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.

Microbial resistance and oxidative stress are two significant health issues associated with chronic illnesses and therapy failures. The antioxidant and antibacterial properties of Euphorbia cuneata Vahl. aerial component extracts made with various polarity solvents were assessed in this work.

Disc diffusion and minimum inhibitory concentration (MIC) tests were used to evaluate the 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, total phenolic and flavonoid contents, and antimicrobial activity of n-hexane, toluene, ethanolic, and aqueous extracts against specific ESKAPE pathogens (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans). High-performance liquid chromatography and gas chromatography-mass spectrometry were used to further characterize the most active extract.

Compared to the aqueous (IC₅₀ = 51.61 µg/mL), toluene (IC₅₀ = 30.57 µg/mL), and n-hexane (IC₅₀ = 128.15 µg/mL) extracts, the ethanolic extract demonstrated the greatest 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (97.90 ± 0.8%; IC₅₀ = 28.52 µg/mL). Additionally, it has the highest levels of flavonoids (40.5 ± 1.5 mg luteolin equivalents/g) and phenolic (80.0 ± 0.2 mg gallic acid equivalents/g). While gas chromatography-mass spectrometry found methyl 12-hydroxy-9-octadecenoate (44.39%) as the main volatile molecule, high-performance liquid chromatography analysis identified caffeic acid, pyrogallol, rutin, and 7-hydroxyflavone as important ingredients. The ethanolic extract showed antifungal activity against C. albicans (MIC = 6.25 mg/mL) and moderate antibacterial activity with the lowest MIC values against S. aureus (450 µg/mL) and E. coli (500 µg/mL).

The ethanolic extract of Euphorbia cuneata demonstrated potent in vitro antioxidant activity and moderate antimicrobial effects, primarily attributable to its high phenolic and flavonoid content. These results support its potential as a natural source of bioactive compounds for further development.

Primary liver cancer is one of the most common malignant tumors in China, which seriously threatens people’s lives and health. In recent years, with the advancement of basic and clinical research, the diagnosis and treatment methods for primary liver cancer have been continually enriched. Traditional Chinese medicine (TCM) has played an important role in the diagnosis and treatment of primary liver cancer, but there is no unified standard for differentiation and treatment, and efficacy evaluation. In order to further standardize the TCM diagnosis and treatment of primary liver cancer, according to the requirements of TCM standardization and related technical guidance documents, the drafting team compiled this guideline through literature research, expert interviews, questionnaire surveys, consensus meetings, etc., for reference by clinicians. This guideline is approved and issued by the China Association of Chinese Medicine, standard number: T/CACM 1575-2024.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for effective therapies. Although miR-125b-5p shows therapeutic potential, its efficacy in metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC and the underlying mechanisms remain unclear. In this study, we aimed to develop a magnetic resonance imaging (MRI)-trackable miR-125b-5p-engineered MSC platform for HCC therapy and to determine whether MASLD attenuates its antitumor efficacy through metabolic reprogramming.

Bone marrow mesenchymal stem cells (MSCs) were genetically engineered to coexpress miR-125b-5p (a therapeutic gene) and ferritin heavy chain (Fth; a MRI reporter gene), enabling sustained delivery and real-time tracking. Orthotopic HCC models with or without MASLD were established to evaluate therapeutic outcomes. In vivo MRI, histological analyses, and bioinformatics approaches were used to assess efficacy and mechanisms.

Transplantation of miR-125b-5p-Fth-MSCs significantly suppressed HCC growth in vivo over an extended period. However, MASLD attenuated this therapeutic effect. Mechanistically, miR-125b-5p directly targeted hexokinase 2 (HK2), inhibiting HCC proliferation and migration through suppression of the PI3K/AKT/mTOR pathway. Fatty acid-induced lipotoxicity upregulated HK2 expression and counteracted the antitumor effects of miR-125b-5p.

Multigene-modified MSCs enable effective, MRI-monitored HCC therapy. MASLD diminishes the efficacy of miR-125b-5p through HK2 upregulation. These findings establish a multimodal theranostic framework for HCC and provide mechanistic insights into MASLD-associated therapeutic resistance.

Mitochondrial DNA (mtDNA) variability, especially heteroplasmy, is believed to affect cellular immunobiogenesis, particularly in monocytes in metabolic syndrome (MetS). This study aimed to identify associations of monocytic mtDNA variability with its phenotypic indices, including cytokine secretion and gene expression, and cardiometabolic parameters in patients with MetS.

The cross-sectional study recruited 87 adult participants, including 34 healthy blood donors (Control group), 21 obese patients (Obesity group), and 32 MetS patients (MetS group). Blood biochemistry tests were performed on venous blood samples, and monocytes (CD14+ cells) were isolated. Monocyte mtDNA was analyzed by next-generation sequencing to identify low (5–10%) and intermediate (10–95%) heteroplasmy, and homoplasmy (≥95%). Expression of genes related to mitochondrial biogenesis, mitochondrial uncoupling, oxidative stress system, and NF-κB signaling was assessed by quantitative real-time polymerase chain reaction. Monocytes cultured with and without lipopolysaccharide for 24 h were analyzed by enzyme-linked immunosorbent assay to assess the cytokine secretion stimulation index.

Monocyte mtDNA showed low variability, but alternative homoplasmies were significantly more common. Intermediate and low heteroplasmy from the protein-coding locus correlated with stenosis (r = 0.396; 95% confidence interval (CI) 0.067–0.647) and low-density lipoprotein levels (r = −0.258; 95% CI −0.45 – −0.043). Intermediate heteroplasmy from the rRNA locus correlated with blood insulin levels (r = −0.228; 95% CI −0.424 – −0.019). D-loop low heteroplasmy correlated with fasting blood glucose (r = 0.275; 95% CI 0.062–0.464). Homoplasmies were associated with creatinine, blood urea nitrogen, and alkaline phosphatase. Intermediate heteroplasmy in mtDNA was associated with the monocyte cytokine secretion stimulation index (R2 = 0.156, P = 0.003). However, there was no significant association between mtDNA variability and the expression of the various genes.

Monocyte mtDNA shows relatively low variability. Low and Intermediate heteroplasmy are associated with cardiometabolic parameters, and intermediate heteroplasmy is associated with the monocyte cytokine secretion stimulation index.

Adeno-associated virus (AAV) vectors have favorable safety and durable transgene expression but are limited in oncology by insufficient tumor specificity and off-target expression. Tumor hypoxia and non-small cell lung cancer (NSCLC)-associated surface ligands offer complementary layers of biological selectivity for more precise gene delivery. This study proposes an NSCLC-directed, hypoxia-responsive AAV architecture that integrates MGS4-guided capsid targeting with dual hypoxia-responsive element (HRE)-gated promoters driving glutamine-modified C-X-C motif chemokine ligand 9-fragment crystallizable region fusion protein (Q-CXCL9-Fc) expression and baculoviral IAP repeat containing 5 (BIRC5)-linked mesothelin (MSLN) silencing. We conceptually designed an AAV vector that combines three layers of NSCLC selectivity: MGS4-guided capsid targeting, hypoxia-gated transcription, and tumor-active promoter control. The capsid displays the MGS4 peptide, isolated by phage display biopanning as a high-affinity ligand for the lung squamous cell carcinoma cell line HCC15 and later shown to internalize into a substantial fraction of NSCLC cell lines and bind a subset of human NSCLC biopsy samples, indicating activity across multiple NSCLC subtypes. The genome encodes Q-CXCL9-Fc under a 4× HRE-cytomegalovirus promoter to sustain C-X-C motif chemokine receptor 3-dependent T-cell recruitment and a miR-30-based short hairpin RNA targeting MSLN under a 4× HRE-BIRC5 promoter to inhibit tumor progression. This architecture is hypothesized to enrich AAV entry into NSCLC lesions via MGS4 while restricting Q-CXCL9-Fc secretion and MSLN silencing to hypoxic, BIRC5-active tumor regions, enabling synergistic enhancement of antitumor immunity and suppression of tumor-intrinsic pathways. The proposed multimodal, hypoxia-responsive AAV platform represents a conceptual precision oncology strategy that couples environmental sensing, tumor-specific transcription, and peptide-defined tropism within a single vector and could inform next-generation NSCLC-directed AAV systems.

The current criterion of biochemical response to ursodeoxycholic acid in primary biliary cholangitis is an alkaline phosphatase (ALP) level of ≤1.67 × the upper limit of normal (ULN) after 12 months of treatment. However, a proportion of patients who meet this parameter may still progress to liver decompensation. This study aimed to optimize the clinical management of primary biliary cholangitis by (1) establishing ALP normalization as a core treatment target, (2) identifying early intervention windows, and (3) developing risk stratification criteria.

This multicenter retrospective study included an internal cohort and an external validation cohort. We assessed the prognostic impact of ALP normalization with Kaplan-Meier and Cox regression. Sankey diagrams and segmented Poisson regression analysis mapped dynamic risk transitions to identify critical intervention windows. Predictive performance (sensitivity/specificity/positive predictive value/negative predictive value (NPV)) of Mayo, Paris II, and Toronto criteria for 12-month ALP normalization was compared.

Patients achieving ALP normalization showed significantly higher complication-free survival versus those with ALP 1.0–1.67 × ULN (89.8% vs. 79.8%; P = 0.016). Segmented Poisson regression identified significant change points at 3.73 and 5.5 months for high-to-medium and medium-to-low risk transitions, respectively. Failure to meet the Toronto criteria at month 3 predicted non-normalization with 95% NPV, whereas Paris II criteria at month 6 provided optimal specificity (73%) for identifying patients who failed to achieve ALP normalization.

ALP normalization significantly improves clinical outcomes. Two subgroups demonstrate low normalization probability and warrant early intervention: (1) patients with ALP ≥ 1.67 × ULN after 3 months and (2) those not meeting Paris II criteria by month 6.

Pancreatic cancer remains a highly lethal malignancy owing to the difficulty of early detection. In 2021, the Chinese Consensus on Early Screening and Surveillance for Pancreatic Cancer in High-risk Individuals was first established. However, the evidence landscape has evolved rapidly, necessitating an updated, evidence-based framework tailored to the Chinese healthcare context. This revised consensus aims to standardize the early screening and surveillance process for high-risk populations in China. A multidisciplinary expert panel comprising 53 specialists from 17 provincial-level regions systematically reviewed the literature using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A modified Delphi process was employed, with consensus predefined as ≥75% agreement. The panel formulated 26 evidence-based recommendations covering screening objectives, the definition of high-risk populations (hereditary susceptibility, new-onset diabetes, chronic pancreatitis, and pancreatic cystic neoplasms), age at screening initiation, surveillance intervals, imaging modalities (magnetic resonance imaging/magnetic resonance cholangiopancreatography, endoscopic ultrasound, computed tomography), surgical indications, and lifestyle modifications. Of these recommendations, 14 are strong and 12 are weak, supported by evidence levels ranging from A to D. Implementation of this consensus in clinical practice will help improve the early diagnosis of stage I pancreatic cancer and high-grade precursor lesions, thereby advancing standardized multidisciplinary care and ultimately improving patient outcomes in China.