Tumor perfusion enhancement effect combined with programmed cell death-Ligand 1 antibody improves the immune microenvironment of solid tumors / 中华超声影像学杂志

Objective:To investigate the tumor perfusion enhancement induced by low intensity ultrasound stimulated microbubble cavitation (USMC) combined with programmed cell death-Ligand 1(PD-L1) antibody on improving the immune microenvironment of solid tumors.Methods:Tumor-bearing mice were divided into 4 groups: Control ( n=26) group, USMC ( n=27) group, anti-PD-L1 ( n=27) group and USMC+ anti-PD-L1 ( n=27) group. USMC treatment was performed with a VINNO 70 ultrasound theranostics system. Tumor perfusion was evaluated by contrast-enhanced ultrasound (CEUS). The anti-tumor efficacy was assessed by the tumor growth curve and the survival time of mice. The number and function of CD8 + T cells, the differentiation of CD4 + T cells, the proportion of MDSC and the phenotype distribution of TAM in tumors were analyzed by flow cytometry. The content of CXCL9, CXCL10 and HIF-1α in tumor were detected by ELISA. The expression of VEGF in tumor tissues was analyzed by immunofluorescence. Results:CEUS showed that the values of PI and AUC of tumors were significantly increased after USMC compared with before USMC (all P<0.05). USMC combined with anti-PD-L1 therapy did suppress the tumor progression. FCM showed the number, the expression of proliferation antigen Ki67, the secretion of IFN-γ and Granzyme B of CD8 + T cells in tumors were higher in combined group than those in other three groups after therapy (all P<0.05). Meantime, the proportion of Th1 was rose while Tregs and MDSC were declined and the polarization of TAM was toward M1 type by combined therapy. ELISA analysis showed that the combined therapy also increased the concentration of CXCL9, CXCL10 and decreased the content of HIF-1α in tumors (all P<0.05). Meanwhile, the immunofluorescence expression of VEGF was significantly lower in combined group than that in the control group after treatment ( P<0.05). Conclusions:Tumor perfusion enhancement by USMC combined with PD-L1 antibody therapy could improve tumor immune microenvironment and USMC might be a novel effective method for potentiating PD-L1 antibody immunotherapy.

Irrigación Activada por Láser en Endodoncia

RESUMEN: El objetivo de la endodoncia es prevenir o curar la periodontitis apical. Por lo tanto, los microorganismos que han colonizado el sistema de canales radiculares deben ser eliminados para promover la regeneración y cicatrización. Desafortunadamente, la existencia de canales accesorios, anastomosis, istmos, así como ramificaciones apicales, genera una compleja red tridimensional en el interior de la raíz, lo que dificulta la eliminación total de bacterias y detritus. La te rapia endodóntica convencional utilizada actualmente presenta una serie de limitaciones.Se ha demostrado que los instrumentos endodónticos dejan un 35 % o más de superficie dentinaria sin tratar. Por otro lado, la imposibilidad de generar un flujo turbulento en el interior de los canales, impide que el irrigante llegue a zonas de difícil acceso. Esto facilita la persistenc ia de biopelículas bacterianas y la supervivencia de un número importante de bacterias viables. La irrigación activada por láser (LAI) ha sido propuesta como una tecnología co-adyuvante a la terapia quimio-mecánica para optimizarla limpieza y desinfección. Los láseresde Er,Cr:YSGG (2780nm) y Er:YAG (2940nm) son los más utilizados. Estas dos longitudes de onda son capaces de ser absorbidas ampliamente por diferentes soluciones irrigantes, teniendo en cuenta un uso seguro y respetando los parámetros clínicos aceptados. La absorción de la energía del láser por parte de los irrigantes, genera burbujas de vapor en el interior del fluido, que liberan fuerzas de cizalla al implosionar. Este fenómeno, denominado cavitación, genera mayor limpieza y desinfección del interior del sistema de canales radiculares, incluso en zonas de difícil acceso. Diversos estudios microbiológicos y microscópicos, han demostrado la efectividad antibacteriana de LAI. Recientemente, se ha publicado que LAI tendría la capacidad de incrementarla capacidad antibacteriana del hipoclorito de sodio a baja concentración (un buen desinfectante pero extraordinariamente tóxico), lo que permitiría trabajar con concentraciones menores y por lo tanto más seguras para el paciente.

ABSTRACT: The goal of endodontics is to prevent or cure apical periodontitis. Therefore, microorganisms that have colonized the root canal system must be eliminated to promote regeneration and healing. Unfortunately, the existence of accessory canals, anastomoses, isthmus, as well as apical ramifications, form a complex three-dimensional network inside the root, which makes difficult the total elimination of bacteria and detritus. Conventional endodontic therapy has several limitations. Endodontic instruments have been shown to leave 35 % or more of the dentin surface untreated. On the other hand, the inability of generating a turbulent flow, prevents the irrigant from reaching areas that are difficult to access. This facilitates the persistence of bacterial biofilms and the survival of a significant number of viable bacteria. Laser-activated Irrigation (LAI) has been proposed as a co-adjuvant to chemo-mechanical therapy to improve cleaning and disinfection. Er, Cr: YSGG (2780nm) and Er: YAG (2940nm) lasers are the most widely used. These two wavelengths are capable of being widely absorbed by different irrigating solutions, taking into account safe use and respecting accepted clinical parameters.The deep absorption of laser energy generates steam bubbles inside the fluid, which release shear forces when imploding. This phenomenon, called cavitation, is responsible for greater cleaning and disinfection within the root canal system, even in areas difficult to access. Several studies have demonstrated the antibacterial effectiveness of LAI through microbiological methods and microscopic techniques. Recently, it has been reported that LAI would have the ability to increase the antibacterial capacity of low concentration of sodium hypochlorite (a good disinfectant but extremely toxic), which would allow working with concentrations that are safer for the patient.

A rare cause of headache and fever in a healthy woman / Una rara causa de cefalea y fiebre en una mujer sana

Abstract Cryptococcocis is a fungal infection that primarily affects immunocompromised hosts; disseminated infection is uncommon in immunocompetent patients. We describe a case of a previously healthy woman without risk factors, who was admitted to the emergency department with headache, fever and altered mental status. As a result, a cryptococcal disseminated infection was diagnosed.

Resumen La criptococosis es una infección por hongos que afecta principalmente a huéspedes inmunodeprimidos; la infección diseminada es infrecuente en pacientes inmunocompetentes. Reportamos el caso de una mujer previamente sana, sin factores de riesgo, ingresada a urgencias por cefalea, fiebre y alteración del estado mental quien posteriormente fue diagnosticada con criptococosis diseminada.

Venturi: dispositivo de cavitação hidrodinâmica para acelerar a síntese de biodiesel / Venturi: hydrodynamic cavitation device to accelerate biodiesel synthesis

RESUMO O objetivo deste trabalho foi avaliar o potencial do Venturi para a síntese de biodiesel a partir de óleo comestível residual em rota metílica. Para tanto, foi construído em escala de laboratório um aparato experimental constituído de um tanque de 5,2 L e um dispositivo Venturi projetado para produzir o fenômeno de cavitação. A produção de biodiesel foi avaliada em três diferentes pressões de entrada do Venturi: 4,4; 2,9; e 1,4 bar. Os teores de ésteres metílicos foram determinados por cromatografia gasosa. O tempo de síntese de 5,2 L de biodiesel, com o Venturi, foi de 23,2 segundos (ou 4,5 segundos por litro de biodiesel produzido), o que equivale a um único ciclo de passagem pelo sistema a pressão máxima (4,4 bar). Nessa condição, o rendimento dos teores de ésteres foi superior a 98%. Não há na literatura outro caso de síntese tão rápida como a encontrada neste trabalho. A caracterização do biodiesel mostrou que os parâmetros viscosidade cinemática, índice de acidez, ponto de entupimento a frio e massa específica estão dentro dos limites estabelecidos pela Agência Nacional de Petróleo. A comparação com outros estudos da literatura mostrou que o Venturi é superior às placas de orifício na síntese de biodiesel.

Abstract The objective of this work was to evaluate the potential of Venturi in the synthesis of biodiesel from residual edible oil in a methyl route. For this purpose, an experimental apparatus consisting of a 5.2 L tank and a Venturi device designed to produce the cavitation phenomenon was constructed in laboratory scale. Biodiesel production was evaluated at three different Venturi inlet pressures: 4.4; 2.9; and 1.4 bar. Methyl esters contents were determined by gas chromatography. Biodiesel synthesis time with the Venturi device was 23.2 seconds (or 4.5 seconds per liter of biodiesel produced), which is equivalent to a single cycle of the system at maximum pressure (4.4 bar). In this condition, the yield of the ester contents was greater than 98%. There is no other case of synthesis as fast as that found in this work. The biodiesel characterization showed that the parameters kinematic viscosity, acidity index, cold clogging point, and specific mass are within the limits established by National Agency of Petroleum Natural Gas and Biofuels (Agência Nacional de Petróleo). The use of Venturi, as a cavitation device, was shown to be more efficient in biodiesel synthesis than other devices, such as orifice plates.

Computational fluid dynamics analysis of the flow of ultrasonic irrigations in root canal / 口腔疾病防治

Objective@#To study the computational fluid dynamics (CFD) characteristics of ultrasonic root canal irrigation when the file was placed at a certain depth in the root canal, to provide a reference for clinical application.@*Methods @#First, scanning laser vibrometry (SLV) was utilized to analyze the characteristics of vibrational ultrasonic files under specific power. Then ICEM CFD 18.0 software was used to establish the root canal ultrasonic irrigation model. The insertion position of the ultrasonic working tip was set 1 mm away from the physiological apical foramen, and cloud images of the results were obtained by FLUENT 18.0 software. Volume fraction, flow velocity and pressure in the root canal were evaluated after setting the computing conditions.@*Results@#The vibration of the ultrasonic working tip was mainly transverse vibration with slight longitudinal vibration. The amplitude of transverse vibration of each part of the working tip was different. Maximum values were observed at the apical end area of the file, and the closer to the base of the file, the smaller the amplitude. The area where the cavitation volume fraction of the rinsing fluid was greater than 0 was concentrated around the working point. The flow rate of the irrigating fluid was up to 2 m/s, within the area 0.2 mm in front of the working tip, the velocity of the irrigating fluid was greater than 0.1 m/s, while within the area 0.8 mm from the root tip, the velocity of the irrigating fluid was small or even zero. The apical pressure value was non-positive when the tip of the file was 1 mm away from the apical foramen in this model.@*Conclusion@# Based on the experimental results, it appears that when the ultrasonic working tip was placed 1 mm short of the working length, the ultrasonic irrigating flow did not overflow the root apical foramen and the irrigation process was relatively safe; the irrigation fluid had a strong irrigation effect within approximately 0.2 mm in front of the working tip.

Application research progress of Er，Cr：YSGG laser in root canal therapy / 口腔疾病防治

@#Erbium，chromium：yttrium scandium gallium garnet（Er，Cr：YSGG）laser is mainly used for root canal treatment，periodontal disease，tooth decay，dentin hypersensitivity，pulp amputation，etc in the field of dentistry.This paper mainly describes the research progress of Er，Cr：YSGG laser in root canal therapy from following four as⁃pects：root canal sealing，sterilization，cavitation effect and the effect on periapical tissue. The experimental results showed that when the operation parameters of Er，Cr：YSGG were 2 ~ 4 w and 20 Hz，it could effectively remove the stained layer of dentin tubules and improve the tightness between materials and dentin. The thermal effect produced by Er，Cr：YSGG energy has a sterilizing effect，while the optical conductivity of the tooth enables the rinse solution to enter deeper tissues，further improving the sterilizing effect. Er，Cr：YSGG also has a cavitation effect，which destroys the surface tension of the deep solution，removing the stain layer and bacteria in the deep layer. However，with the same operation parameters，if Er，Cr：YSGG is not used properly，the thermal effect of Er，Cr：YSGG will cause some damage to the periapical tissues. Therefore，reasonable use time of Er，Cr：YSGG and water cooling conditions are important.

Eminencia ganglionar: Anatomía y patología en resonancia magnética fetal / Ganglionic Eminence: Anatomy and Pathology in Fetal MRI

Se presentan dos casos de resonancia magnética (RM) fetal en los que se detectan anomalías de las eminencias ganglionares (EG): un caso en una gestación única y otro en una gestación gemelar con solo uno de los fetos afectado. Las alteraciones en las eminencias ganglionares son entidades poco frecuentes, con muy pocos casos publicados, tanto por RM como por ecografía fetal, que suelen asociarse con alteraciones neurológicas graves. Se describen los hallazgos por RM de la patología de las EG en estos dos casos, no visibles en la ecografía previa.

We present two cases of fetal MRI where anomalies of the ganglionic eminences (GE) are detected, one case in a single pregnancy and another in a twin gestation with only one of the affected fetuses. Alterations in the ganglionic eminences are rare entities, with very few published cases, both by MRI and fetal ultrasound, which are usually associated with severe neurological alterations. The MR findings of the pathology of the GE in these two cases are described. These findings were not visible on the previous ultrasound.

Research progress of sonodynamic therapy in the field of stomatology / 口腔疾病防治

@#Sonodynamic therapy (SDT) is a cutting-edge method for the biological effects of ultrasound combined with sound-sensitive agents. In recent years, SDT has been a concern of experts and scholars in the oral field, and a series of experimental studies has been carried out. We will introduce the progress of SDT in the field of stomatology from three aspects: the therapeutic mechanism of SDT, the application of SDT in the oral field, and the current situation and future of SDT in the treatment of oral diseases. It is currently believed that singlet oxygen theory, cavitation effects, and induction of apoptosis are the main therapeutic mechanisms. The research of SDT on oral disease prevention mainly focuses on oral tumors (especially squamous cell carcinoma and osteosarcoma) and infectious diseases (such as periodontitis, maxillofacial infection, and oral mucosal disease). Although the current research is still in the experimental stage, with the continuous exploration of sonosensitizers and nanotechnology, SDT will provide great help for the clinical prevention and treatment of oral diseases in the future.

Effects of ultrasound combined with microbubbles on intracellular Ca 2+ homeostasis in carboplatin-treated microenvironment of A549 cell line / 中华超声影像学杂志

Objective To investigate the effects of ultrasound combined with microbubbles on intracellular Ca2+ homeostasis in carboplatin ( CBP )-treated A549 cell and its possible mechanisms of inhibiting A549 cell line activity . Methods According to whether SonoVue was used or not ,and the different dose of CBP ,the groups A-F were arranged as the ultrasound(US) group(group A) ,the ultrasound combined with microbubbles ( USMB) group( group B) ,the low dose CBP ( 100 μg/ml) + US group( group C) ,the low dose CBP+USMB group( group D) ,the high dose CBP ( 200 μg/ml)+ US group ( group E) and the high dose CBP+USMB group( group F) .A549 cells were bathed and washed by a calcium-free buffer , loaded with Ca2+ indicator fluo-4 AM . Real-time images were acquired using laser confocal microscopy .The fluorescence intensity of intracellular calcium ion concentration ([Ca2+ ]i) in individual living cell was observed and the calcium overload was analyzed . Results After ultrasound irradiation ,the normalized fluorescence intensity of [Ca2+ ]i increased rapidly ,then returned to a new homeostasis (selected cells in groups A ,B ,E ,F) or experienced a second calcium oscillation ( some cells in group C and D) . All the selected cells in group B and some cells in group C and D exhibited superimposed oscillations . The calcium overloading time in group D was longer than those of any other groups . Four cells in group A experienced delayed calcium oscillations . Compared with group A ,the selected cells in other groups exhibited a larger amplitude of calcium oscillation( all P < 0 .05) and the selected cells in group B and D exhibited calcium oscillation for a longer period of time( all P <0 .05) . Conclusions In the calcium-free buffer ,US ,USMB , CBP+ US ,CBP + USMB are direct stimuli of calcium overload in A 549 cells . SonoVue ,CBP ,CBP +SonoVue are all synergistic stimuli of calcium overload in A 549 cells irradiated by ultrasound .US ,USMB and CBP may synergistically induce calcium release from intracellular store sites in A 549 cells . Calcium overload is a possible mechanism of ultrasound combined with microbubbles in assisting CBP chemotherapy .

Effects of ultrasound combined with microbubbles on intracellular Ca 2+ homeostasis in carboplatin‐treated microenvironment of A549 cell line / 中华超声影像学杂志

To investigate the effects of ultrasound combined with microbubbles on intracellular Ca2+ homeostasis in carboplatin ( CBP )‐treated A549 cell and its possible mechanisms of inhibiting A549 cell line activity . Methods According to whether SonoVue was used or not ,and the different dose of CBP ,the groups A‐F were arranged as the ultrasound( US) group( group A ) ,the ultrasound combined with microbubbles ( USMB) group( group B) ,the low dose CBP ( 100 μg/ml) + US group( group C) ,the low dose CBP+USMB group( group D) ,the high dose CBP ( 200 μg/ml)+ US group ( group E) and the high dose CBP+USMB group( group F) .A549 cells were bathed and washed by a calcium‐free buffer , loaded with Ca2+ indicator fluo‐4 AM . Real‐time images were acquired using laser confocal microscopy . T he fluorescence intensity of intracellular calcium ion concentration ( [ Ca 2+ ] i ) in individual living cell was observed and the calcium overload was analyzed . Results After ultrasound irradiation ,the normalized fluorescence intensity of [ Ca2+ ] i increased rapidly ,then returned to a new homeostasis ( selected cells in groups A ,B ,E ,F ) or experienced a second calcium oscillation ( some cells in group C and D ) . All the selected cells in group B and some cells in group C and D exhibited superimposed oscillations . T he calcium overloading time in group D was longer than those of any other groups . Four cells in group A experienced delayed calcium oscillations . Compared with group A ,the selected cells in other groups exhibited a larger amplitude of calcium oscillation ( all P ＜ 0 .05 ) and the selected cells in group B and D exhibited calcium oscillation for a longer period of time( all P ＜0 .05) . Conclusions In the calcium‐free buffer ,US ,USMB , CBP+ US ,CBP + USMB are direct stimuli of calcium overload in A 549 cells . SonoVue ,CBP ,CBP +SonoVue are all synergistic stimuli of calcium overload in A 549 cells irradiated by ultrasound .US ,USMB and CBP may synergistically induce calcium release from intracellular store sites in A 549 cells . Calcium overload is a possible mechanism of ultrasound combined with microbubbles in assisting CBP chemotherapy .

Broadband subharmonic active cavitation imaging with high cavitation to tissue ratio / 生物医学工程学杂志

To improve the cavitation-to-tissue ratio (CTR) of cavitation imaging during the treatment with high-intensity focused ultrasound (HIFU), we proposed a pulse inversion based broadband subharmonic cavitation imaging method (PIBSHI). Due to the fact that the subharmonic signal is a unique nonlinear vibration characteristic of cavitation bubbles, we extracted the broadband subharmonic signal to get a high-CTR cavitation imaging. The simulation showed that the subharmonic signal produced by cavitating bubbles with different sizes varied, and the signal was stronger than other subharmonics when the bubbles' resonant frequency was close to 1/2 subharmonic frequency. Further experiment results demonstrated that compared with the conventional B-mode images, broadband subharmonic cavitation imaging (BSHI) has improved the CTR by 5.7 dB, and the CTR was further improved by 3.4 dB when combined with pulse inversion (PI) technology. Moreover, when the bandwidth was set to 100%~140% of the 1/2 subharmonic frequency in PIBSHI, the CTR was the highest and the imaging showed the optimal quality. The study may have reference value for the development of precise cavitation imaging during HIFU treatment, and contribute to improve the safety of HIFU treatment.

The outcomes and bioactivities of microbubble-enhanced ultrasound combined with prothrombin on microwave ablation in rabbit VX2 liver tumors / 中华超声影像学杂志

Objective To investigate the sequential biological effects and outcomes of microbubble-enhanced ultrasound (MEUS) combined with prothrombin on microwave ablation (MWA) in rabbit VX2 liver tumors using examination of transmission electron microscopy ,histopathology and contrast-enhanced ultrasound(CEUS) . Methods Eighty New Zealand rabbits with VX2 liver tumors were randomly divided into 4 groups ( 20 per group ) , including physiological saline group , prothrombin group , cavitation of microbubbles group ( cavitation group ) and cavitation of microbubbles combined prothrombin group (combined group) . After treatment ,the targeted liver tumors in all groups were ablated with MWA . On the 0 ,3 ,7 and 14 d ,the volumes of coagulated areas of 5 rabbits of each group randomly were measured using CEUS . Tissues in ablated areas ,transition areas and surrounding areas were examined under light microscopy with histopathology and transmission electron microscopy to observe the differences among 4 groups . Tumor metastasis was graded using visual method . Results On the 0 ,3 ,7 and 14 d ,the coagulated volumes in combined group were larger than those in remaining 3 groups ( all P ＜ 0 .001) . Under light microscopy with HE stain ,in transition area ,the fibra band in combined group was wider than those in remaining 3 groups on the 7 and 14 d ( all P ＜ 0 .05 ) . The observations under transmission electron microscopy showed that the cellular ultrastructure disorder in ablated area on the 0 d and mitochondrial injury in transition area on the 7 d were more severe in combined group than those in remaining 3 groups . Compared with the remaining 3 groups ,the degree of tumor metastasis in combined group was less ,and the time of ocurrence was later . Conclusions MEUS combined with prothrombin can significantly expand ablation volume ,enhance the necrosis of ablated tissues ,and inhibit tumor metastasis on rabbit VX 2 liver tumors . The fibra bands in the transition areas can promote the organization and repair the surrounding tissue in the ablation areas .

Microbubbles with HIF-1α Antisense Oligonucleotide Enhanced Ultrasound on Inhibition of Tumor Growth / 中国医学影像学杂志

Purpose After the angiotripsy treatment of tumor,tumor blood vessels have different degrees of regeneration,leading to incomplete tumor necrosis,which may be related to the high expression of HIF-lα.To explore the feasibility of microbubble with HIF-1α antisense oligonucleotide combined with ultrasound inhabit tumor growth.Materials and Methods Twenty-four rabbits with VX2 tumor were randomly assigned to three groups:microbubbles with HIF-1α antisense oligonucleotide plus ultrasound (HMB+US) (n=8),microbubbles plus ultrasound (MB+US) (n=8),therapeutic ultrasound alone without microbubbles (US) (n=8).Pulsed focused ultrasound was delivered directly to the tumor surface for 10 minutes during intravenous infusion of microbubbles with HIF-1α antisense oligonucleotide in the experimental group.The control groups were applied only microbubbles or saline injection.The procedure was repeated every 72 hours until the 30th day.Contrast enhanced US and grey scale ultrasonography were acquired after every treatment to get the tumor perfusion images,size and volume measurements.Results The average maximum diameter of the HMB+US,MB+US,and the US groups grows from (1.13±0.19) cm,(1.17±0.21) cm,(1.22±0.17) cm to (1.60±0.45) cm,(2.11 ±0.57) cm,(3.43 ± 0.71) cm within a 30d-experimental period,respectively.No statistical difference in average diameter was observed among three groups before treatment (P＞0.05).The average maximum diameter of the HMB+US group was significantly smaller than that of the two control groups at the end of experiment (P＜0.05),and the average maximum diameter of the MB+US group was significantly smaller than that of the US group (P＜0.05).Conclusion Microbubbles with HIF-1α antisense oligonucleotide can enhance vascular damage effect ofangiotripsy,which can be a novel method for tumor treatment.

Pulsed focused ultrasound combined with micro-bubble contrast agent can open the blood-brain barrier of gliblastoma patients and improve the efficacy of Temozolomide treatment / 解放军医学杂志

Objective This research examined the effect ofmicrobubble contrast agent plus ultrasound on the permeability of blood-brain barrier,and explored whether it affects the efficacy of chemotherapeutic drugs on cerebral glioblastoma.Methods Wistar rats were divided into three groups to find the optimal concentration of ultrasonic contrast agent.To identify the best ultrasound mode that affected the permeability of blood brain barrier,we employed transmission electron microscopy for study of brain ultrastructure.Western blotting was used to detect the tight junction protein claudin-5.Evans blue staining of brain tissues was utilized to identify the best ultrasonic contrast agent concentration and mode.Rat glioma cells (line 9L) were injected into Wistar rats.After temozolomide chemotherapy,the tumor size was measured and the tumor marker GFAP in serum was detected by ELISA.Results The best contrast agent concentration which increases permeability of BBB in rats was found to be lml/kg and the best ultrasound mode was intermittentlytriggered pulses lasting for 10min (with interval was set at 400ms).More Evans blue passed the blood-brain barrier in ultrasonic cavitation effect group than in control group (P＜0.05).After temozolomide chemotherapy,more tumor marker GFAP was detected in ultrasonic cavitation effect group than in control group (P＜0.05).Conclusion The permeability of BBB was increased and more temozolomide went through BBB when the rats were subjected to intermittently triggered ultrasonic pulses and were injected at contrast agent at lml/kg,which could help to achieve better therapeutic efficacy for glioblastoma.

Experimental study of a novel phase change nanodroplets enhanced high intensity focused ultrasound ablation / 中国介入影像与治疗学

Objective To investigate the effect of lipid encapsulated 1,1,2-trichlorotrifluoroethane phase change nanodroplets for high intensity focused ultrasound (HIFU) ablation.Methods The lipid encapsulated 1,1,2-trichlorotrifluoroethane phase change nanodroplets was prepared with membrane hydration method,and its physicochemical properties were examined.The synergistic effect of HIFU ablation was verified with experiments in vitro and in vivo experiments.For in vitro experiment,the isolated bovine liver tissues were irradiated with HIFU (250 W,10 s,continuous wave).For in vivo experiment,the livers of New Zealand rabbits were irradiated with HIFU (200 W,5 s,continuous wave).The volume of coagulative necrosis,energy efficiency factors (EEF) and the volume of the hyperechoic area after HIFU radiation were measured.And the statistical analysis was performed.Results Phase change nanoparticles were spherical in solution and uniform in size.For in vitro experiment,the coagulative necrosis volume,EEF and hyperechoic area of bovine liver tissue injected with nanodroplets were significantly higher than those of untreated bovine liver tissue (t=28.80,19.55,14.30;P=0.01,0.02,0.02) after HIFU.For in vivo experiment,the coagulative necrosis volume,EEF and hyperechoic area of rabbit liver tissue injected with nanodroplets were significantly higher than those of untreated rabbit liver tissue (t=9.41,13.52,15.67;P=0.02,0.01,0.01) after HIFU.Conclusion The lipid encapsulated 1,1,2-trichlorotrifluoroethane phase change nanodroplets can significantly improve the efficiency of HIFU ablation significantly.

Peripapillary vessel density and the relevant factors in highly myopic eyes with peripapillary intrachoroidal cavitation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate peripapillary vessel density and its relationship with other ocular parameters in highly myopic eyes with peripapillary intrachoroidal cavitation (PICC), and to analyze risk factors for PICC.METHODS:Cross-sectional study.A total of 35 highly myopic eyes with PICC, 40 highly myopic eyes without PICC and 35 normal eyes were included in this study.All participants underwent fundus photography and spectral-domain optical coherence tomography (SD-OCT).OCT angiography was also performed to image the retinal vasculature in the peripapillary areas of different sectors, including the radial peripapillary capillaries (RPC) and optic nerve head (ONH) layer.The difference of morphology changes in optic disc and peripapillary vessel density between these three groups were compared.Correlations between peripapillary vessel density and PICC and risk factors for the presence of PICC were analyzed.RESULTS: Significant differences were found among the three groups in spherical equivalent refraction (SER), best-corrected visual acuity (BCVA), axial length, peripapillary atrophy β-zone (β-PPA) area, retinal nerve fiber layer (RNFL) thickness and the presence of tilted optic disc, posterior staphyloma and myopic maculopathy (MMD) (P<0.05).There were significant differences among the three groups in the peripapillary vessel density both in RPC (54.34±5.58, 57.54±7.44, 64.42±3.50) and ONH (51.24±7.43, 52.75±9.96, 61.25±4.15) layers (P<0.001).In highly myopic eyes, vessel density was significantly lower in eyes with PICC than in those without in inferotemporal area both in the RPC (56.76±6.62,63.84±6.02,67.52±4.78) and ONH (56.47±5.79,60.38±4.72,64.18±4.37) layers.The vessel density was significantly correlated with the presence of MMD, β-PPA area and RNFL thickness in the RPC layer, whereas correlated with the presence of MMD, PICC and RNFL thickness in the ONH layer (P<0.05).Tilted optic disc and posterior staphyloma were independent risk factors for the presence of PICC (OR=8.007, 95%CI: 2.045-31.348;OR=7.558, 95%CI: 1.398-50.026).CONCLUSION:Highly myopic eyes with PICC had relatively lower peripapillary vessel densities, especially in the temporal area, than those without.Tilted optic disc and posterior staphyloma were independent risk factors for the presence of PICC.

Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis

Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Geometrical characterization of the cavitation bubble clouds produced by a clinical shock wave device

This study was to optically visualize the cavitation bubbles produced by a clinical shock wave and to look into their geometric features of the resulting cavitation bubbles in relation to the driving shock wave field. A clinical shock wave therapeutic system was taken for shock wave production. The shock wave induced cavitation bubbles were captured by a professional camera under the illumination of a micro-pulse LED light. The light exposure was set to last for the whole life time of bubbles from formation to subsequent collapses. It was shown that the cavitation bubbles appeared mostly in the vicinity of the focus. The bubbles became more and larger as approaching to the focus. The cavitation bubbles formed jet streams which became enlarged (stronger) as the shock wave device output setting increased. The bubble cloud boundary was reasonably fitted to an elongated ellipsoid characteristically similar to the acoustic focal area. The bubble clouds were enlarged as the output setting increased. The geometric features of the cavitation bubbles characteristically similar to those of the focusing acoustic field have potential to provide the therapeutic focal information without time consuming hydrophone measurements of the shock wave field causing damages of the expensive sensor. The present study is limited to the static afterimages of the cavitation bubbles and investigation including the bubble dynamics is suggested to deliver the more realistic therapeutic area of the shock wave therapy.

Efeito do ultrassom na extração e modificação de amidos / Effect of ultrasound on the extraction and modification of starches

RESUMO: O ultrassom é considerado uma tecnologia limpa, por possibilitar menor gasto de energia, de substâncias químicas e menor geração de efluentes. Além disso, proporciona menor tempo de processamento e reduz a necessidade de aplicação de calor em vários processos. Por isso, tem sido alvo de pesquisa e desenvolvimento na indústria de alimentos, tanto para substituir, quanto para aperfeiçoar ou acelerar técnicas convencionais de processamento. Dentre as diferentes possibilidades de utilização na indústria de alimentos, o ultrassom pode ser considerado uma alternativa para substituir ou reduzir a utilização de substâncias químicas em processos de extração ou modificação de amidos. Quando utilizado na extração, possibilita maior pureza do amido obtido. Já na modificação, algumas alterações nos grânulos de amido podem ser provocadas pelo ultrassom, mas dependem da origem botânica, da composição do amido, dos parâmetros do equipamento e das condições de processamento.

ABSTRACT: Ultrasound is considered a clean technology, because it allows lower energy and chemicals compounds consumption as well as lower generation of waste. Furthermore, it provides shorter processing time and reduces the need for heat application in various processes. Therefore, this technology has been studied in the food industry to replace, improve or accelerate conventional processing techniques. Among the different possibilities of use in the food industry, ultrasound might be considered as an alternative to replace or reduce the use of chemicals during the extraction processes or modification of starches. When used in the starch extraction allows a greater purity of the final product. Towards the modification some changes in the starch granules can be caused by ultrasound, but it depends on the botanical source and starch composition, equipment's parameters and processing conditions.

Applications of Sonochemistry in Drug Delivery and Formulations: A Review.

Sonochemistry is the branch of science which deals with passage of ultrasonic waves to enhance or alter chemical reactions. The use of ultrasound in chemical reactions in solution provides specific activation based on a physical phenomenon: acoustic cavitation. The range from 20 kHz to around 1 MHz is used in sonochemistry whereas frequencies far above 1 MHz are used as medical and diagnostic ultrasound. Ultrasonic waves induce chemical effects on the reaction system, such as generation of free radicals which augment the rate of reaction. Besides this, ultrasound may have other mechanical effects on the reaction system, such as increasing the surface area between the reactants, accelerating dissolution rate. This review elucidates several applications of sonochemistry in the pharmaceutical industry including sonophoresis, sonocrystallization, lowering extraction time, solution atomization and crystallization by sonication, melt sonocrystallization and particle rounding technology. This review also gives an idea about the applications of sonocrystallization in formation of aerosols, enhancing inhalation drug delivery and sonochemical preparation of biomaterials. Its significance in transdermal drug delivery, chemotherapy and cell therapy is also discussed herewith. It has been proved that ultrasound can be effectively used for treatment of sewage sludge and degradation of dangerous chemicals including chlorinated hydrocarbons, aromatic compounds, agrochemicals and pesticides from the agricultural industry, explosives, dyes from the textile industry and surfactants etc. The purpose of this review paper is to put forth the information available in the literature so as to promote further research in the field of sonochemistry.