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.

In recent years, the incidence of psychiatric disorders has been steadily increasing, posing significant challenges to both individual health and social stability. Emerging evidence has highlighted a close association between immune cells and the onset and progression of various psychiatric conditions. Traditional approaches for inferring causality, such as randomized controlled trials and observational studies, are often limited by feasibility, bias, and confounding factors. Mendelian randomization (MR), which leverages genetic variants as instrumental variables, provides a powerful alternative for assessing causal relationships between immune cells and psychiatric disorders. This review summarizes recent advances in MR studies investigating the causal links between immune cell profiles and psychiatric disorders, including anxiety, depression, and schizophrenia. By integrating current evidence from MR studies, this review aims to provide new insights and reference points for future research exploring the relationship between immune cells and psychiatric disorders.

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.

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.

Good’s syndrome (GS) is a rare immunodeficiency disorder associated with thymoma, characterized by hypogammaglobulinemia and impaired cellular immunity. Due to its variable clinical presentation and lack of clear diagnostic criteria, GS is often underrecognized or diagnosed with delay.
We report 7 patients diagnosed with GS, including 2 previously reported cases and 5 new cases. Clinical, immunological, and radiological data were analyzed to characterize the spectrum of disease manifestations and outcomes.
The study comprised 6 men and 1 woman, with a mean age of 48 years at thymoma diagnosis and 50 years at immunodeficiency detection. Two patients were diagnosed with thymoma and immunodeficiency simultaneously, while in 5 patients thymoma preceded GS diagnosis by 1 to 2.5 years. Common clinical features included recurrent sinopulmonary infections and autoimmune manifestations, such as myasthenia gravis and lichen planus. Opportunistic infections, including cytomegalovirus and mycobacterial infections were observed. Immunological profiles demonstrated hypogammaglobulinemia, reduced B-cell markers (CD19, CD20), and variable T-cell subsets. Intravenous immunoglobulin replacement therapy led to clinical improvement in most cases. Two patients succumbed to complications related to severe infections.
GS presents with diverse clinical and immunological features, necessitating a high index of suspicion in patients with thymoma and recurrent infections. Early recognition and individualized immunoglobulin replacement therapy are critical for improving outcomes. Our series highlights the need for ongoing monitoring and management of immunodeficiency in thymoma patients.

 Atopic dermatitis (AD) is a chronic inflammatory skin disease with heterogeneous immune dysregulation. Although interleukin-17 (IL-17) signaling is implicated in AD, IL-17-related diagnostic biomarkers and molecular subtypes remain unclear. This study aimed to identify IL-17-associated biomarkers, characterize immune infiltration and subtypes, and explore upstream regulatory mechanisms.
Gene expression datasets (GSE121212, GSE6012) were acquired from the Gene Expression Omnibus database, and an IL-17-related gene set was collected from the Gene Set Enrichment Analysis website (GSEA)(http://www.gsea-msigdb.org/gsea/msigdb/search.jsp). Differential expression (limma) and Weighted Gene Co-expression Network Analysis were integrated to identify candidate genes, followed by feature selection using Least Absolute Shrinkage and Selection Operator and random forest. We evaluated immune cell infiltration by applying the CIBERSORT algorithm alongside single-sample Gene Set Enrichment Analysis. GSEA was applied to investigate underlying biological processes. AD patients were clustered into subtypes relying on IL-17 scores using ssGSEA.
Our integrated analysis identified IL4R and PRSS22 as key IL-17-related diagnostic biomarkers for AD, demonstrating excellent diagnostic accuracy across both training and validation cohorts. Immune-infiltration analyses revealed altered immune-cell composition and correlations observed between the identified biomarkers and specific immune cells. Two distinct AD subtypes were identified based on IL-17 scores, exhibiting immune infiltration patterns and enriched biological pathways. A ceRNA network highlighted potential regulatory mechanisms involving these biomarkers.
IL4R and PRSS22 are robust IL-17-related diagnostic biomarkers for AD, with high predictive power across cohorts. Immune infiltration profiling and IL-17 score-based subtyping reveal AD heterogeneity. These findings provide a foundation for improved diagnosis, molecular stratification, and potential therapeutic targeting in AD.

Cognitive dysfunction (CD) is a common neuropsychiatric manifestation of systemic lupus erythematosus (SLE), but its early identification lacks objective serological markers. This study aimed to explore the predictive value of combined serum interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and neurofilament light chain (NfL) for CD in SLE patients.
A total of 108 SLE patients (January 2018–December 2019) and 50 healthy controls were enrolled. SLE patients were divided into CD group (MoCA score <26, n=49) and non-CD group (MoCA score ≥26, n=59). Serum IL-6, ICAM-1, and NfL levels were detected by ELISA. Logistic regression and ROC curve analyses were performed to evaluate risk factors and predictive efficacy.
Serum IL-6, ICAM-1, and NfL levels were significantly higher in SLE patients than in controls (p<0.05), and further elevated in the CD group. These three markers were independent risk factors for SLE-related CD. The AUC of combined detection (0.852) was significantly higher than individual markers (0.734, 0.712, 0.677).
Serum IL-6, ICAM-1, and NfL have certain predictive value for CD in SLE patients, and the combined detection of these three indicators offers higher predictive value.

MicroRNAs (miRs) play a crucial role in the pathogenesis, progression, and prognosis of cancer, including non-small-cell lung cancer. The purpose of this present study was to investigate the correlation between ‎MIR141‎ expression in peripheral blood mononuclear cells and serum levels of interleukins (IL-6 and IL-8) and CXCL10 in non-small-cell lung cancer patients.
Forty-six patients diagnosed with primary non-small-cell lung cancer and 30 age- and gender-matched healthy controls were recruited in this prospective cohort study. Two 3-mL samples of systemic blood were collected into tubes either containing or without an anticoagulant from all patients before treatment and from healthy controls. PBMCs were isolated, total RNA extracted, and microRNA expression measured using real-time quantitative polymerase chain reaction. Serum cytokine levels were measured by enzyme-linked immunosorbent assay.
MIR141‎ expression in peripheral blood mononuclear cells was significantly higher in non-small-cell lung cancer patients (4.124 [3.259–4.944]) compared to healthy controls (2.181 [1.036–2.946]). The area under the Receiver operating characteristic (ROC) curve, AUC for MIR141,‎ was 0.695 (95% CI, 0.603–0.787), indicating statistically significant diagnostic performance. Serum levels of IL-6, IL-8, and CXCL10 were also markedly elevated in non-small-cell lung cancer patients compared to healthy controls.
Increased expression of MIR141 in peripheral blood mononuclear cells is associated with non-small-cell lung cancer and elevated systemic inflammatory mediators. These findings suggest that peripheral blood MIR141 may serve as a promising non-invasive biomarker for the diagnosis of non-small-cell lung cancer.

The research intended to elucidate the synergistic effects of Eosinophils (Eos) and mast cells (MCs) on human nasal epithelial cells (HNEpCs) in the context of allergic rhinitis (AR), focusing on inflammation, tight junction protein expression, and DNA damage. Cell proliferation capacity was measured using the CCK-8 method, apoptosis was examined via the TUNEL assay, and inflammatory cytokine levels were assayed via ELISA. Western blotting evaluated the protein abundance of tight junction proteins (ZO-1, Occludin) and CD40L/CD40. Immunofluorescence was used to detect γH2AX (DNA damage) as well as subcellular ZO-1/Occludin distribution. Co-immunoprecipitation (Co-IP) was used to analyze the CD40L-CD40 interaction between Eos and MCs. Eos and MCs significantly reduced HNEpC viability and enhanced apoptosis, with the most pronounced effects in the AR+Eos+MC group. Inflammatory cytokine levels were markedly elevated in the Eos+MC and AR+Eos+MC groups, with the highest concentrations observed in the AR+Eos+MC group. Western blot and immunofluorescence analyses showed decreased expression of ZO-1 and Occludin in treatment groups compared to Control, along with a shift in their localization from the cell membrane to the cytoplasm. γH2AX expression, indicating DNA damage, was significantly elevated, with the highest levels observed in the AR+Eos+MC group. Co-immunoprecipitation (Co-IP) analysis confirmed enhanced CD40L–CD40 interaction involving Eos and MCs within the Eos+MC and AR+Eos+MC groups. Eosinophils and mast cells synergistically promote inflammation, disrupt the nasal epithelial barrier, and exacerbate DNA damage. The CD40L-CD40 pathway serves an essential function in their interaction, providing a potential therapeutic target for AR.

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.

Long noncoding RNA SSTR5 antisense RNA 1 (lncRNA SSTR5-AS1) is increased in a variety of tumors, but its molecular mechanism in ovarian cancer (OC) remains unreported.
lncRNA SSTR5-AS1 and signal transducer and activator of transcription 3 (STAT3) expressions in SKOV3 and A2780 cells were interfered (n=3), and the cells were treated with ferroptosis inhibitor Ferrostatin-1. lncRNA SSTR5-AS1 and STAT3 expressions were discovered. The interaction between them was detected by immunoprecipitation assay. The cell malignant progression was evaluated through Transwell and scratch healing assays. Ferroptosis was measured through kits and fluorescent probes; the expression levels of immunosuppressive factors and STAT3/solute carrier family 7 member 11 (SLC7A11) signaling pathway were discovered through Western blot. A transplanted tumor model (n=6 mice per group) was established to evaluate ferroptosis, immunosuppressive factors, and tumor growth in tumor tissues.
lncRNA SSTR5-AS1 was up-regulated on OC cells. LncRNA SSTR5-AS1 and STAT3 bind to each other, and knockdown of lncRNA SSTR5-AS1 can reduce p-STAT3/STAT3 and SLC7A11 protein levels (one-way ANOVA). Knocking down lncRNA SSTR5-AS1 and STAT3 suppressed cell viability, migratory rate, and invasive cell number; increased reactive oxygen species (ROS) and Fe2+ levels; and reduced immunosuppressive factors and ferroptosis proteins. Ferrostatin-1 significantly reversed the effect of knockdown of lncRNA SSTR5-AS1 on ferroptosis. In transplanted tumor tissues, downregulation of lncRNA SSTR5-AS1 can reduce tumor size and volume, show obvious iron deposition, and reduce the secretion of immunosuppressive factors.
Knockdown of lncRNA SSTR5-AS1 induces ferroptosis and reduces the secretion of immunosuppressive factors through the STAT3/SLC7A11 pathway, thereby antagonizing OC.

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.

Gastric cancer is among the most prevalent malignancies worldwide, with a poor prognosis in advanced stages. Overexpression of human epidermal growth factor receptor 2 (HER2, also known as ERBB2) and heat shock protein 90 alpha (HSP90AA1, also known as HSP90α) has been associated with tumor progression. Anethum graveolens, a medicinal plant from the Apiaceae family, has demonstrated anticancer properties in previous studies. This study aimed to evaluate the effects of A graveolens methanolic extract on apoptosis and the expression of HER2, HSP90α, tumor protein p53 (TP53), and caspase-3 genes in the human gastric adenocarcinoma cell line (AGS).
A methanolic extract of the aerial parts of A graveolens was prepared. Cytotoxicity was assessed in AGS and human gingival fibroblast (HUGU) cell lines using the -(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Gene expression was measured by real-time PCR, and apoptosis was evaluated using Annexin V/propidium iodide (PI) staining followed by flow cytometry.
The methanolic extract exhibited dose-dependent cytotoxicity, with a half-maximal inhibitory concentration (IC50) of 1280 μg/mL in AGS cells. Gene expression analysis revealed significant downregulation of HER2 and upregulation of HSP90α, TP53, and caspase-3 in treated AGS cells compared to controls. Apoptosis rates were significantly higher in treated AGS cells, confirming the proapoptotic effect of the extract. A graveolens exerts cytotoxic and proapoptotic effects in AGS cells and modulates key genes involved in gastric cancer progression.
These findings suggest its potential as a natural therapeutic candidate for gastric cancer, warranting further preclinical and clinical investigations.

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.

Pneumocystis jirovecii pneumonia (PJP) is a common opportunistic infection in immunocompromised children, often causing acute fulminant pneumonia with respiratory failure. The prognosis of PJP in human immunodeficiency virus (HIV)-negative children with acute respiratory distress syndrome (ARDS) remains unclear.
This retrospective review (2015–2021) included 20 HIV-negative children with ARDS and PJP. Among them, 17 had hematological malignancies or solid tumors, and 3 had renal disease; 15 survived, 5 did not. Both groups had very low CD4⁺ T cell counts (<0.2×10⁹/L), severe ARDS (partial pressure of oxygen in arterial blood / fraction of inspired oxygen [PaO₂/FiO₂] ratio <150), and elevated lactate dehydrogenase (LDH) and (1,3)-β-D-glucan (BDG) levels. In non-survivors, anti-PJP therapy was initiated approximately 7 days later than in survivors.
Single-cell sequencing revealed CD4⁺/CD8⁺ T cell ratios of 0.16 (survivors) vs 2.13 (non-survivors), with a higher ratio of regulatory T cells (Tregs) to CD4⁺ T cells in non-survivors (33% vs. 10.6%). Non-survivors showed enrichment of neutrophil degranulation and activation pathways and expressed more proapoptotic and proinflammatory signals (e.g., FAS_FASLG, interferon-γ).
Early treatment initiation is critical. Prolonged CD8⁺ T cell deficiency, high Treg expression with proapoptotic genes, and excessive inflammation may predict poor prognosis.

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.

This meta-analysis was conducted to investigate the efficacy and safety of omalizumab in the treatment of allergic rhinitis in adults.
Randomized controlled trials (RCTs) on omalizumab in the treatment of allergic rhinitis in adults were collected by searching PubMed, Cochrane Library, Embase, Web of Science, CNKI, VIP, and Wanfang Data. The search period was from the establishment of each database to October 2024. Stata 15.0 software was used for data analysis. The control group received a placebo or other anti-allergy drugs, while the experimental group received omalizumab, with or without specific immunotherapy.
A total of 8 RCTs were involved in this meta-analysis. The combined analysis exhibited that the effective rate was higher in the omalizumab group than in the control group (RR=1.15; 95% CI, 1.06–1.24) for allergic rhinitis. IgE levels (SMD=−2.82; 95% CI, −4.03 to −1.62) and DNSS (SMD=−1.99; 95% CI, −3.04 to −0.94), DOSS (SMD=−2.95; 95% CI, −4.65 to −1.25) were lower in the omalizumab group compared with the control group. No significant difference was observed in the incidence of adverse events between the two groups (RR=1.15; 95% CI, 0.69–1.93).
Omalizumab is effective and safe in the treatment of adult allergic rhinitis.

To evaluate whether adjunctive Modified GuiPi Decoction provides additional benefit to standard immunosuppressive therapy in adult patients with chronic immune thrombocytopenia (ITP).
This retrospective cohort study included 120 adult patients aged 18–65 years, diagnosed with ITP according to the 2016 Chinese Expert Consensus. Patients received either standard therapy (cyclosporine A plus prednisone; comparison group, n = 60) or standard therapy plus Modified GuiPi Decoction (treatment group, n = 60) between July 2022 and July 2024.
After 12 weeks of treatment, the treatment group showed significantly greater improvement in fatigue severity score (mean reduction: 3.2 vs 1.8) and quality-of-life index (mean increase: 15.4 vs 9.1) compared to the comparison group. However, no significant between-group difference was observed in platelet count recovery (mean increase: 45.3 × 10⁹/L vs 53.1 × 10⁹/L), with the comparison group showing a numerically larger rise. Mild ALT/AST elevations were more pronounced in the treatment group.
In adult ITP patients, adjunctive Modified GuiPi Decoction may offer symptomatic and quality-of-life benefits beyond standard therapy, but did not demonstrate superior hematological response. Caution is warranted regarding potential hepatotoxicity.

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.

Keywords:;; ; ; ; 

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.

Periodontitis is a chronic inflammatory disease driven by dysregulated immune responses to microbial biofilms, in which excessive pro-inflammatory cytokine production contributes to periodontal tissue destruction. Although laser-assisted periodontal flap surgery has been proposed as an adjunctive therapy, its effects on inflammatory mediator regulation remain unclear. This meta-analysis evaluated the effects of laser-assisted periodontal flap surgery on tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP), and their association with clinical outcomes in patients with Stage 3–4, Grade B/C chronic periodontitis.
Randomized controlled trials comparing laser-assisted periodontal flap surgery with conventional flap surgery were systematically retrieved from major English and Chinese databases. Primary outcomes included changes in inflammatory biomarkers measured in gingival crevicular fluid or serum; while probing depth (PD), clinical attachment level (CAL), gingival index, and postoperative pain were secondary endpoints. Meta-analyses used fixed- or random-effects models according to heterogeneity, with sensitivity analyses conducted to assess result robustness.
Twelve randomized controlled trials were included. Laser-assisted therapy significantly reduced early postoperative (24-hour) TNF-α (MD=−0.88, 95% CI −1.01 to −0.75) and IL-6 (MD=−1.41, 95% CI −1.81 to −1.02) compared with conventional surgery, while CRP showed no significant difference. Clinically, adjunctive laser therapy improved short-term probing depth reduction at 3 and 6 months, whereas CAL improvements were not consistently sustained.
Laser-assisted periodontal flap surgery significantly downregulates key inflammatory cytokines in the early postoperative period and may improve short-term outcomes. However, long-term periodontal attachment stability remains uncertain, warranting further well-designed studies with standardized biochemical and clinical assessments.

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.

The aim of this study was to evaluate the clinical and inflammatory outcomes of minocycline hydrochloride combined with tinidazole in patients with chronic periodontitis.
PubMed, Cochrane Library, Embase, CNKI, WanFang Data, and VIP were searched through December 2025 for randomized and nonrandomized controlled studies. Randomized trials were assessed using the Cochrane Risk of Bias tool, while the cohort study was assessed using ROBINS-I. Meta-analysis was conducted using RevMan 5.3. Random-effects models were applied when substantial heterogeneity was present, and sensitivity analyses were performed by excluding the cohort study.
Fourteen studies were included. Compared with the control treatment, combination therapy was associated with greater improvements in gingival index (MD=−0.71; 95% CI, −0.77 to −0.65), probing pocket depth (MD=−0.87; 95% CI, −1.07 to −0.66), clinical attachment level (MD=−0.77; 95% CI, −1.06 to −0.49), plaque index (MD=−0.38; 95% CI, −0.45 to −0.32), and sulcus bleeding index (MD=−0.68; 95% CI, −0.96 to −0.40). Changes were also observed in several inflammatory and immune-related indicators, whereas CRP did not differ significantly between the groups. Substantial heterogeneity was present for most outcomes.
Overall, minocycline hydrochloride combined with tinidazole may provide additional short-term benefits for patients with chronic periodontitis. Nevertheless, these findings should be interpreted cautiously because of methodological limitations, substantial heterogeneity, incomplete safety reporting, and short follow-up periods.

This prospective single-arm study examined associations between peripheral immune-inflammatory biomarkers and changes observed during cognitive rehabilitation in patients with early Alzheimer disease.
Seventy-two patients completed a 12-week structured cognitive rehabilitation program delivered three times weekly. Baseline plasma/serum glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured. Cognitive and functional outcomes were assessed before and after the program. Correlation and multivariable linear regression analyses examined associations between baseline biomarkers and pre–post changes.
After 12 weeks, scores on global cognition, memory, digit span, and semantic fluency increased, whereas Trail Making Test completion times and Activities of Daily Living dependency scores decreased. Among 60 participants with repeat biomarker measurements, GFAP, IL-6, TNF-α, and CRP levels were lower at follow-up. Baseline GFAP, IL-6, TNF-α, and CRP were inversely correlated with change in Montreal Cognitive Assessment score; GFAP showed the strongest correlation (r=−0.48). After adjustment for age, education, and baseline cognition, baseline logGFAP, logIL-6, and TNF-α remained associated with smaller Montreal Cognitive Assessment score changes.
In this uncontrolled cohort, cognitive rehabilitation was associated with short-term cognitive, functional, and biomarker changes. Higher baseline inflammatory biomarker levels were associated with smaller pre–post changes, with GFAP showing the strongest association. These exploratory findings do not establish efficacy or causality and require confirmation in randomized controlled studies.

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.

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.

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.