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.

The current diagnostic biomarkers of acute myocardial infarction (AMI), troponins, lack specificity and exist as false positives in other non-cardiac diseases. Previous studies revealed that cuproptosis, ferroptosis, and immune infiltration are all involved in the development of AMI. We hypothesize that combining the analysis of cuproptosis, ferroptosis, and immune infiltration in AMI will help identify more precise diagnostic biomarkers. The results showed that a total of 19 cuproptosis- and ferroptosis-related genes (CFRGs) were differentially expressed between the healthy and AMI groups. Functional enrichment analysis showed that the differential CFRGs were mostly enriched in biological processes related to oxidative stress and the inflammatory response. The immune infiltration status analyzed by ssGSEA found elevated levels of macrophages, neutrophils, and CCR in AMI. Then, we screened 6 immune-related CFRGs (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4, STAT3) to construct a nomogram for predicting AMI and validated it in the GSE109048 dataset. Moreover, we also identified 5 pivotal miRNAs and 10 candidate drugs that target the 6 feature genes. Finally, RT-qPCR analysis verified that all 6 feature genes were upregulated in both animals and patients. In conclusion, our study reveals the significance of immune-related CFRGs in AMI and provides new insights for AMI diagnosis and treatment.

Background: microRNAs (miRNAs) have drawn more attention to the progression of atherosclerosis (AS), due to their noticeable inflammation function in cardiovascular disease. Macrophages play a crucial role in disrupting atherosclerotic plaque, thereby we explored the involvement of miR-223-3p in the inflammatory response in macrophages. Methods: RT-qPCR was used to analyze the miR-223-3p levels in carotid arteries and serum of AS patients. ROC curve was used to assess the diagnostic value of miR-223-3p. Movat staining was applied to evaluate the morphological differences. FISH was used to identify the expression of miR-223-3p in macrophages of atherosclerotic lesions. Bioinformatic analysis was performed. Double-immunofluorescence and western blot were performed to assess the inflammatory cytokine secretion and p-ERK1/2. C16-PAF was injected into the culture medium of the miR-223-3p mimic/NC-transfected macrophages with ox-LDL. Results: MiR-223-3p was up-regulated in AS patients and was associated with a higher overall survival rate. MiR-223-3p was co-localized with CD68+ macrophages in vulnerable atherosclerotic lesions. MiR-223-3p mimics decreased atherosclerotic lesions, macrophages numbers whereas increased SMCs numbers in the lesions. The TNF-a immune-positive areas were reduced by miR-223-3p mimics. MAP2K1 was negatively associated with miR-223-3p. MiR-223-3p mimics reduced the inflammation and the MEK1/ERK1/2 signaling pathway in vivo and in vitro. C16-PAF reversed the effects of miR-223-3p mimics on inflammation and ERK1/2 signaling pathway. Conclusions: MiR-223-3p negatively regulates inflammatory responses by the MEK1/ERK1/2 signaling pathway. Our study provides new insight into how miR-223-3p protects against atherosclerosis, representing a broader therapeutic prospect for treating atherosclerosis by miR-223-3p.

We aim to explore the impact of Proprotein convertase subtilisin-kexin type 9 (PCSK9) and its inhibitor evolocumab on neointimal hyperplasia. Wild type and PCSK9 knockout (PCSK9^-/-) mice were subjected to ligation of the common carotid artery, with or without subcutaneous injection of evolocumab. Mouse aortic vascular smooth muscle (MOVAS) cells were pretreated with evolocumab or under siRNA-mediated suppression of PCSK9, and then exposed to platelet-derived growth factor type BB(PDGF-BB), a major promoter of MOVAS transformation to a proliferative phenotype. PCSK9 was upregulated in ligated carotid arteries and PDGF-BB-treated MOVAS cells. PCSK9^-/- mice showed decreased intimal area and intimal/media area ratio, downregulation of proliferation and autophagy, which was coincidence with wild-type mice treated with evolocumab. In MOVAS cells fortified with evolocumab or silencing of PCSK9, PCNA, Beclin1, p62, LC3 were downregulated, additionally, EdU-positive cells decreased, cell viability reduced, migration ability was weakened, and the number of autophagosomes and autolysosomes decreased after the treatment. We also identified the PI3K/AKT/mTOR signaling molecules as potential PCSK9 targets mediating proliferative effect in MOVAS cells. To sum up, our results suggest that PCSK9 has intrinsic properties to promote proliferation, migration and autophagy in VSMCs independent of its lipid-regulating role. The proliferative effects of PCSK9 may be mediated by the PI3K/AKT/mTOR signaling pathway. These data provide additional evidence for PCSK9i in cardiovascular disease beyond the low-density lipoprotein (LDL)-lowering benefit.

Compound Kushen injection (CKI) is a type of traditional Chinese medicine that has previously been studied for the treatment of various types of cancer. Previous studies have reported that CKI regulates cell apoptosis by downregulating the PI3K/Akt pathway. The present study aimed to determine whether CKI alleviates heart failure (HF) by attenuating cardiomyocyte apoptosis via the inhibition of the PI3K/Akt pathway. Angiotensin II (Ang II) was used to elicit HF, and osmotic minipumps with either Ang II (2 µg/kg/day) or phosphate‑buffered saline (PBS; 200 µl) were subcutaneously implanted into 6‑week‑old male C57BL/6 mice for 3 weeks. In addition, PBS or CKI (25 mg/kg/day) were subcutaneously infused once a day for 3 weeks. Echocardiography was used to examine hemodynamics. The myocardial injury biomarkers, cardiac troponin I and N‑terminal (NT)‑pro hormone B‑type natriuretic peptide, were assessed using enzyme‑linked immunosorbent assay. Transmission electron microscopy was used to determine the morphology of the myocardium. The rate of apoptosis was detected using TUNEL staining and flow cytometry (FCM), and the expression levels of apoptosis‑related proteins were measured using western blot (WB) analysis. Moreover, H9C2 cells were treated with CKI (2 mg/ml) or LY294002 (an inhibitor of the PI3K/Akt pathway; 25 µmol/l) in combination with Ang II (1 µmol/l) for 48 h. Cell Counting Kit‑8 assay, FCM and WB analysis were performed in the H9C2 cells to examine cell viability, cell cycle distribution and representative signaling proteins. It was found that CKI promoted healthy cardiac function, reduced myocardial structural damage and reduced the rate of cardiomyocyte apoptosis. CKI markedly attenuated the expression of apoptosis‑related proteins in the PI3K/Akt pathway. The results of the in vitro experiments indicated that CKI promoted cardiomyocyte proliferation and inhibited apoptosis, similar to LY294002. On the whole, the present study demonstrates that CKI reduces cardiomyocyte apoptosis, promotes healthy cardiac function and attenuates Ang II‑mediated HF. These ameliorative effects may be associated with the inhibition of the PI3K/Akt pathway.