Highly spontaneous spin polarization engineering of single-atom artificial antioxidases towards efficient ROS elimination and tissue regeneration.

The creation of atomic catalytic centers has emerged as a conducive path to design efficient nanobiocatalysts to serve as artificial antioxidases (AAOs) that can mimic the function of natural antioxidases to scavenge noxious reactive oxygen species (ROS) for protecting stem cells and promoting tissue regeneration. However, the fundamental mechanisms of diverse single-atom sites for ROS biocatalysis remain ambiguous. Herein, we show that highly spontaneous spin polarization mediates the hitherto unclear origin of H2O2-elimination activities in engineering ferromagnetic element (Fe, Co, Ni)-based AAOs with atomic centers. The experimental and theoretical results reveal that Fe-AAO exhibits the best catalase-like kinetics and turnover number, while Co-AAO shows the highest glutathione peroxidase-like activity and turnover number. Furthermore, our investigations prove that both Fe-AAO and Co-AAO can effectively secure the functions of stem cells in high ROS microenvironments and promote the repair of injured tendon tissue by scavenging H2O2 and other ROS. We believe that the proposed highly spontaneous spin polarization engineering of ferromagnetic element-based AAOs will provide essential guidance and practical opportunities for developing efficient AAOs for eliminating ROS, protecting stem cells, and accelerating tissue regeneration.

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.

Quantitative assessment of muscle properties in polymyositis and dermatomyositis using high-frequency ultrasound and shear wave elastography.

Background: Polymyositis (PM) and dermatomyositis (DM) are two common types of idiopathic inflammatory myopathy and can lead to a poor prognosis and quality of life. We designed this cross-sectional study to investigate the abilities of high-frequency ultrasound (HFUS) and shear wave elastography (SWE) to assess muscle properties in patients with PM and DM and to distinguish healthy muscles from diseased muscles with PM and DM. Methods: A total of 60 patients (26 PM cases and 34 DM cases) and 65 matched healthy volunteers were continuously included in the case and control groups, respectively. For the bilateral deltoid, biceps brachii, rectus femoris, and vastus lateralis, the muscle thickness, echo intensity, and longitudinal shear wave velocity (SWV) of all participants were measured using HFUS and SWE. The intra- and interobserver reliability of SWV measurements of patients with PM and DM and the receiver operating characteristic curve for HFUS and SWE for PM and DM were analyzed. Results: Patients with PM and DM had significantly decreased muscle thickness and increased muscle echo intensity compared to healthy controls (P<0.001). The patients' and healthy participants' deltoid, biceps brachii, rectus femoris, and vastus lateralis thickness was 19.75 and 23.00 mm, 20.45 and 22.80 mm, 18.40 and 20.20 mm, and 20.00 and 22.80 mm, respectively. Except for the biceps brachii, the mean SWV in the longitudinal orientation in patients with PM and DM significantly decreased (P<0.01). The mean SWV of the patients' and healthy participants' deltoid, rectus femoris, and vastus lateralis was 2.47 and 2.57 m/s, 1.73 and 1.87 m/s, and 1.57 and 1.77 m/s, respectively. Excellent intra- and interobserver reliability of SWV measurements on the deltoid and rectus femoris of PM and DM patients were found (intraclass correlation coefficient >0.95; P<0.001). The diagnostic performance of echo intensity in lower-extremity proximal muscles for PM and DM was excellent [area under the curve (AUC) >0.9]. The thickness of most muscles displayed moderate diagnostic performance (the AUC ranged from 0.700 to 0.775). The SWV of the vastus lateralis showed a stable performance (AUC =0.741). The combined diagnostic performance of echo intensity and thickness and the combined diagnostic performance of the 3 indicators were relatively high (the AUC ranged from 0.871 to 0.936 and from 0.898 to 0.938, respectively). Muscle thickness and echo intensity showed statistical differences in different disease stages of PM and DM (P'<0.01). Conclusions: HFUS and SWE may serve as imaging biomarkers for the diagnosis of PM and DM by detecting abnormal muscle thinning, enhanced muscle echo intensity, and reduced muscle SWV.

Screening value of lung ultrasound in connective tissue disease related interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD) that can lead to poor quality of life and prognosis. OBJECTIVES: To explore the screening value of lung ultrasound (LUS) for connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: Data of patients with CTD were collected, and each patient underwent LUS, high-resolution computed tomography (HRCT), and pulmonary function tests. Considering HRCT is the gold standard for diagnosing CTD-ILD, patients were divided into CTD-ILD and CTD-non-ILD groups. The LUS and HRCT results were assessed using semiquantitative and Warrick scores, respectively. Pulmonary function results were also collected. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of LUS diagnosis. Spearman correlation analysis was used to analyze the correlation between LUS, HRCT, and lung function indices. RESULTS: A total of 88 patients (65 with CTD-ILD and 23 with CTD-non-ILD) were included in this study. The sensitivity and specificity of LUS for the diagnosis of CTD-ILD were 86.60% and 82.60%, respectively, which was consistent with the HRCT results (P < 0.05). The LUS results (total number of B-lines, frequency of B-line, pleural thickness, and pleural-line irregularity) were positively correlated with the HRCT Warrick score (r = 0.77, 0.76, 0.65 and 0.71, P < 0.05). CONCLUSIONS: LUS may be a promising tool for screening patients with CTD-ILD.

Ultrasound-derived muscle assessment system for older adults: a promising muscle mass estimation tool.

BACKGROUND: Quantitative assessment of muscle mass is a critical step in sarcopenia disease management. Expanding upon the use of ultrasound in foetal growth assessment, we established and validated an ultrasound-derived muscle assessment system for older adults at a risk of sarcopenia. METHODS: A total of 669 older adults were recruited in three cohorts in this cross-sectional study. In cohort 1(n = 103), the most valuable sites for skeletal muscle mass index (SMI) estimation were located among 11 ultrasound scanning sites. An ultrasound-derived SMI estimating algorithm based on muscle thickness (MT) was obtained in the modelling group composed of cohorts 1 and 2 (n = 309). The reliability of the muscle mass estimation equation and the validity of the obtained cut-off values were verified in cohort 3 (n = 257), which was selected as the verification group. RESULTS: In the modelling group, the cut-off values of ultrasound-derived e-SMI for low SMI were 7.13 kg/m2 for men and 5.81 kg/m2 for women. In the verification group, the intraclass correlation between e-SMI and SMI was 0.885. The sensitivity of the e-SMI in detecting low SMI was 93.6% for men and 89.7% for women, and the negative predictive value was 94.9% for men and 94.7% for women. Combined with the handgrip strength and gait speed, the e-SMI had an overall diagnostic sensitivity of 92.7% and a specificity of 91.0% for sarcopenia. CONCLUSION: The ultrasound-derived muscle assessment system can be a promising muscle mass estimation tool and a potential disease classification tool.

Evaluation of connective tissue disease-related interstitial lung disease using ultrasound elastography: a preliminary study.

Background: Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD), which can lead to shortened survival. This article explores the ability of shear wave elastography (SWE) to assess lung surface elastic properties and to distinguish healthy lungs from diseased lungs with connective tissue disease-related interstitial lung disease (CTD-ILD). We aimed to determine whether SWE can be used to assess the severity of CTD-ILD. Methods: A total of 65 CTD-ILD patients and 60 healthy volunteers were included for the case group and the control group, respectively. All participants underwent lung ultrasound (count of B-line and measurement of pleural line thickness) and SWE [measurement of Young's modulus (Emean) and shear wave velocity (SMV) (Cmean)] examinations at 50 lung sites. All participants also underwent an examination with high-resolution computed tomography (HRCT) and a pulmonary function test (PFT). For SWE assessment, the Q-box was set to its minimum size (1 mm) and manually placed on the pleural line, rather than inside the lung, to measure the stiffness of the lung surface. The intra- and inter-reliability of SWE measurements of healthy controls (HC), the receiver operating characteristic (ROC) curve for SWE for CTD-ILD, and correlations between different assessment methods were analyzed. Results: Excellent intra- and inter-reliability of SWE measurements on the mid-anterior lung site of HCs (correlation coefficient >0.97; P<0.01) were found. The results of the lung ultrasound of case group participants were significantly higher than those of HCs at each site (P<0.001). The SWE results revealed a significant increase in both Emean and Cmean in CTD-ILD patients (P<0.001) compared with HCs at certain sites (P<0.001). The areas under the curve (AUC) of Emean and Cmean for CTD-ILD were 0.646 and 0.647 (P<0.05), respectively, and the cutoff values for Emean and Cmean to distinguish CTD-ILD from healthy lungs were 15.81 kPa and 2.31 m/s, respectively. There was no significant correlation between the SWE measured values and the number of B-lines, or the HRCT and PFT results, respectively (P>0.05). Conclusions: As a noninvasive ultrasound elastography (UE) technique, SWE may provide a novel method to differentiate CTD-ILD-affected lungs and healthy lungs. It is a reliable way to measure the stiffness of a healthy lung surface in the supine position. However, the ability of SWE to evaluate the severity of CTD-ILD may be limited.

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.

Quantitative evaluation of the Achilles tendon and supraspinatus tendon in end-stage kidney disease patients: A potential tool for predicting spontaneous tendon rupture.

Many cases of spontaneous tendon rupture in end-stage kidney disease (ESKD) patients have been reported worldwide. Quantitative assessment of tendon has become an important way to improve the prognosis of patients. In the recruited healthy volunteers and ESKD patients, the thickness and shear wave velocity (SWV) of supraspinatus tendons and Achilles tendons were measured and compared among groups. Potential factors related to the tendon SWV of ESKD patients were screened in multiple linear regression. There was no significant difference in the tendon thickness and supraspinatus tendon SWV among groups. SWV of Achilles tendons in long-term dialysis ESKD patients were significantly lower than those in healthy volunteers (5.1 vs. 5.6 m/s, p < 0.01). Ca2+ , creatinine, body mass index, and genders are the significant factors related to the tendon SWV. Shear wave elastography can be used as a potential tool for predicting spontaneous tendon rupture in ESKD patients.

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.

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 treatment efficacy in keloids using high-frequency ultrasound and shear wave elastography: a preliminary study.

The purpose of this study was to investigate the performance of high-frequency ultrasound (HFUS) and shear wave elastography (SWE) in the quantitative evaluation of therapeutic responses of keloids. 43 patients with 76 keloids were recruited into this study. In keloids and symmetrical sites, the skin thickness was measured using HFUS and skin stiffness expressed as elastic moduli (Young's modulus and shear wave velocity) was measured using SWE. The coefficient of variation values were calculated by using difference values of skin elastic moduli and skin thickness. A significant increase of both skin stiffness and thickness appeared in pre-treated keloids compared with post-treated keloids (P < 0.001) and normal controls (P < 0.001), respectively. Stiffness in post-treated keloids and normal skins was significantly different (P < 0.001), while the difference in thickness measurements showed no significance (P = 0.56, >0.05). The coefficient of variation of Young's modulus was the highest when compared between (i) pre-treated keloids and theirs site-matched areas; (ii) pre-treated and post-treated keloids. SWE, which showed greater ability in determining the extent of keloids recovery, may provide an ideal tool to assess the stiffness of keloids and theirs therapeutic response.