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关键词： congenital heart disease   oxidative stress   antioxidant capacity   thiol/disulfide homeostasis   hemoxygenase-1   neonates  

摘要： Objective Oxidative stress is a major contributor to the pathogenesis of cyanotic congenital heart disease (CCHD), yet data in neonates are limited. This study aimed to assess oxidative stress markers, thiol/disulfide homeostasis, and heme oxygenase-1 (HO-1) levels in neonates with CCHD. Study Design A prospective case-control study was conducted, including 62 term neonates with CCHD and 63 healthy controls. Serum levels of total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), native and total thiol, disulfide (SS), and HO-1 were measured within 72 hours of birth. Thiol/disulfide ratios were calculated. Survival-based subgroup and receiver operating characteristic (ROC) analyses were performed. Results CCHD neonates had significantly decreased TAS, elevated TOS and OSI levels, and reduced HO-1, native thiol, and total thiol levels compared with controls (p < 0.001). Disulfide/native thiol and disulfide/total thiol ratios were significantly increased, while the native thiol/total thiol ratio was decreased (p < 0.05), indicating oxidative imbalance. Among nonsurvivors, lower HO-1 and thiol levels and higher oxidative stress markers were observed, though not all reached statistical significance (p > 0.05). ROC analysis showed that TOS (cut-off > 12.96;sensitivity 96.83%) and OSI (cut-off > 0.86;specificity 86.96%) were strong ***-1 and oxidative stress parameters showed excellent diagnostic accuracy (OSI [area under the curve (AUC): 0.942], TOS [AUC: 0.927], TAS [AUC: 0.904], HO-1 [AUC: 0.859]). Conclusion Neonates with CCHD exhibit significant oxidative stress and impaired antioxidant defense early in life. Suppressed HO-1 expression and disturbed thiol/disulfide balance suggest increased vulnerability to oxidative injury. These biomarkers may serve as early indicators for clinical risk stratification and could guide antioxidant-based therapeutic strategies.

关键词： data analysis   N-of-1   personalized medicine  

摘要： N-of-1 trials offer a unique and rigorous methodology for evaluating individualized treatment responses, particularly within the context of personalized medicine. This article provides a comprehensive explanation of the conceptual and methodological underpinnings of N-of-1 trials, with particular emphasis on statistical techniques and considerations critical for their design and analysis. Existing guidelines for planning and conducting these studies are summarized, along with a discussion of the practical and theoretical challenges to their implementation in clinical practice. We provide an overview for clinicians and researchers who may be unfamiliar with the design. As most of the existing guidance has focused on design and implementation considerations, we expand on the statistical analysis. We aim to support researchers and methodologists in understanding and advancing the methodological toolkit necessary for high-quality N-of-1 research.

关键词： Characteristics   Epidemiology   Type 1 diabetes  

摘要： Objective To comprehensively analyze the characteristics of type 1 diabetes and compare the differences between childhood-onset and adult-onset *** Hospital records of patients with type 1 diabetes of all ages were collected from 18 hospitals across 14 prefectures in Northwest China between January 2016 and October 2023. Data included demographic characteristics, manifestation at onset, physical examination, laboratory tests, and management. Based on diagnosis status, participants were classified into newly diagnosed and previously diagnosed groups. Additionally, according to the age at onset, participants were further divided into childhood-onset and adult-onset *** Among the 1,513 individuals with type 1 diabetes, the newly diagnosed group showed a younger median age of onset, lower mean body mass index, and better beta-cell function compared with the previously diagnosed group. Diabetic ketoacidosis at diagnosis was common, and the prevalence of chronic complications increased with disease duration. Most patients in both groups used multiple daily injections. Additionally, patients with childhood-onset type 1 diabetes were more likely to have diabetic ketoacidosis at diagnosis and had higher HbA1c levels at disease onset, lower BMI levels, and lower prevalence of complications compared with those with adult-onset *** This multicenter, hospital-based study provided an overview of the characteristics of patients with type 1 diabetes. These findings may contribute to a better understanding of type 1 diabetes and underscore the importance of long-term diabetic education and management.

关键词： adverse drug reactions   dermatologic reactions   drug safety   GLP-1 receptor agonists   injection-site reactions  

摘要： Aims Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes mellitus and obesity, with once-weekly dosing that supports adherence. However, injection-site reactions (ISRs) and dermatologic events have been recognised, ranging from mild local events to rare systemic hypersensitivity reactions that may cause discontinuation. To evaluate dermatologic and ISR safety of GLP-1 RAs through a meta-analysis of randomised controlled trials (RCTs) and disproportionality analysis of data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS).Materials and Methods PubMed, Embase and Web of Science were searched through December 2024 to identify RCTs reporting ISR or dermatologic outcomes for GLP-1 RAs. Random-effects meta-analysis synthesised trial evidence. A retrospective disproportionality analysis of FAERS data evaluated all approved GLP-1 RAs. Lower bound reporting odds ratios (LB ROR), proportional reporting ratios (PRR) and information components (IC) were *** The pooled meta-analysis of 14 RCTs that reported ISRs (4861 patients;396 ISR events) showed increased ISR risk with GLP-1 RAs versus comparators (risk ratio 3.55;95% confidence interval, 2.35-5.36;I2 = 41.4%). Dermatologic events were infrequent and not significantly elevated. FAERS data analysis revealed potential ISR signals for exenatide and dulaglutide. Exenatide was associated with injection-site haemorrhage (PRR: 27.6;LB ROR: 29.4;IC025: 4.6). Dulaglutide showed disproportionate reporting for injection-site haemorrhage (PRR: 11.5;LB ROR: 11.5;IC025: 3.4).Conclusions GLP-1 RAs are consistently linked to higher ISR risk, especially with exenatide and dulaglutide, while generalised dermatologic events are rare. Clinicians should counsel patients about ISR risk to support adherence and optimise outcomes.