Associations of plaque morphology and location with Intraplaque neovascularization in the carotid artery by contrast-enhanced ultrasound imaging.

Objective: Intraplaque neovascularization (IPN) is a known indicator of plaque vulnerability, and is thus considered a predictor of stroke. The morphology and location of the carotid plaque may be correlated with plaque vulnerability. Therefore, our study aimed to examine the associations of carotid plaque morphology and location with IPN. Methods: A total of 141 patients with carotid atherosclerosis (mean age, 64.99 ± 10.96 years) who underwent carotid contrast-enhanced ultrasound (CEUS) between November 2021 and March 2022 were retrospectively analyzed. IPN was graded according to the presence and location of microbubbles within the plaque. The association of IPN grade with carotid plaque morphology and location was evaluated using ordered logistic regression. Results: Of the 171 plaques, 89 (52%) were IPN Grade 0, 21 (12.2%) were Grade 1, and 61 (35.6%) were Grade 2. IPN grade significantly associated with both plaque morphology and location, with higher grades observed among Type III morphology and common carotid artery plaques. Significant negative association was further shown between IPN grade and serum high-density lipoprotein cholesterol (HDL-C) level. Plaque morphology and location, and HDL-C remained significantly associated with IPN grade after adjusting for confounding factors. Conclusion: The location and morphology of carotid plaques were significantly associated with the IPN grade on CEUS, and therefore show potential as biomarkers for plaque vulnerability. Serum HDL-C was also identified as a protective factor against IPN, and may play a role in the management of carotid atherosclerosis. Our study provided a potential strategy for identification of vulnerable carotid plaques and elucidated the important imaging predictors of stroke.

Manganese-enriched photonic/catalytic nanomedicine augments synergistic anti-TNBC photothermal/nanocatalytic/immuno-therapy via activating cGAS-STING pathway.

As the clinical efficacy of immunotherapy for triple-negative breast cancer (TNBC) remains limited, exploring new immunotherapy approaches is still indispensable. Mn2+ has been proven as a cGAS-STING agonist to remarkably enhance antitumor immunity. Here, we report a combined tumor-therapeutic strategy based on Prussian blue (PB)-mediated photothermal therapy with Mn2+-augmented immunotherapy by synergistically activating the cGAS-STING pathway. Mn-enriched photonic nanomedicine (MnPB-MnOx) were constructed by integrating MnOx onto the surface of Mn-doped PB nanoparticles. All components of MnPB-MnOx are biocompatible and biodegradable, wherein sufficient Mn are endowed through rational nanostructure design, conferring easier cGAS-STING activation. Additionally, tumor hyperthermia strengthened by MnPB under near-infrared light radiation, synergistic with the generation of reactive oxygen species catalyzed by MnOx, double hits cancer cells to release abundant tumor-associated antigens for further promoting immune response stimulation. The local anti-TNBC efficacy of photothermal/immuno-therapy has been proven effective in subcutaneous 4T1-bearing mice. Especially, it has been systematically demonstrated in bilateral orthotopic 4T1-bearing mice that the as-proposed treatment could successfully activate innate and adaptive immunity, and local therapy could engender systemic responses to suppress the distant tumors. Collectively, this work represents a proof-of-concept for a non-invasive Mn-based tumor-immunotherapeutic modality, providing a paradigm for the immunotherapy of metastatic-prone tumors.

Carotid plaque score and ischemic stroke risk stratification through a combination of B-mode and contrast-enhanced ultrasound in patients with low and intermediate carotid stenosis.

Objective: The occurrence of ischemic stroke (IS) is closely related to the characteristics of carotid plaque (CP). Due to the effect of stroke risk stratification based on B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) that has not been studied in patients with low and intermediate carotid stenosis, we construct and validate a CP score and ischemic stroke risk stratification (ISRS) using a combination of B-mode and CEUS, in order to provide new convenient strategies to stratify these patients to prevent stroke. Materials and methods: This retrospective study evaluated 705 patients with low and intermediate carotid stenosis who underwent B-mode and CEUS from November 2021 to April 2023. Qualitative B-mode and CEUS features of carotid plaques were analyzed using a univariable and multivariable logistic regression to construct the CP score. Then, we combined the CP score with Essen stroke risk score (ESRS) to develop ISRS. Results: This study included a total of 705 patients with low and intermediate carotid stenosis, of which 394 were symptomatic patients (with a mean age of 71.03 ± 10.48 years) and 311 were asymptomatic patients (with a mean age of 65.13 ± 10.31 years). Plaque echogenicity, plaque morphology, carotid intima-media thickness in B-mode US and intraplaque neovascularization grading and perfusion pattern in CEUS were significantly associated with IS. The ISRS incorporating these five predictors and ESRS showed good discrimination and calibration in both primary cohort [area under the curve (AUC), 0.91; Hosmer-Lemeshow test, p = 0.903] and validation cohort (AUC, 0.84; Hosmer-Lemeshow test, p = 0.886). Conclusion: We developed an effective and practical tool to identify and stratify patients with low and intermediate carotid stenosis, based on the CP score and ISRS estimation. Our study may provide new insights into managing patients with no indication of surgery.

The Synthesis and Evaluation of Arctigenin Amino Acid Ester Derivatives.

The use of arctigenin (ARG), a traditional medicine with many pharmacological activities, has been restricted due to its poor solubility in water. Five amino acid derivatives of ARG have been synthesized using glycine, o-alanine, valine, leucine, and isoleucine, which have t-butyloxy carbonyl (BOC) as a protective group. In this study, we examined the effects of removing these protective groups. The results showed that the amino acid derivatives have better solubility and nitrite-clearing ability than ARG. Among the compounds tested, the amino acid derivatives without protective group were the best. Based on these results, ARG and its two amino acid derivatives without protective group (ARG8, ARG10) were selected to evaluate their anti-tumor activity in vivo at a dosage of 40 mg/kg. The results indicated that ARG8 and ARG10 both exhibit more anti-tumor activity than ARG in H22 tumor-bearing mice. The tumor inhibition rates of ARG8 and ARG10 were 69.27 and 43.58%, which was much higher than ARG. Furthermore, the mice treated with these compounds exhibited less damage to the liver, kidney and immune organs compared with the positive group. Furthermore, ARG8 and ARG10 improved the serum cytokine levels significantly compared to ARG. In brief, this study provides a method to improve the water solubility of drugs, and we also provide a reference basis for new drug development.

[Impact of instantaneous uniformity of SonoVue microbubbles on binding characteristics of a new contrast agent targeted to choriocarcinoma cells in vitro].

BACKGROUND & OBJECTIVE: At present, the investigation of microbubble contrast agents is a hot spot. Although these contrast agents can increase the ultrasound detection rate of tumor vessels, they lack tissue specificity. This study was to evaluate the impact of instantaneous uniformity of SonoVue microbubbles on binding characteristics, including the adhesion rate and stability, of a new contrast agent targeted to choriocarcinoma cells (JARs) in vitro, in order to establish a foundation to explore targeted ultrasound imaging for localization of tumor cell antigens and increase the early diagnostic rate for tumors. METHODS: The objects were divided into three groups: the uneven microbubble group (n=10), the uniform microbubble group (n=10) and the tiny microbubble group (n=10). The rosette formation rate was counted. JARs were calculated by flow cytometry (FCM). The shape of the rosette was recorded. The targeted contrast agent was prepared by mixing SonoVue microbubbles of different uniformity with rabbit anti-human chorionic gonadotrophin (HCG) antibody. The binding rates of the contrast agent to JARs before and after PBS rinse were analyzed. RESULTS: The binding rate was significantlylower in the uneven microbubble group (60.4+/-1.5)% than in the uniform microbubble group (84.3+/-5.5)% and the tiny microbubble group (90.6+/-6.8)% (P<0.05). The binding rates of different microbubbles to JARs before and after PBS rinse were different. The uniform microbubbles were the most stable ones, with the binding rate of (84.3+/-5.5)% and (82.4+/-3.7)% before and after PBS rinse (P>0.05). The binding rates of the targeted microbubbles labeled with fluorescence to JARs were 72.9%, 81.03% and 88.5% in the uneven microbubble group, the uniform microbubble group and the tiny microbubble group, respectively (P<0.05). CONCLUSIONS: The binding capacity of the targeted SonoVue microbubbles to JARs is related to instantaneous uniformity of the microbubble, which is determined by the shaking method before preparation. Improving instantaneous uniformity of SonoVue microbubbles may increase the binding rate and stability of targeted microbubbles to JARs, thus to improve the image of JARs.

[Binding of targeted microbubble contrast agent to choriocarcinoma cells in vitro].

OBJECTIVE: To observe the cell binding characteristics of SonoVue microbubbles targeting choriocarcinoma cells and provide evidence for clinical ultrasonic localization of the tumor utilizing the microbubbles. METHODS: The targeted microbubbles were prepared by conjugating anti-HCG antibody with the SonoVue microbubbles and added in choriocarcinoma cells or endometrial stromal cells to compare the cell binding rate of the agents under optical microscope and with flow cytometry. RESULTS: Flow cytometry demonstrated a binding rate of 77.6% between the SonoVue microbubbles and anti-HCG antibody. Light microscopy showed that the total rosette formation rate of the choriocarcinoma cells exposed to the targeted microbubble bearing anti-HCG antibody reached (87.8-/+6.3)%, significantly higher than that of the endometrial stromal cells [(9.4-/+1.7)%, P<0.05]. The binding rate of the targeted microbubbles with the choriocarcinoma cells before and after PBS washing were (85.4-/+4.7)% and (83.1-/+3.8)% (P>0.05), respectively, suggesting strong stability of the binding. The binding rate was 81.0% according to the results of flow cytometry. CONCLUSION: The targeted microbubbles as a contrast agent can efficiently bind to the choriocarcinoma cells in vitro with a stability sufficient to resist the blood flow.

[Study on acupuncture treatment of diabetic neurogenic bladder].

OBJECTIVE: To probe into a better therapy for diabetic neurogenic bladder. METHODS: The patients were randomly divided into a treatment group and a control group, 35 cases in each group. The control group were treated with intramuscular injection of Methycobal 250 microg, once every other day; the treatment group were treated with intramuscular injection of Methycobal 250 microg, once every other day, and acupuncture at Guanyuan (CV 4), Shenshu (BL 23), Ciliao (BL 32), Huiyang (BL 35), once every day. The residual urine were compared before and after treatment in the two groups; the effective rate for improvement of symptoms were compared between the two groups. The mental and healthy nursing were conducted for the patients. RESULTS: After treatment, the improving rate for the urgency of urination, frequency of micturition, dribbling urination, urinary incontinence and dysuria in the treatment group was significantly better than that in the control group, but with no significant difference between the two groups in prolongation of urination time. After treatment, the residual urine in the bladder significantly improved in the two groups with more significantly improved in the treatment group than in the control group. CONCLUSION: Methycobal plus acupuncture has a better result than the simple Methyeobal for treatment of diabetic neurogenic bladder, and strengthening nursing care in the treatment can significantly enhance life quality of the patient.

[Changes in the sonographic appearance of the endometrium after different premenopausal tamoxifen therapies].

OBJECTIVE: To assess the effect of different schemes of premenopausal tamoxifen therapy on the endometrium. METHODS: Totally 109 normal premenopausal women positive for high-risk factors of breast cancer were divided into two groups, namely periodic and consecutive tamoxifen treatment groups. Endometrial thickness as examined by vaginal sonography was assessed in relation to duration of tamoxifen use and time from discontinuation of the drug. RESULTS: After one year of tamoxifen use, the mean endometrial thickness in periodic treatment group was 6.5-/+1.4 mm, and 10.2-/+2.0 mm in consecutive treatment group. Endometrial thickness increased with the duration of tamoxifen use at the rate of 0.51 mm/year in the periodic treatment group, and 0.73 mm/year in consecutive treatment group. After discontinuation of tamoxifen, the endometrial thickness in the former group decreased by 1.29 mm/year, and by 1.33 mm/year in the latter. CONCLUSIONS: Endometrial hyperplasia is obviously milder in premenopausal women receiving periodic tamoxifen treatment who are at risk for breast cancer than that in women with consecutive treatment. After discontinuation of the drug, the endometrial thickness decreases at a roughly equal slow rate in the two groups.