Diagnostic efficiency of conventional ultrasound, shear wave elastography, and superb microvascular imaging in evaluating ulnar neuropathy at the elbow.

INTRODUCTION/AIMS: The current diagnosis of ulnar neuropathy at the elbow (UNE) relies mainly on the clinical presentation and nerve electrodiagnostic (EDX) testing, which can be uncomfortable and yield false negatives. The aim of this study was to investigate the diagnostic value of conventional ultrasound, shear wave elastography (SWE), and superb microvascular imaging (SMI) in diagnosing UNE. METHODS: We enrolled 40 patients (48 elbows) with UNE and 48 healthy volunteers (48 elbows). The patients were categorized as having mild, moderate or severe UNE based on the findings of EDX testing. The cross-sectional area (CSA) was measured using conventional ultrasound. Ulnar nerve (UN) shear wave velocity (SWV) and SMI were performed in a longitudinal plane. RESULTS: Based on the EDX findings, UNE severity was graded as mild in 4, moderate in 10, and severe in 34. The patient group showed increased ulnar nerve CSA and stiffness at the site of maximal enlargement (CSA mean at the site of max enlargement [CSAmax] and SWV mean at the site of max enlargement [SWVmax]), ulnar nerve CSA ratio, and stiffness ratio (elbow-to-upper arm), compared with the control group (p < .001). Furthermore, the severe UNE group showed higher ulnar nerve CSAmax and SWVmax compared with the mild and moderate UNE groups (p < .001). The cutoff values for diagnosis of UNE were 9.5 mm2 for CSAmax, 3.06 m/s for SWVmax, 2.00 for CSA ratio, 1.36 for stiffness ratio, and grade 1 for SMI. DISCUSSION: Our findings suggest that SWE and SMI are valuable diagnostic tools for the diagnosis and assessment of severity of UNE.

Site-specific immobilization of Cysteinyl leukotriene receptor 1 through enzymatic DNA-protein conjugation strategy for lead screening.

Immobilization of functional protein, especially G protein-coupled receptors (GPCRs), is particularly significant in various fields such as the development of assays for diagnosis, lead compound screening, as well as drug-protein interaction analysis. However, there are still some challenges with the immobilized proteins such as undefined loads, orientations, and the loss of activity. Herein, we introduced a DNA conjugation strategy into the immobilization of Cysteinyl leukotriene receptor 1(CysLTR1) which enables exquisite molecular control and higher activity of the receptor. We used the bacterial relaxases VirD2 as an immobilized tag fused at the C terminus of CysLTR1. Tyrosine residue(Y29) at the core binding site of the VirD2 tag can react with the single-strand piece of DNA(T-DNA) in the form of a covalent bond. Inspired by this strategy, we developed a new immobilization method by mixing the T-DNA-modified silica gel with the cell lysate containing the expressed VirD2-tagged CysLTR1 for 1 hour. We found that the successful formation of DNA-protein conjugate enables the immobilization of CysLTR1 fast, site-specific, and with minimal loss of activity. The feasibility of the immobilized CysLTR1 was evaluated in drug-protein binding interaction by frontal analysis and adsorption energy distribution analysis. The binding of pranlukast, zafirlukast, and MK571 to the immobilized CysLTR1 was realized, and the association constants presented good agreement between the two methods. Rosmarinic acid was retained in the immobilized CysLTR1 column, and the in-vitro test revealed that the compound binds to the receptor in one type of binding site mode. Despite these results, we concluded that the DNA-protein conjugate strategy will probably open up the possibilities for capturing other functional proteins in covalent and site-specific modes from the complex matrices and the immobilized receptor preserves the potential in fishing out lead compounds from natural products.

Comparison of Angio PLanewave UltraSensitive and Power Doppler Ultrasound in Detecting Synovial Blood Flow in Wrist and Finger Joints of Rheumatoid Arthritis Patients.

RATIONALE AND OBJECTIVES: The purpose of this study is to conduct a comparison between the newly introduced Angio PLanewave UltraSensitive (AngioPLUS) method and the power Doppler ultrasound (PDUS) technique, evaluating the efficacy of these two methods in detecting synovial blood flow in wrist and finger joints of rheumatoid arthritis (RA) patients. Furthermore, the study aimed to investigate the potential associations between the observed blood flow patterns and various symptoms and indicators associated with RA. MATERIALS AND METHODS: A cohort of 101 patients diagnosed with RA was included and subsequently categorized into two groups: 20 male participants (19.80%) and 81 female participants (80.20%). Their grayscale ultrasound, PDUS, and AngioPLUS were utilized to acquire data, and subsequent scoring was conducted. Serological tests of the patients were also performed, and DAS28 scores were calculated. The McNemar and Wilcoxon tests were used to compare the blood flow display rate and grading of PDUS as well as AngioPLUS, respectively. RESULTS: AngioPLUS blood was significantly improved compared to PDUS. In all joints, the proportion of slight and significant improvement in wrist joints was the highest (14.11% and 1.98%, respectively). AngioPLUS was moderately correlated with C-reactive Protein (CRP), Disease Activity Score that includes 28-joint counts, and swollen joint counts and weakly correlated with platelet, hemoglobin, tender joint counts, and CRP before and after treatment. CONCLUSION: Compared to PDUS, AngioPLUS has a better auxiliary diagnostic role in evaluating disease activity and can provide a reference to improve the management of RA further.

Ultrasound-Targeted Microbubble Destruction: Modulation in the Tumor Microenvironment and Application in Tumor Immunotherapy.

Tumor immunotherapy has shown strong therapeutic potential for stimulating or reconstructing the immune system to control and kill tumor cells. It is a promising and effective anti-cancer treatment besides surgery, radiotherapy and chemotherapy. Presently, some immunotherapy methods have been approved for clinical application, and numerous others have demonstrated promising in vitro results and have entered clinical trial stages. Although immunotherapy has exhibited encouraging results in various cancer types, however, a large proportion of patients are limited from these benefits due to specific characteristics of the tumor microenvironment such as hypoxia, tumor vascular malformation and immune escape, and current limitations of immunotherapy such as off-target toxicity, insufficient drug penetration and accumulation and immune cell dysfunction. Ultrasound-target microbubble destruction (UTMD) treatment can help reduce immunotherapy-related adverse events. Using the ultrasonic cavitation effect of microstreaming, microjets and free radicals, UTMD can cause a series of changes in vascular endothelial cells, such as enhancing endothelial cells' permeability, increasing intracellular calcium levels, regulating gene expression, and stimulating nitric oxide synthase activities. These effects have been shown to promote drug penetration, enhance blood perfusion, increase drug delivery and induce tumor cell death. UTMD, in combination with immunotherapy, has been used to treat melanoma, non-small cell lung cancer, bladder cancer, and ovarian cancer. In this review, we summarized the effects of UTMD on tumor angiogenesis and immune microenvironment, and discussed the application and progress of UTMD in tumor immunotherapy.

Colony stimulating factor 1 receptor blockade improves the efficacy of chemotherapy against human neuroblastoma in the absence of T lymphocytes.

Tumor-associated macrophages can promote growth of cancers. In neuroblastoma, tumor-associated macrophages have greater frequency in metastatic versus loco-regional tumors, and higher expression of genes associated with macrophages helps to predict poor prognosis in the 60% of high-risk patients who have MYCN-non-amplified disease. The contribution of cytotoxic T-lymphocytes to anti-neuroblastoma immune responses may be limited by low MHC class I expression and low exonic mutation frequency. Therefore, we modelled human neuroblastoma in T-cell deficient mice to examine whether depletion of monocytes/macrophages from the neuroblastoma microenvironment by blockade of CSF-1R can improve the response to chemotherapy. In vitro, CSF-1 was released by neuroblastoma cells, and topotecan increased this release. In vivo, neuroblastomas formed by subcutaneous co-injection of human neuroblastoma cells and human monocytes into immunodeficient NOD/SCID mice had fewer human CD14+ and CD163+ cells and mouse F4/80+ cells after CSF-1R blockade. In subcutaneous or intra-renal models in immunodeficient NSG or NOD/SCID mice, CSF-1R blockade alone did not affect tumor growth or mouse survival. However, when combined with cyclophosphamide plus topotecan, the CSF-1R inhibitor BLZ945, either without or with anti-human and anti-mouse CSF-1 mAbs, inhibited neuroblastoma growth and synergistically improved mouse survival. These findings indicate that depletion of tumor-associated macrophages from neuroblastomas can be associated with increased chemotherapeutic efficacy without requiring a contribution from T-lymphocytes, suggesting the possibility that combination of CSF-1R blockade with chemotherapy might be effective in patients who have limited anti-tumor T-cell responses.