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Aiming at the problems of low efficiency of attack path search in a large-scale power system, a dangerous attack path search analysis method is proposed, which searches the dangerous attack path in the attack graph of the node threat value quantification to realize the security analysis in the power system. Firstly, the search benefit is defined according to the number of dangerous path changes at different depths, and then the search limit depth of each node is determined by the search benefit. Then, the relative comparison method based on improved Z-score is used to prune the node by considering the node’s characteristics and environment. Finally, an adaptive depth-limited breadth-first search is performed to obtain the attack paths. Experiments show that the proposed method can improve the search efficiency and reduce the search of unnecessary nodes while ensuring the accuracy of the search results of the attack path.

Energy drives the development of human civilization, and hydrogen energy is an inevitable choice under the goal of “global energy transition”. As hydrogen technology continues to advance, solid-state hydrogen storage materials have garnered significant attention as an efficient solution for hydrogen energy storage. However, existing research methods, such as experimental preparation and theoretical calculations, are inefficient and costly. Here, we summarize the latest advancements of high-throughput screening (HTS) and machine learning (ML) solid-state hydrogen storage materials. We elaborate on the advantages of HTS and ML in rapid material screening, performance assessment and prediction, and so on. We place particular emphasis on the exploration and analysis of research progress involving the application of HTS and ML in various types of solid-state hydrogen storage materials. Additionally, we discuss the advantages of integrating HTS and ML, emphasizing the application of this comprehensive strategy in solid-state hydrogen storage. In the realm of hydrogen storage, artificial intelligence plays a dual role. It not only enhances the efficiency of material screening but also offers novel research tools for future material design and development. This will aid in the discovery of new-type high-performance solid-state hydrogen storage materials and facilitate their rapid commercialization and practical application.

Background The circadian variation pattern of sudden cardiac arrest (SCA) occurred in Chinese community including both community healthcare centres and primary hospitals remains unknown. This study analysed the circadian variation of SCA in the Chinese community.Methods Data between 2018 and 2022 from the remote ECG diagnosis system of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine were analysed to examine the circadian rhythm of SCA, stratified by initial shockable (ventricular tachycardia or ventricular fibrillation) versus non-shockable (asystole or pulseless electrical activity) rhythm.Results Among 10 210 cases of SCA, major cases (8736, 85.6%) were non-shockable and 1474 (14.4%) cases were shockable. The circadian rhythm of SCA was as follows: peak time was from 08:00 to 11:59 (30.1%), while deep valley was from 00:00 to 03:59 (7.5%). The proportions of events by non-shockable and shockable events were similar and both reached their peak from 08:00 to 11:59, with a percentage of 29.0% and 36.4%, respectively. Multivariable analysis showed that the relative risk of shockable compared with non-shockable arrests was lower between 00:00 and 03:59 (adjusted OR (aOR): 0.72, 95% CI: 0.54 to 0.97, p=0.028) and 04:00 to 07:59 (aOR: 0.60, 95% CI: 0.46 to 0.79, p

Abstract Background LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective option. Here, we investigate the role of dysregulated miRNA targeting LILRB3 in the AML microenvironment. Methods Potential miRNAs binding to the 3ʹ-untranslated region (3ʹ-UTR) of the LILRB3 mRNA were predicted by bioinformatics websites. Then, we screened miRNAs targeting LILRB3 by quantitative real-time PCR, and the dual luciferase reporter assay. The expression of LILRB3 and microRNA (miR)-103a-2-5p in AML were determined and then their interactions were also analyzed. In vitro, the effects of miR-103a-2-5p were determined by CCK8, colony formation assay, and transwell assay, while cell apoptosis and cell cycle were analyzed by flow cytometry. Cationic liposomes (CLPs) were used for the delivery of miR-103a-2-5p in the AML mouse model, which was to validate the potential roles of miR-103a-2-5p in vivo. Results LILRB3 was upregulated in AML cells while miR-103a-2-5p was dramatically downregulated. Thus, a negative correlation was found between them. MiR-103a-2-5p directly targeted LILRB3 in AML cells. Overexpressed miR-103a-2-5p significantly suppressed the mRNA and protein levels of LILRB3, thereby inhibiting AML cell growth and reducing CD8 + T cell apoptosis. In addition, overexpressed miR-103a-2-5p reduced both the relative expression of Nrf2/HO-1 pathway-related proteins and the ratio of GSH/ROS, leading to the excessive intracellular ROS that may promote AML cell apoptosis. In the mouse model, the delivery of miR-103a-2-5p through CLPs could inhibit tumor growth. Conclusions MiR-103a-2-5p serves as a tumor suppressor that could inhibit AML cell proliferation and promote their apoptosis by downregulating LILRB3 expression, suppressing the Nrf2/HO-1 axis, and reducing the ratio of GSH/ROS. Besides, our findings indicate that miR-103a-2-5p may enhance the CD8 + T cell response by inhibiting LILRB3 expression. Therefore, the delivery of miR-103a-2-5p through CLPs could be useful for the treatment of AML.

Background: Many patients with atrial fibrillation (AF) discontinued oral anticoagulation (OAC) therapy after successful catheter ablation. We aimed to determine the real-world risks and consequences of discontinuing OAC use after catheter ablation for AF. Methods: Patients who underwent successful catheter ablation for AF from January 2004 to December 2020 were divided into continued long-term OAC (On-OAC, n = 1062) and discontinued (Off-OAC, n = 1055) groups. The long-term outcomes including thromboembolic events, major bleeding, all-cause mortality and major adverse cardiovascular events (MACE), were compared between the two groups. Results: The CHA2DS2-VASc score was 3.44 ± 1.12. After a mean follow-up of 37.09 months, thromboembolism risk was higher and major bleeding risk was lower in the Off-OAC than in the On-OAC group (Both log-rank P 0.05), except for a higher major bleeding rate in the On-OAC group (P = 0.002). Patients at high risk for stroke (men and women with scores ≥3 and ≥ 4) had better non-thromboembolic and non-MACE results (Both log-rank P

BackgroundWith population aging, the prevalence of both cancer and atrial fibrillation (AF) have increased. However, there is scarce epidemiological data concerning the comorbid state of cancer and AF in low- and middle-income countries, including China. ObjectiveWe aimed to evaluate the site-, sex-, and age-specific profiles of cancer and AF comorbidities in Chinese populations. MethodsData from the Shanghai Municipal Health Commission database between 2015 and 2020 were screened, covering all medical records of Shanghai residents with medical insurance. Site-specific cancer profiles were evaluated for the population with AF relative to the age- and sex-adjusted population of residents without AF. The sex distribution and peak age of cancer diagnosis were also assessed. ResultsA total of 25,964,447 adult patients were screened. Among them, 22,185 patients presented cancers comorbid with AF (median 77, IQR 67-82 years of age; men: n=13,631, 61.44%), while 839,864 presented cancers without AF (median 67, IQR 57-72 years of age; men: n=419,020, 49.89%), thus yielding a higher cancer prevalence among residents with AF (8.27%) than among those without AF (6.05%; P

The total focusing method (TFM) has been increasingly applied to weld inspection given its high image quality and defect sensitivity. Oblique incidence is widely used to steer the beam effectively, considering the defect orientation and structural complexity of welded structures. However, the conventional TFM based on the delay-and-sum (DAS) principle is time-consuming, especially for oblique incidence. In this paper, a fast full-matrix imaging algorithm in the Fourier domain is proposed to accelerate the TFM under the condition of oblique incidence. The algorithm adopts the Chebyshev polynomials of the second kind to directly expand the Fourier extrapolator with lateral sound velocity variation. The direct expansion maintains image accuracy and resolution in wide-angle situations, covering both small and large angles, making it highly suitable for weld inspection. Simulations prove that the third-order Chebyshev expansion is required to achieve image accuracy equivalent to the TFM with wide-angle incidence. Experiments verify the algorithm’s performance for weld flaws using the proposed method with the transverse wave and the full-skip mode. The depth deviation is within 0.53 mm, and the sizing error is below 15%. The imaging efficiency is improved by a factor of up to 8 compared to conventional TFM. We conclude that the proposed method is applicable to high-speed weld inspection with various oblique incidence angles.

Abstract Background Selectively utilizing alternative mechanisms to repair damaged DNA in essential factors deficient cancer facilitates tumor genetic evolution and contributes to treatment resistance. Synthetic lethality strategies provide a novel scenario to anticancer therapy with DNA repair protein mutation, such as glioma with DNA-PKcs-deficiency, a core factor crucial for non-homologous end joining (NHEJ) mediated DNA damage repair. Nevertheless, the clinical significance and molecular mechanisms of synthetic lethality function by interfering tumor DNA replication remain largely unexplored. Methods Cancer clinic treatment resistance-related replication core factors were identified through bioinformatics analysis and RNA-sequencing and verified in clinical specimens by immunoblotting and in situ Proximity Ligation Analysis (PLA). Then, in vitro and in vivo experiments, including visible single molecular tracking system were performed to determine functional roles, the molecular mechanisms and clinical significance of synthetic lethality on glioma tumors. Results Hyperactive DNA replication and regulator Flap endonuclease 1 (FEN1) provides high efficiency DNA double strand breaks (DSB) repair abilities preventing replication forks collapse during DNA replication which facilitate adaptation to selective pressures. DNA-PKcs deficient glioma cells are highly dependent on FEN1/BRCA1/RAD51 to survival and counteract replication stress. FEN1 protects perturbed forks from erroneous over-resection by MRE11 through regulating of BRCA1-RAD51 and WRN helicase, uncovering an essential genetic interaction between FEN1 and DNA-PKcs in mitigating replication-stress induced tumor genomic instability. Therapeutically, genetic depletion or molecular inhibition of FEN1 and DNA-PKcs perturb glioma progression. Conclusions Our findings highlight an unanticipated synthetic interaction between FEN1/BRCA1/RAD51 and DNA-PKcs when dysfunction leads to incompatible with cell survival under conditions of interrupted replication progression by disrupting addictive alternative tumor evolution and demonstrate the applicability of combined FEN1 and DNA-PKcs targeting in the treatment of glioma.

Background: Left atrial appendage (LAA) closure (LAAC) in atrial fibrillation (AF) patients with the reversed chicken-wing (RCW) LAA is challenging. Aims: To elucidate the LAAC strategy of the RCW-LAA. Methods: A total of 802 AF patients who were enrolled in the LAACablation registry for LAAC procedure were included, 55 of whom presented with the RCW-LAA. The WATCHMAN device was implanted using the standard protocol when the sheath depth was no less than the device depth (the simple group). For those with a sheath depth of less than the device depth (the complex group), device deployment was attempted with acceptable protrusion or after a repeated atrial transseptal puncture (re-ATP) at a more inferior and anterior position. The anatomical and procedural features were compared between groups and before and after the re-ATP. Results: The success rate of LAAC was significantly lower in patients with the RCW-LAA than with the other morphologies (92.7% vs. 98.8%, p = 0.001). Compared with the simple group, the complex group had shorter root depth and shorter neck length, and more LAAs in the complex group were at lower position (all p

Atrial fibrillation (AF) is a common and life-threatening disease. For the patients with AF, more than 90% of the thrombi are formed in the left atrial appendage (LAA), thrombus dislodgement can cause vascular embolism, making them is becoming a high-risk group for stroke. Therefore, identifying the patients with high risk of thrombosis is crucial for advanced stroke warning. To better investigate the mechanism behind thrombus formation in the LAA, this study reconstructed the 3-D Left Atrium (LA) models of six AF volunteer patients by corresponding Computed Tomography (CT) images. Combine the advantages of Computational Fluid Dynamics (CFD), the blood flow field in LA both in AF and sinus heart rate states were studied. The risk of thrombus was evaluated based on the blood viscosity, shear rate thrombus prediction model and Time Average Wall Shear Stress (TAWSS), Oscillatory Shear Index (OSI), and Relative Residence Time (RRT) values. The results showed that the left atrium had lower blood flow velocity and TAWSS values at the LAA in both AF and sinus rhythm, thus the LAA is the most thrombogenic region in the LA. Besides, the RRT value of LAA was generally higher in AF than in sinus rhythm. Therefore, AF carries a higher risk of thrombosis.

Background: Managing patients with atrial fibrillation (AF) and comorbid heart failure (HF) with reduced (HFrEF) or mildly reduced ejection fraction (HFmrEF) is of clinical importance but a great challenge. This study aimed to evaluate the clinical benefit of the combined radiofrequency catheter ablation (RFCA) and left atrial appendage closure (LAAC) procedure in AF patients complicated with systolic HF. Methods: AF patients with HFrEF or HFmrEF who underwent the combined RFCA and LAAC procedure were prospectively enrolled in the LAACablation registry. The procedural complications and long-term outcomes were evaluated. Another cohort of AF patients with systolic HF who did not undergo either RFCA or LAAC were used for prognosis comparison. Results: Among 802 AF patients who underwent the combined procedure, 65 patients were comorbid with systolic HF (25 with HFrEF and 40 with HFmrEF). The overall procedural complication rate was 9.2%, which was mainly attributed to acute decompensated HF (6.2%). Accompanied with markedly reduced AF burden (from median [25th, 75th percentile]: 100 [100, 100] to 0 [0, 1.2]%, p < 0.001), upward trajectories of cardiac function were observed in 51 (78.4%) patients, showing improvement in New York Heart Classification (p < 0.01), natriuretic peptide levels (from 1492 [809, 3259] to 413 [163, 880] pg/mL, p < 0.001) and left ventricular EF (from 42.6 ± 5.3 to 53.8 ± 8.2%, p < 0.001). During the 27-month follow-up period, death, thromboembolism, major bleeding, and HF rehospitalization were observed in three, one, one, and four patients, respectively. The observed event rates showed a significant reduction compared with the non-procedure AF-HF cohort (n = 138; for composite endpoint: hazard ratio: 2.509, 95% confidence interval: 1.415–4.449, p = 0.002) and with the respective rates predicted by risk scores. Conclusions: Combining RFCA and LAAC achieves acceptable safety and credible long-term efficacy in AF patients with systolic HF. Further randomized studies are warranted in a larger patient cohort.

Extant clinical research has underscored that patients suffering from atrial fibrillation (AF) bear an elevated risk for stroke, predominantly driven by the formation of thrombus in the left atrial appendage (LAA). As such, accurately identifying those at an increased risk of thrombosis becomes paramount to facilitate timely and effective treatment. This study was designed to shed light on the mechanisms underlying thrombus formation in the LAA by employing three-dimensional (3D) left atrium (LA) models of AF patients, which were constructed based on Computed Tomography (CT) imaging. The distinct benefits of Computational Fluid Dynamics (CFD) were leveraged to simulate the blood flow field within the LA, using three distinct blood flow models, both under AF and sinus rhythm (SR) conditions. The potential risk of thrombus formation was evaluated by analyzing the Relative Residence Time (RRT) and Endothelial Cell Activation Potential (ECAP) values. The results gleaned from this study affirm that all three blood flow models align with extant clinical guidelines, thereby enabling an effective prediction of thrombosis risk. However, noteworthy differences emerged when comparing the intricacies of the flow field and thrombosis risk across the three models. The single-phase non-Newtonian blood flow model resulted in comparatively lower residence times for blood within the LA and lower values for the Oscillatory Shear Index (OSI), RRT, and ECAP within the LAA. These findings suggest a reduced thrombosis risk. Conversely, the two-phase non-Newtonian blood flow model exhibited a higher residence time for blood and elevated RRT value within the LAA, suggesting an increased risk for thrombosis.

Summary: Background: Atrial fibrillation(AF) has become a significant public health concern in China, with population aging and urbanization. Methods: Data screening was performed for 30,244,930 subjects with medical insurance in the Shanghai Municipal Health Commission database between 2015 and 2020. Patients diagnosed with AF were identified and further assessed for treatment information and clinical outcomes, as well as sex differences and impact of COVID-19 pandemic on AF managment. Findings: AF prevalence was 0.88% in Shanghai, which increased with age and reached 6.70% at subjects 80 years and over. AF was more prevalent in women compared with men (0.89% vs. 0.88%, p

BackgroundDNA damage response (DDR) proficiency is the principal mechanism of temozolomide (TMZ) resistance in glioma. Accumulating evidence has also suggested the determining role of DDR in anticancer immunity. We propose that a comprehensive investigation of the DDR landscape can optimize glioma treatment.MethodsWe identified the pronounced enrichment of DDR in TMZ-resistant glioma cells by RNA sequencing. Nine differentially expressed genes between TMZ-sensitive/resistant glioma cells were selected to construct the DDR score through lasso regression analysis. Two glioma cohorts from TCGA and CGGA were interrogated to evaluate the predictive ability of DDR score. Multiple algorithms were applied to estimate the immunotherapeutic responses of two DDR phenotypes. Immunohistochemistry was used to determine the protein levels of PD-L1 and TGFβ in glioma specimens. The oncoPredict package was employed to predict the candidate chemotherapy agents.ResultsDDR score exhibited a robust prognostic capability in TCGA and CGGA cohorts and served as an independent predictive biomarker in glioma patients. Functional enrichment analyses revealed that high and low DDR score groups were characterized by distinct immune activity and metabolic processes. Elevated levels of infiltrating immune cells (including CD8+ T cells, CD4+ T cells, and dendritic cells) were observed in the high DDR score glioma. Further, high DDR scores correlated with increased mutation burden, up-regulated immune checkpoints, and tumor immunity activation, indicating a profound interplay between DDR score and glioma immunogenicity. In addition, PD-L1 and TGFβ were overexpressed in recurrent glioma specimens compared with primary ones. Finally, we estimated that PI3K inhibitors may serve as latent regimens for high DDR score patients.ConclusionOur study highlighted the promising prognostic role of DDR score in glioma. Individual assessment of DDR status for patients with glioma may provide new clues for developing immunotherapeutic strategies.

Abstract Background Gradual ulnar lengthening is the most commonly used procedure in the treatment of Masada type I/II deformity in patients with hereditary multiple osteochondromas. However, the treatment remains controversial for the recurrence of deformity in growing children. This study aims to evaluate the clinical and radiological outcomes of ulnar gradual lengthening in our clinic. Methods We retrospectively reviewed patients who underwent ulnar lengthening by distraction osteogenesis from June 2008 to October 2017. The carrying angle (CA) and range of motion (ROM) of the forearm and elbow were clinically assessed, and the radial articular angle (RAA) and ulnar shortening (US) were radiologically assessed before lengthening, 2 months after external frame removal, and at the last follow-up. Results The current study included 15 patients (17 forearms) with a mean age of 9.4 ± 2.3 years at the index surgery. The mean follow-up period was 4.2 ± 2.4 years. There were 9 patients (10 forearms) with Masada type I deformity and 6 patients (7 forearms) with Masada type IIb deformity. The mean amount of ulnar lengthening was 4.2 ± 1.2 cm. The mean RAA improved from 37 ± 8 to 30 ± 7° initially (p = 0.005) and relapsed to 34 ± 8° at the last follow-up (p = 0.255). There was a minimal deterioration of US yet significant improvement at the last follow-up compared to pre-op (p < 0.001). At the last follow-up, the mean forearm pronation and elbow flexion increased significantly (p < 0.001 and p = 0.013, respectively), and the mean carrying angle also improved significantly (p < 0.001). No patient with type IIb deformity achieved a concentric radial head reduction. Conclusions Gradual ulnar lengthening significantly reduces cosmetic deformity and improves function in patients with Masada type I/IIb deformity. Our results supported early ulnar lengthening for patients with a tendency of dislocation of the radial head.

Abstract. Background. Catheter ablation is effective in restoring sinus rhythm and left atrial appendage closure (LAAC) is increasingly used for stroke prevention in patients with atrial fibrillation (AF). We aimed to observe the feasibility and safety of performing AF ablation and LAAC in a single (one-stop) procedure. Methods. Consecutive AF patients who underwent the combined procedure of AF ablation and LAAC with WATCHMAN device between March 2017 and September 2018 were prospectively enrolled. Baseline and intra-procedural parameters were evaluated. Three-month and subsequent 1-year follow-up were performed in all and earlier-enrolled subjects, respectively. Results. A total of 178 AF patients (94 males, 68.9 ± 8.1 years) underwent the one-stop procedure with CHA2DS2-VASc score 3.3 ± 1.5 and HAS-BLED score 1.6 ± 1.0, respectively. Pulmonary vein isolation was achieved in all patients while additional linear ablation was applied if the operator deemed necessary, yielding immediate ablation success rate of 98.9% (176/178). In the subsequent LAAC, satisfactory seal (residual leak

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor in RA progression, which promotes fibroblast-like synoviocyte (FLS) proliferation, pannus formation, and the damage of cartilage as well as bone. Resolvin D1 (RvD1) can promote inflammation resolution in acute inflammatory diseases, and recently, effects of RvD1 on chronic inflammatory diseases also attracted attention. This study aimed to examine the effect of RvD1 on pannus formation in RA and the underlying mechanism. Methods Serum levels of RvD1 and CTGF were determined in RA patients and healthy persons by UPLC-MS/MS and ELISA respectively. The levels of CTGF and inflammatory factors were assessed by qRT-PCR and ELISA. MicroRNA expression profile was determined by miRNA microarray. The effects of CTGF, RvD1, and miR-146a-5p on angiogenesis were evaluated with tube formation and chick chorioallantoic membrane (CAM) assays. Collagen-induced arthritis (CIA) mice were constructed to detect the effects of RvD1 and miR146a-5p on RA. STAT3 activation was determined by Western blotting. Results RvD1 levels decreased while CTGF levels increased in RA patients’ serum, and an inverse correlation of the concentrations of RvD1 and CTGF in the serum of RA patients was synchronously observed. In CIA mice, RvD1 suppressed angiopoiesis and decreased the expression of CTGF. Simultaneously, RvD1 significantly decreased CTGF and pro-inflammation cytokines levels in RA FLS. Furthermore, CTGF suppressed angiopoiesis and RvD1 inhibited the proliferation and migration of RA FLS and angiopoiesis. MiRNA microarray and qRT-PCR results showed that RvD1 upregulated miRNA-146a-5p. The transfection experiments demonstrated that miRNA-146a-5p could decrease inflammatory factors and CTGF levels. Moreover, miRNA-146a-5p decreased the proliferation of FLS and angiogenesis in vivo. MiRNA-146a-5p also suppressed angiogenesis and downregulated the expression of CTGF in CIA mice. Finally, Western blot results revealed that miRNA-146a-5p inhibited the activation of STAT3. Conclusion RvD1 is prone to alleviate RA progression through the upregulation of miRNA-146a-5p to suppress the expression of CTGF and inflammatory mediators, thereby decreasing pannus formation and cartilage damage.

BackgroundThe COVID-19 pandemic has led to concerns around its subsequent impact on global health.ObjectiveTo investigate the health-seeking behavior, reflected by ECG utilization patterns, of patients with non-COVID-19 diseases during and after COVID-19 epidemic.MethodsTaking advantage of the remote ECG system covering 278 medical institutions throughout Shanghai, the numbers of medical visits with ECG examinations during the lockdown (between January 23 and April 7, 2020), post-lockdown (between April 8 and December 31, 2020) and post-SARS-CoV-2 (between January 23 and April 7, 2021) periods were analyzed and compared against those during the same periods of the preceding years (2018 and 2019).ResultsCompared with the same period during pre-COVID years, the number of medical visits decreased during the lockdown (a 38% reduction), followed by a rebound post-lockdown (a 17% increase) and a fall to the baseline level in post-SARS-CoV-2 period. The number of new COVID-19 cases announced on a given day significantly correlated negatively with the numbers of medical visits during the following 7 days. Medical visit dynamics differed for various arrhythmias. Whereas medical visits for sinus bradycardia exhibited a typical decrease-rebound-fallback pattern, medical visits for atrial fibrillation did not fall during the lockdown but did exhibit a subsequent increase during the post-lockdown period. By comparison, the volume for ventricular tachycardia remained constant throughout this entire period.ConclusionThe ECG utilization patterns of patients with arrhythmias exhibited a decrease-rebound-fallback pattern following the COVID-19 lockdowns. Medical visits for diseases with more severe symptoms were less influenced by the lockdowns, showing a resilient demand for healthcare.

BackgroundAtrial fibrillation (AF) is the most common arrhythmia, and the incidence increases rapidly all over the world. The global prevalence of AF (age-adjusted) is 0.60% for men and 0.37% for women and the prevalence of AF in China is 0.65%. It is expected that the number of patients with AF will continue to rise in the future worldwide due to population aging.ObjectiveTo explore the prevalence of AF in Chinese community population in 2019 and clarify the prevalence of AF complicated with other arrhythmias and myocardial ischemia (MI) events.MethodsThe remote electrocardiogram (ECG) diagnosis system of Xinhua Hospital was assessed to the screen participants with ECG evidence of AF between January 1 and December 31, 2019. The prevalence rates of AF and its association with other arrhythmias and MI events were analyzed and subgroup analysis was performed between different sexes and age groups.ResultsA total of 22,016 AF cases were identified out of all ECGs derived from the remote ECG diagnosis system in 2019. It is estimated that AF was presented in nearly 10.15 million people in China (age-adjusted standardized rate 0.72%, 95% CI 0.20–1.25%) in 2019 and 62% of the AF cases (6.27 million) affected people aged 65 years and above (age-adjusted standardized rate 3.56%, 95% CI 3.28–3.85%). The prevalence rate of AF in males was higher than that in females (p < 0.001), and the ventricular rate of AF patients was faster in females (p < 0.001) and younger patients (p < 0.001). AF patients with lower ventricular rate (under 60 beats per min) were associated with increased prevalence of ventricular escape/escape rhythm [p < 0.001, odds ratio (OR) 5.14] and third-degree atrioventricular block (p < 0.001, OR 32.05).ConclusionThe prevalence of AF is higher in the Chinese community population than that was previously reported. AF patients complicated with ECG patterns suggesting myocardial infarction is common in men, and stricter measures should be taken to control the common risk factors of AF and coronary heart disease. It is also important that more attention should be paid to recognize fatal arrhythmias, especially in elderly male patients with AF.

Summary: Background: The dynamic trends of pulmonary function in coronavirus disease 2019 (COVID-19) survivors since discharge have been rarely described. We aimed to describe the changes of lung function and identify risk factors for impaired diffusion capacity. Methods: Non-critical COVID-19 patients admitted to the Guangzhou Eighth People's Hospital, China, were enrolled from March to June 2020. Subjects were prospectively followed up with pulmonary function tests at discharge, three and six months after discharge. Findings: Eighty-six patients completed diffusion capacity tests at three timepoints. The mean diffusion capacity for carbon monoxide (DLCO)% pred was 79.8% at discharge and significantly improved to 84.9% at Month-3. The transfer coefficient of the lung for carbon monoxide (KCO)% pred significantly increased from 91.7% at discharge to 95.7% at Month-3. Both of them showed no further improvement at Month-6. The change rates of DLCO% pred and KCO% pred were significantly higher in 0–3 months than in 3–6 months. The alveolar ventilation (VA) improved continuously during the follow-ups. At Month-6, impaired DLCO% pred was associated with being female (OR 5.2 [1.7–15.8]; p = 0.004) and peak total lesion score (TLS) of chest CT > 8.5 (OR 6.6 [1.7–26.5]; p = 0.007). DLCO% pred and KCO% pred were worse in females at discharge. And in patients with impaired diffusion capacity, females’ DLCO% pred recovered slower than males. Interpretation: The first three months is the critical recovery period for diffusion capacity. The impaired diffusion capacity was more severe and recovered slower in females than in males. Early pulmonary rehabilitation and individualized interventions for recovery are worthy of further investigations.

Background: The role of ferroptosis in breast cancer brain metastasis (BCBM) is unclear. This study aimed to explore the ferroptosis-related genes (FRG) relations with the tumor microenvironment, as well as evaluate their values in predicting survival and drug sensitivity in patients with BCBM.Materials and Methods: Genes expression and clinical data were downloaded from Gene Expression Omnibus (GEO). Univariate and multivariate Cox regression analyses were performed to explore the independent prognostic factors. Consensus cluster principal component analysis (PCA) was used to establish the ferroptosis score. Immunological signatures were analyzed by the single-sample gene set enrichment analysis (ssGSEA). Drug sensitivity was evaluated through the estimated half-maximal inhibitory concentration (IC50). Finally, results were validated in external cohorts.Results: Fourteen significantly different FRG were identified between breast cancer (BC) and BCBM tissues. Survival analysis demonstrated HMOX1, PEBP1, KEAP1, and LPCAT3 were significantly associated with overall survival (OS) and relapse-free survival (RFS) (all p < 0.05). High ferroptosis score was correlated with iron ion homeostasis, iron metabolism, higher stromal cells and immune cells scores. Patients with high- and low-ferroptosis scores were characterized by different drug sensitivities. Following external validations, the ferroptosis had distinct expression profiles between the BC and BCBM, and could serve as biomarkers for OS and drug response.Conclusion: Our findings suggested that ferroptosis may be involved in the process of BCBM, and ferroptosis could serve as prognostic biomarkers. Evaluation of ferroptosis may deepen our understanding about the tumor microenvironment, and could help clinicians to make individualized therapy.

Background: The aim of this study was to investigate the efficacy of left atrial appendage closure (LAAC) for primary and secondary stroke prevention in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF).Methods: This pilot study enrolled 36 patients with HCM and AF who underwent LAAC between April 2017 and December 2019, of whom 22 were for primary stroke prevention and 14 were for secondary prevention.Results: The patients enrolled in this study had non-obstructive (86.1%) or mild obstructive (13.9%) HCM. Patients in the Secondary Prevention Group had higher CHA2DS2-VASc scores (5.1 ± 1.4 vs. 2.6 ± 1.6, P < 0.001) and higher HAS-BLED scores (2.8 ± 1.0 vs. 1.5 ± 0.9, P < 0.001) compared with those in the Primary Prevention Group. Successful closure with satisfactory seals (residual leak ≤ 5 mm) was achieved in all patients, with complete occlusion in 86.4% of the Primary Prevention Group and 92.9% of the Secondary Prevention Group. Procedural-related complications included one pericardial effusion and one groin hematoma. One device-related thrombus was identified in the Secondary Prevention Group and resolved after anticoagulation. During a mean follow-up time of 28.4 months, one bleeding event was recorded. There were no thromboembolic events or deaths in either group, with 97.2% of the patients achieving freedom from anticoagulation therapy.Conclusions: Initial results suggest that LAAC can be a safe and feasible alternative for primary and secondary stroke prevention in selected patients with HCM and AF. Further studies with larger samples are required.

Free vibration of summation resonance of suspended-cable-stayed beam is investigated in the article. A 3-DOF model of the coupled structure is built, with the main cable and sling (vertical cable) considered to be geometrically nonlinear, and the beam is taken as linear Euler beam. Hamilton's principle is used to derive the dynamic equilibrium equations of the coupled structure. Then, the dynamic equilibrium equations are solved by means of multiple scales method, the second order approximation solutions of single-modal motion of the coupled structure are obtained. Numerical examples are presented to discuss time history of free vibration of the summation resonance, with and without damping. Additionally, fourth-order Runge-Kutta method is directly used for the dynamic equilibrium equations to complement and verify the analytical solutions. The results show that the coupled structure performs strongly nonlinear and coupled characteristics, which is useful for engineering design.

Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor, and patients with GBM have a median survival of 20 months. Clinical therapy resistance is a challenging barrier to overcome. Tumor genome stability maintenance during DNA replication, especially the ability to respond to replication stress, is highly correlated with drug resistance. Recently, we identified a protective role for RECQ1 under replication stress conditions. RECQ1 acts at replication forks, binds PCNA, inhibits single-strand DNA formation and nascent strand degradation in GBM cells. It is associated with the function of the PARP1 protein, promoting PARP1 recruitment to replication sites. RECQ1 is essential for DNA replication fork protection and tumor cell proliferation under replication stress conditions, and as a target of RECQ1, PARP1 effectively protects and restarts stalled replication forks, providing new insights into genomic stability maintenance and replication stress resistance. These findings indicate that tumor genome stability targeting RECQ1-PARP1 signaling may be a promising therapeutic intervention to overcome therapy resistance in GBM.

Capicua (Cic), a transcriptional repressor frequently mutated in brain cancer oligodendroglioma, is highly expressed in adult neurons. However, its function in the dendritic growth of neurons in the hippocampus remains poorly understood. Here, we confirmed that Cic was expressed in hippocampal neurons during the main period of dendritogenesis, suggesting that Cic has a function in dendrite growth. Loss-of-function and gain-of function assays indicated that Cic plays a central role in the inhibition of dendritic morphogenesis and dendritic spines in vitro. Further studies showed that overexpression of Cic reduced the expression of Ets in HT22 cells, while in vitro knockdown of Cic in hippocampal neurons significantly elevated the expression of Ets. These results suggest that Cic may negatively control dendrite growth through Ets, which was confirmed by ShRNA knockdown of either Etv4 or Etv5 abolishing the phenotype of Cic knockdown in cultured neurons. Taken together, our results suggest that Cic inhibits dendritic morphogenesis and the growth of dendritic spines through Ets.

Introduction It is the common clinical practice to prescribe indefinite aspirin for patients with non-valvular atrial fibrillation (NVAF) post left atrial appendage occlusion (LAAO). However, aspirin as a primary prevention strategy for cardiovascular diseases has recently been challenged due to increased risk of bleeding. Therefore, aspirin discontinuation after LAAO in atrial fibrillation (ASPIRIN LAAO) trial is designed to assess the uncertainty about the risks and benefits of discontinuing aspirin therapy at 6 months postimplantation with a Watchman LAAO device in NVAF patients.Methods and analysis The ASPIRIN LAAO study is a prospective, multicentre, randomised, double-blinded, placebo-controlled non-inferiority trial. Patients implanted with a Watchman device within 6 months prior to enrollment and without pre-existing conditions requiring long-term aspirin therapy according to current guidelines are eligible for participating the trial. Subjects will be randomised in a 1:1 allocation ratio to either the Aspirin group (aspirin 100 mg/day) or the control group (placebo) at 6 months postimplantation. A total of 1120 subjects will be enrolled from 12 investigational sites in China. The primary composite endpoint is stroke, systemic embolism, cardiovascular/unexplained death, major bleeding, acute coronary syndrome and coronary or periphery artery disease requiring revascularisation at 24 months. Follow-up visits are scheduled at 6 and 12 months and then every 12 months until 24 months after the last patient recruitment.Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Xinhua Hospital, Shanghai, China (reference number XHEC-C-2018-065-5). The protocol is also submitted and approved by the institutional Ethics Committee at each participating centre. Results are expected in 2024 and will be disseminated through peer-reviewed journals and presentations at national and international conferences.Trial registration number NCT03821883.

Background. Combined atrial fibrillation (AF) ablation and left atrial appendage closure (LAAC) has been practiced for management of both the symptoms and the high stroke risk of AF. Data of the combined procedure in selected patients with prior stroke are limited. The aim of this study is to compare the safety and efficacy of combined catheter ablation and LAAC between AF patients with and without prior stroke. Methods and Results. This retrospective study enrolled 296 patients who underwent combined procedures of AF ablation and LAAC. Patients were divided into two groups: 81 patients with prior stroke (Stroke group) and 215 patients without prior stroke (Control group). Combined procedures were successfully performed in all the patients. Patients in the Stroke group had higher CHA2DS2-VASc scores (4.9 ± 1.2 vs. 3.2 ± 1.0, P

Background: Recently, the impact of fine particulate matter pollution on cardiovascular system is drawing considerable concern worldwide. The association between ambient fine particulate and the cardiac arrhythmias is not clear now. Objective: To study associations of ambient fine particulate with incidence of arrhythmias in outpatients. Methods: Data was collected from the remote electrocardiogram (ECG) system covering 282 community hospitals in Shanghai from June 24th, 2014 to June 23rd, 2016. ECG was performed for patients admitted to above hospitals with complaining of chest discomfort or palpitation, or for regular check-ups. Air quality data during this time period was obtained from China National Environment Monitoring Center. A generalized additive quasi-Poisson model was established to examine the associations between PM2.5 and cardiac arrhythmias. Results: Cardiac arrhythmias were detected in 202,661 out of 1,016,579 outpatients (19.9%) and fine particulate matter ranged from 6 to 219 μg/m3 during this period. Positive associations were evidenced between fine particulate matter level and prevalence of cardiac arrhythmia by different lag models. Per 10 μg/m3 increase in fine particulate matter was associated with a 0.584%(95%CI:0.346-0.689%, p

Abstract Background Pulmonary vein isolation (PVI), a cornerstone for catheter ablation of atrial fibrillation (AF), remains a complex and time-consuming procedure. Present study introduces a novel, circular-irrigated, deca-channel mapping and ablation catheter (CIDMA), describes the in vitro test results on feasibility, safety, and acute efficacy of the CIDMA catheter. Methods An assembled CIDMA catheter was subjected to a number of in vitro tests. With this catheter, ablation procedures were first performed in a pig’s myocardial strips in vitro to determine the effects in unipolar or bipolar configuration. Results Three catheters were assembled. The adjustable circular diameter was changed from initial state of 32.41 ± 0.61 mm into controlled state of 28.61 ± 0.47 mm (P = 0.013). In the plastic model, the push-ability, torque-ability, and kink resistance of CIDMA catheter were shown to be satisfactory. In vitro, our findings showed that ablation could produce obvious ablation lesions, and unipolar ablation (at length, width and depth of 5.0 ± 1.3, 4.6 ± 0.7, and 4.2 ± 0.6 mm, respectively) was more effective than bipolar (at length, width and depth of 2.8 ± 0.2, 4.2 ± 0.5, and 2.3 ± 0.4 mm, respectively) (P

Three-dimensional (3D) object detection is an important task in the field of machine vision, in which the detection of 3D objects using monocular vision is even more challenging. We observe that most of the existing monocular methods focus on the design of the feature extraction framework or embedded geometric constraints, but ignore the possible errors in the intermediate process of the detection pipeline. These errors may be further amplified in the subsequent processes. After exploring the existing detection framework of keypoints, we find that the accuracy of keypoints prediction will seriously affect the solution of 3D object position. Therefore, we propose a novel keypoints uncertainty prediction network (KUP-Net) for monocular 3D object detection. In this work, we design an uncertainty prediction module to characterize the uncertainty that exists in keypoint prediction. Then, the uncertainty is used for joint optimization with object position. In addition, we adopt position-encoding to assist the uncertainty prediction, and use a timing coefficient to optimize the learning process. The experiments on our detector are conducted on the KITTI benchmark. For the two levels of easy and moderate, we achieve accuracy of 17.26 and 11.78 in AP3D, and achieve accuracy of 23.59 and 16.63 in APBEV, which are higher than the latest method KM3D.

Aim. The feasibility and safety of performing the combined procedure of catheter ablation (CA) and left atrial appendage closure (LAAC) for atrial fibrillation (AF) have been reported by observational studies without controls. The aim of this study was to compare the procedural and long-term outcomes of combined procedures with isolated CA or LAAC. Methods and Results. This study included patients who underwent combined CA and LAAC (combined group), CA alone (CA-only group), or LAAC alone (LAAC-only group). Propensity score matching was used to select controls from the CA-only and LAAC-only groups. Each group contained 76 subjects. The procedures were successfully performed in all the patients. Procedure-related complications of the combined group included one pericardial effusion and two groin haematomas, which did not differ significantly with those of the CA-only group (3.9% vs. 2.6%, P=0.650) or the LAAC-only group (3.9% vs. 2.6%, P=0.650), respectively. The AF-free rate of the combined group was comparable with that of the CA-only group after a mean of 2 years follow-up (67.1% vs. 69.7%, P=0.727). Compared with the LAAC-only group, the combined group achieved similar complete occlusion rate at implant (94.7% vs. 93.4%) and at 45 days (82.9% vs. 85.5%). At the end of follow-up, ischemic stroke and bleeding events of the combined group were low (3.9%) and were comparable with those of the CA-only group (5.3%) and the LAAC-only group (2.6%). Conclusions. The combination of AF-CA and LAAC is safe and efficacious compared with single procedures alone.

Background. Premature ventricular complexes (PVCs) exhibit circadian fluctuation. We determine if PVCs of different origin exhibit specific circadian patterns. Methods. We analyzed Holter recordings from patients with monomorphic PVCs who underwent catheter ablation. PVC circadian patterns were classified as fast-heart rate- (HR-) dependent (F-PVC), slow-HR-dependent (S-PVC), or HR-independent (I-PVC). PVC origins were determined intraprocedurally. Results. In a retrospective cohort of 407 patients, F-PVC and S-PVC typically exhibited diurnal and nocturnal predominance, respectively. Despite decreased circadian fluctuation, I-PVC generally had heavier nocturnal than diurnal burden. PVCs of left anterior fascicle origin were predominantly S-PVC, while those of posterior hemibranch origin were mostly F-PVC. PVCs originating from the aortic sinus of Valsalva (ASV) were predominantly I-PVC, while most PVCs arising from the left ventricular outflow tract (LVOT) were F-PVC. Using a diurnal/nocturnal PVC burden ratio of 0.92 as the cutoff value to distinguish LVOT from ASV origin achieved 97% sensitivity and, as further verification, an accuracy of 89% (16/18) in a prospective cohort of patients with PVCs originating from either ASV or LVOT. In contrast, PVCs originating from right ventricles, such as right ventricular outflow tract, did not show distinct circadian patterns. Conclusions. The circadian patterns exhibit origin specificity for PVCs arising from left ventricles. An analysis of Holter monitoring provides useful information on PVC localization in ablation procedure planning.

Background: Patients with manifest atrioventricular accessory pathways (mAPs) have a greater tendency to develop atrial fibrillation (AF) compared with patients with concealed atrioventricular accessory pathways (cAPs). However, the risk factors of developing AF in patients with various atrioventricular accessory pathways (APs) are not clear. Methods: This retrospective study included 460 symptomatic patients with either cAPs (n = 246) or mAPs (n = 214) who underwent electrophysiological study and successful radiofrequency catheter ablation of APs. Clinical and electrophysiological characteristics were compared between cAPs and mAPs and between AF and non-AF groups with cAPs or mAPs. Independent risk factors of AF were analyzed using multivariate logistic regression. Results: AF was more frequent in mAPs group than in cAPs group (23.4% vs 9.8%, p

Aims. Basal insulin plus oral hypoglycemic agents (OHAs) has not been investigated for early intensive antihyperglycemic treatment in people with newly diagnosed type 2 diabetes. This study is aimed at comparing the short-term (over a period of 12 days) effects of basal insulin glargine plus OHAs and continuous subcutaneous insulin infusion (CSII) on glycemic control and beta-cell function in this setting. Methods. An open-label parallel-group study. Newly diagnosed hospitalized patients with type 2 diabetes and fasting plasma glucose (FPG) ≥11.1 mmol/L or glycated hemoglobin (HbA1c) ≥9% (75 mmol/mol) were randomized to CSII or insulin glargine in combination with metformin and gliclazide. The primary outcome measure was the mean amplitude of glycemic excursions (MAGE), and secondary endpoints included time to reach glycemic control target (FPG

In the bridge engineering, there are some problems about the dynamics that traditional theory cannot solve. So, the theory about stress waves is introduced to solve the related problems. This is a new attempt that the mechanic theory is applied to practical engineering. The stress wave at a junction of the structure composed of beams and strings is investigated in this paper. The structure is studied because the existence of a soft rope makes the transmission of the force in the bridge structure different from the traditional theory, and it is the basis for further research. The equilibrium equations of the displacement and the internal force are built based on the hypothesis. The fast Fourier transform (FFT) numerical algorithm is used to express an incident pulse of arbitrary shape. The analytical solutions are substantiated by comparing with the finite element programs. The conclusion that if the cross section of the string is relatively small, then the energy density of the structure is relatively large, which is disadvantageous to the structure, can be obtained from this paper.

Employing Riccati techniques and the integral averaging method, we establish interval oscillation criteria for the second-order Emden-Fowler neutral delay differential equation $$ [|x'(t)|^{gamma-1}x'(t)]'+q_1(t)|y(t-sigma)|^{alpha-1}y(t-sigma) +q_2(t)|y(t-sigma)|^{eta-1} y(t-sigma)=0, $$ where $tgeq t_0$ and $x(t)=y(t)+p(t)y(t-au)$. The criteria obtained here are different from most known criteria in the sense that they are based on information only on a sequence of subintervals of $[t_0,infty)$, rather than on the whole half-line. In particular, two interesting examples that illustrate the importance of our results are included.

BackgroundThe prevalence of metabolic syndrome (MetS) is growing rapidly in China. Tai chi and dancing are common types of exercise among middle-aged and elderly Chinese. It remains unclear whether these activities are associated with a lower risk of MetS.Methodology/principal findingsA total of 15,514 individuals (6,952 men, 8,562 women) aged 50 to 70 years from the Dongfeng-Tongji Cohort in Shiyan, China participated in a cross-sectional study. Physical activity and other lifestyle factors were assessed with semi-structured questionnaires during face-to-face interviews. MetS was defined by the current National Cholesterol Education Program/Adult treatment Panel III criteria for Asian Americans. The prevalence of MetS was 33.2% in the study population. In the multivariable-adjusted logistic regression analyses, total physical activity levels were monotonically associated with a lower odds of MetS [OR 0.75 comparing extreme quintiles, 95% confidence interval (CI) 0.66-0.86, PConclusions/significanceJogging, tai chi and dancing are associated with a significantly lower risk of having MetS in middle-aged and older Chinese. Future intervention studies should consider the role of jogging, tai chi and dancing in preventing MetS.