Parenteral nutrition (PN)-associated cholestasis (PNAC) is frequently diagnosed in premature infants; however, not all PN-exposed infants develop PNAC. We propose that, in premature infants receiving PN and varying amounts of enteral feeds, differences in the gut microbiome and fecal bile acid content are associated with PNAC development. This study aimed to examine the fecal microbiome and bile acid content of premature infants on PN to determine if there is a relationship with the development of PNAC.

Twenty-two preterm infants had serial bilirubin measurements and fecal samples collected during their neonatal intensive care unit admission. Fecal samples underwent 16S rRNA gene sequencing and bile acid analysis. Binomial regression, adjusting for postmenstrual age with feed amount as a moderator, was used to assess the impact of the fecal microbiome and bile acids on PNAC development.

Cholestatic patients (n = 11) had greater PN and antibiotic exposure (p = 0.020; p = 0.010) and longer neonatal intensive care unit stays (p = 0.0038) than non-cholestatic patients. Microbiome richness was higher in non-cholestatic infants (p < 2E-16), with no difference in β diversity (p = 1.0). Cholestatic infants had a significantly higher abundance of Proteobacteria and Fusobacteriota and a lower abundance of Bacteroidota (p < 2E-16). Akkermansia was abundant in all infants on low feeds; as feed volume increased, Akkermansia abundance significantly increased in non-cholestatic infants (p < 2E-16). Bile acid analysis demonstrated significantly lower deoxycholic acid concentrations in cholestatic infants (p < 2E-16). Metagenomic analysis revealed an increase in Proteobacteria requiring augmented stress responses in non-cholestatic infants.

This is the first study to directly explore the relationship between PNAC susceptibility, the microbiome, and fecal bile acids in preterm infants. The microbiome and bile acid patterns identified here may inform the development of targeted therapeutics for this vulnerable population.

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by systemic inflammation and immune dysregulation, in which macrophages play a key role in organ injury. This study aimed to investigate the role and mechanism of pyruvate dehydrogenase kinase 4 (PDK4) in ACLF to identify therapeutic targets that modulate macrophage function and mitigate ACLF progression.

Single-cell RNA sequencing data from healthy and ACLF liver tissues were analyzed from the Sequence Read Archive database. Transcriptomic data of peripheral blood mononuclear cells from ACLF patients (GSE168048) were also examined. In vitro experiments assessed PDK4 expression and macrophage polarization, and conditioned-medium studies evaluated effects on LO2 hepatocytes. In vivo validation was performed in ACLF mouse models treated with a PDK4 inhibitor.

Single-cell analysis revealed a predominance of M1-polarized hepatic macrophages in ACLF with marked upregulation of PDK4. Peripheral blood mononuclear cell transcriptomics showed that higher PDK4 expression correlated with 28-day mortality. In vitro, PDK4 expression increased in M1 macrophages; PDK4 inhibition attenuated M1 polarization and reduced cytotoxic effects on LO2 cells. In vivo, pharmacologic inhibition of PDK4 suppressed M1 polarization in macrophages, alleviated liver inflammation, and reduced tissue injury. Mechanistically, PDK4 promoted M1 polarization via activation of signal transducer and activator of transcription 1 signaling.

PDK4 is a key pro-inflammatory regulator in ACLF by promoting M1 macrophage polarization. Targeting PDK4 may be a promising strategy to attenuate inflammation and improve clinical outcomes in ACLF.

In the past decade, immune checkpoint inhibitors (ICIs) have dramatically changed cancer treatment, significantly improving outcomes for patients with various malignancies. Nonetheless, their widespread application has resulted in a rise in immune-related adverse events due to excessive immune activation, including immune-mediated hepatotoxicity (IMH). IMH can cause serious complications and even death, underscoring the need for early prediction and intervention. This review outlines the current understanding of risk factors and predictive biomarkers for IMH in cancer patients undergoing ICI therapy, with risk factors divided into patient-associated, tumor-associated, and agent-associated categories. Higher IMH risk is related to female sex, younger age, extreme BMI, Asian ethnicity, and chronic liver disease. Cancer type, prior ICI treatment, dual ICI combination therapy, and the concurrent use of chemotherapy, targeted agents, or other hepatotoxic drugs (e.g., acetaminophen, statins) also increase the risk of IMH. Potential predictive biomarkers encompass circulating blood cells, serum proteins, autoantibodies, cytokines, gene profiles, and the gut microbiome. Despite promising findings, the predictive value of these biomarkers remains inconsistent, and no definitive biomarker has been established for routine clinical use. Large-scale prospective studies are essential to verify the predictive value of these biomarkers and facilitate their integration into clinical practice, thereby providing deeper insights into the early identification and individualized management of IMH during ICI therapy.

Diabetic cardiomyopathy (DCM), a diabetes-specific cardiovascular complication, is pathologically characterized by cardiomyocyte apoptosis, oxidative stress, inflammatory responses, and myocardial fibrosis, distinguishing it from other cardiac disorders, such as hypertension and coronary artery disease. Challenges in early diagnosis, coupled with the limited efficacy and adverse effects of current treatments, have made DCM a significant contributor to heart failure and mortality in patients with diabetes. Natural products, recognized for their diverse sources, structural variety, and multitarget therapeutic potential, have shown promise in preventing and treating DCM. Drawing on advances over the past five years, this review systematically summarizes the pharmacological effects and molecular mechanisms of natural products (e.g., flavonoids, terpenoids, phenylpropanoids, alkaloids, and polysaccharides) in the treatment of DCM, with the aim of providing a theoretical foundation for further research and drug development.

Febrile neutropenia (FN) is one of the acute and serious complications of chemotherapy-induced myelosuppression in tumor patients. Antibiotics and granulocyte colony-stimulating factor are the mainstays of its treatment. However, this therapy still faces many challenges and may trigger drug resistance, as well as adverse effects such as bone pain and vasculitis. How to minimize treatment-related toxicity while ensuring therapeutic efficacy has become a key issue to be addressed in current clinical practice. In recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages in the prevention and treatment of FN. We conducted a comprehensive search of the PubMed, Web of Science, and CNKI databases using keywords such as TCM and FN, covering the period from their establishment to May 2025. Clinical studies have shown that the combination of TCM and modern medicine can significantly reduce the incidence of FN, while also enhancing the number of granulocytes, shortening the duration of fever, improving the quality of life of patients, and reducing other toxic effects of chemotherapy. These results suggest that TCM is a promising and safe complementary therapy. However, more high-quality trials are needed to verify its benefits. This review summarizes the latest progress in the treatment of FN with TCM and discusses future development directions.

Autoimmune pancreatitis (AIP) is a rare immune-mediated form of chronic pancreatitis. It may affect multiple organs, and its heterogeneous clinical manifestations complicate diagnosis and management. Based on the Chinese Guidelines for the Diagnosis and Management of Autoimmune Pancreatitis (Shanghai 2012 Draft), together with the latest domestic and international guidelines and research advances, the present guideline provides 20 recommendations covering four aspects: diagnosis, treatment, follow-up, and prognosis. The aim is to improve the diagnosis and management of AIP in China and ultimately improve patient outcomes.

Perioperative anaphylaxis is a rare, life-threatening, iatrogenic condition that predominantly arises following anesthesia. The unique context of this condition, characterized by the concurrent administration of multiple drugs, patient draping, and altered physiological states, presents significant diagnostic and therapeutic challenges, contributing to a higher mortality rate compared to anaphylaxis in other settings. This narrative review synthesizes the evidence to delineate the evolving etiology, pathophysiology, atypical clinical presentation, evidence-based immediate management, and strategic prevention of perioperative anaphylactic reactions. The primary causative agents include neuromuscular blocking agents, antibiotics, and latex, with emerging culprits such as chlorhexidine, dyes, and novel agents like remimazolam. Diagnosis is complicated by the paucity of cutaneous signs; thus, cardiovascular collapse combined with a low end-tidal carbon dioxide level has emerged as a useful supportive diagnostic indicator that requires integration with the clinical context. Immediate management prioritizes the prompt administration of epinephrine and aggressive fluid resuscitation. Subsequent allergological investigations, primarily via skin testing and serum tryptase/histamine measurement, are paramount for identifying the causative agent and preventing its recurrence. Prevention strategies emphasize meticulous history-taking, risk stratification, and the creation of latex-free environments. Future directions must focus on establishing global surveillance networks, exploring novel biomarkers and risk factors such as the circulating microbiome—a preliminary but promising area of research—and enhancing team preparedness through simulation training to improve patient safety outcomes.

Colorectal cancer histopathological grading relies on the accurate segmentation of glandular structures. Current deep learning–based methods depend heavily on large-scale pixel-level annotations that are labor-intensive and not amenable to clinical practice. Weakly supervised semantic segmentation offers a promising alternative; yet, existing class activation map–based weakly supervised semantic segmentation approaches often produce incomplete, low-quality pseudo-masks that overemphasize discriminative regions and fail to provide reliable supervision for unannotated glandular structures, limiting their suitability for dense histopathology segmentation under sparse supervision. We propose a novel weakly supervised teacher–student framework that leverages sparse pathologists’ annotations and an Exponential Moving Average–stabilized teacher network to generate refined pseudo-masks.

Our framework integrates confidence-based filtering, adaptive fusion of teacher predictions with limited ground truth, and curriculum-guided refinement, enabling the student network to progressively delineate and accurately segment unannotated glandular regions. We validated our framework on an institutional colorectal cancer cohort from The Ohio State University Wexner Medical Center, consisting of 60 hematoxylin and eosin-stained whole-slide images from independent patients with varying degrees of gland differentiation, as well as on public benchmarks including the Gland Segmentation dataset (derived from stage T3–T4 colorectal adenocarcinomas), TCGA-COAD, TCGA-READ, and SPIDER.

The proposed framework achieved strong performance on the institutional dataset despite limited annotations. On the Gland Segmentation dataset, it demonstrated competitive performance compared to both weakly and fully supervised approaches, achieving a mean Intersection over Union of 80.10% ± 1.52 and a mean Dice coefficient of 89.10% ± 2.10. Moreover, cross-cohort evaluations showed robust generalization on TCGA-COAD and TCGA-READ without requiring additional annotations, while reduced performance on SPIDER reflected pronounced domain shift.

Our framework provides an annotation-efficient and generalizable paradigm for accurate gland segmentation in colorectal histopathology, offering a practical pathway toward significantly reducing annotation burdens while preserving high segmentation fidelity.

The gut microbiota engages in a complex, bidirectional dialogue with the liver via the gut–liver axis, and its dysbiosis plays a central role in the initiation and progression of various liver diseases. This review comprehensively integrates recent advances in the common features and etiology-specific patterns of gut microbial dysbiosis in liver diseases, signal decoding of key microbial metabolite axes, gut–liver immune crosstalk mechanisms, the accelerating role of gut barrier disruption, and recent progress in the use of the microbiome as diagnostic and prognostic biomarkers. We focus on analyzing the common patterns of reduced diversity, depletion of beneficial bacteria, and enrichment of pathogenic bacteria associated with gut flora dysbiosis across different liver diseases, ranging from nonalcoholic fatty liver disease and alcoholic liver disease to cirrhosis and hepatocellular carcinoma, as well as their unique etiology-related characteristics. Core findings reveal that microbial metabolites act as key chemical messengers that precisely drive liver disease progression by modulating host metabolic, immune, and inflammatory pathways. Meanwhile, the translocation of microbes and their products resulting from disruption of gut barrier integrity serves as a key accelerator, exacerbating liver injury and related complications. Based on these mechanisms, this review further explores ecological niche remodeling strategies targeting the gut microbiota, including the existing evidence and limitations of fecal microbiota transplantation and probiotics/prebiotics, as well as the prospects of emerging precision interventions such as phage therapy, microbial enzyme inhibitors, and engineered bacteria. Finally, we emphasize the potential and personalized implementation pathways of synergistically integrating microbiota modulation with existing therapies such as antivirals, antifibrotics, immunotherapy, and metabolic surgery. Future research must focus on promoting the translation of microbiome research from association studies to clinical applications through multi-omics integration and prospective clinical trials, ultimately achieving precise prevention and treatment of liver diseases based on gut–liver axis regulation.

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family regulates fundamental processes in both innate and adaptive immunity. Aberrant NF-κB activation, whether through canonical or non-canonical signaling pathways, contributes to chronic inflammation, autoimmunity, allergy, and primary immunodeficiency/autoinflammatory syndromes, while also influencing host defense and tissue repair mechanisms. The present review aims to synthesize molecular architecture, upstream triggers, ubiquitin-centered relay systems, and the dynamic regulation of NF-κB activity. The major findings on the NF-κB signaling pathway encompass its dual molecular mechanisms (canonical and non-canonical), its central roles in immune and inflammatory responses, cell survival, and development, as well as its complex regulatory networks. We interpret NF-κB as a master integrator of diverse signals, essential for both acute and long-term physiological processes. Dysregulation of NF-κB underlies many diseases, and while it is a promising therapeutic target, its ubiquitous functions demand precise modulation to avoid adverse effects. In conclusion, the proper function of the NF-κB signaling pathway is essential for maintaining cellular homeostasis and immune defense; its dysregulation is linked to chronic inflammatory diseases, autoimmune disorders, and cancer, which underscores the pathway’s significance as a therapeutic target. Although it elucidates molecular processes and treatment options, experimental validation of emerging therapeutic concepts such as ubiquitin code editing and spatial immunology remains limited.