Early risk stratification of severe acute liver injury (SLI) that may progress to acute liver failure (ALF), is vital for timely intervention, but no universal prognostic assessment tool covers both conditions. This study aimed to develop a simplified prognostic model for early risk assessment in SLI/ALF patients.

A retrospective cohort study consecutively enrolled SLI patients (including those progressing to ALF) from July 1, 2020 to May 31, 2025. Baseline clinical and laboratory data on admission were collected, with 90-day transplant-free survival as the primary outcome. Independent prognostic factors were screened via Cox regression to build a simplified scoring model, whose performance was compared with the Model for End-Stage Liver Disease (MELD), King’s College Criteria (KCC), and the Acute Liver Failure Study Group Prognostic Index (ALFSG-PI).

Of 302 patients, 190 (62.9%) achieved 90-day transplant-free survival. Multivariate Cox regression identified international normalized ratio (hazard ratio [HR]: 1.118, 95% confidence interval [CI]: 1.050–1.191), platelet count (HR: 0.995, 95% CI: 0.993–0.998), and hepatic encephalopathy grade ≥ 2 (HR: 5.187, 95% CI: 3.403–7.907) as independent predictors, forming the HIP (derived from the above-mentioned three predictors) model. It showed good discrimination (area under the receiver operating characteristic curve [AUC]: 0.82), outperforming MELD (AUC: 0.76, P = 0.019) and KCC (AUC: 0.72, P = 0.002), and performing comparably to ALFSG-PI (AUC: 0.80, P = 0.429). The model also performed robustly in ALF subgroups defined by the American College of Gastroenterology and the 2024 Chinese Medical Association guidelines (AUCs: 0.80 and 0.76, respectively) and achieved an AUC of 0.85 in the validation set.

The HIP model is a simple and effective tool for prognostic risk stratification in SLI/ALF patients, suitable for emergency and primary care to facilitate timely intervention.

Terahertz (THz) radiation is increasingly explored for biomedical applications, however, its non-thermal effects on cellular metabolism and regulatory networks remain insufficiently characterized. This study aimed to investigate how 2.3 THz radiation affects metabolic pathways and membrane-associated signaling in human melanoma cells.

SK-MEL-28 melanoma cells were exposed to 2.3 THz radiation for 45 min using the 1st Novosibirsk free-electron laser. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays. Metabolic alterations were detected by targeted metabolomics using liquid chromatography–tandem mass spectrometry. Gene network analysis was performed using the ANDSystem platform to reconstruct gene and protein interaction networks linking altered metabolites to membrane receptors, lipid raft proteins, and signaling pathways. Overrepresentation analysis of biological processes was applied to identify enriched functional categories.

THz exposure did not affect cell viability but induced significant alterations in purine metabolism, pantothenate/CoA biosynthesis, and the pentose phosphate pathway. Network analysis revealed that these metabolic changes were associated with membrane raft reorganization and receptor-mediated signaling involving epidermal growth factor receptor and G-protein subunits. Additional effects were observed in pathways related to chromatin organization and post-translational regulation.

THz radiation induces coordinated remodeling of metabolic and regulatory networks in melanoma cells without cytotoxicity. These findings highlight the role of membrane-associated signaling in mediating THz-induced cellular responses and provide insight into potential biomedical applications of THz technologies.

Bacterial infections (BIs) are common and severe complications in patients with liver cirrhosis, but global data are limited. Here, we aimed to evaluate the global prevalence, temporal changes, and associated mortality risk of BIs in liver cirrhosis.

We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library for eligible studies published without language restrictions until 11 August 2025. A random-effects model was used for meta-analyses, meta-regression by study year, and pooling adjusted hazard ratios.

Fifty-nine studies, including 1,191,421 patients with cirrhosis, were analyzed. The pooled prevalence of BIs (33 studies) was 35.1% (95% confidence interval (CI): 29.2–41.4). The prevalence of Escherichia coli and Streptococcus spp. was 3.8% (95% CI: 2.5–5.2) and 1.5% (95% CI: 0.8–2.6), respectively. The pooled prevalence of multidrug-resistant bacteria was 6.8% (95% CI: 4.0–11.3). The most common BI sites were the gastrointestinal tract, ascites fluid, and urinary tract. The highest prevalence of BIs was reported in Europe (38.2%; 95% CI: 24.8–53.6), followed by South America (37.5%; 95% CI: 29.7–46.1) and Asia (22.8%; 95% CI: 16.3–30.9). Patients with acute-on-chronic liver failure showed the highest prevalence of BIs (44.2%; 95% CI: 29.7–59.8). A modest increasing trend in BIs prevalence was observed over time. BIs were associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratios 2.22, 95% CI 1.33–3.71).

BIs are prevalent in cirrhosis, especially in acute-on-chronic liver failure, with a modest upward trend and increased mortality risk.

Amatoxin-containing mushroom poisoning causes fatal acute liver failure with >50% mortality despite maximal medical therapy. Interrupting the enterohepatic recirculation of amatoxins is a mechanistically rational but unproven therapeutic strategy. This study aimed to evaluate the efficacy and safety of biliary drainage (BD) in patients with pre-acute liver failure caused by amatoxin-containing mushroom poisoning.

In this prospective cohort study (ChiCTR2300073442), consecutive adults with amatoxin-induced pre-acute liver failure received standardized care (silibinin, N-acetylcysteine, dehydration). Patients undergoing percutaneous or endoscopic BD were compared to non-BD controls. The primary outcome was survival to hospital discharge.

Nine patients were enrolled (mean age: 63.3 ± 15.6 years; 44.4% female). All five patients who underwent BD (performed at a median of three days after ingestion) survived (100%), whereas only one of the four non-BD patients survived (25%; P = 0.048). BD initiated a rapid biochemical recovery: within 48 h, mean alanine and aspartate transaminase levels decreased by 67.6% and 91.6%, respectively, from their peak levels (P < 0.001), and the international normalized ratio decreased from 1.99 to 1.27 (P = 0.008). Non-survivors in the non-BD group progressed to multiorgan failure. Procedure-related complications (transient pancreatitis/amylasemia) occurred in three of the five BD patients but resolved with conservative management.

Timely BD was associated with 100% survival after amatoxin-induced pre-acute liver failure, contrasting sharply with 75% mortality in non-BD controls. The dramatic biochemical improvement after BD supports enterohepatic recirculation interruption as a mechanistic intervention. BD represents a potentially definitive, life-saving intervention for this lethal poisoning as a preliminary finding; larger, multicenter studies are required to confirm the observed association between BD and survival.

This Consensus aims to establish a physician–pharmacist co-management model to standardize the rational clinical application of anti-immunoglobulin E monoclonal antibodies in the treatment of allergic asthma. Focusing on the critical components of physician–pharmacist co-management, key issues related to anti-immunoglobulin E monoclonal antibody therapy were identified through a systematic literature review and clinical practice experience. Evidence quality was evaluated using an evidence grading system, and the Delphi method was applied to reach expert consensus. Centered on omalizumab, the Consensus presents 12 recommendations covering the work model of physician–pharmacist co-management, clinical management pathways, hierarchical diagnosis and treatment systems, as well as training and competency assessment. The Delphi process achieved a high degree of consensus (agreement >80%) on 12 key recommendations, emphasizing a 60-min observation period post-injection and quarterly follow-up evaluations. It establishes a standardized framework for the co-management of omalizumab therapy in allergic asthma. Results highlighted that co-management effectively monitors omalizumab dosage (75–600 mg) and maintains a consensus threshold of >80% for patient safety protocols. The Consensus provides a standardized framework for physician–pharmacist co-management, which is expected to facilitate rational drug use and improve patient care pathways in omalizumab therapy.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 32% of the US adult population. The present study aimed to utilize the All of Us electronic health record-linked large cohort to assess seven metabolic risk factors (MRFs) simultaneously, the impact by ethnicity and age, and clinical presentations of MASLD.

This study included a MASLD group (n = 15,060) and a frequency-matched control group (n = 75,300). Multivariable analyses were performed to compare the frequencies of MRFs and clinical outcomes between the two groups. Type 1 diabetes was not included in the multivariable analysis. Subgroup analyses were conducted according to race and ethnicity, as well as age.

The overall frequency of MASLD was 6.0%. Compared with the control group, individuals with MASLD had significantly higher independent frequencies of obesity (66.1% vs. 41.3%), type 2 diabetes (39.5% vs. 16.9%), hypertension (64.3% vs. 38.6%), hyperlipidemia (59.8% vs. 37.3%), obstructive sleep apnea (28.9% vs. 13.4%), and hypothyroidism (21.2% vs. 13.4%). Obesity was identified as the strongest independent MRF among Asians, Whites, and Hispanics, particularly in individuals younger than 50 years, whereas hypertension was the strongest independent MRF in Blacks. MASLD was also associated with significantly higher frequencies of cardiac events, including coronary artery disease (17.1% vs. 9.4%) and myocardial infarction (7.1% vs. 4.2%); hepatic events, including cirrhosis (7.5% vs. 1.1%) and hepatocellular carcinoma (0.5% vs. 0.1%); and elevated liver enzymes, including alanine aminotransferase (27.7% vs. 10.1%), aspartate aminotransferase (18.0% vs. 6.4%), and alkaline phosphatase (19.8% vs. 13.1%), compared with the control group.

Our study demonstrated that obesity, hypertension, hyperlipidemia, type 2 diabetes, obstructive sleep apnea, and hypothyroidism were independent MRFs for MASLD overall, but the ranking of these MRFs by odds ratios could vary by ethnicity and age. MASLD presents with significantly higher rates of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase elevation, as well as cardiac and hepatic events.

Hepatic encephalopathy (HE) is a neurologic complication of advanced liver disease (e.g., cirrhosis) resulting in impaired functioning and reduced quality of life. This condition is associated with a substantial burden for patients and their caregivers and carries a poor prognosis and increased risk of hospitalization and mortality. This narrative review discusses the burden of HE, precipitating risk factors, and clinical considerations for reducing the risk of overt HE (OHE) recurrence in adults with cirrhosis. Key precipitating factors include certain medications, constipation, dehydration, uncontrolled diabetes mellitus, electrolyte imbalances, gastrointestinal bleeding, infection, and sarcopenia, among others. Identification and treatment of precipitating factors are critical steps in the management of HE. Components of ongoing care include patient and caregiver education, nutritional supplementation and sleep management, pharmacotherapy, and nonpharmacologic interventions (e.g., spontaneous portosystemic shunt embolization and liver transplantation in appropriate patients). Clinical guidelines recommend lactulose therapy as secondary prophylaxis after an initial episode of OHE. Rifaximin is recommended as add-on therapy to lactulose when an additional OHE episode occurs. Polyethylene glycol has been investigated as an alternative to lactulose in patients with acute HE and in those with chronic HE and a poor response to lactulose. Oral L-ornithine-L-aspartate may reduce the risk of OHE recurrence in patients with cirrhosis. Investigational agents include nitazoxanide, fecal microbiota transplantation, and the use of artificial intelligence, app-based technology, and wearable devices to facilitate acute and prophylactic management of HE.

Circular RNAs (circRNAs) are non-coding RNAs characterized by a strictly closed-loop covalent structure. They are abundantly detected in various cells due to their conserved nature. Studies have reported their potential association with chronic liver disease (CLD), including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), with possible roles as diagnostic and prognostic markers. This study aimed to analyze the potential use of serum-derived hsa_circ_101555 as a diagnostic tool for CLD without HCC, and to compare it with other known non-invasive parameters for liver disease severity and inflammation. Additionally, it aimed to evaluate its expression among non-HCC CLD patients, CLD with HCC cases reported in our published (phase I) study, and healthy controls.

A cross-sectional study (phase II) was conducted involving 30 clinically, laboratory, and radiologically diagnosed Egyptian non-HCC CLD patients and 30 healthy subjects. The serum expression level of hsa_circ_101555 was measured using real-time polymerase chain reaction. The diagnostic accuracy was assessed through receiver operating characteristic curve analysis, calculating the area under the curve to determine sensitivity and specificity. The study also compared hsa_circ_101555 levels with established non-invasive parameters such as the Child-Turcotte-Pugh and model for end-stage liver disease scores, as well as inflammatory markers like the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

hsa_circ_101555 demonstrated high diagnostic accuracy (area under the curve of 0.970) at a cutoff point of 2.088 for differentiating non-HCC CLD patients from healthy controls. Elevated circRNA levels were noted in patients with hepatic encephalopathy and ascites, correlating with advanced liver disease scores (Child-Turcotte-Pugh/model for end-stage liver disease scores). Mean circRNA values were highest in HCC cases, followed by non-HCC CLD patients, and lowest in healthy controls.

Serum-derived hsa_circ_101555 demonstrates high diagnostic accuracy in differentiating non-HCC CLD patients from healthy controls. These findings suggest that hsa_circ_101555 has the potential to serve as a reliable non-invasive biomarker for the early diagnosis of CLD, correlating with disease severity and inflammation markers. Further research with larger sample sizes is warranted to validate its clinical utility and enhance the management of CLD.

Sclerocarya birrea (A. Rich) Hochst (Anacardiaceae) is a plant widely used by traditional healers in several African countries to treat numerous illnesses such as Alzheimer’s disease, schizophrenia, inflammation, infections, arterial hypertension, headaches, and others. This study aimed to determine the therapeutic efficacy of Sclerocarya birrea (S. birrea) against glutamate-induced neurotoxicity.

Thirty naïve white mice (Mus musculus Swiss, Muridae), of both genders and weighing between 18 and 25 g, were used in the experiments. Different doses (102.5, 205, and 410 mg/kg) of the extract and vitamin C (100 mg/kg) were administered to the animals one hour before administration of monosodium glutamate (4 mg/kg) for 15 consecutive days. T-maze and Y-maze tests were conducted over three days to assess the animals’ behavioral performance. After behavioral testing, the animals were sacrificed and their brains removed for analysis of oxidative stress parameters.

S. birrea extract reversed glutamate-induced behavioral alterations by significantly (P < 0.001) reducing the latency to reach the platform in the T-maze and significantly increasing the percentage of spontaneous alternation in the Y-maze. The extract also significantly counteracted (P < 0.001) glutamate-induced oxidative stress parameters. The 102.5 and 205 mg/kg doses of the extract significantly (P < 0.001) reduced catalase and reduced glutathione levels, as well as the increase in malondialdehyde levels induced by glutamate.

S. birrea root bark extract exhibits neuroprotective properties that facilitate memory and ameliorate glutamate-induced cognitive deficits in white mice. The results provide partial justification for the traditional medicinal use of S. birrea extract.

As the leading cause of chronic liver disease globally, metabolic dysfunction-associated steatotic liver disease (MASLD) lacks effective therapies. This study aimed to investigate the therapeutic potential and molecular mechanisms of oxytocin (OXT) in MASLD.

Integrated bioinformatics analysis of MASLD datasets was carried out to identify OXT-related metabolic disturbances. Serum OXT levels were quantified using an enzyme-linked immunosorbent assay in 113 MASLD patients and 63 healthy controls. Mechanistic assays were conducted using oleic acid (OA)-induced, lipid-loaded HepG2 cells and high-fat diet-fed C57BL/6 mice, and OXT was administered intraperitoneally in vivo and supplemented in vitro.

Bioinformatics analysis revealed significant changes in OXT expression levels, particularly in fatty acid metabolism. Elevated OXT expression levels in MASLD patients were identified as an independent prognostic factor. In vitro, OXT significantly reduced OA-induced lipid accumulation in HepG2 cells, while in vivo, it decreased body weight, liver injury, and serum cholesterol levels in high-fat diet-fed mice. Mechanistically, OXT enhanced the expression level of phosphorylated AMP-activated protein kinase (AMPK) and suppressed the levels of sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS). Blockade of AMPK with the chemical inhibitor Compound C reversed the ability of OXT to suppress the SREBP1c/FAS axis and reduce lipid accumulation in hepatocytes. Additionally, OXT inhibited the nuclear translocation of SREBP1c in OA-treated cells.

The findings demonstrate that OXT may serve as a potential therapeutic agent for MASLD by regulating the AMPK/SREBP1c/FAS pathway in lipid metabolism.