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.

SARS-CoV-2 infection causes significant acute and long-term morbidity, including persistent pulmonary and muscular dysfunction in athletes. Physical exercise alters circulating microRNA (miR) profiles, and specific microRNAs have documented roles in inflammation, immune regulation, muscle metabolism, and regeneration. This study characterizes circulating microRNAs relevant to COVID-19 pathogenesis and post-viral recovery, including miR-155, miR-146a, the let-7 family, miR-21, miR-424, miR-1, miR-133, miR-499, miR-208, miR-486, and miR-22, and examines how different exercise modalities may modulate these microRNAs to support pulmonary and muscular function in post-COVID-19 athletes. miR-155 and miR-146a are highlighted as modulators of innate and adaptive inflammatory signaling and as mediators of cytokine responses implicated in severe COVID-19. Moreover, several microRNAs, such as miR-21, miR-155, miR-146a, and the let-7 family, converge on NF-κB and related pathways, linking altered miR expression to immune dysregulation and cytokine-driven tissue injury. Additionally, muscle-enriched and metabolism-associated microRNAs regulate myogenesis, mitochondrial biogenesis, and key metabolic pathways (PGC-1α, AMPK, mTOR)-processes essential for muscle repair, endurance recovery, and respiratory muscle support after SARS-CoV-2 infection. Different types of exercise produce distinct miR signatures; notably, moderate-intensity exercise consistently promotes anti-inflammatory and pro-repair miR patterns. We emphasize the therapeutic potential of moderate-intensity exercise as a non-pharmacological strategy to regulate miR expression, reduce cytokine-mediated damage, and support functional recovery in post-COVID-19 athletes. To our knowledge, this is the first study to link exercise-driven miR changes with functional pulmonary and muscular recovery in athletic populations recovering from COVID-19, supporting moderate-intensity exercise as a promising strategy for rehabilitation and performance restoration.

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.

The management of treatment strategies in COVID-19 is critical, especially in patients with type 2 diabetes. Non-enzymatic glycation of transmembrane protease serine 2 and angiotensin-converting enzyme 2 during COVID-19 in patients with diabetes may exacerbate immune dysregulation and inflammation. Elevated inflammatory cytokines such as IL-1, IL-2, IL-6, IL-7, and IL-10, tumor necrosis factor-α, interferon-γ, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1 have been observed in COVID-19 patients. This review aims to assess the relationship between inflammatory markers, including C-reactive protein, and micronutrients (vitamins D and C, zinc, and copper) with the severity of COVID-19 infection in patients with type 2 diabetes. A narrative review was conducted through a comprehensive literature search of English-language articles published between 2000 and 2025. The databases searched included PubMed, Scopus, the ISI Web of Science, Cochrane, and Embase. Search terms included COVID-19, infections, type 2 diabetes mellitus, interleukins, and micronutrients. English-language scientific articles, systematic reviews, and meta-analyses were included, while studies lacking sufficient information, letters, comments, and editorials were excluded. Evidence suggests that immune-boosting components such as proteins, vitamins, and minerals can enhance immunity to infections. Vitamins D and C, zinc, and copper play supportive roles in immune function, potentially modulating the inflammatory response in COVID-19 patients with type 2 diabetes. High levels of inflammatory cytokines correlate with increased disease severity in this population. Understanding the interplay between inflammatory markers and micronutrients may guide improved therapeutic strategies for managing COVID-19 in diabetic patients. Further research is warranted to clarify these relationships and optimize clinical outcomes.

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.

Lung cancer remains a major cause of cancer-related mortality worldwide, with current treatments such as surgery, chemotherapy, and immunotherapy facing limitations, including severe side effects and high costs. Hyperthermia (H) has emerged as a promising strategy to enhance tumor sensitivity to treatments and reduce toxicity. This study investigates the effects of H in enhancing the anti-tumor efficacy of pemetrexed (PEM) and altering the expression profile of hsa-MiR-548c-3p (tumor suppressor) in the A549 cell line.
A549 cells were cultured in DMEM medium and divided into four groups: Control, and treatment with H, PEM, and a combination of H and PEM. Subsequently, cell viability, apoptosis percentage, release rate of LDH, production of ROS, and the expression level of hsa-MiR-548c-3p, CASP 8 and 9, and TYMS genes were measured.
Results revealed that the combination of H and PEM treatment had greater antitumor effects compared to the other groups. The combination of H and PEM significantly reduced cell viability, increased the percentage of apoptosis, LDH release, and ROS production, and upregulated hsa-MiR-548c-3p, CASP 8, and 9, while downregulating TYMS.
The findings suggest that H enhances the chemotherapeutic efficacy of PEM by upregulating hsa-MiR-548c-3p expression and promoting apoptosis in lung cancer cells, making it a promising complementary approach for overcoming drug resistance.

This study aimed to investigate whether propofol-remifentanil anesthesia offers superior perioperative outcomes compared to propofol-fentanyl in pancreatic cancer surgery patients, with a focus on its effects on apoptotic molecules, plasma CXCL10/CXCL13 levels, and postoperative recovery.
A total of 150 pancreatic cancer patients were divided into 2 cohorts receiving either propofol-fentanyl (control group, n=75) or propofol-remifentanil (study group, n=75) anesthesia. We measured perioperative hemodynamics (cardiac index [CI], mean arterial pressure [MAP], heart rate [HR]), T-cell subsets, postoperative recovery indices (eye-opening time, extubation time, spontaneous respiration recovery time), sedation and analgesia levels (via Ramsay sedation score [RSS] and visual analog scale [VAS]), plasma CXCL10/CXCL13 levels, and apoptosis-related proteins (Survivin, Bax, Caspase-4, Bcl-2) using enzyme-linked immunosorbent assays (ELISAs). Adverse reactions were also recorded.
The study group exhibited significant advantages in hemodynamic stability and immune preservation. Despite similar baseline cardiovascular parameters, the remifentanil group maintained better CI, MAP, and HR stability during and after surgery. Flow cytometry analysis revealed better preservation of T-cell immunity (CD4⁺, CD3⁺, CD4⁺/CD8⁺ T cells) at 24 hours post-surgery. The intervention group also demonstrated accelerated postoperative recovery with significantly reduced emergence times (eye-opening, extubation, spontaneous respiration). Notably, the study group had more favorable inflammatory profiles (lower CXCL10/CXCL13 levels) and enhanced apoptotic responses (modulated Bax, Caspase-4, Survivin, and Bcl-2 expression). Clinical outcomes were superior in the study group, with significantly fewer adverse events (2 vs. 9 patients).
Propofol-remifentanil anesthesia provides effective sedation and analgesia in pancreatic cancer surgery, modulates key biological pathways related to apoptosis and inflammation, and improves postoperative recovery. These findings suggest that the choice of anesthesia regimen may have significant implications for perioperative outcomes and potentially long-term prognosis in pancreatic cancer patients. Future research should further explore the underlying mechanisms and long-term clinical benefits of this anesthesia strategy.

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.

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.

Osteoarthritis (OA) is the most common form of arthritis, characterized by pathological changes in joint components. Increasing evidence suggests that helper T (T_H) lymphocytes play a pivotal role in the inflammatory processes associated with OA. Curcumin, the primary polyphenolic compound found in Curcuma longa, exhibits potent antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of curcumin on the gene expression of key transcription factors of T_H1 and T_H2 cells and to explore their associations with clinical and immunological parameters in patients with knee OA.
This mechanistic sub-study presents a secondary molecular analysis of RNA biospecimens from a previously completed double-blind, placebo-controlled clinical trial involving 30 patients with knee OA. Participants were randomly assigned to receive either 80 mg/day of nano-micelle curcumin or a placebo for 3 months. Expression levels of T-box transcription factor 21 (T-bet) and GATA binding protein 3 (GATA3), the key transcription factors of T_H1 and T_H2 cells, respectively, were quantified using SYBR Green-based real-time PCR. Their associations with changes in visual analogue scale (VAS) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and percentages of CD4⁺ and CD8⁺ T cells were analyzed.
Curcumin administration significantly reduced T-bet gene expression compared to baseline and showed a positive correlation with the frequency of CD8⁺ T cells, while GATA3 expression remained unchanged.
These findings may provide a novel molecular perspective on curcumin's potential to influence CD8⁺ T cell dynamics by modulating T_H1-associated transcriptional programs.

Non-alcoholic fatty liver disease (NAFLD) is a major hepatic manifestation of metabolic syndrome and encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). This study aimed to evaluate the contribution of immunological, inflammatory, and metabolic parameters-including cytokine levels, immune cell profiles, and microRNA (miR) expression-in the progression from NAFLD to NASH among individuals with features of metabolic syndrome.
An observational study was conducted between January 2022 and December 2024, enrolling 300 adult patients with radiologically or histologically confirmed NAFLD. Patients underwent comprehensive anthropometric, biochemical, and immunological assessments, including cytokine profiling (interleukin [IL]-6, IL-17, tumor necrosis factor-α [TNF-α], transforming growth factor-β1 [TGF-β1]), immune cell phenotyping (T helper 17 [T_H17], regulatory T cells [Tregs], monocytes), and miR quantification (miR-122, miR-34a). Liver biopsy was performed in 95 selected cases.. The nursing team also assists in coordinating multidisciplinary care and ensuring follow-up compliance, which are vital for long-term disease management and reducing progression to NASH.
Significant elevations were observed in metabolic parameters (body mass index [BMI], homeostatic model assessment for insulin resistance [HOMA-IR]), hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST]), inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], ferritin), and oxidative stress markers (malondialdehyde [MDA]). Adipokines (↑leptin, ↓adiponectin), hepatokines (↑fibroblast growth factor 21 [FGF21], ↑fetuin-A), and cytokines (↑IL-6, ↑TNF-α, ↑IL-17) were markedly altered in patients with biopsy-proven NASH.
This study reinforces that pro-inflammatory cytokines, altered immune cell profiles, and dysregulated miRs serve as promising biomarkers for early identification and potential therapeutic targeting in metabolic syndrome-associated steatohepatitis.

Anaphylaxis is a severe, rapidly progressing, and potentially life-threatening emergency requiring prompt, evidence-based intervention. This study assessed pre-hospital emergency healthcare professionals’ knowledge of anaphylaxis diagnosis, acute management, and treatment protocols in line with current clinical guidelines.
A descriptive cross-sectional study was conducted between February and April 2025 among physicians, paramedics, and emergency medical technicians (EMTs) working in Emergency Medical Services (EMS) stations. Data were collected via a 21-item Google Forms survey covering demographics and key knowledge domains based on established pediatric anaphylaxis guidelines.
A total of 322 professionals participated: paramedics (n = 214, 66.5%), EMTs (n = 73, 22.7%), and physicians (n = 35, 10.9%). Although most reported prior anaphylaxis training (90.0%) and clinical encounters (87.6%), only 52.2% correctly identified all three diagnostic criteria. Regarding pharmacologic management, 81.7% recognized epinephrine as first-line treatment, with physicians performing best (94.3%) compared to paramedics (81.8%) and EMTs (75.3%). Similarly, 81.1% correctly identified the intramuscular route, with physicians again demonstrating superior knowledge (95.5%). However, major deficiencies were noted in appropriate patient positioning (52.2%) and epinephrine auto-injector use (50.6%), with significant inter-professional differences across both domains.
Substantial knowledge gaps exist among pre-hospital emergency providers regarding anaphylaxis diagnosis, patient positioning, and auto-injector administration. Targeted training and standardized protocols are urgently needed to enhance competency and improve patient safety in pre-hospital anaphylaxis management.

Chemokines and their receptors play a central role in mediating the migration of pathogenic T cells into the central nervous system of patients with multiple sclerosis (MS). Vitamin D and curcumin are known to possess anti-inflammatory and immunomodulatory properties; however, their combined effects on T-cell chemokine receptor expression in MS remain poorly defined.
In this study, we investigated the in vitro effects of vitamin D, curcumin, and their combination on CD4⁺ and CD8⁺ T cells expressing CXCR3, CCR6, and CCR4 in patients with relapsing-remitting MS (RRMS). Peripheral blood mononuclear cells were collected from patients in relapse (n=10), remission (n=14), and healthy controls (n=15) and analyzed using flow cytometry.
Relapse patients exhibited elevated frequencies of CXCR3⁺CD4⁺ T cells compared to healthy controls, which normalized following treatment. Increased CCR6⁺CD4⁺ T cells and CXCR3⁺CD8⁺ T cells were also observed in patients, with a significant reduction achieved only after combined treatment with vitamin D and curcumin. The combined treatment further decreased the mean fluorescence intensity of CXCR3 and CCR6 on T cells in relapse patients, while vitamin D alone specifically reduced CCR4⁺CCR6⁺CD4⁺ T cells, a T_H17-like subset enriched during relapse.
These findings indicate that vitamin D and curcumin, particularly in combination, modulate T-cell activity by downregulating chemokine receptor expression and may represent a promising adjunctive approach for controlling immune cell migration in MS.

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that can progress to cirrhosis and liver failure if untreated. Current therapies, mainly corticosteroids, are effective but limited by adverse effects and incomplete responses, prompting the search for safer alternatives. Peiminine, an alkaloid derived from Fritillaria species, has demonstrated anti-inflammatory and antioxidant properties in several disease models. This study evaluated its efficacy in a concanavalin A (ConA)–induced mouse model of AIH.
Male C57BL/6 mice were divided into six groups, including ConA-injured animals, and treatment groups receiving peiminine (3 mg/kg, i.p.), prednisolone (10 mg/kg, i.p.), or their combination.
ConA injection caused sharp increases in ALT (↑ 5.4-fold), AST (↑ 4.8-fold), and ALP (↑ 3.9-fold), alongside marked elevations in MPO activity, nitric oxide, and pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ). Peiminine significantly reversed these alterations—reducing ALT, AST, and ALP by 65% to 75% and restoring IL-4, TGF-β, and SOD activity toward normal values. Pre-treatment provided stronger protection than post-treatment, and outcomes were comparable to those of prednisolone, with combination therapy yielding the greatest improvement across all indices.
These findings indicate that peiminine mitigates immune-mediated hepatic injury by modulating cytokines, reducing oxidative stress, and maintaining liver integrity. Peiminine may represent a promising preventive or adjunct therapy for AIH, warranting further mechanistic and long-term investigations.

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.

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.

 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.

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.

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.

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. 

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.

Common variable immunodeficiency disease (CVID) is the most prevalent symptomatic inborn errors of immunity, determined by defective B cell function, impaired antibody production, and susceptibility to frequent respiratory infections, enteropathy, autoimmunity, and malignancy. Due to the importance of autoimmunity in CVID and the probable role of regulatory B lymphocytes, we aimed to determine the frequency of B10 cells in CVID patients with and without autoimmunity.
A total of 24 CVID patients and 12 healthy controls were enrolled in the study. Patients were divided into two equal groups, with and without autoimmunity. Peripheral blood cells were stained with monoclonal antibodies (mAbs) to identify CD24^hiCD38^hi B cells, CD27^int CD38⁺ (plasmablasts), and CD24^hiCD27⁺ B cells by flow cytometry.
The percentages of B10, CD24^hiCD27⁺ and CD27^int CD38⁺ cells were significantly lower in total CVID patients, CVID patients with autoimmunity and CVID patients without autoimmunity compared to healthy controls (mean±standard deviation (SD) percentage of B10 cells: 6.36±9.21(total CVID), 2.81±5.00 (CVID with autoimmunity), and 3.25±3.5 (CVID without autoimmunity) vs. 13.02±12.45 (healthy controls); CD24^hiCD27⁺ cells: 2.39±3.89, 3±5.20 and 1.78±1.94 vs. 20.38±14.27; CD27^int CD38⁺ cells: 6.80±18.49, 7.40±20.24 and 6.20±17.45 vs. 11.84±5.71). CVID patients without autoimmunity had a higher percentage of CD24^hiCD38^hi cells than CVID patients with autoimmunity (4.73±4.14 vs. 2.62±5.02).
The defect of regulatory B cells plays a significant role in the pathogenesis of autoimmunity in CVID. Further multicenter studies with higher sample sizes are suggested to determine the role of Breg cells in the clinical course of autoimmunity. 

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.

Human cytomegalovirus (HCMV) is a frequent complication in kidney transplant recipients (KTRs), often impacting immune regulation. T_H9 cells, a subset of CD4⁺ T cells, are characterized by their secretion of interleukin-9 (IL-9). This study aimed to analyze the phenotypic profile of T_H9 cells and their associated cytokine expression in KTRs, and to evaluate mRNA levels of IL-4 and transforming growth factor-β (TGF-β), key cytokines involved in T_H9 differentiation.
Ten HCMV⁺ and 10 HCMV⁻ KTRs, along with 10 age- and sex-matched healthy controls, were enrolled. HCMV viral load was quantified using TaqMan real-time polymerase chain reaction. Flow cytometry was used to assess surface markers (CCR6⁺CCR4⁻IL-4Rα⁺CD4⁺) and intracellular IL-9 expression in T_H9 cells. Gene expression levels of IL-4 and TGF-β were also assessed.
Surface staining revealed a significantly higher frequency of CD4⁺CCR4⁻ and CD4⁺CCR6⁺ T cells in HCMV⁻ KTRs compared to HCMV⁺ patients. Conversely, the overall frequency of CD4⁺ T_H9 cells was elevated in HCMV⁺ KTRs. Intracellular staining demonstrated a significant increase in CD4⁺IL-9⁺ and CD4⁺IL-4Rα⁺ T cells in the HCMV⁺ group. Additionally, mRNA expression levels of IL-4 and TGF-β were markedly higher in HCMV⁺ KTRs than in HCMV⁻ counterparts.
These findings suggest a potential role for T_H9 cells and their signature cytokine IL-9 in the antiviral immune response in KTRs. While T_H9 cells may contribute to HCMV-related immune modulation, further research is needed to fully elucidate their protective mechanisms against viral infections.

Keywords: ; ; ; 

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 Warburg effect is one of the most important metabolic alterations in tumor cells. Hypoxia-inducible factor 1-alpha (HIF-1α) targets a broad range of gene promoters in normoxic and hypoxic conditions in cancers. Herein, we investigate the effects of HIF-1α inhibition on cell viability and messenger RNA (mRNA) expression of immune checkpoint receptors (ICRs) in acute myeloid leukemia cell lines.
K-562 and HL-60 cells were treated with silibinin as an HIF-1α inhibitor. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, followed by quantification of V-domain immunoglobulin suppressor of T-cell activation (VISTA), T-cell immunoglobulin and mucin domain 3 (TIM3), and Galectin-9 mRNA expression via quantitative reverse-transcription polymerase chain reaction (qRT-PCR).
The expression levels of VISTA, TIM3, and Galectin-9 decreased after silibinin treatment within both K-562 and HL-60 cells; however, there were some disparities in gene expression levels between the two cell lines. VISTA and TIM3 expression were reduced by approximately 70% in K-562 at the 40% inhibitory concentration (IC40), while no significant changes were observed in HL-60 cells. Conversely, Galectin-9 expression was decreased significantly at both the IC30 and IC40 in HL-60, whereas it was almost consistent in K-562 cells.
 Collectively, we have shown that silibinin could serve as a cytotoxic small-molecule inhibitor and regulate the expression of ICRs, potentially counteracting T-cell exhaustion.

Eosinophilic gastrointestinal diseases (EGIDs) are chronic, T_H2-mediated conditions. Eosinophilic esophagitis (EoE) is the most common type, while non-EoE EGIDs affect other gut segments.
This retrospective study of 111 patients (50 EoE and 61 non-EoE) from 2011 to 2022 compared the clinical aspects of these 2 types.
Dysphagia and food impaction dominated in EoE, while abdominal pain, nausea, and diarrhea were more common in non-EoE EGIDs. Atopic comorbidities were frequent. Diagnostic delays>1 year were more common in EoE (72% vs 47.5%). The overall clinical response rate was 88.29%, with most patients using food avoidance (90.99%) and proton pump inhibitors (94.59%). Clinical relapses occurred in 38.88% over the mean follow-up of 4.62 years and were unaffected by therapy type. Failure to thrive was seen in 26.7%, with no significant intergroup difference.
This study highlights a prolonged diagnostic delay in EoE vs non-EoE EGIDs. Both groups showed similar, favorable response rates, underscoring a need for greater awareness. Prospective studies with standardized measures are required to optimize management.

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.

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.

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. 

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.

This study aimed to assess the clinical symptoms associated with UFs and to evaluate dynamic, longitudinal changes in serum inflammatory markers before and after treatment in women diagnosed with UFs compared with healthy controls.
In this retrospective observational study, 90 women including 60 women diagnosed with UFs and 30 age-matched healthy controls. Uterine fibroids were confirmed by ultrasonography and histopathology. Serum levels of tumor necrosis factor α (TNF-α), interferon β (IFN-β), IFN-γ, C-reactive protein (CRP), and basic fibroblast growth factor (FGF) were measured using standardized enzyme-linked immunosorbent assay kits. Lymphocyte subsets were analyzed via flow cytometry. Patients with UFs underwent medical or surgical treatment based on clinical indications, and inflammatory markers were reassessed 3 months posttreatment.
There were various symptoms such as pelvic pain (66.67%), abnormal bleeding (66.67%), organ-compression symptoms (45%), infertility (26.67%), and miscarriage (18.33%) compared with controls. Women diagnosed with UFs showed a higher lymphocyte count, proinflammatory mediators, and decreased level of interleukins as compared with the healthy population of females.
The observed dynamic pretreatment and posttreatment shifts in serum inflammatory markers suggest involvement of adaptive immunity and angiogenic pathways, highlighting the potential role of inflammatory regulation in improving reproductive outcomes, including preparation for assisted reproductive technologies.

Combined immunodeficiencies (CIDs) represent a rare group of inherited immune disorders in which defects in T- and B-lymphocyte function lead to recurrent infections, immune dysregulation, and an increased tendency toward autoimmune and rheumatologic complications.
A retrospective cross-sectional analysis was performed on 150 patients with CID, diagnosed according to the European Society for Immunodeficiencies (ESID) criteria and followed at the Children’s Medical Center and Mofid Children’s Hospital (Tehran, Iran) between 2009 and 2020. Clinical records, immunologic evaluations, and rheumatologic findings were reviewed, with particular attention to autoantibody detection and disease frequency. Among 150 patients, 42 (28%) exhibited rheumatologic manifestations, with a higher frequency in females. Undifferentiated rheumatoid arthritis, undifferentiated juvenile idiopathic arthritis, and Kawasaki disease were the predominant conditions. Although lower lymphocyte counts and immunoglobulin levels were observed among non-rheumatologic patients, the differences were not statistically significant.
Impairments in T-cell–mediated immunity and antibody synthesis among individuals with CID hinder the recognition of autoantibody-associated rheumatologic disorders and delay diagnosis. Moreover, these conditions often present atypically in immunocompromised hosts; therefore, a vigilant clinical approach is essential for early identification and management.

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.

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.

Breast cancer is a leading malignancy in women. Understanding its clinicopathological traits and microsatellite status is vital for prognosis and treatment planning. This study explored the links between preoperative pan-immune-inflammation value (PIV) and hemoglobin, albumin, lymphocyte, and platelet (HALP) score with breast cancer’s pathological features and microsatellite status and assessed their predictive power for the latter.
This retrospective study analyzed data from 260 breast cancer patients who had surgery between 2022 and 2025. Researchers not involved in the patients’ treatment collected and analyzed the data. HALP and PIV were calculated from preoperative blood tests. Patients were grouped based on the median values of these scores. Associations between the scores and clinicopathological characteristics were examined. Patients were also divided into microsatellite stable (MSS) and microsatellite instability-high (MSI-H) groups, and differences in HALP and PIV between these groups were compared. Receiver operating characteristic curves were used to evaluate the predictive accuracy of HALP and PIV for microsatellite status.
High PIV was linked to younger age and lower ER positivity. High HALP correlated with older age, a higher proportion of clinical stage I patients, and lower HER2 positivity. MSS patients had lower PIV and higher HALP than MSI-H patients. PIV and HALP showed significant correlations with microsatellite status. Both indicators had high AUC values (PIV: 0.867; HALP: 0.879), with 100% sensitivity, indicating strong predictive capabilities.
Preoperative PIV and HALP are closely tied to breast cancer’s pathological features and microsatellite status. They offer high predictive value for microsatellite status, aiding in breast cancer diagnosis and treatment decisions. 

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.