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LIFU-responsive nanomedicine enables acoustic droplet vaporization-induced apoptosis of macrophages for stabilizing vulnerable atherosclerotic plaques

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Bioactive Materials 2022年第10期7卷 120-133页

作者： Jingxin Hou Jun Zhou Meiqi Chang Guangcheng Bao Jie Xu Man Ye Yixin Zhong Shuling Liu Junrui Wang Wei Zhang Haitao Ran Zhigang Wang Yu Chen Dajing Guo department of Radiology Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010PR China Materdicine Lab School of Life SciencesShanghai UniversityShanghai200444PR China Chongqing Key Laboratory of Ultrasound Molecular Imaging&Department of Ultrasound Second Affiliated Hospital of Chongqing Medical UniversityChongqing400010PR China State key laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050PR China department of Radiology Children’s Hospital of Chongqing Medical UniversityChongqing400014PR China

Due to the high risk of tearing and rupture,vulnerable atherosclerotic plaques would induce serious cardiovascular and cerebrovascular diseases.Despite the available clinical methods can evaluate the vulnerability of plaques and specifically treat vulnerable plaques before a cardiovascular event,but the efficiency is still low and undesirable.Herein,we rationally design and engineer the low-intensity focused ultrasound(LIFU)-responsive FPD@CD nanomedicine for the highly efficient treatment of vulnerable plaques by facilely loading phase transition agent perfluorohexane(PFH)into biocompatible PLGA-PEG-PLGA nanoparticles(PPP NPs)and then attaching dextran sulphate(DS)onto the surface of PPP NPs for targeting delivery.DS,as a typical macrophages-targeted molecule,can achieve the precise vaporization of NPs and subsequently controllable apoptosis of RAW 264.7 macrophages as induced by acoustic droplet vaporization(ADV)effect.In addition,the introduction of DiR and Fe3O4 endows nanomedicine with near-infrared fluorescence(NIRF)and magnetic resonance(MR)imaging capabilities.The engineered FPD@CD nanomedicine that uses macrophages as therapeutic targets achieve the conspicuous therapeutic effect of shrinking vulnerable plaques based on in vivo and in vitro evaluation outcomes.A reduction of 49.4%of vascular stenosis degree in gross pathology specimens were achieved throughout the treatment period.This specific,efficient and biosafe treatment modality potentiates the biomedical application in patients with cardiovascular and cerebrovascular diseases based on the relief of the plaque rupture concerns.

关键词： Vulnerable plaques Acoustic droplet vaporization Macrophages Apoptosis Nanomedicine

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IR780 loaded hollow MnO_(2) nanoparticles for dual-mode imaging and enhanced photodynamic therapy of oral squamous cell carcinoma

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BIOCELL 2022年第4期46卷 1079-1088页

作者： WEI PAN YE HE MENGDONG HE FEI WANG LIHUA QIU department of Oral and Maxillofacial Surgery Stomatological Hospital Affiliated to Chongqing Medical UniversityChongqing401147China chongqing Municipal key laboratory of Oral Biomedical Engineering of Higher Education Chongqing Medical UniversityChongqing401147China chongqing key laboratory of ultrasound molecular imaging Chongqing Medical UniversityChongqing400010China

Photodynamic therapy(PDT)has emerged as a novel therapeutic modality for cancer treatment,but its therapeutic efficacy is severely limited by the hypoxic tumor microenvironment(TME).Here we designed an innovative multifunctional nano-platform which consists of a hollow MnO_(2) shell and internal photosensitizer IR780.It is not only used for multimodal imaging of oral squamous cell carcinoma(OSCC),but also for adjustment hypoxic TME to enhance cancer treatment.Hollow MnO_(2) can promote decomposition of tumor endogenous H2O2 to relieve tumor hypoxia,thereby enhancing the effect of photodynamic therapy.Photosensitizer IR780 generates singlet oxygen under laser irradiation to kill tumor cells,playing photodynamic effect,can also act as the contrast agents for photoacoustic and fluorescence multiple imaging,providing potential imaging capability for cancer therapeutic guidance and monitoring.Our research results in this article show that HMnO_(2)-IR780 nanocomposite exhibits good biocompatibility and nontoxicity,strong PA/FL imaging contrast,excellent oxygen production capacity and outstanding photodynamic therapy effect.This finding provides a new idea for multimodal imaging-guided nanotherapy for OSCC.

关键词： Endogenous oxygen generation Tumor hypoxia Multimodal imaging Photodynamic therapy Oral squamous cell carcinoma

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Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system

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International Journal of Oral Science 2022年第3期14卷 297-308页

作者： Liangjing Xin Fuyuan Zhou Chuangwei Zhang Wenjie Zhong Shihan Xu Xuan Jing Dong Wang Si Wang Tao Chen Jinlin Song College of Stomatology Chongqing Medical UniversityChongqing Key Laboratory for Oral Diseases and Biomedical SciencesChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqingChina department of ultrasound The First Affiliated HospitalChongqing Medical UniversityChongqingChina

Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate(4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time,the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2-/-mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment.Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction,ameliorate local inflammation for more predictable periodontitis.

关键词： Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system

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Left Ventricular Systolic Intraventricular Flow Field Assessment in Hyperthyroidism Patients Using Vector Flow Mapping

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第4期35卷 574-578页

作者：周滨瑜王静谢明星刘曼薇吕清 department of ultrasound Hubei Provincial Key Laboratory of Molecular ImagingUnion HospitalTongji Medical CollegeHuazhong University of Science and Technology

Summary： Intraventricular hydrodynamics is considered an important component of cardiac function assessment. Vector flow mapping （VFM） is a novel flow visualization method to describe cardiac pathophysiological condition. This study examined use of new VFM and flow field for assessment of left ventricular （LV） systolic hemodynamics in patients with simple hyperthyroidism （HT）. Thirty-seven simple HT patients were enrolled as HT group, and 38 gender- and age-matched healthy volunteers as control group. VFM model was used to analyze LV flow field at LV apical long-axis view. The follow- ing flow parameters were measured, including peak systolic velocity （Vs）, peak systolic flow （Fs）, total systolic negative flow （SQ） in LV basal, middle and apical level, velocity gradient from the apex to the aortic valve （AV）, and velocity according to half distance （V1/2）. The velocity vector in the LV cavity, stream line and vortex distribution in the two groups were observed. The results showed that there were no significant differences in the conventional parameters such as left ventricular ejection fraction （LVEF）, left ventricular end-diastolic diameter （LVEDD） and left atrium diameter （LAD） between HT group and control group （P〉0.05）. Compared with the control group, a brighter flow and more vortexes were detected in HT group. Non-uniform distribution occurred in the LV flow field, and the stream lines were discontinuous in HT group. The values of Vs and Fs in three levels, SQ in middle and basal levels, AV and V1/2 were higher in HT group than in control group （P〈0.01）. AV was positively correlated with serum free thyroxin （FT4）（r=0.48, P〈0.01）. Stepwise multiple regression analysis showed that LVEDD, FT4, and body surface area （BSA） were the influence factors of △V. The unstable left ventricular sys- tolic hydrodynamics increased in a compensatory manner in simple PIT patients. The present study in- dicated that VFM may be used for early detection of abnormal ventricle contraction in clinical settings.

关键词： hyperthyroidism vector flow mapping left ventricle hydrodynamics flow field

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Echocardiographic Evaluation of Cardiac Dyssynchrony in Patients with Congestive Heart Failure

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2016年第3期36卷 434-441页

作者：秦川张丽章子铭王斌叶舟王勇 Navin C.Nanda 谢明星 department of ultrasound Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyHubei Province Key Laboratory of Molecular Imaging department of ultrasound Central Hospital of Karamay Heart Station/Echocardiography Laboratories The University of Alabama at Birmingham

The present study investigated the application of echocardiography to evaluation of cardiac dyssynchrony in patients with congestive heart failure（CHF）. A total of 348 consecutive CHF patients who were admitted for cardiac resynchronization（CRT） and presented with low ejection fraction（EF） and wide QRS duration were enrolled in this study, along with 388 healthy individuals. Dyssynchrony was assessed based on filling time ratio（FT/RR）, left ventricular pre-ejection delay（PED）, interventricular mechanical delay（IVMD）, longitudinal opposing wall delay（LOWD） and radial septal to posterior wall delay（RSPWD）. Response to CRT was defined as a ≥15% increase in EF. The results showed that FT/RR was decreased while PED, IVMD, LOWD and RSPWD were increased in the CHF group compared with the control group（P〈0.01）. In the CHF group, FT/RR was negatively correlated with the QRS duration, LV end-diastolic diameter（LVESd）, LV end-diastolic volume（LVEDV） and LV end-systolic volume（LVESV）（P〈0.01）, but positively with the LVEF（P〈0.01）. Additionally, PED, IVMD, LOWD and RSPWD were positively correlated with the QRS duration, LVESd, LVEDV and LVESV（P〈0.01）, but negatively with the LVEF（P〈0.01）. The CHF group was divided into three subgroups according to the varying degrees of LVEF. FT/RR decreased successively from the LVEF-1 group to the LVEF-2 group to the LVEF-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order（P〈0.01）. The CHF group was divided into three subgroups according to the varying degrees of QRS duration, and FT/RR decreased successively in a sequence from the QRS-1 group to the QRS-2 group to the QRS-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order（P〈0.01）. Speckle tracking radial dyssynchrony ≥130 ms was predictive of an EF response in patients in QRS-1 group（78% sensitivity, 83% specificity）, those in QRS-2 group（83% sensitivity, 77% specificity） and in QRS-3 group（89% sensitivity, 79% specificity）. In conclusion, echocardiography is a convenient

关键词： echocardiography congestive heart failure cardiac dyssynchrony left ventricular function

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Wave Intensity Analysis of Carotid Artery:A Noninvasive Technique for Assessing Hemodynamic Changes of Hyperthyroid Patients

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2010年第5期30卷 672-677页

作者：张艳容刘曼薇王美玲张丽吕清谢明星项飞翔付倩尹烨华鲁成发严天慰黄艳 key laboratory of molecular imaging of Hubei Province Department of UltrasoundUnion HospitalTongji Medical CollegeHuazhong University of Science and Technology

This study examined the wave intensity (WI) of the carotid artery in patients with hyperthyroid in order to assess the hemodynamic changes of hyperthyroid patients.A total of 86 hyperthyroid patients without cardiac morphological changes and arrhythmia, and 80 healthy control subjects were enrolled in the study.Right common carotid artery (RCCA) was selected for ultrasonic imaging to obtain WI indices, including amplitude of the peak during early systole (W1), amplitude of the peak during late systole (W2), area of the negative wave during mid-systole (NA), interval between R wave of electrocardiogram and W1 (R-1st), interval between W1 and W2 (1st-2nd).The levels of serum thyroid hormones, consisting of free triiodothyronine (FT3), free thyroxin (FT4) and thyroid stimulating hormone (TSH), were measured in hyperthyroid patients.Echocardiographic indices including left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were determined in each subject.The results showed that the W1, W2, NA, and (1st-2nd×HR) in hyperthyroid patients were significantly higher than those in healthy controls.There was no significant difference in LVEF and LVFS between the two groups.FT3 was correlated with W1, W2, NA, (1st-2nd×HR), pulse pressure (PP) and heart rate (HR) in hyperthyroid patients.Several abnormal waves on WI curves were present in 19 hyperthyroid patients during mid-systole.It was concluded that WI technique may prove a real-time, noninvasive, sensitive and convenient tool for assessing the cardiac function and hemodynamic alterations in hyperthyroid patients.

关键词： hyperthyroidism wave intensity hemodynamic echo-tracking

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Cardiovascular Cast Model Fabrication and Casting Effectiveness Evaluation in Fetus with Severe Congenital Heart Disease or Normal Heart

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2016年第2期36卷 259-264页

作者：王瑜曹海燕谢明星贺林韩伟洪柳彭源胡云飞宋本才王静王斌邓诚 department of ultrasound Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyHubei Provincial Key Laboratory of Molecular Imaging laboratory of Anatomy Tongji Medical CollegeHuazhong University of Science and Technology

To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease（control group） and 18 specimens with severe congenital heart disease（case group） from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels（including overall level, atrioventricular and great vascular system, left-sided and right-sided heart）, as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group（P=0.027）. Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group（P=0.046）, while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus.

关键词： severe congenital heart disease fetus cast model anatomy casting effectiveness perfusion

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Dynamic Characteristic Mechanism of Atrial Septal Defect Using Real-Time Three-Dimensional Echocardiography and Evaluation of Right Ventricular Functions

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2017年第1期37卷 140-147页

作者：沙仁高娃张军秦川吕清 department of ultrasound Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyHubei Province Key Laboratory of Molecular ImagingWuhan 430022China department of ultrasound Affiliated Hospital of Inner Mongolia Medical UniversityHuhhot 010059China department of Urology Affiliated Hospital of Inner Mongolia Medical UniversityHuhhot 010059China department of ultrasound Central Hospital of KaramayKaramay 834000China

The dynamic characteristics of the area of the atrial septal defect（ASD） were evaluated using the technique of real-time three-dimensional echocardiography（RT 3DE）, the potential factors responsible for the dynamic characteristics of the area of ASD were observed, and the overall and local volume and functions of the patients with ASD were measured. RT 3DE was performed on the 27 normal controls and 28 patients with ASD. Based on the three-dimensional data workstations, the area of ASD was measured at P wave vertex, R wave vertex, T wave starting point, and T wave terminal point and in the T-P section. The right atrial volume in the same time phase of the cardiac cycle and the motion displacement distance of the tricuspid annulus in the corresponding period were measured. The measured value of the area of ASD was analyzed. The changes in the right atrial volume and the motion displacement distance of the tricuspid annulus in the normal control group and the ASD group were compared. The right ventricular ejection fractions in the normal control group and the ASD group were compared using the RT 3DE long-axis eight-plane（LA 8-plane） method. Real-time three-dimensional volume imaging was performed in the normal control group and ASD group（n=30）. The right ventricular inflow tract, outflow tract, cardiac apex muscular trabecula dilatation, end-systolic volume, overall dilatation, end-systolic volume, and appropriate local and overall ejection fractions in both two groups were measured with the four-dimensional right ventricular quantitative analysis method（4D RVQ） and compared. The overall right ventricular volume and the ejection fraction measured by the LA 8-plane method and 4D RVQ were subjected to a related analysis. Dynamic changes occurred to the area of ASD in the cardiac cycle. The rules for dynamic changes in the area of ASD and the rules for changes in the right atrial volume in the cardiac cycle were consistent. The maximum value of the changes in the right atrial volume occurred in the end-systolic period

关键词： ultrasonic cardiography real-time three-dimension atrial septal defect tricuspid annulus right atrium

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The Value of Conventional Echocardiographic and Tissue Doppler imaging in the Diagnosis of Cardiac Amyloidosis

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2008年第6期28卷 732-736页

作者：张丽谢明星王新房杨亚莉黄君红陈明项飞翔吕清 department of ultrasound Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyHubei Provincial Key Laboratory of Molecular Imaging

Transthoracic echocardiographic characteristics of 17 cases of cardiac amyloidosis （CA）, a rare disease in China, were analyzed in order to improve the understanding of the disease. Seventeen cases of biopsy-proven CA, admitted to Wuhan Union Hospital from June 1994 to September 2008 were retrospectively reviewed. Twenty normal volunteers served as control group. Left atrial and ventricular functions and mitral inflow velocity were measured by two-dimensional, and Doppler echocardiography, and tissue Doppler imaging （TDI）-derived peak systolic wall motion velocities （Sv）, peak early diastolic wall motion velocities （Ev）, and peak late diastolic wall motion （Av） were measured at the septum, lateral, inferior and anterior corners of mitral annulus from the apical 4-and 2 chamber views. Compared with the control group, the interventricular septal thickness （IVSd）, the left ventricular posterior wall （LVPWd）, right ventricular transverse diameter （RVTDd） near the end of diastole and the interauricular septum thickness （IASs）, left atrial anteroposterior diameter （LAADs）, right atrial transverse diameter （RATDs） near the end of systole were increased significantly （all P〈0.05） and left ventricular ejection fraction （LVEF） decreased （P〈0.05） in the CA group. Compared with the control group, Sv, Ev at each wall and Av at almost all walls were significantly decreased in the CA group. In the CA group, Myocardial echoes of interventricular septum and free wall of left ventricle were enhanced evidently and distributed unevenly. The echoes presented as ground glass-like images, with some spotty hyper echoes. Both atria were enlarged, and LVEF decreased, with diastolic function impaired, and mild-moderate hydropericardium found in the CA group. It was concluded that echocardiography was a relatively sensitive and highly specific non-invasive method for the diagnosis of CA.

关键词： echocardiography TDI amyloidosis cardiomyopathy

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Assessment of Age-related Changes in Left Ventricular Twist by Two-dimensional ultrasound Speckle Tracking imaging

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第6期27卷 691-695页

作者：张丽谢明星付曼丽王新房吕清韩伟张静刘莹莹王静项飞翔 department of ultrasound Union Hospital Tongji Medical College Huazhong University of Science and Technology Hubei Provincial Key Laboratory of molecular Imaging

To assess the normal value of left ventricular twist （LVtw） and examine the changes with normal aging by 2-dimensional ultrasound speckle-tracking imaging （STI）, 121 healthy volunteers were divided into three age groups： a youth group （19-45 y old）, a middle-age group （46-64 y old ） and an old-age group （≥65 y old）. Basal and apical short-axis images of left ventricular were acquired to analyse LV rotation （LVrot） and LVrot velocity. LVtw and LVtw velocity was defined as apical LVrot and LVrot velocity relative to the base. Peak twist （Ptw）, twist at aortic valve closure （AVCtw）, twist at mitral valve opening （MVOtw）, untwisting rate （UntwR）, half time of untwisting （HTU）, peak twist velocity （PTV）, time to peak twist velocity （TPTV）, peak untwisting velocity （PUV）, time to peak untwisting velocity （TPUV） were separately measured. The results showed that the normal LV performs a wringing motion with a clockwise rotation at the base and a counterclock- wise rotation at the apex （as seen from the apex）. The LVtw velocity showed a systolic counterclockwise twist followed by a diastolic clockwise twist. Peak twist develops near the end of systole （96%±4.2% of systole）. With aging, Ptw, AVCtw, MVOtw, HTU and PUV increased significantly （P〈0.05） and UntwR decreased significantly （P〈0.05）. However, no significant differences in TPUV, PTV and TPTV were noted among the 3 groups （P〉0.05）. It is concluded that LV twist can be measured non-invasively by 2-dimensional ultrasound STI imaging. The age-related changes of LVtw should be fully taken into consideration in the assessment of LV function.

关键词： echocardiography speckle tracking imaging left ventricular twist rotation

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