Alternative RNA splicing is an essential mechanism linking genetic variation to human diseases. While the signals from genome-wide association studies (GWAS) have been linked to expression quantitative trait loci (eQTL) in previous studies, further work is needed to better elucidate the relationship to other genetic regulatory mechanisms, such as splicing QTLs (sQTL). Here, we performed a genome-wide sQTL analysis to identify variants that might affect RNA splicing in 1,010 non–small cell lung cancer (NSCLC) samples from The Cancer Genome Atlas. The identified sQTLs were largely independent of eQTLs and were predominantly enriched in exonic regions, genetic regulatory elements, RNA-binding protein (RBP) binding sites, and known NSCLC risk loci. In addition, target genes affected by sQTLs (sGenes) were involved in multiple processes in cancer, including cell growth, apoptosis, metabolism, immune infiltration, and drug responses, and sGenes were frequently altered genetically in NSCLC. Systematic screening of sQTLs associated with NSCLC risk using GWAS data from 15,474 cases and 12,375 controls identified an sQTL variant rs156697-G allele that was significantly associated with an increased risk of NSCLC. The association between the rs156697-G variant and NSCLC risk was further validated in two additional large population cohorts. The risk variant promoted inclusion of GSTO2 alternative exon 5 and led to higher expression of the GSTO2 full-length isoform (GSTO2-V1) and lower expression of the truncated GSTO2 isoform (GSTO2-V2), which was induced by RBP quaking (QKI). Mechanistically, compared with GSTO2-V1, GSTO2-V2 inhibited NSCLC cells proliferation by increasing S-glutathionylation of AKT1 and thereby functionally blocking AKT1 phosphorylation and activation. Overall, this study provides a comprehensive view of splicing variants linked to NSCLC risk and provides a set of genetic targets with therapeutic potential. Significance: Analysis of sQTL reveals the role of genetically driven mRNA splicing alterations in NSCLC risk and elucidates that rs156697 variant impacts risk by altering GSTO2 splicing.

Obstructive Sleep Apnea Syndrome (OSAS) affects 13–33% of males and 6–9% of females globally and poses significant treatment challenges, including poor adherence to Continuous Positive Airway Pressure (CPAP) and residual excessive sleepiness (RES). This review aims to elucidate the emerging interest in pharmacological treatments for OSAS, focusing on recent advancements in this area. A thorough analysis of extensive clinical trials involving various drugs, including selective dopamine reuptake inhibitors, selective norepinephrine inhibitors, combined antimuscarinic agents, and orexin agonists, was conducted. These trials focused on ameliorating respiratory metrics and enhancing sleep quality in individuals affected by OSAS. The studied pharmacological agents showed potential in improving primary outcomes, notably the apnea-hypopnea index (AHI) and the Epworth sleepiness scale (ESS). These improvements suggest enhanced sleep quality and symptom management in OSAS patients. With a deeper understanding of OSAS, pharmacological interventions are emerging as a promising direction for its effective management. This review provides a comprehensive overview of the current state of drug research in OSAS, highlighting the potential of these treatments in addressing the disorder’s complex challenges.

Background: By 2020, obstructive sleep apnea (OSA), a prevalent respiratory disorder, had affected 26.6–43.2% of males and 8.7–27.8% of females worldwide. OSA is associated with conditions such as hypertension, diabetes, and tumor progression; however, the precise underlying pathways remain elusive. This study aims to identify genetic markers and molecular mechanisms of OSA to improve understanding and treatment strategies.Methods: The GSE135917 dataset related to OSA was obtained from the GEO database. Differentially expressed genes (DEGs) were subsequently identified. Weighted gene co-expression network analysis (WGCNA) was conducted to pinpoint disease-associated genes. The intersection of these data enabled the identification of potential diagnostic DEGs. Further analyses included Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment studies, exploration of protein–protein interactions based on these genes, and an examination of immune infiltration. Mendelian randomization was employed to validate core genes against the Genome-Wide Association Study database.Results: A total of 194 DEGs were identified in this study. WGCNA network analysis highlighted 2,502 DEGs associated with OSA. By intersecting these datasets, 53 diagnostic DEGs primarily involved in metabolic pathways were identified. Significant alterations were observed in immune cell populations, including memory B cells, plasma cells, naive CD4 T cells, M0 macrophages, and activated dendritic cells. CETN3, EEF1E1, PMM2, GTF2A2, and RRM2 emerged as hub genes implicated in the pathogenesis. A line graph model provides diagnostic insights. Mendelian randomization analysis confirmed a causal link between CETN3 and GTF2A2 with OSA.Conclusion: Through WGCNA, this analysis uncovered significant genetic foundations of OSA, identifying 2,502 DEGs and 194 genes associated with the disorder. Among these, CETN3 and GTF2A2 were found to have causal relationships with OSA.

Splenic tuberculosis is a rare form of extrapulmonary tuberculosis, that is often caused by hematogenous dissemination. A 53-year-old female presented with multiple enlarged lymph nodes and a splenic mass identified during a routine health check. Imaging revealed widespread lymphadenopathy and multiple splenic nodules, raising suspicion for lymphoma. The laboratory findings showed an elevated erythrocyte sedimentation rate and mild liver function abnormalities, with no significant tumor markers or inflammatory indicators. Histopathology of lymph node and splenic biopsies revealed granulomas with epithelioid cells and multinucleated giant cells. Acid-fast staining confirmed the presence of Mycobacterium tuberculosis, indicating the presence of splenic tuberculosis. The patient was treated with a standard anti-tuberculosis regimen and adjunctive hepatoprotective therapy, resulting in clinical improvement, and was discharged in stable condition. This case underscores the diagnostic challenges of splenic tuberculosis due to its non-specific presentation and highlights the importance of histopathological evaluation for timely diagnosis and treatment.

This study aimed to evaluate the clinical significance of the hemoglobin-to-red blood cell distribution width ratio (HRR) in patients with severe obstructive sleep apnea syndrome (OSAS). A retrospective analysis was conducted on 216 patients who underwent polysomnography (PSG) between January 2018 and February 2023. Patients were divided into two groups according to the apnea-hypopnea index (AHI): severe OSAS (n = 131) and non-severe OSAS (n = 85). Comparisons were performed between the two groups regarding baseline characteristics, AHI, minimum blood oxygen saturation (MinSaO₂), and hematological parameters including white blood cell (WBC) count, red blood cell (RBC) count, platelet count (PLT), hemoglobin (Hb), red blood cell distribution width (RDW), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and HRR. Correlation analyses were conducted to assess relationships between AHI, MinSaO₂, and HRR in the severe OSAS group. Receiver operating characteristic (ROC) curve analysis revealed that HRR had an area under the curve (AUC) of 0.84 for predicting severe OSAS, with a sensitivity of 81.68%, specificity of 72.94%, and 95% confidence interval (CI) of 0.784–0.886. The levels of AHI, MinSaO₂, Hb, and HRR were significantly higher in the severe OSAS group. Elevated AHI levels may indicate an increased risk of severe OSAS. HRR may serve as an early predictive biomarker for severe OSAS, facilitating timely intervention and potentially reducing complication risks.

Background: This study integrates transcriptomics and polysomnography (PSG) to investigate the core signaling pathways underlying obstructive sleep apnea (OSA), aiming to elucidate its complex pathophysiological mechanisms. These findings may provide new perspectives on the prevention, diagnosis, and treatment of OSA. Methods: Participants underwent PSG to monitor indicators, such as total sleep time, apnea–hypopnea index (AHI), oxygen desaturation index (ODI) and lowest oxygen saturation (LSO ₂ ). Individuals with AHI > 5 were categorised into the OSA group, while others were classified as the regular snoring group. Total RNA from white blood cells was extracted using the TRIzol method, and transcriptomic data were obtained via high‐throughput sequencing. Weighted Gene Coexpression Network Analysis (WGCNA) and Protein–Protein Interaction (PPI) network analysis were used to identify OSA‐related core genes. Differential gene expression, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore key signaling pathways. Single‐cell sequencing validated the findings, and Mendelian randomization (MR) analysis confirmed causal links between genes and pathways. Results: While no significant differences were observed between the OSA and regular snoring groups in gender, age, or body mass index (BMI), significant disparities were noted in sleep parameters such as AHI, ODI, and LSO ₂ . Principal component analysis (PCA) revealed transcriptomic differences between the groups. WGCNA identified 302 differentially expressed genes (DEGs), with the Palevioletred module significantly correlating with PSG parameters. GO and KEGG analyses implicated core genes in regulating inflammation, viral defence, cell growth, and apoptosis, highlighting the NF‐κB signaling pathway as central to OSA pathogenesis. PPI analysis identified key genes, including CEBPB and SPI1, while single‐cell sequencing suggested NF‐κB pathway activation affecting T cell subgroup distribution. MR confirmed causal relationships between core genes and the NF‐κB pathway. Conclusion: This study identified significant differences in sleep parameters between OSA and regular snoring groups and revealed core genes enriched in the NF‐κB signaling pathway. These findings suggest that targeting the NF‐κB pathway may offer therapeutic benefits for OSA.