Background In patients with alcohol-associated liver disease (ALD), heavy and prolonged alcohol consumption can trigger acute-on-chronic liver failure (ACLF), a condition associated with high early mortality and significant clinical challenges. Early identification of patients at risk is critical for improving outcomes.Aims We conducted a retrospective observational study of patients diagnosed with ALD between January 2000 and December 2024 to develop a predictive model for ACLF.Methods Key clinical indicators were selected using LASSO-regularized logistic regression (LR). The final LR model was visualized as a nomogram and compared with four additional machine learning algorithms. Model performance was evaluated using ten-fold cross-validation and area under the curve (AUC), while feature importance was assessed with Shapley Additive exPlanations values.Results Among 210 patients with ALD, LASSO identified four independent predictors of ACLF: total bilirubin (TBIL), folate, vitamin B12 (VitB12) and the difference from the normal value of prothrombin time (ΔPT). The LR model achieved an AUC of 0.970, indicating excellent predictive accuracy.Conclusion We developed a robust clinical prediction model combining LR and machine learning approaches. TBIL, folate, VitB12 and ΔPT are key prognostic markers that may enable early risk stratification and timely intervention, potentially reducing ACLF incidence in ALD patients.

Pseudoepitheliomatous hyperplasia (PEH), a rare histopathological manifestation of pyoderma gangrenosum (PG), closely resembles squamous cell carcinoma (SCC) and leads to misdiagnosis, yet relevant reported cases remain limited. We report a 71-yearold female who developed abdominal pain and persistent fever after tooth extraction. Subsequent erythema, ulcerative necrotic lesions occurred on her left dorsal hand following frequent intravenous infusion, and lesions paradoxically expanded after surgical debridement. Initial biopsy and pathological consultation suggested SCC with positive surgical margins. However, the rapid progression of the lesion was inconsistent with SCC. Finally, a repeat biopsy confirmed diffuse neutrophilic infiltration with benign PEH, confirming the diagnosis of PG. The patient received systemic immunosuppressive therapy with oral prednisolone and sulfasalazine, systemic symptoms resolved and cutaneous lesions healed completely without recurrence during follow-up. This case highlights that while PEH is a known variant of PG, its potential to mimic malignancy remains a significant diagnostic pitfall that is often underrecognized in clinical practice. Comprehensive evaluation of distinctive clinical manifestations and a repeat biopsy when necessary are crucial for confirming PG, so as to prevent diagnostic delay and unnecessary surgical interventions.

Primary Biliary Cholangitis (PBC) is an autoimmune hepatic disorder characterized by the progressive destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) remains the primary treatment modality; however, a subset of patients exhibits non-responsiveness to UDCA therapy. The objective of this study is to investigate the association between the Prognostic Nutritional Index (PNI) and UDCA treatment non-responsiveness in individuals diagnosed with PBC. This retrospective study encompassed PBC patients who received UDCA therapy (13–15 mg/kg) from June 1, 2014, to December 31, 2021. The criterion for UDCA non-response was defined as an alkaline phosphatase (ALP) level exceeding 1.67 times the upper limit of normal (ULN) after 12 months of UDCA therapy. Logistic regression analysis was utilized to examine the relationship between baseline PNI and response to UDCA. The stableness of the findings was assessed through both unadjusted and adjusted models. The study included 241 patients with PBC (mean age 55.80 ± 11.694 years; 210 (87.1

BACKGROUND:Aspartame (APM) is a widely consumed artificial sweetener that has recently been implicated in the pathogenesis of metabolic disorders. However, the molecular mechanisms linking APM to metabolic-associated fatty liver disease (MAFLD) remain poorly understood. MATERIALS AND METHODS:This study employed a comprehensive analytical strategy, integrating network toxicology, molecular docking, molecular dynamics simulations, machine learning, bulk RNA sequencing and single-cell transcriptomics, Mendelian randomization, and histological validation, to systematically investigate APM-associated molecular targets and their potential role in MAFLD. RESULTS:The ADMETlab3.0 prediction indicated that APM exhibits strong hepatotoxic potential. Network toxicology analysis identified 80 overlapping genes, among which ANPEP demonstrated the lowest binding energy to APM (-8.2 kcal/mol). Molecular dynamics simulations further confirmed the stability of this interaction. Bulk RNA-seq data revealed that ANPEP was significantly upregulated in MAFLD liver tissues (P < 0.001) and achieved robust diagnostic performance (AUC = 0.84, 95% CI: 0.69-1.00, P < 0.01). In mouse models, Anpep expression was significantly elevated (P = 0.005). Mendelian randomization analysis indicated that elevated ANPEP levels were significantly associated with a higher risk of MAFLD (OR = 1.069, 95% CI: 1.017-1.124, P = 0.008). Single-cell sequencing and immunofluorescence analyses consistently confirmed that ANPEP was predominantly localized in CD68⁺ myeloid cells and was markedly upregulated as early as the fibrotic initiation stage of MAFLD (P < 0.01). CONCLUSION:ANPEP was identified as a potential target that links aspartame exposure to MAFLD, and was further associated with inflammation, lipid dysregulation, and fibrosis. These findings suggest that aspartame may not represent a safe strategy for weight management and could increase the risk of liver injury and MAFLD progression.

BackgroundPrimary hepatic angiosarcoma (PHA) is a rare, highly aggressive, and rapid progressive malignant liver tumor, of which the sinusoidal growth pattern represents one of its uncommon morphological subtypes. Nonspecific clinical presentation, absence of characteristic laboratory findings, and variable imaging features often contribute to diagnostic delays. As a result, patients often miss the window for potential treatment interventions. This study aimed to deepen the understanding of the imaging characteristics of PHA in order to enhance the sensitivity of clinical doctors in identifying rare tumors.Case summaryA 75-year-old woman presented with poor appetite and progressive jaundice. Initial imaging studies conducted 4 months before admission did not raise strong suspicion for a rare malignant lesion, which contributed to a prolonged viewing time and subsequently led to the decision to perform a liver biopsy. Eventually, immunohistochemical staining of the percutaneous liver biopsy confirmed the diagnosis of sinusoidal-type PHA. Due to her poor baseline condition and critical status, the patient lost the opportunity to receive antitumor treatment and succumbed to the disease within 2 months of diagnosis.ConclusionThis case underscores the challenges in the early imaging detection of PHA and emphasizes the need for heightened clinical vigilance toward rare liver malignancies. Although histopathology remains the diagnostic gold standard, earlier recognition of suggestive imaging features may prompt a more timely biopsy, enabling prompt treatment and potentially improving outcomes.

Chronic hepatitis B (CHB) is a global disease that can induce severe conditions such as cirrhosis and liver cancer, posing a serious threat to human health. The low functional cure rate of existing antiviral treatment drugs is primarily due to the dysfunctional immune response in CHB patients and the difficulty in clearing intrahepatic cccDNA. This article reviews the latest progress in the research on therapeutic vaccines for CHB, to analyze and discuss the potential impact of current achievements and to outline the prospects for future research, exploring therapeutic strategies for the functional cure of CHB. Therapeutic vaccines are anticipated to activate specific immune responses in CHB patients, break the mechanisms of immune tolerance, and exhibit significant potential in maintaining long-term immune activity. Several therapeutic vaccines have already demonstrated promising therapeutic effects. Therapeutic vaccines are of great significance in the field of CHB treatment. Current research achievements provide strong support for their application, while combined therapy offers new ideas and hope for future treatment directions.

Introduction:Intrahepatic papillary neoplasm of the bile duct (IPNB) with invasive carcinoma is a rare cholangiocarcinoma with the most frequent site of origin being intrahepatic bile ducts. Given its rarity and non-specific clinical presentations, accurate diagnosis plagues clinicians to improve patient outcomes. Case presentation:We present a case of a 31-year-old male who initially exhibited fever. Routine ultrasonography and computed tomography (CT) revealed a large mass in the right liver lobe, suggesting a high likelihood of an infectious lesion. However, multidisciplinary discussion offered a variety of possible scenarios. The patient subsequently underwent an extended right hepatectomy (ERH), and histopathological examination suggested a intrahepatic IPNB with invasive adenocarcinoma. Clinical discussion:The diagnosis and management of IPNB remain challenging, particularly in patients who present with atypical clinical symptoms and lack significant abnormalities in laboratory tests. Early imaging plays a critical role in guiding the diagnostic process. However, comprehensive diagnostic speculations, clinical expertise, and even invasive detections are essential for establishing a definitive diagnosis and determining the appropriate treatment strategy. Given the potential to invasive carcinoma, early detection and resection are vital to improving prognosis.

BACKGROUND & AIMS:Oral and gut health are tightly connected through their microbiome and immunity, including in disease states. The oral adaptive immunity contributes to the severity of inflammatory bowel disease (IBD). However, the role of oral innate immunity, and more specifically the saliva, in gut microbiome and IBD is poorly understood. METHODS:We used 2 mouse models with reduced saliva, nonobese diabetic (NOD) and aquaporin 5 (Aqp5)-/- mice, and recovery of salivation in the NOD mice by treatment with a cystic fibrosis transmembrane regulator corrector to examine the role of salivation in oral and gut microbiome, IBD, and survival. RESULTS:Analysis of the oral microbiome at various conditions revealed that the saliva has a minimal role in shaping the oral microbiome. However, salivation affected the composition of the gut microbiome. Moreover, the lack of saliva significantly delayed development of dextran sodium sulphate-induced colitis, but resulted in a later, age-dependent, rapidly developed weight loss and death. The dual roles of the saliva were caused by 2 immunomodulatory peptides secreted by salivary glands. Fractionation and mass spectroscopy analysis identified trefoil factor 2 (TFF2) as a protective component and the cytokine macrophage migration inhibitory factor (MIF) as the damaging component of the saliva. The effects of the salivary fluid, TFF2, and MIF were primarily due to control of the gut barrier, rather than the gut microbiome. Scavenging salivary TFF2 and MIF with antibodies resulted in exacerbating and protection, respectively, of IBD. CONCLUSIONS:The oral innate immunity has a major role in shaping the gut microbiome through secretion of MIF and TFF2. Control of MIF and TFF2 can benefit the treatment of colitis.

The treatment of end-stage liver disease (ESLD) is limited, and its mortality is high. Accurate application of evaluation model for early identification of ESLD has important clinical significance to improve the prognosis of patients. HBV infection is the main cause of ESLD in China. The application value of various prognostic models for ESLD in patients with hepatitis B needs further evaluation. In this article, the current evaluation models for HBV related ESLD are reviewed.

Immune checkpoint inhibitors (ICIs) have recently been approved for the treatment of cancer, and the number of cancer patients with chronic liver disease (CLD) receiving ICIs is growing rapidly. However, whether CLD affects the efficiency and safety of ICIs is becoming a research focus. This review summarizes the efficiency and safety of ICIs in cancer patients with CLD, including chronic viral hepatitis, non-alcoholic fatty liver disease, autoimmune liver disease, and cirrhosis. Specifically, data on hepatitis B virus reactivation of patients with chronic hepatitis B after ICIs treatment were reviewed, which may help to perfect and standardize the guidelines of treatment and following-up for ICIs in CLD patients.

分析费森尤斯5008S型血液透析机水路系统的结构及其功能,针对该机型1例水路测试阶段故障报警进行维修,通过结合实际维修经验及理论技术,从压力传感器的诊断、电磁阀的泄漏测试等分析总结故障排除的过程,旨在为透析工作的技术维修人员提供相关参考信息.