Junfeng Li

Background: Brucellosis is a systemic disease that can damage one or multiple organs. It can present with different clinical characteristics and nonspecific symptoms. Although local abscess formation secondary to brucellosis has been reported in various organs including spleen and liver, parotid abscess due to brucellosis is a rare event. Case presentation: The patient was a 65 years-old male who was engaged in sheep breeding in Gansu province, the northwestern part of China. He had a 2-year history of lower back pain, a 6-month history of the right knee pain and a 20-day history of pain, swelling, and redness in the right side of his neck. The Brucella spp. was found in the culture of the abscess drainage fluid. He was considered to be parotid abscess and spondylitis due to brucellosis. Antibiotics combined with local drainage achieved clinical improvement in this patient, and formal surgical incision or parotidectomy was avoided. Conclusions: Parotid abscess is a rare complication of brucellosis. This case offers clinical experience for the diagnosis and management of this brucellosis-associated complication.

Human pyrin and HIN domain (PYHIN) family proteins play central roles in the host defense against viral infection. These PYHIN proteins, including IFI16, AIM2, MNDA and PYHIN1, mainly function as intracellular DNA sensors. Among them, IFI16 is supported by the most robust mechanistic evidence, including direct binding to hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the nucleus and subsequent suppression of viral transcription. They recognize HBV DNA in different cellular substructures, triggering innate immune responses and interfering with steps of the viral life cycle. This article reviews the latest research progress of the PYHIN protein in HBV infection, and summarizes its immunoregulatory function and its role in the disease progression. We focus on the important question of the dual antiviral and pro-damage functions of PYHIN. On one hand, PYHIN has the ability to sense HBV DNA and inhibit the replication of the HBV. On the other hand, the host response mediated by PYHIN may also promote chronic inflammation, genomic instability and tumor formation. Furthermore, we collated the mechanism by which HBV evaded inflammasome activation by suppressing PYHIN expression through HBx. Here, we have emphasized the necessity of conducting in-depth mechanism research to clarify the role of the PYHIN family proteins in HBV infection contexts, and proposed the feasibility of implementing precise targeted immunotherapy based on the functions of PYHIN, aiming to provide strategies for achieving hepatitis B cure.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is highly prevalent among patients with cardiovascular disease but remains underrecognized in routine cardiology practice. To address the limited prospective evidence on its progression and clinical impact, we established the CHAIN cohort, a prospective multicenter study enrolling approximately 15 000 adults undergoing coronary evaluation across 40 tertiary hospitals in China. Baseline assessment includes comprehensive cardiometabolic profiling and vibration‐controlled transient elastography for evaluation of liver fibrosis and steatosis. Participants will undergo long‐term follow‐up with repeated liver assessments every 6–12 months. Primary outcomes include liver‐related events and major adverse cardiovascular events, while secondary outcomes include longitudinal changes in liver fibrosis and steatosis and their associations with cardiometabolic risk factors and clinical outcomes. This cohort will provide longitudinal evidence to support risk stratification and integrated heart–liver management in cardiovascular care.

Objective This study evaluated the effects of Huangqi injection (HQI), a standardized Astragalus extract, on the viability and regenerative potential of bone marrow-derived stem cells (BMSCs) in a D-galactosamine and lipopolysaccharide (D-GalN/LPS)-induced mouse model of FHF. Methods BMSCs were cultured in medium supplemented with HQI to generate HQI-treated BMSCs (HQI-BMSCs). Cell viability was assessed using the CCK-8 assay. A murine FHF model was established by intraperitoneal injection of D-GalN/LPS, followed by immediate tail vein transplantation of BMSCs or HQI-BMSCs. Mice were randomly assigned to four groups: normal control, D-GalN + LPS (FHF), D-GalN + LPS + BMSCs, and D-GalN + LPS + HQI-BMSCs. At 4 h post-transplantation, serum levels of alanine aminotransferase (ALT), total bilirubin (TBIL), interleukin-10 (IL-10), and interleukin-6 (IL-6) were measured. Liver tissue was collected for hematoxylin-eosin staining to assess histopathological injury, TUNEL assay to evaluate hepatocyte apoptosis, and immunohistochemistry to detect proliferating cell nuclear antigen (PCNA)-positive cells. PCNA protein expression was further quantified by western blotting. To investigate the contribution of active constituents, BMSCs were also pretreated with AS-IV, a principal bioactive compound in HQI, and effects on stemness-related gene expression, cell cycle progression, and LPS-induced apoptosis were assessed. Results HQI treatment markedly improved BMSC viability. In the FHF model, HQI-BMSC transplantation reduced serum ALT, TBIL, and IL-6 levels, and suppressed hepatocyte apoptosis in liver tissue. Furthermore, AS-IV enhanced the expression of stemness-related genes in BMSCs, promoted G1-to-S/G2 phase progression, and attenuated LPS-induced apoptosis in BMSCs. HQI-BMSCs conferred greater hepatoprotective effects than untreated BMSCs, as evidenced by improved biochemical indices and reduced histopathological damage. Conclusion Bioactive constituents of Astragalus membranaceus preconditioning enhanced the viability, stemness, and therapeutic efficacy of BMSCs in FHF, supporting their use as a potentiated stem cell-based intervention.

Although bone marrow-derived mesenchymal stem cell (BMSC) offers considerable therapeutic potential, the regenerative capacity of these cells is markedly compromised by the adverse microenvironment of the injured liver. Hypoxic preconditioning (HP) enhances the adaptability of BMSC. This study explored HP-BMSC therapy for acute liver failure (ALF), specifically examining the potential regulatory effects involving the VEGF-related factors and B-cell immunity. BMSCs were cultured under normoxic (21% O₂) or HP (1% O₂) conditions for 24 h, followed by protein and mRNA quantification of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), hepatocyte growth factor receptor (c-Met), C-X-C chemokine receptor type 4 (CXCR4), and stromal cell-derived factor-1 (SDF-1) by Western blot and RT-qPCR, respectively. ALF was induced in male C57BL/6J mice through D-galactosamine/LPS administration. Mice were randomized into four experimental groups (n = 6/group): controls, ALF, ALF + normoxic BMSC, and ALF + HP-BMSC. Cell transplantation was carried out through the tail vein immediately 5 min after the injection of the modeling drug. Four hours post-intervention, serum and tissue samples were collected for comprehensive analyses including liver biochemistry, inflammatory mediators, histology, and potential mechanisms. HP significantly enhanced HIF-1α, VEGF, PCNA, c-Met, CXCR4, and SDF-1 expression in BMSC (all P < 0.001). In ALF mice, HP-BMSC treatment produced superior therapeutic outcomes than normoxic BMSC. Liver function improved, as shown by reduced total bilirubin and aminotransferase levels (P < 0.05). The treatment also reduced inflammation, lowering interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) while raising interleukin-10 (IL-10) levels (all P < 0.01). Early regenerative signals were enhanced, with immunofluorescence (IF) showing strong PCNA expression, Western blot indicating elevated hepatic VEGF, c-MET, and HGF proteins, and RT-qPCR confirming increased PDGF and VEGF mRNA levels. Immunohistochemistry (IHC) showed reduced hepatic B lymphocyte infiltration, and IF further revealed expanded CD24⁺CD38⁺ B cell populations. HP BMSC transplantation correlates with early molecular events in acute liver failure mice, including upregulation of VEGF, HGF, and c-Met expression and changes in CD24⁺CD38⁺ B lymphocyte subsets, providing correlative evidence for involvement of the VEGF/c-Met pathway.

Primary biliary cholangitis (PBC) is an autoimmune-mediated cholestatic liver disease characterized by the progressive destruction of intrahepatic bile ducts, which ultimately leads to hepatic fibrosis and cirrhosis. The current first-line therapy, ursodeoxycholic acid, is associated with a high rate of non-response. Moreover, second-line treatments are constrained by variable efficacy and safety concerns. Mesenchymal stem cells (MSCs), owing to their potent immunomodulatory and tissue-repairing capabilities, represent a promising new therapeutic strategy for PBC patients with poor response to conventional therapies. This review systematically outlines the pathogenesis of PBC, focusing on factors including genetics, environment, and immune dysregulation. Furthermore, it examines recent evidence on the mechanisms by which MSCs and their derivatives, such as exosomes, may intervene in PBC progression through immunomodulation, anti-fibrotic effects, and potential hepatic differentiation. This paper also reviews the current status and challenges of the clinical translation of MSCs therapy, and proposes that engineered modification and standardized preparation are the key directions to promote its application. In conclusion, this review provides a theoretical foundation and future directions for deepening the understanding of PBC pathogenesis and developing novel MSC-based therapeutic strategies.

Objective This study examines the association between hepatic steatosis (HS) and liver fibrosis risk in individuals with similar metabolic disorders but differing metabolic dysfunction indicators. Methods A cross-sectional study was conducted at the First Hospital of Lanzhou University from January to November 2024, involving individuals undergoing physical examinations. Laboratory tests, vascular and abdominal ultrasound examinations, and clinical data were collected to assess metabolic characteristics. Logistic regression models were used to explore the relationship between metabolic dysfunction, HS, and liver fibrosis degree. Results A total of 4,006 patients were included, with 1,164 (29.06%) females and 2,157 (53.84%) having HS. Univariate logistic regression identified HS as a risk factor for early liver fibrosis (odds ratio [OR]: 1.67, 95% CI: 1.47–1.89, P < 0.001). However, after adjusting for metabolic dysfunction indicators, the correlation between HS and liver fibrosis risk weakened or reversed. Multivariate analysis, accounting for confounders, found HS to be a protective factor (OR: 0.57, 95% CI: 0.45–0.71, P < 0.001), while body roundness index (OR: 1.62, 95% CI: 1.32– 2.00, P < 0.001) and hyperglycemia (OR: 13.28, 95% CI: 10.76–16.39, P < 0.001) were identified as risk factors. Propensity score matching revealed 880 matched pairs of patients, showing that among those with atherosclerotic plaques (OR: 0.58, 95% CI: 0.42–0.79, P < 0.001) or hyperglycemia (OR: 0.63, 95% CI: 0.43–0.93, P = 0.02), HS was associated with a reduced risk of early liver fibrosis. The non-HS group had the strongest ability to detect early liver fibrosis (AUC: 0.57, 95% CI: 0.52–0.61, P = 0.003). Conclusion Metabolic dysfunction is positively correlated with the risk of liver fibrosis. However, in individuals with metabolic dysfunction, particularly those with atherosclerotic plaque formation, the non-HS population is at a higher risk of early liver fibrosis. Financial support National Natural Science Foundation of China (82360132), Major Science and Technology Innovation Project of Gansu Provincial Health Industry (GSWSZD2024-11), Joint Scientific Research Fund of Gansu Province (23JRRA1489, 24JRRA911), Key Talent Project of Gansu Province (GanZuTongZi [2024] No.4), Open Project of Gansu Provincial Key Laboratory of Extreme Environment Microbiology (EEMRE202401), Key Research and Development Program of Gansu Province (22YF7FA085), Key Project of Traditional Chinese Medicine in Gansu Province (GZKZ-2022-7), Lanzhou Science and Technology Bureau Project (2023-2-76), and Medical Education Development Projects of Lanzhou University (lzuyxcx-2022-131; lzuyxcx-2022-213; lzuyxcx-2022-147).

The annexin superfamily proteins, a family of calcium-dependent phospholipid-binding proteins, are involved in a variety of Ca²⁺-regulated membrane events. Annexin A, expressed in vertebrates, has been implicated in a variety of regulated cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, ferroptosis, and neutrophil extracellular trap-induced cell death (NETosis). Given that inflammation is a key driver of cell death, the roles of Annexin A in inflammation have been extensively studied. In this review, we discuss the regulatory roles of Annexin A in RCD and inflammation, the development of related targeted therapies in translational medicine, and the application of animal models to study these processes. We also analyze current challenges and discuss future directions for improved diagnostic and therapeutic strategies.

PANoptosis is a multimodal form of cell death that involves inflammatory, apoptotic, and necroptotic pathways, playing a key role in the development of liver diseases. This article first outlines the definition and characteristics of PANoptosis, and then explores its mechanisms of action in different types of liver diseases, including acute liver injury, liver failure, metabolic dysfunction‐associated fatty liver disease, and hepatocellular carcinoma. Furthermore, this article analyses the molecular regulatory network of PANoptosis and potential therapeutic targets. Finally, this article summarises the current research on PANoptosis in liver diseases and future research directions, and it reviews the role of the emerging cell death mechanism of PANoptosis in liver diseases.

Liver disease remains a major global health burden, with high morbidity and mortality rates (1). In recent years, continuous progress in biomedical fields such as immune regulation, biomarkers, and new drug research and development has brought new opportunities for the diagnosis and treatment of liver diseases. The complex interactions between diverse immune cell populations in the liver work together to maintain its immune function, ensuring the effective clearance of various infections and abnormal cells (2). Furthermore, the search for specific biomarkers has great significance for the diagnosis, prognosis assessment, and treatment monitoring of liver diseases. Simultaneously, drug development has also brought new hope for the treatment of liver diseases. Through in-depth study of liver immunity, potential biomarkers, and new drug development, it is helpful to better understand the pathogenesis of liver diseases, and provide new targets and methods for disease prevention, diagnosis, and individualized treatment. Notably, our topic explores emerging liver disease regulatory mechanisms, potential biomarkers, and therapeutic strategies, providing a roadmap for future liver disease research and clinical translation. Ananya et al. proposed that previous research focuses on the use of immune cells to prevent autoimmune diseases, while using specific blockers to inhibit their activity or alter their phenotypes to reduce the immunosuppressive properties in the tumor microenvironment. However, in recent years, the research on the mechanism of programmed death of immune cells has provided a new idea for the treatment of immune diseases (3). It has been found that there are various ways of programmed death of immune cells, such as apoptosis, necroptosis, autophagy, pyroptosis and ferroptosis. Proper regulation helps to maintain immune homeostasis, but the imbalance may also lead to autoimmune diseases. Immune cells can limit their attack effects on target organs through specific programmed death mechanisms, such as autophagy and necroptosis, thus avoiding tissue damage (4,5). Secondly, excessive programmed death of immune cells may weaken the body's ability to fight infection and increase susceptibility to infection (6). This indirectly suggests that the precise regulation of the immune cell programmed cell death pathway can inhibit the attack of immune cells on the liver to a certain extent, thus protecting liver cells from further damage. It has become clear that targeted modulation of the programmed death pathway of immune cells is a frontier area of immunotherapy research. By enhancing the survival and function of immune cells, it promotes the clearance of abnormal cells while reducing damage to normal tissues (7). This strategy is applicable to cancer, autoimmune diseases and chronic infections, demonstrating good adaptability and versatility. Notably, targeted modulation of the immune cell programmed cell death pathway may become a new strategy for the treatment of immune-mediated liver injury. Compared with traditional immune modulation, this approach can regulate the immune system more selectively and reduce the occurrence of adverse effects.The regulation of immune cells affects the progression and prognosis of almost all liver diseases, and exploring this mechanism is crucial for biomarker development.The discovery of biomarkers not only reflects the status of immune cells, but also Currently, the application and research of metabolomics in the diagnosis of hereditary metabolic defects, tumors, liver diseases, cardiovascular diseases, psychiatric disorders and other diseases has made rapid development (14). In the future, these technologies will further advance the understanding of the complexity and dynamics of the immune system, provide higher-level support for the continuous advancement of biomedical fields such as biomarkers and new drug discovery, and facilitate their earlier entry into clinical applications.