People’s Hospital of Linqing

Atherosclerosis (AS) is a growing vascular disease linked to plaque buildup, causing blood flow issues. Current diagnosis relies on symptoms and imaging, which are limited for early detection and plaque biology assessment. Treatments focus on symptoms but don’t address root causes, leading to complications. This study aims to find new diagnostic markers and therapies using bioinformatics and machine learning. Data from gene expression omnibus datasets (GSE28829 for gene expression, GSE159677 for single-cell analysis) were analyzed via WGCNA to identify gene modules, Limma for differentially expressed genes, and gene ontology/KEGG for pathway enrichment. Protein-Protein Interaction networks, machine learning (least absolute shrinkage and selection operator, Random Forest, artificial neural network), immune infiltration (CIBERSORT), and single-cell RNA-seq were used. A nomogram model was built, and candidate drugs (e.g., simvastatin) were tested via molecular docking. Key modules (turquoise) and 238 differentially expressed genes linked to immune processes. Four biomarkers (toll like receptor 2, CCR1, interferon regulatory factor 8, CCL4) showed high diagnostic accuracy (AUC > 0.8). Immune analysis revealed altered macrophage/T cell profiles, with biomarkers correlating to monocyte/macrophage activity. The nomogram model was robust, and simvastatin docked strongly to target proteins. toll like receptor 2, CCR1, interferon regulatory factor 8, and CCL4 are novel AS biomarkers linked to immune pathways. The nomogram aids risk prediction, and simvastatin shows potential as a targeted therapy. Findings advance AS understanding and offer tools for early diagnosis and personalized treatment.

Atrial fibrillation (AF) is the most common persistent arrhythmia, contributing substantially to morbidity, mortality, and healthcare burden. The basement membrane is essential for tissue homeostasis and disease regulation. Exploring the relationship between AF and basement membrane–associated genes may provide new insights into the molecular mechanisms of atrial remodeling and arrhythmogenesis. mRNA expression datasets (GSE31821, GSE41177, GSE79768) were obtained from the Gene Expression Omnibus (GEO). The “merge” function in R was used to identify the overlap between basement membrane-related genes and these datasets. Differentially expressed basement membrane-related genes (DEBMRGs) were analyzed through enrichment analysis. Key target genes were screened using Lasso regression, Random Forest, SVM-RFE, and protein–protein interaction (PPI) network analysis. Mendelian randomization (MR) was applied for validation. Immune cell infiltration and gene set variation analysis (GSVA) were further performed. Fifty-five DEBMRGs were identified. PPI network construction and machine learning approaches consistently highlighted ITGA1 and ITGB5 as central genes. MR analysis supported these findings, showing an odds ratio (OR) of 1.033 [95% CI: 1.028–1.038, P = 1.55 × 10−36] for ITGA1 and an OR of 0.891 [95% CI: 0.862–0.921, P = 7.66 × 10−12] for ITGB5. No evidence of heterogeneity or pleiotropy was detected. Immune infiltration analysis revealed significant immune cell differences between AF and control samples. This study identifies ITGA1 and ITGB5 as basement membrane–associated genes linked to AF, providing novel insight into AF pathogenesis. These genes may represent promising biomarkers and therapeutic targets for AF management.

Introduction and AimImmunotherapies targeting tumor-associated macrophages (TAM) to improve antitumor immunity, are promising treatment strategies for many types of cancer. The signal-regulatory protein-α (Sirp-α)/CD47 axis is a key innate immune checkpoint target important in regulating phagocytosis in macrophages. We aimed to determine whether a Sirp-α monoclonal antibody (mAb) could prevent renal cell carcinoma (RCC) progression by acting on macrophages and modifying their phenotype.MethodsWe explored the gene expression signature of macrophages in the RCC microenvironment by analyzing transcriptome data of blood monocytes from patients with RCC vs healthy donors, and macrophages vs non-immune cells in RCC from public databases. We characterized the prevailing macrophage polarization phenotypes and the different ratios of Akt1 and Akt2 in RCC according to cell surface markers and expression profiles, prior to examining the effect of Sirp-α mAb on the M2 macrophage polarization in an in vitro co-culture model of RCC cells with macrophages. The co-culture model included human RCC cell lines and induced M2 macrophages, including a subset that had been transfected to overexpress phosphoinositide 3-kinase (PI3K).Results and ConclusionTreatment of RCC with Sirp-α mAb counteracted the enhanced migration and invasion of RCC as measured in wound healing and transwell assays and in vivo model. Collectively, our data showed that the different ratio of Akt1 and Akt2 of the PI3K/Akt pathway is involved in the RCC-induced M2 polarization of macrophages and that a new mechanism that the Sirp-α mAb inhibited M2 macrophage polarization by regulating components of the PI3K/Akt pathway. Elucidating the mechanism by which Sirp-α mAb inhibits the development of RCC allows us to provide a new theoretical basis for the study of the mAb in RCC immunotherapy.

Emergency departments (EDs) in the US treat large numbers of people with opioid use disorder (OUD), but most health systems do not equip EDs to provide OUD care. CA Bridge has supported the implementation of low-threshold, ED-initiated medications for OUD bundled with harm reduction and patient navigation in more than 80percent of California EDs. Using grant reporting and California controlled substances prescribing data, we assessed CA Bridge implementation from July2022 through December2023, as well as 2022 California statewide ED buprenorphine prescribing. There were 165,671 patient navigator encounters and 44,996 instances of buprenorphine treatment at CA Bridge hospitals; patient navigator and buprenorphine treatment rates at public hospitals were more than 50percent higher than at private hospitals. In 2022, across the entire state, 1,737 California emergency clinicians wrote 6,382 buprenorphine prescriptions; 36percent of the people who were given those prescriptions received a subsequent buprenorphine prescription within forty days. Our findings suggest that EDs can reach large numbers of people with OUD, and buprenorphine uptake is high.

Hypertension is a significant public health concern, especially among younger adults. Effective management of risk factors and adherence to recommended lifestyle changes are crucial for preventing long-term cardiovascular complications. This study analyzed data from 11,514 hypertensive participants aged 18 to 65 from the NHANES 1999–2018. Risk factor targets included BMI, LDL-C, waist circumference, and HbA1c, while lifestyle goals focused on smoking cessation, alcohol consumption, physical activity, sodium, and fiber intake. Statistical analyses involved chi-square tests, t-tests, and multivariate logistic regression. The mean age was 50.66 years, with 50.94% being male. Only 15.62% of participants met the BMI target, 66.02% met the LDL-C target, and 29.19% achieved the waist circumference goal. Regarding lifestyle, 71.32% met the smoking cessation target, but only 23.45% met the physical activity goal, and 14.44% achieved sufficient fiber intake. Overall, just 2.41% of participants met all risk factor targets, and 0.03% met all lifestyle goals. Poorer outcomes were linked to lower socioeconomic status, lower education levels, and the presence of comorbidities. These findings highlight significant gaps in risk factor control and lifestyle adherence among non-elderly hypertensive patients, underscoring the need for tailored interventions to improve cardiovascular outcomes.

This Mendelian randomization study investigated the causal relationship between phosphatidylinositol (PI) levels and hypertrophic cardiomyopathy (HCM) risk, while evaluating the potential mediating role of interleukin-20 receptor subunit alpha (IL-20RA). Leveraging genome-wide association study data from Finnish and European populations, our 2-sample Mendelian randomization analysis revealed a significant inverse association between PI levels and HCM risk (odds ratio [OR] = 0.686, 95% confidence interval [CI]: 0.512–0.921; P = .012), with no evidence of reverse causation. The analysis further demonstrated a positive correlation between PI and IL-20RA levels (OR = 1.090, 95% CI: 1.033–1.149; P = .002), while elevated IL-20RA showed a protective association against HCM (OR = 0.514, 95% CI: 0.302–0.873; P = .014). Mediation analysis indicated that approximately 15.2% of PI’s protective effect was mediated through IL-20RA pathways. These findings suggest PI may mitigate HCM risk partially through IL-20RA-mediated mechanisms, highlighting potential therapeutic targets in lipid-inflammatory pathways for HCM intervention. Further research is needed to validate these observational genetic associations.

The gut-brain-kidney axis represents a dynamic interplay among the gut microbiota, renal function, and neurological processes, emerging as a critical factor in chronic kidney disease (CKD) pathophysiology. This paper reviews recent data on the mechanisms and pathways that integrate gut-brain-kidney signaling and communication, advances in our understanding of this axis, and potential diagnostic and prognostic biomarkers and interventions for CKD. Literature search was conducted on PubMed, Scopus, Web of Science, and Embase using a combination of the keywords gut microbiota, gut microbiome, gut-brain axis, gut-kidney axis, gut-brain-kidney axis, chronic kidney disease, dysbiosis, therapy, metabolites, and neuroinflammation." Relevant studies were selected and synthesized in this narrative review. Gut dysbiosis, characterized by microbial composition and function alterations, contributes to systemic inflammation and metabolic imbalances, exacerbating CKD progression. Uremic toxins such as indoxyl sulfate and p-cresyl sulfate, derived from microbial metabolism, impair kidney function and disrupt neurocognitive health via oxidative stress and neuroinflammation, highlighting the interconnectedness of these systems. Recent advances in high-throughput sequencing and metabolomics have elucidated mechanisms linking gut microbiota and associated metabolites to kidney and brain health, revealing the role of microbial diversity and metabolite profiles in disease outcomes. Studies demonstrate that probiotics, prebiotics, and dietary interventions targeting the gut microbiota can modulate systemic inflammation and reduce uremic toxin levels, offering therapeutic potential. Understanding the bidirectional signaling within the gut-brain-kidney axis opens avenues for novel biomarkers and interventions in CKD management.

Nuclear protein in testis (NUT) carcinoma is a rare disease characterized by aggressive and rapid progression. There is no standard management of primary pulmonary NUT carcinoma until now, and the median overall survival is only 4.4 months. Here, we describe a case where a 48-year-old woman presented with a dry, lasting half a month, and she was diagnosed with primary pulmonary NUT carcinoma and was given chemotherapy, immunotherapy, antiangiogenesis therapy, and palliative radiotherapy. When secondary tumor progression, she was conducted an organoid drug sensitivity test for better guide therapy. The initial two cycles of first-line and second-line treatments in our patient proved effective and improved the overall survival to more than 8 months. This is the first report of the use of an organoid drug sensitivity test for primary pulmonary NUT carcinoma. It provides a new approach for selecting drugs, particularly when multiple lines of treatment have proven ineffective and the next steps are unclear.