BACKGROUND:Atherosclerosis (AS), the primary pathophysiological foundation of coronary artery disease (CAD), initiates through endothelial dysfunction that facilitates lipid deposition and plaque formation. Emerging evidence implicates dipeptidyl peptidase IV (DPP4) in vascular pathologies, yet its mechanistic role in AS-associated endothelial ferroptosis remains undefined. METHODS:Multidisciplinary approaches were employed: 1) Bioinformatic analysis of public databases identified DPP4-ferroptosis-AS associations; 2) Clinical samples measured plasma DPP4 levels across CAD severity strata; 3) Atherogenic progression was compared between DPP4-/-ApoE-/- and ApoE-/- mice under a high-fat diet; 4) Ox-LDL-induced endothelial injury models assessed DPP4-mediated ferroptosis mechanisms combining proteomics, cycloheximide chase assays, and pharmacological modulation of autophagy. RESULTS:Clinical samples analysis revealed a significant increase in plasma DPP4 levels in patients with severe coronary artery stenosis, with DPP4 enrichment observed at plaque. Animal studies demonstrated that DPP4 deficiency attenuated progression of AS and ferroptosis in murine models. Cellular experiments revealed ox-LDL upregulated DPP4 expression, concomitant with increased ferroptosis susceptibility and endothelial dysfunction. DPP4 inhibition preserved endothelial viability by blocking lipid peroxide accumulation. Mechanistically, mouse proteomics revealed that ferroptosis and autophagy pathways were associated with DPP4 in AS. DPP4 destabilized FTH1 via NCOA4-mediated ferritinophagy, proven by concordant rescue effects of chloroquine (autophagy inhibition) and saxagliptin (DPP4 inhibition) on FTH1 preservation. CONCLUSIONS:This study establishes endothelial DPP4 as a regulator of ferritinophagy-driven ferroptosis, inducing endothelial dysfunction in AS. Our findings propose targeting the DPP4-NCOA4-FTH1 axis as a promising strategy to preserve endothelial viability and halt early AS progression, with translational implications for repurposing DPP4 inhibitors in cardiovascular therapeutics.

BACKGROUND:The integrated regulation of microRNAs on macrophage plasticity plays a key role in atherosclerosis. We tested the hypothesis that miR487a-3p and miR6855-3p accelerate atherosclerosis by intensifying macrophage inflammatory response and metabolic dysregulation. METHODS:The microRNA sequencing and messenger RNA sequencing were conducted in peripheral monocytes from patients with coronary artery disease (CAD) and healthy controls. Macrophages in mouse aortas and human coronary arteries were characterized using flow cytometry and immunostaining. Atherosclerosis development was evaluated in male PCSK9 (proprotein convertase subtilisin/kexin type 9)-overexpression mice harboring myeloid cell-specific deficiency of CPE (carboxypeptidase E) or RRM2 (ribonucleotide reductase regulatory subunit M2) and challenged with a high-fat diet. RESULTS:miR487a-3p and miR6855-3p were the top microRNA candidates identified by microRNA sequencing in peripheral monocytes and validated by quantitative real-time polymerase chain reaction, with significant differences between patients with CAD and controls. Both microRNAs were lipid-inducible and secreted extracellularly. KLF5 (Krüppel-like factor 5) and IRF1 (interferon regulatory factor 1) bound to the promoter regions of miR487a-3p and miR6855-3p, respectively, to enhance their transcription. Accordingly, patients with CAD exhibited significantly elevated plasma miR487a-3p and miR6855-3p levels compared with controls, which positively correlated with blood lipid levels and Gensini score (reflecting CAD severity and prognosis). The area under the receiver operating characteristic curve (≈0.83 for each) supported their diagnostic accuracy. Of note, miR487a-3p and miR6855-3p were predominantly expressed in coronary arterial macrophages. The dramatic expansion of miR487a-3p+ and miR6855-3p+ macrophages and the elevated expression of both microRNAs in coronary arteries were positively associated with lesion area in patients with CAD. Mechanistically, transcriptomic analyses and functional assays revealed that elevated miR487a-3p or miR6855-3p promoted macrophage proinflammatory responses, lipid metabolic dysregulation, and foam cell formation. Conversely, inhibition of either microRNA alleviated ox-LDL (oxidized low-density lipoprotein)-induced macrophage inflammatory responses and lipid metabolic dysfunction. Moreover, conditioned medium from miR487a-3p- or miR6855-3p-overexpressing macrophages promoted endothelial cell apoptosis, whereas this effect was attenuated when endothelial cells were exposed to medium from ox-LDL-treated macrophages with microRNA inhibition. Furthermore, integration of downregulated genes from monocyte and macrophage messenger RNA sequencing with TargetScan-predicted targets identified CPE and RRM2 as targets of miR487a-3p and miR6855-3p, respectively. Direct binding was confirmed by dual-luciferase assays and microRNA pulldown. Overexpression of CPE or RRM2 partially reversed the detrimental effects of miR487a-3p and miR6855-3p, respectively, on macrophage phenotypic switching and metabolic dysregulation. Conversely, monocyte-/macrophage-specific depletion of CPE or RRM2 aggravated atherosclerosis progression in hypercholesterolemic mice by instigating macrophage inflammatory responses and lipid metabolic disturbance. CONCLUSIONS:miR487a-3p and miR6855-3p fulfill the criteria of promising biomarkers for CAD diagnosis and prognosis. Mechanistically, they intensify inflammatory responses and disrupt lipid metabolism in macrophages, identifying both microRNAs as potential therapeutic targets for CAD.

BACKGROUND:Intradermal microdroplet injections of botulinum toxin type-A (BoNT/A) effectively ameliorate rosacea-related angiogenesis, but the mechanism remains unclear. OBJECTIVE:To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells. METHODS:A rosacea-like mouse model was induced by LL37 in both Mas-related G-protein-coupled receptor B2 conditional knockout (MrgprB2-/-) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2'-deoxyuridine incorporation assays. The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining. RESULTS:LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2-/- mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization. CONCLUSION:BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.

Melasma is a chronic, acquired hyperpigmentation disease that occurs on light-exposed skin, especially in women of childbearing age. This common dyschromic disorder significantly impairs quality of life, yet treatments are unsatisfactory due to an incomplete understanding of its etiology. Its pathogenesis is multifactorial: ultraviolet (UV) radiation exposure, sex hormone fluctuations, and familial genetics are known triggers. Meanwhile, the persistence of focal hyperpigmentation suggests additional mechanisms beyond enhanced melanocyte activity. Emerging evidence highlights that melasma skin exhibits features of chronic photoaging: solar elastosis, basement membrane (BM) disruption and increased vascularity can be seen in the skin lesions. Senescent dermal fibroblasts under UV stress secrete melanogenic cytokines (e.g., SCF, HGF) that further stimulate melanocytes. In addition, melasma lesions harbor subclinical inflammation: infiltrates of CD4+ T cells, macrophages, and mast cells are visible, accompanied by elevated IL-17 and COX-2, implying an immune-driven component sustains pigment production. Collectively, these observations suggest that melasma behaves as a chronic inflammatory disorder of the skin microenvironment, rather than an isolated pigmentary defect. Concurrently, epidermal alterations such as barrier dysfunction and abnormal melanosome transport exacerbate melanin retention. In this review, by integrating these emerging insights into a unified pathogenic framework, we recognize melasma as a disorder of epidermal–dermal crosstalk and immune modulation, offering novel therapeutic perspectives for this recalcitrant condition.

Background and objective: Coronary artery disease (CAD), the leading cause of mortality, is caused by atherosclerotic plaque buildup in the arteries. The gold standard for the diagnosis of CAD is via X-ray coronary angiography (XCA) during percutaneous coronary intervention, where locating coronary artery stenosis is fundamental and essential. However, due to complex vascular features and motion artifacts caused by heartbeat and respiratory movement, manually recognizing stenosis is challenging for physicians, which may prolong the surgery decision-making time and lead to irreversible myocardial damage. Therefore, we aim to provide an automatic method for accurate stenosis localization. Methods: In this work, we present a convolutional neural network (CNN) with feature-level temporal fusion and attention modules to detect coronary artery stenosis in XCA images. The temporal fusion module, composed of the deformable convolution and the correlation-based module, is proposed to integrate time-varifying vessel features from consecutive frames. The attention module adopts channel-wise recalibration to capture global context as well as spatial-wise recalibration to enhance stenosis features with local width and morphology information. Results: We compare our method to the commonly used attention methods, state-of-the-art object detection methods, and stenosis detection methods. Experimental results show that our fusion and attention strategy significantly improves performance in discerning stenosis (P<0.05), achieving the best average recall score on two different datasets. Conclusions: This is the first study to integrate both temporal fusion and attention mechanism into a novel feature-level hybrid CNN framework for stenosis detection in XCA images, which is proved effective in improving detection performance and therefore is potentially helpful in intraoperative stenosis localization.

Background::The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.Methods::This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.Results::Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs. 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs. 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. Conclusion::This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.

Background: Astaxanthin (ASX), a fat-soluble carotenoid mainly sourced from Haematococcus pluvialis, shows promise for clinical applications in chronic inflammatory diseases. This study investigates whether ASX can mitigate atherosclerosis (AS) by modulating macrophage ferroptosis and provides astaxanthin-loaded polylactic acid-glycolic acid nanoparticles (ASX-PLGA NPs) as comparison. Method: ApoE-/- mice were fed a high-fat diet with ASX or statin intervention. Plaque area, lipid aggregation, collagen content, and ferroptosis-related indicators were assessed. Moreover, ASX-PLGA NPs were synthesized and characterized and were used to pretreat macrophages induced with oxidized low-density lipoprotein (oxLDL). Indicators linked to ferroptosis and oxidative stress were detected. Finally, the expression of nuclear factor erythroid -related factor 2 (NRF2) was evaluated. Results: ASX intervention significantly delayed the progression of AS plaques, characterized by reductions in plaque area and increased collagen fibers. The observed improvements in AS were consistent with statins. ASXPLGA NPs demonstrate good safety and stability and have better therapeutic effects than ASX alone. Indicators linked to ferroptosis and oxidative stress were significantly improved in groups containing ASX in vivo and vitro. Additionally, ASX facilitated the nuclear translocation of NRF2, which could be attenuated with ML385, a specific inhibitor of NRF2. Conclusion: ASX-PLGA NPs have better therapeutic effects than ASX alone. The regulation of NRF2/SLC7A11/ GPX4 represents a novel mechanism by which ASX can counteract ferroptosis and impede AS progression.

Background This study explores the relationship between different ART therapy based on NRTIs, and inflammatory markers, along with fasting blood glucose levels in treatment-naïve people living with HIV (PLWH). Methods We retrospectively analyzed the variations in fasting blood glucose and inflammatory markers and their relationship with different ART regimens in 497 treatment-naïve PLWH at the ART clinic of Zhongnan Hospital of Wuhan University from June 2018 to March 2022. Results From baseline to 24 months, fasting blood glucose, systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV) and lymphocyte-to-monocyte ratio (LMR) in PLWH receiving ART increased, while neutrophillymphocyte ratio (NLR) decreased ( p < .05). In the NNRTIs group, fasting blood glucose, SII, PIV and LMR were higher than before ( p < .05). In the INSTIs group, fasting blood glucose and LMR increased ( p < .05), while NLR was lower ( p < .05). Compared to the INSTIs, fasting blood glucose in the NNRTIs group was higher at 12 and 24 months ( p < .05). At 24 months, both NLR and SII were higher in the NNRTIs group than in the INSTIs group ( p < .05). Conclusions Despite the virus suppression, fasting blood glucose and certain inflammatory markers in PLWH can gradually increase. Compared to NNRTIs, the INSTIs regimen was associated with favorable alterations in the levels of glucose and inflammatory markers.

Purpose:In essential hypertensive patients, cardiac remodeling may be associated with the risk of renal damage in the future which can be reflected by the estimated glomerular filtration rate (eGFR). Through retrospective analysis, we evaluated the potential of cardiac remodeling based on echocardiographic measurements to predict the risk of renal damage in the future with hypertensive patients.Methods:We retrospectively analyzed the relationship between the changes of left heart structure and function and renal damage for 510 patients with hypertension, who were diagnosed between 2016 to 2022. Demography data, clinical data, blood samples and echocardiographic variables were used for survival analysis, and the Cox proportional hazards regression model was used.Results:In our study, we found that age, serum creatinine (SCR), creatine kinase isoenzyme MB (CK MB), abnormal high-sensitivity troponin I (TNI), interventricular septum thickness (IVST) and left ventricular ejection fraction (LVEF) could be used as independent predictors in risk of renal impairment in hypertensive patients (p<0.05). Combined in a score where one point was given for the presence of each of the parameters above, this score could strongly predict renal function damage in the future (p<0.05). In receiver operating characteristics (ROC) curve analyses, the area under the curve of the risk factor score was 0.849 (P<0.001).Conclusion:In essential hypertensive patients, LVEF and IVST can predict the risk of future adverse renal outcomes. Moreover, combining risk variables into a simplified score may enable to assess the risk of renal impairment in hypertensive patients at an early stage.

This study aimed to evaluate the real-world impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the efficacy, safety, and metabolic profiles of patients with chronic heart failure (CHF), both with and without type 2 diabetes mellitus (T2DM). A cohort of 1,130 patients with reduced ejection fraction chronic heart failure (HFrEF) was recruited from Zhongnan Hospital of Wuhan University, spanning January 2021 to August 2023. Among these, 154 patients received SGLT2i therapy, while 131 patients were assigned to a non-SGLT2i group, following specified inclusion and exclusion criteria. The association between SGLT2i therapy and the risk of primary and secondary endpoints was analyzed, alongside the effect of guideline-recommended heart failure medications at varying dosages on Major Adverse Cardiovascular Events (MACE). SGLT2i treatment led to reductions in blood pressure, uric acid, NT-proBNP, and pulmonary artery pressure, while increasing body mass index (BMI) and left ventricular ejection fraction (LVEF) in CHF patients. Multivariate Cox regression analysis revealed that SGLT2i therapy reduced the primary endpoint risk by 40.3

BackgroundCoronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations.MethodsBased on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI.ResultsFive unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments.ConclusionAccording to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Telmisartan, an angiotensin II type 1 receptor (AT1R) blocker, exhibits broad anti-tumor activity. However, in vitro, anti-proliferative effects are shown at doses far beyond the therapeutic plasma concentration. Considering the role of tumor microenvironment in glioma progression, glioma-astrocyte co-cultures were employed to test the anti-tumor potential of low-dose telmisartan. When a high dose was required for a direct anti-proliferative effect on glioma cell lines, a low dose significantly inhibited glioma cell proliferation and migration in the co-culture system. Under co-culture conditions, upregulated IL-6 expression in astrocytes played a critical role in glioma progression. Silencing IL-6 in astrocytes or IL-6R in glioma cells reduced proliferation and migration. Telmisartan (5 μM) inhibited astrocytic IL-6 expression, and its anti-tumor effects were reversed by silencing IL-6 or IL-6R and inhibiting signal transducer and activator of transcription 3 (STAT3) activity in glioma cells. Moreover, the telmisartan-driven IL-6 downregulation was not imitated by losartan, an AT1R blocker with little capacity of peroxisome proliferator-activated receptor-gamma (PPARγ) activation, but was eliminated by a PPARγ antagonist, indicating that the anti-glioma effects of telmisartan rely on its PPARγ agonistic activity rather than AT1R blockade. This study highlights the importance of astrocytic IL-6-mediated paracrine signaling in glioma growth and the potential of telmisartan as an adjuvant therapy for patients with glioma, especially those with hypertension.

BackgroundThe relationship between air pollution and cardiovascular diseases (CVDs) has garnered significant interest among researchers globally. This study employed bibliometric analysis to provide an overview of current research on the association between air pollution and CVDs, offering a comprehensive analysis of global research trends in this area.MethodsAn exhaustive scrutiny of literature pertaining to the nexus between air pollution and CVDs from 2012 to 2022 was conducted through rigorous screening of the Web of Science Core Collection (WoSCC). Publications were exclusively considered in English. Subsequently, sophisticated analytical tools including CiteSpace 6.2.4R, Vosviewer 1.6.19, HistCite 2.1, Python 3.7.5, Microsoft Charticulator, and Bibliometrix Online Analysis Platform were deployed to delineate research trends in this domain.ResultsThe analysis of the dataset, comprising 1,710 documents, unveiled a consistent escalation in scientific publications, peaking in 2022 with a total of 248 publications. Moreover, Environmental Science and Toxicology stood out as the predominant categories. Examination of keyword frequency highlighted the terms 'air pollution', 'cardiovascular disease', and 'particulate matter' as the most prevalent. Notably, the most prolific entities, in terms of authors, journals, organizations, and countries, were identified as Robert D. Brook, Environmental Health Perspectives, Harvard University, and the United States, respectively.ConclusionThe findings presented a notable increase in high-quality publications on this topic over the past 11 years, suggesting a positive outlook for future research. The study concluded with an examination of three key themes in research trends related to air pollution and CVDs: the initial physiological response to pollutant exposure, the pathways through which pollutants are transmitted, and the subsequent effects on target organs. Additionally, various air pollutants, such as particulate matter, nitric dioxide, and ozone, could contribute to multiple CVDs, including coronary heart disease, hypertension, and heart failure. Although some hypotheses have been put forward, the mechanisms of air pollution-related CVDs still need to be explored in the future.

Inflammation and immunity play important roles in the formation of coronary collateral circulation (CCC). The pan-immune-inflammation value (PIV) is a novel marker for evaluating systemic inflammation and immunity. The study aimed to investigate the association between the PIV and CCC formation in patients with chronic total occlusion (CTO). This retrospective study enrolled 1150 patients who were diagnosed with CTO through coronary angiographic (CAG) examinations from January 2013 to December 2021 in China. The Cohen-Rentrop criteria were used to catagorize CCC formation: good CCC formation (Rentrop grade 2–3) and poor CCC formation group (Rentrop grade 0–1). Based on the tertiles of the PIV, all patients were classified into three groups as follows: P1 group, PIV ≤ 237.56; P2 group, 237.56< PIV ≤ 575.18; and P3 group, PIV > 575.18. A significant relationship between the PIV and the formation of CCC was observed in our study. Utilizing multivariate logistic regression and adjusting for confounding factors, the PIV emerged as an independent risk factor for poor CCC formation. Notably, the restricted cubic splines revealed a dose–response relationship between the PIV and risk of poor CCC formation. In terms of predictive accuracy, the area under the ROC curve (AUC) for PIV in anticipating poor CCC formation was 0.618 (95

Background: The atherogenic index of plasma (AIP), determined by the logarithmic transformation of the ratio of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), was found to be a marker of cardiovascular disease. We sought to investigate the correlation between the atherogenic AIP and coronary collateral circulation (CCC) formation in chronic total occlusive (CTOs) patients. Methods: This retrospective cohort study included 665 non-CTOs and 345 CTOs patients. CTOs were divided into 206 CCC poor formation patients and 139 CCC good formation patients according to the Cohen-Rentrop grade. Spearman correlation analysis was carried out to obtain the relationship between AIP and the Rentrop grade. We used multivariate logistic regression analysis to assess CTOs and CCC poor formation risk factors. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold for AIP to predict CTOs and CCC poor formation. The predicted increment of AIP on CTOs and CCC poor formation was evaluated by calculating the Net Reclassification Index (NRI) and the Integrated Discriminant Index (IDI). Results: AIP in CTOs was significantly elevated compared to non-CTOs patients [(1.55 (1.02, 2.59)) vs (1.26 (0.82, 1.90)), p < 0.001] AIP in the CCC poor formation group was significantly higher than that in the CCC good formation group [(1.73 (1.12, 2.90)) vs (1.37 (0.84, 2.13)), p = 0.002]. There was a negative correlation between AIP and the Rentrop grade (r = -0.145, p = 0.007). The results of multivariate logistic regression revealed that AIP was an independent predictor of CTOs (OR = 4.371, 95% CI: 2.436-7.844, p < 0.001) and CCC poor formation (OR = 3.749, 95% CI: 1.628-8.635, p = 0.002). In the ROC analysis, the area under the curve of AIP for identifying CTOs and CCC poor formation was 0.596 (OR = 3.680, 95% CI: 1.490-9.090, p = 0.005) and 0.597 (95% CI: 0.535-0.658, p = 0.002), respectively. Conclusions: Contrary to previous research, we found that AIP is a moderate but not powerful indicator for detecting both CTO patients and poor CCC formation.

Objective: To analyze whether the ratio of total IgE level at week 16 to baseline could be used as an indicator to evaluate clinical efficacy of patients treated with omalizumab.Methods: We retrospectively analyzed the clinical characteristics of 62 patients with moderate-to-severe allergic rhinitis treated with omalizumab, and compared the pre-and post-treatment nasal visual analog scale (n-VAS) scores, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Rhinitis Control Assessment Test (RCAT), improvement in nasal congestion, number of acute episodes of rhinitis, and total IgE levels in serum. The relationship between the efficacy of treatment with omalizumab and the change in total IgE levels before and after treatment was further analyzed.Results: This study included 62 patients with moderate-to-severe allergic rhinitis, of which 48 demonstrated significant improvement after 16 weeks of omalizumab therapy; the results of 16 weeks' omalizumab treatment in 14 patients did not show significant improvements in allergic rhinitis symptoms based on RACT scores. After 16 weeks of omalizumab treatment, the RQLQ score decreased from (36.6 & PLUSMN; 13.7) at baseline level to (9.1 & PLUSMN; 12.6) after 16 weeks treatment.The ratio of total IgE at week 16 to total IgE levels at baseline was (2.9 & PLUSMN; 1.4) KU/L in 62 patients. And the ratio of total IgE levels at week 16 to total IgE levels at baseline was (3.3 & PLUSMN; 1.4) KU/ L for responders and (1.6 & PLUSMN; 0.5) KU/L for non-responders.Conclusion: The ratio of total IgE level at week 16 to baseline significantly correlated with the clinical response to omalizumab in moderate to severe allergic rhinitis patients, when the ratio of total IgE level at week 16 to baseline was & GE;2.0. Omalizumab effectively treated patients with moderate-to-severe allergic rhinitis, and improved their quality of life.

IntroductionThis article aimed to compare the prevalence of dyslipidemia and determine risk factors associated with lipid levels in a cohort of HIV-infected patients receiving two different antiretroviral therapy (ART) regimens, nucleoside reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor (NRTI/NNRTI) and nucleoside reverse transcriptase inhibitor/integrase strand transfer inhibitor (NRTI/INSTI). MethodsThis longitudinal study analyzed 633 HIV-infected patients with complete blood lipid profile records for at least 1 year at the ART clinic of Zhongnan Hospital of Wuhan University, China, from June 2018 to March 2021. Demographic and clinical data, including age, gender, body weight, height, current/former/non-smoker, current drinker, diabetes mellitus, hypertension, were extracted from electronic medical records. Laboratory tests included hematology, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lipoprotein(a) and CD4 cell count. The observation duration of this study was a maximum of 33 months. Data comparisons were performed using the Chi-square test, Student's t-test and Mann-Whitney U test. Generalized linear mixed-effects model (GLMM) and value of p < 0.05 were used to determine factors associated with serum lipid profiles. ResultsIn this study, the effect of the NNRTIs group on the lipid profile over time was mainly an increase in TC and HDL-C, while a decrease in TC/HDL-C and LDL/HDL-C. However, the INSTIs group had higher mean TC and lower HDL-C compared to the NNRTIs group, with significantly increased levels of TC, TG, HDL-C, and LDL-C. In the analysis of dyslipidemia rates, there were significant differences in the prevalence of abnormal TG and TC/HDL-C in HIV-infected patients receiving two different ART regimen groups during different follow-up periods. Dyslipidemia, defined as hypercholesterolemia, hypertriglyceridemia, and low HDL-C, was more prevalent in the INSTIs group, with a higher risk of developing hypertriglyceridemia and a higher TC/HDL-C ratio compared to the NNRTIs group. GLMM analysis suggested significantly higher TG values in the INSTIs group (estimated 0.36[0.10, 0.63], SE 0.14, p = 0.008) compared to the NNRTIs group, even after adjusting for other covariates. In addition, GLMM analysis also showed that age, gender, BMI, CD4 count, and ART duration were associated with dyslipidemia. ConclusionIn conclusion, treatment with both commonly-used ART regimens can increase the mean values of lipid profiles and the risk of dyslipidemia. The findings indicated that TG values were significantly higher in the INSTIs group than in HIV-infected patients receiving the NNRTIs regimens. Longitudinal TG values are independently associated with the clinical types of ART regimens.

Limited evidence showed the association between cold spells and the severity of coronary heart disease (CHD). This study was to investigate the association between cold spells with their different time types and CHD severity. We collected data on CHD patients admitted to the Zhongnan Hospital, Wuhan, China from 2016 to 2021. CHD severity was quantified using the SYNTAX score and transformed into a binomial variable. Daily mean, maximum and minimum temperature were collected during the study period. We first used daily mean temperature to find the optimum definition among multiple thresholds and durations. The daily maximum and minimum temperatures were used to define different types of cold spells (daytime, nighttime and compound) based on the optimum definition. Annual cold spell days were included to assess individual exposure to cold spells. Logistic regression models were performed to fit the association between cold spell days and CHD severity stratified by different tertiles of PM2.5 and NDVI. In this study, 1937 CHD patients were included. The cold spell defined as at least four consecutive days with daily mean temperature below the 5th percentile exhibited the optimum model. We found that a 4-day increase in cold spell days was associated with more severe CHD (OR = 1.170, 95% CI: 1.074, 1.282). Such an association was more pronounced under higher levels of PM2.5 by OR = 1.270 (1.086, 1.494) and lower levels of greenness by OR = 1.240 (1.044, 1.476). Compared with daytime and compound cold spells, nighttime cold spells showed the strongest association with CHD severity by OR = 1.141 (1.026, 1.269). This study showed that exposure to cold spells was positively associated with CHD severity, especially the nighttime cold spells. The association between cold spells and CHD severity was more significant in high levels of PM2.5 and low levels of greenness.

OBJECTIVE:The purpose of this study was to investigate the role of the unfolded protein response, specifically the inositol-requiring enzyme 1 (IRE1) signaling pathway, in hypoxia-induced autophagy in human umbilical venous endothelial cells (HUVECs). METHODS:The expression of IRE1 and autophagy relative protein in HUVECs with hypoxia was explored by Western blotting, qRT-PCR and confocal microscopy. Further, we evaluated the biological effects of HUVECs by tube formation assay and wound healing assay in vitro. Finally, we examined the function of IRE1 in local blood vessels through animal models. RESULTS:Hypoxia activated the IRE1 signaling pathway and induced autophagy in a time-dependent manner in HUVECs and further influenced the biological effects of HUVECs. Intraperitoneal injection of IRE1 inhibitors inhibited local vascular autophagy levels and lipid accumulation in model animals. CONCLUSION:Hypoxia can induce autophagy and activate the IRE1 signaling pathway in HUVECs and the IRE1 signaling pathway is involved in autophagy in hypoxic conditions.

The present study aimed to investigate the association of triglyceride-glucose (TyG) index and neutrophil-to-lymphocyte ratio (NLR) with coronary artery disease (CAD), and evaluate the cumulative value of TyG index and NLR in identifying CAD, as well as the severity of CAD. This retrospective study enrolled 2867 patients who underwent coronary angiography (CAG) for the first time between January 2013 and June 2022 in Zhongnan Hospital of Wuhan University. There were 2109 patients with CAD and 758 patients without CAD. The CAD patients were divided into two groups based on the median of Gensini score (mild stenosis CAD group: Gensini score < 26 points; severe stenosis CAD group: Gensini score ≥ 26 points). To further evaluate the cumulative value of TyG index and NLR in identifying CAD and CAD severity, all patients were classified into four groups based on median of TyG index and NLR: (1) the control group: patients with low-TyG and low-NLR; (2) isolated high-NLR group: patients with low-TyG and high- NLR; (3) isolated high- TyG group: patients with high-TyG and low- NLR; (4) high-TyG combined with high-NLR group: patients with high-TyG and high- NLR. Multivariate logistic regression analysis showed that both the TyG index and NLR were independent risk factors for CAD, and they were also independent risk factors for severe stenosis in CAD (P < 0.05). Compared with the low-TyG and low- NLR group, patients in high-TyG and high- NLR group had a 1.418 times higher odds ratio (OR) of having CAD and a 1.692 times higher OR of having severe stenosis in CAD in the multivariable logistic regression model. It is worth noting that the OR values of the high-TyG and high- NLR group were higher than those of the isolated high-NLR group and the isolated high- TyG group. The ROC analysis showed that the combination of the TyG index and NLR was superior to TyG index or NLR in predicting CAD and CAD severity. Compared to TyG index or NLR, the combination of the TyG index and NLR is beneficial to improve the diagnostic accuracy of CAD and CAD severity.