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.

Colorectal polyp detection from endoscopic images is critical for the early diagnosis of colorectal cancer. However, traditional deep learning methods often suffer from limited generalization when deployed across datasets containing different polyp morphologies. This work aimed to investigate whether vision-language foundation models can facilitate zero-shot generalization across multiple polyp datasets without target-domain fine-tuning.

We introduced a zero-shot colorectal polyp detection framework based on Contrastive Language-Image Pretraining (CLIP) to improve cross-dataset detection performance. Key innovations include: (1) a background patch contrastive loss using pseudo-normal tissue patches to teach the model to distinguish normal mucosa from polyps; (2) attribute-enhanced text prompts that incorporate domain-specific descriptors of polyp appearance, improving the model’s semantic generalization to novel polyp morphologies; and (3) an enhanced CLIP visual adapter with per-layer adaptive feature fusion and generalized mean pooling to capture multi-scale features for better polyp localization. During training, we use one annotated colorectal polyp dataset (e.g., CVC-ColonDB) to learn patch-level image-text correspondence. The model is then evaluated in a zero-shot manner on different polyp datasets (CVC-ClinicDB, Kvasir-SEG, and CVC-300), where we measure both pixel-level.

The framework demonstrated robust zero-shot generalization on unseen test cohorts. Without any dataset-specific fine-tuning, the model achieved a mean pixel-level AUROC of 0.94 and a mean average precision of 0.81 across the 12 leave-one-dataset-out zero-shot transfer settings. In the CVC-ColonDB-source benchmark, the model achieved a mean Dice coefficient of 0.84 across CVC-ClinicDB, Kvasir-SEG, and CVC-300. This high level of performance was consistent across datasets with distinct visual characteristics, underscoring the ability of the model to detect diverse polyp morphologies that it had not been explicitly trained to recognize.

Our findings demonstrate that an anomaly-aware vision-language model significantly improves cross-dataset polyp detection generalization without requiring normal images for training. This multimodal strategy may facilitate the robust deployment of artificial intelligence-based colorectal screening systems by enabling reliable detection of diverse polyp morphologies across different clinical settings. Extension to non-polyp colorectal pathologies (e.g., ulcerative colitis and colorectal tumors) remains an important direction for future work, pending the availability of pixel-level annotated datasets for these lesion categories.

Chronic pelvic pain remains a significant clinical challenge, often refractory to conservative and interventional treatments. Superior hypogastric plexus block is an established technique; however, conventional anterior and posterior approaches may be limited by anatomical variability and potential risks to adjacent structures. Based on these anatomical findings, we propose that a posterior transosseous S1 pedicular approach represents a novel and anatomically robust corridor for accessing the superior hypogastric plexus. We hypothesize that the highly reproducible osseous anatomy of the S1 pedicle, combined with its consistent spatial relationship to the anterior sacral cortex and retroperitoneal compartment, may enable precise and fluoroscopically reproducible instrument guidance toward the plexus. Furthermore, this trajectory may mitigate the anatomical variability and procedural limitations associated with conventional anterior or paravertebral techniques while potentially reducing the risk of inadvertent injury to adjacent visceral, vascular, and neural structures. This concept is based on anatomical reasoning and fluoroscopic observations obtained during cadaveric anatomical orientation, suggesting that a transosseous trajectory through the S1 pedicle toward the anterior sacral cortex may offer improved spatial control and reproducibility compared with soft-tissue-based approaches. The proposed pathway remains conceptual and is not intended for clinical application at this stage. Further cadaveric, imaging-based, and clinical studies are required to evaluate its anatomical validity, safety, and potential clinical relevance.

Primary biliary cholangitis (PBC) significantly impairs health-related quality of life (HRQL), yet the impact of disease stage and fatigue on HRQL and psychological status remains insufficiently quantified. This study aimed to investigate differences in HRQL across disease stages and the impact of fatigue in patients with PBC.

This cross-sectional study recruited 219 patients with PBC from two Chinese tertiary hospitals (2011–2024). After excluding one preclinical case, 218 patients were analyzed. Quality of life was assessed using the validated Chinese versions of the SF-36 and Chronic Liver Disease Questionnaire (CLDQ); psychological status was assessed using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Between-group differences were quantified by mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs). Baseline characteristics were balanced across stages (all P > 0.05).

Of the 218 patients (90.4% female; mean age, 57.2 ± 10.3 years), 41 were in the clinical stage, 75 in the fibrosis stage, and 102 in the cirrhosis stage. SF-36 scores were lowest in the cirrhosis stage (e.g., Physical Functioning MD, 17.26; 95% CI, 6.93–27.59 vs. clinical stage), with similar declines in CLDQ domains. Anxiety was highest in the clinical stage (58.5%; OR vs. cirrhosis, 4.13; 95% CI, 1.92–8.92), whereas depression was highest in the cirrhosis stage (55.9%; OR vs. clinical stage, 4.50; 95% CI, 1.95–10.38). Fatigue prevalence was 66.1% and increased with disease stage. Patients with fatigue had lower SF-36 scores in Physical Functioning, Bodily Pain, Vitality, Mental Health, and Physical Component Summary (e.g., Physical Component Summary MD, 38.22; 95% CI, 10.41–66.02).

HRQL declines progressively with PBC stage. Fatigue is strongly associated with impaired HRQL and is closely interrelated with anxiety and depression. Stage-specific psychological patterns suggest the need for tailored supportive interventions.

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.

The aberrant activation of the mTOR pathway and its crosstalk with other signaling cascades represent key drivers of hepatocellular carcinoma (HCC) progression. mTOR-mediated ferroptosis suppression has been implicated in HCC resistance to chemotherapy. This study aimed to elucidate the mechanisms underlying mTOR inhibitor resistance and to evaluate the therapeutic potential of multidrug combinations in β-catenin-mutant HCC.

MHCC97H and SNU449 cells were transfected with 4EBP1WT, 4EBP1A4, or HSP90β expression plasmids and then treated with rapamycin to assess their effects on ferroptosis and rapamycin sensitivity. The role of 4EBP1 in regulating ferroptosis was further explored by Western blotting, co-immunoprecipitation, and immunofluorescence. The inhibitory effects of mTOR inhibitors (rapamycin, MLN0128), ERK inhibitors (PD901), and their combination (MLN0128 + PD901) on tumor cells were evaluated. HCC mouse models were generated via hydrodynamic tail vein injection of c-Met/β-cateninΔN90 or c-Met/β-cateninΔN90/4EBP1A4 plasmids to evaluate the therapeutic effects of the four treatment regimens.

Rapamycin more potently inhibited mTOR/RPS6 than mTOR/4EBP1 and concurrently induced ferroptosis. 4EBP1A4 promoted ferroptosis and potentiated rapamycin efficacy. Mechanistically, 4EBP1A4 competitively bound HSP90β, displacing Keap1, thereby increasing Keap1–Nrf2 complex formation and promoting Nrf2 degradation. Furthermore, rapamycin, MLN0128, PD901, and their combination reduced p-4EBP1 levels, induced ferroptosis, and inhibited HCC cell proliferation, thereby suppressing tumor growth, with the combination exhibiting the strongest effect.

4EBP1A4 enhances Nrf2 ubiquitination and degradation via the HSP90β/Keap1 axis, relieving mTOR-mediated ferroptosis suppression and synergistically improving rapamycin efficacy. Additionally, rapamycin, MLN0128, and PD901 suppress HCC progression by inducing ferroptosis, with their combination showing superior potency.

Ulinastatin, a broad-spectrum serine protease inhibitor widely used in Asia, has attracted increasing interest for its potential role in critical care. This review summarizes current evidence on its efficacy and safety in acute pancreatitis, severe acute pancreatitis, sepsis, acute respiratory distress syndrome, and perioperative management in cardiac surgery with cardiopulmonary bypass. Meta-analyses suggest that ulinastatin may improve outcomes by reducing mortality, shortening intensive care unit and hospital stays, and attenuating inflammatory responses. In severe acute pancreatitis, its use has been associated with reduced mortality and shorter hospitalization. In sepsis and septic shock, ulinastatin appears to lower all-cause mortality, decrease organ dysfunction scores, and reduce inflammatory markers. Evidence in acute respiratory distress syndrome indicates improvements in the oxygenation index and possible mortality reduction. Perioperative administration during cardiac surgery may mitigate postoperative inflammation and shorten the duration of mechanical ventilation. Despite these encouraging findings, most available studies originate from Asia and are limited by small sample sizes, heterogeneous designs, and inconsistent dosing regimens, which restrict generalizability and prevent standardized recommendations. Additionally, although ulinastatin demonstrates a favorable safety profile with a low incidence of adverse drug reactions, long-term and multinational pharmacovigilance data remain limited. Well-designed international, multicenter randomized controlled trials are required to clarify optimal dosing strategies, confirm clinical efficacy across diverse populations, and determine its independent effects compared with combination therapies. Overall, ulinastatin shows promise as a potential adjunctive therapy in critical care through modulation of inflammation and organ protection, but broader global adoption will depend on higher-quality evidence addressing current methodological gaps.