[Evolution of Research Related to Macrophage Polarization in Atherosclerosis:A Visualization Analysis].

Objective To explore the research status,hotspots,and development tendency of macrophage polarization (MP) in atherosclerosis (AS) by systematically reviewing and visually analyzing the articles published recently in this field,so as to provide new ideas for the basic research and translational research on MP in the prevention and treatment of AS.Methods SCI-Expanded was used as the data source for the retrieval of the articles involving MP in AS from 2012 to 2022.CiteSpace 6.1.R3 was employed to visualize the node information of the publishing country/region,institutions,authors,keywords,and citations.Results A total of 381 papers were included.The number of publications in the world showed an increasing trend year by year.China and the United States were leading this field in the number and centrality of publications,and Shandong University in China contributed the largest number of publications.The analysis of the key words and citations showed that the hotspots and frontiers in this field mainly included the pathogenesis of AS,MP markers,macrophage plasticity regulation,and potential therapeutic targets for AS.Conclusions The research on MP in AS was booming during 2012-2022.The differential gene expression and the molecular mechanism of targeted therapy of MP in AS are the research trends in this field,which will provide new measures for the prevention and treatment of AS.

Differentiation of Malignant and Benign Orbital Space-Occupying Lesions Using Contrast-Enhanced Ultrasound: Added Value From a Time-Intensity Curve-Based Quantitative Analysis.

OBJECTIVES: To evaluate the value of time-intensity curve (TIC) analysis of contrast-enhanced ultrasound (CEUS) signal to differentiate malignant from benign orbital space-occupying lesions. METHODS: The CEUS signal of 111 patients with orbital space-occupying lesions was retrospectively analyzed using SonoLiver software. TIC-related parameters such as the arrival time (AT), rise time (RT), time to peak (TTP), maximum intensity (IMAX), mean transit time (mTT), slope of the increase (RS), and slope of the decrease (DS) were compared between the malignant and benign groups. Receiver operating characteristic (ROC) curve analysis was used to acquire the cutoff values of these parameters for differential diagnosis. RESULTS: TIC patterns were characterized by fast increase and fast decrease in signal intensity in the malignant group, fast increase and a slow decrease in signal intensity in the benign group. The differences in the IMAX, RS, DS, mTT, TTP, and RT between the 2 groups were statistically significant (p <.01), while the difference in the AT were not (p = .672). ROC curve analysis showed that IMAX = 427.20, DS = 34.72, and mTT = 33.55 were the best cutoff values for differential diagnosis of malignant and benign space-occupying lesions. The accuracy rate of CEUS visual evaluation for differential diagnosis was 66.67% (74/111), while TIC quantitative analysis could effectively improve the accuracy to 89.19% (99/111). CONCLUSIONS: TIC analysis can improve CEUS efficiency to differentiate malignant from benign orbital space-occupying lesions.

Macrophage-targeted ultrasound nanobubbles for highly efficient sonodynamic therapy of atherosclerotic plaques by modulating M1-to-M2 polarization.

BACKGROUND AND AIMS: Sonodynamic therapy (SDT) is a new approach for the treatment of atherosclerosis (AS), yet the poor targeting ability of sonosensitizers limits its therapeutic efficacy. Herein, we reported a plaque-targeted nanoplatform modified with macrophage type A scavenger receptor (SR-A)-targeted peptide (designated as SR-A-Ce6NB) to augment the efficacy of low-intensity pulsed ultrasound (LIPUS)-mediated SDT of atherosclerotic plaque. METHODS: SR-A-Ce6NB was fabricated by thin hydration method and biotin-avidin system, and its physicochemical properties, biocompatibility and plaque-targeting ability were investigated. RAW 264.7 cells were used for in vitro experimental studies. Male 6-week-old apolipoprotein E-deficient mice were fed a high-fat diet for 16 weeks to induce aortic atherosclerotic plaques. Plaque-bearing mice were randomly allocated into five groups (n = 6): control group, Ce6 + LIPUS group, Ce6NB + LIPUS group, SR-A-Ce6NB + LIPUS group and atorvastatin group. After treatment in each group, the aortic artery was harvested for Oil red O, H&E, Masson's trichrome staining, immunohistochemical and immunofluorescent staining. RESULTS: SR-A-Ce6NB with high stability and excellent biocompatibility was successfully fabricated. SR-A-Ce6NB could actively target activated macrophages and selectively accumulate in the plaque. SR-A-Ce6NB could be triggered by LIPUS and had a more potent sonodynamic effect than free Ce6 to potentiate SDT. SR-A-Ce6NB-mediated SDT enhanced the anti-atherogenic effect via modulating M1-to-M2 macrophage polarization and had an earlier onset of action on plaque than the statin-mediated effect. No apparent side effect was observed after intravenous SR-A-Ce6NB injection and LIPUS exposure. CONCLUSIONS: Macrophage-targeted nanoplatform SR-A-Ce6NB-mediated SDT provides a safe, effective and preferable anti-atherogenic therapy by mediating M1-to-M2 macrophage polarization.

Molecular imaging research in atherosclerosis: A 23-year scientometric and visual analysis.

Background: Cardiovascular and cerebrovascular diseases are major global health problems, and the main cause is atherosclerosis. Recently, molecular imaging has been widely employed in the diagnosis and therapeutic applications of a variety of diseases, including atherosclerosis. Substantive facts have announced that molecular imaging has broad prospects in the early diagnosis and targeted treatment of atherosclerosis. Objective: We conducted a scientometric analysis of the scientific publications over the past 23 years on molecular imaging research in atherosclerosis, so as to identify the key progress, hotspots, and emerging trends. Methods: Original research and reviews regarding molecular imaging in atherosclerosis were retrieved from the Web of Science Core Collection database. Microsoft Excel 2021 was used to analyze the main findings. CiteSpace, VOSviewer, and a scientometric online platform were used to perform visualization analysis of the co-citation of journals and references, co-occurrence of keywords, and collaboration between countries/regions, institutions, and authors. Results: A total of 1755 publications were finally included, which were published by 795 authors in 443 institutions from 59 countries/regions. The United States was the top country in terms of the number and centrality of publications in this domain, with 810 papers and a centrality of 0.38, and Harvard University published the largest number of articles (182). Fayad, ZA was the most productive author, with 73 papers, while LIBBY P had the most co-citations (493). CIRCULATION was the top co-cited journal with a frequency of 1,411, followed by ARTERIOSCL THROM VAS (1,128). The co-citation references analysis identified eight clusters with a well-structured network (Q = 0.6439) and highly convincing clustering (S = 0.8865). All the studies calculated by keyword co-occurrence were divided into five clusters: "nanoparticle," "magnetic resonance imaging," "inflammation," "positron emission tomography," and "ultrasonography". Hot topics mainly focused on cardiovascular disease, contrast media, macrophage, vulnerable plaque, and microbubbles. Sodium fluoride ⁃PET, targeted drug delivery, OCT, photoacoustic imaging, ROS, and oxidative stress were identified as the potential trends. Conclusion: Molecular imaging research in atherosclerosis has attracted extensive attention in academia, while the challenges of clinical transformation faced in this field have been described in this review. The findings of the present research can inform funding agencies and researchers toward future directions.

Ultrasound-controlled nano oxygen carriers enhancing cell viability in 3D GelMA hydrogel for the treatment of myocardial infarction.

Heart failure is a critical and ultimate phase of cardiovascular ailment that leads to a considerable incidence of disability and mortality. Among various factors contributing to heart failure, myocardial infarction is one of the most frequent and significant causes, which is still difficult to manage effectively. An innovative therapeutic strategy, namely a 3D bio-printed cardiac patch, has recently emerged as a promising approach to substitute damaged cardiomyocytes in a localized infarct region. Nevertheless, the efficacy of this treatment primarily relies on the long-term viability of the transplanted cells. In this study, we aimed to construct acoustically sensitive nano oxygen carriers to improve cell survival inside the bio-3D printed patch. In this study, we initially created nanodroplets capable of phase transition triggered by ultrasound and integrated them into GelMA (Gelatin Methacryloyl) hydrogels, which were then employed for 3D bioprinting. After adding nanodroplets and ultrasonic irradiation, numerous pores appeared inside the hydrogel with improved permeability. We further encapsulated hemoglobin into nanodroplets (ND-Hb) to construct oxygen carriers. Results of in vitro experiments showed the highest cell survival within the patch of ND-Hb irradiated by the low-intensity pulsed ultrasound (LIPUS) group. The genomic analysis discovered that the increased survival of seeded cells within the patch might be related to the protection of mitochondrial function owing to the improved hypoxic state. Eventually, in vivo studies revealed that the LIPUS+ND-Hb group had improved cardiac function and increased revascularization after myocardial infarction. To summarize, our study successfully improved the permeability of the hydrogel in a non-invasive and efficient manner, facilitating the exchange of substances in the cardiac patch. Moreover, ultrasound-controlled oxygen release augmented the viability of the transplanted cells and expedited the repair of infarcted tissues.

Contrast-Enhanced Ultrasonography versus Contrast-Enhanced Magnetic Resonance Imaging in the Diagnosis of Mediastinal Tumors.

The aim of the study was to evaluate and compare contrast-enhanced ultrasound (CEUS) and contrast-enhanced magnetic resonance imaging (CE-MRI) with respect to their value in the differential diagnosis between benign and malignant mediastinal tumors. Forty-two patients with mediastinal tumor underwent CEUS and CE-MRI respectively. The sensitivity, specificity, diagnostic coincidence rate, positive predictive value (PPV) and negative predictive value of the two methods were compared. The value of different enhancement patterns in the differential diagnosis of benign and malignant mediastinal tumors was analyzed. SonoLiver software was used to obtain the dynamic vascular pattern curve (DVPC) of the lesions, and parameters such as arrival time (AT), rise time (RT), time to peak (TTP), maximum intensity/peak intensity (IMAX) and quality of fit (QOF) were extracted from time-intensity curves for quantitative analysis. We found that (i) the specificity of CEUS was higher than that of CE-MRI, and the PPV and diagnostic coincidence rate of CEUS were equal to those of CE-MRI; (ii) the enhancement patterns and DVPC of CEUS differed between the benign and malignant groups, while there was no difference in CE-MRI enhancement intensity; and (iii) AT, RT and TTP in the malignant groups were significantly shorter, while IMAX was significantly higher. In conclusion, the application of quantitative parameters and DVPC of CEUS is worth popularizing. CEUS can be used as an effective alternative and complementary examination for patients who cannot undergo CE-MRI.