Changes in subclinical cardiac abnormalities 1 Year after recovering from COVID-19 in patients without clinical cardiac findings.

Aim: To evaluate the subclinical cardiac involvement in COVID-19 patients without clinical cardiac evidence using cardiac MR imaging. Material and methods: Participants recovered from COVID-19 without cardiac symptoms and no cardiovascular medical history were enrolled in a prospective cohort study. They underwent baseline cardiac MR and follow-up cardiac MR > 300 days after discharge (n = 20). The study also included healthy controls (n = 20). Extracellular volume fraction (ECV), native T1, and 2D strain data were assessed and compared. Results: The ECV values of participants at baseline [30.0% (28.3%-32.5%)] and at follow-up [31.0% (28.0%-32.8%)] were increased compared to the healthy control group [27.0% (25.3%-28.0%)] (both p < 0.001). However, the ECV increase from baseline cardiac MR to follow-up cardiac MR was not significant (p = 0.378). There was a statistically significant difference in global native T1 between baseline [1140 (1108.3-1192.0) ms] and follow-up [1176.0 (1113.0-1206.3) ms] (p = 0.016). However, no native T1 difference was found between the healthy controls [1160.7 (1119.6-1195.4) ms] and the baseline (p = 0.394) or follow-up group (p = 0.168). The global T2 was 41(40-42) ms at follow-up which was within the normal range. In addition, We found a recovery in 2D GLS among COVID-19 participants between baseline and follow-up [-12.4(-11.7 to -14.3)% vs. -17.2(-16.2 to -18.3)%; p＜0.001]. Conclusion: Using cardiac MR myocardial tissue and strain imaging parameters, 35% of people without cardiac symptoms or clinical evidence of myocardial injury still had subclinical myocardial tissue characteristic abnormalities at 300 days, but 2D GLS had recovered.

Early detection of myocardial involvement by non-contrast T1ρ mapping of cardiac magnetic resonance in type 2 diabetes mellitus.

Objective: This study aims to determine the effectiveness of T1ρ in detecting myocardial fibrosis in type 2 diabetes mellitus (T2DM) patients by comparing with native T1 and extracellular volume (ECV) fraction. Methods: T2DM patients (n = 35) and healthy controls (n = 30) underwent cardiac magnetic resonance. ECV, T1ρ, native T1, and global longitudinal strain (GLS) values were assessed. Diagnostic performance was analyzed using receiver operating curves. Results: The global ECV and T1ρ of T2DM group (ECV = 32.1 ± 3.2%, T1ρ = 51.6 ± 3.8 msec) were significantly higher than those of controls (ECV = 26.2 ± 1.6%, T1ρ = 46.8 ± 2.0 msec) (all P < 0.001), whether there was no significant difference in native T1 between T2DM and controls (P = 0.264). The GLS decreased significantly in T2DM patients compared with controls (-16.5 ± 2.4% vs. -18.3 ± 2.6%, P = 0.015). The T1ρ and native T1 were associated with ECV (Pearson's r = 0.50 and 0.25, respectively, both P < 0.001); the native T1, T1ρ, and ECV were associated with hemoglobin A1c (Pearson's r = 0.41, 0.52, and 0.61, respectively, all P < 0.05); and the ECV was associated with diabetes duration (Pearson's r = 0.41, P = 0.016). The AUC of ECV, T1ρ, GLS, and native T1 were 0.869, 0.810, 0.659, and 0.524, respectively. Conclusion: In T2DM patients, T1ρ may be a new non-contrast cardiac magnetic resonance technique for identifying myocardial diffuse fibrosis, and T1ρ may be more sensitive than native T1 in the detection of myocardial diffuse fibrosis.

Inhibition of the P2X7 receptor prevents atrial proarrhythmic remodeling in experimental post-operative atrial fibrillation.

BACKGROUND: Post-operative atrial fibrillation (POAF) is a common complication in patients undergoing cardiac surgery. The purinergic receptor P2X7 (P2X7R) is involved in some cardiovascular diseases, whereas its effects on atrial fibrillation (AF) are unclear. OBJECTIVE: This study was to assess the effect of P2X7R on atrial arrhythmogenic remodeling in the rat model of sterile pericarditis (SP). METHODS: Male Sprague-Dawley (SD) rats were used to induce the SP model. Electrocardiogram, atrial electrophysiological protocol, histology, mRNA sequencing, real-time quantitative PCR, western blot, and Elisa assay were performed. RESULTS: SP significantly up-regulated P2X7R expression; increased AF susceptibility; reduced the protein expression of ion channels including Nav1.5, Cav1.2, Kv4.2, Kv4.3, and Kv1.5; caused atrial fibrosis; increased norepinephrine (NE) level in plasma; promoted the production of inflammatory cytokines such as TNF-α, IL-1ß, and IL-6; increased the accumulation of immune cells (CD68- and MPO- positive cells); and activated NLRP3 inflammasome signaling pathway. P2X7R antagonist Brilliant Blue G (BBG) mitigated SP-induced alterations. The mRNA sequencing demonstrated that BBG prevented POAF mainly by regulating the immune system. In addition, another selective P2X7R antagonist A740003, and IL-1R antagonist anakinra also reduced AF inducibility in the SP model. CONCLUSIONS: P2X7R inhibition prevents SP-induced atrial proarrhythmic remodeling, which is closely associated with the improvement of inflammatory changes, ion channel expression, atrial fibrosis, and sympathetic activation. The findings point to P2X7R inhibition as a promising target for AF (particularly POAF) and perhaps other conditions.

Cardiac T1ρ Mapping Values Affected by Age and Sex in a Healthy Chinese Cohort.

BACKGROUND: To facilitate the clinical use of cardiac T1ρ, it is important to understand the impact of age and sex on T1ρ values of the myocardium. PURPOSE: To investigate the impact of age and gender on myocardial T1ρ values. STUDY TYPE: Cross-sectional. POPULATION: Two hundred ten healthy Han Chinese volunteers without cardiovascular risk factors (85 males, mean age 34.4 ± 12.5 years; 125 females, mean age 37.9 ± 14.8 years). FIELD STRENGTH/SEQUENCE: 1.5 T; T1ρ-prepared steady-state free precession (T1ρ mapping) sequence. ASSESSMENT: Basal, mid, and apical short-axis left ventricular T1ρ maps were acquired. T1ρ maps acquired with spin-lock frequencies of 5 and 400 Hz were subtracted to create a myocardial fibrosis index (mFI) map. T1ρ and mFI values across different age decades, sex, and slice locations were compared. STATISTICAL TESTS: Shapiro-Wilk test, Student's t test, Mann-Whitney U test, linear regression analysis, one-way analysis of variance and intraclass correlation coefficient. SIGNIFICANCE: P value <0.05. RESULTS: Women had significantly higher T1ρ and mFI values than men (50.3 ± 2.0 msec vs. 47.7 ± 2.4 msec and 4.7 ± 1.0 msec vs. 4.3 ± 1.1 msec, respectively). Additionally, in males and females combined, there was a significant positive but weak correlation between T1ρ values and age (r = 0.27), while no correlation was observed between the mFI values and age (P = 0.969). DATA CONCLUSION: We report potential reference values for cardiac T1ρ by sex, age distribution, and slice location in a Chinese population. T1ρ was significantly correlated with age and sex, while mFI was only associated with sex. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

P2X7 receptor inhibition prevents atrial fibrillation in rodent models of depression.

AIMS: Depression, the most prevalent psychiatric disorder, is associated with the occurrence and development of atrial fibrillation (AF). P2X7 receptor (P2X7R) activation participates in the development of depression, but little attention has been given to its role in AF. This study was to investigate the effects of P2X7R on AF in depression models. METHODS AND RESULTS: Lipopolysaccharide (LPS) and chronic unpredictable stress (CUS) were carried out to induce depression in rodents. Behavioural assessments, atrial electrophysiological parameters, electrocardiogram (ECG) parameters, western blot, and histology were performed. Atrial fibrillation inducibility was increased in both LPS- and CUS-induced depression, along with the up-regulation of P2X7R in atria. CUS facilitated atrial fibrosis. CUS reduced heart rate variability (HRV) and increased the expression of TH and GAP43, representing autonomic dysfunction. Down-regulation of Nav1.5, Cav1.2, Kv1.5, Kv4.3, Cx40, and Cx43 in CUS indicated the abnormalities in ion channels. In addition, the expression levels of TLR4, P65, P-P65, NLRP3, ASC, caspase-1, and IL-1ß were elevated in depression models. Pharmacological inhibitor (Brilliant Blue G, BBG) or genetic deficiency of P2X7R significantly mitigated depressive-like behaviours; ameliorated electrophysiological deterioration and autonomic dysfunction; improved ion channel expression and atrial fibrosis; and prevented atrial NLRP3 inflammasome activation in the pathophysiological process of AF in depression models. CONCLUSION: LPS or CUS induces AF and promotes P2X7R-dependent activation of NLRP3 inflammasome, whereas pharmacological P2X7R inhibition or P2X7R genetic deficiency prevents atrial remodelling without interrupting normal atrial physiological functions. Our results point to P2X7R as an important factor in the pathology of AF in depression.

TRPV2 inhibitor tranilast prevents atrial fibrillation in rat models of pulmonary hypertension.

Atrial fibrillation (AF) is common in pulmonary hypertension (PH), whereas the mechanisms and treatments remain to be explored. TRPV2 regulates the structure and function of the cardiovascular system; however, little attention has been given to its role in AF. This study was to determine whether TRPV2 was involved in PH-induced AF and the effects of TRPV2 inhibitor tranilast on AF in rat models of PH. Monocrotaline (MCT) and SU5416/hypoxia (SuHx)-induced PH models were performed to detect atrial electrophysiological parameters. Daily tranilast (a TRPV2 inhibitor) or saline was given starting 1 day before PH establishment. PH increased the susceptibility to AF, with TRPV2 up-regulated in the right atria. Compared to PH rats, tranilast reduced AF inducibility and the prolongations of ERP and APD; mitigated cardiopulmonary remodeling and the increases in P-wave duration and P-R interval; partially reversed the down-regulation of ion channels such as Cav1.2, Nav1.5, Kv4.3, Kv4.2, Kv1.5, Kir2.1, Kir3.1, Kir3.4 as well as connexin (Cx) 40 and Cx43; improved right atrial (RA) fibrosis, enlargement, and myocardial hypertrophy; decreased the accumulation of inflammatory cells; down-regulated inflammatory indicators such as TNF-α, IL-1ß, CXCL1, and CXCL2; and inhibited the activation of the PI3K-AKT-NF-κB signaling pathway. Our results reveal that TRPV2 participates in PH-induced AF, and TRPV2 inhibitor tranilast prevents PH-induced RA remodeling. TRPV2 might be a promising target for PH-induced AF.

TFRC in cardiomyocytes promotes macrophage infiltration and activation during the process of heart failure through regulating Ccl2 expression mediated by hypoxia inducible factor-1α.

BACKGROUND: Cardiac hypertrophy is an initiating link to Heart failure (HF) which still seriously endangers human health. Transferrin receptor (TFRC), which promotes iron uptake through the transferrin cycle, is essential for cardiac function. However, whether TFRC is involved in the process of pathological cardiac hypertrophy is not clear. METHODS: Transverse aortic constriction (TAC) mouse model and mice primary cardiomyocytes treated with isoproterenol (ISO) or phenylephrine (PHE) were used to mimic cardiac hypertrophy in vivo and in vitro. Single cell RNA sequence data from heart tissues of TAC-model mice was obtained from the Gene Expression Omnibus (GEO) database, and was analyzed with R package Seurat. TFRC expression and macrophage infiltration in the heart tissue were tested by immunofluorescent staining. Macrophage polarization was detected by Flow Cytometry. TFRC expressions were detected by qRT-PCR, Western blot, and ELISA. RESULTS: TFRC expression is increased in the pathological cardiac hypertrophy of mice model and positively associated with macrophage infiltration. Furthermore, TFRC in cardiomyocytes recruits and activates macrophages by secreting C-C motif ligand 2 (Ccl2) in the mice heart tissue with TAC surgery or in the primary cardiomyocytes stimulated with ISO or PHE to induce myocardial hypertrophy in vitro. Moreover, we find that TFRC promotes Ccl2 expression in cardiomyocytes via regulating signal transducer and activator of transcription 3 (STAT3). In addition, we find that increased TFRC expression in the HF tissue is regulated by hypoxia-inducible factor-1α (HIF-1α). CONCLUSION: This in-depth study shows that TFRC in cardiomyocytes promotes HF development through inducing macrophage infiltration and activation via the STAT3-Ccl2 signaling, and TFRC expression in cardiomyocytes is regulated by HIF-1α during HF. This study first uncovers the role of TFRC in cardiomyocytes on macrophage infiltration and activation during HF.

Association between the TAPSE to PASP ratio and short-term outcome in patients with light-chain cardiac amyloidosis.

BACKGROUND: Amyloid light-chain cardiac amyloidosis (AL-CA) patients experiencing RV failure have a poorer prognosis. The echocardiographic ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) serves as a non-invasive proxy for evaluating the coupling between the right ventricle (RV) and pulmonary circulation. The aim of this study was to assess the association between the TAPSE/PASP ratio and short-term outcome in patients with AL-CA. METHODS: Seventy-one patients diagnosed with AL-CA were enrolled in this retrospective cohort study.Short-term outcome was defined as 6-month all-cause mortality. Receiver operating characteristic (ROC), logistic regression, and Kaplan-Meier analysis were used in this study. RESULTS: Among seventy-one patients with AL-CA (mean age, 62 ± 8 years, 69% male), 17 (24%) died within the first 6 months (mean follow-up period 55 ± 48 days). Linear regression analysis indicated that the TAPSE/PASP ratio was correlated with RV global longitudinal strain (r = -0.655, p < 0.001), RV free wall thickness (r = -0.599, p < 0.001), and left atrial reservoir strain (r = 0.770, p < 0.001). The time-dependent ROC and the area under the curve (AUC) showed that the TAPSE/PASP ratio was a better predictor (AUC = 0.798; 95% confidence interval (CI): 0.677-0.929) of short-term outcome than TAPSE (AUC = 0.734; 95% CI: 0.585-0.882) and PASP (AUC: 0.730; 95% CI: 0.587-0.874). Multivariate logistic regression showed that patients with the worse TAPSE/PASP (< 0.47 mm/mmHg) and lower systolic blood pressure (< 100 mmHg) had the highest risk of dying. CONCLUSIONS: The TAPSE/PASP ratio is associated with the short-term outcome of patients with AL-CA. The combination of TAPSE/PASP ratio < 0.474 mmHg and SBP < 100 mmHg could identify the subgroup of patients with AL-CA at elevated risk of poor prognosis.

Gelatin methacryloyl (GelMA) loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells(ADSCs) conditioned medium promotes wound healing and vascular regeneration in aged skin.

BACKGROUND: Aging skin is characterized by a disturbed structure and lack of blood supply, which makes it difficult to heal once injured. ADSCs secrete large amounts of cytokines, which promote wound healing and vascular regeneration through paracrine secretion, and the number of cytokines can be elevated by hypoxic pretreating. However, the components of ADSCs are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel synthesized from gelatin and has recently emerged as a potentially attractive material for tissue engineering applications. GelMA loaded with concentrated hypoxic pretreated ADSCs conditioned medium could provide a new method of treating wounds in aged skin. METHODS: Primary ADSCs were isolated from human adipose tissue and characterized by flow cytometry and differentiation test. ADSCs in passages 4-6 were pretreated in the hypoxic and normoxic environments to collect conditioned medium, the conditioned medium was then concentrated to prepare concentrated ADSCs conditioned medium(cADSC-CM)(the one collected from ADSCs under hypoxia was called hypo-CM ,and the one from normoxia was called nor-CM). The concentration of cytokines was detected. After treated with cADSC-CM, the abilities of proliferation, migration, and tube formation of human umbilical vascular endothelial cells (HUVECs) were assayed, and Akt/mTOR and MAPK signal pathway was detected using western blotting. GelMA+hypo-CM hydrogel was prepared, and a comprehensive evaluation of morphology, protein release efficiency, degradation rate, mechanical properties, and rheology properties were performed. Full-thickness skin wounds were created on the backs of 20-month-old mice. After surgery, GelMA, GelMA+F12, GelMA+hypo-CM, and GelMA+nor-CM were applied to the wound surface respectively. H&E, Masson, and immunohistochemistry staining were performed, and a laser Doppler perfusion imager was used to evaluate the blood perfusion. The student's t-test was used for analysis between two groups and a one-way analysis of variance (ANOVA) was used for analysis among multi groups. RESULTS: Our results revealed that 1) wounds in aged skin healed more slowly than that in young skin and exhibited poorer perfusion; 2) hypoxic pretreated ADSCs secreted more cytokines including VEGF by activating HIF1α; 3) hypo-CM promoted proliferation and migration of HUVECs through VEGF/Akt/mTOR and MAPK signal pathway; 4) GelMA-hypoCM accelerated wound healing and angiogenesis in aged skin in vivo. CONCLUSION: GelMA loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells conditioned medium could accelerate wound healing in aged skin by promoting angiogenesis.

Left ventricular myocardial work index and short-term prognosis in patients with light-chain cardiac amyloidosis: a retrospective cohort study.

Background: Reports show that the left ventricular myocardial work index (LVMWI) is a novel parameter for evaluating cardiac function. Decompensated heart failure leads to a high rate of early mortality in advanced patients with light-chain cardiac amyloidosis (AL-CA) and prevents them from a relatively delayed response to chemotherapy. This study aimed to assess the association of the LVMWI with short-term outcomes and to construct a simple model for risk stratification. Methods: A total of 79 patients with an initial diagnosis of AL-CA were included in this retrospective cohort study. LVMWI was calculated by integrating brachial artery cuff blood pressure and left ventricular longitudinal strain (LVLS). The short-term outcome was defined as 6-month all-cause mortality. Receiver operating characteristic (ROC), logistic regression, and Kaplan-Meier analysis were used in this study. Results: The median follow-up time was 21 months (3-36 months), and 23 (29%) patients died in the first 6 months. The time-dependent ROC and the area under the curve (AUC) showed that the LVMWI had the best predictive potential at the 6-month time point [AUC =0.805; 95% confidence interval (CI): 0.690-0.920]. A bivariate prognostic model based on the LVMWI was constructed, and D-dimer showed a synergistic effect with optimum predicted potential (AUC =0.877; 95% CI: 0.791-0.964). Kaplan-Meier analysis demonstrated that patients with two, one, and none of the variates beyond the cut-off value bore a different risk of 6-month all-cause mortality (accumulated mortality was 86%, 30%, 3%, respectively; log-rank, P<0.001). Multivariate nested logistic regression showed that the level of D-dimer provided an incremental prognostic value (Δχ2=10.3; P=0.001) to the value determined from New York Heart Association (NYHA) classification and the LVMWI. Conclusions: The LVMWI is associated with the short-term outcome of patients with AL-CA. The D-dimer test provides additional prognostic information for the LVMWI.

Adipose-Derived Mesenchymal Stem Cells Alleviate Hypertrophic Scar by Inhibiting Bioactivity and Inducing Apoptosis in Hypertrophic Scar Fibroblasts.

Background: As a fibrotic disease with a high incidence, the pathogenesis of hypertrophic scarring is still not fully understood, and the treatment of this disease is also challenging. In recent years, human adipose-derived mesenchymal stem cells (AD-MSCs) have been considered an effective treatment for hypertrophic scars. This study mainly explored whether the therapeutic effect of AD-MSCs on hypertrophic scars is associated with oxidative-stress-related proteins. Methods: AD-MSCs were isolated from adipose tissues and characterized through flow cytometry and a differentiation test. Afterwards, coculture, cell proliferation, apoptosis, and migration were detected. Western blotting and a quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect oxidative stress-related genes and protein expression in hypertrophic scar fibroblasts (HSFs). Flow cytometry was used to detect reactive oxygen species (ROS). A nude mouse animal model was established; the effect of AD-MSCs on hypertrophic scars was observed; and hematoxylin and eosin staining, Masson's staining, and immunofluorescence staining were performed. Furthermore, the content of oxidative-stress-related proteins, including nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), B-cell lymphoma 2(Bcl2), Bcl2-associated X(BAX) and caspase 3, was detected. Results: Our results showed that AD-MSCs inhibited HSFs' proliferation and migration and promoted apoptosis. Moreover, after coculture, the expression of antioxidant enzymes, including HO-1, in HSFs decreased; the content of reactive oxygen species increased; and the expression of Nrf2 decreased significantly. In animal experiments, we found that, at 14 days after injection of AD-MSCs into human hypertrophic scar tissue blocks that were transplanted onto the dorsum of nude mice, the weight of the tissue blocks decreased significantly. Hematoxylin and eosin staining and Masson's staining demonstrated a rearrangement of collagen fibers. We also found that Nrf2 and antioxidant enzymes decreased significantly, while apoptotic cells increased after AD-MSC treatment. Conclusions: Our results demonstrated that AD-MSCs efficiently cured hypertrophic scars by promoting the apoptosis of HSFs and by inhibiting their proliferation and migration, which may be related to the inhibition of Nrf2 expression in HSFs, suggesting that AD-MSCs may provide an alternative therapeutic approach for the treatment of hypertrophic scars.

Impact of perception reduction of employment opportunities on employment pressure of college students under COVID-19 epidemic-joint moderating effects of employment policy support and job-searching self-efficacy.

Based on the stress interaction theory, this research constructed a model to study the joint moderating effects of the perception reduction of employment opportunities under the COVID-19 epidemic on the employment pressure of college students. With two moderating variables introduced, employment policy support and job-searching self-efficacy, this research studied the mechanism and boundary conditions of perception reduction of employment opportunities on employment pressure of college students from both individual and environmental aspects. The study found that during the epidemic if college students perceived fewer employment opportunities, they could have greater employment pressure from themselves, schools, and families; and that under the joint moderation of employment policy support and job-searching self-efficacy, the perception reduction of employment opportunities under the COVID-19 epidemic, the employment pressure of college students, universities, and families were connected, with different adjustment mechanisms. Based on empirical data, this research can provide theoretical enlightenment and practical guidance for the government, universities, and families to alleviate the employment pressure on college students during the epidemic.

Association of cancer antigen 125 with long-term prognosis in light-chain cardiorenal amyloidosis.

BACKGROUND: Light-chain (AL) cardiorenal amyloidosis has been characterized as type 5 cardiorenal syndrome with fluid overload and poor prognosis. Cancer antigen 125 (CA125) has the potential for use in evaluating fluid load and prognosis for heart failure. However, less details for CA125 in AL cardiorenal amyloidosis have been reported. METHODS: Sixty patients diagnosed with AL cardiorenal amyloidosis were enrolled in this retrospective study. Patients were divided into two groups according to the cutoff point of CA125 level (35 U/mL). Logistic regression was used to screen variables associated with CA125. Cox regression analyses was utilized to verify the prognostic potential of CA125. RESULTS: The mean age was 61±8 years, and 68% of the participants were male. Compared to patients with normal CA125 levels (≤35 U/mL), patients with high levels of CA125 (>35 U/mL) had a higher proportion of New York Heart Association class >II, pericardial effusion, and edema, as well as a lower level of albumin and left ventricular longitudinal strain (LVLS). Logistic regression showed age, albumin, and LVLS to be independently associated with CA125. Seventeen (28%) patients died during the follow-up. Multivariate model including CA125, estimated glomerular filtration rate, E/e' and left ventricular ejection fraction showed acceptable prognostic potential (C-index= 0.829, 95%CI 0.749 to 0.909). CA125 remained an independent prognostic factor (HR=1.018, 95%CI 1.005 to 1.031, P=0.008) after adjusting for the remaining three variates and provided a significant incremental effect to the risk determined from them (C-index 0.829 vs 0.784, P=0.037). CONCLUSIONS: Serum CA125 level was associated with long-term prognosis of AL cardiorenal amyloidosis.

Identification of genes and key pathways underlying the pathophysiological association between nonalcoholic fatty liver disease and atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias. The latest studies have revealed a tight correlation between nonalcoholic fatty liver disease (NAFLD) and AF. However, the exact molecular mechanisms underlying the association between NAFLD and AF remain unclear. The current research aimed to expound the genes and signaling pathways that are related to the mechanisms underlying the association between these two diseases. MATERIALS AND METHODS: NAFLD- and AF- related differentially expressed genes (DEGs) were identified via bioinformatic analysis of the Gene Expression Omnibus (GEO) datasets GSE63067 and GSE79768, respectively. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), the construction of a protein-protein interaction (PPI) network, the identification of significant hub genes, and receiver operator characteristic curve analysis were conducted. The gene-disease interactions were analyzed using the Comparative Toxicogenomics Database. In addition, the hub genes were validated by quantitative Real-Time PCR (qRT-PCR) in NAFLD cell model. RESULTS: A total of 45 co-expressed differentially expressed genes (co-DEGs) were identified between the NAFLD/AF and healthy control individuals. GO and KEGG pathway analyses revealed that the co-DEGs were mostly enriched in neutrophil activation involved in the immune response and cytokine-cytokine receptor interactions. Moreover, eight hub genes were selected owing to their high degree of connectivity and upregulation in both the NAFLD and AF datasets. These genes included CCR2, PTPRC, CXCR2, MNDA, S100A9, NCF2, S100A12, and S100A8. CONCLUSIONS: In summary, we conducted the gene differential expression analysis, functional enrichment analysis, and PPI analysis of DEGs in AF and NAFLD, which provides novel insights into the identification of potential biomarkers and valuable therapeutic leads for AF and NAFLD.

Healthy Community-Life Circle Planning Combining Objective Measurement and Subjective Evaluation: Theoretical and Empirical Research.

BACKGROUND: The world faces vast health challenges, and urban residents living in high-density areas have even greater demand for healthy lifestyles. METHODS: Based on the data of points of interest, a field survey, and an interview, we explored the healthy community-life circle in the downtown area of Chengdu, China from two perspectives: objective measurement and subjective perception of residents. We evaluated the coverage rate and convenience in accessing eight types of health service facilities within a 15-min walk using linear and logistics regression models to explore the degree of resident satisfaction with facilities and influencing factors. RESULTS: Results showed significant differences in coverage rates between different districts. The overall convenience in accessing health service facilities decreased gradually from the city center to the outskirts. The social environment, the layout of health service facilities, and residents' travel habits were related to health service facility satisfaction. Results also showed significant differences in various facilities' accessibility satisfaction between objective measurement and residents' perception measurement. Compared with subjective measurement, the objective measurements of accessibility for sports venues (objectively measured average minus perceived average: -1.310), sports zones (-0.740), and specialized hospitals (-1.081) were lower; those for community hospitals (0.095), clinics (1.025), and pharmacies (0.765) were higher; and facility accessibility measured by subjective perception had a more significant impact on health facility satisfaction. Pharmacies (OR: 1.932) and community hospitals (OR: 1.751) had the largest impact among the eight types of facilities. CONCLUSION: This study proposed to construct a healthy community-life circle with a category and hierarchy system.

The Effects of Urban Neighborhood Environmental Evaluation and Health Service Facilities on Residents' Self-Rated Physical and Mental Health: A Comparative and Empirical Survey.

(1) Background: The neighborhood environment has been shown to be an essential factor affecting residents' quality of life and health, but the relationship between the characteristics of health service facilities and health levels is rarely known. (2) Methods: This study used a representative sample (n = 591, 303 women; 288 men, age 18-85 years, lived in Chengdu for an extensive time) of residents living in Chengdu City, China, and took spatial point data and empirical research data to construct an ordered logistic regression model. We contrastively analyzed the influence of different variables in the neighborhood environment and health service facilities on self-rated physical health (SRPH) and self-rated mental health (SRMH). (3) Results: The frequency of use and accessibility of multiple facilities in the health service facilities were significantly associated with self-rated health (SRH). Significant differences occurred between residents' perceived accessibility and actual accessibility of facilities in SRH. Comparing the results of SRPH and SRMH revealed that the influencing factors that affect the two vary. The factors that significantly affect SRMH include neighborhood physical environment evaluation; social environmental evaluation; the frequency of use of the parks and squares, and sports zones; and the accessibility of parks and squares, specialized hospitals, community hospitals, and pharmacies. However, the factors that significantly affect SRPH include the frequency of use of sports venues, general hospitals, and pharmacies and the accessibility of general hospitals. The social environment of the neighborhood is also a non-negligible part, and its interaction with the physical environment of the neighborhood affects the outcome of SRH. (4) Conclusions: Neighborhood environmental characteristics and the layout of health service facilities have significant differential effects on people's physical and psychological health, and this information is of great value in promoting healthy city development and improving the quality of life of urban populations around the world.

The role of altered fatty acid in pathological scars and their dermal fibroblasts.

PURPOSE: The proposed pathological mechanism for scar formation is controversial, and increased attention has been paid to the fatty acids (FAs) in the formation of pathological scars. Notably, FAs are known to be important in inflammation and mechanotransduction, which is closely related to scar formation. Therefore, it is necessary to clarify the roles of FA in scar formation. METHODS: Hypertrophic scar and keloid formed for more than a year and without other treatment, as well as normal skin samples were obtained from patients who underwent plastic surgery. Finally, keloids (n = 10), hypertrophic scars (n = 10), and normal skin samples (n = 10) were collected under informed consent. Primary dermal fibroblasts were isolated and cultured. The amount and variety of FAs were detected by lipid chromatography-mass spectrometry. Immunohistochemistry, real-time PCR, and western blotting were used to verify the expression of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FASN) in the samples and their fibroblasts. Student's t-test, ANOVA, and orthogonal partial least square discriminant analysis were performed for statistical analysis (∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001). RESULTS: Compared with full-thickness normal skin, there were 27 differential FAs in keloids and 15 differential FAs in hypertrophic scars (∗p < 0.05 and variable influence on projection >1.0). The expression of SREBP1 and FASN was lower in pathological scars both at mRNA and protein levels (all ∗p < 0.05). However, the mRNA levels of SREBP1 (∗∗∗p = 0.0002) and FASN (∗∗∗p = 0.0021) in keloid-derived fibroblasts were higher than that in normal skin fibroblasts (NFBs), while the expression in hypertrophic scar-derived fibroblasts was lower than that in NFBs (both ∗p < 0.05). Whereas there was no significant difference in FASN protein expression between keloid-derived fibroblasts and NFBs (p > 0.05). CONCLUSION: FAs involved in pathological scars are abnormally changed in scar formation. Thus, fatty acid-derived inflammation and de novo synthesis pathway of FA may play a key role in the formation of pathological scars.

To Explore Ideas From the Altered Metabolites: The Metabolomics of Pathological Scar.

BACKGROUND: Pathological scars are dermal fibroproliferative disorders due to rapid inflammatory response after dermal injury. The altered metabolites could reflect pathophysiological changes directly. However, it has not cleared how the metabolites change scars. OBJECTIVE: To explore new ideas of pathological scars from the altered metabolites by using ultra-performance liquid chromatography coupled to tandem mass spectrometry and identifying the key genes. METHODS: Keloid (KS, n = 10), hypertrophic scar (HS, n = 10), and normal skin (NS, n = 10) were collected. Ultra-performance liquid chromatography coupled to tandem mass spectrometry was used to identify and characterize metabolites. Differential metabolites were analyzed by orthogonal partial least square discriminant analysis and Student t test. The key pathways were analyzed via Kyoto Encyclopedia of Genes and Genomes, and the related enzymes were verified by real-time Polymerase Chain Reaction, both in tissues and their dermal fibroblasts. RESULTS: Two hundred fourteen metabolites were detected in total, mostly were fatty acids and amino acids. In the KS and NS groups, 65 different metabolites were screened ( P < 0.05), and the polyunsaturated fatty acids (PUFAs) metabolism and butyric acid in keloid should be concerned. The messenger Ribonucleic Acid expression of fatty acid desaturase 1 and fatty acid desaturase 2, which are the key enzyme of PUFA metabolism, were lower in KS and keloid-derived fibroblasts, P < 0.05. In HS group, 17 metabolites were significantly different and branched chain amino acids degradation was the key pathway. Moreover, branched chain keto acid dehydrogenase E1 subunit alpha was lower expressed in HS and their fibroblasts compared with NS, P < 0.05. CONCLUSIONS: Polyunsaturated fatty acids and butyric acid may be associated with the generation of keloids. The pathogenesis of hypertrophic scars may be involved in branched chain amino acids degradation, which is worth paying attention to.

Measurement of Coupling Coordination Degree and Spatio-Temporal Characteristics of the Social Economy and Ecological Environment in the Chengdu-Chongqing Urban Agglomeration under High-Quality Development.

With rapid urbanization and industrialization, ecological disorders and environmental degradation have become serious, and the promotion of the coordinated development of the social economy and ecological environment is not only a pressing problem to be solved, but also an important step towards sustainable development. The coordinated development of the social economy and eco-environment is conducive to sustainable development. Considering the Chengdu-Chongqing urban agglomeration as a case study, this paper adopts panel data and establishes an index system to evaluate the coupling coordination degree (CCD) between the social economy and ecological environment based on the concept of high-quality development. From the perspective of time and space, the changing laws and characteristics of the CCD are analyzed, and the key factors affecting it are determined using regression analysis. The results show the following: (1) the CCD between the social economy and ecological environment of the Chengdu-Chongqing urban agglomeration presents a low level overall; (2) the CCD in more developed regions is significantly higher than that in less developed regions; thus, the characteristics of spatial differences are obvious; (3) the urbanization rate, ratio of actual use of foreign capital and GDP, ratio of total export-import volume and GDP, proportion of days with good air quality, and per capita public green space area are the main factors affecting the coordinated development of the social economy and ecological environment in the Chengdu-Chongqing urban agglomeration; and (4) Chongqing has obvious endogeneity. Finally, corresponding policy recommendations are provided aimed at promoting rapid economic development in the Chengdu-Chongqing urban agglomeration while focusing on environmental protection and promoting high-quality economic development with ecological environmental protection, while putting forward decision-making suggestions for high-quality development of urban agglomerations.

Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine.

BACKGROUND: The clinical features of keloids consist of aberrant proliferation, secretion, differentiation and apoptosis of keloid dermis-derived fibroblasts (KFBs). Notably, the apoptosis rate of KFBs is lower than the proliferation rate. Though the anti-fibrotic effect of adipose-derived stem cells (ADSCs) on keloids has become a hot topic of research, the exact anti-fibrotic mechanism of the paracrine effect remains unclear. This study aimed to find out how the conditioned medium of ADSCs (ADSC-CM) exerts an anti-fibrotic effect in KFBs. METHODS: KFBs and ADSCs were extracted and cultured. Then, ADSC-CM was prepared. Whether ADSC-CM could inhibit KFB growth and induce apoptosis was verified by the use of a cell counting kit-8, an 5-Ethynyl-2-deoxyuridine (Edu) kit and flow cytometry. The expressions of cyclooxygenase-1 (COX-1), COX-2, caspase 3 and B-cell lymphoma-2 (Bcl-2) in ADSC-CM-cultured KFBs were tested by real-time PCR and western blotting. To clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis, a specific COX-2 inhibitor, celecoxib, was applied to KFBs cultured in ADSC-CM. Moreover, we tested the production of arachidonic acid (AA) and prostaglandin E2 (PGE2) by ELISA. Then, we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in vivo. RESULTS: The proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly increased. Caspase 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured KFBs. Furthermore, ADSC-CM strikingly elevated COX-2 mRNA and protein expressions, but COX-1 expression was unaltered. COX-2 inhibitors reduced ADSC-CM-induced apoptosis. Additionally, COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 expression. ADSC-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 inhibition. In the nude mouse model, expressions of AA, COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injection than in the controls. CONCLUSIONS: We showed activation of the COX-2/PGE2 cascade in KFBs in response to ADSC-CM. By employing a specific COX-2 inhibitor, COX-2/PGE2 cascade activation played a crucial role in mediating the ADSC-CM-induced KFB apoptosis and anti-proliferation effects.