Background: Brugada syndrome (BrS) is an inheritable arrhythmia syndrome that can lead to sudden cardiac death in patients while the heart structure is normal. However, the genetic background of more than 65% of BrS probands remains unclear. Objectives: The purpose of this study is to report the variant spectrum in a Chinese cohort with suspected BrS and to analyze their distinct clinical and electrocardiographic features. Methods: Patients with suspected BrS from Tongji Hospital between 2008 and 2021 were analyzed retrospectively. Results: A total of 79 probands were included in this study. Patients with type 1 BrS electrocardiogram (ECG) had a prolonged QRS duration compared to patients with type 2/3 BrS ECG. Of them, 59 probands underwent genetic testing. Twenty-five patients (42.37%) showed abnormal genetic testing results, and eight of them (13.56%) carried pathogenic/likely pathogenic (P/LP) mutations. Mutation carriers presented much more prominent depolarization and repolarization abnormalities than non-carriers, including a prolonged P-wave duration, QRS duration, QTc interval, decreased QRS amplitude, and deviation of the electrocardiographic axes (T-wave axis and R-wave axis). Furthermore, our study identified four novel P/LP mutations: Q3508X in TTN, A990G in KCNH2, G1220E, and D372H (in a representative pedigree) in SCN5A. Conclusions: Our study showed the variant spectrum of a suspected Chinese BrS cohort, and we identified four novel P/LP mutations in TTN, KCNH2, and SCN5A.

As next-generation sequencing develops, there are significant associations between glucokinase regulatory protein (GCKR) variants and many diseases, especially metabolic diseases. However, there is a lack of solid descriptions and summaries of how GCKR variants lead to diseases and a lack of successful translations of drugs targeting this molecular variant. We searched literature datasets, mainly including PubMed and Web of Science, with “GCKR” or “GKRP”, “Variants”, “Hypertriglyceridemia”, “NAFLD”, and “Metabolic diseases” as the search terms. Our review firstly introduces the biological function of the GCKR gene and its encoding protein GKRP and then describes the GCKR variants in different diseases, such as hypertriglyceridemia and NAFLD, revealing that GCKR/GKPR is strongly associated with metabolic diseases. GKPR might be a potential target for T2D and other metabolic diseases. One drug for interfering with the GCK-GKRP complex has been developed and has shown its effectiveness in preclinical studies, with some possible side effects. More and more different-structured drugs should be developed to improve side effects, and more clinical trials should be carried out to determine the best intervention window and timing points to improve prognosis. Taken together, these insights show that GCKR/GKRP is significantly associated with many metabolic diseases via its complex metabolism system and is a potential target in many metabolic diseases.

Objective The objective is to investigate the association of hyperuricaemia and hyperglycaemia with an increased risk of mortality in acute aortic dissection (AAD). Design Retrospective multicentre cohort study. Setting De-identified information of patients was collected from electronic medical records between 2010 and 2021 across five hospitals in China. Participants A total of 2603 AAD patients from 5337 patients who underwent arterial aortic computed tomographic angiography were selected after three rounds of screening. Main outcome measure All-cause in-hospital mortality. Results Of the 2603 patients, 20.3% were women, and the mean age was 54 years old. In-hospital mortality risk escalated linearly with increased levels of uric acid (P non-linearity=0.1699) and serum glucose (P non-linearity=0.2423). The per SD of increment in uric acid was associated with 40% (1.40, 1.22 to 1.60) in HR and 95% CI of AAD all-cause in-hospital mortality and 39% (1.39, 1.22 to 1.58) in serum glucose after full adjustment. Patients with a decrease in uric acid and/or serum glucose within the 7 days preceding admission showed significantly lower in-hospital mortality compared with those without a decrease. Notably, patients exhibiting both hyperuricaemia and serum glucose>180.2 mg/dL faced over double mortality risk (2.21, 1.58 to 3.10) compared with those with normal uric acid and normal serum glucose levels. Conclusions Hyperuricaemia and hyperglycaemia are significantly associated with an increased risk of mortality among AAD patients in the Han Chinese population. These findings suggest the importance of monitoring and managing uric acid and glucose levels in AAD patients to potentially improve outcomes.