Beijing Anzhen Hospital

tRNA-derived small RNAs (tsRNAs) or tRNA-derived fragments (tRFs) are an important class of regulatory molecules whose role in cardiac hypertrophy remains largely unknown. Here, we identified a novel tRF contributing to the regulation of cardiac hypertrophy that we termed CHAtRF (cardiac hypertrophy-associated tRF). The CHAtRF level was increased in mice and in patients with cardiac hypertrophy. CHAtRF deficiency attenuated angiotensin II (AngII)-induced cardiac hypertrophy and restored the heart function, while CHAtRF overexpression enhanced hypertrophic responses. Mechanistically, CHAtRF directly interacts with SRSF5 and blocks SRSF5 to bind with Psmg4 pre-mRNA, which mediates alternative splicing of Psmg4 pre-mRNA and promotes exon 2 skipping of Psmg4. CHAtRF-dependent alternative splicing of Psmg4 inhibits the expression of Psmg4 full-length isoform, resulting in progression of pathological hypertrophy. The ability of CHAtRF to regulate hypertrophy was confirmed in hiPSC-CMs, and CHAtRF serum levels are higher in individuals with myocardial hypertrophy or heart failure. Our findings reveal new insights into the previously unrecognized role of tsRNAs during cardiac hypertrophy, which provide potential novel therapeutic targets for pathological hypertrophy and might serve as potential biomarkers for diagnosing cardiac hypertrophy and heart failure.

Percutaneous vertebroplasty (PVP) is highly effective treatment for osteoporotic vertebral compression fractures (OVCF). There is no clear conclusion regarding the common locations of fractures, and whether recurrent fractures are related to surgery, or changes in local spinal alignment. A total of 164 patients with thoracolumbar OVCF from June 2020 to June 2024 were enrolled. The segmental distribution with initial and recurrent fractures were collected. The impact of surgery on recurrent fractures was analyzed by comparing the segmental distribution of recurrent fractures between groups. 84 patients with T11-L2 OVCF were divided into two groups based on recurrent fractures or not. The gender, age, trauma of patients were measured, imaging indicators including bone cement distribution type, T11-L2 Cobb angle, Cobb angle and height recovery rate of fractured vertebra, and vertebral CT value were measured at the time of initial fracture, immediately after surgery, and recurrent fracture. The influencing factors of recurrent OVCF were explored through inter-group comparative analysis. Both initial and recurrent fractures mostly occurred in the T11-L3, accounting for 80.4% and 63.1%, respectively. In the non-surgical group, the recurrent fractures were found mostly at L1 and L2 levels, accounting for 21.6%; while in the surgical group, the fractures occurred mostly at L1 level, accounting for 14.0%. In 84 patients with T11-L2 OVCF, among surgical patients, average age in the recurrent fracture group was 8.4years older(P<0.001), and the average CT value was 22.9 HU lower (P =0.012) than that in the non-recurrent group. For each 1-year increase in age, the risk of recurrent fractures increased by 7.1%; for each 1 HU decrease in CT value, the risk of recurrent fractures increased by 2.1%. In addition, 78.6% of patients with initial fractures had a history of trauma, and 64.7% of patients with recurrent fractures had a history of trauma. Initial and recurrent OVCF of the thoracolumbar spine commonly occurred in T11 to L3 segments. The segment of initial fracture and surgical treatment were not associated with recurrent fracture location or risk. Advanced age and decreased CT value are risk factors for recurrent fractures. The occurrence of the fracture, mostly depends on the presence of trauma. REGISTRY: www.chictr.org.cn, TRN: ChiCTR2500105987, Registration date: 27 June 2025.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a pivotal regulator of lipid metabolism and a validated therapeutic target in cardiovascular disease (CVD). While its canonical role in mediating low-density lipoprotein receptor (LDLR) degradation underpins its cholesterol-lowering effects, emerging evidence highlights diverse LDLR-independent actions that contribute to cardiovascular pathology. PCSK9 exerts pro-inflammatory, pro-atherosclerotic, pro-thrombotic, and cardiotoxic effects and promotes valvular calcification—thereby influencing vascular, myocardial, and structural heart disease beyond lipid regulation. This review delineates these non-canonical mechanisms, emphasizing PCSK9's roles in vascular inflammation, atherosclerosis, thrombosis, regulated cardiomyocyte death, and calcific aortic valve disease (CAVD). We also address key unresolved questions regarding the “efficacy gap” between pharmacological inhibition and lifelong genetic deficiency and examine the translational implications for next-generation inhibitors, including small molecules, vaccines, and gene-editing therapies. A deeper understanding of PCSK9's pleiotropic functions may inform precision strategies to achieve cardiovascular protection extending beyond LDL-C lowering.

Coronary semantic segmentation in X-ray angiography is essential for computer-aided diagnosis and treatment planning of coronary artery disease (CAD). Despite its importance, this task remains highly challenging due to the complex and interconnected vascular topology, as well as the similar visual characteristics among different branches, making dense pixel-level manual annotation difficult and labor-intensive. To alleviate this burden, we propose a point-supervised coronary semantic segmentation framework that significantly reduces annotation effort without compromising segmentation accuracy. The primary challenge of point label based supervision lies in the model's tendency to overfit sparse point labels, leading to limited generalization to pixel-level predictions. To enrich the supervision signals and stabilize the training process with the sparse point labels, we propose an adaptive foreground mask generation module and a region regularization strategy to ensure accurate semantic guidance while maximizing meaningful coverage of the vascular structures. To enhance coronary topology perception and branch differentiation, we propose a multi-task learning framework that jointly performs keypoint detection and coronary semantic segmentation through a shared feature extraction encoder and two task-specific decoders. The experimental results demonstrate that our point-supervised model achieves performance comparable to fully supervised model, and outperforms the existing state-of-the-art point-supervised semantic segmentation methods.

Pan-arterial diseases, including atherosclerosis (AS), aortic aneurysm and dissection (AAD), and peripheral arterial disease (PAD), impose a substantial global health burden. Although ambient temperature has been implicated in individual arterial conditions, its association with mortality across the pan-arterial spectrum remains incompletely understood. To evaluate the association between ambient temperature and mortality from pan-arterial diseases across the United States. We analysed mortality data for adults aged ≥25 years with AS, AAD, or PAD in the United States CDC WONDER database from 1999 to 2023. Age-adjusted mortality rates (AAMR) and average annual percent change (AAPC) were estimated. Monthly air-temperature metrics (1999-2023) were linked at the United States Census region level. Seasonal variation was assessed using analysis of variance. Associations between temperature and mortality were examined using Spearman correlation, Poisson regression with lag structures, and distributed lag non-linear models (DLNM), with results expressed as relative risks (RR) per 10°F increase in temperature. Between 1999 and 2023, AAMRs declined for AS, AAD, and PAD, yet mortality burden remained substantial. Mortality from all three conditions was consistently higher in winter than in summer across Census regions. Monthly mean temperature was inversely correlated with crude mortality for pan-arterial diseases (P < 0.05). In the Northeast, cumulative RR per +10°F across lags 0-3 months was 0.919 for AS, 0.945 for AAD, and 0.953 for PAD, with similar patterns observed in other regions. DLNM analyses demonstrated a predominantly cold-related excess risk, with acute effects and regional heterogeneity at higher temperatures. Lower ambient temperatures are associated with increased mortality from pan-arterial diseases in the United States. These findings highlight shared vulnerability to cold exposure across arterial diseases and support winter-focused preventive and healthcare preparedness strategies.