Chimeric antigen receptor–natural killer (CAR-NK) cell therapy holds significant promise for cancer immunotherapy due to its efficient recognition and lysis of malignant cells. Despite the potential of CAR-NK therapy as a safer and more effective immunotherapeutic strategy, researchers are actively focusing on addressing its limitations. These include enhancing persistence, optimizing genetic engineering methods, and standardizing the production process for wider clinical applicability. The development of novel generations of CAR-NK cells, combined with a deeper understanding of their behavior in solid tumors, could potentially revolutionize cancer cell therapy and improve patient outcomes in the near future. However, to improve clinical outcomes and facilitate the broader application of CAR-NK cell therapies, we must address challenges related to the optimization of CAR constructs, in vivo persistence, tumor penetration, safety, and regulatory considerations. Overall, the article presents an extensive review of the challenges and potential
strategies for improving the long-term antitumor efficacy of CAR-NK cell therapy, emphasizing the importance of combination therapies, drug delivery methods, and immune checkpoint blockade in enhancing the effectiveness of NK cell–based immunotherapy. The paper provides valuable insights into the intricate mechanisms and potential future applications of these strategies in cancer immunotherapy.

MicroRNAs (miRs) are key post-transcriptional regulators of gene expression and have emerged as important modulators of host responses during viral infections, including coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Growing evidence indicates that miR-370 and miR-493 participate in pathways relevant to COVID-19 pathophysiology, influencing inflammatory signaling, immune cell activity, and cellular processes that may shape viral replication and tissue injury. miR-370 has been linked to the suppression of proinflammatory cytokine production, modulation of lipid- and fibrosis-related pathways, and attenuation of lung inflammatory responses, suggesting a potential protective role during acute infection. miR-493 has been associated with regulation of apoptosis, immune activation, and stress-response pathways, with alterations in its expression correlating with disease severity in several inflammatory conditions. Because interactions between host miRs and viral or host mRNAs can influence viral entry, replication, and immune dysregulation, understanding the specific mechanisms through which miR-370 and miR-493 act is essential for clarifying their relevance in COVID-19. This review synthesizes current evidence on the molecular pathways, validated targets, and potential regulatory roles of miR-370 and miR-493 in SARS-CoV-2 infection, highlighting their promise as biomarkers and their possible utility in improving diagnostic and therapeutic strategies for COVID-19.

Evidence indicates that Long COVID is associated with menstrual cycle disruptions, hormonal changes, immune dysfunction, and persistent inflammation. Owing to these overlapping inflammatory mechanisms, Long COVID may aggravate endometriosis, potentially worsening pelvic pain and increasing the risk of developing the disease. We searched Scopus, PubMed, Google Scholar, and Science Direct for English-language articles from 2000 to 2024. After screening titles and abstracts, the authors assessed the full texts of potentially relevant studies. Studies were included if they provided robust, impactful data pertinent to the topic. Direct clinical evidence indicates that women with endometriosis report worsening of pelvic pain, dysmenorrhea, and fatigue after COVID-19, and that Long COVID causes menstrual cycle irregularities and chronic inflammation. Extrapolation of separate studies in Long COVID and endometriosis, several hypothesized mechanisms may contribute to symptom exacerbation: elevated C-X-C motif chemokine ligand 5 (CXCL5) and vascular endothelial growth factor (VEGF) may promote ectopic endometrial tissue growth and angiogenesis; neutrophil extracellular trap (NET) formation and extracellular matrix (ECM) alterations could further endometriosis progression; stress-related hormonal fluctuations may enlarge lesions; and altered pain perception and fatigue may limit beneficial physical activity. The long-term effects of COVID-19 could exacerbate the severity of endometriosis through several mechanisms.

Ataxia Telangiectasia (AT) is a rare autosomal recessive disease with features of progressive cerebellar atrophy, immunodeficiency, and enhanced cancer susceptibility due to mutations in the ataxia telangiectasia mutated (ATM) gene. However, despite evidence from patients with AT in consanguineous Iranian families, limited information is still available on the genotype-phenotype association. This paper presents a familial case series of AT in Yazd, Iran, with a novel homozygous ATM mutation.
This report examines a consanguine family in Yazd, Iran, with four members presenting with symptoms characteristic of AT, including progressive neurological decline, cerebellar atrophy, immunodeficiency, elevated alpha-fetoprotein, and recurrent infections.
Genetic analysis confirmed a novel homozygous mutation of the ATM gene (c.1834C>A; p.Leu612Ile), which is a non-conservative substitution. It is predicted to result in loss of function, and parents were carriers of the mutation. Treatment included intravenous immunoglobulin, prophylactic antibiotics, and supportive care. One of the patients died due to severe infection despite intervention.
This case series highlights the impact of consanguinity on the occurrence of AT and the supporting role of genetic testing in diagnosing ATM mutations. The results emphasize the need for improved genetic counseling, family planning, early immunological therapy, and culturally tailored public health strategies to effectively manage AT in consanguineous populations.

Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) plays a pivotal role in tumor immune evasion. The efficacy of these treatments is limited by variable patient responses and adverse effects. It is necessary for a deeper understanding of the underlying biological mechanisms.
This study used a 2-step Mendelian randomization (MR) approach to investigate causal relationships among gut microbiota, lipid and amino acid metabolic traits, and PD-1/PD-L1. The summary statistics for 412 traits of the gut microbiome (N=7738), 249 traits of serum metabolites (N=115 078), and 2 traits of PD-1/PD-L1 (N=3301) were derived from publicly genome-wide association studies. The primary method employed for MR was inverse-variance weighted regression. We conducted a series of sensitivity analyses to evaluate the reliability of the causal estimates. Subsequently, mediation analysis was undertaken to elucidate the pathway from gut microbiome to PD-L1, mediated by serum metabolic markers.
Our analyses identified 28 gut microbial traits significantly affecting PD-L1 and 14 affecting PD-1, 8 of which remained consistently linked to PD-L1 after sensitivity analysis. Furthermore, 13 serum lipid and amino acid metabolic traits exhibited significant causal effects on PD-L1, with 6 remaining robust post analysis. Notably, Bacteroides dorei demonstrated a causal effect on PD-L1, mediated 9.6% by the metabolic biomarker phenylalanine.
These findings highlight the intricate interplay among gut microbiome, metabolic biomarkers, and immune regulation. They suggest novel therapeutic targets for cancer treatment that emphasize the value of microbiome and metabolic biomarkers in improving immunotherapy outcomes and promoting personalized medicine.

Sepsis is a life-threatening systemic inflammatory response syndrome marked by high mortality and immune dysfunction. Histamine, synthesized from histidine, by histidine decarboxylase (HDC), regulates immune cell recruitment and inflammatory mediators, playing a key role in inflammatory diseases. The precise mechanisms and clinical significance of histamine in sepsis require further study.
Gene expression data from the Gene Expression Omnibus (GEO) database were analyzed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify differentially expressed histamine-related genes (DEHRGs). Machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF), were utilized to screen diagnostic genes, and a predictive model was constructed and validated using receiver operating characteristic analysis and decision curve analysis (DCA). Functional enrichment, immune infiltration assessment, using single-sample gene set enrichment analysis (ssGSEA), cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), regulatory network construction, and drug prediction were subsequently conducted.
Nine DEHRGs were identified. Three key diagnostic genes-FYN, IL2RB, and MMP8-were selected and validated across multiple cohorts, showing high diagnostic accuracy (area under the curve [AUC]>0.85). The study revealed distinct immune patterns, including increased regulatory T cell (Treg) infiltration in the sepsis group. Two sepsis molecular subtypes with differential immune characteristics were also identified.
This study systematically explored the association between histamine and sepsis pathogenesis, defining a three-gene diagnostic model and elucidating complex immune and molecular regulatory mechanisms. These findings offer new insights for developing targeted diagnostic and therapeutic strategies for sepsis.

Bronchiectasis is a chronic respiratory condition characterized by persistent airway inflammation and recurrent infections, yet its underlying pathogenesis remains incompletely understood. This study aimed to investigate the roles of the lower respiratory tract microbiome and serum cytokine/chemokine profiles in the pathogenesis of bronchiectasis.
In this retrospective study, we enrolled 285 bronchiectasis patients admitted to our hospital between January 2024 and June 2025. Participants were categorized into an acute exacerbation group (n=158) and a clinically stable group (n=127). We compared the two groups in terms of respiratory pathogens, immune function indicators (CD3+, CD4+, CD8+, CD4+/CD8+ ratio, white blood cell count, and neutrophil count), pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-17A), anti-inflammatory cytokines (interleukin-10 and interleukin-4), acute-phase reactants (C-reactive protein, procalcitonin, and serum amyloid A), and chemokines (monocyte chemoattractant protein-1). The involvement of these factors in disease pathogenesis was analyzed.
Significant differences were observed between the groups in the rates of hypoalbuminemia, the presence of dyspnea and hemoptysis, and the oxygenation index in arterial blood gas analysis. Sputum cultures were positive in 103 (65.19%) patients in the acute exacerbation group, compared to 58 (45.67%) in the stable group. Immune markers CD3+, CD4+, CD8+, and the CD4+/CD8+ ratio were lower during acute exacerbation, while WBC and NEUT levels were elevated. Pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, and interleukin-17A) and acute-phase reactants (C-reactive protein, procalcitonin, and serum amyloid A) were significantly higher during exacerbation, whereas anti-inflammatory cytokines (interleukin-10 and interleukin-4) were lower. Monocyte chemoattractant protein-1 levels were also elevated during exacerbation.
Dysbiosis of the lower respiratory tract microbiome, immune dysfunction, and exacerbated inflammatory responses are interrelated and collectively contribute to the pathogenesis of bronchiectasis.

High risk human papillomavirus (HR-HPV) induced cervical intraepithelial neoplasia grade 1 (CIN1) is a low-grade lesion closely associated with persistent viral infection, and clinical management remains challenging. This study aimed to investigate clinical efficacy and immune response of recombinant human interferon α2b vaginal effervescent tablets in CIN1 caused by HR-HPV.
In a retrospective study, 60 patients with HR-HPV and diagnosed with CIN1 from Shandong Provincial Hospital between December 2023 and December 2024 were divided into CT (n=30) and CR (n=30) groups, both groups were treated with conventional therapy, and recombinant human interferon α2b vaginal effervescent tablets were added to the CR group. The main assessment of both groups were inflammatory factor indicators, immune indicators, vaginal microenvironmental factors [hydrogen peroxide (H2O2) positivity, sialidase (SNA) positivity, leukocyte esterase (LE) positivity, N-acetylaminogalactosidase (NAG) positivity], HR-HPV conversion rate and clinical efficacy. Secondary outcomes included life quality scores, complication and adverse effect rates.
After treatment, the indicators of both groups were significantly different from the pre-treatment. The changes in inflammatory indicators, immune indicators, SNA positivity rate, LE positivity rate, HR-HPV conversion rate, clinical efficacy, life quality, complications, and adverse reactions in the CR group were better than those in the CT group. No marked discrepancy was found in the comparison of H2O2 positivity rate and NAG positivity rate between both groups.
Recombinant human interferon α2b vaginal effervescent tablets have significant therapeutic effects, as they alleviate inflammatory reactions, regulate immune indicators, and are worthy of clinical application and promotion.

Sepsis is a life-threatening condition characterized by a dysregulated immune response leading to organ failure. This study examines the immunomodulatory effects of the M13 bacteriophage in a cecal ligation and puncture (CLP) mouse model of sepsis, comparing intravenous and intraperitoneal delivery routes. Key outcomes included cytokine responses, bacterial burden, organ injury, and survival.
Sepsis was induced using the CLP model. M13 phages were verified by transmission electron microscopy and administered via IV or IP injection. Blood samples were collected at 24 hours, 72 hours, and day 5 for white blood cell, cytokine, and liver enzyme analysis. Bacterial burden was assessed by colony counts, liver injury by hematoxylin and eosin histology, and survival was monitored for 14 days.
CLP induction caused marked increases in WBC counts, cytokines, C-reactive protein (CRP), bacterial load, and liver damage. Following phage treatment, inflammatory markers, bacterial burden, and tissue injury declined substantially. IV administration more effectively reduced systemic inflammation, whereas IP administration provided stronger protection of liver and kidney function and resulted in higher survival rates.
M13 phage therapy demonstrates promising immunomodulatory and organ-protective effects in septic mice. The superior organ protection and survival benefits observed with IP delivery suggest potential translational value for targeted phage administration in sepsis management. Future studies should explore dose optimization, combination therapy, and mechanistic pathways to support clinical development.

The airflow limitation is one of the characteristics of chronic obstructive pulmonary disease (COPD), which is not entirely reversible. It seems that factors such as inflammation, hypoxia, and remodeling of pulmonary vessels can increase pulmonary hypertension (PH). This increase in pulmonary arterial hypertension leads to aggravation of disease complications.
Considering the role of immune cells in causing pathological inflammation in the pathogenesis of COPD, it seems that Th17/Treg axis imbalance can be one of the main reasons for the difference in life expectancy in patients with COPD with and without PH.
By measuring and comparing some inflammatory biomarkers in patients with COPD with and without PH, this study tries to introduce these biomarkers to predict the occurrence or nonoccurrence of this complication. This study aims to compare the ratio and activity of Th17 to Treg in patients with COPD with high (20 patients) and normal (20 patients) pulmonary arterial pressure. Five milliliters of blood containing anticoagulant were obtained to isolate peripheral blood mononuclear cells (PBMCs). Then, the ratio of Th17 to Treg, their number, and their activity were evaluated by ELISA, real-time polymerase chain reaction (PCR), and flow cytometry.
Our results show that the amount of inflammatory factors and the population of Th17 cells in patients with COPD with PH is associated with a significant increase in PH compared to patients with COPD without PH, which leads to damage caused by pathological inflammation to the lung tissue and a decrease in the overall survival of the patients.

Allergic rhinitis (AR) is a common inflammatory condition characterized by symptoms such as nasal congestion, rhinorrhea, sneezing, and nasal itching, which significantly impact quality of life. Management includes allergen avoidance, pharmacological therapy, and, in severe cases, immunotherapy. Ipratropium bromide, an anticholinergic agent, is primarily used for managing rhinorrhea by inhibiting acetylcholine-mediated secretion in the nasal mucosa.
To evaluate the effects and side effects of ipratropium bromide nasal spray in combination with low-dose budesonide in patients with allergic rhinitis, a double-blind, randomized, placebo-controlled trial was conducted with 126 patients diagnosed with AR. Participants were randomly assigned to receive one of three treatments: Ipranasal 42 μg + budesonide, Ipranasal 21 μg + budesonide, or placebo + budesonide, over a two-week period. Symptom severity was assessed using the ARIA questionnaire and visual analog scale (VAS) for nasal symptoms at baseline and two weeks after the intervention.
Significant reductions in rhinorrhea were observed in the Ipranasal groups compared to the placebo group. Mild side effects, including nasal and oral dryness, were transient and non-significant. There were no major differences between the 42 μg and 21 μg groups in terms of efficacy or side effects.
Ipratropium bromide nasal spray effectively reduces rhinorrhea in AR patients, with good tolerability. However, it also had moderate effects on nasal congestion. Combination therapy may enhance symptom control, but further studies are needed to assess long-term efficacy and safety.

Cervical cancer is the fourth most prevalent malignancy among women globally. Zinc oxide nanoparticles (ZnO-NPs) possess significant potential in cancer therapy due to their unique physicochemical properties, biocompatibility, and apoptosis-inducing abilities. While ZnO-NPs have been examined in HeLa cells and peripheral blood mononuclear cells (PBMCs) individually, their immunological and angiogenesis-related effects in immune-tumor co-culture systems was insufficiently investigated. This study assessed the apoptotic, anti-angiogenic, and cytokine-modulating effects of ZnO-NPs in a HeLa/PBMC co-culture model.
HeLa cells were co-cultured with PBMCs and treated with ZnO-NPs under different groups. Cytotoxicity was evaluated using MTT assay, apoptosis was analyzed by flow cytometry, and gene expression levels were measured using real-time PCR.
ZnO-NPs significantly reduced HeLa cells viability with a half maximal inhibitory concentration (IC₅₀) of 7 µg/mL, while PBMCs showed more resistance (IC₅₀=40 µg/mL). In the HeLa/PBMC/ZnO co-culture group, gene expression analysis in PBMCs revealed significant upregulation of IL1B, TNF, IFNG, and TGFB1 compared with the HeLa/PBMC group, while IL2 and IL4 expression levels showed no significant changes. VEGFA expression in HeLa cells was reduced in all treated groups, with the greatest decrease in the HeLa/PBMC/ZnO group. Co-culture with PBMCs and ZnO-NP treatment significantly promoted apoptosis in HeLa cells.
In conclusion, ZnO-NPs induce cytotoxic and anti-angiogenic effects on HeLa cells, particularly within a PBMC co-culture setting, highlighting the contribution of immune–tumor interactions to ZnO-NP–mediated anti-cancer responses; however, more investigations at the protein and functional levels are necessary to validate these effects.

Colon cancer, a leading cause of death, demands early detection. We evaluate serum S100 calcium-binding protein A12 (S100A12) and diamine oxidase (DAO) effects on gut dysbiosis/immunity and their combined diagnostic value.
This retrospective study included 105 colon cancer patients (study group), 90 benign lesions, and 105 matched healthy controls. Serum S100A12 and DAO were measured by ELISA (enzyme-linked immunosorbent assay). Gut flora (Escherichia coli, Enterococcus faecalis, Bifidobacterium, Lactobacillus) were cultured; T cell subsets (CD4⁺, CD8⁺, Treg) by flow cytometry. Patients were stratified by median levels into high/low groups. Correlations and diagnostic efficacy were assessed using Pearson test and ROC (receiver operating characteristic) analysis.
Baseline data were comparable among three groups. Fecal flora (E. coli, E. faecalis, Bifidobacterium, Lactobacillus) and T cells (CD4⁺, CD8⁺, regulatory T cells) differed significantly. Serum S100A12 and DAO were elevated in colon cancer versus benign/control groups. High/low subgroups showed disparities in flora and T cells. S100A12 and DAO positively correlated with E. coli/E. faecalis, CD8⁺ T, and Treg, but negatively with Bifidobacterium, Lactobacillus, and CD4⁺ T. The cancer group had reduced CD4⁺ and CD4⁺/CD8⁺ ratio, and elevated CD8⁺ and Treg. Combined S100A12+DAO detection outperformed single markers.
Elevated serum S100A12 and DAO in colon cancer are associated with gut microbiota dysbiosis and immune dysregulation. Their combination shows promise as a potential biomarker for early diagnosis and disease evaluation.

While immune checkpoint inhibitors (ICIs) are a key treatment for advanced gastric cancer (AGC), the prognostic significance of their associated immune-related adverse events (irAEs) remains unclear. This real-world study aims to evaluate irAE incidence and impact on clinical outcomes.
This retrospective study consecutively enrolled 156 patients with AGC who received ICI therapy and completed follow-up between January 2021 and June 2023. Baseline characteristics, treatment regimens, irAE occurrence, and survival data were collected. The prognostic impact of irAEs was assessed by objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
A total of 156 patients were included, of whom 76 (48.72%) developed irAEs. The most  common types were endocrine, cutaneous, and gastrointestinal toxicities, mostly of grades 1-2. Multivariate logistic regression analysis identified age≥70 years (OR=2.615), BMI ≥ 25 kg/m² (OR=5.791), prior chemotherapy (OR=4.954), prior targeted therapy (OR=5.532), ICI combined with chemotherapy (OR=5.456), ICI combined with targeted therapy (OR=2.850), and a history of smoking (OR=3.224) as independent predictors of irAEs. Compared with the non-irAEs group, the irAEs group showed superior clinical efficacy, with a significantly higher ORR (38.16% vs. 20.00%) and DCR (80.26% vs. 66.25%). Kaplan-Meier survival analysis revealed a significant association between the occurrence of irAEs and prolonged survival, with the irAEs group showing superior median PFS (8.0 vs. 5.0 months) and OS (15.0 vs. 10.0 months) compared to the non-irAEs group.
For AGC patients receiving ICI therapy, the development of irAEs correlates significantly with improved survival, serving as a potential biomarker of clinical benefit.

Rheumatoid arthritis (RA) is an autoimmune disease marked by chronic inflammation and progressive joint damage. Early diagnosis is crucial, but current methods lack sensitivity. Circulating microRNAs (miRs), stable in body fluids, have emerged as promising biomarkers. This study aims to evaluate the plasma expression levels of miR-22-3p, miR-126-3p, and miR-760 in patients with RA compared to healthy controls, and to assess their potential as diagnostic biomarkers.
Plasma samples from 50 RA patients and 50 healthy individuals were analyzed using quantitative real-time PCR (qRT-PCR). Correlation of miR expression with disease activity was evaluated, and their diagnostic value was assessed using receiver operating characteristic (ROC) curve analysis. Bioinformatics analysis was conducted to explore the various aspects and functions of the identified miRs. 
The plasma levels of miR-22-3p and miR-126-3p were significantly elevated in RA patients compared to healthy controls. Although miR-760 exhibited an upward trend, the increase did not reach statistical significance. miR-126-3p was positively associated with disease activity. ROC analysis showed area under the curve (AUC) of 0.69 for miR-22-3p, 0.72 for miR-126-3p, and 0.61 for miR-760, with the combined panel improving diagnostic accuracy to an AUC of 0.74. Furthermore, functional enrichment analysis suggested that these miRs are predominantly involved in key biological processes, including regulation of gene expression, cell migration, and epigenetic modifications.
A panel consisting of miR-22-3p, miR-126-3p, and miR-760 may serve as a potential diagnostic biomarker for RA. Further validation in larger and more diverse populations is warranted.

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miR-155-5p is a well-established oncomiR upregulated in a variety of human malignancies, including breast cancer, where its aberrant expression has been documented in both tumor tissue and serum. Given its role as a key modulator of immune-inflammatory pathways and regulatory T cell (Treg) expansion, we aimed to investigate its expression in the peripheral blood mononuclear cells (PBMCs) of breast cancer patients.
This study enrolled sixty (n=60) breast cancer patients and forty (n=40) age-matched healthy controls. The relative expression of miR-155-5p in PBMCs was quantified using qPCR, and Treg cell frequency (defined as CD4⁺CD25⁺Foxp3⁺) was assessed by flow cytometry. 
The expression of miR-155 was significantly increased in PBMCs of breast cancer patients compared with that of the control group, especially in patients with high tumor grade. The number of Treg cells was also increased in PBMCs of patients than in the healthy group, however, no significant correlation was found between the expression levels of miR-155 and Treg cell count (r=-0.16). 
Our findings demonstrate a significant up-regulation of miR-155-5p and a concomitant increase in Treg frequency in breast cancer patients, suggesting its potential role in shaping an immunosuppressive microenvironment. Consequently, miR-155-5p emerges as a promising non-invasive prognostic biomarker, warranting further validation in larger studies.

Antibody-mediated rejection (ABMR) remains a major cause of kidney graft dysfunction despite advances in immunosuppression. Recent evidence suggests that metabolic reprogramming, particularly de novo lipogenesis, may contribute to chronic allograft injury. This study aimed to identify gene signatures associated with lipid metabolism that are linked to chronic active ABMR in renal transplant recipients.
Publicly available microarray datasets and clinical metadata were integrated for 100 biopsy specimens (55 ABMR and 45 controls). After normalization and batch correction, supervised machine-learning models—Random Forest, Support Vector Machine, and Convolutional Neural Network (CNN)—were trained to distinguish ABMR from control samples. Differentially expressed genes related to lipid metabolism pathways were identified and correlated with histopathologic and serologic parameters according to Banff diagnostic criteria.
The CNN model achieved an accuracy of 88% and an AUC-ROC of 0.92, outperforming SVM and RF classifiers. Identified lipid metabolism-related gene signatures showed significant associations with markers of immune activation and graft injury, implicating de novo lipogenesis in the pathogenesis of chronic active ABMR. Functional enrichment analyses further supported dysregulation of fatty-acid biosynthesis pathways.
Integrating transcriptomic profiling with artificial intelligence modeling uncovered lipid- related molecular patterns discriminating chronic active ABMR from stable grafts. These findings provide potential biomarkers and mechanistic insight into metabolic dysregulation underlying antibody-mediated graft injury, offering a foundation for future translational validation.

Diabetic peripheral neuropathy (DPN) is a disabling complication of type 2 diabetes, associated with neuropathic pain and reduced quality of life (QoL). Inflammation is implicated in DPN pathogenesis. We investigated associations between inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), and QoL in DPN patients in Eastern Iran.
One hundred seventeen type 2 diabetic patients from two from two Zabol hospitals/clinics were enrolled. QoL was assessed using WHOQOL-BREF questionnaire, and neuropathy was evaluated using Michigan neuropathy screening instrument (MNSI). Serum CRP and IL-6 levels were measured. Analyses included t-tests, analysis of variance, and linear regression in SPSS.
The prevalence of DPN among patients was 56.4%. Patients with DPN exhibited higher levels of CRP (mean: 4.2±1.8 mg/L) and IL-6 (mean: 5.6±2.1 pg/mL) compared with the non-neuropathic group. Additionally, QoL, particularly in the physical domain, was significantly lower in patients with higher levels of these inflammatory markers. However, multiple linear regression analysis after adjusting for confounding variables (including age, sex, BMI, diabetes duration, and HbA1c) revealed that neither CRP, IL-6, nor BMI were independently associated with QoL in the final model.
The overall regression model was not statistically significant, indicating that the measured variables collectively explained only a small fraction of QoL variance. In univariate analysis, elevated CRP and IL-6 correlated with poorer QoL in neuropathic patients, but these associations did not remain significant after adjusting for confounders. Our findings highlight the need for further research incorporating unmeasured factors, such as pain severity, depression, and medication use, to better understand determinants of QoL in this population.

Allergy-related diseases, driven by type I hypersensitivity reactions, affect over 20% to 25% of the global population and continue to rise. Pollen grains may have allergens that cause hypersensitivity reactions. Pla or 3, Fra e 1, and Bet v 1 are major allergens of pollen grains from the common allergenic trees Platanus orientalis, Fraxinus excelsior, and Betula pendula, respectively, and are employed in this study to design a multi-epitope allergy vaccine using immunoinformatics methods.
The steps after finding the main allergenic epitopes include sequences retrieval, T-cell epitopes selection by IEDB and NetMHCIIpan, B-cell epitopes selection by IEDB, addition of linkers and adjuvant, and construction of multi-epitope vaccine, evaluating antigenicity, allergenicity, and toxicity of vaccine construct, secondary structure prediction, 3-dimensional structure modeling and refinement by GalaxyTBM, validation of the model by ProSA-web, ERRAT, and PROCHECK, and exploring the interaction of the designed molecule with receptor by ClusPro.
The designed vaccine demonstrated favorable properties, including high antigenicity, lack of allergenicity and toxicity, and stable secondary and tertiary structures.
These results suggest that this vaccine has the potential to mitigate allergic responses effectively. However, experimental validation is required to confirm its efficacy and safety.

Gastric cancer is a significant global health issue characterized by a high mortality rate. Recent studies highlight the potential of plant-derived compounds in targeting molecular pathways involved in cancer. This study aimed to evaluate the apoptotic and anticancer effects of Alcea glabrata methanolic extract on gastric cancer cells, focusing on the modulation of HER2, HSP90α, P53, and Caspase-3 gene expression.
The methanolic extract was prepared from the aerial parts of Alcea glabrata. Its antioxidant activity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Human gastric adenocarcinoma (AGS) and human gum fibroblast (HUGU) cell lines were treated with different concentrations of the extract. Cell viability was determined using the MTT assay, and IC₅₀ values were calculated. Apoptosis was analyzed by flow cytometry, and real-time PCR was used to quantify the expression levels of HER2, HSP90α, P53, and Caspase-3.
The extract exhibited potent antioxidant activity, as demonstrated by the DPPH assay. It reduced cell viability in both AGS and HUGU cell lines, with a lower IC₅₀ in AGS cells, indicating selective toxicity toward cancer cells. Flow cytometry revealed a significant increase in apoptosis in AGS cells. Additionally, gene expression analysis showed upregulation of P53 and Caspase-3, and downregulation of HER2 in AGS cells. Changes were less marked in HUGU cells. The extract also demonstrated vigorous antioxidant activity.
Alcea glabrata extract exhibited selective anticancer effects on AGS cells by inducing apoptosis and modulating gene expression. Its antioxidant properties and downregulation of HER2 suggest its potential as a complementary treatment agent for gastric cancer.

Rheumatoid arthritis (RA) involves aberrant JAK-STAT signaling. Adalimumab suppresses inflammation but offers limited immune reconstitution.
This retrospective study compared iguratimod+adalimumab versus adalimumab monotherapy in restoring immune function in RA patients.
A total of 112 RA patients treated between March 2022 and March 2025 were included and divided into a control group (adalimumab) and a study group (iguratimod + adalimumab). Clinical data of patients were collected before and after 24 weeks of treatment, including laboratory indicators [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP); T-lymphocyte subpopulations (CD4+, CD8+, CD4+ /CD8+ ratio)]; phosphorylated signal transducer and activator of transcription 3 (P-STAT3) levels; bone metabolism indicators osteocalcin N-terminal intermediate molecule (N-MID), total type I collagen amino-terminal prolongation peptide (T-P1NP), β-cross-linked C-telopeptide of type I collagen (β‑CTX); pain assessment; American College of Rheumatology 50% improvement criteria (ACR50) response rate; Fugl-Meyer Motor Function Assessment Scale (FMAS) score of upper and lower limbs; and incidence of adverse reactions. After treatment, serum TNF-α, IL-6, CRP levels, CD8+ T lymphocytes, β‑CTX, P-STAT3 levels, and pain assessment of patients in both groups were lower than those before treatment, and the study group was significantly lower; CD4+ T lymphocytes in the 2 groups, CD4+ /CD8+ ratio, N-MID, T-P1NP, limb function score upper and lower limb FMAS score, and ACR50 response rate after treatment were markedly higher in the study group.
In conclusion, iguratimod combined with adalimumab synergistically inhibits the JAK-STAT pathway, significantly improving immune reconstitution and inflammation control in RA, with superior efficacy to adalimumab alone.

This study aimed to characterize serum immune-inflammatory biomarkers in primary aldosteronism (PA) and to evaluate their correlations and independent associations with target organ damage (TOD) using a propensity score–matched cohort design.
This retrospective propensity score–matched (PSM) cohort study included 80 patients initially diagnosed with PA (PA group) and 80 matched patients with essential hypertension (EH group) between February 2021 and February 2025. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein 1 (MCP-1) were measured. TOD assessment included left ventricular mass index (LVMI), carotid intima-media thickness (IMT), and renal parameters (urinary albumin to creatinine ratio [UACR] and estimated glomerular filtration rate [eGFR]). Group comparisons, correlation analyses, and multivariate logistic regression were performed.
After matching, baseline characteristics were balanced. The PA group had significantly higher levels of all four biomarkers and a higher prevalence of cardiac, vascular, and renal damage. Sensitivity analyses confirmed consistent associations across all organ systems. Elevated IL-6 and CRP strongly correlated with TOD indicators and were independently associated with composite TOD in multivariate analysis (IL-6: OR=1.86; CRP: OR=1.52).
PA is associated with a distinct immune-inflammatory phenotype. IL-6 and CRP are independently associated with multi-system TOD and may serve as practical biomarkers for early risk stratification and timely intervention.

Cow’s milk protein allergy is the most common type of food allergy in the first year of life, in which the child’s dairy consumption should be limited, and it can have a significant impact on dental health. This study aimed to assess the frequency of dental caries in children with cow’s milk protein allergy and t to examine he relationship between this outcome and cow’s milk protein allergy.
In this matched case-control study, 51 children aged 2 to 6 years with cow’s milk protein allergy, and 51 healthy children were studied in 2 groups. A questionnaire regarding general information, socioeconomic status, health conditions, habits, nutritional information, dental history, and oral hygiene was completed for all children by asking their parents. Dental examinations were also performed, and the decayed, missing, and filled teeth (dmft) index was calculated. The Wilcoxon signed-rank and McNemar tests were used for statistical analyses, at a significance level of 0.05.
The mean dmft score was 5.74±5.55 in children with cow’s milk protein allergy and 1.92±2.55 in the control group. A significant relationship existed between cow’s milk protein allergy and increased frequency of dental caries. Also, the number of caries-free children was significantly lower in the group with cow’s milk allergy.
Given the significant impact of dairy consumption in the early years of life on dental health, it seems necessary to implement more serious caries prevention measures, such as fluoride therapy and follow-up sessions, in children with cow’s milk protein allergy.

Effective biomarkers are urgently needed to guide chemoimmunotherapy in advanced gastric cancer (AGC) and improve clinical outcomes. This study aimed to explore a blood-based immune score for predicting outcomes in patients with AGC receiving chemoimmunotherapy.
In this retrospective analysis, patients with AGC receiving chemoimmunotherapy were included. Treatment response was assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Peripheral blood immune-inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and C-reactive protein-to-albumin ratio (CAR), and immune cell subsets, including CD4⁺, CD8⁺, and natural killer (NK) cells, were measured pre- and post-treatment. Receiver operating characteristic (ROC) analysis determined optimal cutoffs. Logistic regression identified independent predictors of objective response rate (ORR), and a combined immune-inflammatory score was constructed. Progression-free survival (PFS) was estimated using the Kaplan–Meier method, with risk stratification based on the score. Bootstrap resampling was used for internal validation.
Among 100 patients, the ORR was 46.0%. Multivariate analysis confirmed NLR ≤ 2.5 (adjusted odds ratio [aOR]=0.333), CD8⁺ T cells≥30% (aOR=3.439), and SII ≤ 600 (aOR=0.386) as independent predictors of ORR. The combined score (range 0–3) achieved an area under the curve (AUC) of 0.874 for ORR prediction. During a median follow-up of 15.3 months, patients with a score≥2 (favorable immune profile group) had significantly longer PFS than those with a score≤1 (unfavorable immune profile group) (median PFS: 15.6 vs 7.8 months). Bootstrap internal validation confirmed the stability of the score (concordance index [C-index]=0.814).
The NLR/SII/CD8⁺ T-cell score was associated with treatment response and survival among patients with AGC receiving chemoimmunotherapy, suggesting that it is a hypothesis-generating tool requiring external validation and is not ready for clinical use.

Immune thrombocytopenia (ITP), the commonest pediatric acquired bleeding disorder, involves immune dysregulation; assessing C3/C4, Ig(G/A/M), and lymphocyte subsets has diagnostic value.
A retrospective study enrolled 40 children with ITP (0–18 years, meeting pediatric ITP criteria) admitted to our hospital (January 2023 to March 2025) as the ITP group, and 40 healthy children as controls. Serum IgG, IgA, IgM, C3, C4, lymphocyte subsets (CD3⁺, CD4⁺, and CD8⁺ T cells, CD19⁺ B cells, and CD16⁺CD56⁺ NK cells), autoimmune antibodies, TORCH, EBV, and CMV status were detected. Pearson correlation and receiver operating characteristic curves analyzed correlations and diagnostic efficacy of single/combined indicators, and multivariate logistic regression was used for statistical analysis.
Baseline data were balanced. Compared with controls, ITP patients had higher IgG, lower IgM, C3 and C4, similar IgA; lower CD3⁺ and CD4⁺ percentages and CD4⁺:CD8⁺ ratio, higher CD8⁺ cells, similar CD16⁺/CD56⁺ and CD19⁺; and higher epstein-barr virus/cytomegalovirus and autoantibody positivity. Pearson analysis showed reduced CD4⁺, CD3⁺, C3, C4 and elevated CD8⁺, IgG correlated with lower platelet count. ROC of combined CD4⁺, CD8⁺, C3, C4, IgG gave AUC 0.967, sensitivity 92.5%, specificity 90.0%, outperforming single indices.
Children with ITP have abnormal immunoglobulins, inadequate complement activation, and imbalanced lymphocyte subsets; combined detection of these aids ITP diagnosis and provides clinical basis.

Minimally invasive lung surgery still triggers significant inflammatory and immunosuppressive responses. This retrospective cohort study (January 2021–December 2023) assessed whether erector spinae plane block (ESPB) improves perioperative immune/cytokine balance in lung cancer patients undergoing elective minimally invasive surgery (ESPB, n=58; control, n=65).
Compared with controls, the ESPB group demonstrated superior perioperative outcomes. Hemodynamics at incision were more stable (MAP: 103.24±9.85 vs 112.40±11.23 mm Hg, HR: 86.17±7.91 vs 94.74±9.05 beats/min), and opioid consumption was significantly lower (intraoperative sufentanil: 33.12±3.93 vs 36.75±5.08 μg). Postoperative pain scores were reduced (resting VAS at 1 hour: median 2 vs 4), comfort scores higher (BCS at 1 hour: median 2 vs 1), and patient-controlled analgesia use less frequent (total PCA demands at 48 hours: 18.55±5.14 vs 23.45±5.97).
Immunologically, the ESPB group showed significantly attenuated suppression of cellular immunity, with higher CD3+ (60.92±4.74% vs 56.53±3.27% at 48 hours), CD4+ (38.16±4.29% vs 34.18±4.06% at 48 hours), CD4+/CD8+ ratio (1.23±0.17 vs 1.02±0.23 at 48 hours), and NK cells (21.03±3.45% vs 18.27±2.78% at 48 hours). The cytokine response was also modulated favorably: the rise in proinflammatory IL-6 (26.82±4.65 vs 32.55±5.21 pg/mL at 24 hours) and TNF-α (54.86±7.12 vs 61.55±6.01 pg/mL at 24 hours) was lower, while the anti-inflammatory IL-10 was higher in the ESPB group (28.12±4.43 vs 24.55±5.44 pg/mL at 24 hours).
Clinically, the ESPB group experienced a lower incidence of postoperative dizziness (3.45% vs 13.85%), earlier ambulation (24.36±4.24 vs 27.55±5.17 hours), and a shorter hospital stay (15.16±1.83 vs 17.54±2.39 days).

This study evaluates the association between 24-hour urinary glucose excretion (UGE) and urogenital tract infection (UGTI) risk in patients with type 2 diabetes mellitus receiving sodium-glucose cotransporter 2 inhibitor-containing therapy and explores potential immune-metabolic mechanisms.
This prospective single-center cohort enrolled adults initiating SGLT2 inhibitor-containing therapy between February 2024 and June 2025. Of 412 enrolled patients, 380 were included in the final analysis and followed for up to 12 months. Patients were categorized into quartiles according to 24-hour UGE measured 3 months after treatment initiation. Urinary immune-cell subsets, soluble immune factors, antimicrobial peptides, and glucose-related metabolites were assessed. Time-to-event, restricted cubic spline, mediation, and sensitivity analyses were performed.
Each UGE quartile included 95 patients. The cumulative incidence of pathogen-confirmed UGTI was 10.26% and increased progressively from Q1 to Q4 (3.16%, 7.37%, 12.63%, and 17.89%, respectively). Higher UGE remained independently associated with increased UGTI risk after multivariable adjustment, with a nonlinear positive exposure-response relationship. UGE statistically mediated part of the association between glycemic improvement and infection risk. Higher UGE was also associated with a lower urinary macrophage M1/M2 ratio, reduced interleukin-8 and β-defensin 2 levels, and lower pyruvate, lactate, and citrate levels.
Higher UGE was independently associated with greater UGTI risk and unfavorable urinary immune-metabolic profiles. These observational findings support UGE as a potential clinical mediator but do not establish causality.

This study investigated the gene expression of t-bet, interferon-γ (IFN-γ), GATA3, interleukin-4 (IL-4), RoRγt, IL-17, Foxp3, IL-10, and transforming growth factor-β (TGF-β) as transcription factors and associated cytokines of T-cell subsets, and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), P2X7R, IL-1β, and IL-18 as inflammasome complex-related factors in bipolar disorder (BD) cases compared to healthy controls (HCs).
Whole blood was collected from 48 BD patients and 48 HCs. RNA was then extracted, cDNA was synthesized, and gene expression was assessed using SYBR® Green real-time polymerase chain reaction (PCR) with specific primers.
P2X7R expression was significantly higher in BD patients than in HCs. Additionally, GATA3 and Foxp3 expression levels were significantly lower, and IL-17 expression levels were significantly higher in BD patients than in HCs.
In conclusion, higher levels of inflammation-associated factors and a deregulated balance of T-cell subsets toward a pro-inflammatory status could highlight the importance and involvement of inflammation in the immunopathogenesis of BD.

To evaluate the efficacy of concentrated growth factors (CGF) combined with guided tissue regeneration (GTR) in patients with severe periodontitis.
This retrospective study included 220 patients with severe periodontitis undergoing periodontal regenerative surgery. After propensity score matching, 85 patients treated with CGF plus GTR and 85 treated with GTR alone were analyzed. Overall clinical response, postoperative pain, gingival thickness, alveolar bone parameters, and gingival crevicular fluid levels of IL-17, IL-23, and IL-10 were assessed.
The CGF group showed a significantly higher overall response rate than the GTR-alone group (94.12% vs 75.29%). Pain scores were significantly lower in the CGF group on postoperative day 1, with no significant differences on days 3 and 7. At 3 months, improvements in gingival thickness, alveolar bone height, width, and gray values were greater in the CGF group, although differences were not significant at 6 months. CGF treatment reduced IL-17 and IL-23 levels and increased IL-10 levels; these changes correlated with improvements in gingival and bone regeneration.
CGF combined with GTR may enhance early periodontal tissue regeneration, reduce immediate postoperative pain, and modulate local inflammation in severe periodontitis. Further randomized controlled trials are needed to establish long-term benefits.

Objective: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by decreased platelet count or impaired platelet production. This study employed bioinformatics approaches to analyze gene expression differences among the acute phase (ACU), progressive phase (PRO), and chronic phase (CHR) of ITP.

Methods: The microarray expression analysis dataset GSE23754 from the GEO database was performed. Based on the whole blood transcriptomic data of ITP patients during acute, progressive, and chronic phases, the patients were divided into three groups. GEO2R was used to perform pairwise comparisons of the data among the three groups, identifying three pairs of differentially expressed genes (DEGs) that represent distinct groups. These pairs of DEGs were further cross-compared to select DEGs unique to each stage. Subsequently, tissue specificity analysis, functional enrichment analysis, PPI network interaction analysis, and visualization were conducted.

Results: A total of 62 DEGs were identified in the ACU vs. PRO comparison (2 upregulated, 60 downregulated), 15 DEGs in the CHR vs. PRO comparison (3 upregulated, 12 downregulated), and 26 DEGs in the ACU vs. CHR comparison (1 upregulated, 25 downregulated). There were 10 downregulated genes, including SLC25A37, in the ACU phase; 5 upregulated genes, including VNN1, in the PRO phase; and ALAS2 (regulated by differential loci) and SLC23A2 in the CHR phase. Functional analysis revealed that the ACU phase was predominantly associated with innate immunity, inflammatory responses, and hematopoietic dysfunction, whereas the PRO and CHR phases were primarily linked to metabolic disorders. Protein-protein interaction (PPI) network analysis further untangled key pathways involved in disease progression. The ACU to PRO transition was mediated by the FCGR2B pathway; the ACU to CHR transition was associated with the ACSL1 pathway; and the PRO to CHR transition was regulated by the ALAS2-HBG1 pathway.

Conclusion: Differences in gene expression across the ACU, PRO, and CHR pathological stages may be associated with the pathophysiology of ITP at distinct disease phases. The ALAS2 gene exhibited differential expression in all three pathological stages, suggesting its potential role as a key biomarker in ITP pathogenesis. These findings provide a molecular basis for targeted therapy in ITP.

Heart failure (HF) represents the final stage of multiple cardiovascular disorders. Although LIMK1 regulates cytoskeletal dynamics and contributes to cardiac fibrosis, its exact role in HF remains uncertain.
To establish an in vitro HF model, H9c2 cells were treated with isoproterenol (ISO), and LIMK1 expression was analyzed. LIMK1 was silenced using small interfering RNA to investigate its role in cell injury, hypertrophy, fibrosis, cytoskeletal dynamics, and apoptosis. Oxidative stress, reactive oxygen species (ROS), 8-hydroxy-2’-deoxyguanosine (8-OHdG), MDA, SOD, GSH-Px, NADPH oxidase, inflammation, and mitochondrial function were also assessed. Furthermore, the interplay between LIMK1, ROS, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling was explored using hydrogen peroxide (H2O2; a ROS inducer), diprovocim (an NF-κB activator), and N-acetylcysteine (NAC; a ROS inhibitor).
ISO treatment significantly upregulated the expression of LIMK1 in H9c2 cells. Silencing LIMK1 alleviated ISO-induced myocardial cell damage, hypertrophy, and fibrosis, inhibited Cofilin phosphorylation and F-actin expression, and reduced cell apoptosis and ROS production, thereby mitigating oxidative damage. Furthermore, LIMK1 silencing reduced mitochondrial ROS levels, restored mitochondrial membrane potential, and inhibited the release of inflammatory cytokines. However, H2O2 partially reversed the protective effect of LIMK1 silencing. LIMK1 silencing alleviated inflammatory injury by inhibiting NF-κB phosphorylation and NLRP3 expression, and these effects were partially reversed by an NF-κB activator. NAC alleviated cell damage by inhibiting ROS, and its protective effect was also partially reversed by the NF-κB activator.
In conclusion, silencing LIMK1 can suppress ROS-mediated activation of the NF-κB/NLRP3 pathway, thereby alleviating cardiomyocyte injury and the inflammatory response.

Regulatory T cells (Tregs) play a central role in maintaining immune tolerance and modulating inflammatory responses. Different cellular sources may give rise to Tregs with distinct phenotypic properties, which could influence their clinical applicability in immune-mediated diseases.
In this exploratory comparative study, we performed a comparative flow cytometric analysis of Treg populations derived from mobilized peripheral blood (mPB) and umbilical cord blood (UCB). Tregs were identified based on a standard CD4⁺CD25⁺CD127^low/− gating strategy, followed by phenotypic assessment using markers associated with differentiation (CD45RA/RO, CD27), activation (CD69), and immune checkpoint–related regulation (PD-1, TIM-3).
Our results demonstrate source-dependent differences in the distribution of naive and memory-like Treg subsets, as well as in the expression of activation and checkpoint-associated markers.
These preliminary findings suggest phenotypic heterogeneity between mPB- and UCB-derived Tregs and warrant validation in larger cohorts and functional studies.

Background:

Surgical stress in pediatric adenotonsillectomy can trigger marked immune and inflammatory disturbances. Esketamine, beyond its anesthetic role, has been reported to exhibit immunomodulatory and anti-inflammatory properties. However, its dose-dependent impact on perioperative immune homeostasis in children remains unclear.

Surgical stress in pediatric adenotonsillectomy can trigger marked immune and inflammatory disturbances. Esketamine, beyond its anesthetic role, has been reported to exhibit immunomodulatory and anti-inflammatory properties. However, its dose-dependent impact on perioperative immune homeostasis in children remains unclear. This study aimed to investigate the impact of varying doses of esketamine on perioperative inflammatory cytokines, immune cell balance, and humoral immune markers in pediatric patients undergoing adenotonsillectomy.
Ninety pediatric patients (3–10 years) were retrospectively assigned into three groups based on the esketamine dose they received: low-dose (0.25 mg/kg), medium-dose (0.5 mg/kg), or high-dose (1 mg/kg) esketamine. Serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) were measured to assess systemic inflammation, while CD4⁺/CD8⁺ ratios, immunoglobulin (Ig) A, and IgG were evaluated as immune function indices at baseline, 1 hour, and 24 hours postoperatively. Hemodynamic parameters and clinical recovery indices were also recorded.
Compared with the low-dose and high-dose groups, the 0.5 mg/kg esketamine group showed significantly attenuated elevations in IL-6 and CRP, a faster normalization of the CD4⁺/CD8⁺ ratio, and preservation of IgA levels within near-normal range. These immunological benefits coincided with improved postoperative recovery and fewer adverse events. No significant differences were observed in IgG levels among groups.
This study identifies 0.5 mg/kg as a potential immunoprotective threshold for esketamine, effectively mitigating perioperative immune suppression and excessive inflammation in children undergoing adenotonsillectomy, an insight beyond its known anesthetic properties.

This study aimed to investigate the association between tumor necrosis factor-α (TNF-α) gene polymorphisms and the risk of pulmonary infection following heart valve replacement surgery, while controlling for potential clinical confounders.
A total of 200 patients who underwent heart valve replacement surgery between January 2022 and December 2024 were included. TNF-α genotyping was performed using TaqMan probe-based real-time quantitative PCR. Propensity score matching (PSM, 1:1) was applied to balance baseline characteristics such as age, sex, body mass index, comorbidities, and operative factors. Logistic regression and stratified analyses were used to assess the impact of genetic and clinical risk factors on postoperative pulmonary infection.
After PSM, 51 matched pairs were analyzed. The TNF-α −308A allele (rs1800629) was significantly associated with an increased risk of pulmonary infection. Stratified analysis revealed that this genetic effect was more pronounced in male patients. The infection rate among carriers of the TNF-α −238A allele (rs361525) was 85.7%, significantly higher than that of the GG genotype (44.3%). Prolonged aortic cross-clamp time, extended cardiopulmonary bypass duration, and reduced left ventricular ejection fraction were identified as independent clinical risk factors.
The TNF-α −308G/A polymorphism significantly increases the risk of pulmonary infection following heart valve replacement, particularly in patients with prolonged myocardial ischemia or impaired cardiac function. Preoperative genetic screening and optimization of surgical strategies may help reduce infection risk in high-risk individuals.

Sepsis-induced immunothrombosis is driven in part by dysregulated neutrophil extracellular traps (NETs), yet existing therapies fail to adequately address the oxidative checkpoints that initiate this cascade.

This mechanistic Perspective proposes a paradigm shift toward dual-functional inorganic nanomedicine aimed at modulating both inflammation and coagulation. We discuss emerging evidence supporting a “prevention-plus-clearance” strategy employing PEGylated cerium oxide nanoparticles (nanoceria) surface-grafted with DNase I.

The inorganic core functions as a prolonged superoxide dismutase–like redox buffer through the regenerative Ce³⁺/Ce⁴⁺ cycle, thereby attenuating reactive oxygen species (ROS)-dominant NETosis pathways rather than universally blocking NET formation. In parallel, the surface-immobilized DNase I facilitates enzymatic degradation of extracellular chromatin scaffolds. We hypothesize that this bio-inorganic combination may address the biphasic nature of sepsis pathogenesis by limiting NET initiation while promoting microvascular de-obstruction.

Finally, we outline a translational roadmap required to validate this “circuit-breaker” strategy in vivo, positioning the cerium–NETosis axis as a promising frontier in the management of sepsis-associated coagulopathy.