Background and Purpose—: Reported rates of oral anticoagulation (OAC) use have been low among Chinese patients with atrial fibrillation (AF). With improved awareness, changing guidelines, this situation may be changing over time. We aimed to explore the current status and time trends of OAC use in Beijing. Methods—: We used the data set from the Chinese Atrial Fibrillation Registry (CAFR), a prospective, multicenter, hospital-based registry study involving 20 tertiary and 12 nontertiary hospitals in Beijing. A total of 11 496 patients with AF were enrolled from 2011 to 2014. Results—: Seven thousand nine hundred seventy-seven eligible patients were included in this ancillary study. The proportions of OAC use were 36.5% (2268/6210), 28.5% (333/1168), and 21.4% (128/599) for patients with CHA ₂ DS ₂ -VASc scores ≥2, 1, and 0, respectively. Persistent AF, history of stroke/transient ischemic attack/peripheral embolism, diabetes mellitus, higher body mass index, and tertiary hospital management were factors positively associated with OAC use, whereas older age, previous bleeding, hypercholesterolemia, and established coronary artery disease were factors negatively associated with OAC use. Among patients with CHADS ₂ scores ≥2 and CHA ₂ DS ₂ -VASc scores ≥2, the proportion of OAC use increased from 31.3% to 64.5% and 30.2% to 57.7%, respectively, from 2011 to 2014. Variation in OAC use was substantial among different hospitals. Conclusions—: An improvement of OAC use among Chinese patients with AF in Beijing is observed in recent years although only 36.5% of patients with CHA ₂ DS ₂ -VASc score ≥2 received OAC. However, variations between different hospitals were large, suggesting that better education and awareness are needed to improve efforts for stroke prevention among AF patients. Clinical Trial Registration—: URL: http://www.chictr.org.cn/showproj.aspx?proj=5831 . Unique identifier: ChiCTR-OCH-13003729.

Esophageal squamous cell carcinoma (ESCC) is highly heterogeneous. Our understanding of full molecular and immune landscape of ESCC remains limited, hindering the development of personalised therapeutic strategies. To address this, we perform genomic-transcriptomic characterizations and AI-aided histopathological image analysis of 120 Chinese ESCC patients. Here we show that ESCC can be categorized into differentiated, metabolic, immunogenic and stemness subtypes based on bulk and single-cell RNA-seq, each exhibiting specific molecular and histopathological features based on an amalgamated deep-learning model. The stemness subgroup with signature genes, such as WFDC2, SFRP1, LGR6 and VWA2, has the poorest prognosis and is associated with downregulated immune activities, a high frequency of EP300 mutation/activation, functional mutation enrichment in Wnt signalling and the highest level of intratumoural heterogeneity. The immune profiling by transcriptomics and immunohistochemistry reveals ESCC cells overexpress natural killer cell markers XCL1 and CD160 as immune evasion. Strikingly, XCL1 expression also affects the sensitivity of ESCC cells to common chemotherapy drugs. This study opens avenues for ESCC treatment and provides a valuable public resource to better understand ESCC.

Galectin-3, a β-galactoside-binding lectin, is abnormally increased in cardiovascular disease. Plasma Galectin-3 receives a Class II recommendation for heart failure management and has been extensively studied for multiple cellular functions. The direct effects of Galectin-3 on platelet activation remain unclear. This study explores the direct effects of Galectin-3 on platelet activation and thrombosis. A strong positive correlation between plasma Galectin-3 concentration and platelet aggregation or whole blood thrombus formation was observed in patients with coronary artery disease (CAD). Multiple platelet function studies demonstrated that Galectin-3 directly potentiated platelet activation and in vivo thrombosis. Mechanistic studies using the Dectin-1 inhibitor, laminarin, and Dectin-1^−/− mice revealed that Galectin-3 bound to and activated Dectin-1, a receptor not previously reported in platelets, to phosphorylate spleen tyrosine kinase and thus increased Ca²⁺ influx, protein kinase C activation, and reactive oxygen species production to regulate platelet hyperreactivity. TD139, a Galectin-3 inhibitor in a Phase II clinical trial, concentration dependently suppressed Galectin-3-potentiated platelet activation and inhibited occlusive thrombosis without exacerbating haemorrhage in ApoE^−/− mice, which spontaneously developed increased plasma Galectin-3 levels. TD139 also suppressed microvascular thrombosis to protect the heart from myocardial ischaemia–reperfusion injury in ApoE^−/− mice. Galectin-3 is a novel positive regulator of platelet hyperreactivity and thrombus formation in CAD. As TD139 has potent antithrombotic effects without bleeding risk, Galectin-3 inhibitors may have therapeutic advantages as potential antiplatelet drugs for patients with high plasma Galectin-3 levels. Working model for plasma Galectin-3 directly potentiating platelet activation, and the platelet hyperreactivity suppressing effect of Galectin-3 inhibitor TD139 in coronary artery disease. Accumulated Galectin-3 in plasma directly activates Dectin-1 receptor to potentiate platelet activation (platelet aggregation and ATP release), which enhances in vivo thrombosis and myocardial ischaemia–reperfusion injury. Galectin-3 inhibitor TD139 specifically inhibits Galectin-3-induced platelet hyperreactivity to ameliorate atherothrombosis and myocardial infarction in coronary artery disease.

Background: The association between sodium‐glucose cotransporter 2 inhibitors (SGLT2i) and atrial fibrillation (AF) recurrence after catheter ablation among patients with diabetes and AF remains unclear. Methods and Results: Patients with AF undergoing initial catheter ablation with a history of diabetes from the China AF registry were included. Patients using SGLT2i were identified and matched by propensity score with non‐SGLT2i patients in a 1:3 ratio. The main outcome was AF recurrence during the 18‐month follow‐up. A total of 138 patients with diabetes with SGLT2i therapy and 387 without SGLT2i were analyzed. AF recurrence occurred in 37 patients (26.8%) in the SGLT2i group and 152 patients (39.3%) in the non‐SGLT2i group during a total of 593.3 person‐years follow‐up. The SGLT2i group was associated with lower AF recurrence compared with the non‐SGLT2i group (hazard ratio, 0.63 [95% CI, 0.44–0.90], P =0.007). A total of 4 studies were analyzed in our meta‐analysis demonstrating that SGLT2i was associated with lower AF recurrence after catheter ablation (odds ratio, 0.61 [95% CI, 0.54–0.69]; P <0.001, I ² =0.0%). Conclusions: Our prospective study coupled with a meta‐analysis demonstrated a lower risk of AF recurrence with the use of SGLT2i among patients with diabetes after AF ablation.

BACKGROUND: Frailty is associated with an increased risk of all-cause death and cardiovascular events. However, it is uncertain whether frailty modifies the efficacy and safety of intensive blood pressure control. METHODS: Data from SPRINT (Systolic Blood Pressure Intervention Trial) were used to construct a frailty index. Subgroup differences in intensive blood pressure control treatment effects and safety outcomes were measured on a relative and an absolute scale in patients with and without frailty (defined as a frailty index >0.21) using Cox proportional hazard models and generalized linear models, respectively. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death. RESULTS: A total of 9306 patients (mean age, 67.9±9.4 years), 2560 (26.7%) of whom had frailty, were included in our study. Over a median follow-up of 3.22 years, 561 primary outcomes were observed. Patients with frailty had a significantly higher risk of primary outcome in both the intensive and standard blood pressure control arms (adjusted hazard ratio, 2.10 [95% CI, 1.59–2.77] and 1.85 [95% CI, 1.46–2.35], respectively). Intensive treatment effects on primary and secondary outcomes were not significantly different on a relative scale (except for cardiovascular death [hazard ratio in patients with and without frailty, 0.91 (95% CI, 0.52–1.60) versus 0.30 (95% CI, 0.16–0.59), respectively; P _interaction =0.01]) or absolute scale. There was no significant interaction between frailty and risks for serious adverse events with intensive treatment. CONCLUSIONS: Frailty status was a marker of high cardiovascular risk. Patients with frailty benefit similarly to other patients from intensive blood pressure control without an increased risk of serious adverse events.