Identification and verification of FN1, P4HA1 and CREBBP as potential biomarkers in human atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that can lead to cardiac complications. The mechanisms involved in AF remain elusive. We aimed to explore the potential biomarkers and mechanisms underpinning AF. METHODS: An independent dataset, GSE2240, was obtained from the Gene Expression Omnibus database. The R package, "limma", was used to screen for differentially expressed genes (DEGs) in individuals with AF and normal sinus rhythm (SR). Weighted gene co-expression network analysis (WGCNA) was applied to cluster DEGs into different modules based on functional disparities. Enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction network was constructed, and hub genes were identified using cytoHubba. Quantitative reverse-transcription PCR was used to validate mRNA expression in individuals with AF and SR. RESULTS: We identified 2, 589 DEGs clustered into 10 modules using WGCNA. Gene Ontology analysis showed specific clustered genes significantly enriched in pathways associated with the extracellular matrix and collagen organization. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes were mainly enriched for proteoglycans in cancer, extracellular matrix-receptor interaction, focal adhesion, and the PI3K-Akt signaling pathway. Three hub genes, FN1, P4HA1 and CREBBP, were identified, which were highly correlated with AF endogenesis. mRNA expression of hub genes in patients with AF were higher than in individuals with normal SR, consistent with the results of bioinformatics analysis. CONCLUSIONS: FN1, P4HA1, and CREBBP may play critical roles in AF. Using bioinformatics, we found that expression of these genes was significantly elevated in patients with AF than in individuals with normal SR. Furthermore, these genes were elevated at core positions in the mRNA interaction network. These genes should be further explored as novel biomarkers and target candidates for AF therapy.

Comprehensive analysis of roles of atrial-fibrillation-related genes in lung adenocarcinoma using bioinformatic methods.

Atrial fibrillation (AF) is the most common tachyarrhythmia in the world. Lung cancer is the leading cause of cancer deaths in 93 countries. Previous studies demonstrated that the prevalence of AF was higher in patients with lung cancer. However, research on the associations between AF and lung cancer is still rare. In the present study, we first identified AF-related genes using weighted gene correlation network analysis. We then analyzed the expression profiles, prognosis, immune infiltration, and methylation characteristics of these genes in LUAD patients using bioinformatics analysis. We found several AF-related genes, including CBX3, BUB1, DSC2, P4HA1, and CYP4Z1, which differently expressed between tumor and normal tissues. Survival analysis demonstrated that CYP4Z1 was positively correlated with overall survival in LUAD patients, while CBX3, BUB1, DSC2, and P4HA1 were negatively correlated. Moreover, we found that the methylation level of DSC2 in normal lung tissues was significantly higher than that in tumor tissues, and six methylation sites in the DNA sequences of DSC2 were identified negatively correlated with its expression levels. Immune infiltration analysis suggested that levels of immune cell infiltration were related to gene expression levels in varying degrees. We identified AF-related genes and found these genes were correlated with prognosis, immune infiltration, and methylation levels in lung cancer patients. We also constructed a risk signature based on these genes in LUAD patients. We hoped that the current study could provide a novel insight into roles of AF-related genes in lung cancer patients.

Factors associated with adherence to colonoscopy among individuals who were positive in the preliminary screening for colorectal neoplasms.

OBJECTIVES: This study aimed to investigate the potential factors associated with adherence to colonoscopy among participants who were preliminarily screened positive in a community-based colorectal cancer screening program in China. METHODS: This study analyzed data from 1219 out of 6971 community residents who were identified as positive cases by the well-validated high-risk factor questionnaire (HRFQ) or fecal immunochemical test (FIT) in the preliminary screening stage for colorectal neoplasms. Patients showing adherence to colonoscopy were defined as those who received positive results in a preliminary screening for colorectal neoplasms and later received a colonoscopy examination as required. The associations of social-demographic factors, lifestyle behaviors, history of diabetes, body mass index (BMI), and risk factors in the HRFQ with adherence to colonoscopy were evaluated using logistic regression models. RESULTS: Among 1219 participants who preliminarily screened positive, the top five risk factors reported by the participants were chronic constipation (25.9%), hematochezia (23.5%), family history of CRC in first-degree relatives (22.1%), chronic diarrhea (21.8%), and history of polyps (16.6%). Around 14.2% of participants who preliminarily screened positive reported three or more risk factors, and the proportion was 26.2% among participants who were positive according to both HRFQ and FIT. Among all participants who were preliminarily screened positive, the multivariable results showed that those who were married (OR = 1.58, 95% CI: 1.12, 2.25, p = 0.01), had chronic diarrhea (OR = 1.34, 95% CI: 1.00, 1.78, p = 0.047), and had a positive FIT (OR = 1.60, 95% CI: 1.21, 2.10, p < 0.001 for patients who were negative according to HRFQ but positive according to FIT; OR = 2.12, 95% CI: 1.33, 2.78, p = 0.002 for patients who were positive for both HRFQ and FIT) were more likely to adhere to colonoscopy, while participants with a history of cancer (OR: 0.50, 95% CI: 0.31, 0.79, p = 0.003) were less likely to adhere to colonoscopy. The results among participants who were tested positive according to only HRFQ were similar to those among all participants who were tested positive according to HRFQ or FIT. However, among participants who were tested positive according to only FIT, we only found that those who were married (OR = 2.52, 95% CI: 1.08, 5.90, p = 0.033) had a higher odds of adhering to colonoscopy, while those with a history of diabetes (OR = 0.35, 95% CI: 0.13, 0.96, p = 0.042) were less likely to adhere to colonoscopy. CONCLUSION: Our findings provide evidence supporting the development of tailored interventional strategies that aim to improve adherence to colonoscopy for individuals with a high risk of colorectal neoplasms. Both barriers and facilitators associated with adherence to colonoscopy should be considered in supportive systems and health policies. However, further well-designed prospective studies are warranted to confirm our findings.

Factors associated with positive predictive value of preliminary screening in a two-step screening strategy for colorectal neoplasms in China.

BACKGROUND: The positive predictive value (PPV) of high risk factor questionnaire (HRFQ) plus fecal immunochemical test (FIT) as preliminary screening strategy for colorectal-related neoplasia is relatively low. We aim to explore independent factors associated with PPVs of HRFQ combined FIT for selecting high risk individuals for colonoscopy. METHODS: A total of 6971 residents were enrolled in a community-based screening program. Participants who had positive results of HRFQ and/or FIT and subsequently received colonoscopy were involved. The associations of socio-demographic factors, lifestyle behaviors, and high risk factors of colorectal cancer with PPVs of HRFQ, FIT, and their combination were evaluated by multivariable logistic regression models. RESULTS: Among 572 involved cases, 249 (43.5%) colorectal neoplasms were detected by colonoscopy, including 71 advanced adenoma (12.4%) and 9 colorectal cancer (CRC) (1.6%). The PPVs of preliminary screening were 43.5% for total colorectal neoplasms, 14.0% for advanced neoplasm, and 1.6% for CRC. Adding positive HRFQ to FIT could improve the PPV from 3.5 to 8.0% for detecting CRC. Preliminarily screened positive individuals who were males [adjusted odds ratio (AOR): 1.95, 95% CI 1.31, 2.90; p < 0.001], elders (> 60 years) (AOR: 1.70, 95% CI 1.17, 2.46; p = 0.005), or ex-/current smokers (AOR: 3.04, 95% CI 1.31, 7.09; p = 0.10) had higher odds of PPVs of detecting colorectal neoplasms. CONCLUSIONS: Combining HRFQ and FIT could largely improve PPVs for screening advanced neoplasm and CRC. Gender and age-specific FIT cut-off values as well as initiating ages for CRC screening might be recommended to improve the accuracy and effectiveness of current screening algorithm.

Validation of handheld fundus camera with mydriasis for retinal imaging of diabetic retinopathy screening in China: a prospective comparison study.

OBJECTIVES: To investigate the clinical validity of using a handheld fundus camera to detect diabetic retinopathy (DR) in China. DESIGN AND SETTINGS: Prospective comparison study of the handheld fundus camera with a standard validated instrument in detection of DR in hospital and a community screening clinic in Guangdong Province, China. PARTICIPANTS: Participants aged 18 years and over with diabetes who were able to provide informed consent and agreed to attend the dilated eye examination with handheld tests and a standard desktop camera. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the proportion of those with referable DR (R2 and above) identified by the handheld fundus camera (the index test) compared with the standard camera. Secondary outcome was the comparison of proportion of gradable images obtained from each test. RESULTS: In this study, we examined 304 people (608 eyes) with each of the two cameras under mydriasis. The handheld camera detected 119 eyes (19.5%) with some level of DR, 81 (13.3%) of them were referable, while the standard camera detected 132 eyes (21.7%) with some level of DR and 83 (13.7%) were referable. It seems that the standard camera found more eyes with referable DR, although McNemar's test detected no significant difference between the two cameras.Of the 608 eyes with images obtained by desktop camera, 598 (98.4%) images were of sufficient quality for grading, 12 (1.9%) images were not gradable. By the handheld camera, 590 (97.0%) were gradable and 20 (3.2%) images were not gradable.The two cameras reached high agreement on diagnosis of retinopathy and maculopathy at all the levels of retinopathy. CONCLUSION: Although it could not take the place of standard desktop camera on clinic fundus examination, the handheld fundus camera showed promising role on preliminary DR screening at primary level in China. To ensure quality images, mydriasis is required.