Value of Conventional Ultrasound-based Scoring System in Distinguishing Adenomatous Polyps From Cholesterol Polyps.

BACKGROUND AND AIM: Ultrasound has increased the detection of gallbladder polyps, but it has limitations in evaluating the nature of gallbladder polyps, especially the maximum size of 1.0 to 1.5 cm. We assessed the value of ultrasound scoring system based on independent predictive parameters in distinguishing adenomatous polyps from cholesterol polyps with the maximum size of 1.0 to 1.5 cm. MATERIALS AND METHODS: We enrolled 163 patients with gallbladder polyps (1.0 to 1.5 cm) who underwent ultrasonography and cholecystectomy. Ultrasound image characteristics were compared between cholesterol polyps and adenomatous polyps in the training cohort from April 2018 to January 2020. An ultrasound scoring system was constructed in the training cohort, and its diagnostic performance was evaluated in the validation cohort from February 2020 to February 2021. RESULTS: Maximum size, height/width ratio, stone or sludge, vascularity, and hyperechoic spot were significantly different between cholesterol polyps and adenomatous polyps in the training cohort ( P <0.05). The independent predictive parameters for adenomatous polyps were lower height/width ratio, presence of vascularity and absence of hyperechoic spot. The total score was as follows: (height/width ratio, <0.9=4, ≥0.9=0) + (vascularity, present=3, absent=0) + (hyperechoic spot, absent=2, present=0). The sensitivity, specificity and accuracy of ultrasound scoring system ≥5 for diagnosis of adenomatous polyps in the validation cohort were 73.33%, 80.49%, and 78.57%, respectively. CONCLUSIONS: The ultrasound scoring system aids in distinguishing adenomatous polyps from cholesterol polyps, and effectively decreasing unnecessary cholecystectomy.

Value of high frame rate contrast-enhanced ultrasound in distinguishing gallbladder adenoma from cholesterol polyp lesion.

OBJECTIVES: To compare the diagnostic value of high frame rate contrast-enhanced ultrasound (H-CEUS) in distinguishing gallbladder adenomas from cholesterol polyp lesions with that of CEUS. METHODS: This study enrolled 94 patients with gallbladder polyp lesions (GPLs) who underwent laparoscopic cholecystectomy. CEUS and H-CEUS were performed before surgery. The perfusion features of GPLs and the final diagnosis as determined by both technologies were compared. RESULTS: There were differences in vascular types between gallbladder adenomas and cholesterol polyp lesions observed on H-CEUS (p < 0.05), while there were no differences in vascular types between gallbladder adenomas and cholesterol polyp lesions observed on CEUS (p > 0.05). In the cholesterol polyp lesion group, there were no differences in vascular types between CEUS and H-CEUS (p > 0.05), while the vascular types were different between CEUS and H-CEUS in the gallbladder adenoma group (p < 0.05). The diagnostic value of H-CEUS in distinguishing gallbladder adenomas from cholesterol polyp lesions was better than that of CEUS. CONCLUSIONS: H-CEUS improved the time resolution by increasing the frame rate, which helped to accurately reflect the difference in the microcirculation of GPLs and improved the ability of a differential diagnosis between cholesterol polyp lesions and adenomas. H-CUES may provide an effective means of imaging for patients with GPLs regarding the choice of treatment options. KEY POINTS: • High frame rate CEUS improves the time resolution of CEUS by increasing the frame rate. • High frame rate CEUS is helpful to accurately evaluate the microvascular morphology of a gallbladder polyp lesion in the arterial phase. • High frame rate CEUS helps patients with gallbladder polyp lesions to choose the appropriate treatment means.

[Value of Contrast-enhanced Ultrasound in Differential Diagnosis between Cholesterol Polyp and Gallbladder Adenoma].

Objective To compare the performance of contrast-enhanced ultrasound(CEUS)and ultrasound(US)in the differential diagnosis between cholesterol polyps and gallbladder adenomas. Methods A total of 136 patients with gallbladder polyp lesions(GPLs)and undergoing cholecystectomy in the First Medical Center of Chinese PLA General Hospital from January 2019 to October 2020 were retrospectively analyzed.All the patients underwent US and CEUS examinations before cholecystectomy.US and CEUS images of cholesterol polyps and gallbladder adenomas were compared for the evaluation of the performance of CEUS in the diagnosis of gallbladder adenomas. Results The 136 cases of GPLs included 95 cases of cholesterol polyps and 41 cases of gallbladder adenomas.Cholesterol polyps and gallbladder adenomas showed significant differences in the maximum size of GPLs( Z=-5.189, P<0.001), polyp blood flow signal(χ 2=33.630, P<0.001), vascular stalk width(Z=-7.366, P<0.001), polyp enhancement time(χ 2=22.487, P<0.001), enhancement intensity in arterial phase(χ 2=44.371, P<0.001), polyp vascular morphology(χ 2=53.814, P<0.001)and gallbladder wall integrity(χ 2=13.277, P=0.001).The sensitivity, specificity and accuracy of CEUS in distinguishing gallbladder adenomas from cholesterol polyps were 85.37%, 89.47% and 88.24%, respectively, and the area under the curve was 0.874. Conclusion CEUS can effectively distinguish gallbladder adenomas from cholesterol polyps and help patients with GPLs to select the appropriate treatment.

Efficacy evaluation and mechanism study on inhibition of breast cancer cell growth by multimodal targeted nanobubbles carrying AMD070 and ICG.

To construct targeted nanobubbles carrying both small-molecule CXCR4 antagonist AMD070 and light-absorbing material indocyanine green (ICG), and to study their in vitro multimodal imaging, as well as their mechanism and efficacy of inhibition of breast cancer cell growth. Nanobubbles carrying AMD070 and ICG (ICG-TNBs) were constructed by carbodiimide reaction and mechanical oscillation. The physical characteristics and in vitro multimodal imaging were determined. The binding potential of ICG-TNBs to human breast cancer cells were observed by laser confocal microscopy. CCK-8 and flow cytometry were used to analyze the role of ICG-TNBs + US in inhibiting proliferation and inducing apoptosis of tumor cells. Flow cytometry and Western blotting are used to analyse the ROS generation and molecular mechanisms. ICG-TNBs had a particle size of 497.0 ± 29.2 nm and a Zeta potential of -8.05 ± 0.73 mV. In vitro multimodal imaging showed that the image signal intensity of ICG-TNBs increased with concentration. Targeted binding assay confirmed that ICG-TNBs could specifically bind to MCF-7 cells (CXCR4 positive), but not to MDA-MB-468 cells (CXCR4 negative). CCK-8 assay and flow cytometry analysis showed that ICG-TNBs + US could significantly inhibit the growth of MCF-7 breast cancer cells and promote their apoptosis. Flow cytometry and Western blotting showed that ICG-TNBs + US could significantly raise generation of ROS, reduce the expression of CXCR4, inhibit phosphorylation of Akt, and increase the expression of Caspase3 and Cleaved-caspase3. This indicated that ICG-TNBs could effectively inhibit and block the SDF-1/CXCR4 pathway, thus leading to the apoptosis of MCF-7 cells. ICG-TNBs can specifically bind to CXCR4 positive breast cancer cells, furthermore inhibit growth and promote apoptosis of breast cancer cells combined with ultrasonic irradiation by blocking the SDF-1/CXCR4 pathway. This study introduces a novel concept, method and mechanism for integration of targeted diagnosis and treatment of breast cancer.

Anti-G250 nanobody-functionalized nanobubbles targeting renal cell carcinoma cells for ultrasound molecular imaging.

Traditional imaging examinations have difficulty in identifying benign and malignant changes in renal masses. This difficulty may be solved by ultrasound molecular imaging based on targeted nanobubbles, which could specifically enhance the ultrasound imaging of renal cell carcinomas (RCC) so as to discriminate benign and malignant renal masses. In this study, we aimed to prepare anti-G250 nanobody-functionalized targeted nanobubbles (anti-G250 NTNs) by coupling anti-G250 nanobodies to lipid nanobubbles and to verify their target specificity and binding ability to RCC cells that express G250 antigen and their capacity to enhance ultrasound imaging of RCC xenografts. Anti-G250 nanobodies were coupled to the lipid nanobubbles using the biotin-streptavidin bridge method. The average particle diameter of the prepared anti-G250 NTNs was 446 nm. Immunofluorescence confirmed that anti-G250 nanobodies were uniformly distributed on the surfaces of nanobubbles. In vitro experiments showed that the anti-G250 NTNs specifically bound to G250-positive 786-O cells and HeLa cells with affinities of 88.13% ± 4.37% and 71.8% ± 5.7%, respectively, and that they did not bind to G250-negative ACHN cells. The anti-G250 NTNs could significantly enhance the ultrasound imaging of xenograft tumors arising from 786-O cells and HeLa cells compared with blank nanobubbles, while the enhancement was not significant for xenograft tumors arising from ACHN cells. Immunofluorescence of tumor tissue slices confirmed that the anti-G250 NTNs could enter the tissue space through tumor blood vessels and bind to tumor cells specifically. In conclusion, anti-G250 nanobody-functionalized targeted nanobubbles could specifically bind to G250-positive RCC cells and enhance the ultrasound imaging of G250-positive RCC xenografts. This study has high-potential clinical application value for the diagnosis and differential diagnosis of renal tumors.

Multifunctional nanobubbles carrying indocyanine green and paclitaxel for molecular imaging and the treatment of prostate cancer.

BACKGROUND: Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and resolution, thereby enabling rapid, direct measurements and the tracking of tumour growth and metastasis. Moreover, ultrasound-targeted nanobubble destruction (UTND) provides an effective way to deliver drugs, effectively increasing the content of the drug in the tumour area and reducing potential side effects, thereby successfully contributing to the treatment of tumours. RESULTS: In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs) and studied their applications in ultrasound imaging of prostate cancer as well as their therapeutic effects on prostate cancer when combined with UTND. ICG-PTX NBs were prepared by the mechanical oscillation method. The particle size and zeta potential of the ICG-PTX NBs were 469.5 ± 32.87 nm and - 21.70 ± 1.22 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 2.52%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging, including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect was positively correlated with their concentration. The imaging effects of tumour xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumour xenografts in vivo, the ICG-PTX NBs + US group showed more significant inhibition of cell proliferation and the promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs and the ICG-PTX NBs + US groups were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organs showed no obvious abnormalities in the ICG-PTX NBs and the ICG-PTX NBs + US groups. CONCLUSIONS: ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent that can achieve multimodal imaging, including ultrasound, fluorescence and photoacoustic imaging, and can succeed in the local treatment of prostate cancer providing a potential novel method for integrated research on prostate cancer diagnosis and treatment.

Omethoate treatment mitigates high salt stress inhibited maize seed germination.

Omethoate (OM) is a highly toxic organophophate insecticide, which is resistant to biodegradation in the environment and is widely used for pest control in agriculture. The effect of OM on maize seed germination was evaluated under salt stress. Salt (800mM) greatly reduced germination of maize seed and this could be reversed by OM. Additionally, H2O2 treatment further improved the effect of OM on seed germination. Higher H2O2 content was measured in OM treated seed compared to those with salt stress alone. Dimethylthiourea (DTMU), a specific scavenger of reactive oxygen species (ROS), inhibited the effect of OM on seed germination, as did IMZ (imidazole), an inhibitor of NADPH oxidase. Abscisic acid (ABA) inhibited the effect of OM on seed germination, whereas fluridone, a specific inhibitor of ABA biosynthesis, enhanced the effect of OM. Taken together, these findings suggest a role of ROS and ABA in the promotion of maize seed germination by OM under salt stress.

Downregulation of miR-493 promoted melanoma proliferation by suppressing IRS4 expression.

Accumulating evidence indicated that aberrantly expressed microRNAs play critical roles in the initiation and progression of human cancers. However, the underlying functions of miR-493 in human melanoma remains unknown. Here, our study found that miR-493 expression was downregulated in human melanoma tissues and cells. Overexpression of miR-493 suppressed cell proliferation and cell cycle in human melanoma cell line A375. IRS4 was defined as a target for downregulation by miR-493 and was confirmed by luciferase assay. We also found that knockdown of IRS4 counteracted the proliferation promotion by miR-493 inhibitor. In summary, these results demonstrated that miR-493 acts as a tumor suppressor and inhibits cell proliferation and cell cycle in human melanoma by directly targeting IRS4.

Construction of ultrasonic nanobubbles carrying CAIX polypeptides to target carcinoma cells derived from various organs.

BACKGROUND: Ultrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents. However, available targeted ultrasound contrast agents for molecular imaging of tumors are only achieving imaging in blood pool or one type tumor. No targeted ultrasound contrast agents have realized targeted ultrasound molecular imaging of tumor parenchymal cells in a variety of solid tumors so far. Carbonic anhydrase IX (CAIX) is highly expressed on cell membranes of various malignant solid tumors, so it's a good target for ultrasound molecular imaging. Here, targeted nanobubbles carrying CAIX polypeptides for targeted binding to a variety of malignant tumors were constructed, and targeted binding ability and ultrasound imaging effect in different types of tumors were evaluated. RESULTS: The mean diameter of lipid targeted nanobubbles was (503.7 ± 78.47) nm, and the polypeptides evenly distributed on the surfaces of targeted nanobubbles, which possessed the advantages of homogenous particle size, high stability, and good safety. Targeted nanobubbles could gather around CAIX-positive cells (786-O and Hela cells), while they cannot gather around CAIX-negative cells (BxPC-3 cells) in vitro, and the affinity of targeted nanobubbles to CAIX-positive cells were significantly higher than that to CAIX-negative cells (P < 0.05). Peak intensity and duration time of targeted nanobubbles and blank nanobubbles were different in CAIX-positive transplanted tumor tissues in vivo (P < 0.05). Moreover, targeted nanobubbles in CAIX-positive transplanted tumor tissues produced higher peak intensity and longer duration time than those in CAIX-negative transplanted tumor tissues (P < 0.05). Finally, immunofluorescence not only confirmed targeted nanobubbles could pass through blood vessels to enter in tumor tissue spaces, but also clarified imaging differences of targeted nanobubbles in different types of transplanted tumor tissues. CONCLUSIONS: Targeted nanobubbles carrying CAIX polypeptides can specifically enhance ultrasound imaging in CAIX-positive transplanted tumor tissues and could potentially be used in early diagnosis of a variety of solid tumors derived from various organs.

RUNX3 expression is associated with sensitivity to pheophorbide a-based photodynamic therapy in keloids.

Runt-related transcription factor 3 (RUNX3) has recently been reported to be a possible predictor of sensitivity of cancer cells for photodynamic therapy (PDT), a promising therapeutic modality for keloids. In this study, we aimed to elucidate the implications of RUNX3 for keloid pathogenesis and sensitivity to pheophorbide a-based PDT (Pa-PDT). RUNX3 and proliferating cell nuclear antigen (PCNA) expression were examined in 6 normal skin samples and 32 keloid tissue samples by immunohistochemistry. We found that RUNX3 expression was detected more often in keloid tissues than in dermis of normal skin. In keloid tissues, RUNX3 expression was significantly increased in patients presenting with symptoms of pain or pruritus, and was also significantly related to PCNA expression. The therapeutic effect of Pa-PDT was comparatively investigated in keloid fibroblasts (KFs) with and without RUNX3 expression. Significant differences were found after Pa-PDT between KFs with and without RUNX3 expression in cell viability, proliferative ability, type I collagen expression, generation of reactive oxygen species (ROS), and apoptotic cell death. In addition, RUNX3 expression was significantly decreased after Pa-PDT in KFs, and KFs with downregulation of RUNX3 showed significantly increased cell viability after Pa-PDT. Pa-PDT may be a potential therapeutic modality for keloids, and RUNX3, as a possible contributor to keloid pathogenesis, may improve sensitivity to Pa-PDT in KFs.

Apoptotic effect of pheophorbide a-mediated photodynamic therapy on DMBA/TPA-induced mouse papillomas.

Pheophorbide a (Pa) is a chlorine-based photosensitizer, and Pa-mediated photodynamic therapy (PDT) reportedly exhibits antitumor activity against various malignancies. The aim of our study was to investigate the therapeutic effect of Pa-mediated PDT on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorobol-13-acetate (TPA)-induced mouse papillomas. Thirty mice received a topical application of DMBA/TPA on their backs to induce mouse papillomas. One week after two sessions of Pa-mediated PDT, immunohistochemical stains and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate the apoptotic effects thereof on the papillomas. Among 63 mouse papillomas treated with Pa-mediated PDT, 17.5% of the lesions were completely removed 1 week after the first treatment, while 31.7% disappeared 1 week after the second treatment. Statistical analyses revealed significant differences in therapeutic outcomes for the Pa-mediated PDT group in comparison to a solvent-PDT group and a Pa group. Additionally, a marked downregulation of proliferating cell nuclear antigen expression, as well as upregulation of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerase expression, was noted in the Pa-PDT group, compared to the solvent-PDT group and Pa group. TUNEL assay revealed higher apoptotic cell counts in the Pa-PDT group, although the difference was not statistically significant. Our data demonstrated that Pa-mediated PDT is effective in treating DMBA/TPA-induced mouse papillomas.

The therapeutic effect of Picroside II in renal ischemia-reperfusion induced acute kidney injury: An experimental study.

The microcirculation hemodynamics change and inflammatory response are the two main pathophysiological mechanisms of renal ischemia-reperfusion injury (IRI) induced acute kidney injury (AKI). The treatment of microcirculation hemodynamics and inflammatory response can effectively alleviate renal injury and correct renal function. Picroside II (P II) has a wide range of pharmacological effects. Still, there are few studies on protecting IRI-AKI, and whether P II can improve renal microcirculation perfusion is still being determined. This study aims to explore the protective effect of P II on IRI-AKI and evaluate its ability to enhance renal microcirculation perfusion. In this study, a bilateral renal IRI-AKI model in mice was established, and the changes in renal microcirculation and inflammatory response were quantitatively evaluated before and after P II intervention by contrast-enhanced ultrasound (CEUS). At the same time, serum and tissue markers were measured to assess the changes in renal function. The results showed that after P II intervention, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), serum cystatin C (Cys-C), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as the time-to-peak (TTP), peak intensity (PI) and area under the curve (AUC), and the normalized intensity difference (NID) were all alleviated. In conclusion, P II can improve renal microcirculation perfusion changes caused by IRI-AKI, reduce inflammatory reactions during AKI, and enhance renal antioxidant stress capacity. P II may be a new and promising drug for treating IRI-AKI.

Value of high frame rate contrast enhanced ultrasound in gallbladder wall thickening in non-acute setting.

BACKGROUND: Ultrasound (US) has been widely used in screening and differential diagnosis of gallbladder wall thickening (GWT). However, the sensitivity and specificity for diagnosing wall-thickening type gallbladder cancer are limited, leading to delayed treatment or overtreatment. We aim to explore the value of high frame rate contrast enhanced ultrasound (H-CEUS) in distinguishing wall-thickening type gallbladder cancer (malignant) from GWT mimicking malignancy (benign). METHODS: This retrospective study enrolled consecutive patients with non-acute GWT who underwent US and H-CEUS examination before cholecystectomy. Clinical information, US image and H-CEUS image characteristics between malignant and benign GWT were compared. The independent risk factors for malignant GWT on H-CEUS images were selected by multivariate logistic regression analysis. The diagnostic performance of H-CEUS in determining malignant GWT was compared with that of the gallbladder reporting and data system (GB-RADS) score. RESULTS: Forty-six patients included 30 benign GWTs and 16 malignant GWTs. Only mural layering and interface with liver on US images were significantly different between malignant and benign GWT (P < 0.05). Differences in enhancement direction, vascular morphology, serous layer continuity, wash-out time and mural layering in the venous phase of GWT on H-CEUS images were significant between malignant and benign GWT (P < 0.05). The sensitivity, specificity and accuracy of H-CEUS based on enhancement direction, vascular morphology and wash-out time in the diagnosis of malignant GWT were 93.75%, 90.00%, and 91.30%, respectively. However, the sensitivity, specificity and accuracy of the GB-RADS score were only 68.75%, 73.33% and 71.74%, respectively. The area under ROC curve (AUC) of H-CEUS was significantly higher than that of the GB-RADS score (AUC = 0.965 vs. 0.756). CONCLUSIONS: H-CEUS can accurately detect enhancement direction, vascular morphology and wash-out time of GWT, with a higher diagnostic performance than the GB-RADS score in determining wall-thickening type gallbladder cancer. This study provides a novel imaging means with high accuracy for the diagnosis of wall-thickening type gallbladder cancer, thus may be better avoiding delayed treatment or overtreatment.

Value of Micro Flow Imaging in the Prediction of Adenomatous Polyps.

OBJECTIVE: The aim of this study was to assess the value of micro flow imaging (MFI) in distinguishing adenomatous polyps from cholesterol polyps. METHODS: A total of 143 patients who underwent cholecystectomy for gallbladder polyps were retrospectively analyzed. B-mode ultrasound (BUS), color Doppler flow imaging (CDFI), MFI and contrast-enhanced ultrasound (CEUS) were performed before cholecystectomy. The weighted kappa consistency test was used to evaluate the agreement of vascular morphology among CDFI, MFI and CEUS. Ultrasound image characteristics, including BUS, CDFI and MFI images, were compared between adenomatous polyps and cholesterol polyps. The independent risk factors for adenomatous polyps were selected. The diagnostic performance of MFI combined with BUS in determining adenomatous polyps was compared with CDFI combined with BUS. RESULTS: Of the 143 patients, 113 cases were cholesterol polyps, and 30 cases were adenomatous polyps. The vascular morphology of gallbladder polyps was more clearly depicted by MFI than CDFI, and it had better agreement with CEUS. Differences in maximum size, height/width ratio, hyperechoic spot and vascular intensity on CDFI and MFI images were significant between adenomatous polyps and cholesterol polyps (p < 0.05). The maximum size, height/width ratio, and vascular intensity on MFI images were independent risk factors for adenomatous polyps. For MFI combined with BUS, sensitivity, specificity and accuracy were 90.00%, 94.69% and 93.70%, respectively. Area under the receiver operating characteristic curve (AUC) of MFI combined with BUS was significantly higher than that of CDFI combined with BUS (AUC = 0.923 vs. 0.784). CONCLUSION: Compared with CDFI combined with BUS, MFI combined with BUS had higher diagnostic performance in determining adenomatous polyps.

Contrast-enhanced ultrasound in evaluating the severity of acute kidney injury: An animal experimental study.

PURPOSE: Early assessment of the severity of acute kidney injury (AKI) is critical to the prognosis of patients. Renal microcirculation hemodynamic changes and inflammatory response are the essential links of AKI induced by ischemia-reperfusion injury (IRI). This study aims to explore the value of contrast-enhanced ultrasound (CEUS) based on vascular cell adhesion molecule-1 (VCAM-1) targeted microbubbles (TM) in evaluating the renal microcirculation hemodynamics and inflammatory response of different severity of AKI. METHODS: Eighteen male C57BL/6J mice were randomly divided into three groups (n = 6): sham operation (sham) group, mild IRI-AKI (m-AKI) group, and severe IRI-AKI (s-AKI) group. CEUS based on VCAM-1 TM was used to evaluate renal microcirculation perfusion and inflammatory response. Pearson's correlation was used to analyze the correlation between ultrasonic variables and pro-inflammatory factors. RESULTS: Compared with the sham group, AUC in m-AKI and s-AKI groups was significantly decreased, and s-AKI group was lower than m-AKI group (P < 0.05). NID of m-AKI and s-AKI groups was significantly higher than that of the sham group, and s-AKI group was higher than that of m-AKI group (P < 0.05). There was a linear positive correlation between NID and VCAM-1 protein expression (r = 0.7384, P < 0.05). NID and AUC were correlated with TNF-α and IL-6 levels (P < 0.05). Compared with early AKI biomarkers, CEUS based on VCAM-1 TM has higher sensitivity in evaluating the severity of AKI. CONCLUSIONS: CEUS based on VCAM-1 TM can evaluate renal microcirculation perfusion and inflammatory response in mild and severe AKI, which may provide helpful information for assessing the severity of AKI.

The effects of Spinosad on zebrafish larvae and THP-1 cells: Associated with immune cell damage and NF-kappa B signaling pathway activation.

Spinosad is a highly effective macrolide insecticide with a wide range of applications. However, few studies have been reported on the effects of Spinosad on immune cells. The immune system is an important line of defense in the human body and plays an important role in maintaining the normal functioning of the organism. Meanwhile, macrophages, neutrophils and Thymic T cells are an important component of the immune system. We studied the immunotoxicity of Spinosad using zebrafish and THP-1 cells. In vivo, Spinosad (0-20 µM) did not cause developmental toxicity in zebrafish, but induced damage to immune cells. In vitro, Spinosad (0-20 µM) inhibited THP-1 cells viability and induced mitochondrial damage and oxidative stress production. In further studies, it impaired phagocytosis of THP-1 cells and interfered with lipid metabolism. In addition, we found that Spinosad can promote the formation of the inflammatory body NLRP3 (NLR family, pyrin domain-containing 3) and activate the NF-kappa B (NF-κB) signaling pathway. These results suggest that Spinosad has a potential risk for inducing immunotoxicity. This study has drawn attention to Spinosad-induced immunotoxicity.

A New Perspective for Predicting the Therapeutic Success of RFA in Solid BTNs: Quantitative Initial RFA Ratio by Contrast-Enhanced Ultrasound.

Objective: The short-term therapeutic success of radiofrequency ablation (RFA) in solid benign thyroid nodules is of great concern. The aim of this study was to investigate a new method, initial radiofrequency ablative ratio (IRAR) using contrast-enhanced ultrasound (CEUS), for predicting therapeutic success of RFA in solid benign thyroid nodules (BTNs) immediately and effectively after RFA. Methods: A total of 813 nodules in 776 patients with benign thyroid nodules were treated with RFA from January 2014 to August 2018, among which 120 patients (M:F=41:79) with 120 solid BTNs (small: ≤10ml, n=57; medium: 10-30ml, n=42; large: >30ml, n=21) were enrolled in our study according to the inclusion criteria. The IRAR was defined as the ablative volume ratio immediately after RFA displayed by CEUS. The therapeutic success was evaluated at the 6-month follow-up. The relationship between the IRAR and volume reduction ratio (VRR) at 6-month was analyzed. The marginal regrowth of solid BTNs was also examined by CEUS at the 6 and 12 months of follow-up. Results: In medium and large nodules, the IRAR was significantly and positively correlated with VRR (r= 0.69, P < 0.001) at 6 months after RFA. There was a tendency to achieve therapeutic success (50% VRR: 55/63, 87.3%) when the IRAR exceeded 75%, and marginal regrowth was also relatively slow within 12 months after a single session treatment. No significant correlation between IRAR and VRR of small nodules was found. In conclusion, IRAR is significantly and positively correlated with VRR, which may indicate therapeutic success when it exceeds 75%. Conclusions: CEUS can be used to accurately quantify the IRAR, which is positively correlated with the VRR. Moreover, the IRAR may be used as a parameter to predict the short-term therapeutic success of RFA in solid BTNs.

Quantitative Analysis of Renal Perfusion in Rhabdomyolysis-Induced Acute Kidney Injury Using Contrast-Enhanced Ultrasound: An Experimental Study.

The aim of this study was to evaluate renal perfusion changes in rats with acute kidney injury induced by rhabdomyolysis, using quantitative parameters obtained with contrast-enhanced ultrasound (CEUS). Sprague-Dawley (SD) rats were randomly divided into an experimental group (n = 40) and a control group (n = 20). Each group was further divided into four subgroups (0.5-, 6-, 24- and 72-h groups). Time-intensity curves and related quantitative parameters of the renal cortex and medulla were obtained by CEUS, and the contrast characteristics analyzed for different time points. In the experimental group, the CEUS quantitative parameters for the renal medulla of time to peak (TTP), descending time/2 (DT/2) and area under the curve (AUC) increased, whereas ascending slope (AS) and descending slope (DS) decreased. Similarly, renal cortical AS, DS and AUC in the experimental group differed significantly from those in the control group. With respect to the CEUS quantitative parameters for the renal cortex, AUC increased, and AS and DS decreased. These parameters differed significantly between the experimental and control groups. CEUS is sensitive to change in renal perfusion in rhabdomyolysis-induced acute kidney injury and, thus, has diagnostic value.