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.

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.

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.

Thyroid nodules are increasingly detected in clinical practice, and accurate imaging evaluation is essential for risk stratification, treatment planning, and postoperative surveillance of thyroid cancer. Although ultrasound remains the first-line modality for thyroid nodule assessment, the roles of computed tomography (CT), spectral CT, magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) vary across clinical scenarios, and the optimal integration of these modalities remains insufficiently standardized. In particular, existing studies often focus on individual imaging techniques, while practical guidance on modality selection for initial screening, preoperative anatomical assessment, recurrence monitoring, and high-risk disease evaluation remains limited. This narrative review summarizes the imaging principles, clinical indications, diagnostic value, advantages, and limitations of ultrasound, CT, spectral CT, MRI, and PET-CT in the evaluation of thyroid nodules and thyroid cancer. Future advances should focus on standardized multimodal imaging strategies, quantitative functional imaging, radiomics, and carefully validated artificial intelligence-assisted approaches to improve individualized diagnosis and management of thyroid nodules and thyroid cancer.

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.

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.

The immunosuppressive tumor microenvironment (TME) limits immunotherapy efficacy in intrahepatic cholangiocarcinoma (ICC). Understanding the molecular drivers of this TME is essential for developing new therapies. This study aimed to identify novel oncogenes that modulate the immune landscape of ICC using a multi-omics approach.

We integrated transcriptomic and proteomic data from our ICC cohorts with public datasets (TCGA-CHOL, GSE107943, OEP002768) to identify genes co-upregulated with PD-L1 (CD274). Single-cell RNA sequencing (scRNA-seq) was used to analyze cell-type-specific expression and intercellular communication. Clinical significance was validated through tissue microarrays and multiplex immunofluorescence in an independent ICC cohort.

Multi-omics screening identified TACC3 as a key candidate in ICC. Elevated TACC3 expression in ICC tissues correlated with poor prognosis and promoted tumor cell proliferation and migration. TACC3 activated the STAT3 pathway, increasing PD-L1 transcription. scRNA-seq showed TACC3/PD-L1 interaction in malignant epithelial cells, with PD-L1 co-expressed with FOXP3 in regulatory T cells (Tregs). Cell–cell communication analysis predicted strong interactions between malignant cells and Tregs. TACC3 knockdown reduced PD-L1 expression and inhibited STAT3 and AKT phosphorylation. Clinical validation confirmed co-expression of TACC3, PD-L1, and FOXP3, with high TACC3 levels linked to worse clinicopathological features and shorter progression-free survival.

Our study defines a TACC3-STAT3-PD-L1 axis driving immunosuppression in ICC. TACC3 fosters an immunosuppressive TME by upregulating PD-L1 and is associated with a Treg-rich contexture, suggesting that TACC3 may serve as a potential therapeutic target to overcome ICC immunosuppression.