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Objective The microbial dolomite of the second Member of the Dengying Formation（Deng 2 Member） in the Penglai area of the Sichuan Basin is widely distributed and considered a potential target for deep carbonate oil and gas exploration. Unlike conventional high-quality reservoirs characterized by porosity and karst fractures, the carbonate rocks of the Deng 2 Member mainly consist of microbial dolomite. The genesis and diagenetic evolution of these high-quality reservoirs remain unclear. Methods This study employed petrographic thin sections, scanning electron microscopy (SEM), cathodoluminescence, and computed tomography （CT）scanning to conduct a detailed analysis of the microbial dolomite reservoirs in the Dengying Formation, using field outcrop and core samples. The aim was to gain a deeper understanding of the effects of diagenesis on pore formation and the development of high-quality reservoirs. Results and Conclusion The microbial carbonate reservoirs in the study area were characterized by low porosity and very low permeability, predominantly consisting of fracture-porosity (cavity) type microbial dolomite. The reservoir space was primarily composed of intergranular dissolution pores, residual framework dissolution pores, intragranular dissolution pores, and small to medium-sized dissolution cavities, with minor occurrences of intercrystalline pores and intercrystalline dissolution pores. The Deng 2 Member has undergone multiple diagenetic processes; penecontemporaneous dissolution and early epigenetic dissolution were key factors in enhancing porosity. Significance These findings enhance the understanding of the genesis of high-quality microbial carbonate reservoirs in the Ediacaran System of the Sichuan Basin and provide valuable information for deep oil and gas exploration and development in the region.

Abstract Aim Recent imaging studies have found significant abnormalities in the brain’s functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. Methods We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. Results In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P

Abstract Objective The aim of this study is to evaluate the clinical efficacy of injectable cemented hollow pedicle screw (CICPS) in the treatment of osteoporotic lumbar degenerative diseases through a large sample long-term follow-up study. Additionally, we aim to explore the risk factors affecting interbody fusion. Methods A total of 98 patients who underwent CICPS for transforaminal lumbar interbody fusion (TLIF) for osteoporotic lumbar degenerative disease from March 2011 to September 2017 were analyzed. X-ray and electronic computed tomography (CT) imaging data were collected during preoperative, postoperative, and follow-up periods. The data included changes in intervertebral space height (ΔH), screw failure, cement leakage (CL), and intervertebral fusion. The patients were divided into two groups based on their fusion status one year after surgery: satisfied group A and dissatisfied group B. Surgical data such as operation time, intraoperative bleeding volume and surgical complications were recorded, and visual analog scale (VAS) and Oswestry disability index (ODI) were used to evaluate the improvement of lumbar and leg pain. Results The mean follow-up time was 101.29 months (ranging from 70 to 128 months). A total of 320 CICPS were used, with 26 screws (8.13%) leaking, 3 screws (0.94%) experiencing cement augmentation failure, and 1 screw (0.31%) becoming loose and breaking. The remaining screws were not loose or pulled out. Female gender, decreased bone density, and CL were identified as risk factors affecting interbody fusion (P

Abstract The control of a molecule’s geometry, chirality, and physical properties has long been a challenging pursuit. Our study introduces a dependable method for assembling D 3-symmetric trigonal bipyramidal coordination cages. Specifically, D 2h-symmetric anions, like oxalate and chloranilic anions, self-organize around a metal ion to form chiral-at-metal anionic complexes, which template the formation of D 3-symmetric trigonal bipyramidal coordination cages. The chirality of the trigonal bipyramid is determined by the point chirality of chiral amines used in forming the ligands. Additionally, these cages exhibit chiral selectivity for the included chiral-at-metal anionic template. Our method is broadly applicable to various ligand systems, enabling the construction of larger cages when larger D 2h-symmetric anions, like chloranilic anions, are employed. Furthermore, we successfully produce enantiopure trigonal bipyramidal cages with anthracene-containing backbones using this approach, which would be otherwise infeasible. These cages exhibit circularly polarized luminescence, which is modulable through the reversible photo-oxygenation of the anthracenes.

Abstract Background In this study, we investigated the relationship between the risk of postoperative progressive disease (PD) in breast cancer and depression and sleep disorders in order to develop and validate a suitable risk prevention model. Methods A total of 750 postoperative patients with breast cancer were selected from the First People’s Hospital of LianYunGang, and the indices of two groups (an event group and a non-event group) were compared to develop and validate a risk prediction model. The relationship between depression, sleep disorders, and PD events was investigated using the follow-up data of the 750 patients. Results SAS, SDS, and AIS scores differed in the group of patients who experienced postoperative disease progression versus those who did not; the differences were statistically significant and the ability to differentiate prognosis was high. The area under the receiver operating characteristic (ROC) curves (AUC) were: 0.8049 (0.7685–0.8613), 0.768 (0.727–0.809), and 0.7661 (0.724-–0.808), with cut-off values of 43.5, 48.5, and 4.5, respectively. Significant variables were screened by single-factor analysis and multi-factor analysis to create model 1, by lasso regression and cross-lasso regression analysis to create model 2, by random forest calculation method to create model 3, by stepwise regression method (backward method) to create model 4, and by including all variables for Cox regression to include significant variables to create model 5. The AUC of model 2 was 0.883 (0.848–0.918) and 0.937 (0.893–0.981) in the training set and validation set, respectively. The clinical efficacy of the model was evaluated using decision curve analysis and clinical impact curve, and then the model 2 variables were transformed into scores, which were validated in two datasets, the training and validation sets, with AUCs of 0.884 (0.848–0.919) and 0.885 (0.818–0.951), respectively. Conclusion We established and verified a model including SAS, SDS and AIS to predict the prognosis of breast cancer patients, and simplified it by scoring, making it convenient for clinical use, providing a theoretical basis for precise intervention in these patients. However, further research is needed to verify the generalization ability of our model.

How to capture the dynamic changes and dependencies of user behavior is a vital issue existing in point-of-interest (POI) recommendation. It mainly faces challenges including data scarcity, difficulty in extracting spatio-temporal sequence features and in capturing users?? individuated differences. In order to address these challenges, this paper proposes a time-sequence POI recommendation method based on spatio-temporal vicinity perception and implicit changes of users?? state. This method is aimed at converting the learning of user behavior into the learning of users?? latent state, combined with distance information to introduce spatial information, which effectively captures users?? mobile characteristics. Firstly, the variational autoencoder is utilized to represent the potential state of users. And then the dependency among the latent states is learnt through the graph neural network so as to capture the time-sequence dependence of user behavior. Furthermore, this paper makes use of the attention mechanism and radial basis function to capture the spatial dependence between the user and location candidate sets. Next, this paper evaluates the frequencies of user visiting each location, hence achieving point-of-interest recommendation. Experimental comparison and analysis on three real datasets demonstrate that the temporal recommendation performance of the proposed method is superior to existing benchmark algorithms.

Abstract Background Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women’s Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan. Methods We identified 1,869,050 women aged 50–60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design. Results Study participants’ baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use. Conclusions The 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data.

Abstract Backgrounds A growing body of evidence has highlighted the interactions of lipids metabolism and immune regulation. Nevertheless, there is still a lack of evidence regarding the causality between lipids and autoimmune diseases (ADs), as well as their possibility as drug targets for ADs. Objectives This study was conducted to comprehensively understand the casual associations between lipid traits and ADs, and evaluate the therapeutic possibility of lipid-lowering drug targets on ADs. Methods Genetic variants for lipid traits and variants encoding targets of various lipid-lowering drugs were derived from Global Lipid Genetics Consortium (GLGC) and verified in Drug Bank. Summary data of ADs were obtained from MRC Integrative Epidemiology Unit (MER-IEU) database and FinnGen consortium, respectively. The causal inferences between lipid traits/genetic agents of lipid-lowering targets and ADs were evaluated by Mendelian randomization (MR), summary data-based MR (SMR), and multivariable MR (MVMR) analyses. Enrichment analysis and protein interaction network were employed to reveal the functional characteristics and biological relevance of potential therapeutic lipid-lowering targets. Results There was no evidence of causal effects regarding 5 lipid traits and 9 lipid-lowering drug targets on ADs. Genetically proxied 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition was associated with a reduced risk of rheumatoid arthritis (RA) in both discovery (OR [odds ratio] = 0.45, 95%CI: 0.32, 0.63, P = 6.79 × 10− 06) and replicate datasets (OR = 0.37, 95%CI: 0.23, 0.61, P = 7.81 × 10− 05). SMR analyses supported that genetically proxied HMGCR inhibition had causal effects on RA in whole blood (OR = 0.48, 95%CI: 0.29, 0.82, P = 6.86 × 10− 03) and skeletal muscle sites (OR = 0.75, 95%CI: 0.56, 0.99, P = 4.48 × 10− 02). After controlling for blood pressure, body mass index (BMI), smoking and drinking alchohol, HMGCR suppression showed a direct causal effect on a lower risk of RA (OR = 0.33, 95%CI: 0.40, 0.96, P = 0.042). Conclusions Our study reveals causal links of genetically proxied HMGCR inhibition (lipid-lowering drug targets) and HMGCR expression inhibition with a decreased risk of RA, suggesting that HMGCR may serve as candidate drug targets for the treatment and prevention of RA.

Abstract Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

The study analyzed the electrical properties, mechanical performance, and rheological behavior of three kinds of high plasticizer-content polyvinyl chloride (PVC) composites, herein referred as SCBC, EGC and MCNTC, respectively filled with porous superconductive carbon black (SCB), flake-like expanded graphite (EG), and tubular multi-walled carbon nanotubes (MCNT). The impact of the conductive fillers' morphology on the electrical percolation and viscoelastic percolation performance of the composites were investigated to understand the conductive mechanisms. It revealed that the incorporation of SCB and MCNT can induce both viscoelastic and electrical percolation in the composites. The thresholds for viscoelastic percolation for SCBC and MCNTC are between 2.35-3.11 vol% and 2.72–3.59 vol%, respectively, which are lower than their electrical percolation thresholds of 3.85 vol% for SCBC and 3.65 vol% for MCNTC. The nature of PVC chains, which can transmit force but not electrons, results in a higher electrical percolation threshold than the rheological percolation threshold. Despite MCNT's poorer dispersion, its high aspect ratio and one-dimensional tubular shape enabled it to achieve electrical percolation at a lower loading level. Due to the poor dispersion, EG did not cause either viscoelastic or electrical percolation in the composites within the 0–9 vol% range.

Objective To explore the effect of active vitamin D on renin, (pro) renin receptor (PRR) and NF-κB in rat renal tubular epithelial (NRK-52E) cells in high glucose conditions and elucidate the role of NF-κB. Methods NRK-52E cells were cultured in vitro and divided into 7 groups of control, high glucose, high glucose + PDTC (pyrrolidinedithiocarbamate ammonium) and high glucose + 0.1/1/10/100 nM paricalcitol. mRNA and protein expression of renin, PRR and NF-κB p65 in each group were detected by quantitative polymerase chain reaction (qPCR) and Western blot. ChIP-qPCR was utilized for detecting the relationship between NF-κB p65 and the promoter of renin. Results The expressions of renin, PRR and NF-κB spiked in high-glucose group as compared with control group (P

Abstract The global obesity problem is becoming increasingly serious, with eight of the top ten causes of death in Taiwan in 2020 being related to obesity. Morbid obesity poses a significant threat to one’s health and well-being. In recent years, bariatric surgery has emerged as a more effective treatment option for patients with morbid obesity. However, the procedure is not without risks. This study aims to examine the factors that impact the postoperative efficacy evaluation of patients with morbid obesity. This study uses a retrospective cross-sectional design, with medical records being collected retrospectively. The data was collected from patients who underwent bariatric surgery between July 1, 2017 and June 30, 2020 at a hospital in southern Taiwan. A total of 663 patients were included in the study and were observed for 1 year after the surgery. The independent variables included demographic variables, perceived symptoms variables, perceived lifestyle variables, and surgery-related variables, while the dependent variables included weight loss outcomes and complications. The prognostic factors affecting the postoperative efficacy evaluation of patients with pathological obesity were determined using multiple regression analysis and binary regression analysis. The study found that 65.6% of the participants were female, with an average age of 36.8 years. The results of the multiple regression and binary logistic regression showed that gender, age, BMI, diabetes, and smoking habit were the predictors of postoperative weight loss. Hypertension, diabetes, liver disease, kidney disease, smoking habit, drinking habit, and operation time were the predictors of postoperative complications. The study found that the presence of the aforementioned 12 significant factors can affect the success of weight loss after surgery and the incidence of postoperative complications. This information can serve as a reference for clinical care institutions and patients to improve the postoperative efficacy evaluation.

Abstract Background Propofol is effective and used as a kind of routine anesthetics in procedure sedative anesthesia (PSA) for ureteroscopy. However, respiratory depression and unconscious physical activity always occur during propofol-based PSA, especially in elderly patients. Esketamine has sedative and analgesic effects but without risk of cardiorespiratory depression. The purpose of this study is to investigate whether esketamine can reduce the propofol median effective dose (ED50) for successful ureteroscope insertion in elderly male patients. Materials and methods 49 elderly male patients undergoing elective rigid ureteroscopy were randomly divided into two groups: SK Group (0.25 mg/kg esketamine+propofol) and SF Group (0.1 µg/kg sufentanil+propofol). Patients in both two groups received propofol with initial bolus dose of 1.5 mg/kg after sufentanil or esketamine was administered intravenously. The effective dose of propofol was assessed by a modified Dixon’s up-and-down method and then was adjusted with 0.1 mg/kg according to the previous patient response. Patients’ response to ureteroscope insertion was classified as “movement” or “no movement”. The primary outcome was the ED50 of propofol for successful ureteroscope insertion with esketamine or sufentanil. The secondary outcomes were the induction time, adverse events such as hemodynamic changes, hypoxemia and body movement were also measured. Result 49 patients were enrolled and completed this study. The ED50 of propofol for successful ureteroscope insertion in SK Group was 1.356 ± 0.11 mg/kg, which was decreased compared with that in SF Group, 1.442 ± 0.08 mg/kg (P = 0.003). The induction time in SK Group was significantly shorter than in SF Group (P = 0.001). In SK Group, more stable hemodynamic variables were observed than in SF Group. The incidence of AEs between the two groups was not significantly different. Conclusion The ED50 of propofol with esketamine administration for ureteroscope insertion in elderly male patients is 1.356 ± 0.11 mg/kg, significantly decreased in comparsion with sufentanil. Trial registration Chinese Clinical Trial Registry, No: ChiCTR2300077170. Registered on 1 November 2023. Prospective registration. http://www.chictr.org.cn .

Abstract Background International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib’s cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV. Methods A 3-state partitioned survival model was employed to assess ivosidenib’s cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib’s cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios. Results Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib’s cost and utility values on estimate uncertainty. Conclusions At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50–60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.

Abstract Background Growth hormone (GH) has been proposed as an adjunct in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, especially in women with poor ovarian response. However, it is unclear whether GH supplementation is effective in women with poor embryonic development in the previous IVF cycle. The aim of this study was to evaluate the effectiveness of GH supplementation in IVF/ICSI cycles in women with poor embryonic development in the previous cycle. Methods This is a retrospective cohort study from a public fertility center in China, in which we performed propensity score-matching (PSM) for female age and AFC in a ratio of 1:1. We compared the cumulative live birth rate per started cycle, as well as a series of secondary outcomes. We included 3,043 women with poor embryonic development in the previous IVF/ICSI cycle, of which 1,326 had GH as adjuvant therapy and 1,717 had not. After PSM, there were 694 women in each group. Results After PSM, multivariate analyses showed the cumulative live birth rate to be significantly higher in the GH group than the control group [N = 694, 34.7% vs. N = 694, 27.5%, risk ratio (RR): 1.4 (95%CI: 1.1–1.8)]. Endometrial thickness, number of oocytes retrieved, number of embryos available, and number of good-quality embryos were significantly higher in the GH group compared to controls. Pregnancy outcomes in terms of birth weight, gestational age, fetal sex, preterm birth rate, and type of delivery were comparable. When we evaluated the impact of GH on different categories of female age, the observed benefit in the GH group did not appear to be significant. When we assessed the effect of GH in different AFC categories, the effect of GH was strongest in women with an AFC5-6 (32.2% versus 19.5%; RR 2.0; 95% CI 1.2–3.3). Conclusions Women with poor embryonic quality in the previous IVF/ICSI cycles have higher rates of cumulative live birth with GH supplementation.

Adolescence is a challenging and sensitive developmental period in which mothers and adolescents may be vulnerable to internalizing symptoms. The current study aimed to understand how patterns of changes in mother-adolescent perceived parenting (i.e., mother-adolescent perceived parenting transition profiles) corresponded with trajectories of mothers' and adolescents' internalizing symptoms from early to late adolescence. The current study utilized a three-wave longitudinal data set of 604 adolescents (54% female, M[subscript age] = 12.92, SD = 0.92) and 595 mothers (M[subscript age] = 38.89, SD = 5.74) from Mexican-origin immigrant families and adopted mother-adolescent perceived parenting transition profiles from a previous study. Multiple group analyses showed that mother-adolescent dyads who agreed on high levels of positive parenting across the course of adolescence (i.e., "Stable Both High") experienced the lowest levels of internalizing symptoms, whereas dyads that showed an inconsistent pattern of mixed profile typologies over time (i.e., "Fluctuated") experienced high levels of internalizing symptoms. For mother-adolescent dyads that consistently showed a pattern in which mothers reported more positive parenting compared to their adolescent children (i.e., "Stable Mother High"), mothers experienced low levels of (and even a decrease in) internalizing symptoms, while adolescents experienced considerably high levels of internalizing symptoms over time. The results for the other two parenting transition profiles (i.e., "Change to Both High" and "Change from Both High") are also discussed. The findings highlight the importance of developing separate adaptive interventions to reduce internalizing symptoms for mothers and children by considering their change patterns of perceived parenting during the course of adolescence.

BackgroundAtrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with substantial morbidity and mortality. Oxidative stress (OS) has been implicated in the pathogenesis of AF, suggesting that targeting OS-related genes could offer novel therapeutic opportunities. This study aimed to identify causal OS-related genes contributing to AF through a comprehensive multi-omics Summary-based Mendelian Randomization (SMR) approach.MethodsThis study integrated data from genome-wide association studies (GWAS) with methylation quantitative trait loci (mQTL), expression QTL (eQTL), and protein QTL (pQTL) to explore the relationships between oxidative stress-related (OS-related) genes and AF risk. Genes associated with oxidative stress and AF were obtained from the Nielsen et al. study (discovery) and the FinnGen study (replication). The SMR analysis and HEIDI test were utilized to assess causal associations, followed by Bayesian co-localization analysis (PPH4 > 0.5) to confirm shared causal variants. Multi-omics data were employed to analyze the associations within mQTL-eQTL pathways. A two-sample MR analysis was conducted for sensitivity verification. The significance of findings was determined using a false discovery rate (FDR) < 0.05 and p_HEIDI > 0.01.ResultsAt the DNA methylation level, 19 CpG sites near 7 unique genes were found to have causal effects on AF and strong co-localization evidence support (PPH4 > 0.70). At the gene expression level, six oxidative stress-related genes from eQTLGen and three from GTEx (v8), including TNFSF10, CDKN1A, ALOX15, TTN, PTK2, ALB, KCNJ5, and CASQ2, were found to have causal effects on AF in the sensitivity and co-localization analyses (PPH4 > 0.50). At the circulating protein level, both ALAD (OR 0.898, 95% CI 0.845–0.954, PPH4 = 0.67) and APOH (OR 0.896, 95% CI 0.844–0.952, PPH4 = 0.93) were associated with a lower risk of AF, and APOH was validated in the replication group. After integrating the multi-omics data between mQTL and eQTL, we identified two oxidative stress-related genes, TTN and CASQ2. The methylation of cg09915519 and cg10087519 in TTN was associated with higher expression of TTN and a lower risk of AF, which aligns with the negative effect of TTN gene expression on AF risk. TTN may play a protective role in AF.ConclusionThis study identified several OS-related genes, particularly TTN, as having causal roles in AF, which were verified across three-omics pathways. The findings underscore the importance of these genes in AF pathogenesis and highlight their potential as therapeutic targets. The integration of multi-omics data provides a comprehensive understanding of the molecular mechanisms underlying AF, paving the way for targeted therapeutic strategies.