Objective: Coronary microvascular dysfunction (CMD) is an independent predictor of cardiovascular events in patients with diabetes, while glucose fluctuations worsen vascular lesions. This study aims to examine myocardial microvascular perfusion in patients with type 2 diabetes mellitus (T2DM) and to determine whether uncontrolled blood glucose levels lead to further deterioration of myocardial microvascular function. Design and method: Cardiac magnetic resonance (CMR) examinations were performed on 114 T2DM patients with complaints of atypical chest tightness and 55 matched controls. Obstructive coronary artery disease (CAD) was ruled out in all subjects, who were further divided into four subgroups: Q1 (T2DM-negative [–], glycated hemoglobin A1c [HbA1c] < 5.7%); Q2 (T2DM–, 5.7% <= HbA1c <= 6.4%); Q3 (T2DM-positive [+], HbA1c <7%; and Q4 (T2DM+, HbA1c >= 7%). The correlation between HbA1c levels and myocardial perfusion parameters was also evaluated. Results: Compared with controls, the myocardial perfusion reserve index (MPRI) in patients with T2DM was reduced (P < 0.001) due to decreased stress perfusion index (PI) (P < 0.001). MPRI was decreased in patients with uncontrolled T2DM (Q4) than in patients with controlled T2DM (Q3), with borderline significance (P = 0.065). Compared with controls (Q1), stress T1 reactivity (δT1) was significantly reduced in patients with controlled and uncontrolled T2DM (P = 0.004 and < 0.001, respectively), but elevated in patients with prediabetes (Q2) (P = 0.018). Extracellular volume (ECV) was significantly greater in patients with prediabetes and increased gradually in patients with controlled and uncontrolled T2DM compared with controls (P = 0.011, 0.001, and 0.007, respectively). Furthermore, HbA1c was negatively associated with MPRI and stress δT1, but positively correlated with ECV (β = -1.993, P < 0.001; β = 0.127, P < 0.001; and β = -0.180, P < 0.001, respectively). Conclusions: MPRI was negatively correlated with HbA1c, and its decrease in patients with T2DM was due to a lower increase in stress PI compared with controls. Stress δT1 decreased in patients with T2DM but increased in patients with prediabetes, indicating damage to microvascular perfusion in the prediabetic stage. Elevated ECV persists throughout diabetes.
Background Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status. Methods This study included 34 active patients (AP), 30 inactive patients (IP) with TED, and 45 healthy controls (HC) matched for age, sex, and educational level. Comprehensive clinical details (especially immunoendocrine markers) and resting-state functional magnetic resonance imaging data were collected from each participant. The amplitude of low-frequency fluctuation (ALFF) was used to probe the aberrant alterations of local neural activity. The seed-based functional connectivity (FC) analysis was used to explore the relationship between the insular cortex and each voxel throughout the whole brain. The correlation analysis was conducted to assess the association between insular neurobiomarkers and immunoendocrine parameters. Results When compared with the IP and HC groups, the AP group displayed significantly higher ALFF values in the right insular cortex (INS.R) and lower FC values between the INS.R and the bilateral cerebellum. None of the neurobiomarkers differed between the IP and HC groups. Besides, correlations between insular neurobiomarkers and immunoendocrine markers (free thyroxine, the proportion of T cells, and natural killer cells) were identified in both AP and IP groups. Conclusions This study was novel in reporting that the dysregulation of the insular cortex activity in TED was associated with abnormal peripheral immunoendocrine status. The insular cortex might play a key role in central–peripheral system interaction in TED. Further research is crucial to enhance our understanding of the central–peripheral system interaction mechanisms involved in autoimmune diseases.
Objective: Patients successfully revascularized after acute myocardial infarction (AMI) underwent in-hospital cardiac rehabilitation (CR) and were assessed for their state by the clinical frailty scale (CFS) to investigate the predictive value of the CFS score on the incidence rate of major cardiovascular events within one year. Design and method: A graded CR scheme was developed in a total of 501 patients with AMI, who were treated in the cardiology center of Shanghai Sixth People’s Hospital from May 2020 to May 2022, and the CFS score was assessed based on the CR condition of the patients before discharge. Patients were then categorized into three groups (norm group, vulnerable group, and frail group) according to their CFS score. The difference in one-year major cardiovascular event (all-cause death and re-hospitalization for heart failure) rates among these groups was compared. Logistic regression analysis was performed to explore risk factors affecting cardiovascular events, and an ROC curve was generated to analyze the risk factors in predicting one-year cardiovascular event rates. Finally, an optimal prediction model was developed. Results: The CFS score in AMI patients was positively correlated with age and peak proBNP and inversely correlated with gender difference (P <= 0.001). There were significant differences in the incidence of all-cause death between the frail group and the norm group (P = 0.002), whereas there was no significant difference between the vulnerable group and the norm group (P > 0.05). There was no significant difference in re-hospitalization for heart failure among the three groups (P = 0.710). The CFS score could sensitively predict the 1-year risk of all-cause death in AMI patients (β = 1.89, OR = 6.61, P = 0.001), and the risk model combined with the CFS score had the best predictive effect (AUC = 0.845, P = 0.000). Conclusions: In-hospital CR along with assessment using the CFS score can effectively identify AMI patients with a high risk of death.
Thyroid eye disease (TED) is an organ-specific autoimmune disease secondary largely to hyperthyroid Graves' disease, which profoundly affects patients' visual function, appearance, and physical and mental well-being. Emerging neuroimaging studies have reported alterations in the brains of patients with TED, suggesting that the impact of this autoimmune disease may extend beyond the orbit. This systematic review aims to consolidate the neuroimaging evidence that describes the brain alterations of TED. We analyzed information from thirty-one related studies involving 1349 TED patients and 710 healthy controls, employing multimodal neuroimaging techniques such as structural magnetic resonance imaging (MRI), functional MRI, diffusion MRI, and metabolic MRI. These studies define the brain alterations in regions associated with vision, cognition, and emotion regulation, such as gray matter volume changes, altered functional connectivity and activity, and microstructural modifications, revealing the neurological impact of TED beyond the orbit. Notably, there was convergence across these studies indicating predominant abnormalities within the occipital and parietal lobes. This review underscores the critical role of advanced neuroimaging techniques in unraveling the complex neuropathological mechanism of TED, laying a foundation for future research and potential therapeutic targets.
AIMS:To investigate the alterations of the optic nerve and visual cortex in dysthyroid optic neuropathy (DON), a subgroup of thyroid eye disease (TED). METHODS:Multiple orbital imaging biomarkers related to optic nerve compression and the amplitude of low-frequency fluctuations (ALFF) of the brain were obtained from 47 patients with DON, 56 TED patients without DON (nDON), and 37 healthy controls (HC). Correlation analyses and diagnostic tests were implemented. RESULTS:Compared with HC, the nDON group showed alterations in orbital imaging biomarkers related to optic nerve compression in posterior segments, as well as ALFF of the right inferior temporal gyrus and left fusiform gyrus. DON differed from nDON group mainly in the modified muscle index of the posterior segment of optic nerve, and ALFF of orbital part of right superior frontal gyrus, right hippocampus, and right superior temporal gyrus. Orbital and brain imaging biomarkers were significantly correlated with each other. Diagnostic models attained an area under a curve of 0.80 for the detection of DON. CONCLUSION:The combined orbital and brain imaging study revealed alterations of the visual pathway in patients with TED and DON as well as provided diagnostic value. The initiation of alterations in the visual cortex in TED may precede the onset of DON.
Patients with diabetes have an increased risk of developing heart failure with preserved ejection fraction (HFpEF). This study aimed to compare indices of myocardial deformation and perfusion between patients with type 2 diabetes mellitus (T2DM) with and without HFpEF and to investigate the relationship between myocardial strain and perfusion reserve. This study included 156 patients with T2DM without obstructive coronary artery disease (CAD) and 50 healthy volunteers who underwent cardiac magnetic resonance (CMR) examination at our center. Patients with T2DM were subdivided into the T2DM–HFpEF (n = 74) and the T2DM–non-HFpEF (n = 82) groups. The parameters of left ventricular (LV) and left atrial (LA) strain as well as stress myocardial perfusion were compared. The correlation between myocardial deformation and perfusion parameters was also assessed. Mediation analyses were used to evaluate the direct and indirect effects of T2DM on LA strain. Patients with T2DM and HFpEF had reduced LV radial peak systolic strain rate (PSSR), LV circumferential peak diastolic strain rate (PDSR), LA reservoir strain, global myocardial perfusion reserve index (MPRI), and increased LA booster strain compared to patients with T2DM without HFpEF (all P < 0.05). Furthermore, LV longitudinal PSSR, LA reservoir, and LA conduit strain were notably impaired in patients with T2DM without HFpEF compared to controls (all P < 0.05), but LV torsion, LV radial PSSR, and LA booster strain compensated for these alterations (all P < 0.05). Multivariate linear regression analysis demonstrated that LA reservoir and LA booster strain were independently associated with global MPRI (β = 0.259, P < 0.001; β = − 0.326, P < 0.001, respectively). Further, the difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI. Global stress PI, LA booster, global rest PI, and global MPRI showed high accuracy in diagnosing HFpEF among patients with T2DM (areas under the curve [AUC]: 0.803, 0.790, 0.740, 0.740, respectively). Patients with T2DM and HFpEF exhibited significant LV systolic and diastolic deformation, decreased LA reservoir strain, severe impairment of myocardial perfusion, and elevated LA booster strain that is a compensatory response in HFpEF. Global MPRI was identified as an independent influencing factor on LA reservoir and LA booster strain. The difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI, suggesting a possible mechanistic link between microcirculation impairment and cardiac dysfunction in diabetes. Myocardial perfusion and LA strain may prove valuable for diagnosing and managing HFpEF in the future.
BackgroundThyroid eye disease (TED), particularly its sight‐threatening complication, dysthyroid optic neuropathy (DON), profoundly impacts patients' visual health. The pathological changes in the white matter (WM) fibers within the intracranial visual pathway in TED have been infrequently studied. Understanding these changes holds crucial importance for exploring the pathogenesis and prognosis of TED.PurposeTo utilize fixel‐based analysis (FBA) to clarify the type of microstructural damage occurring in the visual pathway in TED.Study TypeProspective.Subjects28 TED with DON patients (11 males and 17 females), 28 TED without DON (non‐DON) patients (12 males and 16 females), and 28 healthy controls (HCs) (12 males and 16 females).Field Strength/Sequence3 T; multishell diffusion MRI using echo planar imaging.AssessmentFiber density (FD) and fiber‐bundle cross‐section (FC) were calculated to characterize WM microstructural alteration in TED visual pathway. The correlations between FBA metrics and visual field index and mean deviation were examined.Statistical TestsOne‐way analysis of variance, Kruskal–Wallis, t‐tests, Mann–Whitney U, Chi‐square, and Pearson correlation, were conducted with false discovery rate and family wise error corrections. Significance was set at P < 0.05.ResultsBoth DON and non‐DON groups showed significant FD loss in the right optic tract compared with HCs, with DON patients experiencing more severe FD loss. Only DON patients had FD loss in the right optic radiation (OR) compared with the non‐DON patients and HCs, with no FC difference across groups. FD in DON patients' ORs significantly correlated with visual field index (r = 0.857) and mean deviation (r = 0.751).Data ConclusionBoth DON and non‐DON affect the WM microstructure of the visual pathway to varying extents. Visual field metrics can reflect the severity of FD damage to the OR in the visual pathway of DON patients.Evidence Level2.Technical EfficacyStage 3.
Background Radiomics analysis of orbital magnetic resonance imaging (MRI) shows preliminary potential for intravenous glucocorticoid (IVGC) response prediction of thyroid eye disease (TED). The current region of interest segmentation contains only a single organ as extraocular muscles (EOMs). It would be of great value to consider all orbital soft tissues and construct a better prediction model. Methods In this retrospective study, we enrolled 127 patients with TED that received 4·5 g IVGC therapy and had complete follow-up examinations. Pre-treatment orbital T2-weighted imaging (T2WI) was acquired for all subjects. Using multi-organ segmentation (MOS) strategy, we contoured the EOMs, lacrimal gland (LG), orbital fat (OF), and optic nerve (ON), respectively. By fused-organ segmentation (FOS), we contoured the aforementioned structures as a cohesive unit. Whole-orbit radiomics (WOR) models consisting of a multi-regional radiomics (MRR) model and a fused-regional radiomics (FRR) model were further constructed using six machine learning (ML) algorithms. Results The support vector machine (SVM) classifier had the best performance on the MRR model (AUC = 0·961). The MRR model outperformed the single-regional radiomics (SRR) models (highest AUC = 0·766, XGBoost on EOMs, or LR on OF) and conventional semiquantitative imaging model (highest AUC = 0·760, NaiveBayes). The application of different ML algorithms for the comparison between the MRR model and the FRR model (highest AUC = 0·916, LR) led to different conclusions. Conclusions The WOR models achieved a satisfactory result in IVGC response prediction of TED. It would be beneficial to include more orbital structures and implement ML algorithms while constructing radiomics models. The selection of separate or overall segmentation of orbital soft tissues has not yet attained its final optimal result.
PurposeWe aimed to evaluate the spontaneous neuronal activity and functional connectivity pattern variations using resting-state functional magnetic resonance imaging (rs-fMRI) measures, such as amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and functional connectivity (FC), in patients with thyroid-associated ophthalmopathy (TAO). MethodA total of 24 active TAO patients, 26 inactive TAO patients, and 27 matched healthy controls (HCs) were included. First, ALFF and fALFF were used to detect local neural activity changes, the MRI data were analyzed, and regions with group differences were taken as seeds. Second, FC analysis was performed to explore the altered connection between seeds and other brain regions. A correlation analysis was performed to assess the relationship between functional brain activity and clinical indices and neuropsychiatric behaviors. ResultsCompared to HCs, both active and inactive TAO patients exhibited significantly lower ALFF values in the right calcarine (Calcarine_R) and left postcentral gyrus (Postcentral_L). Active TAO patients also showed significantly higher ALFF values in the left caudate nucleus (Caudate_L) and increased fALFF values in the superior lobe of the right cerebellum (Cerebelum_Crus1_R). Moreover, both active and inactive TAO patients demonstrated decreased FC within the left postcentral gyrus (Postcentral_L) compared to HCs. Additionally, active TAO patients exhibited lower FC compared to inactive TAO patients. The ALFF values in the Calcarine_R of active TAO patients positively correlated with disease duration (r = 0.5892, p = 0.0049) and the Hamilton Anxiety Rating Scale (HARS; r = 0.5377, p = 0.0119). Furthermore, the ALFF value in the Calcarine_R of inactive TAO patients negatively correlated with visual functioning (r = -0.5449, p = 0.0072), while the ALFF values in the Caudate_L of active TAO patients positively correlated with visual functioning (r = 0.6496, p = 0.0014). ConclusionWe found that the Caudate_L and Cerebelum_Crus1_R related to motor control and coordination in active TAO patients exhibit significant compensatory mechanisms; whereas, the Calcarine_R and Postcentral_L related to visual and somatosensory cortices show varying degrees of impairment. Our findings complement the functional neural mechanism of TAO.
Thyroid eye disease (TED) is a complex autoimmune disorder that impairs various orbital structures, leading to cosmetic damage and vision loss. Magnetic resonance imaging (MRI) is a fundamental diagnostic tool utilized in clinical settings of TED, for its accurate demonstration of orbital lesions and indication of disease conditions. The application of quantitative MRI has brought a new prospect to the management and research of TED, offering more detailed information on morphological and functional changes in the orbit. Therefore, many researchers concentrated on the implementation of different quantitative MRI techniques on TED for the exploration of clinical practices. Despite the abundance of studies utilizing quantitative MRI in TED, there remain considerable barriers and disputes on the best exploitation of this tool. This could possibly be attributed to the complexity of TED and the fast development of MRI techniques. It is necessary that clinical and radiological aspects of quantitative MRI in TED be better integrated into comprehensive insights. Hence, this review traces back 30 years of publications regarding quantitative MRI utilized in TED and elucidates this promising application in the facets of imaging techniques and clinical practices. We believe that a deeper understanding of the application of quantitative MRI in TED will enhance the efficacy of the multidisciplinary management of TED. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.
Abstract The accumulation of foam cells in arterial intima and the accompanied chronic inflammation are considered major causes of neoatherosclerosis and restenosis. However, both the underlying mechanism and effective treatment for the disease are yet to be uncovered. In this study, we combined transcriptome profiling of restenosis artery tissue and bioinformatic analysis to reveal that NLRP3 inflammasome is markedly upregulated in restenosis and that several restenosis‐related DEGs are also targets of mulberry extract, a natural dietary supplement used in traditional Chinese medicine. We demonstrated that mulberry extract suppresses the formation of ox‐LDL‐induced foam cells, possibly by upregulating the cholesterol efflux genes ABCA1 and ABCG1 to inhibit intracellular lipid accumulation. In addition, mulberry extract dampens NLRP3 inflammasome activation by stressing the MAPK signaling pathway. These findings unveil the therapeutic value of mulberry extract in neoatherosclerosis and restenosis treatment by regulating lipid metabolism and inflammatory response of foam cells.
Objectives To investigate the pathological interplay between immunity and the visual processing system (VPS) in thyroid eye disease (TED). Methods A total of 24 active patients (AP), 26 inactive patients (IP) of TED, and 27 healthy controls (HCs) were enrolled. Orbital magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were conducted for each participant. Multiple MRI parameters of the intraorbital optic nerve (ON) were assessed. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated. Correlation analyses were carried out on the above parameters and clinical characteristics. Results Visual functioning scores differentiated between the AP and IP groups. The ON subarachnoid space and ON sheath diameter were significantly higher in AP than in IP. Six vision-related brain regions were identified in TED patients compared with HCs, including right calcarine (CAL.R), right cuneus (CUN.R), left postcentral gyrus (PoCG.L), right middle temporal gyrus (MTG.R), left superior frontal gyrus (SFG.L), and left caudate (CAU.L). The brain activity of MTG.R, SFG.L, and CAU.L differentiated between the AP and IP groups. The correlation analysis revealed a close association among the vision-related brain regions, MRI parameters of ON, and clinical characteristics in AP and IP, respectively. Conclusions Combined orbital and brain neuroimaging revealed abnormalities of the VPS in TED, which had a close correlation with immune statuses. Vision-related brain regions in TED might be possibly altered by peripheral immunity via a direct or indirect approach. Clinical relevance statement The discovery of this study explained the disparity of visual dysfunction in TED patients with different immune statuses. With the uncovered neuroimaging markers, early detection and intervention of visual dysfunction could be achieved and potentially benefit TED patients. Key Points • Patients with different immune statuses of thyroid eye disease varied in the presentation of visual dysfunction. • The combined orbital and brain neuroimaging study identified six altered vision-related brain regions, which had a significant correlation with the MRI parameters of the intraorbital optic nerve and immunological characteristics. • Peripheral immunity might possibly give rise to alterations in the central nervous system part of the visual processing system via a direct or indirect approach.
Neutrophil extracellular traps (NETs) play an important role in abdominal aortic aneurysm (AAA) formation; however, the underlying molecular mechanisms remain unclear. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may exert therapeutic effects on AAA through their immunomodulatory and regenerative abilities. This study aimed to examine the role and mechanism of MSC-EVs in regulating the development of NET-mediated AAA. Excessive release of NETs was observed in patients with AAA, and the levels of NET components were associated with the clinical outcomes of the patients. Datasets from the Gene Expression Omnibus database were analyzed and revealed that the PI3K/AKT pathway and ferroptosis were strongly associated with NETosis during AAA formation. Further experiments verified that NETs promoted AAA formation by inducing ferroptosis in smooth muscle cells (SMCs) by inhibiting the PI3K/AKT pathway. The PI3K agonist 740 Y-P, the ferroptosis inhibitor ferrostatin-1, and Padi4 deficiency significantly prevented AAA formation. MSC-EVs attenuated AAA formation by reducing NET release in an angiotensin II-induced AAA mouse model. In vitro experiments revealed that MSC-EVs reduced the release of NETs by shifting NETosis to apoptosis. Our study indicates an important role for NET-induced SMC ferroptosis in AAA formation and provides several potential targets for AAA treatment.
Myeloid-derived suppressor cells (MDSCs) occupy a pivotal role in the intricate pathogenesis of the autoimmune disorder, Type 1 diabetes mellitus (T1DM). Since our previous work demonstrated that trichosanthin (TCS), an active compound of Chinese herb medicine Tian Hua Fen, regulated immune response, we aimed to clarify the efficacy and molecular mechanism of TCS in the treatment of T1DM. To this end, T1DM mouse model was established by streptozotocin (STZ) induction. The mice were randomly divided into normal control group (Ctl), T1DM group (STZ), TCS treated diabetic group (STZ + TCS) and insulin-treated diabetic group (STZ + insulin). Our comprehensive evaluation encompassed variables such as blood glucose, glycosylated hemoglobin, body weight, pertinent biochemical markers, pancreatic histopathology, and the distribution of immune cell populations. Furthermore, we meticulously isolated MDSCs from the bone marrow of T1DM mice, probing into the expressions of genes pertaining to the advanced glycation end product receptor (RAGE)/NF-κB signaling pathway through RT-qPCR. Evidently, TCS exhibited a substantial capacity to effectively counteract the T1DM-induced elevation in random blood glucose, glycosylated hemoglobin, and IL-6 levels in plasma. Pathological scrutiny underscored the ability of TCS to mitigate the damage incurred by islets. Intriguingly, TCS interventions engendered a reduction in the proportion of MDSCs within the bone marrow, particularly within the IL-6+ MDSC subset. In contrast, IL-10+ MDSCs exhibited an elevation following TCS treatment. Moreover, we observed a significant down-regulation of relative mRNA of pro-inflammatory genes, including arginase 1 (Arg1), inducible nitric oxide synthase (iNOS), RAGE and NF-κB, within MDSCs due to the influence of TCS. It decreases total MDSCs and regulates the balance between IL-6+ and IL-10+ MDSCs thus alleviating the symptoms of T1DM. TCS also down-regulates the RAGE/NF-κB signaling pathway, making it a promising alternative therapeutic treatment for T1DM. Collectively, our study offered novel insights into the underlying mechanism by which TCS serves as a promising therapeutic intervention for T1DM.
To explore radiological changes of the lacrimal gland (LG) in Graves' ophthalmopathy (GO) and whether a combination of MRI parameters and clinical indicators would be more effective in predicting individual clinical manifestation of GO compared to clinical activity scores (CAS) assessment.A total of 28 patients with GO (56 eyes) and 14 healthy controls (HCs) (28 eyes) were enrolled between July 2020 and July 2021. Patients were classified into the active GO group (CAS ≥ 3) and the inactive GO group (CAS < 3). MRI data and clinical data of LG were collected. The diagnostic performance of MRI parameters and models was assessed by receiver operating characteristic curve analysis. Logistic regression predictive models for staging GO were compared.LG in GO groups had significantly higher Ktrans, Ve, IAUC, ADC, and T2-mapping values (p = 0.006, p < 0.001, p < 0.001, p = 0.048, and p = 0.001, respectively), and significant lower Kep and Vp values (p < 0.001 and p < 0.001 respectively). There were statistically significant differences in T2-mapping value (p < 0.001), the proportion of mild or no obvious redness of conjunctiva (p < 0.001), and the proportion of swelling of caruncle or plica (p < 0.001) between inactive and active groups. In MRI based logistic regression model, the T2-mapping value was an independent risk factor (AUC = 0.832). When combining MRI and clinical indicators, T2-mapping value and age resulted in independent risk factors (AUC = 0.928). Swelling of eyelids, redness of the conjunctiva, swelling of the conjunctiva, swelling of caruncle or plica, and spontaneous retrobulbar pain could be replaced by other objective indicators (AUC = 0.937, 0.852, 0.876, 0.896, and 0.891, respectively).There were significant differences in MRI quantitative parameters of LG between HCs and GO patients. The combination of the T2-mapping value of LG and clinical indicators improved the stage prediction of Graves' ophthalmopathy compared to CAS, thus providing a new idea for enhancing the objectification level of GO data collection.
Background Various studies have highlighted the role of circular RNAs (circRNAs) as critical molecular regulators in cardiovascular diseases, but its role in abdominal aortic aneurysm (AAA) is unclear. This study explores the potential molecular mechanisms of AAA based on the circRNA-microRNA (miRNA)-mRNA competing endogenous RNA (ceRNA) network and immune cell infiltration patterns. Methods The expression profiles of circRNAs (GSE144431) and mRNAs (GSE57691 and GSE47472) were obtained from the Gene Expression Omnibus (GEO). Then, the differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) between AAA patients and healthy control samples, and the target miRNAs of these DEmRNAs and DEcircRNAs were identified. Based on the miRNA-DEmRNAs and miRNA-DEcircRNAs pairs, the ceRNA network was constructed. Furthermore, the proportion of the 22 immune cell types in AAA patients was assessed using cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. The expressions of key genes and immune cell infiltration were validated using clinical specimens. Results A total of 214 DEmRNAs were identified in the GSE57691 and GSE47472 datasets, and 517 DEcircRNAs were identified in the GSE144431 dataset. The ceRNA network included 19 circRNAs, 36 mRNAs, and 68 miRNAs. Two key genes, PPARG and FOXO1, were identified among the hub genes of the established protein-protein interaction between mRNAs in the ceRNA network. Moreover, seven types of immune cells were differentially expressed between AAA patients and healthy control samples. Hub genes in ceRNA, such as FOXO1, HSPA8, and RAB5C, positively correlated with resting CD4 memory T cells or M1 macrophages, or both. Conclusion In conclusion, a ceRNA interaction axis was constructed. The composition of infiltrating immune cells was analyzed in the abdominal aorta of AAA patients and healthy control samples. This may help identify potential therapeutic targets for AAA.
Background: Heart failure is a serious complication resulting from left ventricular remodeling (LVR), especially in patients experiencing acute anterior myocardial infarction (AAMI). It is crucial to explore the predictive parameters for LVR following primary percutaneous coronary intervention (PPCI) in patients with AAMI. Methods: A total of 128 AAMI patients who were reperfused successfully by PPCI were enrolled sequentially from June 2018 to December 2019. Cardiovascular magnetic resonance (CMR) was performed at the early stage (<7 days) and after the 6-month follow-up. The patients were divided into LVR and non-LVR groups according to the increase of left ventricular end diastolic volume (LVEDV) measured by the second cardiac magnetic resonance examination ≥20% from baseline. (3) Results: The left ventricular ejection fraction (LVEF), the global longitudinal strain (GLS), the peak circumferential strain in infarcted segments, and the infarct size (IS) remained significantly different in the multivariate logistic regression analysis (all p < 0.05). The area under the receiver operating characteristic curve of Model 1, wherein the GLS was added to the LVEF, was 0.832 (95% CI 0.758–0.907, p < 0.001). The C-statistics for Model 2, which included the infarct-related regional parameters (IS and the peak circumferential strain in infarcted segments)was 0.917 (95% CI 0.870–0.965, p < 0.001). Model 2 was statistically superior to Model 1 in predicting LVR (IDI: 0.190, p = 0.002). (4) Conclusions: Both the global and regional CMR parameters were valuable in predicting LVR in patients with AAMI following the PPCI. The local parameters of the infarct zones were superior to those of the global ones.