Novel insight into MDA-7/IL-24: A potent therapeutic target for autoimmune and inflammatory diseases.

Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24) is a pleiotropic member of the IL-10 family of cytokines, and is involved in multiple biological processes, including cell proliferation, cell differentiation, tissue fibrosis, the inflammatory response, and antitumor activity. MDA-7/IL-24 can regulate epithelial integrity, homeostasis, mucosal immunity and host resistance to various pathogens by enhancing immune and inflammatory responses. Our recent study revealed the mechanism of MDA-7/IL-24 in promoting airway inflammation and airway remodeling through activating the JAK/STAT3 and ERK signaling pathways in bronchial epithelial cells. Herein, we summarize the cellular sources, inducers, target cells, signaling pathways, and biological effects of MDA-7/IL-24 in several allergic and autoimmune diseases. This review also synopsizes recent advances in clinical research targeting MDA-7/IL-24 or its receptors. Based on these advancements, we emphasize its potential as a target for immunotherapy and discuss the challenges of developing immunotherapeutic drugs targeting MDA-7/IL-24 or its receptors in autoimmune and inflammatory disorders.

IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ.

Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.

Risk factors for mortality in surgical patients on combined continuous renal replacement therapy and extracorporeal membrane oxygenation: single-center retrospective study.

OBJECTIVE: In patients receiving extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT) is increasingly being used for renal replacement and fluid management. However, critically ill surgical patients receiving combined ECMO and CRRT tend to have a high mortality rate, and there are limited studies on this population. Therefore, we aimed to investigate the risk factors for mortality in surgical patients receiving combined ECMO and CRRT. METHODS: Data of surgical patients who underwent ECMO between December 2013 and April 2023 were retrospectively reviewed. Univariate and multivariate logistic regression analysis were used to identify the risk variables. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff value of albumin and age to predict death. RESULTS: A total of 199 patients on ECMO support were screened, of which 105 patients were included in the final analysis. Of 105 patients, 77 (73.33%) were treated with CRRT. Veno-arterial ECMO was performed in 97 cases (92.38%), and the rest were veno-venous ECMO (n = 8, 7.62%). Cardiovascular-related surgery was performed in the main patients (n = 86, 81.90%) and other types of surgery in 19 patients. In surgical patients on ECMO support, the logistic regression analysis showed that CRRT implantation, male sex, and age were the independent risks factors for mortality. Furthermore, the ROC curve analysis showed that age 48.5 years had the highest Youden index. In surgical patients on combined CRRT and ECMO, age, valvular heart disease, and albumin were the independent risk factors for prognosis. Albumin had the highest Youden index at a cutoff value of 39.95 g/L for predicting mortality, though the overall predictive value was modest (area under ROC 0.704). Age had the highest Youden index at a cutoff value of 48.5 years for predicting mortality. CONCLUSIONS: In our cohort of surgical patients requiring ECMO, which consisted mostly of patients undergoing cardiovascular surgery requiring VA-ECMO, the need for CRRT was an independent risk factor for mortality. In the subset of patients on combined CRRT and ECMO, independent risk factors for mortality included higher age, lack of valvular heart disease, and lower serum albumin.

Belumosudil, ROCK2-specific inhibitor, alleviates cardiac fibrosis by inhibiting cardiac fibroblasts activation.

Cardiac fibrosis is thought to be the hallmark of pathological hypertrophic remodeling, of which the myofibroblast transdifferentiation is the key cell biological event. However, there is still no specific and effective therapeutic agent approved for cardiac fibrosis. To investigate the effects of belumosudil, the first ρ-associated kinase-2 (ROCK2)-specific inhibitor, on cardiac hypertrophy, fibrosis, and dysfunction induced by pressure overload, the transverse aortic constriction (TAC) or sham operation was carried out on wild-type C57BL/6 mice (male, 6-8 wk old) under pentobarbital anesthesia. After that, mice were randomly divided into three groups: sham operation + vehicle, TAC + vehicle, TAC + 50 mg·kg-1·day-1 belumosudil. We found that belumosudil effectively ameliorated cardiac hypertrophy, fibrosis, and dysfunction in TAC mice. To elucidate the underlying mechanism, we inhibited the expression of ROCK2 in vitro by either belumosudil or siRNA. We showed that the inhibition of ROCK2 by either belumosudil or knockdown suppressed cardiac fibroblasts activation and proliferation significantly induced by transforming growth factor-ß1 (TGF-ß1). Furthermore, our study confirmed ROCK2 mediates cardiac fibrosis by interacting with TGF-ß1/mothers against decapentaplegic homolog 2 (Smad2) pathway. Taken together, we demonstrated that belumosudil ameliorates cardiac hypertrophy and fibrosis induced by TAC via inhibiting cardiac fibroblasts activation. In conclusion, belumosudil may be a promising therapeutic drug for cardiac hypertrophy and fibrosis induced by myocardial pressure overload.NEW & NOTEWORTHY Although ρ-associated kinase-2 (ROCK2) is the main isoform of ρ-associated kinases (ROCKs) in the heart and more important in cardiac hypertrophy and fibrosis than ρ-associated kinase-1 (ROCK1), there has not been any pharmacological approach to inhibit ROCK2 selectively. Our study demonstrates for the first time that belumosudil, the first ROCK2-specific inhibitor, effectively ameliorates cardiac hypertrophy, fibrosis, and dysfunction induced by TAC via inhibiting cardiac fibroblasts activation.

IL-37 protects against airway remodeling by reversing bronchial epithelial-mesenchymal transition via IL-24 signaling pathway in chronic asthma.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown. We aimed to explore the effect and mechanism of IL-24 on EMT and to verify whether IL-37 could alleviate IL-24-induced EMT in chronic asthma. METHODS: BEAS-2B cells were exposed to IL-24, and cell migration was assessed by wound healing and Transwell assays. The expression of EMT-related biomarkers (E-cadherin, vimentin, and α-SMA) was evaluated after the cells were stimulated with IL-24 with or without IL-37. A murine asthma model was established by intranasal administration of house dust mite (HDM) extracts for 5 weeks, and the effects of IL-24 and IL-37 on EMT and airway remodeling were investigated by intranasal administration of si-IL-24 and rhIL-37. RESULTS: We observed that IL-24 significantly enhanced the migration of BEAS-2B cells in vitro. IL-24 promoted the expression of the EMT biomarkers vimentin and α-SMA via the STAT3 and ERK1/2 pathways. In addition, we found that IL-37 partially reversed IL-24-induced EMT in BEAS-2B cells by blocking the ERK1/2 and STAT3 pathways. Similarly, the in vivo results showed that IL-24 was overexpressed in the airway epithelium of an HDM-induced chronic asthma model, and IL-24 silencing or IL-37 treatment could reverse EMT biomarker expression. CONCLUSIONS: Overall, these findings indicated that IL-37 mitigated HDM-induced airway remodeling by inhibiting IL-24-mediated EMT via the ERK1/2 and STAT3 pathways, thereby providing experimental evidence for IL-24 as a novel therapeutic target and IL-37 as a promising agent for treating severe asthma.

Microbial Contamination Characteristics on Touch Surfaces in Outpatient Self-Service Facilities.

BACKGROUND: With the development of science and technology, self-service facilities have been widely used in hospitals. This study aimed to assess the microbial contamination characteristics on touch surfaces in outpatient, self-service facilities from Monday to Friday. METHODS: Touch surfaces in outpatient facilities were swabbed and surveyed for total microbial growth before and after work every morning. Selected bacteria were identified to screen for pathogenic organisms. RESULTS: There were 360 samples collected, 87 samples (24.2%) were culture-positive. Staphylococcus species were the main microbial contamination. The three most common bacteria were S. hominis, S. epidermidis and S. hemolyticus. After work, more microbial contamination was found on Monday (p = 0.029). There was no difference in sample positive rates between self-service facilities and manual service area. Although, the antibiotic resistance patterns of different staphylococcus species were different, the overall drug resistance rate is low. Only one S. aureus was methicillin-Sensitive S. aureus. CONCLUSIONS: The self-service facilities' touch surfaces microbial contamination were similar to manual service area, but the more used, the more microbial contamination was found. Hospitals should enhance cleaning times of self-service facilities to keep them clean, especially on Mondays.

Outcome analysis for prediction of intraaortic balloon pump support failure and long-term survival in high-risk patients undergoing mitral valve surgery.

The outcome predictors of intra-aortic balloon pump (IABP) in patients who undergo mitral valve surgery remain unknown. This study aimed to retrospectively review valvular surgery in patients who received an IABP to identify the predictors of failure of IABP support and anticipate the necessary therapy. This retrospective observational study recruited a total of 157 consecutive patients who underwent open-heart mitral valve surgery with IABP implantation intraoperatively or postoperatively. Univariate and multivariate logistic regression analyses were performed to identify the risk factors attributed to 30-day mortality. Follow-up data of survivors were collected to investigate the effect of IABP support to evaluate long-term outcomes. The overall 30-day mortality was 35.7% (56 patients). The following factors that contributed to 30-day mortality included sepsis (P < .001, OR: 5.627, 95%CI: 2.422-11.683); IABP implantation postoperatively rather than intraoperatively (P = .001, OR: 6.395, 95%CI: 2.085-19.511); right heart failure (P = .042, OR: 3.419, 95%CI: 1.225-12.257); and lack of subvalvular apparatus preservation (P = .033, OR: 3.710, 95%CI: 1.094-13.167). Furthermore, follow-up data of these patients showed an estimation of 5-year and 10-year survival rates of 58.9% and 35.7%, respectively. Patients with intraoperative IABP demonstrated better long-term survival outcomes when compared to those with postoperative IABP (χ2  = 4.291, P = .038). In summary, this study distinguished the preoperative predictors of 30-day mortality of IABP-support in mitral valve surgery patients. These results indicated that early intervention with IABP should be taken into consideration in case of hemodynamic instability in critically ill patients undergoing mitral valve surgery.

Long-Term Results of Surgical Atrial Fibrillation Radiofrequency Ablation: Comparison of Two Methods.

BACKGROUND: This retrospective study aimed to evaluate the long-term results of two kinds of surgical atrial fibrillation radiofrequency ablations in concomitant cardiac operations. METHODS: We enrolled 129 patients from January 2006 to December 2015 and performed cardiac operations concomitantly with surgical atrial fibrillation. The patients were divided into a biatrial MAZE group (94 patients) and a left atrial MAZE group (35 patients). A preoperative baseline was compared with intraoperative and postoperative data. Similarly, complications and follow-up results were compared. A matching process based on propensity-score was performed to equalise the potential prognostic factors in both groups and to formulate a balanced 2:1 matched cohort study. RESULTS: There were four deaths (4.3%) in the biatrial MAZE group and one death in left atrial MAZE group due to multiple organ failures followed by low cardiac output. No permanent pacemaker implantations were used in either group. The sinus rhythm maintenance rates at the 6-month, 1-year, 6-year and 8-year follow-ups between the biatrial MAZE group and the left atrial MAZE group were not significantly different (84.7%, 83.3%, 67.3%, and 58.8% vs. 84.9%, 77.4%, 61.1%, and 50%, p>0.05). Similarly, between the propensity-score matched groups, there were no significant differences. CONCLUSION: The left atrial MAZE ablation for the patients with mitral valve diseases who needed open cardiac operation was safe and effective when compared with the biatrial MAZE ablation group.

DACT1 is involved in human placenta development by promoting Wnt signaling.

OBJECTIVE: The aim of this study was to evaluate the expression of DACT1 in human placenta tissue and the relationship between DACT1 and target genes of the Wnt signaling pathway. METHOD: Real-time PCR and western blotting were used to detect the expression of DACT1 and the target genes of Wnt signaling pathway in human placenta tissue. And the relationship between them was analyzed using SPSS 19. RESULTS: Real-time PCR results showed that DACT1 expression was significantly higher in 49- to 71-day placenta tissues (mean value = 0.020) than that in 39- to 48-day (the mean value = 0.009). The mRNA expressions of the Wnt signaling pathway target genes, CCND1, CCND2, FOSL1, DAB2 and JUN, were also increased expressed in human placenta tissues. Significant positive associations between DACT1 and CCND1, CCND2, FOSL1, DAB2 and JUN were observed. Western blotting analysis showed that the protein expression of DACT1, CCND1, CCND2, FOSL1, DAB2 and JUN displayed the increasing trend in 43-, 49- and 71-day placenta samples. CONCLUSION: DACT1 might play an important role in human placenta development via promoting Wnt signaling.

Super-Structured Wet-Adhesive Hydrogel with Ultralow Swelling, Ultrahigh Burst Pressure Tolerance, and Anti-Postoperative Adhesion Properties for Tissue Adhesion.

Wet-adhesive hydrogels have been developed as an attractive strategy for tissue repair. However, achieving simultaneously low swelling and high burst pressure tolerance of wet-adhesive hydrogels is crucial for in vivo application which remains challenges. Herein, a novel super-structured porous hydrogel (denoted as PVA/PAAc-N+ ) is designed via facile moisture-induced phase separation-solvent exchange process for obtaining porous polyvinyl alcohol (PVA) hydrogel as dissipative layer and in situ photocuring technology for entangling quaternary ammonium-functionalized poly(acrylic acid)-based wet-adhesive layer (PAAc-N+ ) with the porous surface of PVA layer. Benefitting from the ionic crosslinking between quaternary ammonium ions and carboxylate ions in PAAc-N+ wet-adhesive layer as well as the high crystallinity induced by abundant hydrogen bonds of PVA layer, the hydrogel has unique ultralow swelling property (0.29) without sacrificing adhesion strength (63.1 kPa). The porous structure of PVA facilitates the mechanical interlock at the interface between PAAc-N+ wet-adhesive layer and tough PVA dissipative layer, leading to the ultrahigh burst pressure tolerance up to 493 mm Hg and effective repair for porcine heart rupture; the PVA layer surface of PVA/PAAc-N+ hydrogel can prevent postoperative adhesion. By integrating ultralow swelling, ultrahigh burst pressure tolerance, and anti-postoperative adhesion properties, PVA/PAAc-N+ hydrogel shows an appealing application prospect for tissue repair.

Impact of heart failure and preoperative platelet count on the postoperative short-term outcome in infective endocarditis patients.

BACKGROUND: Heart failure (HF) and platelet count are often considered risk factors for mortality in patients with infective endocarditis (IE); however, their effects on various complications have not been elucidated. HYPOTHESIS: We speculated that HF and platelet count have significant impact on the short-term outcomes of IE. METHODS: This single-center retrospective study analyzed data from 320 IE patients who underwent surgery. A multivariate Cox proportional hazards model was used to identify the risk factors for adverse outcomes. The effect of the platelet count on the prognosis of patients with HF was determined by subgroup analysis and Kaplan-Meier analysis. RESULTS: The study population was divided into the HF group (n = 102) and the non-HF group (n = 218). The median age of the total population was 44.5 years (31-56 years), of which 227 (70.94%) patients were male. The incidence rates of 1-year all-cause mortality, cardiac outcomes, and composite outcomes were respectively almost sixfold, fourfold, and threefold higher in the HF group than in the non-HF group (all p < 0.001). In multivariate Cox regression analysis, HF was an independent risk factor for 1-year all-cause mortality, cardiac outcomes, cerebral outcomes, and composite outcomes. The Kaplan-Meier survival curves revealed that the patients with both HF and thrombocytopenia demonstrated the worst composite outcomes than the patients of the other groups (log-rank p < 0.001). In the HF group, the platelet count was significantly associated with mortality and composite outcomes. CONCLUSIONS: HF and preoperative platelet count are significantly associated with 1-year all-cause mortality and adverse outcomes postoperatively in IE patients. Patients with HF and thrombocytopenia have the worst short-term prognosis.

Development and validation of a postoperative bleeding complications prediction model in infective endocarditis.

OBJECTIVES: Bleeding complications are one of the most serious postoperative complications after cardiac surgery and are associated with high mortality, especially in patients with infective endocarditis (IE). Our objectives were to identify the risk factors and develop a prediction model for postoperative bleeding complications in IE patients. METHODS: The clinical data of IE patients treated from October 2013 to January 2022 were reviewed. Multivariate logistic regression analysis was used to evaluate independent risk factors for postoperative bleeding complications and develop a prediction model accordingly. The prediction model was verified in a temporal validation cohort. The performance of the model was evaluated in terms of its discrimination power, calibration, precision, and clinical utility. RESULTS: A total of 423 consecutive patients with IE who underwent surgery were included in the final analysis, including 315 and 108 patients in the training cohort and validation cohort, respectively. Four variables were selected for developing a prediction model, including platelet counts, systolic blood pressure, heart failure and vegetations on the mitral and aortic valves. In the training cohort, the model exhibited excellent discrimination power (AUC = 0.883), calibration (Hosmer-Lemeshow test, P = 0.803), and precision (Brier score = 0.037). In addition, the model also demonstrated good discrimination power (AUC = 0.805), calibration (Hosmer-Lemeshow test, P = 0.413), and precision (Brier score = 0.067) in the validation cohort. CONCLUSIONS: We developed and validated a promising risk model with good discrimination power, calibration, and precision for predicting postoperative bleeding complications in IE patients.

Randomized evidence on graft patency after off-pump versus on-pump coronary artery bypass grafting: An updated meta-analysis.

BACKGROUND: The debate between off-pump CABG (OPCAB) and on-pump CABG (ONCAB) has been ongoing for decades. We aimed to provide a comprehensive update of the current randomized controlled trials (RCTs) in evaluating the graft patency of OPCAB versus ONCAB. MATERIALS AND METHODS: A literature search was conducted in PubMed, EMBASE, and the Cochrane Library databases until April 30, 2021. All RCTs from 2003 to 2020 comparing the results of graft patency between OPCAB and ONCAB were included. We compared the overall graft occlusion between the two groups, and subgroup analyses were conducted based on different types of conduits and target territories, crossover from off-pump to on-pump rate, and the length of follow-up. RESULTS: Sixteen RCTs were identified, with 5743 grafts in the OPCAB group and 5898 in the ONCAB group. OPCAB was associated with a higher risk of occlusion in the overall graft (RR: 1.31; 95% CI, 1.17-1.46), saphenous vein graft (SVG) (RR: 1.40; 95% CI, 1.23-1.59), grafts to left anterior descending (LAD) territory (RR: 1.52; 95% CI, 1.11-2.08) and left circumflex artery (LCX) territory (RR: 1.45; 95% CI, 1.19-1.76), while no significant difference was observed between the two groups in respect of arterial conduits and grafts to right coronary artery (RCA) territory. Furthermore, the lower crossover rate and longer length of follow-up appeared to reduce the association between OPCAB and lower graft patency. CONCLUSIONS: The current meta-analysis indicates that, compared with ONCAB, graft patency is poorer with OPCAB for overall grafts, SVG grafts, grafts to LAD and LCX territories, whereas the results remain comparable for arterial conduits and grafts to RCA territory.

A New Minimally Invasive Method of Transverse Aortic Constriction in Mice.

Transverse aortic constriction (TAC) in mice is the most popular model to mimic pressure overload heart disease. In this study, we developed a convenient, quick, and less invasive new TAC mice model. Briefly, after anesthetization, endotracheal intubation was then performed, and the endotracheal tube was connected to a ventilator. The second intercostal space was opened and then the home-made retractors were used to push aside the thymus gently. A tunnel under the aortic arch was made and a segment of 6-0 monofilament polypropylene suture which had been threaded through a specifically modified blunted 26-gauge syringe needle was passed through the tunnel. A blunted 27-gauge needle was placed parallel to the transverse aorta and then three knots were tied quickly. After ligation, the spacer was removed promptly and gently to achieve a constriction of 0.4 mm in diameter. Five weeks after TAC, cardiac hypertrophy, fibrosis, and left ventricular dysfunction were observed. The mouse was anesthetized with pentobarbital (50 mg/kg) via intraperitoneal injection. Endotracheal intubation under direct vision was then performed and the endotracheal tube was connected to a ventilator. The second intercostal space was opened and then the home-made retractors were used to push aside the thymus gently. A tunnel under the aortic arch was made and a segment of 6-0 monofilament polypropylene suture which had been threaded through a specifically modified blunted 26-gauge syringe needle was passed through the tunnel.

Disheveled binding antagonist of ß-catenin 1 interacted with ß-catenin and connexin 43 in human-induced pluripotent stem cells-derived cardiomyocytes.

Previously, we demonstrated that the disheveled binding antagonist of ß-catenin 1 (DACT1) was involved in atrial fibrillation by regulating the reorganization of connexin 43 and ß-catenin in cardiomyocytes. Little is known, however, about DACT1 in human normal myocardial cells. Therefore, we used cardiomyocytes (CMs) derived from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to investigate the role of DACT1 and its connection with ß-catenin and connexin 43. While the ESC-CMs and iPSC-CMs were differentiated using commercial differentiation kits, the cardiac-specific markers were detected by immunofluorescence. The expression level of DACT1 was detected using western blotting, whereas the interaction of DACT1 and connexin 43 or ß-catenin was detected by immunofluorescence and co-immunoprecipitation (co-IP) assays. Both H1-CMs and SF-CMs were immunostained for cardiac-specific markers, including Troponin I, Troponin T, α-actinin, NKX2.5, and GATA6. While DACT1 was not expressed in both H1 ESCs and SF-iPSCs, it was, however, highly expressed in differentiated CMs, being also localized in the cytoplasm and the nucleus of differentiated CMs. Interestingly, the DACT1 expression in different nuclei was different in the same multinucleated cell. Moreover, DACT1 colocalized with ß-catenin in both the cytoplasm and nucleus of differentiated CMs, and it also colocalized with connexin 43 in the perinuclear region and the gap junctions of differentiated CMs. Co-IP results showed that DACT1 could directly bind to ß-catenin and connexin 43. Taken together, DACT1 interacted with ß-catenin and connexin 43 in human-induced pluripotent stem cells-derived cardiomyocytes.

Neutrophil Gelatinase-associated Lipocalin: A Potential Predictor of Embolic Events in Endocarditis.

BACKGROUND: As the complication of infective endocarditis (IE), embolic events are associated with increased mortality and morbidity. However, there are no reliable indicators to predict embolism. The aim of this study was to evaluate neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker to identify IE patients at high risk of embolism. METHODS: We conducted a prospective observational study of IE patients from January 2018 to December 2020. Plasma NGAL levels were measured in 88 IE patients (37 patients with embolic events and 51 patients without embolic events), 91 noninfectious heart valve disease patients, and 20 healthy blood donors by enzyme-linked immunosorbent assay. Native valve tissue was obtained from 16 IE patients and 16 noninfectious heart valve disease patients. Western blot and immunohistochemical staining were performed to detect NGAL and matrix metalloproteinase-9. RESULTS: Higher levels of NGAL were observed in IE patients than in noninfectious heart valve disease patients (P < .001) or healthy blood donors (P < .01). In addition, NGAL levels were higher in IE patients with embolic events compared with patients not having embolic events (P < .001). Receiver-operating characteristics analysis demonstrated that NGAL acted as a potential embolic events predictor with the cutoff value of 166.78 ng/mL. The IE patients with higher NGAL levels had significantly more severe native valve morphologic changes. The NGAL was colocalized with matrix metalloproteinase-9, and their expression in the valves of IE patients was higher than in those of noninfectious heart valve disease patients. CONCLUSIONS: Neutrophil gelatinase-associated lipocalin is a potential predictor of embolic events in IE. That may be attributed to its potency of increasing the proteolytic activity of matrix metalloproteinase-9, which leads to valve morphologic impairment.

IL-24 Contributes to Neutrophilic Asthma in an IL-17A-Dependent Manner and Is Suppressed by IL-37.

PURPOSE: Neutrophilic asthma is associated with asthma exacerbation, steroid insensitivity, and severe asthma. Interleukin (IL)-24 is overexpressed in asthma and is involved in the pathogenesis of several allergic inflammatory diseases. However, the role and specific mechanism of IL-24 in neutrophilic asthma are unclear. We aimed to elucidate the roles of IL-24 and IL-37 in neutrophilic asthma, the relationships with IL-17A and the mechanisms regulating neutrophilic asthma progression. METHODS: Purified human neutrophils were isolated from healthy volunteers, and a cell coculture system was used to evaluate the function of IL-24 in epithelium-derived IL-17A-dependent neutrophil migration. IL-37 or a small interfering RNA (siRNA) targeting IL-24 was delivered intranasally to verify the effect in a murine model of house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic asthma. RESULTS: IL-24 enhanced IL-17A production in bronchial epithelial cells via the STAT3 and ERK1/2 signaling pathways; this effect was reversed by exogenous IL-37. Anti-IL-17A monoclonal antibodies reduced neutrophil chemotaxis induced by IL-24-treated epithelial cells in vitro. Increased IL-24 and IL-17A expression in the airway epithelium was observed in HDM/LPS-induced neutrophilic asthma. IL-37 administration or IL-24 silencing attenuated neutrophilic asthma, reducing IL-17A levels and decreasing neutrophil airway infiltration, airway hyperresponsiveness, and goblet cell metaplasia. Silencing IL-24 inhibited T-helper 17 (Th17) immune responses, but not Th1 or Th2 immune responses, in the lungs of a neutrophilic asthma model. CONCLUSIONS: IL-24 aggravated neutrophilic airway inflammation by increasing epithelium-derived IL-17A production, which could be suppressed by IL-37. Targeting the IL-24/IL-17A signaling axis is a potential strategy, and IL-37 is a potential candidate agent for alleviating neutrophilic airway inflammation in asthma.

Increased glucose variability is associated with major adverse events in patients with infective endocarditis undergo surgical treatment.

BACKGROUND: This study aimed to investigate the prognostic value of glucose variability (GV) in predicting postoperative major adverse events (MAEs) in patients with infective endocarditis (IE) who underwent surgical treatment. METHODS: This retrospective observational study included a total of 381 consecutive patients who underwent surgical treatment in our institution from October 2007 to August 2019. The MAEs included all-cause death, stroke, myocardial infarction, acute heart failure, IE recurrence, acute renal failure and sepsis. Postoperative GV in the first 24 hours was measured by the mean 24-hour glucose, standard deviation, coefficient of variation (CV) and mean amplitude of glycemic excursions. Univariate and multivariate logistic regression analyses were performed to identify the independent association of GV with MAEs. RESULTS: Of the 381 patients, 79 (20.7%) developed MAEs. The 30-day mortality of the overall study cohort was 5.23%. The multivariate logistic regression analysis indicated that 24-hour GV, measured as the CV [odds ratio (OR) =1.49, 95% CI, 1.23-3.57, P=0.012], was significantly associated with MAEs in IE patients. For every 10% increase in 24-hour CV, there was a 49% increase in the risk of MAEs. Furthermore, compared to patients in the low tertile of GV, patients in the top tertile of 24-hour GV had a higher 30-day mortality and an increased incidence of heart failure and hemodialysis as well as longer ventilation support. CONCLUSIONS: The results of this retrospective investigation demonstrated that increased GV measured by CV is an independent predictor of postoperative MAEs in patients undergoing surgical treatment for IE.

Respiratory nursing care with Angong Niuhuang pill for patients with chronic obstructive pulmonary disease following cardiac surgery.

AIM: Angong Niuhuang pill (ANP) is a traditional Chinese medicine (TCM) drug widely used for treating stroke. This study aimed to investigate the effect of ANP on respiratory nursing outcomes in chronic obstructive pulmonary disease (COPD) patients following cardiac surgery. METHODS: A total of 80 COPD patients following cardiac surgery were enrolled and randomized into the control group receiving routine postoperative nursing and ANP group additionally receiving ANP treatment for 3 days (n = 40 for both group). The frequency of back percussion, time of back percussion, amount of expectoration, arterial blood gas levels were compared between groups. RESULTS: Compared to the control group, the ANP group had a significantly shorter daily mean time of back percussion at day 3 (p = .036) and day 7 (p = .014). The daily mean amount of expectoration was higher at day3 (p = .018) but lower at day 7 (p = .043) in the ANP group than in the control group. In addition, the ANP group had significantly higher hemoglobin saturation (SpO2 ) and partial pressure of oxygen (PaO2 ) but lower partial pressure of carbon dioxide (PaCO2 ) at both day 3 and day 7 than the control group (all p < .05). Furthermore, the time of postoperative aerosol inhalations (p = .041), pulmonary infection rate (p = .025) and postoperative hospital stay (p = .036) were significantly reduced in the ANP group. The ANP group had significantly lower TCM symptom scores at day 3 and day 7 after surgery. CONCLUSION: These results suggested that ANP treatment can effectively promote the postoperative recovery and respiratory nursing outcomes in COPD patients following cardiac surgery.

Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model.

BACKGROUND: Myocardial injury is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to test the hypothesis that melatonin could attenuate myocardial injury in a rat CPB model. METHODS: Eighteen male Sprague-Dawley rats were randomly divided into three groups, n = 6 for each group: the sham operation (SO) group, CPB group and melatonin group. Rats in the SO group underwent cannulation without CPB, rats in CPB group intraperitoneal injected an equal volume of vehicle daily for 7 days before being subjected to CPB and rats in melatonin group intraperitoneal injected 20 mg/kg of melatonin solution daily for 7 days before being subjected to CPB. After 120 min for CPB, the expression levels of plasma interleukin (IL) -6, IL-1ß, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), creatine kinase (CK) -MB and cardiac troponin T (cTnT) were measured. Reactive oxygen species (ROS) were detected by dihydroethidium (DHE). Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Mitochondrial damage and autophagosomes were detected by electron microscopy. Apoptosis inducing factor (AIF) was detected by immunofluorescence. The expression of B cell lymphoma/leukemia2 associated X (Bax), B cell lymphoma/leukemia 2 (Bcl-2), cytochrome C (Cyto-C), cleaved caspase-9, AKT, p-AKT, signal transducer and activator of transcription 3 (STAT3), p-STAT3, LC3, P62, mechanistic target of rapamycin kinase (mTOR), p-mTOR and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using western blotting. RESULTS: Melatonin significantly decreased the levels of IL-1ß, IL-6, MDA, CK-MB and cTnT and increased the levels of SOD and GSH-Px, all of which were altered by CPB. Melatonin reduced cardiomyocyte superoxide production, the apoptosis index and autophagy in cardiomyocytes induced by CPB. The AKT, STAT3 and mTOR signaling pathways were activated by melatonin during CPB. CONCLUSION: Melatonin may serve as a cardioprotective factor in CPB by inhibiting oxidative damage, apoptosis and autophagy. The AKT, STAT3 and mTOR signaling pathways were involved in this process.