Chinese Medical Journal最新文献

Abstract: Cardiometabolic risk encompasses the interconnected conditions of cardiovascular diseases (CVDs), type 2 diabetes (T2D), and other metabolic diseases, which are leading global health challenges. The American Heart Association (AHA) has introduced "Life's Essential 8" (LE8), a framework emphasizing eight key lifestyle and health factors, including diet, physical activity, smoking, sleep health, body weight, blood glucose, blood lipids, and blood pressure to optimize cardiovascular health and reduce the burden of cardiometabolic risk. This review examined the associations between individual and combined lifestyle factors and the development and progression of cardiometabolic risk, using CVD and T2D as representative conditions. Evidence highlighted that adherence to healthy lifestyle behaviors, such as maintaining a balanced diet, engaging in physical activity, avoiding smoking, and achieving a healthy weight, significantly reduced the risks of CVD, T2D, and hypertension. Studies showed that adherence to 3-4 healthy lifestyle factors lowers the risk of transition from baseline to diabetes, complications, and mortality. Despite the proven benefits, barriers such as limited access to healthy food and safe environments for physical activity hinder widespread adoption. Addressing these challenges requires innovative public health interventions and personalized strategies targeting high-risk populations. This review underscored the importance of promoting and adhering to LE8 principles to reduce the global burden of cardiometabolic risk and improve overall health outcomes.

Background: Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is an emerging subtype with specific clinicopathological features and therapeutic strategies. However, limited studies are available on the molecular characteristics and prognosis of triple-negative breast cancer (TNBC).

Method: This study was conducted using the clinicopathological and genomic data of 1006 TNBCs, which were extracted from The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), and Sir Run Run Shaw Hospital of Zhejiang University (SRRSH) cohorts. The clinicopathological features, survival outcomes, molecular characteristics, and immune profiles of TNBCs based on HER2 status were evaluated.

Result: Patients were stratified into HER2-low (N = 676) and HER2-zero (N = 330) groups according to their HER2 status. We found HER2-low TNBCs had a lower histological grade and Ki67 index compared to the HER2-zero subgroup in the SRRSH cohort. However, no significant association has been found between the HER2 status and the disease-free survival (DFS), recurrence-free survival (RFS), or overall survival (OS) in TNBCs. Genomic mutation analysis showed that the HER2-low TNBCs exhibited higher mutated frequencies of PIK3CA, MUC17, and PTEN, while FAT3, RYR2, and CSMD3 were more frequently mutated in the HER2-zero subgroup. Furthermore, the combined mutation of PIK3CA and MUC17, which had a higher frequency in the HER2-low subgroup, was associated with poorer survival in TNBCs. Immune profile analysis revealed a higher percentage of plasma cells in patients with low HER2 expression.

Conclusion: Taken together, our study reflected the impact of the HER2 status on the clinicopathological and molecular features of TNBCs, which might offer additional introspection and improvement for translational studies and therapeutic decisions for TNBCs.

Background: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) improves beta-cell function in animals and humans with diabetes. Herein, we aimed to investigate the effects of SGLT2i on beta-cell regeneration, trace the origin of regenerated beta cells, and reveal the potential mechanism.

Methods: Type 2 and type 1 diabetic mice were treated with canagliflozin (10 mg/kg), dapagliflozin (1 mg/kg), or vehicle. Islet morphology was evaluated to investigate beta-cell regeneration. Inducible pancreatic neurogenin 3 (Ngn3)+ progenitor lineage-tracing mice and alpha-cell lineage-tracing mice were used to trace the origin of regenerated cells. Mouse and human islets, alpha cells, and beta cells were incubated with dapagliflozin (12.5 μmol/L) or vehicle. Insulin and glucagon-like peptide-1 (GLP-1) release, gene expression, and RNA sequencing analysis were performed to clarify the direct actions of SGLT2i and to screen potential targets. Alpha cells were transfected with peroxisome proliferator-activated receptor-γ coactivator 1α (Ppargc1α) plasmid or with Ppargc1α siRNA, followed by incubation with or without dapagliflozin to confirm the effects of Ppargc1α in alpha-cell phenotype conversion.

Results: SGLT2i increased islet and beta cell areas in type 2 diabetic mice and showed a similar trend in type 1 diabetic mice. SGLT2i induced alpha-cell dedifferentiation into Ngn3+ progenitors and promoted progenitor differentiation toward beta cells. In cultured diabetic mouse and human islets and in stressed alpha cells, SGLT2i increased supernatant insulin and active GLP-1 levels, downregulated alpha-cell-specific marker expression, and upregulated the expression of endocrine progenitor- and beta-cell-specific markers, including prohormone convertase 1/3. Although dapagliflozin did not affect beta cells directly, it affected alpha cells (457 upregulated and 235 downregulated genes). Ppargc1α, a coactivator participating in oxidative phosphorylation, was identified as a potential target. By using overexpression and knockdown, we confirmed that Ppargc1α participated in SGLT2i-induced regulation of alpha-cell phenotype conversion.

Conclusions: Alpha-cell regression to progenitors and progenitor differentiation toward beta cells represent a novel pathway for beta-cell neogenesis induced by SGLT2i in diabetes, with Ppargc1α playing a role in this process.