Identification of key genes associated with acute myocardial infarction using WGCNA and two-sample mendelian randomization study.

OBJECTIVE: Acute myocardial infarction (AMI) is a severe condition with high morbidity and mortality rates. This study aimed to identify hub genes potentially associated with AMI and assess their clinical utility in predicting AMI occurrence. METHODS: Gene microarray data were obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted on samples from patients with AMI and control samples to identify modules significantly associated with AMI. GO and KEGG analyses were applied to investigate the potential functions of these hub genes. Lastly, the mendelian randomization (MR) method was applied to analyze the causal relationship between the hub gene TNF and AMI. RESULTS: 285 differentially expressed genes (DEGs) were identified through WCGNA and were clustered into 6 modules. The yellow module appeared most relevant to AMI. Further exploration through GO and KEGG pathway enrichment showed that key hub genes in the yellow module were linked to positive regulation of cytokine production, cytokine receptor binding, NF-kappa B signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. The top 10 genes identified through Cytoscape software analysis were IL1B, TNF, TLR4, TLR2, FCGR3B, MMP9, CXCL8, TLR8, ICAM1, and JUK. Utilizing inverse variance weighting (IVW) analysis, we discovered a significant association between TNF and AMI risk, with an OR of 0.946 (95% CI = 0.911-0.984, p = 0.005). CONCLUSIONS: The result of this study indicated that TNF, TLR2, TLR4, IL1B and FCGR3B may be potential biodiagnostic markers for AMI. TNF can inhibit inflammatory and oxidative stress responses in AMI, exerting a protective role in the heart.

Changing epidemiology of inflammatory bowel disease in children and adolescents.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) is rising worldwide, but epidemiological data on children and adolescents are lacking. Understanding the global burden of IBD among children and adolescents is essential for global standardization of methodology and treatment options. METHODS: This is a cross-sectional study based on aggregated data. We estimated the prevalence and incidence of IBD in children and adolescents between 1990 and 2019 according to the Global Burden of Disease Study 2019 (GBD 2019). Age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) were used to compare the burden and trends between different regions and countries. RESULTS: In 2019, there were 25,659 new cases and 88,829 prevalent cases of IBD among children and adolescents globally, representing an increase of 22.8% and 18.5%, respectively, compared to 1990. Over the past 30 years, the incidence and prevalence of IBD among children and adolescents have been highest in high SDI regions, with the most significant increases in East Asia and high-income Asia Pacific. At the age level, incidence and prevalence were significantly higher in the 15-19-year-old age group, while the < 5-year-old group showed the most significant increase in incidence and prevalence. CONCLUSION: The incidence of IBD in children and adolescents is significantly on the rise in some countries and regions, and IBD will remain an important public health issue with extensive healthcare and economic costs in the future. The reported IBD burden in children and adolescents at the global, regional, and national levels will assist in the development of more precise health policies.

Ferroptosis in ulcerative colitis: Potential mechanisms and promising therapeutic targets.

Ulcerative colitis (UC) is a complex immune-mediated chronic inflammatory bowel disease. It is mainly characterized by diffuse inflammation of the colonic and rectal mucosa with barrier function impairment. Identifying new biomarkers for the development of more effective UC therapies remains a pressing task for current research. Ferroptosis is a newly identified form of regulated cell death characterized by iron-dependent lipid peroxidation. As research deepens, ferroptosis has been demonstrated to be involved in the pathological processes of numerous diseases. A growing body of evidence suggests that the pathogenesis of UC is associated with ferroptosis, and the regulation of ferroptosis provides new opportunities for UC treatment. However, the specific mechanisms by which ferroptosis participates in the development of UC remain to be more fully and thoroughly investigated. Therefore, in this review, we focus on the research advances in the mechanism of ferroptosis in recent years and describe the potential role of ferroptosis in the pathogenesis of UC. In addition, we explore the underlying role of the crosslinked pathway between ferroptosis and other mechanisms such as macrophages, neutrophils, autophagy, endoplasmic reticulum stress, and gut microbiota in UC. Finally, we also summarize the potential compounds that may act as ferroptosis inhibitors in UC in the future.

Identification of platelet-related subtypes and diagnostic markers in pediatric Crohn's disease based on WGCNA and machine learning.

Background: The incidence of pediatric Crohn's disease (PCD) is increasing worldwide every year. The challenges in early diagnosis and treatment of PCD persist due to its inherent heterogeneity. This study's objective was to discover novel diagnostic markers and molecular subtypes aimed at enhancing the prognosis for patients suffering from PCD. Methods: Candidate genes were obtained from the GSE117993 dataset and the GSE93624 dataset by weighted gene co-expression network analysis (WGCNA) and differential analysis, followed by intersection with platelet-related genes. Based on this, diagnostic markers were screened by five machine learning algorithms. We constructed predictive models and molecular subtypes based on key markers. The models were evaluated using the GSE101794 dataset as the validation set, combined with receiver operating characteristic curves, decision curve analysis, clinical impact curves, and calibration curves. In addition, we performed pathway enrichment analysis and immune infiltration analysis for different molecular subtypes to assess their differences. Results: Through WGCNA and differential analysis, we successfully identified 44 candidate genes. Following this, employing five machine learning algorithms, we ultimately narrowed it down to five pivotal markers: GNA15, PIK3R3, PLEK, SERPINE1, and STAT1. Using these five key markers as a foundation, we developed a nomogram exhibiting exceptional performance. Furthermore, we distinguished two platelet-related subtypes of PCD through consensus clustering analysis. Subsequent analyses involving pathway enrichment and immune infiltration unveiled notable disparities in gene expression patterns, enrichment pathways, and immune infiltration landscapes between these subtypes. Conclusion: In this study, we have successfully identified five promising diagnostic markers and developed a robust nomogram with high predictive efficacy. Furthermore, the recognition of distinct PCD subtypes enhances our comprehension of potential pathogenic mechanisms and paves the way for future prospects in early diagnosis and personalized treatment.

Core decompression vs. allogenic non-vascularized bone grafting in patients with osteonecrosis of the femoral head.

Background: Core decompression and allogenic non-vascularized bone grafting are used in the early stage of osteonecrosis of the femoral head for a period. Since the comparison of the core decompression and allogenic non-vascularized bone grafting are less reported, the purpose of our study was to investigate the difference of two procedures in patients with the osteonecrosis of the femoral head. Methods: Between January 2018 and January 2019, 59 patients (64 hips) were divided into core decompression group and non-vascularized bone grafting group according to their procedures. The primary outcomes are visual analog score (VAS) and Harris hip score. Survivorship was analyzed with the collapse of the femoral head or conversion to total hip arthroplasty (THA) as the endpoint. Results: At the final follow-up, two hips underwent THA in the core decompression group and three hips in the allogenic non-vascularized bone grafting group. The radiographic survival rates were 76.9% and 77.3%, respectively, in both groups. The VAS of the core decompression group was 6.08 ± 1.164 and 3.30 ± 1.431 before and 2 years after operation (P < 0.05), respectively. The VAS of the allogenic non-vascularized bone grafting group was 6.00 ± 1.209 and 3.15 ± 1.537 before and 2 years after operation (P < 0.05), respectively. The Harris hip score of the core decompression group was 52.49 ± 6.496 before operation, and 2 years after operation, it increased by 81.14 ± 8.548 (P < 0.05); The Harris hip score of allogenic the non-vascularized bone grafting group was 53.56 ± 5.925 and 81.33 ± 7.243 before and 2 years after operation (P < 0.05), respectively. In the core decompression group, body mass index (BMI) >25 kg/m2 was correlated with the collapse of femoral head or conversion to THA [P < 0.05; 95% confidence interval (CI), 0.006-1.334], and Association Research Circulation Osseous (ARCO) III was correlated with the collapse of femoral head or conversion to THA (P < 0.05; 95% CI, 2.514-809.650). In the allogenic non-vascularized bone grafting group, age, BMI, and ARCO stage were significantly associated with the collapse of femoral head or conversion to THA (P > 0.05). Conclusion: The clinical survival rate of the femoral head in the core decompression group was slightly better than that in the allogenic non-vascularized bone grafting group. There was no significant difference in the radiographic survival rate of the femoral head between the two groups. Both groups can alleviate pain and improve functional of patients, but there was no significant difference in the degree of improvement. In the core decompression group, BMI >25 kg/m2 and ARCO III correlated with the collapse of femoral head or conversion to THA. In the allogenic non-vascularized bone grafting group, no association was found between age, BMI, and ARCO stage and the collapse of femoral head or conversion to THA. Level of evidence: III.

Development and Validation of Nomogram-Based Prognosis Tools for Patients with Extremity Osteosarcoma: A SEER Population Study.

Objective: Osteosarcoma, usually occurring in the extremities, is the most common malignant bone tumour. The purpose of this study is to develop and validate nomogram-based prognosis tools for survival (OS) and cancer special survival (CSS) of patients with osteosarcoma of the extremities via the application of survival analysis. Materials and Methods: A total of 1427 patients diagnosed with osteosarcoma of the extremities during 2004-2015 were selected from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results- (SEER-) Medicare database. The samples were randomly assigned to either the training set (n = 856) or the validation cohort (n = 571). Kaplan-Meier (K-M) survival analysis was conducted to calculate patients' 1-, 3-, and 5-year OS and CSS rates. Cox proportional hazard ratio (HR) regression models were employed to identify and examine the factors that have a significant impact on OS and CSS with data from the training cohort. Results: The results of univariate and multivariate analyses performed in the training cohort indicated that older age, increased tumour size, higher grade, distant tumour extension, amputation, or no surgery (all HR > 1, P < 0.05) were risk predictors of poor OS and CSS. Subsequently, the independent prognosis signatures were utilised to construct nomograms. The concordance index (C-index), calibration plot, and decision curve analysis (DCA) were simultaneously used to validate the nomograms. The internally validated C-index values of the OS and CSS prediction models for the training set were 0.752 (95% confidence interval [CI]: 0.738-0.765) and 0.754 [95% CI: 0.740-0.768], respectively. Then, the models were validated in the validation cohort population, which also demonstrated the models had good reliability for prognostication. Conclusions: The SEER cohort of patients with osteosarcoma of the extremities can be employed to produce effective tools that can assist in prognosis modelling.