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.

Predictive Factors of Nonmalignant Pathological Diagnosis and Final Diagnosis of Ultrasound-Guided Cutting Biopsy for Peripheral Pulmonary Diseases.

This study aimed to explore the predictive factors of nonmalignant pathological diagnosis and final diagnosis of ultrasound-guided cutting biopsy for peripheral pulmonary diseases. A total of 470 patients with peripheral lung disease diagnosed as nonmalignant by ultrasound-guided cutting biopsy in the First Affiliated Hospital of Guangxi Medical University from January 2017 to May 2020 were included. Ultrasound biopsy was performed to determine the correctness of pathological diagnosis. Independent risk factors of malignant tumor were predicted by multivariate logistic regression analysis. Pathological biopsy results showed that 162 (34.47%) of the 470 biopsy data were specifically benign, and 308 (65.53%; malignant lesions: 25.3%, benign lesions: 74.7%) were nondiagnostic findings. The final diagnoses were benign in 387 cases and malignant in 83 cases. In the nondiagnostic biopsy malignant risk prediction analysis, lesion size (OR = 1.025, P = 0.005), partial solid lesions (OR = 2.321, P = 0.035), insufficiency (OR = 6.837, P < 0.001), and presence of typical cells (OR = 34.421, P = 0.001) are the final important independent risk factors for malignant tumors. In addition, 30.1% (25/83) of patients with nonmalignant lesions who were finally diagnosed with malignant tumors underwent repeated biopsy, and 92.0% (23/25) were diagnosed during the second repeated biopsy. 59.0% (49/83) received additional invasive examination. Nondiagnostic biopsy predictors of malignant risk include lesion size, partial solid lesions, insufficiency, and presence of atypical cells. When a nonmalignant result is obtained for the first time, the size of the lesion, whether the lesion is subsolid, and the type of pathology obtained should be reviewed.

The Effectiveness of Local Governments' Policies in Response to Climate Change: An Evaluation of Structure Planning in Arden, Melbourne.

It is widely acknowledged that climate change has caused serious environmental issues, including drought, bushfires, floods, and heatwaves, and urban sustainability is currently seriously threatened as a result. Arden is one of the key urban regeneration areas set to experience dramatic residential changes under Melbourne's development blueprint within the next 20 years. The Arden Structure Plan (2022) outlines specific implementation steps but does not go into detail about the strategies and tactics used to address climate change and urban sustainability. Therefore, there are still problems with the plan, including a lack of information and time-bound development targets, ambiguous public engagement, little focus on urban crime, and insufficient climate change adaptation measures. The plan also considers affordable housing, a mixed-use development pattern that will significantly decrease environmental harm, and active transportation options, primarily walking and bicycling. Considering climate change, this plan will make Arden a suitable location for population growth. This paper aims to evaluate the Arden Structure Plan and make recommendations on how to improve the plan's urban sustainability and climate change considerations. Furthermore, it provides guidance on whether Arden is a suitable location for Melbourne's population growth in light of the climate change impacts anticipated to occur by 2100.

Contribution of the Ultrasound Techniques in the Evaluation of Knee Joint Damage in the Case of Pigmented Villonodular Synovitis and Rheumatoid Arthritis.

OBJECTIVES: This is a prospective study to evaluate the clinical value of high-frequency ultrasound (HFUS), superb microvascular imaging (SMI), and contrast-enhanced ultrasound (CEUS) in differentiation of pigmented villonodular synovitis (PVNS) and highly active rheumatoid arthritis (RA). METHODS: Twenty PVNS patients and 24 active RA patients were selected to undergo HFUS, SMI, and CEUS examinations. The characteristics of HFUS, SMI, and CEUS in PVNS and RA were compared, and the differential diagnosis performances of HFUS, SMI, and CEUS in PVNS and RA were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: There were statistically significant in joint effusion, synovial thickness, synovial morphology, synovial echo, synovial vessel shape, synovial enhanced direction, and enhanced pattern between PVNS and RA (P < .05). However, no statistically significant were found in bone erosion, synovial boundary, blood signal grading of synovium, synovial enhanced strength, and CEUS quantitative parameters (including PI, TTP, S, MTT, and AUC) (P > .05). The AUC of HFUS, SMI, and CEUS for differential diagnosis PVNS and RA were 0.832, 0.675, and 0.817, respectively. The AUC of HFUS + SMI, HFUS + CEUS, SMI + CEUS, HFUS + SMI + CEUS were 0.923, 0.940, 0.817, and 0.940, respectively. The AUC of HFUS + SMI and HFUS + CEUS was higher than that of each alone (P < .05). CONCLUSIONS: HFUS, SMI, and CEUS can be used as supplementary methods for diagnosis and differential diagnosis in PVNS and active RA. What is more, the combination of HFUS + SMI and HFUS + CEUS was suggested.

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.