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.

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.

Shear wave elastography-based skin assessment system for systemic sclerosis: a supplement or alternative to conventional ultrasound?

Background: Although shear wave elastography (SWE) has been found to have the potential to evaluate skin lesions in systemic sclerosis (SSc), current research fails to answer the following questions: (I) can high-frequency ultrasound (HFUS) and SWE at multiple sites throughout the body distinguish SSc subtypes; (II) is HFUS and SWE at every site equally affected by clinical characteristics; and (III) is SWE a supplement or a choice to HFUS. This prospective study aimed to compare the value of SWE-based skin stiffness and HFUS-based skin thickness in distinguishing different SSc subtypes, verify the influence of clinical features on SWE and HFUS, and provide a basis for the screening of the optimal evaluation sites and indicators in the future. Methods: Forty-nine limited and 51 diffuse SSc patients were included in this study. Their skin was assessed at 17 sites by palpation using the modified Rodnan skin score (mRSS), skin thickness measured by HFUS, and skin stiffness by SWE. Clinical features, including age, sex, body mass index, and disease duration, were collected. Results: The diffuse SSc patients had higher skin stiffness at most sites (P<0.05), except for the finger, foot, and forehead, and a thicker skin layer at most sites (P<0.05), except for the finger. The area under the curve (AUC) of HFUS, SWE, and the combination of the two in distinguishing diffused and limited SSc were 0.866, 0.921, and 0.973, respectively. The differences were statistically significant (combination vs. SWE, P=0.002, combination vs. HFUS, P=0.021). Longer disease duration was associated with a thinner skin layer at the forearm, arm, chest wall, abdominal wall, and thigh in limited SSc, including the leg in diffused SSc. SWE was less affected by clinical features than HFUS. SWE could achieve greater discrimination between different mRSSs at multiple sites, such as fingers and arms, than HFUS. Conclusion: For the assessment of SSc skin, SWE has several advantages over HFUS, including less influence by clinical features and greater sensitivity to discriminate different mRSSs. SWE has the potential to become a primary imaging assessment tool as well as HFUS.

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.

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.

Tunable Structured MXenes With Modulated Atomic Environments: A Powerful New Platform for Electrocatalytic Energy Conversion.

Owing to their rich surface chemistry, high conductivity, tunable bandgap, and thermal stability, structured 2D transition-metal carbides, nitrides, and carbonitrides (MXenes) with modulated atomic environments have emerged as efficient electrochemical energy conversion systems in the past decade. Herein, the most recent advances in the engineering of tunable structured MXenes as a powerful new platform for electrocatalytic energy conversion are comprehensively summarized. First, the state-of-the-art synthetic and processing methods, tunable nanostructures, electronic properties, and modulation principles of engineering MXene-derived nanoarchitectures are focused on. The current breakthroughs in the design of catalytic centers, atomic environments, and the corresponding structure-performance correlations, including termination engineering, heteroatom doping, defect engineering, heterojunctions, and alloying, are discussed. Furthermore, representative electrocatalytic applications of structured MXenes in energy conversion systems are also summarized. Finally, the challenges in and prospects for constructing MXene-based electrocatalytic materials are also discussed. This review provides a leading-edge understanding of the engineering of various MXene-based electrocatalysts and offers theoretical and experimental guidance for prospective studies, thereby promoting the practical applications of tunable structured MXenes in electrocatalytic energy conversion systems.

Modulating Electron Transfer in Vanadium-Based Artificial Enzymes for Enhanced ROS-Catalysis and Disinfection.

Nanomaterials-based artificial enzymes (AEs) have flourished for more than a decade. However, it is still challenging to further enhance their biocatalytic performances due to the limited strategies to tune the electronic structures of active centers. Here, a new path is reported for the de novo design of the d electrons of active centers by modulating the electron transfer in vanadium-based AEs (VOx -AE) via a unique Zn-O-V bridge for efficient reactive oxygen species (ROS)-catalysis. Benefiting from the electron transfer from Zn to V, the V site in VOx -AE exhibits a lower valence state than that in V2 O5 , which results in charge-filled V-dyz orbital near the Fermi level to interfere with the formation of sigma bonds between the V- d z 2 and O-pz orbitals in H2 O2 . The VOx -AE exhibits a twofold Vmax and threefold turnover number than V2 O5 when catalyzing H2 O2 . Meanwhile, the VOx -AE shows enhanced catalytic eradication of drug-resistant bacteria and achieves comparable wound-treatment indexes to vancomycin. This modulating charge-filling of d electrons provides a new direction for the de novo design of nanomaterials-based AEs and deepens the understanding of ROS-catalysis.

Conjugated Coordination Porphyrin-based Nanozymes for Photo-/Sono-Augmented Biocatalytic and Homologous Tumor Treatments.

Porphyrin-based nanozymes (Porzymes) have shown promising application potential to fight against tumors using catalytically generated reactive oxygen species from the excessively produced H2O2 in the tumor microenvironment. However, the low coordination porphyrin (CP) loading ratio, difficult controllable nanostructure, low bioavailability, and low biocatalytic activities of current established Porzymes have severely limited their antitumor applications. Here, a novel malignant melanoma cell membrane-coated Pd-based CP nanoplatform (Trojan Porzymes) has been synthesized for biocatalytic and homologous tumor therapies. The Trojan Porzymes exhibit a high CP loading ratio, uniform nanoscale size, single-atom nanostructure, homologous targeted ability, and high-efficiency photo/sono-augmented biocatalytic activities. The enzyme-like biocatalytic experiments display that the Trojan Porzymes can generate abundant •OH via chemodynamic path and 1O2 via visible light or ultrasound excitation. Then we demonstrate that the Trojan Porzymes show homologous targeting ability to tumor cells and can achieve efficient accumulation and long-term retention in cancer tissues. Our in vivo data further disclose that the photo/sono-assisted chemodynamic therapies can significantly augment the treatment efficiency of malignant melanoma. We believe that our work will afford a new biocatalytic and homologous strategy for future clinical malignant melanoma treatments, which may inspire and guide more future studies to develop individualized biomedicine in precise tumor therapies.

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.

Application of ultrasound elastography in the evaluation of muscle strength in a healthy population.

BACKGROUND: To investigate the validity of shear wave elastography (SWE) for the evaluation of muscle strength compared with isokinetic muscle testing, and to assess the influence of demographic factors such as height, weight, and body mass index (BMI) on the shear wave velocity (SWV). METHODS: Sixty healthy volunteers were consecutively enrolled. SWE was used to measure the SWV of the right quadriceps femoris in a relaxed position, in a tensive position, and under loads of 1 and 2 kg. Muscle strength parameters including peak torque (PT), PT to body weight ratio (PT/BW), and total work (TW) were evaluated using isokinetic muscle testing. The SWV of the rectus femoris in different positions were compared using the Friedman test and the Kruskal-Wallis test, and the SWV and muscle strength parameters were compared between different genders and age groups using the Mann-Whitney U test. Additionally, Spearman's correlation coefficient was used to evaluate the correlation between SWV and muscle strength, as well as the possible effects of height, weight, and BMI on SWV. RESULTS: As the load increased, the SWV of the rectus femoris increased (P<0.001). In the relaxed position, there was no significant correlation between the SWV and the results of isokinetic muscle testing. With increasing load, the SWV and the results of isokinetic muscle testing were not significantly correlated (r=-0.256--0.392, P<0.05). In the 1 kg load position, height and weight were not significantly correlated with SWV (r=-0.261--0.393, P<0.05). In the relaxed position, there were no significant differences in the maximum, minimum, or mean SWV of the rectus femoris between different genders and age groups (P>0.05). However, under a 1 kg load, the maximum, minimum, and mean SWV of the females in this study were significantly higher than those of the males (4.49±0.60 vs. 3.98±0.68 m/s; 2.55±0.61 vs. 2.20±0.63 m/s; and 3.51±0.60 vs. 3.06±0.58 m/s; P=0.003, 0.028, and 0.004, respectively). Furthermore, there were significant differences in the maximum and mean velocities between the groups aged 20-34 and 35-60 years (4.11±0.62 vs. 4.47±0.70 m/s; 3.17±0.53 vs. 3.52±0.69 m/s; P=0.045 and 0.044, respectively). CONCLUSIONS: Ultrasound elastography (UE) shows potential for the measurement of muscle strength. The SWV of muscles demonstrate an increasing trend with the increase of impedance. Additionally, age and gender have a significant effect on SWV, while the effects of height, weight, and BMI require further investigation.

A measurement method of knee joint space width by ultrasound: a large multicenter study.

BACKGROUND: Although plain radiology is the primary method for assessing joint space width (JSW), it has poor sensitivity to change over time in regards to determining longitudinal progression. We, therefore, developed a new ultrasound (US) measurement method of knee JSW and aimed to provide a monitoring method for the change of JSW in the future. METHODS: A multicenter study was promoted by the Professional Committee of Musculoskeletal Ultrasound, the Ultrasound Society, and the Chinese Medical Doctor Association. US study of knee specimens determined the landmarks for ultrasonic measurement of knee JSW. The US of 1,272 participants from 27 centers was performed to discuss the feasibility and possible influencing factors of knee JSW. The landmarks for US measurement of knee JS, the inflection point of medial femoral epicondyle and the proximal end of the tibia, were determined. RESULTS: The mean knee JSW1 (medial knee JSW) was 8.57±1.95 mm in females and 9.52±2.31 mm in males. The mean knee JSW2 (the near medial knee JSW) was 9.07±2.24 mm in females and 10.17±2.35 mm in males. The JSW values of males were significantly higher than those of females, with a statistical difference. JSW values were negatively correlated with age and body mass index (BMI) to different degrees and positively correlated with height. CONCLUSIONS: The novel US measurement method can be used to measure knee JSW.

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.

Ultrasound assessment in psoriatic arthritis (PsA) and psoriasis vulgaris (non-PsA): which sites are most commonly involved and what features are more important in PsA?

BACKGROUND: The aim of this study was to find out the most commonly involved sites and the most important ultrasonic features in psoriatic arthritis (PsA). METHODS: In total, 120 PsA patients and 320 psoriasis vulgaris (non-PsA) patients were assessed by grayscale and power Doppler (PD) ultrasound (US). Joints, tendons, enthesis, and bursa changes were observed. Weights of affected anatomical sites of PsA patients (overall weights >90%) were calculated. Affected anatomical sites between PsA and non-PsA patients were compared. Ultrasonic features of joint, tendon, entheses, and bursa changes between PsA and non-PsA patients were also compared. Finally, the test performance of ultrasonic features for the diagnosis of PsA was calculated. RESULTS: The anatomical sites with the highest weights were the Achilles tendon, quadriceps tendon, and knee; weights of these anatomical sites were all more than 5%. Among the affected anatomical sites of PsA patients, most of the anatomical sites were more greatly affected in the PsA patients than in the non-PsA patients (all P<0.05). The comparison of the affected Achilles tendon, quadriceps tendon, MTP1, subacromial-subdeltoid bursa, MCP4, and MCP3 showed no significance between PsA and non-PsA patients (all P>0.05). Joint synovial thickening, joint PD signal grades, joint bone erosions, tendon sheath synovial thickening, tendon sheath PD signals, enthesis bone erosions, and enthesis PD signals in PsA patients were higher than in non-PsA patients (all P<0.05). Joint PD signal grades, joint bone erosions, enthesis bone erosions, and enthesis PD signals showed the highest specificities, which were 96.06%, 95.15%, 96.93%, and 94.63% respectively. CONCLUSIONS: The most common involvement sites of PsA were the Achilles tendon, quadriceps tendon, and knee, and some sites in non-PsA patients were also highly involved. The most important features in PsA included joint PD signal grades, joint bone erosion, entheses bone erosions, and entheses PD signals in US assessment.

Experimental study of TNF-α receptor gene transfection by ultrasound-targeted microbubble destruction to treat collagen-induced arthritis in rats in vivo.

Ultrasound-targeted microbubble destruction (UTMD) is a novel method for gene transfection. The aim of the present study was to identify the most suitable method of tumor necrosis factor (TNF)-α receptor (TNFR) gene transfection using UTMD for systemically treating a rat model of collagen-induced arthritis (CIA). Plasmids encoding the TNFR and enhanced green fluorescent protein (EGFP) with or without microbubbles were locally injected into the skeletal muscle and synovial membrane of CIA rats. The rats were divided into the following 6 groups: i) Group 1, plasmid + microbubble + ultrasound (muscle group); ii) group 2, plasmid + microbubble + ultrasound (joint group); iii) group 3, plasmid + ultrasound; iv) group 4, plasmid + microbubble; v) group 5, plasmid only and; vi) group 6, untreated controls. Rats were sacrificed at 2, 4 and 8 weeks of treatment. The transfection efficiency of the plasmids in the muscle or synovium was observed by fluorescence microscopy. Arthritis scores were calculated and serum levels of TNF-α were measured prior to and following treatment. Bilateral ankle joints were obtained and stained to observe synovial inflammation and the expression of TNF-α. EGFP expression was detected in all treated groups at each time point, and the fluorescence intensity of groups 1 and 2 was significantly greater than that of the other groups (P<0.05). For groups 1 and 2, the reductions in joint scores and serum levels of TNF-α were significant compared with the other groups (P<0.05). The number of synovial inflammatory cells and the synovial expression of TNF-α presented similar results among all experimental groups and no significant difference was observed between groups 1 and 2. Therefore, the results of the present study suggest that UTMD significantly enhanced the efficiency of TNFR gene transfection in the muscle and inflamed synovium of rats with. Regardless of whether the transfected TNFR gene was injected into the muscle or joint, it was continuously expressed in the rats for at least 8 weeks, which may improve arthritic symptoms and reduce the levels of inflammatory factors in the synovial tissues and peripheral blood.

Quantitative Assessment of Skin Stiffness Using Ultrasound Shear Wave Elastography in Systemic Sclerosis.

This study was aimed at investigating the performance of ultrasound shear wave elastography (US-SWE) in the assessment of skin (the dermis) stiffness in patients with systemic sclerosis (SSc). The thickness and elastic modulus of the skin were measured using US-SWE at 6 sites in 60 SSc patients and 60 healthy volunteers: the bilateral middle fingers and forearms and the anterior chest and abdomen. To evaluate clinical scores, the measurements were also extended to 17 skin sites in 30 patients. The diagnostic performance of US-SWE in the differentiation of SSc from healthy skin was determined by receiver operating characteristic (ROC) curve analysis, and the reliability of the measurement was evaluated with intra- and inter-class correlation coefficients. The results of US-SWE were compared with modified Rodnan skin thickness scores. Our results indicated that (i) the elastic modulus values were significantly higher in SSc patients than in controls, with or without normalization by skin thickness; (ii) receiver operating characteristic analysis revealed normalized US-SWE cutoff values with a very high accuracy for right and left fingers (areas under the curve = 0.974 and 0.949), followed by left forearm (0.841), anterior abdomen (0.797), right forearm (0.772) and anterior chest (0.726); (iii) the reliability of US-SWE measurements was good for all examined sites with intra-observer correlation coefficients of 0.845-0.996 and inter-observer correlation coefficients of 0.824-0.985; and (iv) total scores of skin involvement determined at 17 sites (modified Rodnan skin thickness scores) correlated with skin stiffness (r = 0.832) and thickness (r = 0.736). In conclusion, US-SWE is a quantitative method with high specificity, sensitivity and reliability in the detection of SSc involvement. This non-invasive, real-time and operator-independent imaging technique could be an ideal tool for the assessment of SSc disease.

Quantification of skin lesions using high-frequency ultrasound and shear wave elastography in port-wine stain patients: a clinical study.

BACKGROUND: This study aimed to assess the different types of port-wine stain (PWS) skin lesions quantitatively using high-frequency ultrasound (US) and shear wave elastography (SWE) before and after treatment, and investigate the feasibility and application value of high-frequency US and SWE in PWSs. METHODS: A total of 195 PWS patients with 238 skin lesions before treatment and 72 follow-up PWS patients with 90 skin lesions were assessed using high-frequency US and SWE. The skin lesions were divided into four groups: pink-type, purple-type, thickened-type, and nodular-type PWSs. Gray-scale US was used to observe normal skin, observe the skin changes of lesions, and assess the skin thickness. The thickened skin was calculated. Power Doppler (PD) signal grades were used to assess the skin blood signals. SW velocity (in m/s) and Young's elastic modulus (in kPa) were used to assess the stiffness of normal skin and skin lesions. The heightened SWE was also calculated. RESULTS: The dermis hypoechogenicity, thickness of thickened skin, and skin PD signal grades were significantly higher in all PWS-type groups compared with the normal-skin group (all P<0.05). The thickened skin and skin PD signal grades in the nodular-type and thickened-type group were significantly thicker and higher than those in the pink-type and purple-type group (all P<0.05). The PD signal grades in the purple-type was significantly higher than that in the pink-type group (P<0.05). All SWE values of PWS lesions were significantly higher in the transverse section than those in the longitudinal section (all P<0.05). The differences in heightened Emean, Emin, Cmean, and Cmin between each PWS group and the normal-skin group were not significant. The heightened Emax and Cmax in the nodular-type PWS group was significantly higher than those in the normal-skin group and pink-type, and purple-type PWS groups (all P<0.05). The heightened Emax and Cmax were significantly higher in the thickened-type PWS group than those in the normal-skin group (all P<0.05). In the evaluation of therapeutic effects, the ratio of dermis hypoechogenicity in pink-type lesions significantly decreased, and thickened skins in all groups were significantly thinned (all P<0.05). The differences of PD signal grades, heightened Emax, and Cmax in all groups between pre-treatment and post-treatment showed no significance. CONCLUSIONS: High-frequency US and SWE show feasibility and application values assessing PWS skin lesions. Their features include dermis hypoechogenicity, thicker skin, higher PD signal grades, higher Emax, and higher Cmax. Thicker skin is thus the best feature for assessing therapeutic effect.

Evaluation of the healthy median nerve elasticity: Feasibility and reliability of shear wave elastography.

The present study applied the shear wave elastography (SWE) to the median nerve in order to investigate the feasibility and reliability of its use in 40 healthy volunteers. Shear wave velocities of the median nerve on bilateral forearms and right carpal tunnel were obtained with relaxing or stretching conditions. The inter- and intraobserver agreements and differences of nerve elasticity among groups were evaluated using intraclass correlation coefficients, the paired t test, and the Wilcoxon signed-rank test, respectively. The stiffness of the site was expressed by 3 types of values: mean, minimum, and maximum shear-wave velocities. The inter- and intraobserver agreements were excellent (0.852-0.930) on the right forearm. No differences were detected between the bilateral forearm (mean: P = .14), while the values of different body sites and postures were statistically different (P < .001). SWE, as a noninvasive and objective tool, reached a good consistency in evaluating the healthy median nerve. Further studies are essential to investigate the detailed influencing factors and provide an insight of SWE to estimate both the normal nerve and peripheral neuropathy.

Sonographic appearance of fluid in peripheral joints and bursae of healthy asymptomatic Chinese population.

BACKGROUND: High frequency ultrasound is often used to measure the thickness of fluid in peripheral joints and bursae of healthy asymptomatic populations. Two major steps critical to this procedure are obtaining the detection rates and analyzing the relevant factors. METHODS: Healthy Chinese adult volunteers with no history of arthritis, past trauma or surgery and joint pain were enrolled in this study. Ultrasonography was performed on the bilateral shoulders, elbows, wrists, metacarpophalangeal joints (MCP) 1-5, proximal interphalangeal joints (PIP) 1-5, distal interphalangeal joints (DIP) 2-5, suprapatellar knees, ankles, metatarsophalangeal joints (MTP) 1-5, subacromial and subdeltoid bursae, deep infrapatellar bursae, retrocalcaneal bursae and long biceps tendons in B mode. Average size of fluid thickness and detection rate were calculated and correlated with demographic parameters. Mean + 1.64 SD was defined as the upper limit of the 95% reference range. RESULTS: One hundred and fifty-two volunteers (71 males and 81 females) with mean age of 48.0±14.1 years were enrolled. Both the highest detection rate and the thickest fluid were found in the suprapatellar knee (82.9%, 3.7±1.7 mm). There was no significant difference between the left and right side of the same structure in the detection rate and the fluid thickness. Females had a higher detection rate and fluid thickness than males in most examined structures, especially in the upper-limb joints. The greatest number of examined structures was found to be affected by age, and all of the correlations were positive (r from 0.118 to 0.510, P<0.05). Positive correlations were found in the long biceps tendon and MTP1 between detection rate and body mass index (BMI) (r=0.251 and 0.123, respectively, P<0.05), and in the long biceps tendon between effusion thickness and BMI (r=0.228, P<0.05). The upper limits of the 95% reference range for peripheral joints and bursae were determined. CONCLUSIONS: Fluid in certain peripheral joints of healthy asymptomatic populations can be associated with gender, age or BMI. This study provided reference values for future comparisons with pathological conditions among Chinese populations.

Ultrasound-Targeted Microbubble Destruction Delivery of Insulin-Like Growth Factor 1 cDNA and Transforming Growth Factor Beta Short Hairpin RNA Enhances Tendon Regeneration and Inhibits Scar Formation In Vivo.

Ultrasound-targeted microbubble destruction (UTMD), which has been successfully used for the treatment of many diseases, offers a promising noninvasive approach for target-specific gene delivery. This study investigated the UTMD delivery of insulin-like growth factor 1 (IGF-1) cDNA and transforming growth factor beta (TGF-ß) short hairpin RNA for Achilles tendon injury in rats. Briefly, 168 rats with an injured Achilles tendon were randomly divided into seven groups: (1) IGF-1 + UTMD, (2) TGF-ß + UTMD, (3) IGF-1 + TGF-ß + UTMD, (4) control, (5) IGF-1, (6) TGF-ß, and (7) IGF-1 + TGF-ß. At 2, 4, 8, and 12 weeks post treatment, six rats from each group were euthanized. IGF-1 expression and TGF-ß expression were evaluated using an adhesion index score, pathological examination, quantitative real-time reverse transcription polymerase chain reaction, Western blotting, and biomechanical measurement. The lowest adhesion index score, the lightest inflammation, the highest 4,6-diamidino-2-phenylindole nuclear counter signals, the highest IGF-1 expression, and the lowest TGF-ß expression were observed in group 3 (p < 0.05). Furthermore, higher expression of IGF-1 mRNA was observed in groups 1 and 3, while lower expression of TGF-ß mRNA was observed in groups 2 and 3 (p < 0.05). The UTMD groups showed a higher transfection efficiency than the groups without UTMD. Downregulation of type III collagen and upregulation of type I collagen were observed in groups 1-3. Moreover, during weeks 4, 8, and 12, greater maximum load and tensile stress were observed in group 3 compared to the other groups (p < 0.05), while the highest tendon stiffness was observed in week 12 (p < 0.05). To conclude, the results suggest that UTMD delivery of IGF-1 and TGF-ß offers a promising treatment approach for tendon injury in vivo.