Clinical sonochemotherapy of inoperable pancreatic cancer using diagnostic ultrasound and microbubbles: a multicentre, open-label, randomised, controlled trial.

OBJECTIVES: Sonochemotherapy, which uses microbubble (MB)-assisted ultrasound (US) to deliver chemotherapeutic agents, has the potential to enhance tumour chemotherapy. The combination of US and MB has been demonstrated to prolong the survival of patients with pancreatic cancer. This phase 2 clinical trial aimed to determine the clinical efficacy and safety of sonochemotherapy for inoperable pancreatic ductal adenocarcinoma by using US and MB. METHODS: Eighty-two patients with stage III or IV pancreatic cancer were recruited from July 2018 to March 2021 and followed up until September 2022. US treatment was performed with a modified diagnostic US scanner for 30 min after chemotherapeutic infusion. The primary endpoint was overall survival (OS), and the secondary endpoints were Eastern Cooperative Oncology Group (ECOG) status < 2, progression-free survival (PFS), disease control rate (DCR), and adverse events. RESULTS: Seventy-eight patients were randomly allocated (40 to chemotherapy and 38 to sonochemotherapy). The median OS was longer with sonochemotherapy than with chemotherapy (9.10 vs. 6.10 months; p = 0.037). The median PFS with sonochemotherapy was 5.50 months, compared with 3.50 months (p = 0.080) for chemotherapy. The time of ECOG status < 2 was longer with sonochemotherapy (7.20 months) than with chemotherapy (5.00 months; p = 0.029). The DCR was 73.68% for sonochemotherapy compared with 42.50% for the control (p = 0.005). The incidence of overall adverse events was balanced between the two groups. CONCLUSIONS: The use of sonochemotherapy can extend the survival and well-being time of stage III or IV pancreatic cancer patients without any increase in serious adverse events. TRIAL REGISTRATION: ChineseClinicalTrials.gov ChiCTR2100044721 CLINICAL RELEVANCE STATEMENT: This multicentre, randomised, controlled trial has proven that sonochemotherapy, namely, the combination of diagnostic ultrasound, microbubbles, and chemotherapy, could extend the overall survival of patients with end-stage pancreatic ductal adenocarcinoma from 6.10 to 9.10 months without increasing any serious adverse events. KEY POINTS: • This is the first multicentre, randomised, controlled trial of sonochemotherapy for clinical pancreatic cancer treatment using ultrasound and a commercial ultrasound contrast agent. • Sonochemotherapy extended the median overall survival from 6.10 (chemotherapy alone) to 9.10 months. • The disease control rate increased from 42.50% with chemotherapy to 73.68% with sonochemotherapy.

Guided longer pulses from a diagnostic ultrasound and intraclot microbubble enhanced catheter-directed thrombolysis in vivo.

The mechanism of ultrasound thrombolysis (UT) is generally attributed to cavitation. The insufficiency of microbubbles (MB) to serve as cavitation nuclei in the vessel-obstructing thrombi significantly reduces the effectiveness of UT. Taking advantage of the widely performed catheter-directed therapy (CDT), in a thrombo-embolized rabbit IVC model with a simultaneous catheter directed rt-PA thrombolysis procedure, guided moderate mechanical index longer pulses from a modified diagnostic ultrasound transducer, combined with an intraclot infusion of MB, significantly accelerated the thrombolysis process. The higher thrombolysis efficacy score and consistent elevated post-treatment plasma concentration level of D-Dimer, a product of fibrinolysis, both indicated the superiority of CDT + UT over CDT/UT alone. Pathologic examination of the treated occluded IVC segments revealed an almost complete dissolution of the thrombi treated with CDT + UT. There was no evidences of thrombo-embolism or local thrombus formation in the cardiac-pulmonary vessels. Combined with intraclot infusion of MB, guided longer pulse ultrasound from a diagnostic transducer is able to safely and significantly improve a catheter-directed thrombolysis procedure. It thus has the potential to achieve earlier clot removal, administration of a lower dosage of thrombolytic agent and, consequently, a lower incidence of thrombolysis-related side effects.

The Efficacy of Single-Agent Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Biologically Selected Patients with Non-Small-Cell Lung Cancer: A Meta-Analysis of 19 Randomized Controlled Trials.

OBJECTIVE: To determine the efficacy of first-generation single-agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in advanced non-small-cell lung cancer patients with known EGFR mutation status, we undertook this pooled analysis. METHOD: We searched for randomized controlled trials (RCTs) in Medline, Embase, the Cochrane Controlled Trials Register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. RESULTS: Out of 2,129 retrieved articles, 19 RCTs enrolling 2,016 patients with wild-type EGFR tumors and 1,034 patients with mutant EGFR tumors were identified. For these EGFR mutant patients, single-agent EGFR-TKI therapy improved progression-free survival (PFS) over chemotherapy: the summary hazard ratios (HRs) were 0.41 (p < 0.001) for the first-line setting and 0.46 (p = 0.02) for the second-/third-line setting. For those EGFR wild-type patients, single-agent EGFR-TKI therapy did not do as well as chemotherapy in the first-line setting (HR = 1.65, p = 0.03) and in the second-/third-line setting (HR = 1.27, p = 0.006). No statistically significant difference was observed in terms of overall survival (OS). Using platinum-based doublet chemotherapy as a common comparator, indirect comparison showed the superior efficacy of single-agent EGFR-TKI therapy over EGFR-TKIs added to chemotherapy in PFS [HR = 1.35 (1.03, 1.77), p = 0.03]. Additionally, a marginal trend towards the same direction was found in the OS analysis [HR = 1.16 (0.99, 1.35), p = 0.06]. Interestingly, for those EGFR wild-type tumors, single-agent EGFR-TKI therapy was inferior to EGFR-TKIs added to chemotherapy in PFS [HR = 0.38 (0.33, 0.44), p < 0.001] and OS [HR = 0.83 (0.71, 0.97), p = 0.02]. CONCLUSIONS: For these EGFR mutant patients, single-agent EGFR-TKI therapy prolonged PFS over chemotherapy. However, single-agent EGFR-TKI therapy was inferior to chemotherapy in PFS for those EGFR wild-type patients. Single-agent EGFR-TKI therapy could improve PFS over the combination of EGFR-TKIs and chemotherapy in these EGFR mutant patients. However, EGFR-TKIs combined with chemotherapy could provide additive PFS and OS benefit over single-agent EGFR-TKI therapy in those EGFR wild-type patients.

Combination of real time three-dimensional echocardiography with diagnostic catheterization to derive left ventricular pressure-volume relations.

AIMS: The aim of this study was to investigate the left ventricular (LV) myocardial contractility index-Emax using transesophageal real time three-dimensional echocardiography (RT3DE) combined with catheterization. METHODS: Transesophageal RT3DE (single beat, X7-2 × matrix, iE33, Philips) was used to obtain real time LV volumes in pigs. Volumes were integrated with LV pressures from conductance catheterization (CC) to create RT3DE pressure-volume relations. At the same time, CC was used for measuring conventional pressure-volume relations that served as reference. The slope Emax was determined from RT3DE and CC end-systolic pressure-volume relations. All measurements were made at rest and during dobutamine infusion. RESULTS: In six pigs, the mean ± SD (mmHg/mL) values were Emax-CC 1.86 ± 1.1 and Emax-RT3DE 1.78 ± 1.2 (P = 0.502) at baseline. On dobutamine, mean Emax-CC was 3.43 ± 1.5 and Emax-RT3DE 3.60 ± 1.23 (P = 0.171). Bland-Altman analysis showed good agreements between the RT3DE- and CC-derived Emax for measurements performed at baseline and on dobutamine. CONCLUSIONS: Emax can be determined from RT3DE integrated with catheterization-derived pressures. RT3DE is a promising method for enhancing clinical applicability of pressure-volume relations for assessment of myocardial contractility.

Validation of admittance computed left ventricular volumes against real-time three-dimensional echocardiography in the porcine heart.

The admittance and Wei's equation is a new technique for ventricular volumetry to determine pressure-volume relations that addresses traditional conductance-related issues of parallel conductance and field correction factor. These issues with conductance have prevented researchers from obtaining real-time absolute ventricular volumes. Moreover, the time-consuming steps involved in processing conductance catheter data warrant the need for a better catheter-based technique for ventricular volumetry. We aimed to compare the accuracy of left ventricular (LV) volumetry between the new admittance catheterization technique and transoesophageal real-time three-dimensional echocardiography (RT3DE) in a large-animal model. Eight anaesthetized pigs were used. A 7 French admittance catheter was positioned in the LV via the right carotid artery. The catheter was connected to an admittance control unit (ADVantage; Transonic Scisense Inc.), and data were recorded on a four-channel acquisition system (FA404; iWorx Systems). Admittance catheterization data and transoesophageal RT3DE (X7-2; Philips) data were simultaneously obtained with the animal ventilated, under neuromuscular blockade and monitored in baseline conditions and during dobutamine infusion. Left ventricular volumes measured from admittance catheterization (Labscribe; iWorx Systems) and RT3DE (Qlab; Philips) were compared. In a subset of four animals, admittance volumes were compared with those obtained from traditional conductance catheterization (MPVS Ultra; Millar Instruments). Of 37 sets of measurements compared, admittance- and RT3DE-derived LV volumes and ejection fractions at baseline and in the presence of dobutamine exhibited general agreement, with mean percentage intermethod differences of 10% for end-diastolic volumes, 14% for end-systolic volumes and 9% for ejection fraction; the respective intermethod differences between admittance and conductance in eight data sets compared were 11, 11 and 12%. Admittance volumes were generally higher than those obtained by RT3DE, especially among the larger ventricles. It is concluded that it is feasible to derive pressure-volume relations using admittance catheterization in large animals. This study demonstrated agreements between admittance and RT3DE to within 10-14% mean intermethod difference in the estimation of LV volumes. Further investigation will be required to examine the accuracy of volumes in largest ventricles, where intermethod divergence is greatest.

[Changes of serum neuron-specific enolase and serum ferritin levels in patients with pneumoconiosis].

OBJECTIVE: To investigate the changes in serum neuron-specific enolase (NSE) and serum ferritin (SF) in patients with pneumoconiosis and their relationship with the onset of pneumoconiosis. METHODS: The serum NSE and SF levels in the peripheral blood of patients with pneumoconiosis were measured by electrochemical fluorescence immunoassay. RESULTS: The patients with first-stage pneumoconiosis and second-stage pneumoconiosis had significantly higher serum NSE and SF levels than the control group (23.0264±14.0410 and 44.9776±26.5208 ng/ml vs 8.1480±3.7512 ng/ml, P < 0.05; 267.2515±186.5809 and 579.1371±433.9326 ng/ml vs 120.8613±74.2809 ng/ml, P < 0.05), and the patients with second-stage pneumoconiosis had significantly higher serum NSE and SF levels than those with first-stage pneumoconiosis (P < 0.05). After treatment, the serum NSE level decreased significantly in the patients with pneumoconiosis (21.1675±17.5942 ng/ml vs 33.4490±21.6948 ng/ml, P < 0.05), but it was still significantly higher than that in the control group (P < 0.05). The treatment did not produce significant changes in SF level among these patients (P > 0.05). CONCLUSION: Patients with pneumoconiosis have elevated serum NSE and SF levels, which may be related to the onset and progression of this disease.

Marijuana use is inversely associated with liver steatosis detected by transient elastography in the general United States population in NHANES 2017-2018: A cross-sectional study.

BACKGROUND: The impact of marijuana on the general population is largely unknown. The present study aimed to assess the association between marijuana use and liver steatosis and fibrosis in the general United States population utilizing data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This cross-sectional study was performed with data from the 2017-2018 cycle of NHANES. The target population comprised adults in the NHANES database with reliable vibration controlled transient elastography (VCTE) results. The median values of the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to evaluate liver steatosis and fibrosis, respectively. After adjusting for relevant confounders, a logistic regression analysis was used to assess the association between marijuana use and liver steatosis and fibrosis. RESULTS: A total of 2622 participants were included in this study. The proportions of never marijuana users, past users, and current users were 45.9%, 35.0%, and 19.1%, respectively. Compared to never marijuana users, past and current users had a lower prevalence of liver steatosis (P = 0.184 and P = 0.048, respectively). In the alcohol intake-adjusted model, current marijuana use was an independent predictor of a low prevalence of liver steatosis in people with non-heavy alcohol intake. The association between marijuana use and liver fibrosis was not significant in univariate and multivariate regression. CONCLUSION: In this nationally representative sample, current marijuana use is inversely associated with steatosis. The pathophysiology is unclear and needs further study. No significant association was established between marijuana use and liver fibrosis, irrespective of past or current use.

Endothelial adhesion of targeted microbubbles in both small and great vessels using ultrasound radiation force.

The effectiveness of microbubble-mediated ultrasound molecular imaging and drug delivery has been significantly affected by the axial laminar flow of vessels which prevents ultrasound contrast agents (UCAs) from targeting vascular endothelium. Studies show that acoustic manipulation could increase targeted UCA adhesion in microcirculation and some small vessels. In this study we demonstrate that ultrasound radiation force (USRF) can also significantly enhance the targeted adhesion of microbubbles in both small and great vessels. Our results indicate that the UCA adhesion targeted to ICAM-1 expressed on mouse cremaster microvascular endothelial cells increase about 9-fold when USRF is applied at 1 MHz and 73.9 kPa. The adhesion of anti-CD34 microbubbles to the endothelia of rat abdominal aorta was visually analyzed using scanning electron microscopy for the first time and thousands of microbubbles were found attached to the aortic endothelia after USRF application at the same acoustic parameters. Our data illustrate that targeted adhesion of anti-CD34 microbubbles is possible in normal abdominal aorta and we demonstrate the potential of using USRF in molecular imaging of a vascular target.

[Destruction of Walker-256 tumor vasculature by a novel ultrasound cavitation technique].

OBJECTIVE: To explore the feasibility of disrupting tumor microcirculation by the cavitation of microbubbles enhanced ultrasound (US) and analyze its pathological mechanism. METHODS: Twenty-four SD male rats with subcutaneously transplanted Walker-256 tumor were divided into 3 groups, i.e. ultrasound plus microbubbles group (US + MB), US group and sham group. Pulsed US was delivered to tumor for 3 minutes during an intravenous infusion of microbubbles at 0.2 ml/kg in the US + MB group. The control groups received only the US exposure or the MB injection. Tumor perfusion was visualized with contrast enhanced ultrasound before and 0 min after treatment. Finally the pathological examination was performed. RESULTS: The contrast perfusion of Walker-256 tumors vanished immediately after treatment in the US + MB group and the gray scale value (GSV) decreased from 121 ± 12 (pre-treatment) to 81 ± 9 (post-treatment, P < 0.01). There was no significant difference of GSV before and after treatment in two control groups (P > 0.05). The GSV values were 112 ± 14 and 111 ± 12 pre-treatment and 113 ± 14 and 103 ± 13 post-treatment in the sham and US groups. The pathological examination showed remarkable hemorrhage, endothelial injuries, increased intercellular edema and in situ thrombosis. CONCLUSION: Microbubble-enhanced ultrasound can significantly disrupt tumor vasculature and block its circulation. And it may become a novel physical anti-angiogenetic therapy for tumor.

Optimal treatment occasion for ultrasound stimulated microbubbles in promoting gemcitabine delivery to VX2 tumors.

Ultrasound stimulated microbubbles (USMB) is a widely used technology that can promote chemotherapeutic delivery to tumors yet the best treatment occasion for USMB is unknown or ignored. We aimed to determine the optimal treatment occasion for USMB treatment to enhance tumor chemotherapy to achieve the highest drug concentration in tumors. Experiments were conducted on VX2 tumors implanted in 60 rabbits. Gemcitabine (GEM) was intravenously infused as a chemotherapeutic agent and USMB was administered before, during or after chemotherapy. USMB was conducted with a modified diagnostic ultrasound at 3 MHz employing short bursts (5 cycles and 0.125% duty cycle) at 0.26 MPa in combination with a lipid microbubble. Subsequently, tumor blood perfusion quantitation, drug concentration detection, and fluorescence microscopy were performed. The results showed that the group that received USMB treatment immediately after GEM infusion had the highest drug concentration in tumors, which was 2.83 times that of the control group. Fifteen tumors were then treated repeatedly with the optimal USMB-plus-GEM combination, and along with the GEM and the control groups, were studied for tumor growth, tumor cell proliferation, apoptosis, and related cytokine contents. The combined treatment significantly inhibited tumor growth and promoted apoptosis. The levels of related cytokines, including HIF-1α, decreased after six combination therapies. These results suggest that the optimal treatment occasion for USMB occurs immediately after chemotherapy and tumor hypoxia improves after multiple combination therapies.

Chemotherapy Augmentation Using Low-Intensity Ultrasound Combined with Microbubbles with Different Mechanical Indexes in a Pancreatic Cancer Model.

The aim of the study was to explore the optimal mechanical indexes (MIs) for low-intensity ultrasound (LIUS) combined with microbubbles to enhance tumor blood perfusion and improve drug concentration in pancreatic cancer-bearing nude mice. Fifty-four nude mice bearing bilateral pancreatic tumors on the hind legs were randomly divided into three groups (the MI was set at 0.3, 0.7 and 1.1 in groups A, B and C, respectively). Five nude mice in each group were intravenously injected with the fluorescent dye DiR iodide (DiIC18(7),1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide); for each mouse, one tumor was treated with LIUS combined with microbubbles, and the contralateral tumor was exposed to sham ultrasound. In vivo fluorescence imaging was performed to detect the enrichment of intratumoral DiR iodide. Twelve mice in each group were intravenously injected with doxorubicin (DOX) and underwent ultrasound therapy as described above. Tumor blood perfusion changes were quantitatively evaluated with pre- and post-treatment contrast-enhanced ultrasound (CEUS, MI = 0.08). One hour after the post-treatment CEUS, nude mice were sacrificed to determine the DOX concentration in tumor tissue; one mouse in each group was sacrificed after ultrasound treatment for tumor hematoxylin-eosin staining examination. CEUS quantitative analysis and in vivo fluorescence images confirmed that LIUS at MI = 0.3 combined with microbubbles was able to enhance tumor blood flow and increase regional fluorescence dye DiR iodide concentration. The DOX concentration on the therapeutic side was significantly higher than that on the control side after ultrasound-stimulated (MI = 0.3) microbubble cavitation (USMC) treatment (1.45 ± 0.53 µg/g vs. 1.07 ± 0.46 µg/g, t = -5.163, p = 0.001). However, in groups B and C, there were no significant differences in DOX concentration between the therapeutic and control sides (Z = -0.297, -0.357, p = 0.766, 0.721). No hemorrhage or other tissue damage was observed in hematoxylin-eosin-stained tumor specimens of both sides in all groups. LIUS at MI = 0.3 combined with microbubbles was able to enhance tumor blood perfusion and improve local drug concentration in nude mice bearing pancreatic cancer.

Ultrasound-Targeted Microbubble Destruction Accelerates Angiogenesis and Ameliorates Left Ventricular Dysfunction after Myocardial Infarction in Mice.

Failure of coronary recanalization within 12 h or no flow in the myocardium after percutaneous coronary intervention is associated with high mortality from myocardial infarction, and insufficient angiogenesis in the border zone results in the expansion of infarct area. In this study, we examined the effects of ultrasound-targeted microbubble destruction (UTMD) on angiogenesis and left ventricular dysfunction in a mouse model of myocardial infarction. Fifty-four mice with MI were treated with no UTMD, ultrasound (US) alone or UTMD four times (days 1, 3, 5 and 7), and another 18 mice underwent sham operation and therapy. Therapeutic US was generated with a linear transducer connected to a commercial diagnostic US system (VINNO70). UTMD was performed with the VINNO70 at a peak negative pressure of 0.8 MPa and lipid microbubbles. Transthoracic echocardiography was performed on the first and seventh days. The results indicated that UTMD decreased the infarct size ratio from 78.1 ± 5.3% (untreated) to 43.3 ± 6.4%, accelerated angiogenesis and ameliorated left ventricular dysfunction. The ejection fraction increased from 25.05 ± 8.52% (untreated) to 42.83 ± 9.44% (UTMD). Compared with that in other groups, expression of vascular endothelial growth factor and endothelial nitric oxide synthase and release of nitric oxide were significantly upregulated after UTMD treatment, indicating angiogenesis. Therefore, UTMD is a potential physical approach in the treatment of myocardial infarction.

Animal model of ascending aortic stenosis in rabbits without endotracheal intubation.

BACKGROUND AND AIM: Experimental animal studies of left ventricular hypertrophy (LVH) usually involve endotracheal intubation, which is associated with a risk of serious tracheal injury and other significant negative sequelae. We developed an animal model of pressure overload hypertrophy caused by constriction of the ascending aorta in rabbits that does not require endotracheal intubation. METHODS: New Zealand White rabbits of either sex (1.94 +/- 0.12 kg) were randomly assigned to the aortic banding (AB) group (n = 9) and the sham-operated group (n = 8). The sternum was carefully incised along the midline to avoid injury to the parietal pleura. Then, the intervention group underwent AB with three to zero Prolene proximal to the innominate artery without endotracheal intubation. To investigate the effects of the surgical procedure on physiological parameters, echocardiography, histology, and electron microscopy were performed to assess functional and structural hypertrophy at various time intervals. RESULTS: Banding of the ascending aorta created the expected increases in both aortic velocity and the pressure gradient between proximal and distal aorta coarctation. The pressure overload resulted in a robust LVH assessed by transthoracic echocardiography and histology. The animals did not experience severe mechanical ventilatory impairment. CONCLUSION: We developed a safe, efficient, and reproducible method of producing LVH in rabbits without the need for endotracheal intubation and mechanical ventilation. Ultimately, this model will facilitate focused study of the mechanisms involved with LVH progression.

Stable Low-Dose Oxygen Release Using H2O2/Perfluoropentane Phase-Change Nanoparticles with Low-Intensity Focused Ultrasound for Coronary Thrombolysis.

After the onset of myocardial infarction, extensive coronary thrombus and oxygen supply insufficiency lead to severe myocardial damage and heart failure. Recently, ultrasound-irradiated phase-change nanoparticles have been recognized for their cardiovascular thrombolysis potential. Therefore, we sought to establish a novel treatment method using hydrogen peroxide (H2O2)/perfluoropentane (PFP) phase-change nanoparticles with low-intensity focused ultrasound (LIFU) for the simulation of acute coronary thrombolysis and myocardial preservation. There were three groups in our study: Group A consisted of phosphate-buffered saline (PBS) as the blank control, group B consisted of SonoVue microbubbles and group C consisted of H2O2/PFP phase-change nanoparticles. The H2O2/PFP phase-change nanoparticles were prepared using a double-emulsification process. The in vitro experiments were conducted in an artificial circulatory system connected to an LIFU system and dissolved oxygen detector. Thrombolysis efficiency and oxygen release efficiency were compared among the groups. H2O2/PFP nanoparticles with 3% H2O2 (average size: 456.7 ± 31.2 nm, charge: -37.5 ± 5.22 mV) was the optimal selection in group C because of the stable loading capacity and stable low-dose oxygen release efficiency in the in vitro experiments. Thrombolytic weight loss and loss rates in group C (322.0 ± 40.8 mg, 54.8 ± 5.7%) were significantly higher than those in group A (36.2 ± 18.1 mg, 5.5 ± 2.5%) and group B (91.0 ± 11.9 mg, 14.3 ± 2.4%) (p < 0.01). The innovative method using H2O2/PFP phase-change nanoparticles with LIFU exhibited high thrombolytic efficiency and stable low-flow oxygen supply in the artificial circulatory system, providing a solid experimental foundation for the establishment of a novel treatment method for acute myocardial infarction.

Clinical Value of Ultrasound-Guided Minimally Invasive Biopsy in the Diagnosis or Treatment of Breast Nodules.

PURPOSE: To explore the clinical value of ultrasound-guided minimally invasive biopsy of breast nodules for diagnosis and treatment of patients with no positive clinical signs on manual breast examination. METHODS: We performed a retrospective review of 136 patients with no signs on breast palpation who underwent ultrasound-guided minimally invasive biopsy. A total of 63 patients underwent breast nodule resection from October 2018 to December 2019 at the General Hospital of Central Theater Command of the People's Liberation Army. Clinical data, including indications for minimally invasive biopsy or resection, pathological and surgical results were retrospectively analyzed. RESULTS: A total of 199 patients were studied; 136 underwent minimally invasive biopsy and 63 underwent resection. No severe surgical complications occurred. Minimally invasive biopsy of breast nodules was superior to resection with respect to operation time, incision length, and postoperative complication rate. CONCLUSION: Ultrasound-guided minimally invasive biopsy of breast nodules is feasible for treatment of patients with negative breast nodules and can achieve accurate diagnosis and satisfactory resection.

Circular RNA hsa_circ_0007059 restrains proliferation and epithelial-mesenchymal transition in lung cancer cells via inhibiting microRNA-378.

As newly discovered non-coding RNA (ncRNA), circular RNA (circRNA) has become a research hotspot in manifold cancers. But, the influences of hsa_circ_0007059 in lung cancer remain obscure. Expression of hsa_circ_0007059 in lung cancer tissues was firstly determined through RT-qPCR. After overexpressing hsa_circ_0007059, cell viability, apoptosis, p53/CyclinD1, Bax and Pro/Cleaved-Caspase-3 and EMT-correlative factors (E-cadherin, Vimetin, Twist1 and Zeb1) were tested in A549 and H1975 cells. MiR-378 expression in lung cancer tissues and cells was evaluated after miR-378 mimic transfection. Wnt/ß-catenin and ERK1/2 pathways were finally evaluated in A549 and H1975 cells. Inhibition of hsa_circ_0007059 was discovered in lung cancer tissues. Overexpressed hsa_circ_0007059 evidently restrained cell proliferation, elevated p53 and repressed CyclinD1 expression, meanwhile triggered apoptosis and enhanced Bax and Cleaved-Caspase-3 expression. Increased hsa_circ_0007059 abated EMT via enhancement of E-cadherin and inhibition of Vimentin, Twist and Zeb1 in A549 and H1975 cells. MiR-378 was up-regulated in lung cancer tissues, declined by hsa_circ_0007059 overexpression in A549 and H1975 cells. Overexpressed hsa_circ_0007059 hindered Wnt/ß-catenin and ERK1/2 pathways via suppressing miR-378 in A549 and H1975 cells. The investigations manifested that hsa_circ_0007059 abated cell proliferation and EMT process in lung cancer cells via inactivation of Wnt/ß-catenin and ERK1/2 pathways via suppressing miR-378.

Intra-clot Microbubble-Enhanced Ultrasound Accelerates Catheter-Directed Thrombolysis for Deep Vein Thrombosis: A Clinical Study.

Insufficiency of microbubbles in the vessel-obstructing thrombus significantly reduces the effectiveness of ultrasound thrombolysis. With catheter-directed thrombolysis (CDT), microbubbles can be delivered directly into the thrombus. In this study, we combined CDT with intra-clot microbubble-enhanced ultrasound thrombolysis (IMUT) to investigate its safety and efficiency in thrombolysis in patients with acute lower limb deep vein thrombosis (DVT). For IMUT, a 1-MHz air-backed transducer directed 100-µs-pulse-length and 100-Hz-pulse-repetition pressure at 1 MPa was used. Thirteen DVT patients in the study group were treated with CDT and IMUT. Forty-three DVT patients in the historical control group were treated with CDT alone. The results indicated that the average thrombolysis time of the study group was significantly shorter (5.23 ± 1.59 d) than that of the control (10.00 ± 2.69 d), and the overall urokinase dosage of the study group ([3.82 ± 1.68] × 106 IU) was lower than that of the control ([4.99 ± 2.26] × 106 IU). No procedure-related complications were noted in either group. Therefore, combining CDT with IMUT can improve thrombolysis safely and efficiently.

Stable cavitation using acoustic phase-change dodecafluoropentane nanoparticles for coronary micro-circulation thrombolysis.

BACKGROUND: The thrombolysis in micro-circulation after acute myocardial infarction has been an unsolved issue, as elimination effect of acute thrombolysis and primary intervention were unsatisfied. Stable cavitation using acoustic phase-change nanoparticles may have potential for thrombolysis. Therefore, we sought to investigate a novel treatment method with dodecafluoropentane (DDFP) nanoparticles for rapid and effective thrombolysis in an in-vitro artificial vascular system, as a mimicking preparation of coronary circulation. METHODS: To simulate thrombus embolism in coronary circulation, an in-vitro artificial vascular system was established with cavitation effect using DDFP nanoparticles. For PBS blank control (group A), SonoVue microbubbles (group B) and DDFP nanoparticles (group C), the durations for cavitation effect were recorded and the thrombolysis efficiency with low intensity focused ultrasound irradiation in the in-vitro vascular system were analyzed with weight loss and pathological changes of thrombus before and after thrombolysis. RESULTS: The optimal conditions for acoustic cavitation effect were power of 6 W for 20 min by ultrasound irradiation at 37 °C. The weight loss and weight loss rates of thrombus in group C (189.4 ±â€¯30.2 mg and 34.2 ±â€¯5.7%) were higher than those in group A (30.2 ±â€¯16.0 mg and 5.2 ±â€¯2.1%) and group B (84.0 ±â€¯20.4 mg and 14.6 ±â€¯1.5%) (P < 0.01, all). The duration for cavitation effect in group C (32.8 ±â€¯3.9 min) was also longer than those in group A (0.0 ±â€¯0.0 min) and group B (5.3 ±â€¯0.3 min) (P < 0.01, all). CONCLUSIONS: By stable and sustaining cavitation in targeted area, DDFP nanoparticles with ultrasound irradiation have significantly increased the thrombolysis efficiency, which has provided a powerful experimental foundation for potential coronary thrombolysis.

Effect of Microbubble-Enhanced Ultrasound on Radiofrequency Ablation of Rabbit Liver.

Microbubble-enhanced ultrasound (MEUS) can non-invasively disrupt and block liver blood perfusion. It may potentially overcome the heat sink effect during a thermal ablation and consequently enhance radiofrequency ablation (RFA) of the liver. We propose a new strategy combining RFA with MEUS. For ultrasound treatment, an 831-kHz air-backed focused transducer directed 400-cycle bursts at 4.3 MPa to the liver at a 9-Hz rate. The treatment was nucleated by a lipids microbubble forming MEUS. Eighteen surgically exposed rabbit livers were treated using MEUS combined with RFA; the other 32 livers were treated using MEUS (n = 14) or RFA (n = 18) alone and served as the controls. Contrast ultrasound imaging confirmed that MEUS treatment significantly reduced liver blood perfusion by cutting contrast peak intensities in half (44.7%-54.1%) without severe liver function damage. The ablated liver volume treated using MEUS combined with RFA was 2.8 times greater than that treated using RFA alone. In conclusion, RFA of the liver can be safely and greatly enhanced by combination with MEUS pre-treatment.

Ultrasound and Intra-Clot Microbubbles Enhanced Catheter-Directed Thrombolysis in Vitro and in Vivo.

Insufficient penetration of microbubbles (MBs) into the vessel-obstructing thrombi significantly reduces the effectiveness of ultrasound thrombolysis (UT). The widely performed catheter-directed therapy (CDT) makes it possible to increase the local concentration of MBs in the clot. In an occluded vessel with a bypass, treatment of fresh human whole blood clots with CDT-based UT (intra-clot injection of MBs and urokinase, with ultrasound exposure) resulted in a significantly higher percentage of weight loss (35.32 ± 15.42%), compared with CDT alone (19.64 ± 4.71%), non-CDT-based UT (systemic administration of urokinase and MBs, with ultrasound exposure, 8.79 ± 3.02%) and systemic thrombolysis (7.90 ± 2.14). Ultrasound and intra-clot MB enhancement of CDT was further confirmed by a rabbit IVC thrombolysis study, where CDT-based UT resulted in significantly more effective thrombolysis compared with CDT alone. In summary, combining CDT with intra-clot MB-induced acoustic cavitation can improve thrombolysis.