KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter.

Krüppel-like factor 13 (KLF13), a zinc finger transcription factor, is considered as a potential regulator of cardiomyocyte differentiation and proliferation during heart morphogenesis. However, its precise role in the dedifferentiation of vascular smooth muscle cells (VSMCs) during atherosclerosis and neointimal formation after injury remains poorly understood. In this study, we investigated the relationship between KLF13 and SM22α expression in normal and atherosclerotic plaques by bioanalysis, and observed a significant increase in KLF13 levels in the atherosclerotic plaques of both human patients and ApoE-/- mice. Knockdown of KLF13 was found to ameliorate intimal hyperplasia following carotid artery injury. Furthermore, we discovered that KLF13 directly binds to the SM22α promoter, leading to the phenotypic dedifferentiation of VSMCs. Remarkably, we observed a significant inhibition of platelet-derived growth factor BB-induced VSMCs dedifferentiation, proliferation, and migration when knocked down KLF13 in VSMCs. This inhibitory effect of KLF13 knockdown on VCMC function was, at least in part, mediated by the inactivation of p-AKT signaling in VSMCs. Overall, our findings shed light on a potential therapeutic target for treating atherosclerotic lesions and restenosis after vascular injury.

Genome-wide DNA methylation of lesional and peri-lesional skin in vitiligo: a comparative and integrated analysis of multi-omics in Chinese population.

Several studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investigated DNA methylation levels in six lesional skin, six peri-lesional skin, and eight healthy skin samples using an Illumina 850 K methylation chip. We then integrated DNA methylation data with transcriptome data to identify differentially methylated and expressed genes (DMEGs) and analyzed their functional enrichment. Subsequently, we compared the methylation and transcriptome characteristics of all skin samples, and the related genes were further studied using scRNA-seq data. Finally, validation was performed using an external dataset. We observed more DNA hypomethylated sites in patients with vitiligo. Further integrated analysis identified 264 DMEGs that were mainly functionally enriched in cell division, pigmentation, circadian rhythm, fatty acid metabolism, peroxidase activity, synapse regulation, and extracellular matrix. In addition, in the peri-lesional skin, we found that methylation levels of 102 DMEGs differed prior to changes in their transcription levels and identified 16 key pre-DMEGs (ANLN, CDCA3, CENPA, DEPDC1, ECT2, DEPDC1B, HMMR, KIF18A, KIF18B, TTK, KIF23, DCT, EDNRB, MITF, OCA2, and TYRP1). Single-cell RNA analysis showed that these genes were associated with cycling keratinocytes and melanocytes. Further analysis of cellular communication indicated the involvement of the extracellular matrix. The expression of related genes was verified using an external dataset. To the best of our knowledge, this is the first study to report a comprehensive DNA methylation profile of clinical vitiligo and peri-lesional skin. These findings would contribute to future research on the pathogenesis of vitiligo and potential therapeutic strategies.

Transcriptome analysis of frontal fibrosis alopecia revealed involvement of immune cells and ferroptosis.

BACKGROUND: Frontal fibrosis alopecia (FFA) is a primary cicatricial alopecia and has received increasing attention in recent years. However, the pathogenesis of FFA has not been fully elucidated. METHODS AND RESULTS: Herein, we collected the transcriptome data of scalp lesions of seven patients with FFA and seven healthy controls. The differential expression analysis and weighted gene co-expression network analysis were conducted and we identified 458 differentially expressed genes (DEGs) in two key modules. Later, we performed functional enrichment analysis and functional modules identification, revealing the participation of immune response and fatty acid metabolism. Based on the results, we processed further studies. On the one hand, we analyzed the infiltrating immune cells of FFA through CIBERSORT algorithm, indicating the activation of M1 macrophage and CD8+ T cell. On the other hand, considering lipid metabolism of FFA and oxidative stress of hair follicle cells in alopecia, we explored the potential ferroptosis of FFA. By intersection of DEGs and ferroptosis-related genes from FerrDb database, 19 genes were identified and their expression was validated in an external dataset containing 36 FFA cases and 12 controls. Then, we used LASSO algorithms to construct a four-gene diagnostic model, which achieved an AUC of 0.924 in validation dataset. Additionally, the immune cells were found to be related to ferroptosis in FFA. CONCLUSION: Taken together, this study contributed to reveal the molecular mechanisms of FFA and is expected to inspire future research on treatment.

In situ electro-generated Ni(OH)2 synergistic with Cu cathode to promote direct ammonia oxidation to nitrogen.

To solve the problem of low removal rate and poor N2 selectivity in direct electrochemical ammonia oxidation (EAO), commercial Ni foam and Cu foam were used as anode and cathode of the EAO system, respectively. The coupling effect between the cathode and anode promoted nitrogen cycling during the reaction process, which improved N2 selectivity of the reaction system and promoted it to achieve a high ammonia removal rate. This study showed that the thin Ni(OH)2 with oxygen vacancy formed on the surface of Ni foam anode played an effective role in the dimerization of intermediate products in ammonia oxidation to form N2. This electrochemical system was used to treat real goose wastewater containing 422.5 mg/L NH4+-N and 94.5 mg/L total organic carbon (TOC). After treatment, this electrochemical system achieved good performance with an ammonia removal rate of 87%, N2 selectivity of 77%, and TOC removal rate of 72%. Therefore, this simple and efficient system with Ni foam anode and Cu foam cathode is a promising method for treating ammonia nitrogen wastewater.

DNA methylation profiling and integrative multi-omics analysis of skin samples reveal important contribution of epigenetics and immune response in the pathogenesis of acne vulgaris.

The regulatory effect of DNA methylation on the pathogenesis of acne vulgaris is completely unknown. Herein we analyzed the DNA methylation profile in skin samples of acne vulgaris and further integrated it with gene expression profiles and single-cell RNA-sequencing data. Finally, 31,134 differentially methylated sites and 770 differentially methylated and expressed genes (DMEGs) were identified. The multi-omics analysis suggested the importance of DNA methylation in inflammation and immunity in acne. And DMEGs were verified in an external dataset and were closely related to early inflammatory acne. Additionally, we conducted experiments to verify the mRNA expression and DNA methylation level of DMEGs. This study supports the significant contribution of epigenetics to the pathogenesis of acne vulgaris and may provide new ideas for the molecular mechanisms of and potential therapeutic strategies for acne vulgaris.

Prevalence and risk factors of acne scars in patients with acne vulgaris.

BACKGROUND: Acne scar is a persistent complication of acne vulgaris. However, the prevalence and risk factors are still unclear. This study aimed to assess the global prevalence and risk factors of acne scars in patients with acne. MATERIALS AND METHODS: A systematic search of published studies in three databases was performed and the meta-analyses were conducted. RESULTS: Finally, we included 37 studies involving 24 649 acne patients. And, the pooled prevalence of acne scars in these patients was 47% (95% confidence interval [CI]: 38-56%). Besides, the differences in prevalence were observed based on the subgroup analysis for age, gender, acne severity, source of patients, and so on. Subsequently, we quantified the relationship of three risk factors with acne scars: male gender (odds ratio [OR]: 1.58, 95% CI: 1.19-2.09), positive family history of acne (OR: 2.73, 95% CI: 1.26-5.91), and acne severity (OR for moderate acne: 2.34, 95% CI: 1.54-3.57; OR for severe acne: 5.51, 95% CI: 2.45-12.41). CONCLUSION: Herein, we found that 47% of acne patients suffered from acne scars and identified three risk factors: male gender, positive family history of acne, and acne severity. In order to reduce acne scarring, attention and effective therapy early in the course of acne is important.

Sex differences on outcomes following left atrial appendage occlusion in atrial fibrillation: A systematic review and meta-analysis.

There is a lack of sufficient data on sex-related differences in outcomes of nonvalvular atrial fibrillation (AF) patients following left atrial appendage occlusion (LAAO). We conducted a meta-analysis to investigate the procedural complications and long-term outcomes after LAAO in women versus men. We screened Medline, EMBASE, Cochrane Center Register of Controlled Trials, and Clinical Trials.gov. The inclusion criteria were studies targeting the sex-related differences in outcomes in nonvalvular AF patients treated by LAAO. Procedural endpoints of interest included success rate, pericardial complications, major bleeding, and vascular complications during hospitalization. Long-term outcomes included all-cause mortality and ischemic stroke during follow-up. Studies that merely considered sex in the subgroup analysis were not included. Six observational studies with a total of 64,035 patients were identified. The procedural success rates did not differ between sexes (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.89-1.09, p = 0.77), while women experienced more pericardial complications (OR: 1.78, 95% CI: 1.58-2.01, p < 0.00001), major bleedings (OR: 2.04, 95% CI: 1.75-2.39, p < 0.00001), and vascular complications (OR: 1.75, 95% CI: 1.41-2.17, p < 0.00001) than men. The sensitivity analysis performed by removing the largest study showed good stability. The long-term mortality and stroke rates did not differ between women and men in either the 1-year subgroup or the 2-year subgroup. In conclusion, despite comparable procedural success rates, women have a significantly higher incidence of pericardial complications, major bleeding, and vascular complications following LAAO. The long-term mortality and stroke rates do not differ between the sexes.

Blood Urea Nitrogen for Short-Term Prognosis in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction.

Purpose: Cardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI). Our study aimed to evaluate the short-term prognostic value of admission blood urea nitrogen (BUN) in patients with CS complicating AMI. Materials and Methods: 218 consecutive patients with CS after AMI were enrolled. The primary endpoint was 30-day mortality. The association of admission BUN and 30-day mortality and major adverse cardiovascular event (MACE) was investigated by Cox regression. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) further examined the predictive value of BUN. Results: During a period of 30-day follow-up, 105 deaths occurred. Compared to survivors, nonsurvivors had significantly higher admission BUN (p < 0.001), creatinine (p < 0.001), BUN/creatinine (p = 0.03), and a lower glomerular filtration rate (p < 0.001). The area under the curve (AUC) of the 4 indices for predicting 30-day mortality was 0.781, 0.734, 0.588, and 0.773, respectively. When compared to traditional markers associated with CS, the AUC for predicting 30-day mortality of BUN, lactate, and left ventricular ejection fraction were 0.781, 0.776, and 0.701, respectively. The optimal cut-off value of BUN for predicting 30-day mortality was 8.95 mmol/L with Youden-Index analysis. Multivariate Cox analysis indicated BUN >8.95 mmol/L was an important independent predictor for 30-day mortality (HR 2.08, 95%CI 1.28-3.36, p = 0.003) and 30-day MACE (HR 1.85, 95%CI 1.29-2.66, p = 0.001). IDI (0.053, p = 0.005) and NRI (0.135, p = 0.010) showed an improvement in the accuracy for mortality prediction of the new model when BUN was included compared with the standard model of predictors in previous scores. Conclusion: An admission BUN >8.95 mmol/L was robustly associated with increased short-term mortality and MACE in patients with CS after AMI. The prognostic value of BUN was superior to other renal markers and comparable to traditional markers. This easily accessible index might be promising for early risk stratification in CS patients following AMI.

Diacerein attenuates vascular dysfunction by reducing inflammatory response and insulin resistance in type 2 diabetic rats.

AIM: To examine the effect of diacerein on vascular dysfunction in type 2 diabetic rats and elucidate the mechanism of diacerein. METHODS: In a rat model, type 2 diabetes was induced by high-fat diet and streptozotocin. Vascular function was assessed in vascular reactivity experiment. The effect of diacerein (10 or 20 mg/kg/day) on blood glucose, inflammation and insulin signaling, and modulators in vascular tissue in diabetic rats were investigated by molecular and biochemical approaches. RESULTS: In this study, diacerein inhibited diabetes-induced vascular dysfunction. Diacerein treatment normalized blood glucose, insulin tolerance test, inflammatory cytokine levels and nitric oxide synthases expression in diabetic rats. Moreover, diacerein inhibited NF-κB and NLRP3 pathways and activated insulin signaling pathway related proteins IRS-1 and AKT in diabetic rats. CONCLUSION: Diacerein improved vascular function effectively in diabetic rats by suppressing inflammation and reducing insulin resistance. These results suggest that diacerein may represent a novel therapy for patients with diabetes.

Risk stratification of ST-segment elevation myocardial infarction (STEMI) patients using machine learning based on lipid profiles.

BACKGROUND: Numerous studies have revealed the relationship between lipid expression and increased cardiovascular risk in ST-segment elevation myocardial infarction (STEMI) patients. Nevertheless, few investigations have focused on the risk stratification of STEMI patients using machine learning algorithms. METHODS: A total of 1355 STEMI patients who underwent percutaneous coronary intervention were enrolled in this study during 2015-2018. Unsupervised machine learning (consensus clustering) was applied to the present cohort to classify patients into different lipid expression phenogroups, without the guidance of clinical outcomes. Kaplan-Meier curves were implemented to show prognosis during a 904-day median follow-up (interquartile range: 587-1316). In the adjusted Cox model, the association of cluster membership with all adverse events including all-cause mortality, all-cause rehospitalization, and cardiac rehospitalization was evaluated. RESULTS: All patients were classified into three phenogroups, 1, 2, and 3. Patients in phenogroup 1 with the highest Lp(a) and the lowest HDL-C and apoA1 were recognized as the statin-modified cardiovascular risk group. Patients in phenogroup 2 had the highest HDL-C and apoA1 and the lowest TG, TC, LDL-C and apoB. Conversely, patients in phenogroup 3 had the highest TG, TC, LDL-C and apoB and the lowest Lp(a). Additionally, phenogroup 1 had the worst prognosis. Furthermore, a multivariate Cox analysis revealed that patients in phenogroup 1 were at significantly higher risk for all adverse outcomes. CONCLUSION: Machine learning-based cluster analysis indicated that STEMI patients with increased concentrations of Lp(a) and decreased concentrations of HDL-C and apoA1 are likely to have adverse clinical outcomes due to statin-modified cardiovascular risks. TRIAL REGISTRATION: ChiCTR1900028516 ( http://www.chictr.org.cn/index.aspx ).

Prognostic value of neutrophil-lymphocyte ratio in cardiogenic shock complicating acute myocardial infarction: A cohort study.

BACKGROUNDS: Cardiogenic shock (CS) is the most severe complication after acute myocardial infarction (AMI) with mortality above 50%. Inflammatory response is involved in the pathology of CS and AMI. In this study, we aimed to evaluate the prognostic value of admission neutrophil-lymphocyte ratio (NLR) in patients with CS complicating AMI. METHODS: Two hundred and seventeen consecutive patients with CS after AMI were divided into two groups according to the admission NLR cut-off value ≤7.3 and >7.3. The primary outcome was 30-day all-cause mortality and the secondary end-point was the composite events of major adverse cardiovascular events (MACE), including all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal haemorrhage and non-fatal stroke. Cox proportional hazard models were performed to analyse the association of NLR with the outcome. NLR cut-off value was determined by Youden index. RESULTS: Patients with NLR > 7.3 were older and presented with lower lymphocyte count, higher admission heart rate, B-type natriuretic peptide, leucocyte, neutrophil and creatinine (all P < .05). During a period of 30-day follow-up after admission, mortality in patients with NLR > 7.3 was significantly higher than in patients with NLR ≤ 7.3 (73.7% vs. 26.3%, P < .001). The incidence of MACE was also remarkably higher in patients with NLR > 7.3 (87.9% vs. 53.4%, P < .001). After multivariable adjustment, NLR > 7.3 remained an independent predictor for higher risk of 30-day mortality (HR 2.806; 95%CI 1.784, 4.415, P < .001) and MACE (HR 2.545; 95%CI 1.791, 3.617, P < .001). CONCLUSIONS: Admission NLR could be used as an important tool for short-term prognostic evaluation in patients with CS complicating AMI and higher NLR is an independent predictor for increased 30-day all-cause mortality and MACE.

Chronic kidney disease in the shadow of COVID-19: insights from the bibliometric analysis.

OBJECTIVE: This study aims to present the current status and frontiers of research on COVID-19 in relation to chronic kidney disease through bibliometric analysis and visualization. METHODS: Access to information through the Web of Science Core Collection, retrieved from December 2019 to May 2023. The bibliometric visualization of countries, institutions, and keywords was analyzed using VOSviewer. RESULTS: A total of 1038 publications are included. The global scientific community showed a high level of collaborative consensus. The three countries with the most publications are the USA, China, and the UK. The institution with the most publications is Harvard Medical School. The research frontier for 2020 is thrombosis, for 2021 is telemedicine, for 2022 is depression, and for 2019-2023 is the COVID-19 vaccines. CONCLUSIONS: This is the first bibliometric report to establish a link between COVID-19 and CKD. The USA, China, and some European countries and their institutions are major contributors to these publications. Thrombosis, telemedicine, depression, and COVID-19 vaccines are current hot topics in the field and have the potential to shape future research trends.

A Journey of Challenges and Victories: A Bibliometric Worldview of Nanomedicine since the 21st Century.

Nanotechnology profoundly affects the advancement of medicine. Limitations in diagnosing and treating cancer and chronic diseases promote the growth of nanomedicine. However, there are very few analytical and descriptive studies regarding the trajectory of nanomedicine, key research powers, present research landscape, focal investigative points, and future outlooks. Herein, articles and reviews published in the Science Citation Index Expanded of Web of Science Core Collection from first January 2000 to 18th July 2023 are analyzed. Herein, a bibliometric visualization of publication trends, countries/regions, institutions, journals, research categories, themes, references, and keywords is produced and elaborated. Nanomedicine-related academic output is increasing since the COVID-19 pandemic, solidifying the uneven global distribution of research performance. While China leads in terms of publication quantity and has numerous highly productive institutions, the USA has advantages in academic impact, commercialization, and industrial value. Nanomedicine integrates with other disciplines, establishing interdisciplinary platforms, in which drug delivery and nanoparticles remain focal points. Current research focuses on integrating nanomedicine and cell ferroptosis induction in cancer immunotherapy. The keyword "burst testing" identifies promising research directions, including immunogenic cell death, chemodynamic therapy, tumor microenvironment, immunotherapy, and extracellular vesicles. The prospects, major challenges, and barriers to addressing these directions are discussed.

Inhibition of fatty acid uptake by TGR5 prevents diabetic cardiomyopathy.

Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise involvement of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. Here we show decreased plasma bile acid levels in both male and female participants with diabetic myocardial injury. Additionally, we observe increased myocardial lipid accumulation and cardiac dysfunction in cardiomyocyte-specific TGR5-deleted mice (both male and female) subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic db/db genetic background. Further investigation reveals that TGR5 deletion enhances cardiac fatty acid uptake, resulting in lipid accumulation. Mechanistically, TGR5 deletion promotes localization of CD36 on the plasma membrane through the upregulation of CD36 palmitoylation mediated by the palmitoyl acyltransferase DHHC4. Our findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, which highlights the therapeutic potential of targeting TGR5 in the management of diabetic cardiomyopathy.

The lncRNA GAS5 upregulates ANXA2 to mediate the macrophage inflammatory response during atherosclerosis development.

Inflammatory macrophages play a crucial role in atherosclerosis development. The long non-coding RNA growth arrest-specific 5 (GAS5) regulates THP-1 macrophage inflammation by sponging microRNAs. The purpose of this study was to investigate the regulatory mechanism of GAS5 in atherosclerosis development. GSE40231, GSE21545, and GSE28829 datasets from the Gene Expression Omnibus database were integrated after adjusting for batch effect. Differential analysis was performed on the integrated dataset and validated using the Genotype-Tissue Expression and GSE57691 datasets. Potential biological functions of GAS5 and annexin A2 (ANXA2) were identified using gene set enrichment analysis (GSEA). ssGSEA, CIBERSORTx, and ImmuCellAI algorithms were used to identify immune infiltration in plaque samples. GAS5 and ANXA2 expression levels in RAW264.7 cells treated with oxidized low-density lipoprotein (ox-LDL) were measured by qRT-PCR and Western blot. Small interfering and short hairpin RNA were used to silence GAS5 expression. Plasmids of ANXA2 were used to establish ANXA2 overexpression. Apoptosis and inflammatory markers in macrophages were detected by Western blot. Aortic samples from APOE-/- mice were collected to validate the expression of GAS5 and ANXA2. GAS5 expression was significantly increased during atherosclerosis. GAS5 expression was positively correlated with macrophage activation and ANXA2 expression in plaques. Furthermore, ANXA2 upregulation was also related to the activation of macrophage. GSEA indicated similar biological functions for GAS5 and ANXA2 in plaques. Moreover, in vitro experiments showed that both GAS5 and ANXA2 contributed to macrophage apoptosis and inflammation. Rescue assays revealed that the inflammatory effects of GAS5 on macrophages were ANXA2-dependent. In vivo experiments confirmed the highly expression of Gas5 and Anxa2 in the plaque group. We identified the atherogenic roles of GAS5 and ANXA2 in the inflammatory response of macrophages. The inflammatory response in ox-LDL-treated macrophages was found to be mediated by GAS5-ANXA2 regulation, opening new avenues for atherosclerosis therapy.

Aerobic exercise inhibits renal EMT by promoting irisin expression in SHR.

To determine the effect of aerobic exercise in different intensities on renal injury and epithelial-mesenchymal transformation (EMT) in the kidney of spontaneously hypertensive rats (SHR) and explore possible mechanisms, we subjected SHR to different levels of 14-week aerobic treadmill training. We tested the effects of aerobic exercise on irisin level, renal function, and EMT modulators in the kidney. We also treated angiotensin II-induced HK-2 cells with irisin and tested the changes in EMT levels. The data showed low and moderate aerobic exercise improved renal function and inhibited EMT through promoting irisin expression in SHR. However, high-intensity exercise training had no effect on renal injury and EMT in SHR but did significantly activate STAT3 phosphorylation in the kidney. These results clarify the mechanisms of exercise in improving hypertension-related renal injury and suggest that irisin might be a therapeutic target for patients with kidney injury.

Acne and risk of mental disorders: A two-sample Mendelian randomization study based on large genome-wide association data.

Background: Despite a growing body of evidence that acne impacts mental disorders, the actual causality has not been established for the possible presence of recall bias and confounders in observational studies. Methods: We performed a two-sample Mendelian randomization (MR) analysis to evaluate the effect of acne on the risk of six common mental disorders, i.e., depression, anxiety, schizophrenia, obsessive-compulsive disorder (OCD), bipolar disorder, and post-traumatic stress disorder (PTSD). We acquired genetic instruments for assessing acne from the largest genome-wide association study (GWAS) of acne (N = 615,396) and collected summary statistics from the largest available GWAS for depression (N = 500,199), anxiety (N = 17,310), schizophrenia (N = 130,644), OCD (N = 9,725), bipolar disorder (N = 413,466), and PTSD (N = 174,659). Next, we performed the two-sample MR analysis using four methods: inverse-variance weighted method, MR-Egger, weighted median, and MR pleiotropy residual sum and outliers. Sensitivity analysis was also performed for heterogeneity and pleiotropy tests. Results: There was no evidence of a causal impact of acne on the risk of depression [odds ratio (OR): 1.002, p = 0.874], anxiety (OR: 0.961, p = 0.49), OCD (OR: 0.979, p = 0.741), bipolar disorder (OR: 0.972, p = 0.261), and PTSD (OR: 1.054, p = 0.069). Moreover, a mild protective effect of acne against schizophrenia was observed (OR: 0.944; p = 0.033). Conclusion: The increased prevalence of mental disorders observed in patients with acne in clinical practice was caused by modifiable factors, and was not a direct outcome of acne. Therefore, strategies targeting the elimination of potential factors and minimization of the occurrence of adverse mental events in acne should be implemented.

An Intelligent Diagnostic Model for Melasma Based on Deep Learning and Multimode Image Input.

INTRODUCTION: The diagnosis of melasma is often based on the naked-eye judgment of physicians. However, this is a challenge for inexperienced physicians and non-professionals, and incorrect treatment might have serious consequences. Therefore, it is important to develop an accurate method for melasma diagnosis. The objective of this study is to develop and validate an intelligent diagnostic system based on deep learning for melasma images. METHODS: A total of 8010 images in the VISIA system, comprising 4005 images of patients with melasma and 4005 images of patients without melasma, were collected for training and testing. Inspired by four high-performance structures (i.e., DenseNet, ResNet, Swin Transformer, and MobileNet), the performances of deep learning models in melasma and non-melasma binary classifiers were evaluated. Furthermore, considering that there were five modes of images for each shot in VISIA, we fused these modes via multichannel image input in different combinations to explore whether multimode images could improve network performance. RESULTS: The proposed network based on DenseNet121 achieved the best performance with an accuracy of 93.68% and an area under the curve (AUC) of 97.86% on the test set for the melasma classifier. The results of the Gradient-weighted Class Activation Mapping showed that it was interpretable. In further experiments, for the five modes of the VISIA system, we found the best performing mode to be "BROWN SPOTS." Additionally, the combination of "NORMAL," "BROWN SPOTS," and "UV SPOTS" modes significantly improved the network performance, achieving the highest accuracy of 97.4% and AUC of 99.28%. CONCLUSIONS: In summary, deep learning is feasible for diagnosing melasma. The proposed network not only has excellent performance with clinical images of melasma, but can also acquire high accuracy by using multiple modes of images in VISIA.

LncRNA GAS5 downregulates NLRP3 inflammasome activation-mediated pyroptosis in sepsis-induced myocardial injury by targeting SIRT3/AMPKα.

An increasing body of studies has demonstrated the significance of long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) in inflammation and myocardial injury in septic shock. This research aims to determine whether GAS5 contributes to the pathological development of sepsis-induced cardiac damage and NLRP3 inflammasome-mediated myocardial cell pyroptosis. Cecal ligation and puncture (CLP) surgery was used to cause septic shock in C57BL/6 wild-type mice. After CLP, inflammatory, pyroptosis parameters of myocardial tissue, survival rate, and Murine Sepsis Score (MSS) were assessed to evaluate the involvement of GAS5 in the mouse myocardial depression. To investigate GAS5's function in lipopolysaccharide (LPS) induced myocardial cell pyroptosis, gain- and loss-of-function experiments were conducted in vitro on HL-1 cells. Our findings indicated that CLP dramatically reduced survival rates, MSS, SIRT3 and p-AMPK expression, and activated the Nuclear factor-κB (NF-κB) pathway and NLRP3 inflammasome-mediated pyroptosis. The NF-κB and pyroptosis pathways were greatly elevated while SIRT3/p-AMPKα was dramatically decreased as a result of GAS5 being downregulated. Meanwhile, the regulatory effect could be suppressed by SIRT3 and AMPKα activator. Our observations supported the idea that GAS5 has a crucial protective impact against myocardial inflammation and pyroptosis in sepsis.

The Association of Thyroid Hormones With Cardiogenic Shock and Prognosis in Patients with ST Segment Elevation Myocardial Infarction (STEMI) Treated with Primary PCI.

BACKGROUND: Cardiogenic shock (CS) is the leading cause of the death in patients with ST elevation myocardial infarction (STEMI). Thyroid dysfunction is related to prognosis of patients with myocardial infarction. Hence, the aim of this study is to explore the relationship between thyroid hormones (free triiodothyronine [FT3] and free thyroxine [FT4]) and CS. METHODS: A total of 1270 patients with STEMI treated with percutaneous coronary intervention (PCI) were consecutively enrolled in our study. Patients were classified into two groups according to with or without CS during hospitalization. Stepwise multivariate logistic analysis was conducted to investigate the association of thyroid hormones and CS. Restricted cubic spline method was employed to further explore the relationship between CS and thyroid hormones. RESULTS: Patients who developed CS (n=103) had lower FT3 and higher FT4 upon admission. The stepwise logistic analysis showed both FT3 (P=0.038) and FT4 (P=0.024) were independently related to CS. Restricted cubic splines indicated that lower FT3 (<2.25 pg/ml) or higher FT4 (>1.25 ng/dl) were correlated with higher prevalence of CS. Over 2.5 years' follow-up, patients (n=294) with low FT3 (<2.85 pg/ml) and high FT4 (>=0.88 ng/dl) had the highest all-cause mortality (18.2%), whereas patients (n=293) with high FT3 and low FT4 had the lowest all-cause mortality (3.8%) (P for trend <0.0001). CONCLUSIONS: Both FT3 and FT4 were independently associated with in-hospital CS development in patients with STEMI treated with PCI. Patients with lower range of FT3 and upper range of FT4 had the worst outcomes in long-term follow-up.