The triglyceride-glucose (TyG) index and the triglyceride-to-HDL cholesterol (TG/HDL) ratio have emerged as surrogate markers of insulin resistance, but their predictive value for gestational diabetes mellitus (GDM) remains uncertain. This retrospective cohort study included 4,239 pregnant women, among whom 919 developed GDM and 3,320 had normal glucose tolerance. Demographic, anthropometric, and biochemical parameters were collected during early pregnancy, specifically at 8–13 gestational weeks (first trimester), OGTT-related glucose and insulin measurements (FIN, 1hPIN, 2hPIN) were obtained later at 24–28 weeks during the routine 75-g OGTT, after at least 8 hours of overnight fasting. Logistic regression, restricted cubic spline models, correlation analysis, age-stratified analyses, and mediation analysis were performed to evaluate associations of TyG and TG/HDL ratio with GDM. A nomogram model was constructed and internally validated using a random training/validation split. Higher TyG and TG/HDL ratio levels were independently associated with increased GDM risk (TyG: aOR 4.07, 95

OBJECTIVE:Diabetic Foot Ulcers (DFUs) represent a prevalent and serious complication of diabetes, frequently resulting in persistent wounds and delayed healing. This research explores the healing effects of mesenchymal stem cells (MSCs) on DFUs and examines the involvement of Notch signaling in this therapeutic process. METHODS:BALB/c mice were induced with diabetes using streptozotocin (STZ) and divided into five groups: Control, Model, MSCs Treatment, MSCs + Notch Inhibition, and MSCs + Notch Activation. Wound healing was monitored, and tissue samples were analyzed using histological and molecular techniques. RESULTS:Our results demonstrated that MSCs treatment significantly accelerated wound healing, as evidenced by improved histopathology and enhanced expression of CD31, VEGF, FGF, and PECAM-1 in MSCs-treated groups. Notch activation further enhanced MSCs-mediated healing, as shown by increased Notch1 and Jagged-1 protein levels. Conversely, the MSCs + Notch Inhibition Group showed reduced healing and similar results to the Model Group, with lower expression of Notch1 and Jagged-1. CONCLUSION:These findings suggest that MSCs promote DFU healing, and Notch signaling plays a crucial role in enhancing MSC-mediated repair. Our results highlight the potential of MSC-based therapies combined with Notch pathway modulation as a promising strategy for improving DFU treatment and wound healing in diabetic patients.

BACKGROUND:C1q/TNF-related proteins (CTRPs) belong to the adipokine family. Here, we aimed to assess the relation of CTRP4 levels in serum and perivascular adipose tissue (PVAT) with coronary artery disease (CAD), and investigate the effect of CTRP4 on atherosclerosis and the underlying mechanisms. METHODS:CTRP4 levels were examined in serum and epicardial adipose tissue (a major PVAT) from patients with CAD. Atherosclerotic lesions were analysed in CTRP4‒/‒/ApoE‒/‒ and ApoE‒/‒ mice. The paracrine effects of CTRP4 on atherosclerosis were tested by supplementation with CTRP4, either via PVAT transplantation or tail vein injection in CTRP4-/-/ApoE-/- mice. CTRP4-interacting proteins were identified using immunoprecipitation and mass spectrometry. RESULTS:CTRP4 levels were lower in serum and epicardial adipose tissue of patients with CAD compared to non-CAD controls. CTRP4 knockout promoted atherosclerosis in ApoE‒/‒ mice. Supplementation of CTRP4, but not receptor for advanced glycation end-products (RAGE)- and toll-like receptor 4 (TLR4)-binding incompetent CTRP4 mutant, either through adipose tissue transplantation from wild-type mice or intravenous injection of recombinant protein, attenuated atherosclerosis in CTRP4‒/‒/ApoE‒/‒ mice. In macrophages, CTRP4 protein, but not the mutant, suppressed the expression of lipopolysaccharide-induced inflammatory cytokines. Mechanistically, the anti-atherogenic effects of CTRP4 were mediated by the engagement and inhibition of RAGE and TLR4. CONCLUSIONS:Decreased CTRP4 levels in serum and epicardial adipose tissue are associated with CAD in patients. CTRP4 deficiency promotes the development of atherosclerosis in ApoE‒/‒ mice, whereas CTRP4 supplementation attenuates atherosclerosis via binding and inhibition of RAGE and TLR4. These results suggest that CTRP4 is a novel anti-inflammatory and anti-atherogenic adipokine inversely associated with CAD and a potential therapeutic target.

BACKGROUND:Apo (apolipoprotein) AI glycation has been implicated in HDL (high-density lipoprotein) dysfunction, but its site-resolved landscape, clinical relevance, relationship with diabetic atherosclerosis, and underlying mechanisms remain incompletely defined. METHODS:We performed unbiased site-resolved glycation proteomics in 860 patients with type 2 diabetes and coronary atherosclerosis (CAS) and 294 controls with type 2 diabetes without CAS to define the plasma apo AI glycation landscape. Apo AI glycation signatures associated with diabetic CAS were identified using integrated unsupervised and supervised analyses. An Apo AI Glycation Index was developed using least absolute shrinkage and selection operator regression and evaluated in training, testing, and independent validation cohorts. To assess functional relevance, a glycation-resistant apo AI mutant, cross-linked apo AI (apo AICL), was engineered and tested under glycation conditions using surface plasmon resonance, in vitro and in vivo reverse cholesterol transport assays, HDL remodeling analyses, and atherosclerosis models. RNA sequencing, macrophage-specific knockout models, receptor-binding assays, signaling inhibition, and cholesterol efflux rescue experiments were used to investigate the underlying macrophage pathway. RESULTS:Apo AI glycation patterns differed between patients with type 2 diabetes with and without CAS, with K96 and K106/107 emerging as prominent disease-associated glycation sites. The Apo AI Glycation Index was independently associated with CAS and coronary artery disease in patients with type 2 diabetes and was inversely associated with HDL-mediated reverse cholesterol transport and lecithin-cholesterol acyltransferase activity. Compared with native apo AI, apo AICL showed reduced key-site glycation, preserved structural stability, enhanced binding affinity to lecithin-cholesterol acyltransferase, and improved HDL-mediated reverse cholesterol transport under glycation conditions. In diabetic mouse models, apo AICL attenuated HDL dysfunction and atherosclerotic lesion formation compared with glycated apo AI. These data support a candidate mechanism in which glycated apo AI enhances RAGE (receptor for advanced glycation end products) interaction and activates ERK1/2 (extracellular signal-regulated kinase 1/2)-NF-κB (nuclear factor κB)/p65 signaling, leading to upregulation of NR2C2 (nuclear receptor subfamily 2 group C member 2). LXRα (liver X receptor α) activation and macrophage NR2C2 deficiency restored cholesterol efflux in glycated apo AI-treated macrophages. CONCLUSIONS:This study provides a comprehensive site-resolved map of apo AI glycation in patients with diabetes and identifies the Apo AI Glycation Index as a glycation signature associated with diabetic CAS and impaired HDL function. Experimental data support a mechanism in which site-specific apo AI glycation contributes to HDL dysfunction and macrophage cholesterol efflux impairment through RAGE-associated NR2C2-LXRα signaling. Glycation-resistant apo AICL preserves HDL function and attenuates atherosclerosis in preclinical models, supporting site-specific apo AI glycation as a mechanistically relevant feature of diabetic atherosclerosis. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05659043.

Background Type 2 diabetes mellitus (T2DM) involves alterations in lipid metabolism beyond conventional cholesterol profiles. We examined whether specific plasma lipidomic signatures are related to pericoronary adipose tissue (PCAT) inflammation and coronary artery disease (CAD) burden. Methods This cross-sectional analysis included 176 T2DM participants from the GADA study. PCAT inflammation was measured by the fat attenuation index (FAI), CAD burden by Gensini/SYNTAX scores and plasma lipid species by targeted LC-MS. Multivariable regression were used to identify lipid species associated with FAI and CAD burden. For lipid species linked to both, mediation analyses were performed. Results We quantified 660 lipid molecular species across 20 classes. Five species were associated with FAI: sphingomyelin (SM) (34:4), phosphatidylcholines (PC) (16:0/20:4), Lysophosphatidylethanolamine (LPE) (18:1), LPE (20:4), and LPE (18:2). The three LPE species remained independently associated with both Gensini and SYNTAX scores after adjustment for clinical risk factors, conventional lipid measures, triglycerides, and hsCRP. Mediation analyses indicated that FAI accounted for part of the associations between these LPE species and CAD burden. Conclusions In T2DM patients, circulating LPE (18:1), LPE (20:4), and LPE (18:2) were associated with both PCAT inflammation and CAD burden. These findings point to altered LPE metabolism as a lipid-inflammatory signature linked to residual atherosclerotic burden beyond conventional lipid and glycemic measures.

Cancer-associated signaling pathways, particularly the ALK/LTK receptor tyrosine kinases and their ligand ALKAL2, have recently been implicated in chronic inflammation and myocardial remodeling. However, the relationship between ALKAL2 and coronary artery disease (CAD) pathogenesis in type 2 diabetes mellitus (T2DM) remains undefined. From January 2019 to December 2020, patients with type 2 diabetes mellitus (T2DM) undergoing coronary angiography were consecutively enrolled at Ruijin Hospital. Plasma ALKAL2 levels were measured using an ELISA assay. The association between ALKAL2 and CAD severity was assessed by Spearman correlation analysis. Logistic regression models were used to measure the association between ALKAL2 and CAD risk. 275 T2DM patients with CAD and 275 age- and sex-matched T2DM patients without CAD were included in the final analysis. Plasma ALKAL2 levels were increased in T2DM patients with CAD (0.25 [0.21, 0.37] ng/mL, median [IQR] vs. 0.18 [0.14, 0.24]ng/mL) (p < 0.001) and were positively associated with CAD severity (Spearman rho = 0.53, p < 0.001). Multivariate analysis revealed that plasma ALKAL2 levels were independently associated with the incidence of CAD after adjusting for LDL-C, hsCRP, and other traditional risk factors (OR, 2.24 [95

OBJECTIVE:To decipher the diagnostic value of serum cystatin C (CysC), β2-microglobulin (β2-MG) and α-Klotho in early acute kidney injury (AKI) caused by acute myocardial infarction (AMI). METHODS:This study screened 176 eligible patients and established two groups of AKI group (n = 51) and non-AKI group (n = 125). This study measured and compared the serum CysC, β2-MG, α-Klotho, serum creatinine (Scr), blood urea nitrogen (BUN), creatine kinase isoenzymes MB (CK-MB) and cardiac troponin T (cTnI) between the two groups. This study further analyzed correlations of CysC, β2-MG and α-Klotho with Scr and BUN, and the relationship of various indicators with AKI, with receiver operating characteristic (ROC) curves plotted. RESULTS:AKI group was detected with significant changes in baseline data compared with non-AKI group. Serum CysC, β2-MG and α-Klotho had significantly positive correlations with Scr and BUN. CK-MB, Scr, BUN, CysC, β2-MG, and α-Klotho were independent risk factors for AKI in AMI patients. The AUC, sensitivity, and specificity of CysC for predicting AKI were 0.840, 0.627, and 0.984; which were 0.835, 0.784, and 0.864 for β2-MG; 0.881, 0.824, and 0.832 for α-Klotho; as well as 0.913, 0.843, and 0.880 when using three indicators jointly. Joint detection had better predictive performance for AKI than any single indicator. CONCLUSION:Serum CysC, β2-MG and α-Klotho are significantly positively correlated with reduced renal function and are independent risk factors for AKI, exhibiting high early diagnostic value for AKI in AMI patients.

BACKGROUND AND AIMS:Nuclear receptors (NRs) are involved in cardiovascular physiology and pathology. Dosage-sensitive sex reversal, adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (Dax1) is a co-repressor of several protective NRs. However, whether Dax1 influences atherosclerosis remains unclear. This study aims to explore the role of Dax1 in atherogenesis and find a pharmacological approach targeting Dax1 to prevent atherosclerosis. METHODS:Dax1 levels were examined in human atherosclerotic arteries. Atherosclerosis animal models were established in mice with macrophage-specific Dax1 knockdown following AAV8-PCSK9 administration and double knockout of macrophage Dax1 and ApoE to evaluate the role of Dax1. Transcriptomic and proteomic analyses were employed to decipher the underlying mechanisms. 2'-Deoxycytidine, an inhibitor of Dax1, was used to verify the effects of Dax1 in macrophages and in mice with atherosclerosis. RESULTS:Dax1 mRNA level was up-regulated among NRs in atherosclerotic arteries compared to non-atherosclerotic arteries. The elevation of Dax1 was prominent in the macrophages of atherosclerotic arteries. Macrophage-specific Dax1 knockout mice had less atherosclerosis than controls. Mechanistically, Dax1 inhibited liver X receptor alpha (LXRα), and interacted directly with transcription factor EB (TFEB) to suppress autophagy, resulting in lipid accumulation and inflammation in macrophages. Additionally, 2'-deoxycytidine concentration dependently decreased Dax1 levels, enhanced autophagy, reduced lipid accumulation, and inhibited atherosclerosis in mice. CONCLUSIONS:This study demonstrates that Dax1 levels are increased in atherosclerotic plaques. Dax1 promotes atherosclerosis by interacting with TFEB to suppress autophagy and inhibiting LXRα for lipid transport in macrophage, indicating that Dax1 is a potential target for atherosclerosis.

BACKGROUND:Type 2 diabetes is strongly associated with impaired collateralization, which increases the risk of cardiovascular complications, such as myocardial infarction and heart failure. This study explored the immune cell dynamics in patients with type 2 diabetes with chronic total occlusion and their impact on collateralization. METHODS:Peripheral blood mononuclear cells were extracted from patients with type 2 diabetes with chronic total occlusion, exhibiting either good or poor collateralization. Single-cell RNA sequencing was conducted to profile the quantitative and transcriptomic dynamics of immune cells in these 2 groups. Moreover, coculture experiments were executed, and ischemic models of the hindlimb and myocardium were induced in diabetic mice to corroborate the single-cell RNA sequencing findings. Additional validation was attained by conducting an analysis on a separate cohort of patients. RESULTS:Single-cell RNA sequencing of peripheral blood mononuclear cells identified elevated levels of mucosal-associated invariant T (MAIT) cells in patients with poor collateralization. In diabetic mice, inhibition of MAIT cell activation significantly improved angiogenesis under ischemic conditions. In vitro, MAIT cell-derived CCL3L1 (C-C motif chemokine ligand 3-like 1) drove macrophage polarization toward a proinflammatory phenotype through CCR5 (C-C chemokine receptor type 5) interaction. Furthermore, an independent patient cohort confirmed that elevated MAIT cell levels represent an independent risk factor for poor collateralization. CONCLUSIONS:These findings highlight the critical role of MAIT cells in regulating collateralization in type 2 diabetes chronic total occlusion patients and propose circulating MAIT cell levels as a potential biomarker for predicting and intervening in poor collateralization.

AIMS:Vasostatin-2, a bioactive peptide derived from chromogranin A, has cardiovascular-protective and anti-inflammatory properties. However, its role in injury-induced vascular remodelling remains unclear. This study aimed to investigate whether serum vasostatin-2 levels are related to restenosis in patients following percutaneous coronary intervention (PCI), and whether this peptide influences vascular neointimal hyperplasia in a mouse model of femoral artery injury. METHODS AND RESULTS:Serum vasostatin-2 levels were evaluated in patients with (n = 442) and without (n = 442) restenosis after PCI. Recombinant vasostatin-2 or saline was administered in a mouse model of femoral artery injury. A combination of multi-omics (Bulk RNA sequencing, CUT&Tag detection, and glutathione S-transferase pull-down/mass spectrometry analysis) was employed to investigate underlying mechanisms. Patients with restenosis had lower serum vasostatin-2 levels than those without restenosis (P < 0.001). Vasostatin-2 protein significantly inhibited neointimal hyperplasia and suppressed the vascular smooth muscle cell (VSMC) phenotype switch after injury. Mechanistically, vasostatin-2 was proven to bind angiotensin-converting enzyme 2 (ACE2) and activate the downstream nuclear receptor subfamily 1 group D member 1 (NR1D1)-growth arrest-specific 1 (Gas1) pathway, thereby facilitating apoptosis of VSMCs and inhibiting their proliferation. ACE2-binding incompetent vasostatin-2 mutants and NR1D1 deficiency in VSMCs weakened vasostatin-2 effect on neointimal hyperplasia in mice. CONCLUSION:Decreased serum vasostatin-2 levels are associated with coronary artery restenosis in patients with coronary angioplasty. Vasostatin-2 attenuates vascular injury-induced neointimal growth in mice and inhibits the proliferation of VSMCs in vitro through the ACE2/NR1D1/Gas1 pathway.

Infantile hemangioma (IH) is the most common type of benign vascular tumor found in infants and young children. Hemangioma-derived endothelial cells within the lesion from birth to three months of age are the primary characteristic of IH. (hemangioma-derived endothelial cells, HemECs) proliferated rapidly and formed hemangioma masses, most of which gradually regressed spontaneously within the next 1 to 5 years of age and continued to improve until the age of 6 to 12 years. But 10–15

Nuclear receptors (NRs) are ligand-dependent transcription factors that play essential roles in maintaining metabolic homeostasis and regulating disease progression through the control of metabolism, inflammation, and cellular differentiation. Due to their central position in these pathways, NRs have emerged as critical therapeutic targets in a range of metabolic and cardiovascular disorders, including diabetes, metabolic dysfunction-associated steatotic liver disease ([MASLD]; previously termed non-alcoholic fatty liver disease [NAFLD]), and atherosclerosis. This review summarizes current understanding of the molecular mechanisms by which NRs regulate metabolic function, with particular emphasis on their contributions to disease pathogenesis. We further outline recent advances from preclinical and clinical studies that explore NR-targeted therapeutic strategies. A deeper understanding of NR biology in metabolic and cardiovascular contexts holds promise for the development of more effective and selective interventions.

IntroductionThe gut microbiota metabolite, short-chain fatty acids (SCFAs), can protect against multiple cardiovascular diseases, while the molecular targets and underlying mechanisms need to be elucidated. One of the primary mechanisms of SCFA benefits was the direct activation of a group of G-protein-coupled receptors (GPCRs), termed free fatty acid receptors (FFARs), the FFAR2 (GPR43), and FFAR3 (GPR41). At present, the distribution of FFAR2/3 in cardiac cells has not been entirely clarified.MethodsUsing 18 public single-cell RNA-seq and single-nuclear RNA-seq data of human and mouse hearts, we illustrate the entire atlas of FFAR2/3 distribution in different regions and cell types in normal and infarcted hearts.Results and discussionWe present the atlas of FFAR2/3 in the whole human body, normal and infarcted hearts at single-cell resolution. We also illustrated the entire atlas of FFAR2/3 in normal/ischemic hearts of newborn and adult mice by combining public and newly built sc/snRNA-seq datasets. These findings provide valuable information on the possible effect of SCFAs via FFAR2/3 in the heart and valuable references for future studies.

Background: Parental postpartum co-morbid anxiety and depression negatively impact personal well-being, family dynamics, and child developmental outcomes. This study investigates the prevalence of co-morbid anxiety and depression in both mothers and fathers during the first 2 years postpartum in China, and to explore its associations with parental family support, maternal health-related quality of life (HRQoL), and child development. Methods: This cross-sectional study was conducted in China, involving families with children aged 0-2 years who participated in community child health care. Data were collected via questionnaires administered to parents by pediatricians and nurses at community health service (CHS) centers. Path analysis was utilized to test the hypothesized model, which links parental co-morbid anxiety and depression to parental family support, maternal HRQoL, and child development. Results: A total of 2073 pairs of both parents who completed the survey were included in the final analyses. The prevalence of maternal and paternal co-morbid anxiety and depression, was 5.7 % and 4.4 %, respectively. Among mothers, the prevalence ranged from 4.3 % to 6.5 % within the first 6 months, and 7.9 % in the second year. After adjusting for covariates, severe family dysfunction was significantly associated with maternal and paternal co-morbid anxiety and depression. The path analysis showed that maternal co-morbid anxiety and depression were directly associated with child development and maternal HRQoL. Conclusions: These findings highlight the importance of prioritizing family support, addressing both depression and anxiety, involving both parents and extending support beyond the first year postpartum.

BackgroundVulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease.MethodsTo reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography.ResultsMacrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques.ConclusionElevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.

Background Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS 2 NDs) for enhancing collateral formation and improving prognosis. Results Our study shows that MoS 2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS 2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS 2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H 2 O 2 , •O 2 - , and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells. Conclusions Overall, this study investigated the specific mechanism by which MoS 2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential. Graphical Abstract

Objective: The proliferation and migration of hemangioma stem cells (HemSCs) induced apoptosis and adipose differentiation as well as increased the sensitivity of HemSCs to propranolol (PPNL). MiR-27a-3p negatively controlled the peroxisome-proliferator-activated receptor γ (PPAR-γ) level, counteracting the effect of PPAR-γ on HemSC progression and PPNL resistance. OMT accelerated HemSC progression and adipocyte differentiation via modulating the miR-27a-3p/PPAR-γ axis, inhibiting HemSC resistance to PPNL. In tumor-forming experiments, OMT exhibited a dose-dependent inhibitory effect on the volume of IH PPNL-resistant tumors, which was partially dependent on the regulation of m6A methylation transfer enzyme METTL3 and the miR-27a-3p/PPAR-γ axis, thereby inducing apoptosis. Conclusions: We conclude that OMT regulates IH and influences PPNL resistance via targeting the miR-27a-3p/PPAR-γ signaling pathway through m6A modification.

Background: A recent high-throughput sequencing study revealed an anomalous underexpression of circular RNA UBAP2 (circUBAP2) in acute myocardial infarction (AMI), yet its biological function within this context remains elusive. This study aims to unravel whether circUBAP2 is instrumental in modulating the pathogenesis of AMI and to illuminate the underlying molecular mechanisms at play. Results: circUBAP2 was abnormally low expressed in AMI. Inducing circUBAP2 ameliorated hypoxiainduced myocardial cell injury by enhancing cellular viability, and decreasing lactate dehydrogenase release, apoptosis, inflammation, and oxidative damage. circUBAP2 targeted miR-148b-3p, miR-148b3p overexpression offset circUBAP2-induced cardioprotection. Cyclin-dependent kinase inhibitor 1B (CDKN1B) was mediated by miR-148b-3p, and CDKN1B upregulation suppressed the deleterious effect of circUBAP2 silencing on hypoxic AC16 cells. In addition, overexpression of circUBAP2 improved myocardial injury, decreased myocardial cell apoptosis, and alleviated inflammation and oxidative stress in AMI mice. Conclusions: circUBAP2 ameliorates AMI by competitively binding to miR-148b-3p and mediating CDKN1B expression. (c) 2023 Pontificia Universidad Catolica de Valparaiso. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

妊娠期高血糖可对母体和子代产生诸多近期和远期的不良影响，严重危害孕妇及围生儿健康，孕期积极饮食和运动干预，必要时增加胰岛素等药物治疗控制血糖水平，加强妊娠期高血糖孕期及产后管理，有助于减少母婴并发症，改善妊娠结局，提高人口素质。

Background The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases in diabetes. We investigated whether N-epsilon-carboxymethyllysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery. Methods This study consisted of 242 T2DM patients with coronary angiographically documented CTO. Blood samples were obtained and demographic/clinical characteristics were documented. The coronary collateralization of these patients was defined according to Rentrop or Werner classification. Serum CML levels were evaluated using ELISA assay. Receiver operating characteristic curve and multivariable regression analysis were performed. Results 242 patients were categorized into poor CCV group or good CCV group (107 vs. 135 by the Rentrop classification or 193 vs. 49 by the Werner classification, respectively). Serum CML levels were significantly higher in poor CCV group than in good CCV group (110.0 ± 83.35 vs. 62.95 ± 58.83 ng/ml by the Rentrop classification and 94.75 ± 78.29 ng/ml vs. 40.37 ± 28.69 ng/ml by Werner classification, both P < 0.001). Moreover, these CML levels were also significantly different across the Rentrop and Werner classification subgroups (P < 0.001). In multivariable logistic regression, CML levels (P < 0.001) remained independent determinants of poor CCV according to the Rentrop or Werner classification after adjustment of traditional risk factors. Conclusions This study suggests that higher serum CML level is associated with poor collateralization in T2DM patients with CTO.