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AnteayerPLOS ONE Medicine&Health

Interactions of plumbagin with five common antibiotics against <i>Staphylococcus aureus in vitro</i>

by Songtao Bie, Qiuyue Mo, Chen Shi, Hui Yuan, Chunshuang Li, Tong Wu, Wenlong Li, Heshui Yu

Staphylococcus aureus is the main culprit, causing a variety of severe clinical infections. At the same time, clinics are also facing the severe situation of antibiotic resistance. Therefore, effective strategies to address this problem may include expanding the antimicrobial spectrum by exploring alternative sources of drugs or delaying the development of antibiotic resistance through combination therapy so that existing antibiotics can continue to be used. Plumbagin (PLU) is a phytochemical that exhibits antibacterial activity. In the present study, we investigated the in vitro antibacterial activity of PLU. We selected five antibiotics with different mechanisms and inhibitory activities against S. aureus to explore their interaction with the combination of PLU. The interaction of combinations was evaluated by the Bliss independent model and visualized through response surface analysis. PLU exhibited potent antibacterial activity, with half maximal inhibitory concentration (IC50) and minimum inhibitory concentration (MIC) values against S. aureus of 1.73 μg/mL and 4 μg/mL, respectively. Synergism was observed when PLU was combined with nitrofurantoin (NIT), ciprofloxacin (CPR), mecillinam (MEC), and chloramphenicol (CHL). The indifference of the trimethoprim (TMP)-PLU pairing was demonstrated across the entire dose-response matrix, but significant synergy was observed within a specific dose region. In addition, no antagonistic interactions were indicated. Overall, PLU is not only a promising antimicrobial agent but also has the potential to enhance the growth-inhibitory activity of some antibiotics against S. aureus, and the use of the interaction landscape, along with the dose-response matrix, for analyzing and quantifying combination results represents an improved approach to comprehending antibacterial combinations.

Association between vitamin D and endometriosis among American women: National Health and Nutrition Examination Survey

by Baoli Xie, Ming Liao, Yingqin Huang, Fu Hang, Nana Ma, Qianwen Hu, Jiawei Wang, Yufu Jin, Aiping Qin

Endometriosis is a multifactorial disease associated with inflammation. Vitamin D has anti-inflammatory, antiproliferative, anti-oxidative, and immunomodulatory effects. Whether vitamin D levels are correlated with endometriosis is a subject of ongoing debate. This study aimed to examine the association between endometriosis and serum vitamin D levels. From the National Health and Nutrition Examination Survey, this study examined the cross-sectional data of American women aged 20–54 years from 2001 to 2006. After adjusting for covariates, multivariable logistic regression analysis was used to assess correlations. A total of 3,232 women were included in this study. The multiple linear regression model demonstrated a negative correlation between the serum 25-hydroxyvitamin D3 (cholecalciferol) concentration and the risk of endometriosis after controlling for all confounding variables. The odds ratio was 0.73 with a 95% confidence interval of 0.54–0.97 in the adequate vitamin D level group compared with the insufficient vitamin D level group. Our results showed that endometriosis was inversely correlated with serum 25-hydroxyvitamin D3 levels. Further research is needed to establish a causal relationship and determine the potential benefits of maintaining sufficient vitamin D levels for endometriosis prevention.

Evaluation of the therapeutic efficiency and efficacy of blood purification in the treatment of severe acute pancreatitis

by Hongwei Huang, Zhongshi Huang, Menghua Chen, Ken Okamoto

This study aimed to evaluate the therapeutic efficacy and effect of blood purification (BP) therapy on severe acute pancreatitis (SAP). Information on 305 patients (BP group 68, control group 237) diagnosed with SAP was retrieved from the Medical Information Mart for Intensive Care IV (MIMIC IV) database. Firstly, the influence of BP treatment was preliminarily evaluated by comparing the outcome indicators of the two groups. Secondly, multiple regression analysis was used to screen the mortality risk factors to verify the impact of BP on the survival outcome of patients. Then, the effect of BP treatment was re-validated with baseline data. Finally, cox regression was used to make the survival curve after matching to confirm whether BP could affect the death outcome. The results indicated that the BP group had a lower incidence of shock (p = 0.012), but a higher incidence of acute kidney injury (AKI) (p p = 0.133), indicating that BP treatment had no significant effect on the survival outcome of patients with SAP. Although BP is beneficial in stabilizing hemodynamics, it has no effect on short- and long-term mortality of patients. The application of this technology in the treatment of SAP should be done with caution until appropriate BP treatment methods are developed, particularly for patients who are not able to adapt to renal replacement therapy.

Association of Kawasaki disease with urbanization level and family characteristics in Taiwan: A nested case–control study using national-level data

by Chung-Fang Tseng, Hsiao-Chen Lin, Chung-Yuh Tzeng, Jing-Yang Huang, Chih-Jung Yeh, James Cheng-Chung Wei

Kawasaki disease (KD) is an inflammatory vasculitis disorder of unknown etiology. It is a rare but fatal disease and the leading cause of acquired coronary heart disease in children under the age of 5 years. We examined the association of KD with the demographics of family members, parents’ characteristics, and perinatal factors in Taiwanese children. This nested case–control study used data from Taiwan’s Health and Welfare Data Science Center and initially included children born in Taiwan between January 1, 2006, and December 31, 2015 (n = 1,939,449); the children were observed for KD development before the age of 5 years (n = 7870). The control group consisted of children without KD who were matched with each KD case by sex and birth date at a ratio of 8:1. The odds ratio (ORs) of the aforementioned associations were estimated using conditional logistic regression. The risk of KD decreased in children with younger parents [

Influencing factors of falls among older adults in Chinese retirement institutions: A systematic review and meta-analysis

by Xiaoxing Huang, Yunlan Jiang, Yaxin Liu, Liyin Shen, Jing Pan, Yue Zhang

Background

The incidence of falling has always been high among the elderly, and it was easy to cause injuries to the elderly and seriously affect their quality of life. There were many studies have been conducted on risk factors affecting the fall of the elderly, but the results widely, retirement institutions as a gathering place for the elderly, there was currently no comprehensive analysis of the factors related to elderly falls in pension institutions. This study aimed to explore the influencing factors of falls among older adults in Chinese nursing homes.

Methods

Chinese and English databases were searched for literature published from database inception to 5 April 2023 on the influencing factors of falls among older adults in Chinese nursing homes. Two reviewers independently screened articles, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using RevMan 5.4 software.

Results

Eleven studies involving 3503 participants were included in the meta-analysis. The pooled estimate of falls among older adults in Chinese nursing homes was 32% [95% confidence interval (95%CI) (24.0%, 39.0%)]. The main influencing factors for falls among older adults in Chinese nursing homes were age (Odds Ratio (OR) = 1.53), gender (OR = 5.50), visual impairment (OR = 2.30), sedative-hypnotics (OR = 2.36), fear of falling (OR = 2.95), hypertension (OR = 3.72), static balance (OR = 2.02), three or more chronic diseases (OR = 5.63), cognitive status (OR = 2.64), walking aid use (OR = 1.98), fall-related chronic diseases (OR = 2.48), self-awareness of abilities (OR = 2.43), and frequent reminders for fall prevention (OR = 0.10).

Conclusion

Falls among older adults in Chinese nursing homes were common, and there were many influencing factors. Timely screening and intervention should be implemented to reduce the adverse consequences of falls on older adults.

Trial registration

Registration number: CRD42023421099.

Diagnostic accuracy of endocytoscopy via artificial intelligence in colorectal lesions: A systematic review and meta‑analysis

by Hangbin Zhang, Xinyu Yang, Ye Tao, Xinyi Zhang, Xuan Huang

Background

Endocytoscopy (EC) is a nuclei and micro-vessels visualization in real-time and can facilitate "optical biopsy" and "virtual histology" of colorectal lesions. This study aimed to investigate the significance of employing artificial intelligence (AI) in the field of endoscopy, specifically in diagnosing colorectal lesions. The research was conducted under the supervision of experienced professionals and trainees.

Methods

EMBASE, PubMed, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI) database, and other potential databases were surveyed for articles related to the EC with AI published before September 2023. RevMan (5.40), Stata (14.0), and R software (4.1.0) were used for statistical assessment. Studies that measured the accuracy of EC using AI for colorectal lesions were included. Two authors independently assessed the selected studies and their extracted data. This included information such as the country, literature, total study population, study design, characteristics of the fundamental study and control groups, sensitivity, number of samples, assay methodology, specificity, true positives or negatives, and false positives or negatives. The diagnostic accuracy of EC by AI was determined by a bivariate random-effects model, avoiding a high heterogeneity effect. The ANOVA model was employed to determine the more effective approach.

Results

A total of 223 studies were reviewed; 8 articles were selected that included 2984 patients (4241 lesions) for systematic review and meta-analysis. AI assessed 4069 lesions; experts diagnosed 3165 and 5014 by trainees. AI demonstrated high accuracy, sensitivity, and specificity levels in detecting colorectal lesions, with values of 0.93 (95% CI: 0.90, 0.95) and 0.94 (95% CI: 0.73, 0.99). Expert diagnosis was 0.90 (95% CI: 0.85, 0.94), 0.87 (95% CI: 0.78, 0.93), and trainee diagnosis was 0.74 (95% CI: 0.67, 0.79), 0.72 (95% CI: 0.62, 0.80). With the EC by AI, the AUC from SROC was 0.95 (95% CI: 0.93, 0.97), therefore classified as excellent category, expert showed 0.95 (95% CI: 0.93, 0.97), and the trainee had 0.79 (95% CI: 0.75, 0.82). The superior index from the ANOVA model was 4.00 (1.15,5.00), 2.00 (1.15,5.00), and 0.20 (0.20,0.20), respectively. The examiners conducted meta-regression and subgroup analyses to evaluate the presence of heterogeneity. The findings of these investigations suggest that the utilization of NBI technology was correlated with variability in sensitivity and specificity. There was a lack of solid evidence indicating the presence of publishing bias.

Conclusions

The present findings indicate that using AI in EC can potentially enhance the efficiency of diagnosing colorectal abnormalities. As a valuable instrument, it can enhance prognostic outcomes in ordinary EC procedures, exhibiting superior diagnostic accuracy compared to trainee-level endoscopists and demonstrating comparability to expert endoscopists. The research is subject to certain constraints, namely a limited number of clinical investigations and variations in the methodologies used for identification. Consequently, it is imperative to conduct comprehensive and extensive research to enhance the precision of diagnostic procedures.

Physiological changes of microalga <i>Dunaliella parva</i> under the treatment of PEG, CaCl<sub>2</sub>

by Qiman Zou, Limei Huang, Jinghui Gu, Bingbing Pang, Changhua Shang

Carotenoids are antioxidants, which reduce various chronic diseases of human, and have many industrial applications. The halophilic Dunaliella parva (D. parva) is rich in carotenoids. The compounds CaCl2 and PEG are the popular metabolic enhancers. To further enhance carotenogenesis, D. parva was treated with two compounds polyethylene glycol (PEG) and CaCl2. Application of CaCl2 and PEG enhanced the carotenoids contents and the antioxidant activities of carotenoids compared to control group (no treatment of CaCl2 or PEG). The highest carotenoids contents were obtained by treating D. parva with 40 ppm CaCl2 (3.11 mg/g dry weight, DW) and 80 ppm PEG (2.78 mg/g DW) compared with control group (1.96 mg/g DW). When D. parva was treated with 40 ppm CaCl2 and 80 ppm PEG, protein contents reached the highest values (90.28 mg/g DW and 89.57 mg/g DW) compared to that of control group (73.42 mg/g DW). The antioxidant activities of carotenoids samples were determined. Generally, the antioxidant activities of carotenoids from D. parva treated with PEG and CaCl2 were superior to that of control group. The antioxidant activities of carotenoids mainly contained reducing power, hydroxyl radical scavenging activity and superoxide radical scavenging activity. The reducing powers of carotenoids extracts from 20 ppm CaCl2 group (2.07%/mg carotenoids) and 120 ppm PEG group (1.59%/mg carotenoids) were significantly higher than that of control group (2 group (70.33%/mg carotenoids) and 80 ppm PEG group (65.94%/mg carotenoids) were significantly higher than that of control group (D. parva.

Electroacupuncture attenuates inflammatory pain via peripheral cannabinoid receptor type 1 signaling pathway in mice

by Tsung-Jung Ho, Ching-Fang Lin, Jhong-Kuei Chen, Yen-Lun Kung, Li-Kung Wu, Chen-Ying Chang Chien, Chun-Ping Huang

Pain is strongly associated with neuro-immune activation. Thus, the emerging role of the endocannabinoid system in neuro-inflammation is important. Acupuncture has been used for over 2500 years and is widely accepted for the management of pain. Our study aimed to investigate the effects of electroacupuncture on the regulation of cannabinoid receptor type 1 within the peripheral nervous system. Inflammatory pain was induced by injecting Complete Freund’s adjuvant to induce mechanical and thermal hyperalgesia. Electroacupuncture significantly attenuated the mechanical and thermal sensitivities, and AM251, a cannabinoid receptor type 1 antagonist, eliminated these effects. Dual immunofluorescence staining demonstrated that electroacupuncture elevated expression of cannabinoid receptor type 1, co-localized with Nav 1.8. Furthermore, electroacupuncture significantly reduced levels of Nav 1.8 and COX-2 by western blot analysis, but not vice versa as AM251 treatment. Our data indicate that electroacupuncture mediates antinociceptive effects through peripheral endocannabinoid system signaling pathway and provide evidence that electroacupuncture is beneficial for pain treatment.

Traumatic brain injury and risk of heart failure and coronary heart disease: A nationwide population-based cohort study

by Ching-Hui Huang, Chao-Tung Yang, Chia-Chu Chang

Background

This study examined the long-term risks of heart failure (HF) and coronary heart disease (CHD) following traumatic brain injury (TBI), focusing on gender differences.

Methods

Data from Taiwan’s National Health Insurance Research Database included 29,570 TBI patients and 118,280 matched controls based on propensity scores.

Results

The TBI cohort had higher incidences of CHD and HF (9.76 vs. 9.07 per 1000 person-years; 4.40 vs. 3.88 per 1000 person-years). Adjusted analyses showed a significantly higher risk of HF in the TBI group (adjusted hazard ratio = 1.08, 95% CI = 1.01–1.17, P = 0.031). The increased CHD risk in the TBI cohort became insignificant after adjustment. Subgroup analysis by gender revealed higher HF risk in men (aHR = 1.14, 95% CI = 1.03–1.25, P = 0.010) and higher CHD risk in women under 50 (aHR = 1.32, 95% CI = 1.15–1.52, P Conclusion

Our results suggest that TBI increases the risk of HF and CHD in this nationwide cohort of Taiwanese citizens. Gender influences the risks differently, with men at higher HF risk and younger women at higher CHD risk. Beta-blockers have a neutral effect on HF and CHD risk.

Effect of pueraria on left ventricular remodelling in HFrEF: A systematic review and meta-analysis

by Lipeng Shi, Lumei Huang, Erqian Yin, Jingwei Deng, Xuqin Du

Background

Heart failure with reduced ejection fraction (HFrEF) is a prevalent cardiovascular disease globally, posing a significant burden on healthcare and society. Left ventricular remodelling is the primary pathology responsible for HFrEF development and progression, leading to increased morbidity and mortality. Pueraria, a traditional Chinese herbal medicine and food, is commonly used in China to treat HFrEF. Accumulating evidence suggests that pueraria can effectively reverse left ventricular remodelling in HFrEF patients. This meta-analysis aims to assess the impact of pueraria on left ventricular remodelling in HFrEF patients.

Methods

Eight electronic databases, including PubMed, EMBASE, Clinicaltrials.gov, Cochrane Library, Wanfang, CNKI, CQVIP, and CBM were searched for literature from inception to June 2023. All randomized controlled trials (RCTs) using pueraria in the treatment of HFrEF were included. The Cochrane Risk of Bias tool was utilized for RCTs’ methodological evaluation, while Review Manager 5.4.1 was used to analyze the data.

Results

Nineteen RCTs with a total of 1,911 patients (1,077 males and 834 females) were identified. Meta-analysis indicated that combination medication of pueraria and conventional medicine (CM) was superior to the CM alone in raising left ventricular ejection fraction (LVEF; MD = 6.46, 95% CI, 4.88 to 8.04, P CI, -6.55 to -3.01, P CI, -5.98 to -1.99, P CI, -185.30 to -67.03, P CI, 2.54 to 4.59, P CI, 41.77 to 89.31, P CI, 1.57 to 5.83, P = 0.0009). Regarding safety, no difference was observed for adverse events (RR = 0.59, 95% CI, 0.22 to 1.54, P = 0.28).

Conclusion

The use of pueraria combined with conventional medicine in HFrEF patients has superiority over conventional medicine alone in ameliorating cardiac function and reversing left ventricular remodeling. Moreover, combination medication has no increase in adverse drug events. Given some limitations, more prudence and high-quality clinical trials are needed in the future to verify the conclusions.

The mediting role of psychological resilience on the negative effect of pain in patients with rheumatoid arthritis: A cross-sectional study

by Shuang Xu, Qiongyu Zhang, Jiayan Zhou

The objective of this study was to investigate the direct effects of pain-induced depression and anxiety, as well as the mediating role of psychological resilience, on the psychological distress associated with rheumatoid arthritis. The method involved a sample of 196 patients with rheumatoid arthritis and applied the Hospital Anxiety and Depression Scale, Connor–Davidson Resilience Scale, and visual analog scale for pain. Bivariate and path analyses were performed, and a multiple mediational model was utilized. Results showed that all correlations among study variables were significant (p

Maternal exposure to SSRIs or SNRIs and the risk of congenital abnormalities in offspring: A systematic review and meta-analysis

by Weiyi Huang, Robin L. Page, Theresa Morris, Susan Ayres, Alva O. Ferdinand, Samiran Sinha

Background

The association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors.

Methods

A literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study.

Results

Twenty-one cohort studies and seven case-control studies were included in the meta-analysis. Compared to non-exposure, maternal exposure to SNRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.64 with 95% CI: 1.36, 1.97), anomalies of the kidney and urinary tract (pooled OR: 1.63 with 95% CI: 1.21, 2.20), malformations of nervous system (pooled OR: 2.28 with 95% CI: 1.50, 3.45), anomalies of digestive system (pooled OR: 2.05 with 95% CI: 1.60, 2.64) and abdominal birth defects (pooled OR: 2.91 with 95%CI: 1.98, 4.28), while maternal exposure to SSRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.25 with 95%CI: 1.20, 1.30), anomalies of the kidney and urinary tract (pooled OR: 1.14 with 95%CI: 1.02, 1.27), anomalies of digestive system (pooled OR: 1.11 with 95%CI: 1.01, 1.21), abdominal birth defects (pooled OR: 1.33 with 95%CI: 1.16, 1.53) and musculoskeletal malformations (pooled OR: 1.44 with 95%CI: 1.32, 1.56).

Conclusions

SSRIs and SNRIs have various teratogenic risks. Clinicians must consider risk-benefit ratios and patient history when prescribing medicines.

Vitamin K2 (MK-7) attenuates LPS-induced acute lung injury via inhibiting inflammation, apoptosis, and ferroptosis

by Yulian Wang, Weidong Yang, Lulu Liu, Lihong Liu, Jiepeng Chen, Lili Duan, Yuyuan Li, Shuzhuang Li

Acute lung injury (ALI) is a life-threatening disease that has received considerable critical attention in the field of intensive care. This study aimed to explore the role and mechanism of vitamin K2 (VK2) in ALI. Intraperitoneal injection of 7 mg/kg LPS was used to induce ALI in mice, and VK2 injection was intragastrically administered with the dose of 0.2 and 15 mg/kg. We found that VK2 improved the pulmonary pathology, reduced myeloperoxidase (MPO) activity and levels of TNF-α and IL-6, and boosted the level of IL-10 of mice with ALI. Moreover, VK2 played a significant part in apoptosis by downregulating and upregulating Caspase-3 and Bcl-2 expressions, respectively. As for further mechanism exploration, we found that VK2 inhibited P38 MAPK signaling. Our results also showed that VK2 inhibited ferroptosis, which manifested by reducing malondialdehyde (MDA) and iron levels, increasing glutathione (GSH) level, and upregulated and downregulated glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) expressions, respectively. In addition, VK2 also inhibited elastin degradation by reducing levels of uncarboxylated matrix Gla protein (uc-MGP) and desmosine (DES). Overall, VK2 robustly alleviated ALI by inhibiting LPS-induced inflammation, apoptosis, ferroptosis, and elastin degradation, making it a potential novel therapeutic candidate for ALI.

Comparison of national and international sedentary behaviour and physical activity guidelines for older adults: A systematic review and quality appraisal with AGREE II

by Amy Huang, Ellen Wang, Stephanie Sanger, Alexandra Papaioannou, Isabel B. Rodrigues

Most older adults 65 years and older accumulate over 8.5 hours/day of sedentary time, which is associated with increased risk of metabolic syndromes and falls. The impact of increased sedentary time in older adults has prompted development of sedentary behaviour guidelines. The purpose of our review was to compare national and international sedentary behaviour and physical activity guidelines for older adults and appraise the quality of guidelines using AGREE II. We conducted our search in Medline, Embase, Global Health, Web of Science, CINAHL, and relevant grey literature. We included the most recent guidelines for older adults written in English. We identified 18 national and international guidelines; ten of the 18 guidelines included sedentary behaviour recommendations while all 18 included physical activity recommendations for older adults. The ten sedentary behaviour guidelines were developed using cohort studies, knowledge users’ opinions, systematic reviews, or other guidelines while the physical activity guidelines were developed using randomized controlled trials, systematic reviews, meta-analysis, and overview of reviews. The definition of sedentary behaviour and the recommendations were inconsistent between the guidelines and were based on very low to low quality and certainty of evidence. All guidelines provided consistent recommendations for aerobic and resistance training; the recommendations were developed using moderate to high quality and certainty of evidence. Only eight physical activity guidelines provided recommendations for balance training and six on flexibility training; the balance training recommendations were consistent between guidelines and based on moderate quality evidence. Further work is needed to develop evidenced-based sedentary behaviour recommendations and flexibility training recommendations for older adults.

Construction of a standardized training system for hospital infection prevention and control for new medical staff in internal medicine ICUs based on the Delphi method

by Linfei Wu, Li Tang, Linli Zhuang, Wenyi Xie, Min Liu, Jianfang Li

In China, studies have shown nosocomial infections contribute to increased mortality rates, prolonged hospital stays, and added financial burdens for patients. Previous studies have demonstrated that effective infection control training can enhance the quality of infection control practices, particularly in intensive care unit (ICU) settings. However, there is currently no universally accepted training mode or program that adequately addresses the specific needs of ICU medical staff regarding nosocomial infection control. The objective of this study was to develop a standardized training system for preventing and controlling hospital-acquired infections among new medical staff in the internal medicine ICU. Our methodology encompassed an extensive literature review, technical interviews focusing on key events, semi-structured in-depth interviews, and two rounds of Delphi expert correspondence. We employed intentional sampling to select 16 experts for the Delphi expert consultation. Indicators were chosen based on an average importance score of >3.5 and a coefficient of variation of

Identification and validation of aging-related genes in atrial fibrillation

by Yong Zhou, Chao Sun, Yingxu Ma, Yunyin Huang, Keke Wu, Shengyuan Huang, Qiuzhen Lin, Jiayi Zhu, Zuodong Ning, Ningyuan Liu, Tao Tu, Qiming Liu

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the clinic. Aging plays an essential role in the occurrence and development of AF. Herein, we aimed to identify the aging-related genes associated with AF using bioinformatics analysis. Transcriptome profiles of AF were obtained from the GEO database. Differential expression analysis was performed to identify AF-specific aging-related genes. GO and KEGG enrichment analyses were performed. Subsequently, the LASSO, SVM-RFE, and MCC algorithms were applied to screen aging-related genes. The mRNA expression of the screened genes was validated in the left atrial samples of aged rapid atrial pacing-induced AF canine models and their counterparts. The ROC curves of them were drawn to evaluate their diagnostic potential. Moreover, CIBERSORT was used to estimate immune infiltration. A correlation analysis between screened aging-related genes and infiltrating immune cells was performed. A total of 24 aging-related genes were identified, which were found to be mainly involved in the FoxO signaling pathway, PI3K-Akt signaling pathway, longevity regulating pathway, and peroxisome according to functional enrichment analysis. LASSO, SVM-RFE, and MCC algorithms identified three genes (HSPA9, SOD2, TXN). Furthermore, the expression levels of HSPA9 and SOD2 were validated in aged rapid atrial pacing-induced AF canine models. HSPA9 and SOD2 could be potential diagnostic biomarkers for AF, as evidenced by the ROC curves. Immune infiltration and correlation analysis revealed that HSPA9 and SOD2 were related to immune cell infiltrates. Collectively, these findings provide novel insights into the potential aging-related genes associated with AF. HSPA9 and SOD2 may play a significant role in the occurrence and development of AF.
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