Nanocatalytic NO gas therapy against orthotopic oral squamous cell carcinoma by single iron atomic nanocatalysts.

Oral squamous cell carcinoma (OSCC) has been being one of the most malignant carcinomas featuring high metastatic and recurrence rates. The current OSCC treatment modalities in clinics severely deteriorate the quality of life of patients due to the impaired oral and maxillofacial functions. In the present work, we have engineered the single-atom Fe nanocatalysts (SAF NCs) with a NO donor (S-nitrosothiol, SNO) via surface modification to achieve synergistic nanocatalytic NO gas therapy against orthotopic OSCC. Upon near-infrared laser irradiation, the photonic hyperthermia could effectively augment the heterogeneous Fenton catalytic activity, meanwhile trigger the thermal decomposition of the engineered NO donor, thus producing toxic hydroxyl radicals (•OH) and antitumor therapeutic NO gas at tumor lesion simultaneously, and consequently inducing the apoptotic cell death of tumors via mitochondrial apoptosis pathway. This therapeutic paradigm presents an effective local OSCC therapeutics in a synergistic manner based on the nanocatalytic NO gas therapy, providing a promising antitumor modality with high biocompatibility.

In this work, we have engineered the NIR-triggered NO liberating donor module RSNO onto single-atom Fe nanocatalysts for synergized nanocatalytic therapy and NO gas therapy against orthotopic OSCC with high therapeutic selectivity, efficacy and biocompatibility.

Ultrasound Elastography Assessment of Knee Intra-Articular Adhesions at Varying Knee Angles.

We aimed to verify the feasibility of using shear wave elastography (SWE) to quantify knee scars and the elastic modulus of scar tissues. Overall, 16 participants underwent SWE assessments and range-of-motion measurement and completed the Knee Injury and Osteoarthritis Outcome Score. The inter-rater reliability for SWE in the suprapatellar bursa, below the patellar tendon, and in the medial and lateral trochlear groove remained within 0.861-0.907. The SWE values in the four regions increased with increasing knee angle, and significant differences were observed between the values for below the patellar tendon and the suprapatellar bursa at knee flexion angles of 60° and 90°. The SWE values of the medial and lateral trochlear groove at 30°, 60°, and 90° knee flexion were higher on the affected side. A negative correlation was observed between the SWE values for the lateral trochlear groove at 0°, 30°, and 60° and those for below the patellar tendon at 0° and the suprapatellar bursa at 30° with both active and passive knee extension. The suprapatellar bursa value at 60° exhibited a positive correlation with both knee flexion and passive knee flexion, whereas that of the suprapatellar bursa at 90° exhibited a positive correlation with both the range of motion and passive range of motion. SWE is a replicable and effective method for detecting scar strength in the knee joint.

NINJ1 Facilitates Abdominal Aortic Aneurysm Formation via Blocking TLR4-ANXA2 Interaction and Enhancing Macrophage Infiltration.

Abdominal aortic aneurysm (AAA) is a common and potentially life-threatening condition. Chronic aortic inflammation is closely associated with the pathogenesis of AAA. Nerve injury-induced protein 1 (NINJ1) is increasingly acknowledged as a significant regulator of the inflammatory process. However, the precise involvement of NINJ1 in AAA formation remains largely unexplored. The present study finds that the expression level of NINJ1 is elevated, along with the specific expression level in macrophages within human and angiotensin II (Ang II)-induced murine AAA lesions. Furthermore, Ninj1flox/flox and Ninj1flox/floxLyz2-Cre mice on an ApoE-/- background are generated, and macrophage NINJ1 deficiency inhibits AAA formation and reduces macrophage infiltration in mice infused with Ang II. Consistently, in vitro suppressing the expression level of NINJ1 in macrophages significantly restricts macrophage adhesion and migration, while attenuating macrophage pro-inflammatory responses. Bulk RNA-sequencing and pathway analysis uncover that NINJ1 can modulate macrophage infiltration through the TLR4/NF-κB/CCR2 signaling pathway. Protein-protein interaction analysis indicates that NINJ1 can activate TLR4 by competitively binding with ANXA2, an inhibitory interacting protein of TLR4. These findings reveal that NINJ1 can modulate AAA formation by promoting macrophage infiltration and pro-inflammatory responses, highlighting the potential of NINJ1 as a therapeutic target for AAA.

Conventional and contrast-enhanced ultrasound in the differential diagnosis of recurrent dermatofibrosarcoma protuberans and postoperative scar.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) has a high recurrence rate after resection. Because of the lack of specific manifestations, recurrent DFSP is easily misdiagnosed as post-resection scar. A few series have reported ultrasound findings of recurrent DFSP; moreover, the usefulness of contrast-enhanced ultrasound in differentiating recurrent DFSP has not been studied. OBJECTIVE: We investigated conventional and contrast-enhanced ultrasound in the differential diagnosis of recurrent DFSP and post-resection scar. METHODS: We retrospectively evaluated the findings of conventional and contrast-enhanced ultrasound in 34 cases of recurrent DFSP and 38 postoperative scars examined between January 2018 and December 2022. RESULTS: The depth and vascular density of recurrent DFSP were greater than those of postoperative scars (P < 0.05). On gray-scale ultrasound, recurrent DFSP lesions were more commonly irregular, heterogeneous, and hypoechoic, with finger-like projections and ill-defined borders. Postoperative scar was more likely to appear as hypoechoic and homogeneous with well-defined borders (P < 0.05). On color Doppler ultrasound, recurrent DFSP was more likely to feature rich arterial and venous blood flow, and postoperative scar was more likely to display poor blood flow (P < 0.05). On contrast-enhanced ultrasound, recurrent DFSP was more likely to feature heterogeneous hyper-enhancement, and postoperative scar was more likely to display homogeneous iso-enhancement (P < 0.05). Recurrent DFSP presented a higher peak and sharpness than postoperative scar (P < 0.05). CONCLUSION: Conventional and contrast-enhanced ultrasound produced distinct features of recurrent DFSP and post-resection scar, which could improve the accuracy of differential diagnosis.

Integrative multi-omics analyses reveal vesicle transport as a potential target for thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysm (TAA) refers to dilation and enlargement of the thoracic aorta caused by various reasons. Most patients have no apparent symptoms in the early stage and are subject to a poor prognosis once the aneurysm ruptures. It is crucial to identify individuals who are predisposed to TAA and to discover effective therapeutic targets for early intervention. METHODS: We conducted a label-free quantitative proteomic analysis among aorta tissue samples from TAA patients to screen differentially expressed proteins (DEPs) and key co-expression modules. Two datasets from Gene Expression Omnibus (GEO) database were included for integrative analysis, and the identified genes were subjected to immunohistochemistry (IHC) validation. Detailed vesicle transport related enrichment analysis was conducted and two FDA-approved drugs, chlorpromazine (CPZ) and chloroquine (CQ), were selected for in vivo inhibition of vesicle transport in mice TAA model. The diameter of thoracic aorta, mortality and histological differences after interventions were evaluated. RESULTS: We found significant enrichments in functions involved with vesicle transport, extracellular matrix organizing, and infection diseases in TAA. Endocytosis was the most essential vesicle transport process in TAA formation. Interventions with CPZ and CQ significantly reduced the aneurysm diameter and elastin degradation in vivo and enhanced the survival rates of TAA mice. CONCLUSIONS: We systematically screened the aberrantly regulated bioprocesses in TAA based on integrative multi-omics analyses, identified and demonstrated the importance of vesicle transport in the TAA formation. Our study provided pilot evidence that vesicular transport was a potential and promising target for the treatment of TAA.

Development and validation of a nomogram for identifying venous thromboembolism following oral and maxillofacial oncological surgery with simultaneous reconstruction.

OBJECTIVES: This study aimed to establish and validate a novel predictive model for venous thromboembolism (VTE) in patients undergoing oral and maxillofacial oncological surgery with simultaneous reconstruction. MATERIAL AND METHODS: A total of 372 patients were selected, and their demographic data, comorbidities, medical history, laboratory variables, postoperative Caprini scores, perioperative indicators, and procedures were recorded and analyzed to build the model. The predictive model is displayed as a nomogram. RESULTS: The incidence of VTE was 20.7% (77/372). Several factors were found to be significantly associated with VTE, including age (67 vs. 56 years, P < 0.001), preoperative level of D-dimer (0.56 vs. 0.36 mg/L, P < 0.001), proportion of female patients (46.8% vs. 33.6%, P = 0.032), hypertension (33.8% vs. 21%, P = 0.019). The predictive model was composed of age, gender, and preoperative D-dimer level, with good discriminative ability, as reflected by an area under the curve (AUC) of 0.756, the 95% confidence interval (CI) was 0.696-0.816. Moreover, it showed favorable diagnostic performance compared with both the 2005 (AUC 0.646, 95% CI = 0.578-0.714) and 2010 (AUC 0.627, 95% CI = 0.559-0.694) versions of the Caprini risk assessment model. For patients with malignant tumor, neoadjuvant chemotherapy was also an independent risk factor. CONCLUSIONS: This novel predictive model consists of three readily available clinical variables that show good diagnostic performance in predicting postoperative VTE.

Shear Wave Elastography for Assessment of Changes in Abdominal Soft Tissues after Lipoabdominoplasty.

BACKGROUND: The changes in the elasticity of the abdominal skin, subcutaneous tissues and muscles after lipoabdominoplasty are still unknown. The aim of this study was to provide an objective assessment of tissue elasticity after lipoabdominoplasty using ultrasound elastography. METHODS: A total of 21 female patients (31-41 years old) who underwent lipoabdominoplasty from Oct 2019 to Mar 2022 were included in this retrospective study. The elastography values of the skin, subcutaneous tissues and abdominal muscles were obtained with the ultrasound shear wave elasticity imaging system pre-operation (Pre) and 6 months post-operation (Post) at four different points. RESULTS: Twenty-one female patients were included. The elasticity of the abdominal skin, subcutaneous tissues, rectus abdominis and external oblique abdominis significantly increased at 6 months post-operation. The improvements in abdominal soft tissue elasticity were not uniform across the examined points. CONCLUSIONS: Significant changes in the elasticity of the abdominal skin, subcutaneous tissues and muscles were observed after lipoabdominoplasty. Ultrasound elastographic assessment was objective and feasible for evaluating the effect of lipoabdominoplasty on abdominal soft tissue. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Ultrasonography characteristics of cystic components in primary salivary gland tumors.

OBJECTIVES: The present study aimed to characterize the ultrasonography (US) features of cystic components in salivary gland tumors (SGTs). MATERIALS AND METHODS: A total of 207 patients (218 lesions) with pathologically confirmed primary SGTs were analyzed. Preoperative US revealed the presence of cystic components in lesions. Lesion size, shape, margin, and US findings of the cystic components, including number, distribution, margin, occupying rate, and internal characteristics, were evaluated. RESULTS: Similarities were observed between the US performance of benign SGTs (B-SGTs) and malignant SGTs (M-SGTs) with cystic components. Differences in sex and age of patients, number, distribution, and internal characteristics of cystic components were statistically significant. For SGTs with cystic components, the proportions of M-SGTs to ill-defined margins (P = 0.002), eccentric distribution (P = 0.019), and none of the internal characteristics (P = 0.019) were significantly higher than those of B-SGTs. Younger age (P = 0.001), eccentric distribution (P = 0.034) and ill-defined margin (P < 0.001) were risk factors for diagnosing M-SGTs. Cystic component features needed to be combined with lesion indicators (border and shape) to improve diagnostic sensitivity. CONCLUSIONS: US features of the B-SGTs and M-SGTs were significantly different. Cystic component is of interest in the US-related differential diagnosis of B-SGT and M-SGT. CLINICAL RELEVANCE: Cystic components are potentially valuable in the differential diagnosis of B-SGTs and M-SGTs on US.

Diagnostic value of shear wave elastography quantification combined with conventional ultrasound in salivary gland tumors.

Background: The histopathological classification of salivary gland tumors is extremely complex. The imaging manifestations of some tumors are nonspecific. It is particularly important to improve the value of ultrasound in the diagnosis of salivary gland tumors. This study aimed to analyze the diagnostic value of different parameters of shear wave elastography (SWE) in the quantitative diagnosis of salivary gland tumors, and to evaluate the value of SWE combined with conventional ultrasound. Methods: The study was conducted retrospectively. Patients who underwent salivary gland tumor resection from April 2021 to November 2022 in the Ninth People's Hospital, Shanghai Jiaotong University School of Medicine were randomly recruited to the study. A total of 305 masses were divided into an elastography group (150 cases) and a control group (155 cases). The control group underwent conventional ultrasonography, whereas the elastography group underwent conventional ultrasonography and elastography. The Young's modulus E of the mass was quantitatively measured in the elastography group, including maximum cross-sectional area (S), maximum Young's modulus (Emax), mean Young's modulus (Emean), and Young's modulus standard deviation (SD). Pathologic diagnosis was used as the reference standard to determine the cut-off of shear wave elastography of salivary gland tumors, and the diagnostic performance of the 2 groups was compared. Results: In the elastography group, the diagnostic value of Emax·S (the product of the maximum Young's modulus of the mass and the maximum cross-sectional area of the mass) in the differential diagnosis of malignant tumors (MT) and non-malignant tumors (NMT) was the highest, with a sensitivity and specificity of 72.0% and 80.0%, respectively. The diagnostic value of Emax/D (the quotient of the maximum Young's modulus of the mass and the maximum diameter of the mass) in the differential diagnosis of pleomorphic adenoma (PA) and adenolymphoma (AL) was the highest, with a sensitivity and specificity of 62.3% and 82.4%, respectively. The receiver operating characteristic (ROC) curves for the diagnosis of salivary gland tumors were compared between the elastography group and the control group. The area under the curve (AUC) of the elastography group was 0.915, the sensitivity, specificity, and Youden index were 84.0%, 88.0%, and 0.720, respectively. The AUC of the control group was 0.906, the sensitivity, specificity, and Youden index were 76.0%, 90.0%, and 0.660, respectively, which is the main finding of the study. Conclusions: SWE can be used as a complementary method for the diagnosis of salivary gland tumors, which has certain value in improving the diagnostic performance. As a result, the sensitivity is improved but the specificity is worsened by addition of SWE to B-mode ultrasound and color Doppler flow imaging (CDFI).

The effect of thickness and elastic modulus of the anterior talofibular ligament on anterior ankle joint stiffness: A subject-specific finite element study.

Ankle sprain is a frequent type of sports injury leading to lateral ligament injury. The anterior talofibular ligament (ATFL) is a primary ligamentous stabilizer of the ankle joint and typically the most vulnerable ligament injured in a lateral ankle sprain (LAS). This study aimed to quantitively investigate the effect of the thickness and elastic modulus of ATFL on anterior ankle joint stiffness (AAJS) by developing nine subject-specific finite element (FE) models under acute injury, chronic injury, and control conditions of ATFL. A 120 N forward force was applied at the posterior calcaneus leading to an anterior translation of the calcaneus and talus to simulate the anterior drawer test (ADT). In the results, the ratio of the forward force to the talar displacement was used to assess the AAJS, which increased by 5.85% in the acute group and decreased by 19.78% in the chronic group, compared to those of the control group. An empirical equation described the relationship between AAJS, thickness, and elastic modulus (R-square 0.98). The equation proposed in this study provided an approach to quantify AAJS and revealed the effect of the thickness and the elastic modulus of ATFL on ankle stability, which may shed light on the potential diagnosis of lateral ligament injury.