International Journal of General Medicine最新文献

Background: We conducted a Mendelian randomization study in conjunction with a network pharmacology study to provide an analytical elucidation of the potential causal relationship between blood pressure and antihypertensive drugs and rheumatoid arthritis.

Methods: First, a Mendelian randomization analysis was performed using large-scale GWAS data to assess the causal associations of systolic/diastolic blood pressure and 12 antihypertensive drug classes with rheumatoid arthritis. The analytical model of inverse variance weighting was primarily utilized. Second, we constructed a "drug-component-target-disease" regulatory network graph and analyzed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Third, we validated some of the mined data through molecular docking technology using BIOVIA Discovery Studio 2019. Finally, animal experiments were performed to verify.

Results: The results indicated that elevated diastolic blood pressure was significantly associated with an increased risk of rheumatoid arthritis. Among antihypertensive drugs, adrenergic neuron blockers, central antihypertensives, and potassium-sparing diuretics/aldosterone antagonists reduced the risk of rheumatoid arthritis. Sensitivity analyses demonstrated the absence of pleiotropy or heterogeneity. In addition, after network pharmacology research, the molecular docking of its active ingredients with their targets was carried out, and the link potential was relatively ideal. Construction of a rat model of rheumatoid arthritis, Western blotting assay for Endothelin Receptor Type B (EDNRB), Angiotensin II Receptor Type (AGTR) expression level. Western blot analysis showed elevated EDNRB and AGTR levels in the model group, with spironolactone group significantly reducing these levels, though still higher than methotrexate group.

Conclusion: The findings of our study indicate that elevated diastolic blood pressure is associated with an increased risk of rheumatoid arthritis. However, three classes of antihypertensive medications, namely adrenergic neuron blockers, central antihypertensives, and potassium-sparing diuretics and aldosterone antagonists, have been demonstrated to exert beneficial effects on rheumatoid arthritis.

Lung cancer remains a leading cause of cancer-related mortality worldwide, and immunotherapy has emerged as a promising treatment modality. However, its efficacy is limited to a subset of patients, necessitating predictive biomarkers for personalized treatment strategies. DNA methylation (DNAm) is increasingly recognized as a crucial regulators of gene expression and immune responses in the tumor microenvironment. This review focuses on DNAm as a key epigenetic biomarker for predicting and enhancing immunotherapy efficacy in lung cancer. We highlight DNAm changes in key immune-related genes and their association with tumor phenotype, immune cell infiltration, and response to immune checkpoint inhibitors (ICIs). The review also evaluates established and emerging genomic and non-genomic biomarkers, including tumor mutational burden (TMB), microsatellite instability (MSI), PD-L1 expression, tumor-infiltrating lymphocytes (TILs), and immunosuppressive cytokines in case of lung cancer immunotherapy. Furthermore, the potential for integrated epigenetic signatures and minimally invasive diagnostic approaches, such as liquid biopsies, is discussed. Finally, we address the challenges and future directions for translating epigenetic biomarkers into clinical practice to improve immunotherapy outcomes and reduce immune-related adverse events.

Background: Low-density lipoprotein receptor-related protein (LRP) is integral to protein synthesis and contributes significantly to tumor initiation and growth. However, the role of LRP-related mRNAs (LRPMRs) in KIRC progression remains unclear. Our study investigates the potential use of LRPMRs as prognostic markers in patients with KIRC.

Methods: Clinical and transcriptomic data of KIRC patients were obtained from The Cancer Genome Atlas (TCGA) database for model construction and performance evaluation. A nomogram integrating clinical characteristics and the risk model was then established. To explore the clinical significance and underlying mechanisms, we analyzed the tumor microenvironment (TME), evaluated tumor mutational burden (TMB), performed gene set enrichment analysis, and predicted drug sensitivity. The mRNA expression was assessed using RT-qPCR.

Results: A six-LRPMR-based model was developed and provided significant prognostic information. Kaplan-Meier analysis demonstrated worse survival outcomes for high-risk (H-R) patients (p < 0.001). A nomogram incorporating the risk model showed improved predictive accuracy compared with the clinical model alone (AUC = 0.761). GSEA highlighted proximal tubule transport and propanoate metabolism pathways as significantly enriched in the low-risk (L-R) group, while the H-R group displayed enrichment in CD22-mediated BCR regulation and FCGR activation pathways. Higher TMB in the H-R cohort predicted a poor prognosis. TME analysis suggested that H-R patients may respond less favorably to immunotherapy. Drug sensitivity analysis indicated that H-R patients were more sensitive to Staurosporine and Sabutoclax, whereas L-R patients were more sensitive to dihydrorotenone and osimertinib. RT-qPCR validated differential mRNA expression between KIRC and normal cells.

Conclusion: This six-LRPMR-based prognostic model provides valuable insights for prognosis assessment and personalized treatment selection in KIRC.

Patients with rheumatoid arthritis (RA) exhibit a significantly higher incidence of secondary osteoporosis compared to the general population, leading to substantially increased fracture risk, compromised quality of life, and poorer prognosis. Traditional views attribute this primarily to inflammatory activity, immobilization, and glucocorticoid use. However, the emergence of osteoimmunology has revealed deeper mechanisms, demonstrating that RA-induced osteoporosis represents a classic paradigm of osteoimmune dysregulation. This review systematically synthesizes recent advances (past 5-10 years) in understanding the pathophysiology of RA-induced osteoporosis from an osteoimmunological perspective. Research indicates that within the synovial and bone marrow microenvironments of RA, activated immune cells and stromal cells secrete abundant pro-inflammatory cytokines and express signaling molecules. This process severely disrupts core regulatory pathways of bone remodeling, leading to a profound imbalance characterized by excessive bone resorption and inadequate bone formation. Key mediators of this imbalance include dysregulation of the RANKL/RANK/OPG system and upregulation of potent inhibitors of the bone-forming Wnt pathway. Complex interactions between immune cells and bone cells are critical in establishing a localized bone-destructive microenvironment. Emerging research areas, including gut microbiota dysregulation, epigenetic mechanisms, and neuro-immune interactions, provide novel insights into these mechanisms. This review emphasizes that dysregulation of the osteoimmune system constitutes the core pathophysiological basis of RA-induced osteoporosis. A deeper understanding of these mechanisms is crucial for developing targeted bone-protective therapies and guiding future clinical strategies.

Objective: To investigate the therapeutic effects of Gupishengji-Huazhuojiedu Decoction (GHD) in inducing remission in Crohn's disease (CD) and to explore its potential underlying mechanisms.

Methods: A two-stage exploratory study was conducted. Stage one included a retrospective analysis (17 GHD, 27 infliximab [IFX]) and a prospective single-arm trial (n=8), assessing clinical remission (CDAI <150), endoscopic response (≥50% SES-CD reduction), and inflammatory biomarkers (CRP, fecal calprotectin). Stage two applied network pharmacology, machine learning (random forest, LASSO, XGBoost), and immunohistochemistry to explore GHD mechanisms.

Results: In the retrospective analysis, the GHD group exhibited a higher clinical remission rate than the IFX group (88.2% vs 51.9%, p=0.01), with trends toward higher clinical response (88.2% vs 63.0%, p=0.07) and endoscopic remission rates (58.8% vs 37.0%, p=0.16). In the prospective study, 87.5% (7/8) of patients achieved both clinical remission and endoscopic response after 12 weeks of treatment. CDAI, SES-CD, CRP, and fecal calprotectin levels were all significantly reduced compared with baseline (p<0.05). Bioinformatics analysis identified 13 key functional components (KFCGs) from GHD, and intersection of their 369 targets with CD differentially expressed genes yielded 36 candidate genes. Machine learning further prioritized six feature genes (IDO1, PRKG2, TGM2, ALDH1A2, ACPP, CASP1). Immune infiltration analysis revealed differences in immune cell populations between CD patients and healthy controls. Immunofluorescence experiments confirmed that GHD treatment significantly reduced the expression of CASP1, IDO1, CD11c, CD83, KLRG1, and CD45RO in intestinal mucosal tissue (p<0.05).

Conclusion: This study suggests that GHD may induce remission in CD through a multi-component, multi-target mechanism, particularly by modulating pathways related to CASP1 and IDO1, thereby improving clinical symptoms and endoscopic findings. The underlying mechanism may involve regulation of the intestinal immune-inflammatory microenvironment. GHD holds promise as a potential traditional Chinese medicine strategy for treating CD, but further validation in larger randomized controlled trials is warranted.

Acute promyelocytic leukemia(APL), a distinct subtype of acute myeloid leukemia(AML), has garnered significant attention in recent years regarding its pathogenesis and the molecular basis of its treatment response. With the rapid advancement of proteomics and metabolomics technologies, researchers can now delve deeper into revealing the molecular characteristics of acute promyelocytic leukemia and the regulatory role of its microenvironment. This review summarizes the latest research progress in proteomics and metabolomics within the acute promyelocytic leukemia field, focusing on analyzing the critical role of the the promyelocytic leukemia-retinoic acid receptor alpha (PML::RARα) fusion gene fusion protein in regulating cellular metabolism and protein expression. Furthermore, the article explores the importance of the immune system in acute promyelocytic leukemia treatment response and the impact of all-trans retinoic acid/arsenic trioxide therapy on the proteome and metabolome. By synthesizing existing research findings, this review aims to discuss how proteomic and metabolomic data elucidate the pathological mechanisms and therapeutic targets of acute promyelocytic leukemia, providing a theoretical basis for future precision medicine and translational research.

Objective: To explore the relationship between the triglyceride-glucose index (TyG), the monocyte to high-density lipoprotein cholesterol ratio (MHR) and the severity of coronary artery disease (CAD) under different glucose metabolism states.

Methods: A retrospective analysis was conducted on 526 patients who underwent coronary angiography (CAG) for the first time in the Affiliated Hospital of Xuzhou Medical University from January 2024 to January 2025. Among them, there were 122 patients in the non-CAD group and 404 patients in the CAD group. According to the Gensini score, the CAD group was further divided into a mild group (n = 147) and a moderate-to-severe group (n = 257). Meanwhile, they were divided into normal glucose regulation (NGR), prediabetes (Pre-DM), and diabetes mellitus (DM) groups according to the glucose metabolism state. Multivariate Logistic regression, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curve analyses were used.

Results: Both the TyG index and MHR were independent risk factors for the occurrence and severity of CAD (P<0.05). In the DM group, the TyG index was significantly associated with the severity of CAD (OR=4.30, 95% CI: 1.48-12.49, P<0.01); in the NGR group, MHR was significantly associated with the severity of CAD (OR=436.1, 95% CI: 15.4-12342, P<0.001). RCS analysis suggested a significant linear positive correlation between the TyG index and the severity of CAD (P-overall=0.006, P-non-linear=0.917), while there was a non-linear relationship between MHR and the severity of CAD (P-overall=0.007, P-non-linear=0.033). ROC analysis showed that the area under the curve (AUC) of the combined prediction was 0.655, higher than that of the TyG index (0.618) and MHR (0.631).

Conclusion: TyG index and MHR can serve as independent biomarkers of new-onset CAD severity. In DM patients, TyG offers greater predictive value, while MHR is more predictive in NGR individuals.

Background: Lactobacillus paracasei (LP) may affect the efficacy of clopidogrel (CLP).

Methods:  Forty Sprague-Dawley (SD) rats were randomly divided into control group, LP group, CLP group, LP (pretreatment) + CLP group, and CLP + LP(posttreatment) group (n=6-8). The administration doses of CLP and LP in rats were 6.75 mg/kg/d and 10⁹ CFU/d, respectively, for 14 consecutive days. Tail vein blood was collected to detect blood drug concentration, platelet function. Then, a thrombosis model was constructed using 20% FeCl₃, the complete vascular occlusion time, thrombus weight, and thrombus inhibition rate, inflammatory factors, gut microbiota, short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO) and mucosal barrier were evaluated.

Results:  Compared with the CLP group, the blood concentrations of AM and CA in the combined group were significantly decreased, while platelet aggregation (MPA) and platelet reaction index (PRI) were significantly increased. After model construction, the thrombosis formation time was significantly prolonged, the thrombus weight was significantly reduced, and the thrombus inhibition rate was significantly; the secretions of TNF-α, IL-1β, P-selectin, GPIIb/IIIa, and D-dimer were significantly decreased in the combined group. The structure of gut microbiota also changed significantly after CLP treatment, and LP combined with CLP could improve the dysbiosis caused by CLP through increasing SCFAs and decreasing TMAO. In addition, the expressions of ZO-1, Occludin, and P-gp were increased in the combined groups. It should be noted that there is a directional discrepancy between the changes in platelet function indices (MPA and PRI) and in vivo thrombosis outcomes, which may be related to the multi-factorial regulation of in vivo thrombosis.

Conclusion: LP may regulate the structure of gut microbiota (increasing SCFA-producing bacteria and inhibiting TMAO-producing bacteria), thereby protecting the intestinal mucosal barrier, inhibiting inflammatory responses, and cooperatively acting with CLP to inhibit platelet activation and improve coagulation function, although the specific mechanism needs further verification.

The cervical spine, a critical junction between the head and torso, is a rare but significant site for both primary and metastatic tumors. While primary tumors of the cervical spine are uncommon, certain types, such as chordomas and giant cell tumors, are particularly notable for their potential to affect this region. Metastatic lesions, although more frequent, present unique diagnostic and therapeutic challenges due to the complex anatomy of the cervical spine. Imaging is indispensable for the evaluation of cervical spine tumors, serving as the foundation for diagnosis, treatment planning, and monitoring therapeutic outcomes. Radiography, CT and MRI are the primary modalities used to assess tumor morphology, extent and relationship to surrounding structures. However, imaging alone may not always yield a definitive diagnosis, as some tumors lack distinctive features. Nevertheless, a combination of clinical presentation, epidemiological factors, and imaging findings often enables radiologists and clinicians to narrow the differential diagnosis and guide further management. Precise imaging interpretation is essential to prevent devastating clinical consequences resulting from diagnostic error, such as irreversible neurological damage, avoidable death, and significant long-term disability. This review provides a comprehensive overview of tumors that can involve the cervical spine, emphasizing their clinical and imaging characteristics. By highlighting key diagnostic features and discussing the latest advancements in imaging technology, aims to enable physicians in radiology, pathology, and clinical departments to gain a more comprehensive understanding of the imaging, pathological, and clinical characteristics of cervical spine tumors, thereby reducing misdiagnosis rates and alleviating the burden on patients.

[This corrects the article DOI: 10.2147/IJGM.S545850.].