Profiles of Cough and Associated Risk Factors in Nonhospitalized Individuals With SARS-CoV-2 Omicron Variant Infection: Cross-Sectional Online Survey in China.

BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

Association Between Interleukin-6 Gene Polymorphism and Severity of Coronary Artery Disease in Patients with Diabetes.

Introduction: Previous studies have identified diabetes as a risk factor for coronary heart disease. This study determined the correlation between the IL-6 gene -572 G/C polymorphism and the incidence and severity of coronary heart disease in patients with diabetes. Methods: One hundred four patients with diabetes who were admitted to our hospital from January 2019 to December 2020 were retrospectively enrolled in the current study. These patients were divided into a diabetes only group (group A, 27 patients) and a diabetes complicated by coronary heart disease group (group B, 77 patients). Seventy patients in the latter group were further divided into low, medium, and high Syntax score groups based on coronary angiography results. A correlation analysis between IL-6, blood lipids, and the IL-6 -572 G/C gene levels was performed. Results: The serum IL-6 level in patients with the IL-6-572G/C-GG genotype was higher than patients with the GC and CC genotypes. In patients with diabetes, the presence of the IL-6-572G/C-GG and GC genotypes was associated with a significantly increased risk of developing coronary heart disease. Patients with the IL-6-572G/C-GG genotype and diabetes were shown to have more severe coronary artery lesions compared to patients with the CC genotype. Moreover, the G allele of the IL-6-572G/C gene was linked to a higher risk of coronary heart disease and more severe coronary artery lesions in patients with diabetes compared to the C allele. Conclusion: The IL-6-572G/C gene polymorphism is associated with the incidence and severity of coronary heart disease in patients with diabetes.

Smoking index and COPD duration as potential risk factors for development of osteoporosis in patients with non-small cell lung cancer - A retrospective case control study evaluated by CT Hounsfield unit.

Objective: To investigate the effect of smoking index (calculated as number of cigarettes per day × smoking years) and chronic obstructive pulmonary disease (COPD) duration on osteoporosis (OP)evaluated by opportunistic chest CT in patients with non-small cell lung cancer (NSCLC). Methods: A total of 101 patients diagnosed with NSCLC were included in our cohort study. Among them, 50 patients with a history of smoking and COPD were assigned to the experimental group, while 51 patients without a history of smoking and COPD were assigned to the control group. Hounsfield unit (HU) value was measured by conventional chest CT to investigate the bone mineral density; and the mean values of axial HU value in the upper, middle and lower parts of T4, T7, T10 and L1 vertebral bodies were measured as the study variables. Results: There were no significant differences in gender, age, body mass index, type of lung cancer, clinical stage of lung cancer and comorbidities between the two groups (P = 0.938，P = 0.158，P = 0.722,P = 0.596,P = 0.813,P = 0.655). The overall mean HU values of T4, T7, T10, L1 in the experimental group were 116.60 ± 30.67, 110.56 ± 30.03, 109.18 (96.85-122.95), 94.63 (85.20-104.12) and 106.86 ± 22.26, respectively, which were significantly lower than those in the control group (189.55 ± 34.57, 174.54 ± 35.30, 172.73 (156.33-199.50), 158.20 (141.60-179.40) and 177.50 ± 33.49) (P ＜0.05). And in the experimental group, smoking index and COPD duration were significantly and negatively correlated with HU values (r = -0.627, -0.542, P ＜0.05, respectively). Conclusion: Patients with NSCLC who have a history of smoking and COPD exhibit a notably lower HU value compared to the control groups. Additionally, it has been observed that the smoking index and duration of COPD may be influential factors affecting bone mineral density in NSCLC patients.

Ultrasonic Elastography-guided Pleural Biopsy for the Diagnosis of Pleural Effusion: A Multicenter Prospective Study of Diagnostic Test Performance.

Rationale: The diagnostic yield of traditional ultrasound-guided pleural biopsy remains unsatisfactory, particularly when the pleural thickness is ⩽5 mm and/or no pleural nodules are detected. Pleural ultrasound elastography (UE) has a better diagnostic yield than traditional ultrasound for malignant pleural effusion (MPE). However, studies on UE-guided pleural biopsies are lacking. Objectives: To evaluate the feasibility and safety of UE-guided pleural biopsy. Methods: In this multicenter prospective single-arm trial, patients with pleural effusion whose pleural thickness was ⩽5 mm with no pleural nodules were enrolled between July 2019 and August 2021. The diagnostic yield of UE-guided pleural biopsy for pleural effusion and its sensitivity for detecting MPE were evaluated. Results: Ninety-eight patients (mean age, 62.4 ± 13.2 yr; 65 men) were prospectively enrolled. The diagnostic yield of UE-guided pleural biopsy for making any diagnosis was 92.9% (91/98), and its sensitivity for MPE was 88.7% (55/62). In addition, its sensitivity for pleural tuberculosis was 69.6% (16/23). The rate of postoperative chest pain was acceptable, and there was no pneumothorax. Conclusions: UE-guided pleural biopsy is a novel technique for diagnosing MPE with good diagnostic yield and sensitivity. Clinical trial registered with https://www.chictr.org.cn (ChiCTR2000033572).

Atorvastatin ameliorated PM2.5-induced atherosclerosis in rats.

PM2.5 provokes atherosclerotic events. Atorvastatin presents anti-inflammatory and antioxidant activities, and may ameliorate PM2.5-induced atherosclerosis development. The purpose of this study was to investigate the cardiotoxic effect of fine particulate matter (PM2.5) on atherosclerosis (AS) in rats, and the intervention effects of atorvastatin (ATO) on PM2.5-induced AS development. AS model was established using 32 male Wistar rats through intraperitoneal injection of vitamin D3 combined with a high-fat diet (10% fat and 4% cholesterol). The rats were randomly divided into 4 groups: control group, PM2.5-exposed group, ATO group, and ATO treated PM2.5-exposed group. PM2.5 increased levels of TC, TG, LDL, MDA, IL-6, and TNF-α, as well as decreased SOD levels. Besides, PM2.5 also enhanced AI. After the treatment of ATO, most levels of various contents in serum, including TC, TG, LDL, MDA, IL-6, TNF-α, hS-CRP, and ox-LDL, significantly decreased compared to the PM2.5-exposed group. Moreover, after the treatment of ATO, AI was significantly reduced compared to the PM2.5-exposed group. In addition, PM2.5 exacerbated the nuclear translocation and ATO resulted in an obvious decrease in PM2.5-induced nuclear translocation. The present study suggests that PM2.5 could induce oxidative damage and systemic inflammatory response in atherosclerosis model rats, while ATO could ameliorate PM2.5-induced atherosclerosis development, possibly by lowering lipid, inhibiting inflammation, and suppressing oxidation.

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

A Systematic Review and Meta-Analysis Comparing the Safety and Efficacy of Spinal Anesthesia and Spinal Anesthesia Combined with Obturator Nerve Block in Transurethral Resection of Bladder Tumors.

Background: Transurethral resection of bladder tumors (TURBT) is the main surgical treatment for bladder cancer, but during TURBT, it is easy to stimulate the obturator nerve passing close to the lateral side of the bladder wall and induce involuntary contraction of the adductor muscle group of the thigh innervated by it, which will affect the surgical process and lead to adverse reactions. Obturator nerve block (ONB) helps to prevent the obturator nerve reflex. This study systematically evaluated and meta-analyzed the reports on the co-application of ONB and spinal anesthesia (SA) in TURBT in recent years to provide evidence for clinical diagnosis and treatment. Methods: The clinical randomized controlled literature studies of ONB combined with SA in TURBT published in PubMed, EMBASE, the Cochrane Library, CNKI (China National Knowledge Infrastructure), and Wanfang databases from January 2000 to December 2021 were searched. After screening the qualified literature studies, the literature quality was assessed by the Jadad scale. The incidence of obturator nerve reflex, the incidence of bladder perforation, length of hospital stay, and tumor recurrence rate were used as outcome indicators. The meta-analysis was performed with the R language toolkit. Results: A total of 444 articles were initially retrieved, and after the screening, a total of 8 articles were included in the selection, and a total of 635 patients with ureterovesical tumor resection were included. The meta-analysis showed that the use of SA + ONB anesthesia during TURBT was associated with a smaller incidence of bladder perforation (RR = 0.24, 95% CI (0.11, 0.53), Z = -3.48, P=0.0005), a smaller incidence of obturator nerve reflex (RR = 0.22, 95% CI (0.13, 0.36), Z = -6.11, P=0.0001), a significantly shorter length of hospital stay (MD = -1.81, 95% CI (-2.65, -0.97), Z = -4.24, P=0.0001), and a significantly lower tumor recurrence rate (RR = 0.46, 95% CI (0.29, 0.73), Z = -3.30, P=0.001) compared with SA alone. Conclusion: The application of SA combined with ONB in TURBT can effectively reduce the incidence of obturator nerve reflex, reduce the incidence of bladder perforation, shorten the hospital stay and reduce the tumor recurrence rate.

Identification of hub genes in bladder cancer based on weighted gene co-expression network analysis from TCGA database.

BACKGROUND: Muscular invasive bladder cancer (MIBC) is a common malignant tumor in the world. Because of their heterogeneity in prognosis and response to treatment, biomarkers that can predict survival or help make treatment decisions in patients with MIBC are essential for individualized treatment. AIM: We aimed to integrate bioinformatics research methods to identify a set of effective biomarkers capable of predicting, diagnosing, and treating MIBC. To provide a new theoretical basis for the diagnosis and treatment of bladder cancer. METHODS AND RESULTS: Gene expression profiles and clinical data of MIBC were obtained by downloading from the Cancer Genome Atlas database. A dataset of 129 MIBC cases and controls was included. 2084 up-regulated genes and 2961 down-regulated genes were identified by differentially expressed gene (DEG) analysis. Then, gene ontology analysis was performed to explore the biological functions of DEGs, respectively. The up-regulated DEGs are mainly enriched in epidermal cell differentiation, mitotic nuclear division, and so forth. They are also involved in the cell cycle, p53 signaling pathway, PPAR signaling pathway, and so forth. The weighted gene co-expression network analysis yielded five modules related to pathological stages and grading, of which blue and turquoise were the most relevant modules for MIBC. Next, Using Kaplan-Meier survival analysis to identify further hub genes, the screening criteria at p ≤ .05, we found CNKSR1, HIP1R, CFL2, TPM1, CSRP1, SYNM, POPDC2, PJA2, and RBBP8NL genes associated with the progression and prognosis of MIBC patients. Finally, immunohistochemistry experiments further confirmed that CNKSR1 plays a vital role in the tumorigenic context of MIBC. CONCLUSION: The research suggests that CNKSR1, POPDC2, and PJA2 may be novel biomarkers as therapeutic targets for MIBC, especially we used immunohistochemical further to validate CNKSR1 as a therapeutic target for MIBC which may help to improve the prognosis for MIBC.

Microglia Polarization in Alzheimer's Disease: Mechanisms and a Potential Therapeutic Target.

Neuroinflammation regulated by microglia is one of the important factors involved in the pathogenesis of Alzheimer's disease (AD). Activated microglia exhibited phenotypes termed as M1 and M2 phenotypes separately. M1 microglia contribute to the development of inflammation via upregulating pro-inflammatory cytokines, while M2 microglia exert anti-inflammation effects through enhancing the expression of anti-inflammation factors. Moreover, M1 and M2 microglia could be mutually transformed under various conditions. Both M1 and M2 microglia are implicated in AD. Amyloid-ß (Aß) and hyperphosphorylated tau are two major components of AD pathological hallmarks, neuritic plaques, and neurofibrillary tangles. Both Aß and hyperphosphorylated tau were involved in microglial activation and subsequent inflammation, which further contribute to neuronal and synaptic loss in AD. In this review, we summarized the roles of M1 and M2 microglia in AD and underlying mechanisms, which will provide an insight into the role of microglia in the pathogenesis of AD and highlight the therapeutic potential of modulating microglia.

Identification of SLITRK6 as a Novel Biomarker in hepatocellular carcinoma by comprehensive bioinformatic analysis.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the adult liver and morbidity are increasing in recent years, however, there is still no effective strategy to prevent and diagnose HCC. Therefore, it is urgent to research the effective biomarker to predict clinical outcomes of HCC tumorigenesis. In the current study, differentially expressed genes in HCC and normal tissues were investigated using the Gene Expression Omnibus (GEO) dataset GSE144269 and The Cancer Genome Atlas (TCGA). Gene differential expression analysis and weighted correlation network analysis (WGCNA) methods were used to identify nine and 16 key gene modules from the GEO dataset and TCGA dataset, respectively, in which the green module in the GEO dataset and magenta module in TCGA were significantly correlated with HCC occurrence. Third, the enrichment score of gene function annotation results showed that these two key modules focus on the positive regulation of inflammatory response and cell differentiation, etc. Besides, PPI network analysis, mutation analysis, and survival analysis found that SLITRK6 had high connectivity, and its mutation significantly impacted overall survival. In addition, SLITRK6 was found to be low expressed in tumor cells. To summarize, SLITRK6 mutation was found to significantly affect the occurrence and prognosis of HCC. SLITRK6 was confirmed as a new potential gene target for HCC, which may provide a new theoretical basis for personalized diagnosis and chemotherapy of HCC in the future.

Unearthing of Key Genes Driving the Pathogenesis of Alzheimer's Disease via Bioinformatics.

Alzheimer's disease (AD) is a neurodegenerative disease with unelucidated molecular pathogenesis. Herein, we aimed to identify potential hub genes governing the pathogenesis of AD. The AD datasets of GSE118553 and GSE131617 were collected from the NCBI GEO database. The weighted gene coexpression network analysis (WGCNA), differential gene expression analysis, and functional enrichment analysis were performed to reveal the hub genes and verify their role in AD. Hub genes were validated by machine learning algorithms. We identified modules and their corresponding hub genes from the temporal cortex (TC), frontal cortex (FC), entorhinal cortex (EC), and cerebellum (CE). We obtained 33, 42, 42, and 41 hub genes in modules associated with AD in TC, FC, EC, and CE tissues, respectively. Significant differences were recorded in the expression levels of hub genes between AD and the control group in the TC and EC tissues (P < 0.05). The differences in the expressions of FCGRT, SLC1A3, PTN, PTPRZ1, and PON2 in the FC and CE tissues among the AD and control groups were significant (P < 0.05). The expression levels of PLXNB1, GRAMD3, and GJA1 were statistically significant between the Braak NFT stages of AD. Overall, our study uncovered genes that may be involved in AD pathogenesis and revealed their potential for the development of AD biomarkers and appropriate AD therapeutics targets.

Risk Prediction in Patients With Heart Failure With Preserved Ejection Fraction Using Gene Expression Data and Machine Learning.

Heart failure with preserved ejection fraction (HFpEF) has become a major health issue because of its high mortality, high heterogeneity, and poor prognosis. Using genomic data to classify patients into different risk groups is a promising method to facilitate the identification of high-risk groups for further precision treatment. Here, we applied six machine learning models, namely kernel partial least squares with the genetic algorithm (GA-KPLS), the least absolute shrinkage and selection operator (LASSO), random forest, ridge regression, support vector machine, and the conventional logistic regression model, to predict HFpEF risk and to identify subgroups at high risk of death based on gene expression data. The model performance was evaluated using various criteria. Our analysis was focused on 149 HFpEF patients from the Framingham Heart Study cohort who were classified into good-outcome and poor-outcome groups based on their 3-year survival outcome. The results showed that the GA-KPLS model exhibited the best performance in predicting patient risk. We further identified 116 differentially expressed genes (DEGs) between the two groups, thus providing novel therapeutic targets for HFpEF. Additionally, the DEGs were enriched in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to HFpEF. The GA-KPLS-based HFpEF model is a powerful method for risk stratification of 3-year mortality in HFpEF patients.

Comparison of Periarticular Injection and Intra-articular Injection for Pain Management After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

PURPOSE: Local infiltration analgesia, an essential component of multimodal analgesia after total knee arthroplasty (TKA), can be classified into periarticular injection (PAI) and intra-articular injection (IAI) as per administration techniques. Currently, there is no definite answer of the optimal choice between the two techniques. This meta-analysis aims to determine whether PAI provides superiority of pain relief and functional recovery than IAI after TKA. DESIGN: Systematic review and meta-analysis. METHODS: Comparative studies that compared PAI and IAI in patients after TKA were searched in the Embase, PubMed, MEDLINE, and the Cochrane Library databases. The primary outcomes were visual analog scale scores for pain and opioid consumption. The secondary outcomes were complications, function of recovery, and length of hospital stay. FINDINGS: Four randomized controlled trials and two case-controlled studies with a total of 769 patients were enrolled. There were no significant differences in mean visual analog scale scores at postoperative day 0 (P = .17) and day 1 (P = .27), maximum visual analog scale scores at day 0 (P = .89) and day 1 (P = .82), total opioid consumption at day 1 (P = .96), opioid complications (P = .15), and length of hospital stay (P = .84) between PAI and IAI. CONCLUSIONS: Based on the available evidence, PAI does not offer superior effects at pain control and discharge than IAI after TKA. However, owing to the limited sample size and heterogeneity of the included studies, further large well-designed randomized controlled trials are still needed to validate this conclusion. REGISTRATION: The protocol has been registered in the PROSPERO international database under number CRD42020165138.

Clinical features and outcomes of seven patients with COVID-19 in a family cluster.

BACKGROUND: The family cluster is one of most important modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission throughout China, and more details are needed about how family clusters cause the spread of coronavirus disease 2019 (COVID-19). CASE PRESENTATION: We retrospectively reviewed 7 confirmed cases from one family cluster. Both clinical features and laboratory examination results were described. Patient 1 had been in close contact with someone who was later confirmed to have COVID-19 in Wuhan City before he returned back to his hometown. He had dinner with 6 other members in his family. All the persons developed COVID-19 successively except for one older woman who neither had dinner with them nor shared a sleeping room with her husband. Six patients had mild or moderate COVID-19 but one older man with underlying diseases progressed into the severe type. After general and symptomatic treatments, all the patients recovered. CONCLUSIONS: In a family cluster, having dinner together may be an important mode for the transmission of SARS-CoV-2. In this setting, most cases are mild with a favorable prognosis, while elderly patients with underlying diseases may progress into the severe type. For someone who has close contact with a confirmed case, 14-day isolation is necessary to contain virus transmission.

IFN regulatory Factor-1 induced macrophage pyroptosis by modulating m6A modification of circ_0029589 in patients with acute coronary syndrome.

BACKGROUND: Pyroptosis is identified as a novel form of inflammatory programmed cell death and has been recently found to be closely related to atherosclerosis (AS). We found that IFN regulatory factor-1(IRF-1) effectively promotes macrophage pyroptosis in patients with acute coronary syndrome (ACS). Subsequent studies have demonstrated that circRNAs are implicated in AS. However, the underlying mechanisms of circRNAs in macrophage pyroptosis remain elusive. METHODS: We detected the RNA expression of hsa_circ_0002984, hsa_circ_0010283 and hsa_circ_0029589 in human PBMC-derived macrophages from patients with coronary artery disease (CAD). The lentiviral recombinant vector for hsa_circ_0029589 overexpression (pLC5-GFP-circ_0029589) and small interference RNAs targeting hsa_circ_0029589 and METTL3 were constructed. Then, macrophages were transfected with pLC5-GFP-circ_0029589, si-circ_0029589 or si-METTL3 after IRF-1 was overexpressed and to explore the potential mechanism of hsa_circ_0029589 involved in IRF-1 induced macrophage pyroptosis. RESULTS: The relative RNA expression level of hsa_circ_0029589 in macrophages was decreased, whereas the N6-methyladenosine (m6A) level of hsa_circ_0029589 and the expression of m6A methyltransferase METTL3 were validated to be significantly elevated in macrophages in patients with ACS. Furthermore, overexpression of IRF-1 suppressed the expression of hsa_circ_0029589, but induced its m6A level along with the expression of METTL3 in macrophages. Additionally, either overexpression of hsa_circ_0029589 or inhibition of METTL3 significantly increased the expression of hsa_circ_0029589 and attenuated macrophage pyroptosis. CONCLUSION: Our observations suggest a novel mechanism by which IRF-1 facilitates macrophage pyroptosis and inflammation in ACS and AS by inhibiting circ_0029589 through promoting its m6A modification.

IFN Regulatory Factor 1 Mediates Macrophage Pyroptosis Induced by Oxidized Low-Density Lipoprotein in Patients with Acute Coronary Syndrome.

BACKGROUND: Atherosclerosis (AS) is recognized as a chronic inflammatory disease. It is caused by the interaction between inflammatory cells such as macrophages, dendritic cells, and lipoproteins. Evidence has revealed that macrophage pyroptosis in lesion contributes to the formation of the necrotic core and thinning of the fibrous cap, which plays crucial roles in the onset of acute coronary syndrome (ACS). IFN regulatory factor 1 (IRF-1) is a pleiotropic transcription factor involved in various immune processes and cell death. We propose that IRF-1 may be implicated in macrophage pyroptosis in the pathogenesis of AS and ACS. METHODS: Patients with stable angina, unstable angina, acute myocardial infarction, and clinical presentation of chest pain were enrolled. The expression of IRF-1 in human PBMC-derived macrophages was analyzed. Then, overexpression and inhibition of IRF-1 was performed in macrophages from patients with ACS to explore the possible role and mechanism of IRF-1 involvement in macrophage pyroptosis. RESULTS: The expression of IRF-1 in macrophages was upregulated in ACS patients. The overexpression or inhibition of IRF-1 effectively modulated caspase-1 activation, as well as macrophage lysis, expression of gasdermin D-N (GSDMD-N), production of IL-1ß and IL-18, and activation of NLRP3-ASC inflammasome, which were all inhibited by caspase-1 inhibitor. Further experiments revealed that pyroptosis and the downstream inflammatory response in AS induced by IRF-1 is a process that is dependent on reactive oxygen species (ROS) generation. CONCLUSION: Our observations suggest that IRF-1 potently activates ox-LDL-induced macrophage pyroptosis and may play an important role in AS and ACS.

Sodium butyrate alleviates lipopolysaccharide-induced endometritis in mice through inhibiting inflammatory response.

Endometritis is commonly occurred in dairy cows after calving and results in a great deal of property damage. Although numerous studies have been performed to find the therapeutic agents for endometritis, the incidence of this disease remains high. Short-chain fatty acids (SCFAs), the major metabolic products of anaerobic bacteria fermentation in the gut, have been reported to exhibit anti-inflammatory properties. Therefore, the purpose of this study was to investigate the protective effects and mechanisms of sodium butyrate (SB) on lipopolysaccharide (LPS)-induced endometritis in mice. The mice were administered by intraperitoneal injection of SB at 1 h before LPS injection. 24 h later, the uterus tissues were collected. Hematoxylin and eosin (H & E) stained sections of uterus were used to determine the degree of the damage. Uterine myeloperoxidase (MPO) activity was used to analyze neutrophil granulocytes concentration. The levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were measured by ELISA. The activation of the NF-κB signaling pathway proteins were detected by Western blot analysis. The results showed that SB significantly attenuated the pathological injury of the uterus tissues. SB also suppressed LPS-induced MPO activity and the production of inflammatory cytokines TNF-α and IL-1ß. Furthermore, Western blot analysis showed that SB inhibited the activation of NF-κB signaling pathway. In addition, SB could inhibit histone deacetylases. In summary, SB protects against LPS-induced endometritis through HDAC inhibition.