transcription quantitative polymerase chain reaction. Associations between GPRASP1 expression and clinicopathological variables were statistically analyzed. Results: GPRASP1 mRNA expression was significantly up-regulated in central tumor tissues and paired adjacent non-tumor liver tissues (p = 0.034). Elevated GPRASP1 expression was detected in 80% of HBsAg-positive PLC patients. GPRASP1 levels were significantly inversely correlated with hepatitis B surface antibody titers. Higher GPRASP1 expression was positively correlated with lymphocyte infiltration (τ = 0.816, p = 0.007). Moreover, GPRASP1 expression was negatively correlated with serum total bilirubin (r = −0.636, p = 0.026), direct bilirubin (r = −0.622, p = 0.031), and indirect bilirubin (r = −0.727, p = 0.007). Conclusion: GPRASP1 is overexpressed in PLC tissues, particularly in HBsAg-positive patients, and its expression is associated with host immune response and hepatic functional markers. GPRASP1 may serve as a potential diagnostic biomarker for PLC and may provide novel insights into its diagnosis.

G-protein coupled receptor-associated sorting protein 1 (GASP1) is a secreted protein that has been reported to be associated with various malignant tumors. However, its role in primary liver cancer (PLC) remains largely unexplored. The aim of this study was to evaluate the expression and clinical significance of GASP1 in PLC, as well as to investigate its potential as a clinical biomarker. To achieve this, we conducted RT-qPCR experiments to assess the transcriptional levels of GASP1 in tumor tissues from cancer patients compared to adjacent non-tumor liver tissues. Statistical analyses were performed to examine the associations between GASPl levels and various clinicopathological factors. Our results demonstrated that the mRNA expression level of GASP1 was significantly higher in PLC tumor center tissues compared to matched adjacent non-tumor liver tissues (P=0.034). Additionally, Fisher's exact test revealed a significant association between GASP1 expression and lymphocyte infiltration (P=0.018), suggesting that GASP1 may play an important role in the tumor microenvironment (TME) of PLC. Notably, we observed that among PLC patients exhibiting lymphocyte infiltration, a majority were hepatitis B patients or carriers of the hepatitis B virus (HBV). This observation indicates a potential relationship between GASP1 expression and HBV infection in the pathogenesis of PLC. We also identified elevated GASP1 expression in the majority of AFP-positive patients and HBsAg-positive patients, suggesting a potential correlation between GASP1 expression and both AFP levels and HBV status in PLC. Furthermore, our findings indicated that GASP1 expression exhibits a negative correlation with HBsAb (r=-0.609, P=0.035), TBIL (r=-0.636, P=0.026), DBIL (r=-0.622, P=0.031), and IBIL (r=-0.727, P=0.007), while demonstrating a positive correlation with lymphocyte infiltration (τ=0.816, P=0.007). In summary, our findings emphasize that GASP1 may serve as a novel biomarker for PLC and its expression levels are associated with clinicopathological features. This insight offers a new perspective for the diagnosis and treatment of PLC.

Background: Hepatocellular carcinoma (HCC) poses ongoing difficulties for public health systems due to its high incidence and poor prognosis. Huqi formula (HQF), a well-known prescription in traditional Chinese medicine, has demonstrated notable clinical effectiveness in the treatment of HCC. However, the mechanisms underlying its therapeutic effects have yet to be completely elucidated. Purpose: This study aimed to investigate the anti-HCC effects of HQF and its underlying mechanisms. Methods: Chemical profiling and quantification of HQF were conducted by LC–MS and HPLC. Orthotopic and subcutaneous tumor models were established through hydrodynamic injection of Akt/Nras plasmids and subcutaneous injection of c-Met/sgPten cells, respectively, to evaluate the therapeutic effects of HQF on HCC. Network pharmacology, RNA-Seq, molecular docking, Western blot, and flow cytometry were employed to assess the anti-HCC mechanisms. Results: LC–MS analysis identified 41 components, with HPLC quantification showing salvianolic acid B as the most abundant compound (0.303%). In Akt/Nras and c-Met/sgPten-induced HCC models, HQF significantly reduced tissue damage, improved liver function, and inhibited HCC progression. Mechanistic studies revealed that HQF induced apoptosis in HCC cells by downregulating p-PI3K, p-AKT, and p-mTOR expression, with molecular docking indicating the strongest binding affinity between salvianolic acid B and PI3K. HQF further enhanced CD4⁺ and CD8⁺ T cell infiltration within the tumor microenvironment. When combined with PD-1 therapy, HQF improved therapeutic efficacy against HCC. Finally, toxicity assays confirmed the safety profile of HQF. Conclusion: HQF demonstrated significant anti-HCC effects and a synergistic effect with PD-1, could be used as an alternative therapeutic agent for HCC. Graphical

Background and aim: Diagnosing high-risk varices (HRV) is crucial for determining the prognosis and treatment strategy in patients with hepatocellular carcinoma (HCC). Although the Baveno VI consensus guidelines have been validated for assessing HRV in patients with liver cirrhosis, their applicability to those with HCC remains uncertain. This study aims to evaluate the effectiveness of the Baveno VI criteria in screening for HRV in patients with HCC.Methods: We searched for English-language articles related to Baveno criteria and HCC across PubMed, Embase, Web of Science, and Cochrane databases, covering publications from their inception until April 19, 2024. Our meta-analysis was conducted using STATA 14.0 and Meta-Disc 1.4 software. We assessed the quality of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We analyzed pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) using a random-effects model and constructed a summary receiver operating characteristic (SROC) curve. Based on established consensus, the favorable Baveno VI criteria were defined as a liver stiffness measurement (LSM) < 20 kPa and a platelet count (PLT) > 150×10⁹/L to exclude HRV. This study is registered with PROSPERO under the registration number CRD42024533946.Results: We finally brought four studies, including 1277 patients with HCC, into this meta-analysis. The SEN, SPE, DOR, and AUC of favorable Baveno VI criteria in screening HRV in patients with HCC were 0.90 (95% CI: 0.81–0.95), 0.33 (95% CI: 0.25–0.41), 4.44 (95% CI: 2.14–9.22), and 0.59 (95% CI: 0.55–0.64), respectively. The LR+ and LR- of the favorable Baveno VI criteria were 1.34 (95% CI: 1.19–1.50) and 0.30 (95% CI: 0.16–0.58), respectively. Subgroup and meta-regression analyses indicated that BCLC and Child-Pugh stages likely contribute to the heterogeneity in the SPE.Conclusions: The favorable Baveno VI criteria may not effectively screen HRV in patients with HCC. However, the current evidence is insufficient, and further studies with larger sample sizes and detailed patient subgroups are needed.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024533946.

Purpose: To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation. Methods: A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. Results: A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1− 14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5− 11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1− 95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7− 64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups. Conclusion: Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.

Hepatocellular carcinoma (HCC) is still a public health disease with its high prevalence and morbidity. Short of early diagnosis biomarkers and effective therapy, the treatment of HCC patients hasn’t achieved ideal effect. Hypoxia is a hallmark of HCC, which is mainly induced by imbalance of tumor cell proliferation and insufficient supply of oxygen. Recently, amounting evidence suggested lncRNAs, especially hypoxia-related lncRNAs play a pivotal role in regulating HCC. Hypoxia-related lncRNAs are involved in altering glucose metabolism, maintaining of cancer stem cell-like properties (CSCs), cell apotosis, proliferation and immune escape, which all contribute to the poor prognosis of HCC patients. The novel identified hypoxia-related lncRNAs could be the potential target or biomarkers of HCC, which are beneficial to the clinical treatment. Herein, we summarized currently reported hypoxia-related lncRNAs and their related mechanisms, providing potential application and future perspective of hypoxia-related lncRNAs as a potential therapeutic target.

Background: Hepatocellular carcinoma (HCC) is a common clinical malignant tumor of the digestive system. Hu-Qi-Zheng-Xiao (HQZX) decoction has been clinically found to prolong the survival of patients with hepatocellular carcinoma and improve the quality of patients’ survival, but its antitumor biological mechanism is still unclear. Methods: A nude mouse hollow fiber hepatocellular carcinoma model was constructed to analyze the in vivo efficacy of HQZX decoction against 7 different hepatocellular carcinoma cells. The subcutaneous graft tumor model was again validated. In vitro, the effect of HQZX decoction on the growth and metastasis of the cell line with the highest growth inhibition was evaluated. The cell line with the best efficacy response screened was again used to construct a hollow fiber hepatocellular carcinoma model and hollow fiber conduit cells were extracted to detect the expression of HIF-1α, VEGF, EMT-related molecules, LCSCs-related molecules, and to observe the density of the subcutaneous vascular network of hollow fiber conduits. The liver metastasis model of splenic injection was constructed to observe the effect of HQZX decoction on tumor metastasis. Results: The hollow fiber hepatocellular carcinoma model was evaluated for the efficacy of HQZX decoction, and it was found to have the highest growth inhibition of LM3-luc cells. In vitro, the CCK8 assay revealed that HQZX decoction could inhibit tumor migration and invasion and promote apoptosis. In addition, the mechanism study of extracting cells from hollow fiber tubes found that HQZX decoction could inhibit metastasis-associated HIF-1α, VEGF, EMT-related molecules, and LCSCs-related molecules expression. capillary network around subcutaneous fiber tubes was reduced in the HQZX decoction gavage group of mice. It inhibited tumor metastasis in nude mice. Conclusions: HQZX decoction inhibited the growth of a variety of hepatocellular carcinoma cells. HQZX decoction suppressed the expression of metastasis-associated VEGF, EMT-related molecules, and LCSCs-related molecules and inhibited tumor angiogenesis and growth and metastasis, which may be related to the inhibition of the HIF-1α signaling pathway. It reveals that HQZX decoction may be a promising herbal compound for anti-HCC therapy, and also reveals the accurate feasibility of the hollow fiber hepatocellular carcinoma model for in vivo pharmacodynamic evaluation and mechanism study.

The objective of this study is to analyze and summarize the characteristics of the clinical data of patients with systemic lupus erythematosus (SLE) complicated with liver failure, and to improve the cognition of the disease. The clinical data of patients with SLE complicated with liver failure hospitalized in Beijing Youan Hospital from January 2015 to December 2021 were collected retrospectively, including general information and laboratory examination data, and the clinical characteristics of the patients were summarized and analyzed. Twenty-one SLE patients with liver failure were analyzed. The diagnosis of liver involvement was earlier in 3 cases than that of SLE, and later in 2 cases. Eight patients were diagnosed with SLE and autoimmune hepatitis at the same time. The medical history is between 1 month and 30 years. This was the first case report of SLE complicated with liver failure. We found that: (1) among the 21 patients, organ cysts (liver and kidney cysts) were more common and the proportion of cholecystolithiasis and cholecystitis was higher than that in previous studies, but the proportion of renal function damage and joint involvement was lower. (2) The inflammatory reaction was more obvious in SLE patients with acute liver failure. The degree of liver function injury in SLE patients with autoimmune hepatitis was less than that in patients with other liver diseases. (3) The use of glucocorticoid in SLE patients with liver failure was worthy of further discussion. Key Points• Patients with SLE complicated with liver failure have a lower proportion of renal impairment and joint involvement.• The study firstly reported SLE patients with liver failure.• Glucocorticoids in the treatment of SLE patients with liver failure are worthy of further discussion.

Serum Interleukins as Potential Prognostic Biomarkers in HBV-Related Acute-on-Chronic Liver Failure: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is relatively common in China and has complex pathogenesis, difficult clinical treatment, and poor prognosis. Immune status is an important factor affecting ACLF prognosis. Interleukins are a family of secreted lymphocyte factors that interact with a host of cell types including immune cells. These signaling molecules play important roles in transmitting information; regulating immune cells; mediating the activation, proliferation, and differentiation of T and B cells; and modulating inflammatory responses. Many studies have investigated the correlation between interleukin expression and the prognosis of HBV-ACLF. This review focuses on the potential use of interleukins as prognostic biomarkers in HBV-ACLF. References were mainly identified through PubMed and CNKI search, including relevant studies published until December 2021. We have summarized reports of several promising diagnostic interleukin biomarkers that predict susceptibility to HBV-ACLF. The use of biomarkers to understand early prognosis can help devise different therapeutic measures and improve patient survival. Ongoing research on prognostic biomarkers of HBV-ACLF is promising, and future preclinical and clinical studies are warranted.