Wenlu Zong, Yuning Chu, Yingjie Guo, Pin Meng, Chen Hao, Xiaoyan Yin, Zibin Tian, Xiaoyu LiDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyu Li, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email lixiaoyu@qdu.edu.cn Zibin Tian, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email tianzb@qdu.edu.cnIntroduction: Intrapancreatic fat deposition (IPFD) is an ectopic fat phenotype associated with metabolic abnormalities. However, the clinical heterogeneity of IPFD in relation to generalized adiposity remains insufficiently characterized. This study aimed to explore clinical profiles associated with IPFD using unsupervised clustering and characterize their metabolic features.Methods: In this retrospective, single-center cross-sectional study, 558 adults undergoing non-contrast abdominal computed tomography were included. K-means clustering was performed using age, body mass index (BMI), pancreas-to-spleen attenuation difference, fasting plasma glucose (FPG), and triglyceride (TG) levels. Clinical characteristics, metabolic comorbidities, and circulating biomarkers were compared across the derived exploratory clusters.Results: Three exploratory clinical phenotypes were identified: an obesity-dominant cluster (n=140), an FPD-like cluster characterized by greater IPFD (n=182), and a reference cluster (n=236). The FPD-like cluster showed the lowest pancreas-to-spleen attenuation difference, older age, and lower BMI than the obesity-dominant cluster. In contrast, the obesity-dominant cluster showed stronger associations with metabolic dysfunction-associated steatotic liver disease and higher uric acid levels. Free fatty acid concentrations were highest in the FPD-like cluster. Differences in glycemic and lipid-related characteristics should be interpreted cautiously because FPG and TG were included as clustering variables.Conclusion: In this exploratory cross-sectional analysis, a cluster characterized by greater IPFD, older age, and lower BMI than the obesity-dominant cluster was associated with less favorable metabolic characteristics. These findings suggest that IPFD may provide complementary information beyond BMI-based assessment; however, the identified clusters should be considered exploratory clinical profiles rather than validated biological subtypes. External validation in independent populations and longitudinal studies are required to confirm their reproducibility and clinical relevance.Keywords: intrapancreatic fat deposition, unsupervised machine learning, phenotypic heterogeneity, metabolic dysfunction, lipotoxicity
BackgroundDepressive symptoms among long-term care (LTC) residents are heterogeneous. This study aimed to identify latent classes of depressive symptoms among older adults in Chinese LTC homes and examine their associations with social support.MethodsA cross-sectional study included 329 older adults from 11 LTC homes. Depressive symptoms and social support were measured using the PHQ-9 and Perceived Social Support Scale. Latent class analysis (LCA) identified symptom patterns, and multinomial logistic regression evaluated associations with social support.ResultsLCA identified three clinically interpretable classes: low depressive symptoms (54.1%), somatic-dominant depressive symptoms (22.5%), and severe-spectrum depressive symptoms (23.4%). The severe-spectrum group exhibited the highest physical dependency, multimorbidity, and social isolation. Higher levels of perceived support from family and friends were associated with lower odds of belonging to the severe-spectrum group.ConclusionDepressive symptoms in LTC residents can be described by clinically interpretable symptom patterns. Perceived social support may be relevant to depressive symptom differentiation in LTC residents and may inform psychosocial care in LTC settings.
Hypertension has paradoxical prothrombotic-hemorrhagic predisposition toward cerebral infarction and intracerebral hemorrhage (ICH), but the mechanism remains poorly understood. We observed Angiotensin II (Ang II) inhibited coagulation by activating antithrombin through heparin-like acceleration of antithrombin-thrombin interaction. Ang II allosterically modulates the 386-397 loop of antithrombin to enhance thrombin inhibition. In vivo, single injection of Ang II inhibited coagulation, alleviating thrombosis and aggravating ICH. Conversely, anti-Ang II monoclonal antibody promoted coagulation, aggravating thrombus formation and alleviating ICH. Notably, the blockage or deficiency of Ang II receptor had no significant effect on the alleviated thrombus formation or aggravated hemorrhage elicited by Ang II, suggesting the phenotypes were independent of Ang II receptor. In hypertensive mice, anti-Ang II monoclonal antibody significantly promoted coagulation and ameliorated ICH. These results identify Ang II as a key coagulation regulator with heparin-like function, suggesting that targeting Ang II-coagulation pathway could be a novel strategy to mitigate cerebral bleeding. Here, the authors show that angiotensin II acts as a key coagulation regulator with heparin-like antithrombin activation function in mediating hemorrhage. Targeting the angiotensin II coagulation pathway could be a novel strategy to mitigate cerebral bleeding events.
ObjectiveThis study aimed to explore autoantibody clusters and their correlations with clinical features in 644 myasthenia gravis (MG) patients.MethodsMedical records of 664 MG patients were reviewed. Five autoantibodies (AChR, MuSK, titin, RyR, and LRP4) were selected for cluster analysis. The various clinical manifestations were compared between clusters. Separate association analyses between individual autoantibodies and clinical manifestations as well as among different MGFA subtypes were also performed without prior clustering.ResultsTwo separate autoantibody clusters were identified, with significantly different clinical manifestations. Cluster 1 (485 patients) was characterized by higher proportions of RyR-, titin-, and AChR-, while cluster 2 (179 patients) had higher proportions of RyR+, titin+, and AChR+. Cluster 2 patients were older and had elevated QMG scores and odds of complications, particularly hypertension, diabetes, cardiovascular and cerebrovascular diseases, and eye conditions. Individual antibody analysis revealed that male cases were more likely to be AChR+ and titin+, and older age was associated with AChR+, RyR+, and titin+. Among MGFA subtypes, significant differences were detected in AChR, MuSK, titin, complications, thymoma, and hypertension. As MG severity increased from types I to V, AChR+, RyR+, and titin+ proportions peaked at stage IIa. MuSK+ patients were relatively rare and mostly present in the subtype b group. Type b patients had higher MuSK+ prevalence and increased cardiovascular and cerebrovascular disease incidence rates than type a cases.ConclusionOverall, cluster 2 features were less favorable to patients. This study provides valuable insights into the clinical and autoantibody profiles of Chinese MG patients.
