Non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) figure prominently in the list of prevalent and resistant cancers that reveal significant differences in response to immunotherapy. Neoantigens, specific antigens resulting from tumor mutations, play an important role in provoking immune responses and the success of immunotherapy. This review scrutinizes the quantitative and qualitative differences in neoantigens in NSCLC and PDAC and their impact on the efficacy of immunotherapy. The evidence suggests that the higher mutational burden, greater diversity, and different quality of neoantigens in NSCLC compared with PDAC are among the key drivers contributing to the enhanced susceptibility to immunotherapy in this cancer. These differences could pave the way for the development of personalized therapies and novel strategies to improve treatment outcomes in resistant cancers.

Mannose-binding lectin (MBL) is a critical component of the innate immune system, serving a vital role in the body’s initial defense against pathogens. Sepsis, a severe condition triggered by an excessive immune response to infection, has been linked to variations in the MBL2 gene that affect MBL levels and functionality. Numerous studies across various populations have examined the role of MBL-2 promoter polymorphisms (H>L and Y>X), but their results have been conflicting. This study aims to investigate the genetic connection between MBL promoter polymorphisms and susceptibility to sepsis through a meta-analysis of previously published articles.
A thorough literature search was conducted using PubMed, Scopus, and ScienceDirect to locate relevant articles for the meta-analysis. Rigorous inclusion and exclusion criteria were implemented to ensure data accuracy. All analyses were performed using Comprehensive Meta-Analysis Software v4.
Seven studies were included, examining the role of MBL-2 promoter genetic variants in sepsis (H>L: n=3, sepsis cases: 449, control: 687; Y>X: n=6, sepsis cases: 1211, control: 1694). Egger’s regression analysis and funnel plots suggested no publication bias. Heterogeneity analysis indicated homogeneity among the data. The meta-analysis showed no association between MBL-2 promoter variants and susceptibility to sepsis. The trial sequential analysis highlighted the need for further studies on MBL-2 promoter variants in sepsis to draw a definitive conclusion.
The promoter variants of the MBL-2 gene (H>L and Y>X) do not appear to increase the risk of sepsis. Further investigation is needed to confirm this conclusion, including more participants from diverse populations and larger sample sizes.

Pediatric rhinitis is a common recurrent disorder that may progress to asthma or sinusitis in severe cases. This study aimed to compare the efficacy of different doses of glucocorticoid nasal spray combined with loratadine for rhinitis in children, and provide evidence for optimizing clinical treatment.
A total of 150 children with rhinitis admitted from June 2022 to June 2024 were divided into three groups: group I (low-dose group, n=50), group II (medium-dose group, n=50), and group III (high-dose group, n=50). Patients in all three groups were treated with a glucocorticoid nasal spray with loratadine combined with antihistamines. The immune function, serum inflammatory factor level, quantitative Lund-Kennedy score by nasal endoscopy, nasal symptom score, Quality of Life Questionnaire (RQLQ) scores, clinical efficacy, incidence of adverse events, and treatment compliance were assessed.
Post-treatment, all indices improved in the three groups. The percentages of CD4⁺ and CD8⁺ T cells, IL-10 content, and clinical efficacy in groups II and III were significantly higher than those in group I, while the immunoglobulin E (IgE), IL-6 and IL-17 content, the quantitative Lund-Kennedy score of nasal endoscopy, the children’s nasal symptom scores, the RQLQ scores, and the incidence rate of adverse events were below in group I. No significant differences were found between groups II and III in all indices, nor in treatment compliance across the three groups.
Loratadine combined with a glucocorticoid nasal spray therapy effectively improves clinical outcomes, inflammation, immune function, symptoms, and quality of life in rhinitis in children, with high clinical application value.

Natural killer (NK) cells contribute to the development of Rheumatoid Arthritis (RA). Increased expression of programmed cell death protein 1 (PD-1), encoded by the PDCD1 gene, indicates NK cell exhaustion, a process that may be influenced by microRNAs (miRNAs). In this study, we examined PD-1 expression on NK cells from RA patients and evaluated whether miRNAs modulate this pathway.
Although antibiotics are critical for treating infections, they can provoke harmful immune responses by releasing bacterial components that overstimulate the immune system. Such responses may lead to excessive inflammation or cytokine storms. To address this risk, we assessed the immune safety of a newly designed chimeric endolysin, ZAM-MSC, and compared its effects with traditional antibiotics using transcriptomic, proteomic, and computational analyses.
We analyzed public gene and protein expression datasets from antibiotic-treated human cells and performed in silico studies on ZAM-MSC. Differential expression analysis and pathway enrichment were conducted, alongside structural modeling of the endolysin and its predicted interactions with immune receptors.
Antibiotic treatment strongly activated inflammatory genes and pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In contrast, ZAM-MSC minimally affected immune-related gene expression, with downregulation of interleukin-6 receptor (IL6R) and tumor necrosis factor receptor 1A (TNFRSF1A). Structural modeling showed weak interactions with Toll-like receptors, and epitope analysis predicted low immunogenicity. These results suggest ZAM-MSC may offer a safer antimicrobial alternative, though all protein-level findings are based on computational predictions and require experimental validation. 

Postoperative infections (POIs) significantly contribute to morbidity and mortality following partial hepatectomy for hepatocellular carcinoma (HCC). While the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) are recognized biomarkers for immune-inflammatory and nutritional status, their combined predictive value for POIs in liver surgery requires further investigation. This study evaluates SII and PNI as preoperative predictors for infections in this patient population.
A retrospective observational study was conducted on 300 patients undergoing partial hepatectomy between 2022 and 2024. Preoperative laboratory data were used to calculate SII and PNI, with POIs identified within 30 days based on CDC guidelines. Statistical analyses, including multivariate logistic regression, were performed to compare infected and non-infected cohorts and identify independent predictors of infection.
Of the 300 patients, 96 (32%) developed POIs. The infected group exhibited significantly higher SII (1142 ± 618 vs 792 ± 450) and lower PNI (40.1 ± 5.8 vs 46.4 ± 5.9) than the non-infected group. Multivariate analysis confirmed high SII (OR 2.85) and low PNI (OR 3.26; 95% CI, 2.01–5.12) as independent predictors. Furthermore, infections were associated with prolonged hospitalization, increased ICU admissions, and higher 30-day mortality.
Preoperative SII and PNI are effective, independent predictors of POIs in patients undergoing hepatectomy for liver cancer. Integrating these biomarkers into routine evaluation enhances risk stratification and guides perioperative optimization. Early identification through these indices allows for targeted interventions, such as nursing-led nutritional support and intensified surveillance, to reduce complications and improve surgical outcomes.

Exhausted T cells are phenotypically and functionally heterogeneous, from progenitor- to terminally-exhausted T cells. We evaluated gene expression profile of CD8⁺ T cells in acute leukemia to characterize the phenotype of exhausted T cells.
Blood samples were collected from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients prior to treatment and from control subjects. Additionally, samples were obtained from ALL patients after induction therapy. TCF7, NFATc1, IRF4, and BATF gene expression was then evaluated in isolated CD8⁺ T cells.
CD8⁺ T cells from ALL patients showed higher expression of TCF7 and NFATc1 compared to the control group. The two study groups did not have a significant difference in the expression of BATF and IRF4. When compared to the control group, CD8⁺ T cells of AML patients showed an elevated expression level of NAFTc1 and IRF4. Significant differences were not found between the two study groups in AML when it came to the expression of BATF and TCF7.
To our findings, the majority of CD8⁺ T cells found in ALL patients consist of progenitor-exhausted T cells.

Childhood asthma and eczema are common chronic diseases that significantly affect the health of children and parents. These children experience physical and psychosocial problems, including behavioral and emotional disturbances. This study was conducted to identify the psychological issues such as children's attachment, maternal emotion regulation, and child-parent relationship in children with autoimmune disorders, especially asthma and eczema.
This cross-sectional study included80 mother-child pairs (40 with asthma and 40 with eczema) recruited from Yazd autoimmune clinics between 2022 and 2023. Exclusion criteria included additional physical or psychiatric illnesses in parents and parental drug addiction. Participants completed a demographic questionnaire and three validated questionnaires: Children's Attachment Questionnaire, Gross Emotion Regulation Strategies Questionnaire, and Pianta Mother-Child Relationship Questionnaire.
Results analysis and comparison showed that both the asthma and eczema groups have moderate levels of secure attachment with a 25% achieving favorable score. Emotion regulation showed very low desirability (up to 25% for its subscales). Geographical location had a slight but significant effect on attachment and emotion regulation. Scores of the Pianta mother-child relationship scale were generally positive. No significant effects were observed in relation to the child's gender, occupation, and educational status of the mothers.
This study found moderate levels of children's secure attachment and maternal emotion regulation in both groups and favorable mother-child relationships in children aged 5 to 12 years with asthma and eczema. Only a small percentage of children demonstrated secure attachment, reflecting existing research linking childhood illness to parental distress and impaired child development.

To investigate the feasibility and effectiveness of targeted lung recruitment and the titration of optimal positive end-expiratory pressure (PEEP) in neonates under the guidance of lung ultrasound.
The atelectasis neonates from June 2022 to June 2024 in the Neonatology Department of People's Hospital of Pidu were collected and randomly divided into a lung ultrasound scoring (LUS) group and an oxygen (OXY) group, both of which were given mechanical ventilation treatment. The lung recruitment and optimal PEEP were performed by the LUS and OXY methods, respectively. The optimal PEEP and the respiratory and hemodynamic indexes of the two groups were compared before and after lung recruitment and after the optimal PEEP was titrated.
After the intervention, the dynamic lung compliance (Cdyn) in the LUS group increased by 38.2% compared with the baseline (from 30.6 ± 4.3 to 42.3 ± 5.1 mL/cmH₂O), which was significantly higher than the 21.4% increase in the OXY group (from 29.8 ± 4.1 to 35.6 ± 4.8 mL/cmH₂O). The improvement in PaO2/FiO2 in the LUS group was 22.5% higher than in the OXY group. There was no statistically significant difference in the incidence of complications between the two groups.
Lung ultrasound can guide neonatal lung recruitment and optimal PEEP titration, improving lung compliance and oxygenation without affecting the safety of treatment.

Immune and inflammatory factors influence endometrial cancer outcomes, the pan-immune inflammation value (PIV) shows potential but remains underexplored.
This study aims to evaluate the relationship between preoperative PIV, T cell subtypes, and surgical prognosis in endometrial cancer patients, providing insights for prognostic markers and predictive models. We conducted a prospective observational study involving 101 endometrial cancer patients from August 2022 to August 2024. Based on prognosis within 6 months post-surgery, patients were divided into good and poor prognosis groups. We compared clinical characteristics, inflammatory indices, and T cell immune profiles between the groups.
The mean age of participants was 50.12 years, with 23 patients experiencing a poor prognosis. The poor prognosis group exhibited significantly higher proportions of advanced International Federation of Gynecology and Obstetrics (FIGO) stage, larger tumor diameter, elevated neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and PIV. Conversely, this group showed lower proportions receiving neoadjuvant chemotherapy, CD4⁺ T cells, and CD4⁺CD8⁺ T cell ratios. Notably, elevated PIV emerged as an independent risk factor for poor prognosis, while increased CD4+ T cell proportion and CD4⁺CD8⁺ ratio were protective.
PIV is significantly associated with poor prognosis in endometrial cancer, serving as an independent risk factor. Higher CD4+ T cell counts and CD4+:CD8+ ratios provide protective benefits. The constructed logistic regression model demonstrates strong predictive capability for post-surgical outcomes. However, limitations, including sample size and short follow-up, necessitate further investigation in larger cohorts.

Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunodeficiency, partial albinism, recurrent infections, and progressive neurologic dysfunction. Unless patients undergo successful hematopoietic cell transplantation (HCT), a majority of them die during childhood because of an accelerated phase of immune dysfunction and hemophagocytic lymphohistiocytosis (HLH). Herein, we aim to describe the laboratory diagnosis, clinical manifestations, and genetic findings in three patients with CHS.
Three patients with partial albinism associated with CHS were included in this study. Immunological screening tests were done. Leukocyte granules in peripheral blood smear (PBS) and hair shafts were examined. Subsequently, genetic analyses were performed by Whole Exome Sequencing (WES) followed by Sanger sequencing for all patients and their parents.
Initial immunology screening tests were within normal limits. Light microscopy studies of patients’ PBS showed giant granules in the leukocyte cytoplasm. Furthermore, there were evenly distributed melanin granules in the patients' hair shafts. Variant analysis of the LYST gene identified three splicing site defects: one known variant, c.7060-1G>A in intron 24, and two novel variants, c.2363+2T>C in intron 5, and c.10702-3A>G in intron 47.
Hair shaft assay and PBS are rapid and suitable tests in early diagnosis and differentiation in CHS patients. WES results revealed 2 novel splice site variants that might contribute to earlier and more accurate diagnosis. This facilitates early enrolment of CHS patients in the HCT protocol-the optimal treatment path-and enables prenatal diagnosis for affected families.

Bronchial asthma (BA) has a complex pathogenesis involving immune imbalance and airway remodeling (AR). Cannabinoid receptor 2 (CB2) plays a role in inflammation regulation, so this study explored the therapeutic potential of a CB2 inverse agonist on BA rats’ AR and Th1/Th2 imbalance, and its mechanism via Toll-like receptor 4/nuclear factor kappa B(TLR4/NF-κB) pathway.
Twenty-seven male SD rats (180-220 g) were divided into control (CG), model (MG), and intervention (IG) groups (n=9 each). MG/IG were BA-modeled by ovalbumin (OVA) sensitization (days 1/8: 100 μg OVA +1 mg aluminum hydroxide gel, i.p.) and 1% OVA aerosol challenge (day 15, 3×/week, 8 weeks). IG received CB2 inverse agonist (5 mg/kg, i.p., 3×/week, 4 weeks); CG/MG got saline. T_H1/T_H2 cytokines, subsets, AR parameters, and lung TLR4/NF-κB-related molecules were detected.
Compared with CG, MG had T_H1/T_H2 imbalance, higher AR indices, upregulated TLR4/NF-κB, shorter asthma latency, and longer attack duration. vs. MG, IG reversed T_H1/T_H2 imbalance, reduced TLR4/NF-κB-related protein/mRNA (except elevated NFKBIA).
CB2 inverse agonist has BA prevention/treatment potential by regulating Th1/Th2 balance, inhibiting AR, and acting on the TLR4/NF-κB pathway.

Volatile anesthetics, particularly sevoflurane, have demonstrated cardioprotective properties during cardiac surgery. However, their immunomodulatory mechanisms at the molecular level remain unclear. Given the close relationship between cardiac injury and immune responses, understanding how anesthetic agents influence immune-related pathways may provide new insights into perioperative myocardial protection.
This study aimed to explore the immunological and molecular mechanisms underlying the effects of sevoflurane anesthesia on cardiomyocytes in patients undergoing coronary artery bypass grafting (CABG).
Gene expression data (GSE4386) from myocardial tissues of CABG patients anesthetized with sevoflurane or propofol were analyzed. Differentially expressed genes (DEGs) were identified using R software, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction networks were constructed to identify key immune-associated hub genes. A total of 211 DEGs were identified. Functional enrichment revealed that these genes were predominantly associated with immune and inflammatory processes, including leukocyte activation, cytokine–cytokine receptor interaction, neutrophil extracellular trap formation, and chemokine signaling pathways. Hub genes such as ITGAM, PTPRC, TYROBP, TLR2, and TLR4 were identified as central immune regulators potentially mediating the cardioprotective and immunomodulatory effects of sevoflurane.
Sevoflurane anesthesia may confer myocardial protection after CABG by modulating immune-related signaling pathways and inflammatory gene expression. These findings highlight the immunoregulatory potential of volatile anesthetics, providing novel perspectives for immune-targeted strategies in perioperative cardiac management.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains a major neurological complication in people living with HIV despite effective antiretroviral therapy. Neurotoxicity caused by viral proteins, particularly the HIV-1 transactivator of transcription (Tat), contributes significantly to HAND. Although N-methyl-D-aspartate receptors (NMDARs) in astrocytes are known to regulate aquaporin-4 (AQP4) the mechanisms by which Tat influences NMDAR signaling and AQP4 expression remain unclear. This study investigated how HIV-1 Tat regulates AQP4 expression in astrocytes through the NMDAR/CaMKII/AC/cAMP/PKA signaling pathway and how secondary Ca²⁺ dynamics modulate this process.
Astrocytic Ca²⁺ influx was measured using the Fluo-3 AM probe. Western blotting quantified AQP4, NR1, NR2A/B, CaMKII, p-CaMKII, PKA, and PKG expression. Real-time quantitative polymerase chain reaction (RT-qPCR) assessed mRNA levels of AQP4 and NMDAR-related genes. Enzyme-linked immunosorbent assay (ELISA) evaluated nitric oxide synthase activity, adenylate cyclase activity, and intracellular cAMP levels. Pharmacologic inhibitors—MK-801 (NMDAR blocker), H89 (PKA inhibitor), and KT5823 (protein kinase G [PKG] inhibitor)—were applied to investigate pathway interactions.
HIV-1 Tat induced robust activation of NMDAR, resulting in increased Ca²⁺ influx and sequential activation of the CaMKII/AC/cAMP/PKA pathway, ultimately elevating AQP4. After prolonged Tat exposure (approximately 36 hours), a secondary surge in Ca²⁺ activated PKG, which acts as a protective negative feedback mechanism to inhibit excessive NMDAR activity, thereby stabilizing Ca²⁺ influx and preventing abnormal overexpression of AQP4. Cotreatment with MK-801, H89, or KT5823 suppressed Tat-induced Ca²⁺ influx and attenuated AQP4 upregulation, although persistent Tat exposure gradually restored Ca²⁺ elevations through compensatory mechanisms.
HIV-1 Tat dynamically regulates AQP4 expression in astrocytes via the NMDAR/CaMKII/AC/cAMP/PKA pathway, with PKG-mediated feedback contributing to later stabilization. These findings highlight AQP4 as a potential therapeutic target for HAND. 

Iran has an extensive governmental network of primary health care facilities and hospitals. In 2019, the integration of asthma-related services into this network was designed and pilot-tested. Primary health care providers (PHCPs) and family physicians (FPs) are the main members of the care provision team and are responsible for case identification and management.
The pilot was conducted from November 2019 through April 2020 in seven areas-Kerman, Maragheh, Ahvaz, Kashan, Urmia, Karun, and Qazvin-covering both urban and rural locations and a population of approximately one million people. Our objective was to report indicators related to the integration of asthma identification, referral, and management within the existing primary health care system.
In total, 350,894 individuals were screened for asthma by PHCPs. The observed proportion of positive (probable) cases among those screened was 2.48%. Key process indicators included screening uptake (34%), attendance of referred cases at physician visits (83%), and follow-up adherence (49% of confirmed cases).
We conclude that improving screening uptake and the accuracy of asthma case detection by PHCPs are the most effective strategies for enhancing care provision efficiency. The findings of the pilot project have significant implications for understanding efficient integration of asthma-related services. The results indicate that integrating asthma care into primary health services is feasible and can improve early detection and care coordination, informing policy decisions for broader implementation and resource planning.