Search

Background and Aim: Tamoxifen has been used in the management of breast cancer. The available evidence on the effect of tamoxifen on lipoprotein(a) and apolipoproteins is controversial. Hence, this meta-analysis of randomized controlled trials (RCTs) was conducted to increase the quality of evidence on the effect of tamoxifen on lipoprotein(a) and apolipoproteins., Methods: Eligible RCTs published up to September 2023 were carefully selected following a comprehensive search. Thereafter, a meta-analysis was conducted using a random-effects model and the results were presented as the weighted mean difference (WMD) with a 95 % confidence interval (CI)., Results: The results from the random-effects model indicated a rise in ApoA-I (WMD: 16.24 mg/dL, 95 % CI: 5.35, 27.12, P = 0.003), and a decrease in ApoB (WMD: -9.37 mg/dL, 95 % CI: -15.16, -3.59, P = 0.001) and lipoprotein(a) (WMD: -3.24 mg/dL, 95 % CI: -5.66, -0.83, P < 0.001) concentrations following tamoxifen administration in women. Furthermore, a more pronounced decrease in ApoB (WMD: -12.86 mg/dL, 95 % CI: -19.78, -5.93, P < 0.001) and elevation in ApoA-1 levels (WMD: 51.97 mg/dL, 95 % CI: 45.89, 58.05, P < 0.001) were identified in a single study on patients with breast cancer., Conclusion: The current meta-analysis demonstrated an increase of ApoA-I and a decrease of ApoB and lipoprotein(a) levels after treatment with tamoxifen in women., Competing Interests: Declaration of competing interest There was no conflict of interest declared by the authors., (Copyright © 2024. Published by Elsevier Inc.)

It is important for people to disengage attention from a distraction, which can help them complete the task at hand as quickly as possible. Recent studies have shown that people's attention stays longer on reward-distractors than on loss-distractors, and a delay in attentional disengagement is noted when reward-distractors are present. However, few studies have examined whether attentional disengagement from an evaluative distractor relies upon working memory (WM) components. In the present study, we used an attentional disengagement paradigm in which reward- or loss-distractors were presented at a central location and the target was presented at a peripheral location, in combination with different WM tasks. The results from Experiment 1 showed that participants were slower to disengage their attention from a central reward-distractor than a loss-distractor regardless of cognitive load when the phonological loop component of WM was involved. The results from Experiment 2 revealed that people had difficulty in shifting their attention away from a reward-distractor in comparison to a loss-distractor when spatial WM was low, whereas no such difference was observed when spatial WM was high. We conclude that WM components differently modulate attentional disengagement from evaluative distractors. That is, the processing of evaluative (reward and loss) distractors may rely on the same cognitive resources as the spatial WM component, but not the phonological loop component., (© 2024 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Herein, a Y-type compound ( 67dMeOTPA-FQ ) and a T-type compound ( 58dMeOTPA-FQ ) based on furo[2,3- b ]quinoxaline were synthesized. The theory calculation shows the S 1 and T 1 of both compounds own a charge-transfer feature while their T 2 states have a local excitation feature. The calculated k RISC(T2-S1) is one to 2 orders of magnitude larger than k RISC(T1-S1) . Thus, the nonadiabatic spin-vibronic mechanism involved in the T 2 state is suggested to be responsible for the thermally activated delayed fluorescence (TADF) feature. Meanwhile, when 2-methyl-9,10-bis(naphthalen-2-yl)anthracene is selected as host, the maximum luminance of the device based on 67dMeOTPA-FQ is up to 104215 cd·m -2 , and the external quantum efficiency (EQE) keeps in the 8.2-8.0% range with the luminance changed from 55.0 cd·m -2 to 90000 cd·m -2 , only 2.4% efficiency roll-off. As for 58dMeOTPA-FQ , a slightly lower EQE of 7.1-6.7% with the luminance range of 1-40000 cd·m -2 was achieved for orange-red emission. Both the reverse intersystem crossing (RISC) and triplet-triplet annihilation mechanisms are supposed to concurrently contribute to the utilization of triplet excitons and suppress the notorious efficiency roll-off observed in TADF-based devices.

Objectives: Colistin sulphate for injection (CSI) became clinically available in China in July 2019. To date, there is no published data regarding its usage in children. Our research group has been following data on the efficacy and safety of CSI in Chinese paediatric patients with carbapenem-resistant organism infections. The purpose of this short communication is to provide a brief overview of the findings to date., Methods: We reviewed the electronic medical records of paediatric patients (aged 9-17 y) who were administered CSI during their hospital stay at Tongji Hospital in Wuhan, China, between June 2021 and November 2023. Drug efficacy was evaluated based on clinical and microbiological outcomes, while drug safety was assessed using surveillance markers that reflect adverse reactions., Results: A total of 20 patients met the inclusion criteria. The predominant pathogens were Klebsiella pneumoniae (8 strains), followed by Acinetobacter baumannii (5 strains) and Pseudomonas aeruginosa (2 strains). The clinical response rate of CSI was 85%, with a bacterial clearance rate of 79%. None of the patients experienced colistin-related nephrotoxicity or neurotoxicity during the treatment., Conclusions: In this real-world setting, CSI demonstrated a high level of clinical response and was well tolerated for the treatment of carbapenem-resistant organism infections in Chinese children., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Light-weight, high-strength, aluminum (Al) alloys have widespread industrial applications. However, most commercially available high-strength Al alloys, like AA 7075, are not suitable for additive manufacturing due to their high susceptibility to solidification cracking. In this work, a custom Al alloy Al 92 Ti 2 Fe 2 Co 2 Ni 2 is fabricated by selective laser melting. Heterogeneous nanoscale medium-entropy intermetallic lamella form in the as-printed Al alloy. Macroscale compression tests reveal a combination of high strength, over 700 MPa, and prominent plastic deformability. Micropillar compression tests display significant back stress in all regions, and certain regions have flow stresses exceeding 900 MPa. Post-deformation analyses reveal that, in addition to abundant dislocation activities in Al matrix, complex dislocation structures and stacking faults form in monoclinic Al 9 Co 2 type brittle intermetallics. This study shows that proper introduction of heterogeneous microstructures and nanoscale medium entropy intermetallics offer an alternative solution to the design of ultrastrong, deformable Al alloys via additive manufacturing., (© 2024. The Author(s).)

Objective: Schizophrenia often occurs during youth, and psychosis risk syndrome occurs before the onset of psychosis. The aim of this study was to determine whether the visual event-related potential responses in youths with psychosis risk syndrome were defective in the presence of interference stimuli and associated with their clinical outcomes., Methods: A total of 223 participants, including 122 patients with psychosis risk syndrome, 50 patients with emotional disorders, and 51 healthy control subjects, were assessed. Baseline EEG was recorded during the three-stimulus visual oddball task. The event-related potentials induced by square pictures with different colors were measured. Almost all patients with psychosis risk syndrome were followed up for 12 months and were reclassified into three subgroups: conversion, symptomatic, and remission. The differences in baseline event-related potential responses were compared among the clinical outcome subgroups., Results: The average N2 amplitude of the psychosis risk syndrome group was significantly less negative than that in the healthy control group (d=0.53). The baseline average N2 amplitude in the conversion subgroup was significantly less negative than that in the symptomatic (d=0.58) and remission (d=0.50) subgroups and in the healthy control group (d=0.97). The average N2 amplitude did not differ significantly between the symptomatic and remission subgroups (d=0.02). However, it was significantly less negative in the symptomatic and remission subgroups than in the healthy control group (d=0.46 and d=0.38). No statistically significant results were found in the P3 response., Conclusions: Youths with psychosis risk syndrome had significant N2 amplitude defects in attention processing with interference stimuli. N2 amplitude shows potential as a prognostic biomarker of clinical outcome in the psychosis risk syndrome., Competing Interests: The authors report no financial relationships with commercial interests.

The variety of highly efficient red/near-infrared (NIR) materials with thermally activated delayed fluorescence (TADF) feature is extremely limited so far, and it is necessary to expand the candidate pool of excellent red/deep-red emitters. However, how to control the energy level alignment of the 1 CT (singlet charge transfer) state and the 3 LE (triplet local excitation) state to improve the emission efficiency of materials remains a challenge. Herein, based on our previously reported green fluorescent material 67dTPA-FQ, three new donor-acceptor type TADF materials (TQ-oMeOTPA, TsQ-oMeOTPA and SQ-oMeOTPA) were designed by introducing 4,4'-dimethoxy triphenylamine (MeOTPA) as the donor, and introduced S atoms on the acceptors to enhance the spin-orbit coupling (SOC) and CT effects. The theoretical calculations showed that the newly introduced MeOTPA and S atom successfully enhanced the CT effect of the materials, not only shifting the luminescence peak to the deep red region but also effectively adjusting the energy level alignment of the excited state, accelerating the reverse intersystem crossing process. Finally, the organic light-emitting diodes based on SQ-oMeOTPA exhibit an external quantum efficiency of 19.1%, with an emission peak at 619 nm. This work not only expands the candidate inventory of red TADF materials, but also proves the feasibility of designing emitters by adjusting the excited state energy levels, greatly broadening the diversity of TADF emitters in design, and providing a powerful means for rapidly screening efficient emitters in the future., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: The deleterious impact of aggressive behavior on college students necessitates urgent mitigation. To explore the influencing factors and underlying mechanisms of aggressive behaviors among college students, this study aims to validate the mediating roles of life satisfaction, meaning in life, and depression by examining the relationship between physical exercise and aggressive behaviors among college students., Methods: The Physical Activity Rating Scale-3 (PARS-3), Satisfaction with Life Scale, Meaning in Life Questionnaire, Chinese Version DASS-21 and 12-item Perception of Aggression Scale (POAS) were tested on 1596 college students from three universities in western China, and SPSS 26.0 and Mplus 8.3 were used for analysis., Results: Physical exercise exhibited a significant negative correlation with both aggressive behaviors and depression among college students (r = -0.57, P < 0.001; r = -0.36, P < 0.001), as well as a significant positive correlation with life satisfaction and meaning in life (r = 0.45, P < 0.001; r = 0.27, P < 0.001). Regarding the impact of physical exercise on aggressive behaviors among college students, the mediating effects of life satisfaction, meaning in life, and depression were significant. The respective effect sizes were -0.11, -0.08, and -0.03. The chain mediation effect of life satisfaction through depression was also found to be significant, with an effect size of -0.02., Conclusion: This study elucidates the mechanistic pathways through which physical exercise influences aggressive behavior among college students. The relationship between physical exercise and aggressive behavior is influenced by the individual mediating effects of life satisfaction, meaning in life, and depression, as well as the chain mediation effect of life satisfaction through depression. These findings provide a novel perspective on the prevention and intervention of aggressive behaviors among college students in China and potentially worldwide. This suggests that more attention should be paid to the organic combination of students' physical activity and mental health education., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Liu et al.)

Background: The global population is aging. It is estimated that by 2050, the proportion of the elderly population will reach 16%. Various studies have suggested that elderly people have a greater incidence of CKD. These elderly patients are also susceptible to cardiovascular disease (CVD), which is the leading cause of death, resulting in poor prognosis in this population. However, CVD in such patients is often insidious and lacks early markers for effective evaluation. Fortunately, several studies have recently proposed biomarkers associated with this process., Summary: This study aimed to summarize the early biomarkers of CVD in elderly patients with CKD to provide a basis for its prevention and treatment., Key Messages: This review outlines four categories of potential early biomarkers. All of them have been shown to have some clinical value for these patients, but more research is still needed., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Morin suggested that one of the reasons for the difficulty in standardizing graphic codes is that the production of spoken language reduces the need for graphic codes. Here we try to extend their claims from a psychological perspective, which allows us to conclude that the puzzle of ideography is perhaps related to human psychological traits and psychological evolution.

Endovascular sonothrombolysis has gained significant attention due to its benefits, including direct targeting of the thrombus with sonication and reduced side effects. However, the small aperture of endovascular transducers restricts the improvement of their potential clinical efficiency due to inefficient acoustic radiation. Hence, in an earlier study, we used vortex ultrasound with an endovascular ultrasound transducer to induce shear stress and enhance the clot lysis. In this study, the vortex acoustic transduction mechanism was investigated using numerical simulations and hydrophone tests. Following this characterization, we demonstrated the performance of the vortex ultrasound transducer in thrombolysis of retracted clots in in vitro tests. The test results indicated that the maximum lysis rates were 79.0% and 32.2% with the vortex ultrasound for unretracted and retracted clots, respectively. The vortex ultrasound enhanced the efficiency of the thrombolysis by approximately 49%, both for retracted and unretracted clots, compared with the typical non-vortex ultrasound technique. Therefore, the use of endovascular vortex ultrasound holds promise as a potential clinical option for the thrombolysis of retracted clots., Competing Interests: Howuk Kim, Bohua Zhang, Huaiyu Wu, Chengzhi Shi, and Xiaoning Jiang are inventors of several intravascular sonothrombolysis technologies that were licensed to SonoVascular. Xiaoning Jiang has served as a consultant and a scientific advisor for SonoVascular, Inc., (© 2023 Author(s).)

The production effect (PE) is the finding that reading words aloud rather than silently during study leads to improved memory. We used electroencephalography (EEG) techniques to detect the contributions of recollection, familiarity, and attentional processes to the PE in recognition memory, using Chinese stimuli. During the study phase, participants encoded each list item aloud, silently, or by performing a non-unique aloud (control) task. During the test phase, they made remember/know/new recognition judgments. We recorded EEG data in both phases. The behavioral results replicated the typical pattern with English stimuli: Recognition was better in the aloud condition than in the silent (and control) condition, and this PE was due to enhanced recollection and familiarity. At study, the amplitude of the P3b ERP component was greater in the aloud than in the silent/control conditions, suggesting that reading aloud increases attention or preparatory processing during the intention phase. At test, the recollection-based LPC old/new effect was largest in the aloud condition; however, the familiarity-based FN400 old/new effect was equivalent between the aloud condition and the silent/control conditions. Only the LPC effect correlated with the behavioral effect. Moreover, multivariate pattern analysis (MVPA) showed that accurate classification of items as 'aloud' versus 'new' mainly occurred in the later period of the recognition response, consistent with the LPC old/new effect. Our findings suggest that the within-subject PE in recognition memory reflects enhanced attention and distinctiveness, rather than increased memory strength. More broadly, our findings suggest that encoding strategies such as production enhance recollection more than familiarity., Competing Interests: Declaration of competing interest The authors declare that they know of no personal relationships or competing financial interests that could have influenced the conducting or reporting of this research., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Thromboembolism in blood vessels can lead to stroke or heart attack and even sudden death unless brought under control. Sonothrombolysis enhanced by ultrasound contrast agents has shown promising outcome on effective treatment of thromboembolism. Intravascular sonothrombolysis was also reported recently with a potential for effective and safe treatment of deep thrombosis. Despite the promising treatment results, the treatment efficiency for clinical application may not be optimized due to the lack of imaging guidance and clot characterization during the thrombolysis procedure. In this paper, a miniaturized transducer was designed to have an 8-layer PZT-5A stacked with an aperture size of 1.4 × 1.4 mm 2 and assembled in a customized two-lumen 10-Fr catheter for intravascular sonothrombolysis. The treatment process was monitored with internal-illumination photoacoustic tomography (II-PAT), a hybrid imaging modality that combines the rich contrast of optical absorption and the deep penetration of ultrasound detection. With intravascular light delivery using a thin optical fiber integrated with the intravascular catheter, II-PAT overcomes the penetration depth limited by strong optical attenuation of tissue. In-vitro PAT-guided sonothrombolysis experiments were carried out with synthetic blood clots embedded in tissue phantom. Clot position, shape, stiffness, and oxygenation level can be estimated by II-PAT at clinically relevant depth of ten centimeters. Our findings have demonstrated the feasibility of the proposed PAT-guided intravascular sonothrombolysis with real-time feedback during the treatment process.

Background: Diabetic nephropathy (DN) is one of the most devastating microvascular complications of diabetes, with a high prevalence and poor prognosis. Early intervention is crucial to improve the outcomes of DN. CXCL8 is related to podocyte damage in incipient DN; however, the role and expression level of CXCL8 have never been elucidated, especially in those with undiminished creatinine clearance., Methods: Consecutive inpatients with type 2 diabetes were included in this study. Patients were assigned into four groups based on the Mogensen stage, reflecting pathological features through clinical manifestations: non-DN group, hyperfiltration group, microalbuminuria group and overt DN group. Clinical and laboratory data were retrospectively collected and analyzed. Urinary CXCL8 (uCXCL8) was measured using an enzyme-linked immunosorbent assay (ELISA) method and adjusted for urinary creatinine (Cr) from the same urine sample., Results: In total, 88 eligible consecutive inpatients with type 2 diabetes were included in this study. uCXCL8 was differentially expressed in different stages of incipient DN; it decreased in the hyperfiltration phase of incipient DN (1.40±1.01 pg/μmol Cr) and was highly expressed in patients in the microalbuminuria stage (5.01±4.01 pg/μmol Cr). uCXCL8 was positively correlated with age, diabetes course, cystatin C and urinary albuminuria-to-creatinine ratio, but negatively correlated with estimated glomerular filtration rate ( P <0.05). uCXCL8 was a risk factor for classic DN after adjusting for age, diabetes course and cystatin C (OR = 1.17, 95% CI 0.98-1.4, P =0.045)., Conclusion: CXCL8 played an important role in the progression of incipient DN. The unique expression profile of uCXCL8 may provide a reference for understanding the prognosis and mechanisms of incipient DN progression. uCXCL8 was an independent risk factor for the development of classic DN., Competing Interests: The authors declare that they have no conflict of interests., (© 2023 He et al.)

Robotic prostheses and powered exoskeletons are novel assistive robotic devices for modern medicine. Muscle activity sensing plays an important role in controlling assistive robotics devices. Most devices measure the surface electromyography (sEMG) signal for myoelectric control. However, sEMG is an integrated signal from muscle activities. It is difficult to sense muscle movements in specific small regions, particularly at different depths. Alternatively, traditional ultrasound imaging has recently been proposed to monitor muscle activity due to its ability to directly visualize superficial and at-depth muscles. Despite their advantages, traditional ultrasound probes lack wearability. In this paper, a wearable ultrasound (US) transducer, based on lead zirconate titanate (PZT) and a polyimide substrate, was developed for a muscle activity sensing demonstration. The fabricated PZT-5A elements were arranged into a 4 × 4 array and then packaged in polydimethylsiloxane (PDMS). In vitro porcine tissue experiments were carried out by generating the muscle activities artificially, and the muscle movements were detected by the proposed wearable US transducer via muscle movement imaging. Experimental results showed that all 16 elements had very similar acoustic behaviors: the averaged central frequency, -6 dB bandwidth, and electrical impedance in water were 10.59 MHz, 37.69%, and 78.41 Ω, respectively. The in vitro study successfully demonstrated the capability of monitoring local muscle activity using the prototyped wearable transducer. The findings indicate that ultrasonic sensing may be an alternative to standardize myoelectric control for assistive robotics applications.

This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis (CVST). This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20% to 40% of the cases, and the incidence of CVST has increased since the outbreak of the coronavirus disease 2019 pandemic. Compared with conventional anticoagulant or thrombolytic drugs, sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves. However, previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes (e.g., recanalization within 30 min) in treating large, completely occluded veins or arteries. Here, we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wave-matter interaction-induced shear stress to enhance the lytic rate substantially. Our in vitro experiment showed that the lytic rate was increased by at least 64.3% compared with the nonvortex endovascular ultrasound treatment. A 3.1-g, 7.5-cm-long, completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot in vitro. Furthermore, we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins. This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies., (Copyright © 2023 Bohua Zhang et al.)

Nanoparticles containing thrombolytic medicines have been developed for thrombolysis applications in response to the increasing demand for effective, targeted treatment of thrombosis disease. In recent years, there has been a great deal of interest in nanoparticles that can be navigated and driven by a magnetic field. However, there are few review publications concerning the application of magnetic nanoparticles in thrombolysis. In this study, we examine the current state of magnetic nanoparticles in the application of in vitro and in vivo thrombolysis under a static or dynamic magnetic field, as well as the combination of magnetic nanoparticles with an acoustic field for dual-mode thrombolysis. We also discuss four primary processes of magnetic nanoparticles mediated thrombolysis, including magnetic nanoparticle targeting, magnetic nanoparticle trapping, magnetic drug release, and magnetic rupture of blood clot fibrin networks. This review will offer unique insights for the future study and clinical development of magnetic nanoparticles mediated thrombolysis approaches.

Thromboembolism in vessels often leads to stroke or heart attack and even sudden death unless brought under control. Sonothrombolysis based on ultrasound contrast agents has shown promising outcome in effective treatment of thromboembolism. Intravascular sonothrombolysis transducer was reported recently for unprecedented sonothrombolysis in vitro. However, it is necessary to provide an imaging guide during thrombolysis in clinical applications for optimal treatment efficiency. In this article, a dual mode ultrasound catheter was developed by combining a 16-MHz high-frequency element (imaging transducer) and a 220-kHz low-frequency element (treatment transducer) for sonothrombolysis in vitro. The treatment transducer was designed with a 20-layer PZT-5A stack with the aperture size of 1.2×1.2 mm 2 , and the imaging transducer with the aperture size of 1.2×1.2 mm 2 was attached in front of the treatment transducer. Both transducers were assembled into a customized 2-lm 10-Fr catheter. In vitro experiment was carried out using a bovine blood clot. Imaging tests were conducted, showing that the backscattering signals can be obtained with a high signal-to-noise ratio (SNR) for the 16-MHz imaging transducer. Sonothrombolysis was performed successfully that the volume of clot was reduced significantly after the 30-min treatment. The size changes of clot were observed clearly using the 16-MHz M-mode imaging during the thrombolysis. The findings suggest that the proposed ultrasound-guided intravascular sonothrombolysis can be enhanced since the position of treatment transducer can be adjusted with the target at the clot due to the imaging guide.

Venous thromboembolism (VTE) is a condition in which blood clots form within the deep veins of the leg or pelvis to cause deep vein thrombosis. The optimal treatment of VTE is determined by thrombus properties such as the age, size, and chemical composition of the blood clots. The thrombus properties can be readily evaluated by using photoacoustic computed tomography (PACT), a hybrid imaging modality that combines the rich contrast of optical imaging and deep penetration of ultrasound imaging. With inherent sensitivity to endogenous chromophores such as hemoglobin, multispectral PACT can provide composition information and oxygenation level in the clots. However, conventional PACT of clots relies on external light illumination, which provides limited penetration depth due to strong optical scattering of intervening tissue. In our study, this depth limitation is overcome by using intravascular light delivery with a thin optical fiber. To demonstrate in vitro blood clot characterization, clots with different acuteness and oxygenation levels were placed underneath ten-centimeter-thick chicken breast tissue and imaged using multiple wavelengths. Acoustic frequency analysis was performed on the received PA channel signals, and oxygenation level was estimated using multispectral linear spectral unmixing. The results show that, with intravascular light delivery, clot oxygenation level can be accurately measured, and the clot age can thus be estimated. In addition, we found that retracted and unretracted clots had different acoustic frequency spectrum. While unretracted clots had stronger high frequency components, retracted clots had much higher low frequency components due to densely packed red blood cells. The PACT characterization of the clots was consistent with the histology results and mechanical tests., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interest to disclose., (© Korean Society of Medical and Biological Engineering 2022.)

Thrombo-occlusive disease is one of the leading causes of death worldwide. There has been active research on safe and effective thrombolysis in preclinical and clinical studies. Recently, the dual-frequency transcutaneous sonothrombolysis with contrast agents [microbubbles (MBs)] has been reported to be more efficient in trigging the acoustic cavitation, which leads to a higher lysis rate. Therefore, there is increasing interest in applying dual-frequency technique for more significant efficacy improvement in intravascular sonothrombolysis since a miniaturized intravascular ultrasound transducer typically has a limited power output to fully harness cavitation effects. In this work, we demonstrated this efficacy enhancement by developing a new broadband intravascular transducer and testing dual-frequency sonothromblysis in vitro. A broadband intravascular transducer with a center frequency of 750 kHz and a footprint size of 1.4 mm was designed, fabricated, and characterized. The measured -6-dB fractional bandwidth is 68.1%, and the peak negative pressure is 1.5 MPa under the driving voltage of 80 V pp . By keeping one frequency component at 750 kHz, the second frequency component was selected from 450 to 650 kHz with an interval of 50 kHz. The in vitro sonothrombolysis tests were conducted with a flow model and the results indicated that the MB-mediated, dual-frequency (750+500 kHz) sonothrombolysis yields an 85% higher lysis rate compared with the single-frequency treatment, and the lysis rate of dual-frequency sonothrombolysis increases with the difference between the two frequency components. These findings suggest a dual-frequency excitation technique for more efficient intravascular sonothrombolysis than conventional single-frequency excitation.

Recent in vitro work has revealed that a forward-viewing intravascular (FVI) transducer has sonothrombolysis applications. However, the safety of this device has yet to be evaluated. In this study, we evaluated the safety of this device in terms of tissue heating, vessel damage and particle debris size during sonothrombolysis using microbubbles or nanodroplets with tissue plasminogen activator, in both retracted and unretracted blood clots. The in vitro and ex vivo sonothrombolysis tests using FVI transducers revealed a temperature rise of less than 1°C, no vessel damage as assessed by histology and no downstream clot particles >500 µm. These in vitro and ex vivo results indicate that the FVI transducer poses minimal risk for sonothrombolysis applications and should be further evaluated in animal models., Competing Interests: Conflict of interest disclosure X.J. has financial interest in Sonovascular, Inc. (Chapel Hill, NC, USA) which licensed an intravascular sonothrombolysis technology from North Carolina State. P.D. is an inventor on several patents describing the low-boiling-point phase change nanodroplets described here, and is a co-founder of Triangle Biotechnology, Inc. (Chapel Hill, NC, USA), which has licensed these patents. Z.X. has financial interest in HistoSonics., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

This paper reports a novel technique using the rotational magnetic field oscillation and low-intensity sub-megahertz ultrasound stimulation of magnetic microbubbles (MMBs) to promote the nanodroplets (NDs) phase transition and improve the permeation of NDs into the blood clot fibrin network to enhance the sonothrombolysis efficiency. In this study, the influence of different treatment methods with a combination of MMBs and NDs on the thrombolysis rate of both unretracted and retracted clots were investigated, including the stable and inertial cavitation, tPA effects, MMBs/NDs concentration ratio, sonication factors (input voltage, duty cycle) and rotational magnetic field factors (flux density, frequency). We demonstrated that tPA-mediated magneto-sonothrombolysis in combining NDs with MMBs could significantly enhance in vitro lysis of both unretracted clots (85 ± 8.3%) and retracted clots (57 ± 6.5%) in a flow model with 30 min treatment. The results showed that the combination of MMBs and NDs substantially improves in vitro lysis of blood clots with an unprecedented lysis rate., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We aim to develop a nanodroplet (ND)-mediated intravascular ultrasound (US) transducer for deep vein thrombosis treatments. The US device, having an efficient forward directivity of the acoustic beam, is capable of expediting the clot dissolution rate by activating cavitation of NDs injected onto a thrombus. We designed and prototyped a multi-pillar piezoelectric stack (MPPS) transducer composed of four piezoelectric stacks. Each stack was made of five layers of PZT-4 plates, having a dimension of 0.85 × 0.85 × 0.2 mm 3 . The transducer was characterized by measuring the electrical impedance and acoustic pressure, compared to simulation results. Next, in-vitro tests were conducted in a blood flow mimicking system using the transducer equipped with an ND injecting tube. The miniaturized transducer, having an aperture size of 2.8 mm, provided a high mechanical index of 1.52 and a relatively wide focal zone of 3.4 mm at 80 V pp , 0.96 MHz electric input. The mass-reduction rate of the proposed method (NDs + US) was assessed to be 4.1 and 4.6 mg/min with and without the flow model, respectively. The rate was higher than that (1.3-2.7 mg/min) of other intravascular ultrasound modalities using micron-sized bubble agents. The ND-mediated intravascular sonothrombolysis using MPPS transducers was demonstrated with an unprecedented lysis rate, which may offer a new clinical option for DVT treatments. The MPPS transducer generated a high acoustic pressure (~3.1 MPa) at a distance of approximately 2.2 wavelengths from the small aperture, providing synergistic efficacy with nanodroplets for thrombolysis without thrombolytic agents., (Copyright © 2021. Published by Elsevier B.V.)

One major challenge in current microbubble (MB) and tissue plasminogen activator (tPA)-mediated sonothrombolysis techniques is effectively treating retracted blood clots, owing to the high density and low porosity of retracted clots. Nanodroplets (NDs) have the potential to enhance retracted clot lysis owing to their small size and ability to penetrate into retracted clots to enhance drug delivery. For the first time, we demonstrate that a sub-megahertz, forward-viewing intravascular (FVI) transducer can be used for ND-mediated sonothrombolysis, in vitro. In this study, we determined the minimum peak negative pressure to induce cavitation with low-boiling point phase change nanodroplets and clot lysis. We then compared nanodroplet mediated sonothrombolysis to MB and tPA mediate techniques. The clot lysis as a percent mass decrease in retracted clots was 9 ± 8%, 9 ± 5%, 16 ± 5%, 14 ± 9%, 17 ± 9%, 30 ± 8%, and 40 ± 9% for the control group, tPA alone, tPA + US, MB + US, MB + tPA + US, ND + US, and ND + tPA + US groups, respectively. In retracted blood clots, combined ND- and tPA-mediated sonothrombolysis was able to significantly enhance retracted clot lysis compared with traditional MB and tPA-mediated sonothrombolysis techniques. Combined nanodroplet with tPA-mediated sonothrombolysis may provide a feasible strategy for safely treating retracted clots., Competing Interests: Competing interestsXiaoning Jiang has financial interest in Sonovascular, Inc. who licensed an intravascular sonothrombolysis technology from NC State. Paul Dayton is an inventor on several patents, describing the low-boiling point phase change nanodroplets described here, and is a co-founder of Triangle Biotechnology, Inc., which has licensed these patents. Zhen Xu has financial interest in HistoSonics., (© The Author(s) 2021.)

Previous work revealed that a forward-viewing intravascular (FVI) transducer can be used for microbubble (MB)-mediated sonothrombolysis and that the clot lysis was dependent on MB concentration. This study examined the effects of combining tissue plasminogen activator (tPA) with MB-mediated FVI sonothrombolysis. In vitro clot lysis and passive cavitation experiments were conducted to study the effect of low-dose tPA in FVI sonothrombolysis with varying MB concentrations. Enhanced FVI sonothrombolysis was observed in cases in which ultrasound (US) was combined with tPA or MBs compared with control, tPA alone or US alone. The lysis rate of US + tPA + MBs was improved by up to 130%, 31% and 8% for MB concentrations of 106, 107 and 108 MBs/mL, respectively, compared with MBs + US alone. Changes in stable and inertial cavitation doses were observed, corresponding to changes in clot lysis in MB-mediated FVI sonothrombolysis with and without tPA., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Thrombosis is an extremely critical clinical condition where a clot forms inside a blood vessel which blocks the blood flow through the cardiovascular system. Previous sonothrombolysis methods using ultrasound and microbubbles (MBs) often have a relatively low lysis rate due to the low microbubbles concentration at clot region caused by blood flow in the vessel. To solve this problem, the magnetic microbubbles (MMBs) that can be retained by an outer magnetic field against blood flow are used in this study. Here we report the development of a new method using the rotational magnetic field to trap and vibrate magnetic microbubbles at target clot region and then using an intravascular forward-looking ultrasound transducer to activate them acoustically. In this study, we investigated the influence of different blood flow conditions, vessel occlusion conditions (partial and fully occluded), clot ages (fresh, retracted), ultrasound parameters (input voltage, duty cycle) and rotational magnetic field parameters (amplitude, frequency) on the thrombolysis rate. The results showed that the additional use of magnetic microbubbles significantly enhances in vitro lysis of blood clot., (Copyright © 2019 Elsevier B.V. All rights reserved.)