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Background: There are no clear conclusions as to whether inflammatory proteins and plasma metabolites influence erectile dysfunction (ED)., Aim: In this research, we used Mendelian randomization (MR) analysis to discover a causal relationship between inflammatory proteins, plasma metabolites, and ED., Methods: Raw data with ED, inflammatory proteins, and plasma metabolites were obtained from the MRC IEU OpenGWAS and FinnGen database. After a series of screenings, the remaining single nucleotide polymorphisms were selected as instrumental variables or MR analysis to assess the relationship between genetically predicted inflammatory proteins or plasma metabolites and the pathogenesis of ED., Outcomes: The relationship between inflammatory factors and ED was fully analyzed and elaborated., Results: In the inverse variance-weighted method, there exists a significant causal relationship between 4 types of genetically predicted inflammatory proteins and 50 types of plasma metabolites with the incidence of ED. The primary discovery is that 3 inflammatory proteins, fibroblast growth factor 5, interleukin-22 receptor subunit alpha-1, and protein S100-A12, can impact the risk of ED through plasma metabolites., Clinical Implications: ED metabolites and inflammatory proteins are also closely associated with cardiovascular diseases, warranting further exploration., Strengths and Limitations: Our analysis is based on a European population, limiting its generalizability, the genome-wide association study dataset for ED has a relatively small number of cases, and we hope for larger genome-wide association study datasets for future validation., Conclusion: This study has identified that inflammatory proteins can influence ED through plasma metabolites., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Adverse drug events (ADEs) are common in clinical practice and can cause significant harm to patients and increase resource use. Natural language processing (NLP) has been applied to automate ADE detection, but NLP systems become less adaptable when drug entities are missing or multiple medications are specified in clinical narratives. Additionally, no Chinese-language NLP system has been developed for ADE detection due to the complexity of Chinese semantics, despite ˃10 million cases of drug-related adverse events occurring annually in China. To address these challenges, we propose DKADE, a deep learning and knowledge graph-based framework for identifying ADEs. DKADE infers missing drug entities and evaluates their correlations with ADEs by combining medication orders and existing drug knowledge. Moreover, DKADE can automatically screen for new adverse drug reactions. Experimental results show that DKADE achieves an overall F1-score value of 91.13%. Furthermore, the adaptability of DKADE is validated using real-world external clinical data. In summary, DKADE is a powerful tool for studying drug safety and automating adverse event monitoring., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The aim of this study was to investigate the expression of smoothened protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells., Methods: The expression of Smo pxrotein in RA synovial tissue was examined by immunohistochemistry. Real-time PCR and western blotting techniques were employed to measure the expression of Shh signalling components in EA.hy926 endothelial cells exposed to TNF-α in the presence or absence of cyclopamine (a Smo-specific antagonist). Lastly, the effect of cyclopamine and Smo small interfering RNA on apoptosis induced by TNF-α and actinomycin D (ActD) was determined., Results: We found that Smo was highly expressed in synovial tissues of RA, especially in endothelial cells, compared with the trauma group. TNF-α significantly increased the expression of Shh signalling components in EA.hy926 endothelial cells, while cyclopamine decreased the expression of Shh signalling components. EA.hy926 endothelial cells treated with various concentrations of cyclopamine (2-8 μmol/l) showed a significant decrease in cell viability and cell survival rate, and an increase in the rate of cell apoptosis compared with endothelial cells treated with TNF-α and ActD (P < 0.05). EA.hy926 endothelial cells transfected with Smo-siRNA also showed a lower cell survival rate and higher apoptotic rate, compared with cells in the control group (P < 0.05)., Conclusion: The Shh signalling pathway plays a role in regulating endothelial cell apoptosis in a Smo-dependent manner., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the feasibility and safety of non-robotically assisted totally thoracoscopic closure for atrial septal defect (ASD) on perfused beating hearts., Methods: Twenty-four patients (8-45 years, mean 14.4 ± 18.7) underwent ASD closure on beating hearts by a totally thoracoscopic approach without the aid of a robotic surgical system. Additional 72 patients undergoing totally thoracoscopic ASD closure on cardioplegic arrested hearts were selected as a control. Cardiopulmonary bypass (CPB) was achieved peripherally. The aorta was not cross-clamped in the study group but it was cross-clamped in the control group., Results: ASD closure was successful in all study and control group patients without in-hospital mortality or major complications. The total duration of operation (76 ± 9 vs. 98 ± 6 min, P = 0.012), CPB time (32 ± 5 vs. 48 ± 4 min, P = 0.001), duration of intensive care stay (10.0 ± 5.1 vs. 19.2 ± 4.2 h, P = 0.003) and post-operative hospital stay (4.5 ± 0.8 vs. 5.0 ± 1.1 days, P = 0.045) in the study group were shorter than in the control group. There was no statistically significant difference in the proportion of patients requiring in-operation blood transfusion between study group and control group (25.0 vs. 36.1%, P = 0.226). Follow-up transthoracic echocardiography on Day 5 and Day 30 showed no residual shunts in study or control group patients., Conclusions: Non-robotically assisted totally thoracoscopic closures of ASD on perfused beating hearts are feasible and safe. These procedures are associated with a shorter operation time and a shorter hospital stay than in surgeries on cardioplegic arrested hearts.

This study was aimed at identifying sex pheromones of the rat (Rattus norvegicus). We characterized the volatiles and semivolatiles of rat preputial gland and voided urine by using gas chromatography-mass spectrometry (GC-MS) and quantified them by their GC areas (abundances) and percentage of GC areas (relative abundances). Although all the compounds other than 4-heptanone and phenol detected were shared by males and females, the quantities for some of these sex-common compounds exhibited sexual dimorphism and decreased with gonadectomy. Thus, these compounds might be sex pheromones. Among them, squalene from preputial glands and 2-heptanone and 4-ethyl phenol from urine were 3 major compounds. They were richer in males and could be suppressed by castration. Adding any of the 3 compounds (at a concentration higher than its physiological level in male urine) to castrated male urine (CMU) increased the attractiveness of CMU to sex-naive females. Adding the 3 together (at the levels in normal male urine) to CMU significantly increased the attractiveness of CMU to females. However, such combination did not fully restore females' preference for urine from intact males, suggesting that some other trace compounds such as 4-heptanone and phenol might also play some roles in sex attractiveness. Thus, squalene, 2-heptanone, and 4-ethyl phenol were indeed male pheromone molecules in rats. Our study also indicates that E,E-beta-farnesene and E-alpha-farnesene, both richer in females than males, might be putative female pheromones.