Implementing mind mapping in small-group learning to promote student engagement in the medical diagnostic curriculum: a pilot study.

BACKGROUND: Medical diagnostics is a pivotal bridge curriculum that receives much less attention from undergraduates in non-clinical medicine health profession programs with less student engagement and poor performance. Mind mapping is an active learning strategy for graphically presenting radiant thinking to culture clinical reasoning. The purpose of this study was to explore whether students' comprehensive diagnostic skills are enhanced through increased student engagement by employing mind mapping. METHODS: We implemented mind mapping in small-grouped workshops with 86 junior undergraduates from preventive medicine program, for physical diagnostic sessions including physical examination (PE) maneuver, electrocardiogram (ECG) interpretation and medical history collection. We also conducted assessments of the above skills, as well as online surveys regarding their expectation on this course, self-evaluation of mind mapping in teaching and the learning process of all the modules. RESULTS: Group members employing mind mapping in all PE sessions obtained higher scores in the heart and lung systems during the PE maneuver exam. Similarly, groups that made more in-depth mind maps achieved higher scores on the ECG quiz. In addition, groups displaying mind maps for history taking from normal classes and reformed class exhibited greater completeness of medical history with both standardized patients and real patients, which was consistent with increased collection of accompanying symptoms. Mind mapping was valued by the majority of students for its benefits in terms of acquiring PE maneuver, theoretical knowledge, medical history collection and medical records writing, clinical reasoning, communication skills, sense of teamwork and cooperation, professionalism and humanistic literacy. DISCUSSION: The visual feature of mind mapping evoked extensive behavioral engagement in all groups, as did cognitive and emotional engagement, as the majority of students expressed their willingness and affective reactions. In the short term, the positive feedbacks encourage growing engagement. The continuous benefits of mind mapping require long-term observation.

Association between macro- and microvascular damage and sarcopenia index in individuals with type 2 diabetes mellitus.

Sarcopenia was recently reported to be relevant to an increased macro-and microvascular disease risk. Sarcopenia index (SI) has been identified as a surrogate marker for sarcopenia. The aim of the present study was to investigate the association between macro- and microvascular disease and SI in patients with type 2 diabetes mellitus (T2DM). A total of 783 patients with T2DM were enrolled in this cross-sectional study. The SI was calculated by (serum creatinine [mg/dL]/cystatin C [mg/L]) × 100. The subjects were divided into three groups according to SI tertiles: T1 (41.27-81.37), T2 (81.38- 99.55), and T3 (99.56-192.31). Parameters of macro- and microvascular complications, including diabetic retinopathy (DR), micro- and macroalbuminuria (MAU), diabetic peripheral neuropathy (DPN), and lower extremity peripheral artery disease (LEAD) were evaluated. Multivariate logistic regression analysis revealed that when taking the top tertile of SI as a reference, an increasing trend of the prevalence of DR, MAU, DPN, and LEAD were presented (all P for trend  < 0.05), where the OR (95% CI) for DR prevalence was 1.967 (1.252-3.090) in T2, 2.195 (1.278-3.769) in T1, for MAU was 1.805 (1.149-2.837) in T2, 2.537 (1.490-4.320) in T1, for DPN was 2.244 (1.485-3.391) in T2, 3.172 (1.884-5.341) in T1, and for LEAD was 2.017 (1.002-4.057) in T2, 2.405 (1.107-5.225) in T1 (all P < 0.05). Patients with lower SI were more inclined to have an increased risk of macro- and microvascular damage in T2DM population, which may be related to sarcopenia.

Sex Difference in the Association Between Serum Versican and Albuminuria in Patients with Type 2 Diabetes Mellitus.

Introduction: Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes. DKD is associated with oxidative stress and inflammation. Versican (VCAN), a chondroitin sulphate proteoglycan, has been proven to participate in oxidative stress and inflammation. This study aimed to explore the overall and sex-based relationship between serum VCAN levels and albuminuria in patients with type 2 diabetes mellitus (T2DM). Methods: 428 patients with T2DM and 84 healthy individuals were enrolled. Patients with diabetes were separated into normal albuminuria, microalbuminuria, and macroalbuminuria groups, according to their urinary albumin/creatinine ratio (UACR). Serum VCAN levels were tested using an enzyme-linked immunosorbent assay. Results: Compared with males, female patients were older, and had higher total cholesterol and high-density lipoprotein cholesterol, but lower body mass index, diastolic blood pressure, glycated hemoglobin A1, alanine aminotransferase, urinary albumin (UA), and serum creatinine (SCr) (P < 0.05). The VCAN levels in male patients with T2DM were significantly higher than those in the healthy individuals. Male patients with T2DM with albuminuria (micro and macro) had higher levels of VCAN than in patients with normal albuminuria; the highest level was seen in patients with macroalbuminuria (P < 0.05). In male patients with T2DM, serum VCAN correlated positively with systolic blood pressure, blood urea nitrogen, UA, SCr, and UACR, but correlated negatively with the estimated glomerular filtration rate. The area under the receiver operating characteristic curve of serum VCAN to diagnose albuminuria was 0.702, with a corresponding cut-off value of 0.399 ng/mL (P < 0.001). However, the association between serum VCAN and UACR was not observed in female patients with T2DM. Conclusion: Serum VCAN levels correlated positively with the severity of albuminuria in male patients with T2DM.

Reply to Mahat, R.K.; Rathore, V. Comment on "Xiang et al. Association between the Triglyceride-Glucose Index and Vitamin D Status in Type 2 Diabetes Mellitus. Nutrients 2023, 15, 639".

We are pleased to see that Mahat and Rathore [...].

Association of Serum Bilirubin Levels with Macro- and Microvascular Complications in Chinese People with Type 2 Diabetes Mellitus: New Insight on Gender Differences.

Background: Previous studies suggested protective effects of bilirubin against cardiovascular disease, with a possible gender difference. However, the relationship between serum total bilirubin (TBIL) with diabetic macro- and microvascular complications remains unknown. We aimed to examine the association of macro- and microvascular complications with serum TBIL levels. Methods: Serum TBIL was measured in 648 patients with T2DM. Demographic and clinical data were obtained from the inpatient medical record system. Serum TBIL was measured with an automatic biochemistry analyzer according to routine protocols. Parameters of vascular complications, including ankle-brachial index, carotid intima-media thickness, estimated glomerular filtration rate and the urinary albumin to creatinine ratio, were measured and calculated. The association between TBIL and diabetic macro- and microvascular complications was analyzed. Results: In multivariable logistic regression, after adjustment for age, sex, body mass index and diabetic duration, higher serum TBIL levels were significantly associated with decreased odds of microalbuminuria (OR = 0.31, [95% CI] 0.16-0.61, P = 0.003) and chronic kidney disease (OR = 0.19, [95% CI] 0.09-0.41, P < 0.001). These associations were only found in male but not in female patients. However, no significant relationship was found between TBIL and peripheral arterial disease or carotid hypertrophy. Conclusion: Our findings suggest that physiological higher TBIL level might be a protective factor for diabetic microvascular complications.

BMF-AS1/BMF Promotes Diabetic Vascular Calcification and Aging both In Vitro and In Vivo.

Vascular calcification and aging often increase morbidity and mortality in patients with diabetes mellitus (DM); however, the underlying mechanisms are still unknown. In the present study, we found that Bcl-2 modifying factor (BMF) and BMF antisense RNA 1 (BMF-AS1) were significantly increased in high glucose-induced calcified and senescent vascular smooth muscle cells (VSMCs) as well as artery tissues from diabetic mice. Inhibition of BMF-AS1 and BMF reduced the calcification and senescence of VSMCs, whereas overexpression of BMF-AS1 and BMF generates the opposite results. Mechanistic analysis showed that BMF-AS1 interacted with BMF directly and up-regulated BMF at both mRNA and protein levels, but BMF did not affect the expression of BMF-AS1. Moreover, knocking down BMF-AS1 and BMF suppressed the calcification and senescence of VSMCs, and BMF knockout (BMF-/-) diabetic mice presented less vascular calcification and aging compared with wild type diabetic mice. In addition, higher coronary artery calcification scores (CACs) and increased plasma BMF concentration were found in patients with DM, and there was a positive correlation between CACs and plasma BMF concentration. Thus, BMF-AS1/BMF plays a key role in promoting high glucose-induced vascular calcification and aging both in vitro and in vivo. BMF-AS1 and BMF represent potential therapeutic targets in diabetic vascular calcification and aging.

Association between the Triglyceride-Glucose Index and Vitamin D Status in Type 2 Diabetes Mellitus.

BACKGROUND: Vitamin D deficiency (VDD) increases the risk for type 2 diabetes mellitus (T2DM), which might be related to insulin resistance (IR). We aimed to explore the association between the triglyceride-glucose (TyG) index, a reliable indicator of IR, and VDD in patients with T2DM. METHODS: There were 1034 participants with T2DM enrolled in the Second Xiangya Hospital of Central South University. The TyG index was calculated as ln (fasting triglyceride (TG, mg/dL) × fasting blood glucose (mg/dL)/2). VDD was defined as 25-hydroxyvitamin D [25(OH)D] level <50 nmol/L. RESULTS: Correlation analysis showed a negative association between the TyG index and 25(OH)D level. After adjustments for clinical and laboratory parameters, it was revealed that when taking the Q1 quartile of TyG index as a reference, an increasing trend of VDD prevalence was presented in the other three groups divided by TyG index quartiles, where the OR (95% CI) was 1.708 (1.132-2.576) for Q2, 2.041 (1.315-3.169) for Q3, and 2.543 (1.520-4.253) for Q4 (all p < 0.05). CONCLUSIONS: Patients with higher TyG index were more likely to have an increased risk of VDD in T2DM population, which may be related to IR.

Long noncoding RNA SNHG1 alleviates high glucose-induced vascular smooth muscle cells calcification/senescence by post-transcriptionally regulating Bhlhe40 and autophagy via Atg10

Long noncoding RNAs (lncRNAs) are emerging regulators of vascular diseases, yet their role in diabetic vascular calcification/aging remains poorly understood. In this study, we identified a down-expressed lncRNA SNHG1 in high glucose (HG)-induced vascular smooth muscle cells (HA-VSMCs), which induced excessive autophagy and promoted HA-VSMCs calcification/senescence. Overexpression of SNHG1 alleviated HG-induced HA-VSMCs calcification/senescence. The molecular mechanisms of SNHG1 in HA-VSMCs calcification/senescence were explored by RNA pull-down, RNA immunoprecipitation, RNA stability assay, luciferase reporter assay, immunoprecipitation and Western blot assays. In one mechanism, SNHG1 directly interacted with Bhlhe40 mRNA 3′-untranslated region and increased Bhlhe40 mRNA stability and expression. In another mechanism, SNHG1 enhanced Bhlhe40 protein SUMOylation by serving as a scaffold to facilitate the binding of SUMO E3 ligase PIAS3 and Bhlhe40 protein, resulting in increased nuclear translocation of Bhlhe40 protein. Moreover, Bhlhe40 suppressed the expression of Atg10, which is involved in the process of autophagosome formation. Collectively, the protective effect of SNHG1 on HG-induced HA-VSMCs calcification/senescence is accomplished by stabilizing Bhlhe40 mRNA and promoting the nuclear translocation of Bhlhe40 protein. Our study could provide a novel approach for diabetic vascular calcification/aging. (AU)

Long noncoding RNA SNHG1 alleviates high glucose-induced vascular smooth muscle cells calcification/senescence by post-transcriptionally regulating Bhlhe40 and autophagy via Atg10.

Long noncoding RNAs (lncRNAs) are emerging regulators of vascular diseases, yet their role in diabetic vascular calcification/aging remains poorly understood. In this study, we identified a down-expressed lncRNA SNHG1 in high glucose (HG)-induced vascular smooth muscle cells (HA-VSMCs), which induced excessive autophagy and promoted HA-VSMCs calcification/senescence. Overexpression of SNHG1 alleviated HG-induced HA-VSMCs calcification/senescence. The molecular mechanisms of SNHG1 in HA-VSMCs calcification/senescence were explored by RNA pull-down, RNA immunoprecipitation, RNA stability assay, luciferase reporter assay, immunoprecipitation and Western blot assays. In one mechanism, SNHG1 directly interacted with Bhlhe40 mRNA 3'-untranslated region and increased Bhlhe40 mRNA stability and expression. In another mechanism, SNHG1 enhanced Bhlhe40 protein SUMOylation by serving as a scaffold to facilitate the binding of SUMO E3 ligase PIAS3 and Bhlhe40 protein, resulting in increased nuclear translocation of Bhlhe40 protein. Moreover, Bhlhe40 suppressed the expression of Atg10, which is involved in the process of autophagosome formation. Collectively, the protective effect of SNHG1 on HG-induced HA-VSMCs calcification/senescence is accomplished by stabilizing Bhlhe40 mRNA and promoting the nuclear translocation of Bhlhe40 protein. Our study could provide a novel approach for diabetic vascular calcification/aging.

Icariin attenuates the calcification of vascular smooth muscle cells through ERα - p38MAPK pathway.

Objective: To investigate the relationship between icariin and the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) and the signal pathway involved. Methods: We applied a universally accepted calcification model of VSMCs induced by ß glycerophosphate. Then the VSMCs calcification was observed by treatment with icariin and/or inhibitors of estrogen receptors (ERs) and p38-mitogen-activated protein kinase (MAPK) signaling. Results: Icariin inhibited osteoblastic differentiation and mineralization of VSMCs due to decreased ALP activity and Runx2 expression. Further study demonstrated that icariin exerted this suppression effect through activating p38-MAPK but not extracellular-regulated kinase, JNK or Akt. An inhibitor of p38-MAPK partially reversed the inhibitory effects of icariin on osteoblastic differentiation. Interestingly, treatment of VSMCs with an ER antagonist ICI182780 and a selective ERα receptor antagonist PPT attenuated icariin-mediated inhibition effect of VSMCs calcification, associated with suppression of p38-MAPK phosphorylation. Conclusions: Icariin inhibited the osteoblastic differentiation of VSMCs, and that the inhibitory effects were mediated by p38-MAPK pathways through ERα.

Analysis of the relationship between serum alanine aminotransferase and body composition in Chinese women.

Objective: To investigate the relationships between serum alanine aminotransferase (ALT) and body composition among postmenopausal women in China. Methods: A cross-sectional study was conducted with 776 postmenopausal women in China from May to July 2008. Clinical information was collected using a standardized questionnaire. Measures of body composition were obtained using dual X-ray absorptiometry. Body lean mass and fat mass indices were calculated by dividing total body lean/fat weight (kg) by body height squared (kg/m2). Blood samples were collected to assess liver and renal functions and lipid profiles. Analysis of variance, Pearson correlations, and multiple regression were used to analyze the associations between serum ALT and body composition. Results: We found negative relationships of serum ALT with age, menopause duration, and serum HDL-C levels. Serum ALT was positively correlated with BMI, serum TG levels, and the lean mass index and fat mass index. In a multivariate model adjusted for age, menopause duration, serum TG, and HDL-C levels, a 1-unit increase in the fat mass index was associated with a 0.176 U/L increase in ALT (95% CI 0.020 to 0.050, P < 0.001). Conclusion: Serum ALT was positively associated with the body fat mass index of postmenopausal women in China.

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases.

Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are closely related to a variety of biological and functional aspects of human health. When the exosomal ncRNAs undergo tissue-specific changes due to diverse internal or external disorders, they can cause tissue dysfunction, aging, and diseases. In this review, we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases. In addition, we explore the current knowledge on the roles of exosomal miRNAs, lncRNAs, and circRNAs in human health and diseases, including cancers, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and infectious diseases, to determine their potential implication in biomarker identification and therapeutic exploration.

Roles and functions of antisense lncRNA in vascular aging.

Vascular aging is a major cause of morbidity and mortality in the elderly population. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), forming the intima and media layers of the vessel wall respectively, are closely associated with the process of vascular aging and vascular aging-related diseases. Numerous studies have revealed the pathophysiologic mechanism through which lncRNA contributes to vascular aging, hence more attention is now paid to the role played by antisense long non-coding RNA (AS-lncRNA) in the pathogenesis of vascular aging. Nonetheless, only a small number of studies focus on the specific mechanism through which AS-lncRNA mediates vascular aging. In this review, we summarize the roles and functions of AS-lncRNA with regards to the development of vascular aging and vascular aging-related disease. We also aim to deepen our understanding of this process and provide alternative therapeutic modalities for vascular aging-related diseases.

The Role of SGLT2 Inhibitors in Vascular Aging.

Vascular aging is defined as organic and functional changes in blood vessels, in which decline in autophagy levels, DNA damage, MicroRNA (miRNA), oxidative stress, sirtuin, and apoptosis signal-regulated kinase 1 (ASK1) are integral thereto. With regard to vascular morphology, the increase in arterial stiffness, atherosclerosis, vascular calcification and high amyloid beta levels are closely related to vascular aging. Further closely related thereto, at the cellular level, is the aging of vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Vascular aging seriously affects the health, economy and life of patients, but can be delayed by SGLT2 inhibitors through the improvement of vascular function. In the present article, a review is conducted of recent domestic and international progress in research on SGLT2 inhibitors,vascular aging and diseases related thereto, thereby providing theoretical support and guidance for further revealing the relationship between SGLT2 inhibitors and diseases related to vascular aging.

Clinical expert consensus on standard care of blood glucose for residents in senior care facility in China (2021 edition).

With the demographic changes, more and more elderly people have chosen to spend their retirement life in a senior care facility. The elderly people in senior care facility are commonly suffering from various geriatric syndromes, including declined daily living activities, cognitive dysfunction, frailty, comorbidities, and polypharmacy, which make them vulnerable to adverse effects, like hypoglycemia and fall. Therefore, layered management is necessary for this population with group disparities. However, the staff in senior care facility vary greatly in concepts and skills on management of senile diabetic population, which needs urgently to be standardized and improved. For this purpose, based on literature review and panel discussion, 28 recommendations are proposed in respect of the standardized management of blood glucose, covering the comprehensive assessment, layered management and grouping, exercise, nutrition, glucose monitoring, identification and treatment of severe hyperglycemia, identification of macrovascular and microvascular complications, management of hypoglycemic drugs, falls and choking and other common problems, blood glucose screening, hypoglycemia prevention, and blood glucose management in major public health events or serious natural disasters. This guideline aims to standardize management skills of medical staff and caregivers in senior care facility for the blood glucose of elderly people and improve their quality of life.

ICAM-1 deletion delays the repair process in aging diabetic mice.

BACKGROUND: The delayed repair process in the aging diabetic population is becoming an alarming public health concern. ICAM-1 plays an important role in orchestrating the repair process by mediating neutrophil recruitment and phagocytosis. However, little is known about the role of ICAM-1 in aging diabetic repair. METHODS: By causing injury in aging diabetic mice with ICAM-1 deletion (AD-ICAM-1-/-), we found that AD-ICAM-1-/- mice exhibited a delayed repair process with incomplete re-epithelialization and reduced angiogenesis. Additionally, high-throughput Illumina sequencing was performed to evaluate the microbiota of such mice. RESULTS: The results indicate that the microbiota of the AD-ICAM-1-/- injury site differed taxonomically at both the phylum and genus levels. Neutrophil recruitment and phagocytic function were also reduced in the AD-ICAM-1-/- group. Notably, major inflammatory biomarker expression was also detected in AD-ICAM-1-/- injured tissue. CONCLUSIONS: Overall, this study demonstrated that AD-ICAM-1-/- mice exhibit delayed repair. In addition, neutrophil recruitment and phagocytic activity were impaired in the AD-ICAM-1-/- group, which may have allowed microbes to colonize the injury site.

A Perspective on Roles Played by Immunosenescence in the Pathobiology of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. Aging is the most significant risk factor for late-onset AD. The age-associated changes in the immune system are termed immunosenescence. A close connection between immunosenescence and AD is increasingly recognized. This article provides an overview of immunosenescence and evidence for its role in the pathogenesis of AD and possible mechanisms as well as the outlook for drug development.

Adiponectin attenuates the premature senescence of vascular smooth muscle cells induced by high glucose through mTOR signaling pathway.

OBJECTIVE: Cardiovascular diseases and vascular aging are common in patients with diabetes. High glucose is a major cause of vascular aging and cardiovascular diseases. Premature senescence of vascular smooth muscle cells (VSMCs) is one of the main contributors to vascular aging. Adiponectin has been demonstrated to have an anti-aging effect. The present study explored the mechanisms by which adiponectin protects VSMCs against high-glucose-induced senescence. METHODS: Senescence-associated ß-galactosidase (SA-ß-gal) staining was used to detect senescence cells. Western blot was used for measuring protein levels. Flow cytometry was carried out to detect the cell cycle and telomeric repeat amplification protocol (TRAP)-polymerase chain reaction (PCR) silver staining was selected to measure the telomerase activity. RESULTS: Premature senescence of VSMCs was induced by high glucose (30 mM) in a time-dependent manner, which was verified by an increased number of senescence cells, p21 and p53 expression, as well as the decreased proliferation index. High glucose reduced telomerase activity of VSMCs via inhibition of the AMPK/TSC2/mTOR/S6K1 pathway and activation of the PI3K/Akt/mTOR/S6K1 pathway, while adiponectin treatment significantly increased telomerase activity of VSMCs through activation of AMPK/TSC2/mTOR/S6K1 signaling and inhibition of PI3K/Akt/mTOR/S6K1 signaling. CONCLUSION: Adiponectin attenuated the high-glucose-induced premature senescence of VSMCs via increasing telomerase activity of VSMCs, which was achieved by activation of AMPK/TSC2/mTOR/S6K1 signaling and inhibition of PI3K/Akt/mTOR/S6K1 signaling.

Roles and mechanisms of MFG-E8 in vascular aging-related diseases.

The aging of the vasculature plays a crucial role in the pathological progression of various vascular aging-related diseases. As endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are essential parts in the inner and medial layers of vessel wall, respectively, the structural and functional alterations of ECs and VSMCs are the major causes of vascular aging. Milk fat globule-epidermal growth factor 8 (MFG-E8) is a multifunctional glycoprotein which exerts a regulatory role in the intercellular interactions involved in a variety of biological and pathological processes. Emerging evidence suggests that MFG-E8 is a novel and outstanding modulator for vascular aging via targeting at ECs and VSMCs. In this review, we will summarise the cumulative roles and mechanisms of MFG-E8 in vascular aging and vascular aging-related diseases with special emphasis on the functions of ECs and VSMCs. In addition, we also aim to focus on the promising diagnostic function as a biomarker and the potential therapeutic application of MFG-E8 in vascular aging and the clinical evaluation of vascular aging-related diseases.

LncRNA-ES3 inhibition by Bhlhe40 is involved in high glucose-induced calcification/senescence of vascular smooth muscle cells.

Long noncoding RNAs (lncRNAs) have been investigated as novel regulatory molecules involved in diverse biological processes. Our previous study demonstrated that lncRNA-ES3 is associated with the high glucose-induced calcification/senescence of human aortic vascular smooth muscle cells (HA-VSMCs). However, the mechanism of lncRNA-ES3 in vascular calcification/aging remained largely unknown. Here, we report that the expression of basic helix-loop-helix family member e40 (Bhlhe40) was decreased significantly in HA-VSMCs treated with high glucose, whereas the expression of basic leucine zipper transcription factor (BATF) was increased. Overexpression of Bhlhe40 and inhibition of BATF alleviated calcification/senescence of HA-VSMCs, as confirmed by Alizarin Red S staining and the presence of senescence-associated ß-galactosidase-positive cells. Moreover, we identified that Bhlhe40 regulates lncRNA-ES3 in HA-VSMCs by binding to the promoter region of the lncRNA-ES3 gene (LINC00458). Upregulation or inhibition of lncRNA-ES3 expression significantly promoted or reduced calcification/senescence of HA-VSMCs, respectively. Additionally, we identified that lncRNA-ES3 functions in this process by suppressing the expression of miR-95-5p, miR-6776-5p, miR-3620-5p, and miR-4747-5p. The results demonstrate that lncRNA-ES3 triggers gene silencing of multiple miRNAs by binding to Bhlhe40, leading to calcification/senescence of VSMCs. Our findings suggest that pharmacological interventions targeting lncRNA-ES3 may be therapeutically beneficial in ameliorating vascular calcification/aging.