MRI-CEUS Fusion-Guided Lymphatic Mapping as a Preoperative Strategy for Lymphedema Patients Undergoing Lymphaticovenous Anastomosis Surgery.

OBJECTIVES: Contrast-enhanced ultrasound (CEUS) is useful in mapping lymphatic vessels in upper limb lymphedema, this study was aimed to evaluate its efficiency in lower limb lymphedema and investigate whether magnetic resonance lymphangiography (MRL) enhance the efficiency of CEUS. METHODS: This retrospective study enrolled 48 patients with lymphedema undergoing lymphaticovenous anastomosis (LVA) surgery who received MRL and/or CEUS in addition to conventional indocyanine green (ICG) lymphangiography. The number of anastomotic sites and the duration per site (DPS) for LVA surgery were described and compared. RESULTS: Among the 48 patients subjected to analysis, it was observed that 12 (25%), 20 (41.67%), and 16 (33.33%) of them received ICG, ICG+CEUS, and ICG+CEUS+MRL, respectively. The ICG+CEUS group demonstrated a significant increase in the number of LVAs (median, 5 [range, 4 - 7]), compared to the ICG group (median, 2 [range, 1 - 4]) (p < .001). Moreover, the ICG+CEUS+MRL group exhibited a higher number of LVAs (median, 8 [range, 7 - 8.25]) compared to both the ICG+CEUS and ICG groups (p < .001). For lower limb lymphedema, the ICG+CEUS+MRL group displayed an elevated number of LVAs (median, 8 [interquartile range, 7 - 9]) (p = .003), in contrast to the ICG group (median, 3 [interquartile range, 1.75 - 4.25]). Furthermore, the DPS in the ICG+CEUS+MRL group (median, 50.56 [interquartile range, 48.13 - 59.29]) (p = .005) exhibited a remarkable decrease when compared to the ICG group (median, 131.25 [interquartile range, 86.75 - 198.13]). CONCLUSION: MRL-CEUS fusion demonstrates superior performance in the identification of lymphatic vessel for lymphedema.

Agomirs upregulating carboxypeptidase E expression rescue hippocampal neurogenesis and memory deficits in Alzheimer's disease.

BACKGROUND: Adult neurogenesis occurs in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. The neuronal stem cells in these two neurogenic niches respond differently to various physiological and pathological stimuli. Recently, we have found that the decrement of carboxypeptidase E (CPE) with aging impairs the maturation of brain-derived neurotrophic factor (BDNF) and neurogenesis in the SVZ. However, it remains unknown whether these events occur in the hippocampus, and what the role of CPE is in the adult hippocampal neurogenesis in the context of Alzheimer's disease (AD). METHODS: In vivo screening was performed to search for miRNA mimics capable of upregulating CPE expression and promoting neurogenesis in both neurogenic niches. Among these, two agomirs were further assessed for their effects on hippocampal neurogenesis in the context of AD. We also explored whether these two agomirs could ameliorate behavioral symptoms and AD pathology in mice, using direct intracerebroventricular injection or by non-invasive intranasal instillation. RESULTS: Restoration of CPE expression in the hippocampus improved BDNF maturation and boosted adult hippocampal neurogenesis. By screening the miRNA mimics targeting the 5'UTR region of Cpe gene, we developed two agomirs that were capable of upregulating CPE expression. The two agomirs significantly rescued adult neurogenesis and cognition, showing multiple beneficial effects against the AD-associated pathologies in APP/PS1 mice. Of note, noninvasive approach via intranasal delivery of these agomirs improved the behavioral and neurocognitive functions of APP/PS1 mice. CONCLUSIONS: CPE may regulate adult hippocampal neurogenesis via the CPE-BDNF-TrkB signaling pathway. This study supports the prospect of developing miRNA agomirs targeting CPE as biopharmaceuticals to counteract aging- and disease-related neurological decline in human brains.

Predictive Model for the Diagnosis of Benign/Malignant Complex Cystic and Solid Breast Nodules.

PURPOSE: To develop an ultrasound predictive model to differentiate between benign and malignant complex cystic and solid nodules (C-SNs). METHODS: A total of 211 patients with complex C-SNs rated as American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) category 4 or 5 on the ultrasound reports were included in the study, from June 2018-2021. Multivariate stepwise logistic regression analysis was used to establish a predictive model, based on clinical and ultrasound features. The diagnostic performance of the model was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: A total of 109 breast nodules, including 74 benign nodules (67.89%) and 35 malignant nodules (32.11%), were detected by surgical pathology or puncture biopsy. Multivariate analysis showed that the blood flow (BF) of complex C-SNs (p = 0.03), cystic fluid transmission (p = 0.02), longitudinal diameter (p < 0.001), and age (p = 0.03) were independent risk factors for malignant complex cystic and solid breast nodules. The ultrasound model equation was Z=-12.14+2.24×X12+1.97×X20+0.40×X7+0.11×X0; M=ez1+ez (M is the malignancy score, e = 2.72). The area under the curve (AUC) was 0.89, which indicated good predictive utility for the model. CONCLUSIONS: A prediction model incorporating major risk factors can predict the malignant C-SNs with accuracy.

Deep learning and ultrasound feature fusion model predicts the malignancy of complex cystic and solid breast nodules with color Doppler images.

This study aimed to evaluate the performance of traditional-deep learning combination model based on Doppler ultrasound for diagnosing malignant complex cystic and solid breast nodules. A conventional statistical prediction model based on the ultrasound features and basic clinical information was established. A deep learning prediction model was used to train the training group images and derive the deep learning prediction model. The two models were validated, and their accuracy rates were compared using the data and images of the test group, respectively. A logistic regression method was used to combine the two models to derive a combination diagnostic model and validate it in the test group. The diagnostic performance of each model was represented by the receiver operating characteristic curve and the area under the curve. In the test cohort, the diagnostic efficacy of the deep learning model was better than traditional statistical model, and the combined diagnostic model was better and outperformed the other two models (combination model vs traditional statistical model: AUC: 0.95 > 0.70, P = 0.001; combination model vs deep learning model: AUC: 0.95 > 0.87, P = 0.04). A combination model based on deep learning and ultrasound features has good diagnostic value.

Effects of microplastics and lead exposure on gut oxidative stress and intestinal inflammation in common carp (Cyprinus carpio L.).

Microplastics (MPs) are increasingly being detected in freshwater environments, which have the potential to cause combined toxicity with other contaminants on aquatic organisms. To reveal the ecological risks, the combined effects of lead (Pb) and polyvinyl chloride microplastics (MPs) were explored in the gut of common carp (Cyprinus carpio L.). The results confirmed that exposure of Pb alone accelerated Pb accumulation, increased oxidative stress, and activated the inflammation response of the gut. However, the aforementioned effects all decreased under the co-exposure of Pb and MPs. In addition, MPs altered intestinal microbial community of common carp, especially the abundance of immune system-related species. All measured variables were organized for partial least square path modeling, which revealed the combined effects of Pb and MPs on inflammation response. The results implied that MPs reduced inflammation response in two ways, including the reduction of intestinal Pb accumulation and the alteration of the intestinal microbial community. Overall, this study provides a novel aspect of ecological effects on aquatic animals from Pb and MPs exposure. The interesting results remind us that when exploring the ecological risks of MPs, combined effects from other toxic substances must be considered simultaneously.

A Case of Pure Mucinous Breast Carcinoma in a 25-Year-Old Female Who Showed Complete Pathological Response to Neoadjuvant Chemotherapy despite Poor Clinical Response.

INTRODUCTION: Mucinous breast carcinoma is a rare histologic subtype of primary breast cancers accounting for 1-6%. It is a rare histological variant in young patients and usually presents without lymph node involvement, and its pathological response to neoadjuvant chemotherapy is rarely reported. CASE PRESENTATION: Pure mucinous breast carcinoma in a 25-year-old female was treated with neoadjuvant chemotherapy every 3 weeks for 8 cycles. After the fifth cycle, the mass size showed no change. We performed modified radical mastectomy in the left breast and axillary lymph node clearance. However, the pathological report showed a complete elimination of both the breast tumor and axillary lymph nodes, which were filled with mucus but did not contain malignant cells. DISCUSSION: Chemotherapy was profoundly effective against the tumor cells, but ineffective against large amounts of extracellular mucus. Even though the cancer cells were sensitive to chemotherapy, the volume of mucinous cancer couldnot be reduced. CONCLUSION: In summary, the evaluation criteria of tumor response to chemotherapy based on maximum diameter only should be considered insufficient for mucinous carcinoma.

Author Correction: Diagnostic value of ultrasound features and sex of fetuses in female patients with papillary thyroid microcarcinoma.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Diagnostic value of ultrasound features and sex of fetuses in female patients with papillary thyroid microcarcinoma.

Little work has been done on the prediction of papillary thyroid microcarcinoma in female patients who have given birth to children, which may be different from other people. We performed a retrospective review of female patients who underwent thyroidectomy, aiming at identifying special predictors of papillary thyroid microcarcinoma in female patients who have given birth to children. Univariate analysis was used to identify potential covariates for the prediction of papillary thyroid microcarcinoma. Multivariable logistic regression analysis was used to identify independent predictors and construct a regression model based on a training cohort (246 patients) and then the regression model was validated using an independent cohort (80 patients). We found that having not more than one boy, taller-than-wide shape, poorly defined margin, marked hypoechogenicity, and microcalcification were independent risk factors for the papillary thyroid microcarcinoma in multivariate analyses. The combined predictive formula had a high predictive effect for papillary thyroid microcarcinoma (AUC = 0.938 for training cohort and 0.929 for validation cohort, respectively). The combined predictive formula has clinical value in the prognosis of papillary thyroid microcarcinoma and it may be simple and effective to ask fertility condition of patients to increase the US diagnosis accuracy of papillary thyroid microcarcinoma.

A preliminary study on the expression and clinical value of platelet-derived growth factor BB, hypoxia inducible factor-1α and C-C motif chemokine receptor-2 in peripheral blood during the pathogenesis of Graves' disease.

INTRODUCTION: Platelet-derived growth factor BB (PDGF-BB) plays an important role in the development of GD (Graves' disease). However, it is still unknown whether PDGF-BB is expressed in peripheral blood and whether the expression of PDGF-BB contributes to GD. We aim to study the expression of PDGF-BB, hypoxia inducible factor (HIF)-1α and C-C motif chemokine receptor (CCR)-2 in peripheral blood of patients with GD and explore its effect and potential mechanism in pathogenesis. MATERIAL AND METHODS: 41 patients with GD (GD group) and forty-five healthy people (control group) were chosen. The concentration of PDGF-BB and HIF-1α in peripheral blood specimens were detected and compared between the two groups. The expression of CCR2 in macrophages in the peripheral blood specimens were examined using FCM (Flow Cytometry). RESULTS: Both PDGF-BB and HIF-1α were expressed in human peripheral blood from the two groups. Compared with specimens from healthy people, there were statistically increased concentrations of PDGF-BB and HIF-1α in the GD group (P < 0.05). The proportion of CCR2-positive macrophages in peripheral blood in the GD group was significantly higher than that in the control group (P < 0.05). CONCLUSIONS: CCR2-positive macrophages may induce the expression of PDGF-BB through HIF-1α signal, and the high expression of PDGF-BB may be involved in the pathogenesis of GD.

Comparing pharmacokinetics and metabolism of diltiazem in normotensive Sprague Dawley and Wistar Kyoto rats vs. spontaneously hypertensive rats in vivo.

BACKGROUND: In order to identify a suitable rodent model for preclinical study of calcium antagonists, the pharmacokinetics and metabolism of one of the prototypes diltiazem (DTZ) in normotensive Sprague Dawley (SDR) was compared with Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) following 5 mg/kg twice daily for five doses given by subcutaneous injection. METHODS: Pharmacokinetic data were analyzed by standard procedures assuming a one-compartment model with first-order input using Rstrips(®), and differences between the groups were considered significant when p<0.05. RESULTS: Plasma concentrations of DTZ were higher in the SHR than the normotensive SDR and WKY rats, although the differences did not reach statistical significance (p>0.05). Plasma concentrations of the active metabolites N-desmethyl DTZ (MA), deacetyl DTZ (M1) and deacetyl N-desmethyl DTZ (M2) were significantly higher in the SHR and WKY rats than the SDR, which was attributed to higher DTZ concentrations and also genetic factors. CONCLUSIONS: Although the differences were mainly quantitative and very small, the study has shown for the first time that the metabolism profiles of DTZ in SHR and WKY rats were closer to humans than SDR, and they may be more preferable rat models to study pharmacokinetic and metabolism studies of DTZ or similar agents.

Pharmacokinetics and metabolism of diltiazem following multiple doses: comparing normotensive rat vs. hypertensive rat models in vivo.

In order to identify a suitable rodent model for preclinical study of calcium antagonists, pharmacokinetics and metabolism of diltiazem (DTZ) were compared in normotensive SD and hypertensive SHR rat models following multiple doses (5 mg/kg twice daily for 5 doses). Plasma concentrations of DTZ and its major metabolites appeared to be higher in the SHR than the SD rats, although the differences did not reach statistical significance (p > 0.05). The preliminary results suggest metabolism profile of DTZ in the SHR may be closer to humans than the SD rats and may be more preferred in pre-clinical drug development studies for DTZ.

Pharmacokinetics and metabolism of diltiazem in rats: comparing single vs repeated subcutaneous injections in vivo.

The objective of the study was to determine the effect of repeated administration on the pharmacokinetics and metabolism of diltiazem (DTZ) using an in vivo rat model. Male SD rats (n = 6-10 per group) weighing 350-450 g were used. Each rat received either a single 20 mg/kg dose of DTZ by subcutaneous (s.c.) injection or 5 mg/kg s.c. twice daily for five doses. Plasma concentrations of DTZ and its major metabolites were determined by HPLC for up to 8 h. Compared with the single dose, repeated administration resulted in higher dose normalized plasma concentrations of DTZ (AUC 26.4+/-14.2 vs 13.9+/-11.5 microg-h/ml), longer apparent half-life (t(1/2) = 12.5+/-14.6 vs 3.7+/-1.4 h) and lower systemic clearance (CL = 1.1+/-1.0 vs 2.9+/-2.7 l/h/kg). Higher dose normalized plasma concentrations, longer t(max), but shorter apparent t(1/2) of the major metabolites were observed following the repeated administration. The results also suggest that possible binding of DTZ may occur at the site of injection when administered subcutaneously in the higher dose.