BACKGROUND:Primary mitral regurgitation (PMR) induces right ventricular (RV) pressure and volume overload, yet RV functional assessment remains challenging with conventional echocardiography due to its complex geometry. The value of four-dimensional automated right ventricular quantification (4D-RVQ) in PMR remains underexplored. METHODS AND RESULTS:In this prospective study, 141 participants (36 mild, 31 moderate, 35 severe PMR, and 39 controls) underwent comprehensive echocardiography, including 2D speckle-tracking and 4D-RVQ. The RV-pulmonary artery (PA) coupling index was derived as the ratio of RV free wall longitudinal strain (RVFWLS) to pulmonary artery systolic pressure (PASP). Both 2D and 4D RVFWLS and RV global longitudinal strain showed a significant progressive decline with increasing PMR severity (P < 0.001), outperforming conventional parameters like TAPSE. The RV-PA coupling index demonstrated the strongest correlation with RVEF (r = -0.631, P < 0.001). 4D-RVQ parameters showed good agreement with 2D-derived values. Notably, the 4D RV-PA coupling index exhibited superior discriminatory power for moderate-or-greater PMR (AUC: 0.893, 95% CI: 0.809-0.977), slightly outperforming the 2D index. Despite the preservation of LV ejection fraction even in severe PMR, RV dysfunction was apparent by the moderate stage. CONCLUSIONS:4D-RVQ provides a comprehensive and sensitive assessment of RV function in PMR. RV strain parameters and the RV-PA coupling index are superior to conventional measures for detecting early RV dysfunction. Its integration into clinical practice can improve the detection of right heart function with significant PMR by directly quantifying the pathophysiological hallmark of RV-PA uncoupling.

Rejection following heart transplantation remains a significant challenge in the medical science. In addition to the immune response, the inflammatory response and microvascular endothelial damage can exacerbate rejection; however, current therapies focus primarily on the immune response. Numerous studies have confirmed that miR-126 regulates vascular inflammation and promotes angiogenesis. To achieve the precise targeted delivery of miR-126, macrophage biomimetic ultrasound phase-change cationic nanoparticles carrying miR-126 (miR-126-MCNPs) are synthesized. Incorporation of the macrophage membrane enhances the anti-phagocytic and inflammatory targeting of nanoparticles, thereby prolonging the circulation time and promoting aggregation in the transplanted heart. Using ultrasound-targeted microbubble destruction (UTMD), the perfluoropentane nanoparticle core undergoes a phase change in the ultrasound irradiation zone, allowing the targeted delivery of macrophage membranes and miR-126, and significantly improving the transfection efficiency of the miR-126. Consequently, anti-inflammatory effects are achieved, such as inhibition of macrophage and CD3+ T cells infiltration, and alteration of M2-type macrophage differentiation. In addition, this study demonstrates that the combination of miR-126-MCNPs with UTMD can alleviate the extent of vascular endothelial and interstitial fibrosis in transplanted hearts, increase angiogenesis, and improve microcirculation and cardiac function. This research provides a new strategy for the precision-targeted therapy of cardiac transplant rejection.

Myocardial ischemia-reperfusion injury (MIRI) is a secondary pathological process that occurs after restoration of blood flow during the treatment of acute myocardial infarction. The effective prevention of MIRI is pivotal for optimizing therapeutic efficacy and improving long-term patient outcomes. In this study, we developed an ultrasound-driven, multilevel targeted bionic microbubble motor (CsA@NM-MBs motors) that can break through the vascular endothelial and cell membrane barriers to achieve precise, targeted drug delivery. The CsA@NM-MBs motors were coated with a neutrophil membrane, a highly biocompatible membrane with natural inflammatory targeting abilities, enabling active homing to damaged areas. Upon application of an external ultrasound field, the CsA@NM-MBs motors actively crossed the vascular endothelial barrier and reached the myocardial tissue in the MIRI area with precision. With the aid of ultrasound-targeted microbubble destruction (UTMD) technology, acoustic pores are formed on the cell membrane, enabling it to break through the cell barrier. The driving force generated by the explosion enables CsA to be delivered into cells, thereby achieving safe and efficient drug release. This ultrasound-driven cell membrane biomimetic multilevel targeting strategy significantly enhanced the enrichment and delivery efficiency of CsA at the injury site, providing a new approach for the treatment of MIRI.

OBJECTIVES:The therapeutic goals for alopecia areata (AA) are to suppress local immune inflammation, restore hair follicle structure, and improve surrounding blood perfusion. However, current efficacy evaluations largely rely on subjective clinical observation and lack objective quantitative methods. High-frequency ultrasound (HFUS) can clearly display the location and morphology of hair follicles. Combined with microvascular assessment techniques, it enables quantitative detection of low-velocity blood flow and related parameters, providing an objective basis for evaluating AA treatment efficacy. METHODS:Forty-five patients with AA who received intralesional therapy underwent HFUS (measuring epidermal/dermal thickness and hair follicle length/width) and ultrasound microvascular assessment, including spectral Doppler measurement of peak systolic velocity (PSV), resistance index (RI), and power Doppler measurement of vascular index (VI) before and after treatment. Patients were divided into a responder group (n = 37) and an ineffective group (n = 8) based on the reduction rate of the SALT score. The Mann-Whitney U test and Wilcoxon signed-rank test were used for comparisons between groups and within the responder group (pre-treatment versus post-treatment), respectively. RESULTS:Baseline characteristics showed no statistically significant differences (all p > .05). Patients in the ineffective group exhibited poorer hair follicle morphology (shorter length, greater width, and lower length-to-width ratio), but higher PSV and VI compared to the responder group (p < .05). In the responder group, treatment significantly improved hair follicle morphology, increased PSV and VI (p < .05), but RI showed no change. CONCLUSIONS:(1) HFUS technology can observe changes in AA hair follicle structure during the diagnosis and treatment process, evaluating the effectiveness of treatment regimens in improving AA disease progression. (2) SMI combined with Doppler flow parameters can monitor changes in the perifollicular microcirculation in AA, reflecting the improvement of microcirculation during the diagnosis and treatment of AA. (3) The synergistic application of HFUS and SMI technologies can provide an objective imaging basis for the clinical evaluation of AA treatment efficacy, demonstrating promising clinical application prospects.

OBJECTIVE:The aim of this study was to integrate multimodal intratumoral and peritumoral ultrasound radiomic features with clinical data to construct a predictive model for central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) and to explore its clinical utility. METHODS:A total of 470 PTC patients who underwent 2-dimensional (2D) ultrasound, color Doppler flow imaging (CDFI), and strain elastography (SE) were enrolled between June 2021 and September 2023. Patients were randomly divided into a training group (n = 329) and a validation group (n = 141) in a 7:3 ratio. Imaging features were extracted from multimodal intratumoral and peritumoral ultrasound images, followed by feature selection. A multimodal intratumoral and peritumoral ultrasound radiomics model was constructed using machine learning algorithms. Univariate and multivariate logistic regression analyses identified independent clinical predictors, which were used to build a clinical model. The ultrasound radiomics model was then integrated with the clinical model to form a combined model (the RadClip model). RESULTS:The multimodal intratumoral and peritumoral radiomics model achieved AUCs of 0.936 and 0.843 in the training and validation groups. Multivariate analysis identified male, high elasticity score, irregular margins, hyperechoic areas, and the presence of suspicious lymph nodes as independent predictors of CLNM (P < .05). The clinical model achieved AUCs of 0.750 and 0.735 in the training and validation groups, respectively. The RadClip model demonstrated significantly superior predictive performance compared to both the clinical and radiomics models, achieving AUCs of 0.948 and 0.867 in the training and validation groups, respectively (Delong, P < .05). CONCLUSION:The RadClip model demonstrates excellent predictive efficacy for preoperative detection of CLNM in PTC.

Purpose: The aim of this study was to develop and validate a predictive model for early refractoriness to transarterial chemoembolization (TACE)-termed early TACE refractoriness (ETR)-in patients with hepatocellular carcinoma (HCC). The model integrates contrast-enhanced CT (CECT) shell features (annular features at the tumor-liver parenchyma interface) with the Vision-Mamba (Vim) architecture, known for its efficiency in handling high-resolution medical images. Patients and Methods: This study was a two-center and retrospective study. Patients from center 1 were divided into the training set (n=254) and validation set (n=108), while patients from center 2 were used as the testing set (n=75). A joint model was constructed to predict ETR, and four Vim models without clinical features and 14 machine learning models based on clinical features were also developed for comparison. Model performance was evaluated by the accuracy, area under the curve (AUC), calibration curve, sensitivity, specificity, decision curve analysis (DCA) and Delong test. SHapley Additive exPlanations(SHAP) analysis were used to explain the predictions. Results: The combined model based on the Vim framework performs better than others. The AUC of the combined model in the training set, validation set and test set were 0.959, 0.956 and 0.942, respectively. The calibration curve and DCA verified the practicality of the combined model in clinical practice. SHAP provides a visual interpretation of the model. Conclusion: The Vim-based model integrating CECT and shell features shows promise for ETR prediction, offering a preliminary stratification tool. However, it remains a promising step rather than a definitive solution, requiring prospective validation due to the retrospective design and limited validation.

Acute rejection (AR) is an important cause of heart graft injury and failure. Accurate diagnosis of AR is essential to achieving early intervention and improving the prognosis of patients. Current clinical monitoring of AR requires repeated invasive endocardial biopsies, and there is an urgent need to develop a noninvasive diagnostic technique. As antigen-presenting cells, macrophages play an important role in adaptive immunity, such as the early activation of T cells in AR, and are considered to be key drivers of AR. Macrophage membrane biomimetic microbubbles (MB-M phi) inherit a variety of functional proteins from the macrophage membranes. They can recognize and target the inflammatory site in the heart and use ultrasound imaging signals to determine the inflammatory progression of AR. This "ultrasound probe" can be regarded as a dynamic tracer and visualization tool for the behavior of macrophages. MB-M phi prepared in this study showed superior stability and ultrasound imaging performance, and its ability to adhere to inflammatory vascular endothelial cells was significantly better than that of ordinary microbubbles (MB). In the rat allograft model, the signal intensity of the MB-M phi group was significantly higher than that of the ordinary microbubbles group. In addition, after injection of MB-M phi, the signal intensity in the allograft group was significantly higher than that in the isograft group, and the pathological results confirmed that the signal intensity of MB-M phi was positively correlated with the number of macrophages infiltrating the transplanted heart and the progression of AR. These findings indicate that macrophage membrane biomimetic microbubbles can mimic the inflammatory chemotactic behavior of macrophages and noninvasively detect AR in heart transplantation, which provides a new molecular imaging tool for early diagnosis.

Stem cell therapies are emerging as promising strategies for repair after myocardial infarction (MI), but the repair efficacy is limited by the poor cardiac microenvironment represented by the inflammatory response, as well as oxidative stress, and adverse electrical coupling. Here, we developed an injectable supramolecular hydrogel (HCPA) that modulates the infarct microenvironment and accelerates myocardial repair by encapsulating human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs). HCPA hydrogel not only exhibited excellent reactive oxygen species (ROS) response in order to minimize oxidative stress but also possessed desirable electrical conductivity for the reintegration of electrical impulses. Critically, RNA sequencing demonstrated that the PPARα/NFκB pathway contributed significantly to the HCPA hydrogel-promoted macrophage polarization from M1-type to M2-type, thus alleviating inflammatory responses. HCPA hydrogel harboring hiPSC-CMs increased retention of hiPSC-CMs and improved cardiac function in MI mice. This study represents a new integrated therapeutic option for MI and provides insights for the development of novel biomaterials in the field of tissue engineering.

INTRODUCTION:Lysine succinylation is an emerging post-translational modification critically involved in cardiovascular pathophysiology. Malate dehydrogenase 1 (MDH1), a core enzyme of the malate-aspartate shuttle that maintains cardiomyocyte redox homeostasis, is implicated in myocardial injury, yet the regulatory role and specific mechanism of MDH1 succinylation in myocardial ischemia/reperfusion (I/R) injury remain incompletely understood. OBJECTIVE:This study aims to elucidate the functional role and underlying molecular mechanism of site-specific lysine succinylation of MDH1 in myocardial I/R injury. METHODS:Global succinylome profiling was performed on cardiac tissue from murine I/R models. Target succinylation was validated by immunoprecipitation and Western blot. AAV9 vectors encoding wild-type MDH1 (MDH1-WT) or succinylation-deficient mutant (MDH1-K298R) were constructed for cardiac-specific delivery. Molecular docking and co-immunoprecipitation identified the upstream succinyltransferase, and virtual screening identified Ethyl rosmarinate (ER) as a Carnitine palmitoyltransferase 1A (CPT1A)-stabilizing compound. RESULTS:MDH1 K298 succinylation was significantly decreased in I/R-injured hearts compared with sham-operated control hearts. In vivo cardiac overexpression of MDH1-WT suppressed ferroptosis and ameliorated myocardial I/R injury, whereas MDH1-K298R failed to confer such protection, indicating that the cardioprotective effect of MDH1 is dependent on K298 succinylation. Mechanistically, K298 succinylation enhanced MDH1 protein stability by inhibiting its ubiquitin-proteasomal degradation, thereby preserving redox homeostasis required for glutathione peroxidase 4 (GPX4) activity. Importantly, CPT1A was identified as the succinyltransferase responsible for MDH1 K298 succinylation. ER alleviated myocardial I/R injury by preventing Carnitine palmitoyltransferase 1A (CPT1A) degradation and consequently enhancing MDH1 K298 succinylation. CONCLUSION:Our findings uncover a critical cardioprotective role of the CPT1A-MDH1 succinylation axis via suppressing ferroptosis during myocardial I/R injury, and identify ER as a CPT1A-stabilizing compound with promising therapeutic potential for ischemic heart disease.

Background Acute rejection (AR) continues to be a leading cause of mortality following heart transplantation. Endomyocardial biopsy, the current gold standard for monitoring, is limited by its invasiveness. Macrophage infiltration into the myocardial interstitium is an early hallmark of AR, targeting these specific cells offers a novel strategy for the accurate and stable noninvasive detection of rejection signals. To address this unmet clinical need, we developed a macrophage-targeted ultrasound contrast agent — phosphatidylserine nanobubbles (PS-NBs). Methods PS-NBs were fabricated and their targeting ability toward macrophages was evaluated. Heterotopic heart transplantation models were established, and PS-NBs were injected for ultrasound molecular imaging. Signal intensity (SI) was compared between allografts and isografts. Imaging results were validated via H&E and CD68 immunohistochemical staining. Results PS-NBs can effectively target macrophages. In allografts, PS-NBs exhibited significantly higher SI compared to control NBs. The SI of PS-NBs in the allograft group at seven days post-transplantation was stronger than that at three days, and significantly exceeded the SI observed in the isograft group. Crucially, a strong positive correlation was observed between PS-NB SI and macrophage infiltration density. Conclusion By specifically targeting macrophages that infiltrate in the myocardial interstitium, PS-NBs enable the highly accurate, stable, and noninvasive early detection of AR via ultrasound molecular imaging. This innovative strategy represents a key methodological improvement over current detection. Importantly, owing to their high in vivo biocompatibility, PS-NBs demonstrate considerable promise for future clinical translation.

PURPOSE:Human epidermal growth factor receptor 2 (HER2) is a key biomarker for clinical management and prognostic evaluation of breast cancer patients. This study was aimed at assisting the preoperative and non-invasive prediction of HER2-low breast cancer using multimodal ultrasound imaging and clinicopathological indicators, providing valuable imaging information for clinical precision diagnosis and personalized treatment strategies, especially in the application of antibody-drug conjugates such as T-DXd. MATERIALS AND METHODS:This retrospective study included 147 pathologically confirmed breast cancer patients from two institutions: 101 in the training set and 46 in the external validation set. All patients underwent multimodal ultrasound (grayscale, color Doppler, elastography, and contrast-enhanced imaging) and had complete clinicopathological data. Patients were categorized as HER2-negative, HER2-low, or HER2-positive based on immunohistochemistry. Logistic regression was used to construct predictive models. RESULTS:Compared with the HER2-negative group, low Ki-67, PR positivity, longer rise time (RT), and lower Emax values were independent predictors of HER2-low status (p < 0.05), yielding an AUC of 0.876, sensitivity 0.833, and specificity 0.781. Compared with HER2-positive cancers, HER2-low cases showed low Ki-67, ER/PR positivity, low Emax, and a DVPC pattern characterized by an initial increase followed by a subsequent decline as independent predictors (p < 0.05), with an AUC of 0.929, sensitivity 0.905, and specificity 0.856. External validation confirmed robust model performance (AUC = 0.925 and 0.918 for HER2-low vs. negative and positive, respectively). CONCLUSION:A model integrating multimodal ultrasound and clinicopathological factors effectively predicts HER2-low breast cancer, offering valuable imaging-based support for clinical decision-making.

AIMS:Pro-inflammatory macrophages are critical mediators of the viral myocarditis (VMC) pathological process. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a key enzyme involved in one-carbon metabolism, plays an essential regulatory role in macrophage function. However, the regulatory effect of MTHFD2 on macrophages in VMC remains unclear. Here, we investigated whether MTHFD2 regulates macrophage function to exert a protective effect against coxsackievirus B3 (CVB3)-induced myocarditis. METHODS AND RESULTS:To establish the VMC model, 6-week-old C57BL/6J and BALB/c mice were intraperitoneally injected with CVB3, and blood samples from the mice were examined for targeting analysis of folate metabolism-related compounds. The myeloid cell-specific MTHFD2 knockout mice Mthfd2fl/flLyz2-Cre+ (MTHFD2-KO-Mϕ) and littermate mice underwent peripheral blood proteomic analysis. We observed activation of the one-carbon metabolism folate cycle and upregulation of MTHFD2 in macrophages during myocarditis. Furthermore, CVB3-infected MTHFD2-KO-Mϕ mice exhibited higher cardiac immunocyte infiltration, especially pro-inflammatory macrophages, aggravated myocardial injury, and cardiac dysfunction. MTHFD2 knockdown also enhanced the migration of bone marrow-derived macrophages and increased their polarization towards a pro-inflammatory phenotype. Proteomic analysis identified Rap1 as a direct downstream target of MTHFD2 in VMC. Specifically, MTHFD2 modulated integrin-regulated monocyte-macrophage migration via Rap1a and reduced cellular pro-inflammatory differentiation in VMC by inhibiting Rap1/p38 MAPK signalling. Both MTHFD2 administration and high-folate diet feeding reduced cardiac inflammation and fibrosis and improved cardiac function in mice with VMC. CONCLUSION:We identified MTHFD2 as an immune regulator of monocyte-macrophage homeostasis to protect against CVB3-induced VMC. Targeted regulation of MTHFD2 is a potential therapeutic option for VMC clinically.

Donor heart-resident C-C chemokine receptor 2 (CCR2+) macrophages induce the recruitment of CCR2+ monocytes to a transplanted hearts through the secretion of monocyte chemoattractant protein-1 (MCP-1), which mediates the incidence of acute rejection (AR). In this study, we synthesized MCP-1 peptide-modified polyethylene glycol-poly (lactic-co-glycolic) acid (PEG-PLGA) nanoparticles loaded with the sonosensitizer dihydroporphyrin e6 (Ce6) and administered them via intramyocardial injection and used in combination with sonodynamic therapy (SDT) to selectively deplete donor cardiac-resident and infiltrating CCR2+ macrophages. In vitro experiments confirmed that Ce6-NP-MCP-1 targets and has chemotactic effects on CCR2+ macrophages, thereby enhancing the therapeutic efficacy of STD. In mouse heart grafts, the chemotactic effect of Ce6-NP-MCP-1 on CCR2+ macrophages has been used to induce donor heart-resident and infiltrating CCR2+ macrophages to aggregate and phagocytose nanoparticles in combination with SDT to induce macrophage apoptosis. This therapy inhibits the number of donor heart-resident CCR2+ macrophages and downregulates the expression of proinflammatory cytokines and inflammatory infiltration. In addition, it significantly prolongs the allograft survival time. Therefore, CCR2-targeted nanoparticles combined with SDT for the selective depletion of donor heart-resident CCR2+ macrophages provide a promising paradigm for AR target treatment.

OBJECTIVE:Acoustically activatable perfluoropropane droplets (PD) have been utilized to enhance the reperfused zone in acute myocardial infarction small animal models. Despite the correlation with infarct size, the enhanced area consistently overestimates infarct size. We hypothesized that the enhanced area correlates with risk area, and that hypo-enhanced areas (HEA) within the enhanced zone represent the ultimate infarct size. METHODS:Intravenous PD was administered in the reperfusion period following a 90 min period of ischemia in 30 pigs. Injections were given at either 30 min, 1 d or 7 d following reperfusion to determine what the enhanced regions within the reperfused zone following acoustic activation (AA) were detecting. Correlations of the enhanced and unenhanced regions with the infarct size using delayed enhancement magnetic resonance imaging (DE-MRI) were determined. RESULTS:AA within the reperfused zone was evident in 26 pigs (9/10 pigs injected at 30 min post-reperfusion, 9/10 pigs injected at 1 d and 8/10 pigs injected at 7 d). In the 26 pigs with AA, the extent of enhancement was significantly larger than the infarct size by DE-MRI, and correlated more closely with risk area (r = 0.55, p = 0.0002). A HEA within the enhanced region was observed in 21 of the 26 pigs with AA, and the spatial extent of HEA correlated with infarct size (r = 0.85; p < 0.0001). CONCLUSION:AA of intravenous PD enhances the risk area following reperfusion. However, it is the extent of hypo-enhancement within the enhanced region that predicts infarct size irrespective of the time AA is performed following reperfusion.

Objective:We aimed to establish a model to estimate the energy required for microwave ablation (MWA) to achieve the desired effect and analyze the factors influencing its therapeutic efficacy. Materials and Methods:We retrospectively analyzed 117 patients with benign thyroid nodules. A quadratic regression model was established to analyze the relationship between the technical parameters of MWA and volume reduction rate (VRR). Both univariate and multivariate logistic regression analyses were used to identify factors influencing the efficacy of MWA treatment. Results:The volume of nodules continued to decrease at 1, 3, 6, and 12 months after ablation, and the mean of VRR was 77.5 ± 15.9% at 12 months after ablation. Among these nodules, 72 (61.5%) had a VRR ≥ 75%, whereas 45 (38.5%) had a VRR < 75%. The energy volume ratio was significantly correlated with the VRR. When the VRR ≥ 75%, the energy volume ratio ranges 784-2,274 J/mL. Among all parameters, only the energy volume ratio and calcification were independent factors influencing the treatment efficacy for benign thyroid nodules (P < 0.05). Conclusions:The efficacy of the treatment was optimized when the energy volume ratio of the MWA fell within a certain range. The energy volume ratio and calcification are related to the efficacy of MWA treatment.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Laminar blood flow represents the normal physiological state of blood circulation, but it also acts as a natural physiological barrier for the effective diffusion of drugs to the lesion site. Here, we report a bioinspired strategy in which reconfigurable vortexlike swarms of magnetic swimming nanobots actively disrupt the laminar flow to deliver drugs in a manner similar to how bacteria seek food. The drug was released from the cavity of biodegradable, submicron pentosan flask-like nanobots, aggregates as the dynamic rotating drug fluid under a rotating magnetic field. The vortexlike nanobot swarm successfully overcame the laminar barrier near the thrombus in a rat inferior vena cava stenosis thrombosis model, which was observed by ultrasound blood flow imaging. Furthermore, the clinical feasibility of nanobots swarm for enhancing thrombolytic efficacy through drug aggregation after breaking the laminar flow was further confirmed in a rat deep vein thrombosis model. This bionic active targeting approach overcomes the laminar flow barrier and restricts the release of drugs by the swarm-induced vortex fluid to facilitate targeted drug delivery, which is expected to be an innovative method to enhance drug delivery efficiency.

Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.

OBJECTIVES:This study aims to apply high-frequency ultrasound (HFUS) in conjunction with ultra-micro angiography (UMA) technology to observe the ultrasound characteristics of facial lesions in patients with papulopustular rosacea (PPR). It will also quantitatively evaluate the changes before and after treatment, thereby assessing the feasibility and application value of this combined technique in evaluating the treatment efficacy for PPR. METHODS:We conducted a prospective study involving 63 patients with PPR who visited the dermatology department between May 2024 and March 2025. Two attending dermatologists independently evaluated the most severe lesions on each patient's cheeks (marked area) and performed follow-up evaluations at the end of the fourth week of treatment, as well as calculated the therapeutic efficacy index. We utilized HFUS, equipped with a 33 Hz linear array probe, in conjunction with UMA technology to conduct ultrasound scans of the marked areas of patients at baseline and at the end of the fourth week of treatment. This allowed us to obtain ultrasound characteristics and perform statistical analyses. RESULTS:The dermatologists classified the PPR patients based on the therapeutic efficacy index into cured (6 cases), significantly improved (23 cases), improved (29 cases), and ineffective (5 cases). By the end of the fourth week of treatment, significant changes were observed in non-quantitative features, including epidermal morphology, the subepidermal low-echogenic band, dermal echogenicity, sebaceous gland echogenicity, and the echoes of inflammatory papules, compared to baseline (p < .01). Simultaneously, quantitative parameters, including thickness ratio, maximum diameter of hair follicles, maximum diameter of facial skin microvessels, peak systolic velocity, time average maximum velocity, and color pixel percentage (CPP), all significantly decreased (p < .01). Spearman correlation analysis indicated a strong correlation between quantitative parameters, such as CPP and the relative change ratio of color pixel percentage, and the therapeutic efficacy index at the end of the fourth week of treatment (0.70 ≤ |r| < 0.90, p < .01). CONCLUSIONS:HFUS combined with UMA technology can be effectively used for the quantitative evaluation of treatment efficacy in PPR.