Immunothrombosis, the interplay between immune activation and coagulation, contributes to disease progression in inflammatory disorders. Its role in hepatitis B virus–related acute-on-chronic liver failure (HBV-ACLF) and the involvement of neutrophil extracellular traps (NETs) remain unclear. This study aimed to elucidate NETs-mediated immunothrombosis in HBV-ACLF.

Liver single-cell RNA sequencing data from HBV-ACLF patients and healthy controls were analyzed to define immune and endothelial transcriptional profiles. A cohort of 46 HBV-ACLF patients, 20 chronic hepatitis B patients, and 20 healthy controls was assessed for circulating NETs, endothelial injury markers, and coagulation parameters. Histopathology and in vitro assays examined NETs distribution and endothelial interactions.

NETs were markedly elevated in HBV-ACLF and correlated with endothelial injury markers (syndecan-1, von Willebrand factor, soluble thrombomodulin), coagulopathy, and prognostic scores. Histology revealed NETs colocalization with endothelial cells and platelets within hepatic microthrombi. NETs from patient neutrophils impaired endothelial integrity and enhanced procoagulant activity in vitro. Mechanistically, toll-like receptor 2 (TLR2) and complement component 5a receptor 1 (C5aR1) signaling were involved in NETs formation, and their pharmacological inhibition reduced NETs generation.

NETs are associated with endothelial injury and immunothrombosis in HBV-ACLF. Mechanistic analyses suggest a role for TLR2 and C5aR1 pathways in NETs formation, indicating potential targets for future therapeutic investigation.

The pathogenic role of MIR142 genetic abnormalities in the development of primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is unexplored. The objective of this study was to investigate the frequency, spectrum, and functional significance of mutations in the MIR142 gene in primary CNS DLBCL.

Direct Sanger sequencing of the MIR142 gene was performed in tumor tissue from 35 patients with primary DLBCL of the CNS. In silico prediction of microRNA (miRNA)–target interactions, enrichment analysis of target gene ontologies, and prediction of the secondary structure and minimum free energy of the miRNA hairpin were performed.

The mutation frequency was 37.1% (95% confidence interval: 23.2–53.7%). The vast majority of the identified single-nucleotide variants were located outside the regions encoding mature miRNA chains. In silico analysis showed that the n.29A>G mutation located in the seed sequence of miR-142-5p resulted in a significant reduction in the number of potential targets and alterations to the interaction spectrum. All single-nucleotide variants identified in the study patients caused a change in minimum free energy and affected the shape and length of the hairpin stem of pri-miRNA. The results indicate the fragility of the pri-miR-142 hairpin.

The frequency of gene mutations in primary DLBCL of the CNS significantly exceeds that reported for systemic DLBCL.

Combined traumatic brain injury (CTBI) remains a leading cause of disability/mortality among workers, yet which routine biochemical tests that predict infectious complications remain controversial. We aimed to identify the most informative serum markers for early diagnosis and prognosis of such complications.

In this retrospective observational study, 80 acute CTBI patients (40 without vs. 40 with mainly bacterial infectious complications) and 40 healthy controls were analyzed. Serum collected at 24, 72, and 168 h was assayed for protein fractions, metabolic markers, lipid peroxidation indices, antioxidant activity, endogenous intoxication markers, acids/minerals, and relevant enzymes.

The study found that the most important prognostic indicator for infectious complications was a simultaneous increase in α1-globulins, β-globulins, diene conjugates, superoxide dismutase, medium- and low-molecular-weight substances in erythrocytes, erythrocyte oligopeptides, and lactate at 24 h after injury (p < 0.001). A significant increase in sialic acids, uronic acids, total Ca and P, and low-density lipoproteins was observed at 72 h after injury (p < 0.001). Notably, individual components from the 24-h panel demonstrated high standalone predictive value, with areas under the curve of diene conjugates (0.91), erythrocyte oligopeptides (0.87), β-globulin (0.86), α1-globulin (0.82), and superoxide dismutase (0.82), respectively. The elevation of these biomarker profiles was significantly correlated with worse clinical outcomes, including longer intensive care unit stay and ventilation duration.

This study identified a set of biochemical markers associated with infectious complications in patients with CTBI. These biochemical parameters may serve as additional diagnostic and prognostic criteria for the management of infectious complications in patients with СTBI.

Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease. Its molecular etiology remains poorly defined, hindering the development of mechanism-based diagnostics and therapies. Therefore, this study aimed to identify key molecular drivers and causal biomarkers of PSC by integrating transcriptomics, machine learning, and genetic causal inference.

We deployed a computational framework combining transcriptomics, network biology, machine learning, and genetic causal inference. Peripheral blood transcriptomes from PSC patients and controls were analyzed to identify disease-associated modules. Candidate genes were refined via protein-protein interaction networks and a multi-algorithm machine learning screen. Causal inference was performed using two-sample Mendelian randomization, integrating plasma protein quantitative trait loci with PSC genome-wide association study summary statistics.

Transcriptomic analysis revealed a PSC-associated module enriched in ribosome biogenesis and protein homeostasis pathways. A machine learning-optimized nine-gene signature (including PTMA, SUMO1, Shwachman-Bodian-Diamond syndrome (SBDS), RPL7, EIF1AX, ANP32A, PCNA, FAM98A, and MPHOSPH6) achieved high diagnostic accuracy (mean AUC = 0.908) and was consistently downregulated in PSC. This signature was linked to a remodeled immune microenvironment characterized by myeloid skewing and specific transcriptional-immune covariation patterns. Mendelian randomization identified SBDS as a putatively causal protective factor, where genetically instrumented higher plasma SBDS protein levels were robustly associated with a lower PSC risk (inverse variance weighted odds ratio = 0.525, 95% CI: 0.356–0.773, P = 0.001). Sensitivity analyses supported the validity of the Mendelian randomization assumptions.

Our study establishes disrupted ribosome homeostasis as a causal pathway in PSC and nominates plasma SBDS as a high-confidence diagnostic biomarker and therapeutic target. The integrative framework provides a generalizable strategy for discovering causal biomarkers in complex diseases.

Pulmonary arterial hypertension (PAH) is a progressive cardiovascular disease with an increasing global burden. Although hemolytic disorders are established causes of PAH, their contribution to the global PAH burden remains unclear. This study aimed to evaluate the association between hemolysis-associated disorders and PAH incidence and to identify the relative contribution of hemolytic disorder subtypes compared with socio-demographic factors.

Using Global Burden of Disease 2021 data, temporal trends in the age-standardized incidence rate (ASIR) of PAH were analyzed using Joinpoint regression. Pearson correlation analysis assessed associations between PAH ASIR and the age-standardized prevalence rates of hemolytic disorder subtypes, hemolysis-related infections, malnutrition, and the Socio-demographic Index (SDI). Random forest regression was used to quantify the contributions of hemolytic disorders to PAH ASIR. Geographic distributions of PAH incidence and hemolytic disorder prevalence were compared, and Bayesian age-period-cohort modeling was used to project their burdens through 2050.

Global PAH ASIR increased from 0.50 to 0.52 per 100,000 from 1990 to 2021. The prevalence of hemoglobinopathies and hemolytic anemias correlated positively with PAH ASIR (R = 0.61, P = 7.70 × 10-22). The random forest model explained 73% of the variance in PAH ASIR (R² = 0.73, P = 0.01), with G6PD trait (percentage increase in mean squared error [%IncMSE]: 18.43), other hemoglobinopathies/hemolytic anemias of unknown etiology (%IncMSE: 18.38), and vitamin A deficiency (%IncMSE: 17.27) identified as the top predictors, surpassing SDI (%IncMSE: 13.25) and sex (%IncMSE: 1.25). Temporal changes in hemolytic disorder prevalence strongly mirrored changes in PAH incidence (R = 0.76, P = 6.34 × 10-39). Exploratory analyses suggested that natural product exposures may contribute to the unexplained hemolytic burden that drives PAH. Projections indicated a continued rise through 2050 in both PAH burden (ASIR increasing from 0.52 in 2022 to 0.57 per 100,000) and hemolytic disease burden (prevalence rising from 27,760.54 to 31,863.72 per 100,000).

Hemolysis-associated disorders, particularly G6PD trait, other hemoglobinopathies/hemolytic anemias, and vitamin A deficiency, are the predominant contributors to the global PAH burden. The projected continued rise in hemolytic disorder prevalence through 2050 signals a persistent exacerbation of the global PAH burden, underscoring the urgent need for targeted prevention strategies.

Post-stroke dysphagia management research has primarily focused on screening, assessment, and intervention strategies, with limited objective indicators for evaluating nursing care quality. This study aimed to develop a dysphagia nursing quality evaluation index system for neurosurgical inpatients with stroke.

Using the “structure-process-outcome” three-dimensional quality model as the theoretical framework, a preliminary quality evaluation index system was constructed through literature analysis and group discussion. A two-round Delphi expert consultation was conducted among 25 purposively selected clinical experts from tertiary Class A hospitals, with inclusion criteria requiring a bachelor’s degree or higher, an intermediate professional title or above, and at least 10 years of clinical experience in stroke nursing or related fields. The analytic hierarchy process was used to determine indicator weights. Outcome measures included expert authority coefficients (Cr), Kendall’s W concordance coefficient, internal consistency reliability (Cronbach’s α), and the final indicator structure.

The Cr values were 0.87 and 0.88 across the two rounds. Kendall’s W concordance coefficient increased from 0.207 to 0.235 (P < 0.001), indicating statistically significant expert agreement. The final index system comprised 3 first-level indicators, 11 second-level indicators, and 44 third-level indicators, with all indicator definitions and weights determined. The overall Cronbach’s α was 0.86, indicating preliminary internal consistency.

This study developed a dysphagia nursing quality evaluation index system for neurosurgical inpatients with stroke using the three-dimensional quality model and the Delphi method. The system showed acceptable expert authority, statistically significant expert agreement, and preliminary internal consistency, suggesting potential applicability for nursing quality monitoring in neurosurgical wards and Neurosurgery Intensive Care Units. Further clinical validation is needed before routine implementation.

Lipid metabolism reprogramming drives malignant proliferation and invasiveness in hepatocellular carcinoma (HCC). Beyond supplying energy and membrane components, lipids function as signaling molecules that modulate tumor cell epigenetics and the microenvironment. Accumulating research has clarified the implications of these metabolic alterations in HCC, providing a rationale for targeted therapies. This review summarizes key alterations in lipid metabolism within HCC and explores their mechanistic contributions to tumor progression. It further examines how lipid metabolic shifts in immune and stromal cells of the tumor microenvironment promote HCC advancement. Finally, we discuss the therapeutic potential of targeting lipid metabolism in liver cancer treatment.

Given that hemodynamic fluctuations acutely escalate the risk of devastating rebleeding and secondary neurological deficits in unsecured ruptured intracranial aneurysms, this study aimed to synthesize the best available evidence for blood pressure management in this population and to provide an evidence-based foundation for clinical nursing practice.

A systematic search was conducted in domestic and international databases and relevant websites for evidence pertaining to blood pressure management in patients with ruptured intracranial aneurysms, including clinical practices, guidelines, expert consensuses, evidence summaries, and systematic reviews/meta-analyses. The search period covered database inception up to June 2025. Two researchers independently performed literature quality assessments and evidence extraction, with particular attention to nursing-relevant evidence on hemodynamic monitoring, bedside assessment, complication prevention, fluid management, and follow-up coordination.

A total of 17 studies were included, comprising 11 guidelines, 4 expert consensuses, and 2 clinical decision entries. The synthesized evidence yielded 32 recommendations, structured into 6 core clinical domains: personnel and environmental configuration, individualized blood pressure targeting, precision hemodynamic monitoring, complication prevention, fluid therapy strategy, and longitudinal follow-up protocols. These recommendations further clarified key nursing responsibilities in triage coordination, continuous blood pressure surveillance, neurological assessment, delayed cerebral ischemia surveillance, fluid balance monitoring, and long-term follow-up.

Blood pressure management in patients with ruptured intracranial aneurysms should be individualized and multidisciplinary. The synthesized evidence highlights key nursing priorities in hemodynamic monitoring, delayed cerebral ischemia surveillance, fluid management, and follow-up coordination, and may inform standardized clinical nursing protocols.

Acute leukemias with chimeric fusion genes involving FET (FUS, EWSR1, and TAF15) family proteins and ETS (E26 transformation-specific)-like transcription factors often present with unique clinical and pathological characteristics. This mini-review aims to summarize the clinical and pathological features of acute leukemia cases harboring rearrangements involving the fused in sarcoma (FUS) or Ewing sarcoma breakpoint region 1 (EWSR1) genes.

An extensive literature review was performed on reported acute leukemia cases with fusions involving FUS or EWSR1. The details of the reported cases, as well as summarized information, are presented.

Rare cases of acute leukemia have been found to harbor either FUS or EWSR1 gene rearrangements with ETS or non-ETS proteins as partners and demonstrate heterogeneous clinical and pathological features. Acute leukemias carrying FUS gene rearrangements present with diverse immunophenotypes and are predominantly, but not exclusively, acute myeloid leukemia (AML), with ERG as the most frequent fusion partner. In contrast, acute leukemias with EWSR1 gene rearrangements more commonly present as B-cell acute lymphoblastic leukemia (ALL) and mixed phenotypic acute leukemia (MPAL), with ZNF384 as the predominant partner. At present, FUS::ERG-positive AML is the only specific entity with a FET::ETS fusion that is formally recognized in the World Health Organization 5th edition hematolymphoid tumor classification (WHO-HEM5) and the International Consensus Classification (ICC) systems. Cytogenetic karyotyping and fluorescence in situ hybridization remain crucial tools for detecting chromosomal translocations in over half of acute leukemias harboring FUS or EWSR1 gene rearrangements. However, a subset of patients may exhibit a normal karyotype and require advanced molecular diagnostic methods. EWSR1-rearranged leukemias can be difficult to distinguish from Ewing sarcoma and therefore require particular attention.

As more cases and additional data become available, it may be justified to expand this category of acute leukemias to include other specific acute leukemia entities with fusions involving FET::ETS, such as FUS::FLI1 and FUS::FEV, in addition to FUS::ERG-positive AML. However, additional data are required to support such subclassification. In contrast, AML cases with EWSR1 rearrangements are exceedingly rare and display considerable variability. Cases of B-ALL or B/myeloid MPAL with the EWSR1::ZNF384 fusion may be more appropriately classified together with other ZNF384-rearranged leukemia subtypes. Advanced molecular diagnostic methods, especially RNA-based next-generation sequencing, are suggested to improve the accurate diagnosis of acute leukemias with FUS or EWSR1 fusions. Additional pathologic workup, particularly immunohistochemical staining with hematopoietic markers, is highly recommended to differentiate EWSR1-rearranged leukemia from Ewing sarcoma.