Large language models (LLMs) are rapidly advancing medical artificial intelligence, offering revolutionary changes in health care. These models excel in natural language processing (NLP), enhancing clinical support, diagnosis, treatment, and medical research. Breakthroughs, like GPT-4 and BERT (Bidirectional Encoder Representations from Transformer), demonstrate LLMs’ evolution through improved computing power and data. However, their high hardware requirements are being addressed through technological advancements. LLMs are unique in processing multimodal data, thereby improving emergency, elder care, and digital medical procedures. Challenges include ensuring their empirical reliability, addressing ethical and societal implications, especially data privacy, and mitigating biases while maintaining privacy and accountability. The paper emphasizes the need for human-centric, bias-free LLMs for personalized medicine and advocates for equitable development and access. LLMs hold promise for transformative impacts in health care.

Background: The cardiomyocyte apoptosis is considered as one of major contributions to cardiac remodeling after myocardial infarction (MI). Numerous studies find that circular RNAs (circRNAs) play pivotal roles in a variety of biological functions. However, the role of circ_0068655 in MI and human induced pluripotent stem-derived cardiomyocytes (HCMs) remains unknown. Methods: The expression of circ_0068655, miR-498, and PRKC apoptosis WT1 regulator (PAWR) in human MI heart tissues and hypoxia subjected HCMs was evaluated with qRT-PCR and Western blot. The effects of circ_0068655 on hypoxia-induced apoptotic death and cell migration in HCMs were evaluated with qRT-PCR, cell viability, cell death ELISA (POD), and Caspase-3 activity assay, and Trans-well assay, respectively. Furthermore, luciferase assay, qRT-PCR, biotin-labeled miRNA pulldown assay, and Western blot were employed in the functional studies. Results: We found that the expression of circ_0068655 and PAWR was enhanced in MI patients and hypoxia subjected HCMs; by contrast, the expression of miR-498 decreased. Inhibited expression of circ_0068655 in HMCs counteracted hypoxia-induced apoptotic death and impaired cell migration, in sharp contrast to circ_0068655 knockdown. We identified that circ_0068655 sponged an endogenous miR-498 to sequester and inhibit its activity, leading to the increased PAWR expression. Conclusions: Our findings reveal that the expression of circ_0068655 can promote cardiomyocyte apoptosis through the modulation of miR-498-PAWR axis in vitro, which highlights the diagnostic and therapeutic value of circ_0068655 in patients with MI.

Objective. MicroRNAs have been revealed to be involved in the development of atherosclerosis. The present study is aimed at exploring the potential of miR-99a-5p as a therapy for atherosclerosis. We suspected that miR-99a-5p might inhibit NLRP3 inflammasome activation and promote macrophage autophagy via constraining mTOR, therefore, alleviating atherosclerosis. Methods. The cell viability in ox-LDL-induced THP-1 macrophages was assessed by CCK-8 assay. Bioinformatic analysis was used to predict the target genes of miR-99a-5p. The binding between miR-99a-5p and mTOR was confirmed by luciferase reporter assay. In vivo, a high-fat-diet-induced atherosclerosis model was established in apolipoprotein E knockout mice. Hematoxylin-eosin, oil red O, and Sirius red staining were performed for the determination of atherosclerotic lesions. MTOR and associated protein levels were detected by Western blot analysis. Results. miR-99a-5p inhibited NLRP3 inflammasome activation and promoted macrophage autophagy by targeting mTOR. Enforced miR-99a-5p significantly reduced the levels of inflammasome complex and inflammatory cytokines. Furthermore, miR-99a-5p overexpression inhibited the expression of mTOR, whereas mTOR overexpression reversed the trend of the above behaviors. In vivo, the specific overexpression of miR-99a-5p significantly reduced atherosclerotic lesions, accompanied by a significant downregulation of autophagy marker CD68 protein expression. Conclusion. We demonstrated for the first time that miR-99a-5p may be considered a therapy for atherosclerosis. The present study has revealed that miR-99a-5p might inhibit NLRP3 inflammasome activation and promote macrophage autophagy by targeting mTOR, therefore, alleviating atherosclerosis.

Diabetic cardiomyopathy is a myocardial structural and functional abnormality directly caused by diabetes and is a principal factor in the development of cardiovascular complications in patients with diabetes. The study aims to investigate the role of circOGDH in the development of DCM and elucidate its precise underlying mechanisms. We established two well-characterized diabetic mouse models, C57BL/6J and db/db, and assessed cardiac function by serum lactate dehydrogenase activity assay and echocardiography, as well as quantitative histological analyses of the extent of myocardial fibrosis in combination with HE staining and Masson trichrome staining. The results demonstrated that there was a significant upregulation of circOGDH expression levels in myocardial tissues of mice in a diabetic state, accompanied by the increased expression of key effector proteins of PANoptosis. It is noteworthy that the knockdown of circOGDH led to a substantial enhancement in cardiac function indices, a reduction in the area of myocardial fibrosis, and the effective inhibition of the PANoptosis process in myocardial tissues. In the H9c2 cells model, silencing of circOGDH also exhibited significant protective effects, including increased cell survival, reduced levels of oxidative stress, decreased apoptosis, and suppressed expression of PANoptosis-related proteins. Subsequent employing RNA pull-down, RNA immunoprecipitation, and co-immunoprecipitation experimental methods have elucidated, for the first time, the molecular mechanism by which circOGDH specifically targets and regulates RIPK3 through the HMGB1 signaling pathway. The present study definitively demonstrated that upregulation of circOGDH expression in a diabetic state could exacerbate pathological damage in DCM by activating the HMGB1-RIPK3 signaling pathway.

Obesity and overweight, as determined by the body mass index (BMI), are harmful to metabolic health. However, the BMI can not reflect body composition or fat distribution. The fat-free mass index (FFMI) and the fat mass index (FMI) can provide more information on body composition. The aim of the observational research was to determine whether the FMI and the FFMI are significantly associated with the risk of developing diabetes and prediabetes. The investigators included data for 10,085 National Health and Nutrition Examination Survey (2011–2018) participants aged over 20 years who underwent dual-energy X-ray absorptiometry (DXA). The FFMI and the FMI were determined based on total fat mass and lean mass measured by DXA. Diabetes and prediabetes status were determined by medical history and laboratory examination. Logistic regression analyses were performed to explore the correlations between the FMI/FFMI and the risk of developing diabetes/prediabetes. Restricted cubic spline analysis was used to explore underlying nonlinear associations. In the present study, 1,135 patients were diagnosed with diabetes, 3,258 had prediabetes, and 5,692 were classified as control participants. The FFMI (odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.04–1.16) and the FMI (OR = 1.08, 95% CI = 1.04–1.12) were independently related to an increased risk of developing diabetes. Moreover, the FFMI (OR 1.08, 95% CI 1.02–1.16) and the FMI (OR 1.07, 95% CI 1.02–1.13) also independently correlated with a rising risk of developing prediabetes. The restricted cubic spline (RCS) outcomes suggested that the associations are approximately linear. Both the FMI and the FFMI significantly correlated with the danger of developing diabetes and prediabetes, and the correlations are approximately linear.