NF-κB affected the serum levels of TNF-α and IL-1ß via activation of the MAPK/NF-κB signaling pathway in rat model of acute pulmonary microthromboembolism.

Pulmonary thromboembolism caused by thrombi blocking major pulmonary artery and its branches, is a frequently encountered phenomenon and an important cause of high morbidity and mortality in lung diseases and may develop into persistent pulmonary hypertension (PH). Nuclear factor-κB (NF-κB) signaling pathway had been reported participated in the formation and development of PH by promoting inflammatory response. The aim of this study was to investigate the effects of NF-κB activation on the serum levels of tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß) in acute pulmonary microthromboembolism (APMTE) rats. Rats were randomized into five groups. APMTE group received jugular vein injection of autologous thrombus, while control group rats received normal saline injection. Pulmonary hemodynamic parameters were measured through ECHO-guided transthoracic puncture. Pulmonary vascular morphological changes were analyzed by HE. The expression changes of NF-κB and serum TNF-α、IL-1ß levels were detected by enzyme-linked immunosorbent assay. Protein expression of the MAPK/NF-κB signaling pathway including p-IκBα, p-p38 MAPK, p-NF-κB p65, IκBα, p38 MAPK, and NF-κB p65 was determined using western blot analysis. Compared with control group, the expression of NF-κB in lung tissue and the levels of serum TNF-α and IL-1ß rats were higher, a significant reduction in IκBα and elevation in the phosphorylation of IκBα, p38 MAPK, and NF-κB p65 were found in APMTE group rats. And UK administration reversed the APMTE-induced increase in TNF-α, IL-1ß, p-IκBα, p-MAPK, and p-NF-κB protein. Furthermore, the levels of NF-κB, TNF-α, and IL-1ß were positively correlated with mean pulmonary artery. And the levels of TNF-α and IL-1ß were positively correlated with NF-κB. These findings suggest that the activation of MAPK/NF-κB pathway as a critical driver of increasing TNF-α and IL-1ß level in APMTE rats and UK exerted protective effects against APMTE-induced PH may be related to the downregulation of the MAPK/NF-κB signaling pathway.

A nomogram for predicting left atrial thrombus or spontaneous echo contrast in non-valvular atrial fibrillation patients using hemodynamic parameters from transthoracic echocardiography.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a high risk of stroke. This study was designed to investigate the relationship between hemodynamic parameters and left atrial thrombus/spontaneous echo contrast (LAT/SEC) in non-valvular atrial fibrillation (NVAF) patients and establish a predictive nomogram that integrates hemodynamic parameters with clinical predictors to predict the risk of LAT/SEC. Methods: From January 2019 to September 2022, a total of 354 consecutive patients with NVAF were enrolled in this cross-sectional study at the First Affiliated Hospital of Guangxi Medical University. To identify the optimal predictive features, we employed least absolute shrinkage and selection operator (LASSO) regression. A multivariate logistic regression model was subsequently constructed, and the results were visualized with a nomogram. We evaluated the model's performance using discrimination, calibration, and the concordance index (C-index). Results: We observed a 38.7% incidence of SEC/TH in NVAF patients. Independent influencing factors of LAT/SEC were identified through LASSO and multivariate logistic regression. Finally, four indicators were included, namely, previous stroke/transient ischaemic attack (OR = 4.25, 95% CI = 1.57-12.23, P = 0.006), left atrial volume index (LAVI) (OR = 1.04, 95% CI = 1.01-1.06, P = 0.001), S/D ratio (OR = 0.27, 95% CI = 0.11-0.59, P = 0.002), and left atrial acceleration factor (OR = 4.95, 95% CI = 2.05-12.79, P = 0.001). The nomogram, which incorporated these four influencing factors, demonstrated excellent predictive ability. The training set had a C-index of 0.878, while the validation set had a C-index of 0.872. Additionally, the calibration curve demonstrated great consistency between the predicted probabilities and the observed outcomes, and the decision curve analysis confirmed the important clinical advantage of the model for patients with NVAF. Conclusion: Our findings indicate that an enlarged left atrium and abnormal hemodynamic parameters in the left atrial and pulmonary veins are linked to a greater risk of LAT/SEC. Previous stroke/transient ischaemic attack, LAVI, the S/D ratio, and left atrial acceleration factor were independently associated with LAT/SEC in NVAF patients. With the incorporation of these four variables, the developed nomogram effectively predicts the risk of LAT/SEC and outperforms the CHA2DS2-VASc score.

Speckle-Tracking Echocardiography Predicts Adverse Left Ventricular Remodeling After Valve Replacement in Rheumatic Mitral Stenosis.

Background: Rheumatic mitral stenosis(RMS) may leads to left ventricular remodeling (LVR), which can persist even after valve surgery. Identifying markers for early structure and function in patients with rheumatic heart disease who are at risk for adverse LVR after surgery can help determine the optimal timing of intervention. This study aimed to investigate whether preoperative parameters of global left ventricular long-axis strain (LVGLS) and mechanical discretization (MD) could predict postoperative adverse LVR. Methods: A total of 109 adult patients with RMS and 50 healthy controls were enrolled in this study. Baseline clinical features, conventional echocardiography results, LVGLS, and MD were compared between the two groups. Pre- and post-surgery echocardiography measurements were collected, and adverse LVR was defined as a>15% increase in left ventricular end-diastolic volume or >10% decrease in left ventricular ejection fraction. Binary regression analysis was used to determine independent predictors of poor left ventricular remodeling. Results: The variables associated with adverse LVR in this study were LVGLS (P<0.001, odds ratio: 1.996, 95% CI: 1.394-2.856) and MD (P=0.011, odds ratio: 1.031, 95% CI: 1.007-1.055). The poorly reconstructed group had lower absolute values of LVGLS and higher MD than the healthy control group and the non-poorly reconstructed group. A LVGLS cutoff of -15.0% was the best predictor for patients with poorly reconstructed LVR (sensitivity: 75.7%; specificity: 100.0%; AUC: 0.93), and a MD cutoff of 63.8ms was the best predictor (sensitivity: 63.8%; specificity: 98.6%; AUC: 0.88). Conclusion: Speckle tracking echocardiography has potential value for predicting the progression of adverse LVR and for identifying non-responders among patients with RMS undergoing surgery.

Deep learn-based computer-assisted transthoracic echocardiography: approach to the diagnosis of cardiac amyloidosis.

Myocardial amyloidosis (CA) differs from other etiological pathologies of left ventricular hypertrophy in that transthoracic echocardiography is challenging to assess the texture features based on human visual observation. There are few studies on myocardial texture based on echocardiography. Therefore, this paper proposes an adaptive machine learning method based on ultrasonic image texture features to identify CA. In this retrospective study, a total of 289 participants (50 cases of myocardial amyloidosis; Hypertrophic cardiomyopathy: 70 cases; Uremic cardiomyopathy: 92 cases; Hypertensive heart disease: 77 cases). We extracted the myocardial ultrasonic imaging features of these patients and screened the features, and four models of random forest (RF), support vector machine (SVM), logistic regression (LR) and gradient decision-making lifting tree (GBDT) were established to distinguish myocardial amyloidosis from other diseases. Finally, the diagnostic efficiency of the model was evaluated and compared with the traditional ultrasonic diagnostic methods. In the overall population, the four machine learning models we established could effectively distinguish CA from nonCA diseases, AUC (RF 0.77, SVM 0.81, LR 0.81, GBDT 0.71). The LR model had the best diagnostic efficiency with recall, F1-score, sensitivity and specificity of 0.21, 0.34, 0.21 and 1.0, respectively. Slightly better than the traditional ultrasonic diagnosis model. In further subgroup analysis, the myocardial amyloidosis group was compared one-by-one with the patients with hypertrophic cardiomyopathy, uremic cardiomyopathy, and hypertensive heart disease groups, and the same method was used for feature extraction and data modeling. The diagnostic efficiency of the model was further improved. Notably, in identifying of the CA group and HHD group, AUC values reached more than 0.92, accuracy reached more than 0.87, sensitivity equal to or greater than 0.81, specificity 0.91, and F1 score higher than 0.84. This novel method based on echocardiography combined with machine learning may have the potential to be used in the diagnosis of CA.

Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertension.

Backgroud: In-situ thrombosis is a significant pathophysiological basis for the development of pulmonary hypertension (PH). However, thrombolytic therapy for in-situ thrombus in PH was often hampered by the apparent side effects and the low bioavailability of common thrombolytic medications. Nanoscale cyclic RGD (cRGD)-decorated liposomes have received much attention thanks to their thrombus-targeting and biodegradability properties. As a result, we synthesized urokinase-loaded cRGD-decorated liposome (UK-cRGD-Liposome) for therapy of in-situ thrombosis as an exploration of pulmonary hypertensive novel therapeutic approaches. Purpose: To evaluate the utilize of UK-cRGD-Liposome for targeted thrombolysis of in-situ thrombus in PH and to explore the potential mechanisms of in-situ thrombus involved in the development of PH. Methods: UK-cRGD-Liposome nanoscale drug delivery system was prepared using combined methods of thin-film hydration and sonication. Induced PH via subcutaneous injection of monocrotaline (MCT). Fibrin staining (modified MSB method) was applied to detect the number of vessels within-situ thrombi in PH. Echocardiography, hematoxylin-eosin (H & E) staining, and Masson's trichrome staining were used to analyze right ventricular (RV) function, pulmonary vascular remodeling, as well as RV remodeling. Results: The number of vessels with in-situ thrombi revealed that UK-cRGD-Liposome could actively target urokinase to in-situ thrombi and release its payload in a controlled manner in the in vivo environment, thereby enhancing the thrombolytic effect of urokinase. Pulmonary artery hemodynamics and echocardiography indicated a dramatical decrease in pulmonary artery pressure and a significant improvement in RV function post targeted thrombolytic therapy. Moreover, pulmonary vascular remodeling and RV remodeling were significantly restricted post targeted thrombolytic therapy. Conclusion: UK-cRGD-Liposome can restrict the progression of PH and improve RV function by targeting the dissolution of pulmonary hypertensive in-situ thrombi, which may provide promising therapeutic approaches for PH.

A novel method for measuring pulmonary artery pressure by high-frequency ultrasound-guided transthoracic puncture in rats.

Objectives: The success of the rat model of pulmonary hypertension (PH) is primarily dependent on the measurement of pulmonary artery pressure. We herein demonstrate a novel method for measuring pulmonary artery pressure through a high-frequency ultrasound-guided transthoracic puncture in rats. The efficacy and time of this novel method are also discussed. Methods: A single subcutaneous injection of monocrotaline (MCT) was used to establish a rat model of PH. Through the heat shaping method, the tip of that puncture cannula was maintained at a certain angle after the needle core was removed. In-plane real-time guided trocar puncture of the right ventricular outflow tract was performed in the short-axis section of the parasternal aorta. The external pressure sensor was used to record the real-time waveform of right ventricular systolic pressure, pulmonary artery systolic pressure, and diastolic pressure. Results: The success rates of which using this novel method in the model group and the control group were 88.5 and 86.7%, respectively. The time of puncture pressure measurement was 164 ± 31 and 235 ± 50 s, respectively. The right ventricular systolic blood pressure, pulmonary systolic blood pressure, and diastolic blood pressure of the model group were higher than those of the control group. Conclusion: The modified method for trocar is helpful for accurately positioning pulmonary artery manometry. The method described in this paper has a high success rate and short operation time. It can simultaneously measure systolic blood pressure, diastolic blood pressure, and mean pressure of the right ventricle and pulmonary artery. It has a broad application prospect in verifying the rat PH model and pulmonary artery pressure monitoring.

Three-dimensional echocardiographic comparison of left ventricular geometry and systolic function between dilated cardiomyopathy and mitral regurgitation with similar left ventricular dilation.

PURPOSE: This study aimed to analyze left ventricular (LV) remodeling in patients with LV dilation using three-dimensional (3D) echocardiography, and to compare geometry and systolic function between patients with dilated cardiomyopathy (DCM) and with mitral regurgitation (MR) but similar LV dimension. METHODS: Cross-sectional study of 60 DCM and 60 MR patients with LV end diastolic diameter (LVEDD) > 35 mm/m2 , and of 60 healthy control volunteers. RESULTS: Despite a similar LVEDD, DCM patients showed a significantly higher 3D sphericity index (3D-SI) than MR patients, whereas 3D ejection fraction (3D-EF) was significantly lower (P < .01). There was a linear relationship between 3D-EF and 3D-SI in both DCM and MR patients (r = -0. 745 and r = -0. 642, respectively; both P < .001). Receiver operating characteristic (ROC) curves showed that 3D-SI had could better discriminate between DCM and MR (sensitivity 90%; specificity 73%; AUC 0.852, P < .01) than other variables. The area under the ROC curve of 3D-SI was significantly larger than that of 3D-EF for detecting heart failure in both patients with DCM and MR. CONCLUSIONS: LV geometry appears to be more spherical and associated with worse systolic function in DCM than in MR patients, in spite of similar LV dimensions. Systolic function correlated significantly with 3D-SI, which provided a better description of LV remodeling and could be a stronger indicator of heart failure in patients with LV dilation.

Anticoagulation in atrial fibrillation and cognitive decline: A systematic review and meta-analysis.

BACKGROUND: It is well known that atrial fibrillation (AF) carried a high risk of cognitive decline, which is independent of stroke or transient ischemic attack (TIA). Whether anticoagulation is associated with reduced risk of cognitive decline in participants with AF still remains controversial. We conducted a systematic review and meta-analysis to explore the effect of anticoagulation on the risk of cognitive decline in patients with AF. METHODS: We systematically searched the PubMed, Embase and the Cochrane Database for eligible studies published up to January 2018. Risk ratios (RR) with 95% confidence interval (CI) for cognitive decline were extracted, and pooled estimations were calculated using the fixed effects model. Subgroup analyses were further performed. RESULTS: Eight relevant articles involved 454,273 patients were ultimately included in this meta-analysis. We found that anticoagulation was associated with reduced risk of cognitive impairment as compared with nonanticoagulation (RR 0.72, 95% CI 0.69-0.75, I 11.5%). This reduction was still significant after adjustment for stroke and TIA (RR 0.72, 95% CI 0.69-0.74, I 0.0%). In the subgroup analyses, the incidence of cognitive decline was significantly decreased in those treated with anticoagulation compared to no treatment (RR 0.72, 95% CI 0.69-0.75, I 0.0%), but the cognitive benefit showed no significant difference between anticoagulant and antiplatelet treatment (RR 1.01, 95% CI 0.68-1.50, I 46.8%). CONCLUSION: Anticoagulation is associated with cognitive benefit in participants with AF independent of stroke and TIA, but it was not superior to antiplatelet drugs in reducing the risk of cognitive decline.

Usefulness of three-dimensional spherical index to assess different types of left ventricular remodeling: A meta-analysis.

BACKGROUND: Left ventricular (LV) remodeling after myocardial injury, volume or pressure overload is characterized by a change in LV shape from an ellipse to more of a sphere. The usefulness of 3-dimensional (3D) sphericity index (SpI) for accurate evaluation of LV remodeling remains uncertain despite extensive research. METHODS: We searched Pubmed, Embase, Web of Science, and Cochrane databases to identify relevant studies from January 1, 1990 to August 1, 2016. The quality of each study was evaluated using the Newcastle-Ottawa Scale. Meta regression and sensitivity and subgroup analyses based on patterns of LV remodeling were performed. RESULTS: Thirteen studies with a total of 1064 patients were included in this meta-analysis. There was evidence of obvious heterogeneity (I = 82.4%; P < .001), which was mainly accounted for by the pattern of remodeling according to meta-regression. The result of subgroup meta-analyses suggested that SpI in patients with eccentric remodeling was significantly higher compared with control group (95% confidence interval [CI], 0.78-1.10). No statistic difference was found in LV SpI between healthy controls and patients with concentric hypertrophy (95% CI, -0.89 to 0.16) or myocardial injury (95% CI, -0.13 to 0.41). CONCLUSION: 3D SpI can be widely used to assess LV remodeling in patients with eccentric remodeling, but has limitations in predicting concentric hypertrophy and regional or chronic myocardial injury.

Distribution of PCDD/Fs and organometallic compounds in sewage sludge of wastewater treatment plants in China.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), organotin and organolead compounds were measured in sewage sludge samples collected from 24 wastewater treatment plants from 18 cities of 13 provinces in China. Total international toxicity equivalent (I-TEQ) values were evaluated for PCDD/Fs. The total concentration of PCDD/Fs ranged from 104.0 to 1661 pg/g dry weight (d.w.) and 2.51-75.21 pg I-TEQ/g d.w., indicating that all I-TEQs were below Chinese legislation limit value regulated for land application. The concentrations ranged from 258 to 3886, 126 to 1129, and 84-2133 ng/g as Sn d.w., for tributyltin (TBT), dibutyltin (DBT), and diphenyltin (DPhT), respectively. On the other side, organolead concentrations ranged from 85 to 668 with an average of 279 ng/g as lead. High concentrations of organolead compounds in sewage sludge indicated that the environmental impact of organolead compounds remains in China.

Distribution and characterization of organochlorine pesticides and polycyclic aromatic hydrocarbons in surface sediment from Poyang Lake, China.

The concentrations of organochlorine pesticides (OCPs) and 16 priority polycyclic aromatic hydrocarbons (PAHs) were investigated in the sediments from Poyang Lake, the largest freshwater lake in China. The results showed that the total concentrations of four hexachlorocyclohexane (HCH) isomers (α-HCH, ß-HCH, γ-HCH, δ-HCH), three dichlorodiphenyltrichloroethane (DDT) homologs and their metabolites (p,p'-DDD, o,p'-DDD, p,p'-DDE, p,p'-DDT, o,p'-DDT, o,p'-DDE), sodium pentachlorophenate and PAHs varied from 0.536±0.330 to 6.937±2.655, 14.421±5.260 to 82.871±31.258, 15.346±6.935 to 48.254±16.836, and 33.0±11.5 to 369.1±138.5 µg/kg, respectively. The concentrations of HCH isomers followed the order: γ-HCH>ß-HCH>δ-HCH>α-HCH. The most dominant γ-HCH ranged from 0.253±0.155 to 3.465±1.010 µg/kg, suggesting a recent input of lindane. p,p'-DDD was the most dominant pollutant of DDTs, with a mean concentration of 31.684±13.530 µg/kg. The ratios of (DDE+DDD)/DDT ranged from 75±24 to 360±115, indicating no recent input of DDTs. The PAHs were mainly originated from liquid fossil fuel combustion and leakage, except at Pojiang River estuary, where the pyrogenic source (coal, grass and wood combustion) was dominant. Several PAH metabolites were identified and the possible degradation pathways were proposed.