Polymerized Network-Based Artificial Peroxisome Reprogramming Macrophages for Photoacoustic Imaging-Guided Treatment of Rheumatoid Arthritis.

Artificial peroxisomes (AP) with enzyme-mimetic catalytic activity and recruitment ability have drawn a great deal of attention in fabricating protocell systems for scavenging reactive oxygen species (ROS), modulating the inflammatory microenvironment, and reprogramming macrophages, which is of great potential in treating inflammatory diseases such as rheumatoid arthritis (RA). Herein, a macrophage membrane-cloaked Cu-coordinated polyphthalocyanine-based AP (CuAP) is prepared with a macrocyclic conjugated polymerized network and embedded Cu-single atomic active center, which mimics the catalytic activity and coordination environment of natural superoxide dismutase and catalase, possesses the inflammatory recruitment ability of macrophages, and performs photoacoustic imaging (PAI)-guided treatment. The results of both in vitro cellular and in vivo animal experiments demonstrated that the CuAP under ultrasound and microbubbles could efficiently scavenge excess ROS in cells and tissues, modulate microenvironmental inflammatory cytokines such as interleukin-1ß, tumor necrosis factor-α, and arginase-1, and reprogram macrophages by polarization of M1 (proinflammatory phenotype) to M2 (anti-inflammatory phenotype). We believe this study offers a proof of concept for engineering multifaceted AP and a promising approach for a PAI-guided treatment platform for RA.

Ultrasound-augmented cancer immunotherapy.

Cancer is a growing worldwide health problem with the most broadly studied treatments, in which immunotherapy has made notable advancements in recent years. However, innumerable patients have presented a poor response to immunotherapy and simultaneously experienced immune-related adverse events, with failed therapeutic results and increased mortality rates. Consequently, it is crucial to develop alternate tactics to boost therapeutic effects without producing negative side effects. Ultrasound is considered to possess significant therapeutic potential in the antitumor field because of its inherent characteristics, including cavitation, pyrolysis, and sonoporation. Herein, this timely review presents the comprehensive and systematic research progress of ultrasound-enhanced cancer immunotherapy, focusing on the various ultrasound-related mechanisms and strategies. Moreover, this review summarizes the design and application of current sonosensitizers based on sonodynamic therapy, with an attempt to provide guidance on new directions for future cancer therapy.

Effect of an artificial intelligence-assisted system on endoscopic diagnosis of superficial oesophageal squamous cell carcinoma and precancerous lesions: a multicentre, tandem, double-blind, randomised controlled trial.

BACKGROUND: Despite the usefulness of white light endoscopy (WLE) and non-magnified narrow-band imaging (NBI) for screening for superficial oesophageal squamous cell carcinoma and precancerous lesions, these lesions might be missed due to their subtle features and interpretation variations among endoscopists. Our team has developed an artificial intelligence (AI) system to detect superficial oesophageal squamous cell carcinoma and precancerous lesions using WLE and non-magnified NBI. We aimed to evaluate the auxiliary diagnostic performance of the AI system in a real clinical setting. METHODS: We did a multicentre, tandem, double-blind, randomised controlled trial at 12 hospitals in China. Eligible patients were aged 18 years or older and underwent sedated upper gastrointestinal endoscopy for screening, investigation of gastrointestinal symptoms, or surveillance. Patients were randomly assigned (1:1) to either the AI-first group or the routine-first group using a computerised random number generator. Patients, pathologists, and statistical analysts were masked to group assignment, whereas endoscopists and research assistants were not. The same endoscopist at each centre did tandem upper gastrointestinal endoscopy for each eligible patient on the same day. In the AI-first group, the endoscopist did the first examination with the assistance of the AI system and the second examination without it. In the routine-first group, the order of examinations was reversed. The primary outcome was the miss rate of superficial oesophageal squamous cell carcinoma and precancerous lesions, calculated on a per-lesion and per-patient basis. All analyses were done on a per-protocol basis. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100052116) and is completed. FINDINGS: Between Oct 19, 2021, and June 8, 2022, 5934 patients were randomly assigned to the AI-first group and 5912 to the routine-first group, of whom 5865 and 5850 were eligible for analysis. Per-lesion miss rates were 1·7% (2/118; 95% CI 0·0-4·0) in the AI-first group versus 6·7% (6/90; 1·5-11·8) in the routine-first group (risk ratio 0·25, 95% CI 0·06-1·08; p=0·079). Per-patient miss rates were 1·9% (2/106; 0·0-4·5) in AI-first group versus 5·1% (4/79; 0·2-9·9) in the routine-first group (0·37, 0·08-1·71; p=0·40). Bleeding after biopsy of oesophageal lesions was observed in 13 (0·2%) patients in the AI-first group and 11 (0·2%) patients in the routine-first group. No serious adverse events were reported by patients in either group. INTERPRETATION: The observed effect of AI-assisted endoscopy on the per-lesion and per-patient miss rates of superficial oesophageal squamous cell carcinoma and precancerous lesions under WLE and non-magnified NBI was consistent with substantial benefit through to a neutral or small negative effect. The effectiveness and cost-benefit of this AI system in real-world clinical settings remain to be further assessed. FUNDING: National Natural Science Foundation of China, 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University, and Chengdu Science and Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Nanomaterials-Enabled Physicochemical Antibacterial Therapeutics: Toward the Antibiotic-Free Disinfections.

Bacterial infection continues to be an increasing global health problem with the most widely accepted treatment paradigms restricted to antibiotics. However, the overuse and misuse of antibiotics have triggered multidrug resistance of bacteria, frustrating therapeutic outcomes, and leading to higher mortality rates. Even worse, the tendency of bacteria to form biofilms on living and nonliving surfaces further increases the difficulty in confronting bacteria because the extracellular matrix can act as a robust barrier to prevent the penetration of antibiotics and resist environmental damage. As a result, the inability to eliminate bacteria and biofilms often leads to persistent infection, implant failure, and device damage. Therefore, it is of paramount importance to develop alternative antimicrobial agents while avoiding the generation of bacterial resistance to prevent the large-scale growth of bacterial resistance. In recent years, nano-antibacterial materials have played a vital role in the antibacterial field because of their excellent physical and chemical properties. This review focuses on new physicochemical antibacterial strategies and versatile antibacterial nanomaterials, especially the mechanism and types of 2D antibacterial nanomaterials. In addition, this advanced review provides guidance on the development direction of antibiotic-free disinfections in the antibacterial field in the future.

An Extracellular Vesicle-Cloaked Multifaceted Biocatalyst for Ultrasound-Augmented Tendon Matrix Reconstruction and Immune Microenvironment Regulation.

The healing of tendon injury is often hindered by peritendinous adhesion and poor regeneration caused by the accumulation of reactive oxygen species (ROS), development of inflammatory responses, and the deposition of type-III collagen. Herein, an extracellular vesicles (EVs)-cloaked enzymatic nanohybrid (ENEV) was constructed to serve as a multifaceted biocatalyst for ultrasound (US)-augmented tendon matrix reconstruction and immune microenvironment regulation. The ENEV-based biocatalyst exhibits integrated merits for treating tendon injury, including the efficient catalase-mimetic scavenging of ROS in the injured tissue, sustainable release of Zn2+ ions, cellular uptake augmented by US, and immunoregulation induced by EVs. Our study suggests that ENEVs can promote tenocyte proliferation and type-I collagen synthesis at an early stage by protecting tenocytes from ROS attack. The ENEVs also prompted efficient immune regulation, as the polarization of macrophages (Mφ) was reversed from M1φ to M2φ. In a rat Achilles tendon defect model, the ENEVs combined with US treatment significantly promoted functional recovery and matrix reconstruction, restored tendon morphology, suppressed intratendinous scarring, and inhibited peritendinous adhesion. Overall, this study offers an efficient nanomedicine for US-augmented tendon regeneration with improved healing outcomes and provides an alternative strategy to design multifaceted artificial biocatalysts for synergetic tissue regenerative therapies.

Ultrasound-Targeted Microbubble Destruction-Mediated Cell-Mimetic Nanodrugs for Treating Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that mainly affects joints, and it can lead to disability and damage to vital organs if not diagnosed and treated in time. However, all current therapeutic agents for RA have limitations such as high dose, severe side effects, long-term use, and unsatisfactory therapeutic effects. The long-term use and dose escalation of methotrexate (MTX) may cause mild and severe side effects. To overcome the limitations, it is critical to target drug delivery to the inflamed joints. In this work, we constructed a folic acid-targeted and cell-mimetic nanodrug, MTX-loaded mesoporous silica composite nanoplatform (MMPRF), which can regulate drug release under ultrasound (US) and microbubble (MB) mediation. The targeted delivery and drug therapy were investigated through in vitro RAW264.7 cell experiments and in vivo collagen-induced arthritis animal experiments. The result showed that the targeting ability to the joints of MMPRF was strong and was more significant after US and MB mediation, which can potently reduce joint swelling, bone erosion, and inflammation in joints. This work indicated that the US- and MB-mediated MMPRF not only would be a promising method for synergistic targeted treatment of RA but also may show high potential for serving as a nanomedicine for many other biomedical fields.

Many-body cavity quantum electrodynamics with driven inhomogeneous emitters.

Quantum emitters coupled to optical resonators are quintessential systems for exploring fundamental phenomena in cavity quantum electrodynamics (cQED)1 and are commonly used in quantum devices acting as qubits, memories and transducers2. Many previous experimental cQED studies have focused on regimes in which a small number of identical emitters interact with a weak external drive3-6, such that the system can be described with simple, effective models. However, the dynamics of a disordered, many-body quantum system subject to a strong drive have not been fully explored, despite its importance and potential in quantum applications7-10. Here we study how a large, inhomogeneously broadened ensemble of solid-state emitters coupled with high cooperativity to a nanophotonic resonator behaves under strong excitation. We discover a sharp, collectively induced transparency (CIT) in the cavity reflection spectrum, resulting from quantum interference and collective response induced by the interplay between driven inhomogeneous emitters and cavity photons. Furthermore, coherent excitation within the CIT window leads to highly nonlinear optical emission, spanning from fast superradiance to slow subradiance11. These phenomena in the many-body cQED regime enable new mechanisms for achieving slow light12 and frequency referencing, pave a way towards solid-state superradiant lasers13 and inform the development of ensemble-based quantum interconnects9,10.

Engineering Cell Membrane-Cloaked Catalysts as Multifaceted Artificial Peroxisomes for Biomedical Applications.

Artificial peroxisomes (APEXs) or peroxisome mimics have caught a lot of attention in nanomedicine and biomaterial science in the last decade, which have great potential in clinically diagnosing and treating diseases. APEXs are typically constructed from a semipermeable membrane that encloses natural enzymes or enzyme-mimetic catalysts to perform peroxisome-/enzyme-mimetic activities. The recent rapid progress regarding their biocatalytic stability, adjustable activity, and surface functionality has significantly promoted APEXs systems in real-life applications. In addition, developing a facile and versatile system that can simulate multiple biocatalytic tasks is advantageous. Here, the recent advances in engineering cell membrane-cloaked catalysts as multifaceted APEXs for diverse biomedical applications are highlighted and commented. First, various catalysts with single or multiple enzyme activities have been introduced as cores of APEXs. Subsequently, the extraction and function of cell membranes that are used as the shell are summarized. After that, the applications of these APEXs are discussed in detail, such as cancer therapy, antioxidant, anti-inflammation, and neuron protection. Finally, the future perspectives and challenges of APEXs are proposed and outlined. This progress review is anticipated to provide new and unique insights into cell membrane-cloaked catalysts and to offer significant new inspiration for designing future artificial organelles.

Ultrasound-augmented anti-inflammatory exosomes for targeted therapy in rheumatoid arthritis.

Rheumatoid arthritis (RA), one of the systemic autoimmune diseases, features dysregulated inflammation that can eventually lead to multi-joint destruction and deformity. Although current clinical RA treatment agents including non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biological agents can alleviate symptoms, there can be long-term drug dependence and considerable side effects. To promote the course of RA from inflammation to resolution and ultimately terminate the vicious cycle of recrudescence, it is important to regulate the pro-/anti-inflammatory abilities of macrophages for constructing an immunosuppressive or anti-inflammatory microenvironment. Macrophage-derived exosomes can be homed or targeted to inflammatory tissues or cells; however, the insufficient anti-inflammatory abilities and intrinsic off-target effects of these exosomes often result in unsatisfactory treatment effects, which remains a challenge in the treatment of RA. Here, we proposed a novel kind of inherent anti-inflammatory exosome (AI-Exo), which was prepared via integrating RAW264.7 macrophage-derived exosomes and a powerful anti-inflammatory immune modulator interleukin-10 by an electroporation method. Then, non-invasive ultrasound was used to increase the permeability of blood vessels and augment the targeted accumulation of AI-Exo to inflammatory tissues, which could promote macrophage polarization to M2 phenotypes, relieve inflammation symptoms, stimulate resolution, and accelerate tissue repair against collagen-induced arthritis. This work intensely supports that ultrasound-augmented AI-Exo has significant targeted anti-inflammatory therapeutic effects, and the combined mechanism of anti-inflammation and pro-resolution gives unique insights into the treatment of not only RA but also other inflammatory diseases, which provides an effective strategy and a promising prospect for future wider biomedical applications and clinical transformations.

Measuring Correlations from the Collective Spin Fluctuations of a Large Ensemble of Lattice-Trapped Dipolar Spin-3 Atoms.

We perform collective spin measurements to study the buildup of two-body correlations between ≈10^{4} spin s=3 chromium atoms pinned in a 3D optical lattice. The spins interact via long range and anisotropic dipolar interactions. From the fluctuations of total magnetization, measured at the standard quantum limit, we estimate the dynamical growth of the connected pairwise correlations associated with magnetization. The quantum nature of the correlations is assessed by comparisons with analytical short- and long-time expansions and numerical simulations. Our Letter shows that measuring fluctuations of spin populations for s>1/2 spins provides new ways to characterize correlations in quantum many-body systems.

A Library of ROS-Catalytic Metalloenzyme Mimics with Atomic Metal Centers.

MetalN-coordinated centers supported by carbonaceous substrates have emerged as promising artificial metalloenzymes (AMEs) to mimic the biocatalytic effects of their natural counterparts. However, the synthesis of well-defined AMEs that contain different atomic metalN centers but present similar physicochemical and coordination structures remains a substantial challenge. Here, 20 different types of AMEs with similar geometries and well-defined atomic metalN-coordinated centers are synthesized to compare and disclose the catalytic activities, substrate selectivities, kinetics, and reactive oxygen species (ROS) products. Their oxidase (OXD)-, peroxidase (POD)-, and halogen peroxidase (HPO)-mimetic catalytic behaviors are systematically explored. The Fe-AME shows the highest OXD- and HPO-mimetic activities compared to the other AMEs due to its high vmax (0.927 × 10-6 m s-1 ) and low Km (1.070 × 10-3 m), while the Cu-AME displays the best POD-like performance. Furthermore, theoretical calculation reveals that the ROS-catalytic paths and activities are highly related to the electronic structures of the metal centers. Benefiting from its facile adsorption of H2 O2 molecule and lower energy barrier to generating •O2 - , the Fe-AME displays higher ROS-catalytic performances than the Mn-AME. The engineered AMEs show not only remarkably high ROS-catalytic performances but also provide new guidance toward developing metalN-coordinated biocatalysts for broad application fields.

Percutaneous contrast-enhanced ultrasound for localization and qualitative diagnosis of sentinel lymph nodes in cutaneous malignant melanoma of lower extremities: a preliminary study.

BACKGROUND: To explore the feasibility of sentinel lymph node (SLN) tracing by percutaneous contrast-enhanced ultrasound (pCEUS) in patients with cutaneous malignant melanoma (CMM) and the ability to enhance patterns of SLNs in diagnosing lymph nodes (LNs) metastases. METHODS: Fifty-three patients with CMM of the lower extremities treated at our hospital were included in the study. All the participants received pCEUS preoperatively. The enhanced lymphatic channels (LCs) and associated SLNs were observed and tracked in real-time. The number of enhanced LCs and enhancing patterns of SLNs were recorded. Subsequently, SLNs localized by pCEUS were pathologically examined. RESULTS: Of the 53 cases, SLNs were successfully localized by pCEUS in 48 cases. In total, there were 59 detected SLNs averaging 1.23±0.42 SLNs per case. The main lymphatic drainage patterns (LDPs) were the following: one enhanced LC pointed to one or more than one SLN, and multiple enhanced LCs pointed to one or multiple SLNs. There were four enhancing patterns of SLNs (uniform, annular, uneven, and no enhancement), among which the first two were considered benign nodes, while the latter two were considered metastatic nodes. With pathological results as the gold standard, the diagnostic sensitivity and specificity by pCEUS were 90.9% and 75.0%, respectively. CONCLUSIONS: Contrast-enhanced ultrasound (US) is a feasible approach for SLN identification in patients with CMM of the lower extremities. Enhancing patterns of SLNs may help predict metastasizing SLNs. This novel method may be a promising technique for clinical application.

Pd-Single-Atom Coordinated Biocatalysts for Chem-/Sono-/Photo-Trimodal Tumor Therapies.

The diversity, complexity, and heterogeneity of malignant tumor seriously undermine the efficiency of mono-modal treatment. Recently, multi-modal therapeutics with enhanced antitumor efficiencies have attracted increasing attention. However, designing a nanotherapeutic platform with uniform morphology in nanoscale that integrates with efficient chem-/sono-/photo-trimodal tumor therapies is still a great challenge. Here, new and facile Pd-single-atom coordinated porphyrin-based polymeric networks as biocatalysts, namely, Pd-Pta/Por, for chem-/sono-/photo-trimodal tumor therapies are designed. The atomic morphology and chemical structure analysis prove that the biocatalyst consists of atomic Pd-N coordination networks with a Pd-N2 -Cl2 catalytic center. The characterization of peroxidase-like catalytic activities displays that the Pd-Pta/Por can generate abundant •OH radicals for chemodynamic therapies. The ultrasound irradiation or laser excitation can significantly boost the catalytic production of 1 O2 by the porphyrin-based sono-/photosensitizers to achieve combined sono-/photodynamic therapies. The superior catalytic production of •OH is further verified by density functional theory calculation. Finally, the corresponding in vitro and in vivo experiments have demonstrated their synergistic chem-/sono-/photo-trimodal antitumor efficacies. It is believed that this study provides new promising single-atom-coordinated polymeric networks with highly efficient biocatalytic sites and synergistic trimodal therapeutic effects, which may inspire many new findings in reactive oxygen species-related biological applications across broad therapeutics and biomedical fields.

Preliminary study on the influencing factors of shear wave elastography for peripheral nerves in healthy population.

This study took shear wave elastography (SWE) technology to measure the shear wave velocity (SWV) of peripheral nerve in healthy population, which represents the stiffness of the peripheral nerves, and research whether these parameters (location, age, sex, body mass index (BMI), the thickness and cross-sectional area(CSA) of the nerve) would affect the stiffness of the peripheral nerves. 105 healthy volunteers were enrolled in this study. We recorded the genders and ages of these volunteers, measured height and weight, calculated BMI, measured nerve thickness and CSA using high-frequency ultrasound (HFUS), and then, we measured and compared the SWV of the right median nerve at the middle of the forearm and at the proximal entrance of the carpal tunnel. The SWV of the median nerve of the left side was measured to explore whether there exist differences of SWV in bilateral median nerve. Additionally, we also measured the SWV of the right tibial nerve at the ankle canal to test whether there is any difference in shear wave velocity between different peripheral nerves. This study found that there existed significant differences of SWV between different sites in one nerve and between different peripheral nerves. No significant difference was found in SWV between bilateral median nerves. Additionally, the SWV of peripheral nerves was associated with gender, while not associated with age or BMI. The mean SWV of the studied male volunteers in median nerve were significantly higher than those of female (p < 0.05). Peripheral nerve SWE measurement in healthy people is affected by different sites, different nerves and genders, and not associated with age, BMI, nerve thickness or CSA.

Ultrasound combined with SDF-1α chemotactic microbubbles promotes stem cell homing in an osteoarthritis model.

Osteoarthritis (OA) is a common joint disease in the middle and old age group with obvious cartilage damage, and the regeneration of cartilage is the key to alleviating or treating OA. In stem cell therapy, bone marrow stem cell (BMSC) has been confirmed to have cartilage regeneration ability. However, the role of stem cells in promoting articular cartilage regeneration is severely limited by their low homing rate. Stromal cell-derived factor-1α (SDF-1α) plays a vital role in MSC migration and involves activation, mobilization, homing and retention. So, we aim to develop SDF-1α-loaded microbubbles MB(SDF-1α), and to verify the migration of BMSCs with the effect of ultrasound combined with MB(SDF-1α) in vitro and in vivo. The characteristics of microbubbles and the content of SDF-1α were examined in vitro. To evaluate the effect of ultrasound combined with chemotactic microbubbles on stem cell migration, BMSCs were injected locally and intravenously into the knee joint of the OA model, and the markers of BMSCs in the cartilage were detected. We successfully prepared MB(SDF-1α) through covalent bonding with impressive SDF-1α loading efficacy loading content. In vitro study, ultrasound combined with MB(SDF-1α) group can promote more stem cell migration with highest migrating cell counts, good cell viability and highest CXCR4 expression. In vivo experiment, more BMSCs surface markers presented in the ultrasound combined with MB(SDF-1α) group with or without exogenous BMSCs administration. Hence, ultrasound combined with MB(SDF-1α) could promote the homing of BMSCs to cartilage and provide a novel promising therapeutic approach for OA.

Relaxation of the Collective Magnetization of a Dense 3D Array of Interacting Dipolar S=3 Atoms.

We report on measurements of the dynamics of the total magnetization and spin populations in an almost unit-filled lattice system comprising about 10^{4} spin S=3 chromium atoms, under the effect of dipolar interactions. The observed spin population dynamics is unaffected by the use of a spin echo and fully consistent with numerical simulations of the S=3 XXZ spin model. On the contrary, the observed magnetization decays slower than in simulations and, surprisingly, reaches a small but nonzero asymptotic value within the longest timescale. Our findings show that spin coherences are sensitive probes to systematic effects affecting quantum many-body behavior that cannot be diagnosed by merely measuring spin populations.

Determination of reference ranges for normal upper trapezius elasticity during different shoulder abduction using shear wave elastography: a preliminary study.

The purpose of this study was to determine the reference ranges of normal upper trapezius (UT) elasticity during different shoulder abduction using shear wave elastography (SWE). Mean shear wave velocity (SWV) of UT elasticity in eighty healthy participants were measured at left and right shoulder 0° abduction and 90° passive abduction (L0°, R0°, L90°, R90°) with SWE. The effects of potential factors (gender, UT thickness, age, and body mass index) on UT elasticity were analyzed. The reference ranges of normal UT elasticity were calculated by using the normal distribution method. UT elasticity was significantly different among various shoulder abduction (P < 0.0001). UT elasticity was significantly higher in males at both L90° (P < 0.05) and R90° (P < 0.01) than in females. The reference ranges of normal UT elasticity were 2.90-4.01 m/s at L0° and 3.01-4.29 m/s at R0°, and were 4.90-6.40 m/s in males and 4.40-6.20 m/s in females at L90°, 5.20-7.02 m/s in males and 4.71-6.80 m/s in females at R90°. Our results suggest that gender should be considered when determining the reference ranges of normal UT elasticity at L90° and R90° with SWE. These values may provide quantitative baseline measurements for the assessment of UT muscle strain in the future.

Ultrasound-targeted microbubble destruction augmented synergistic therapy of rheumatoid arthritis via targeted liposomes.

Rheumatoid arthritis (RA) can lead to joint destruction and deformity, which is a significant cause of the loss of the young and middle-aged labor force. However, the treatment of RA is still filled with challenges. Though dexamethasone, one of the glucocorticoids, is commonly used in the treatment of RA, its clinical use is limited because of the required high-dose and long-term use, unsatisfactory therapeutic effects, and various side-effects. Ultrasound-targeted microbubble destruction (UTMD) can augment the ultrasonic cavitation effects and trigger drug release from targeted nanocarriers in the synovial cavity, which makes it a more effective synergistic treatment strategy for RA. In this work, we aim to utilize the UTMD effect to augment the synergistic therapy of RA by using polyethylene glycol (PEG)-modified folate (FA)-conjugated liposomes (LPs) loaded with dexamethasone sodium phosphate (DexSP) (DexSP@LPs-PEG-FA). The UTMD-mediated DexSP@LPs-PEG-FA for targeted delivery of DexSP including a synergistic ultrasonic cavitation effect and drug therapy were investigated through in vitro RAW264.7 cell experiments and in vivo collagen-induced arthritis SD rat model animal experiments. The results show the DexSP release from targeted liposomes was improved under the UTMD effect. Likewise, the folate-conjugated liposomes displayed targeting association to RAW264.7 cells. Together with the application of ultrasound and microbubbles, liposomes-delivered DexSP potently reduced joints swelling, bone erosion, and inflammation in both joints and serum with a low dose. These results demonstrated that UTMD-mediated folate-conjugated liposomes are not only a promising method for targeted synergistic treatment of RA but also may show high potential for serving as nanomedicines for many other biomedical fields.

Transfection of TGF-ß shRNA by Using Ultrasound-targeted Microbubble Destruction to Inhibit the Early Adhesion Repair of Rats Wounded Achilles Tendon In vitro and In vivo.

BACKGROUND: Tendon injury is a major orthopedic disorder. Ultrasound-targeted microbubble destruction (UTMD) provides a promising method for gene transfection, which can be used for the treatment of injured tendons. OBJECTIVE: The purpose of this study was to investigate the optimal transforming growth factor beta (TGF-ß) short hairpin RNA (shRNA) sequence and transfection conditions using UTMD in vitro and to identify its ability for inhibiting the early adhesion repair of rats wounded achilles tendons in vivo. METHODS: The optimal sequence was selected analyzing under a fluorescence microscope and quantitative real-time reverse transcription polymerase chain reaction in vitro. In vivo, 40 rats with wounded Achilles tendons were divided into five groups: (1) control group, (2) plasmid group (3) plasmid + ultrasound group, (4) plasmid + microbubble group, (5) plasmid + microbubble + ultrasound group, and were euthanized at 14 days post treatment. TGF-ß expression was evaluated using adhesion scores and pathological examinations. RESULTS: The optimal condition for UTMD delivery in vitro was 1W/cm2 of output intensity and a 30% duty cycle with 60 s irradiation time (P < 0.05). The transfection efficiency of the plasmid in group 5 was higher than that in other groups (P < 0.05). Moreover, the lowest adhesion index score and the least expression of TGF-ß were shown in group 5 (P < 0.05). When compared with the other groups, group 5 had a milder inflammatory reaction. CONCLUSION: The results suggested that UTMD delivery of TGF-ß shRNA offers a promising treatment approach for a tendon injury in vivo.

Quantitative Assessment of Keloids Using Ultrasound Shear Wave Elastography.

This study was aimed at investigating the value of shear wave elastography (SWE) in quantitative evaluation of keloids. A total of 87 patients with 139 keloids were enrolled. Vancouver scar scale (VSS) scores were recorded. Thickness and blood flow grade were evaluated using high-frequency ultrasound. Skin stiffness (mean speed of shear wave, Cmean) was evaluated using SWE in both transverse and longitudinal sections. All measurements were performed in both keloids and site-matched unaffected skin (normal controls). The reliability of measurements was evaluated using intra- and inter-class correlation coefficients by two observers. Inter- and intra-observer repeatability was excellent (correlation coefficient > 0.99, p < 0.01). The SWE results revealed a significant increase in Cmean in keloids (p < 0.001) compared with the normal controls. Cmean in the longitudinal section was greater than that in the transverse section for keloids (p < 0.001). Cmean was highly positively correlated with VSS score (r = 0.904, p < 0.001), moderately positively correlated with thickness (r = 0.490, p < 0.001) and less positively correlated with blood flow (r = 0.231, p < 0.01). This non-invasive, tolerable and convenient imaging technique could be an effective tool for objectively evaluating keloid stiffness in the future, thus laying a foundation for the treatment and evaluation of keloids.