Nanomedicines for high­intensity focused ultrasound cancer treatment and theranostics (Review).

High-intensity focused ultrasound (HIFU) is a promising and representative non-invasive therapeutic method for treating cancer with a high degree of efficacy. This non-invasive method induces tumour cell necrosis by increasing the local temperature and mechanical pressure. However, the clinical application of HIFU is limited given its low penetration depth and the incidence of off-target side effects. With their promising structural adjustability and targeting ability, nanomedicines have been adopted to improve the ablative efficacy of HIFU in the treatment of cancer. By selectively changing the acoustic environment (tissue structure, density and blood supply) of tumour tissue, these nanomedicines may allow for lower HIFU doses and treatment duration, while additionally achieving a higher degree of efficacy. The use of nanomedicines may also enable cancer theranostics of HIFU, allowing for precise cancer therapeutics. The present review aimed to provide an overview of advances in nanomedicines for HIFU cancer treatment and theranostics, stating their current limitations and future perspectives.

Subtraction coronary CT angiography in patients with high heart rate.

All the previous subtraction coronary CT angiography (CCTA) had strict heart rate (HR) inclusion criteria. In this study, a new subtraction method was applied to patients with various HR. The post-contrast scan time was respectively 3.5 s after ascending aorta peak enhancement while HR >80 bpm, 4 s while 65≤ HR ≤80 bpm and 4.5 s while HR <65 bpm. Forty-six patients who underwent the new subtraction protocol were enrolled and patients were stratified into the high HR group (≥70 bpm) and low HR group (<70 bpm). Eighteen patients with 15 severe calcification segments and 25 stent segments further received invasive coronary angiography (ICA). In all included patients, the coronary artery enhancement was compared between the high and low HR groups. In patients with ICA performed, the image quality improvement and diagnostic effectiveness for detection of significant coronary segments stenosis (>50%) were compared between the conventional CCTA and subtraction CCTA and between the high HR group and low HR group, respectively. All enrolled patients got sufficient coronary artery enhancement. In patients with ICA performed, receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the diagnosis of significant stenosis was 0.93 in subtraction CCTA and 0.73 in conventional CCTA (p < 0.05). Furthermore, there were no significant differences in image quality improvement, specificity, positive predictive value and accuracy between the high HR group and low HR group. The new subtraction CCTA method broadened the clinical availability for patients with high HR.

PD-L2 Serves as a Potential Prognostic Biomarker That Correlates With Immune Infiltration and May Predict Therapeutic Sensitivity in Lower-Grade Gliomas.

Although patients with lower-grade gliomas (LGGs; grades II and III) have a relatively favorable prognosis, patients frequently relapse and tend to progress to higher-grade gliomas, leading to treatment resistance, poor survival, and ultimately treatment failure. However, until now, thorough research has not yet been reported on the relationship between PD-L2 and immune infiltration and therapeutic sensitivity to immunotherapy and TMZ-based chemotherapy of LGGs. In this study, we found that the expression of PD-L2 is upregulated in glioma, with high PD-L2 expression predicting a worse prognosis. Univariate and multivariate Cox regression analysis both indicated that PD-L2 represented an independent prognostic factor with high accuracy in survival prediction for LGGs. A nomogram comprising of age, grade, IDH mutation, and PD-L2 was established for predicting OS. Additionally, PD-L2 was found to be remarkably correlated with immune infiltration and some anti-tumor immune functions. The degree of PD-L2 expression was also found to be strongly related to the prediction of therapeutic sensitivity to immunotherapy and TMZ-based chemotherapy. Furthermore, immunohistochemistry demonstrated that PD-L2 and the macrophage biomarker CD68 were both increased in glioma, with PD-L2 expression having a strong positive connection with CD68 expression. Taken together, PD-L2 is a prognostic biomarker for LGGs patients that may provide novel insights into glioma individualized therapeutic strategies and guide effective immunotherapy and chemotherapy.

14-3-3 Proteins are Potential Regulators of Liquid-Liquid Phase Separation.

The 14-3-3 family proteins are vital scaffold proteins that ubiquitously expressed in various tissues. They interact with numerous protein targets and mediate many cellular signaling pathways. The 14-3-3 binding motifs are often embedded in intrinsically disordered regions which are closely associated with liquid-liquid phase separation (LLPS). In the past ten years, LLPS has been observed for a variety of proteins and biological processes, indicating that LLPS plays a fundamental role in the formation of membraneless organelles and cellular condensates. While extensive investigations have been performed on 14-3-3 proteins, its involvement in LLPS is overlooked. To date, 14-3-3 proteins have not been reported to undergo LLPS alone or regulate LLPS of their binding partners. To reveal the potential involvement of 14-3-3 proteins in LLPS, in this review, we summarized the LLPS propensity of 14-3-3 binding partners and found that about one half of them may undergo LLPS spontaneously. We further analyzed the phase separation behavior of representative 14-3-3 binders and discussed how 14-3-3 proteins may be involved. By modulating the conformation and valence of interactions and recruiting other molecules, we speculate that 14-3-3 proteins can efficiently regulate the functions of their targets in the context of LLPS. Considering the critical roles of 14-3-3 proteins, there is an urgent need for investigating the involvement of 14-3-3 proteins in the phase separation process of their targets and the underling mechanisms.

A Preliminary Study on the Diagnostic Efficacy of Proton Magnetic Resonance Spectroscopy at 3.0T in Rabbit With VX2 Liver Tumor.

BACKGROUND: To investigate the diagnostic efficacy of choline (Cho) value of magnetic resonance spectroscopy (MRS) in rabbit with VX2 liver tumor via comparative and quantitative analysis with the choline compounds concentration measured by enzyme linked immunosorbent assay (ELISA). METHODS: MRS was performed on normal liver and VX2 tumor. The Cho value of VX2 tumor was compared with that of normal liver. Tissues were harvested for ELISA to detect the concentrations of acetylcholine (ACh), glycophorophosphygholine (GPC) and phosphochorine (PC). The diagnostic performance of Cho value and concentrations of choline compounds were assessed by receiver operating characteristic (ROC) curve and area under ROC curve (AUC). The specificity and sensitivity were discussed by the maximum Youden's index. RESULTS: The concentration of ACh was obviously higher than that of GPC and PC both in VX2 tumor and normal liver (P < 0.01). Furthermore, the concentration differences among ACh, GPC and PG were the third power of 10. Both the ACh concentration and Cho value of MRS in VX2 tumor were significantly higher than those in normal liver (P < 0.01). The AUC of ACh in VX2 tumor was 0.883, when the cutoff value was 7259000, the sensitivity and specificity of the diagnosis of liver cancer were 94.4% and 77.8%, respectively. The AUC of Cho in VX2 tumor was 0.807, when the cutoff value was 28.35, the sensitivity and specificity of the diagnosis of liver cancer were 83.3% and 77.8%, respectively. CONCLUSION: The change of Cho value in MRS between liver cancer and normal liver was consistent with the changes of concentrations of choline compounds measured by ELISA, especially the change of ACh concentration. The diagnostic efficiency of Cho value and that of choline compounds concentration in liver cancer were extremely similar, with the AUC more than 0.8. We conclude that MRS may be applied as an important, non-invasive biomarker for the diagnosis of liver cancer.

The Structure Biology of Tau and Clue for Aggregation Inhibitor Design.

Tau is a microtubule-associated protein that is mainly expressed in central and peripheral nerve systems. Tau binds to tubulin and regulates assembly and stabilization of microtubule, thus playing a critical role in neuron morphology, axon development and navigation. Tau is highly stable under normal conditions; however, there are several factors that can induce or promote aggregation of tau, forming neurofibrillary tangles. Neurofibrillary tangles are toxic to neurons, which may be related to a series of neurodegenerative diseases including Alzheimer's disease. Thus, tau is widely accepted as an important therapeutic target for neurodegenerative diseases. While the monomeric structure of tau is highly disordered, the aggregate structure of tau is formed by closed packing of ß-stands. Studies on the structure of tau and the structural transition mechanism provide valuable information on the occurrence, development, and therapy of tauopathies. In this review, we summarize recent progress on the structural investigation of tau and based on which we discuss aggregation inhibitor design.

A Preliminary Study of CT Texture Analysis for Characterizing Epithelial Tumors of the Parotid Gland.

OBJECTIVE: The aim of this study was to explore and validate the diagnostic performance of whole-volume CT texture features in differentiating the common benign and malignant epithelial tumors of the parotid gland. MATERIALS AND METHODS: Contrast-enhanced CT images of 83 patients with common benign and malignant epithelial tumors of the parotid gland confirmed by histopathology were retrospectively analyzed, including 50 patients with pleomorphic adenoma (PA) and 33 patients with malignant epithelial tumors. Quantitative texture features of tumors were extracted from CT images of arterial phase. The diagnostic performance of texture features was evaluated via receiver operating characteristic (ROC) curve and area under ROC curve (AUC). The specificity and sensitivity were respectively discussed by the maximum Youden's index. RESULTS: All the texture features were subject to normal distribution and homoscedasticity. Energy, mean, correlation, and sum entropy of epithelial malignancy group were significantly higher than those of PA group (P<0.05). There were no statistically significant differences between PA group and epithelial malignancy group in uniformity, entropy, skewness, kurtosis, contrast, and difference entropy (P>0.05). The AUC of each texture feature and joint diagnostic model was 0.887 (energy), 0.734 (mean), 0.739 (correlation), 0.623 (sum entropy), 0.888 (energy-mean), 0.883 (energy-correlation), 0.784 (mean-correlation). The diagnostic efficiency of energy-mean was the best. Based on the maximum Youden's index, the specificity of energy-correlation was the highest (97%) and the sensitivity of energy was the highest (97%). CONCLUSION: Energy, mean, correlation, and sum entropy can be the effective quantitative texture features to differentiate the benign and malignant epithelial tumors of the parotid gland. With higher AUC, energy and energy-mean are superior to other indexes or joint diagnostic models in differentiating the benign and malignant epithelial tumors of the parotid gland. CT texture analysis can be used as a noninvasive and valuable means of preoperative assessment of parotid epithelial tumors without additional cost to the patients.

Improving the diagnosis of common parotid tumors via the combination of CT image biomarkers and clinical parameters.

BACKGROUND: Our study aims to develop and validate diagnostic models of the common parotid tumors based on whole-volume CT textural image biomarkers (IBMs) in combination with clinical parameters at a single institution. METHODS: The study cohort was composed of 51 pleomorphic adenoma (PA) patients and 42 Warthin tumor (WT) patients. Clinical parameters and conventional image features were scored retrospectively and textural IBMs were extracted from CT images of arterial phase. Independent-samples t test or Chi-square test was used for evaluating the significance of the difference among clinical parameters, conventional CT image features, and textural IBMs. The diagnostic performance of univariate model and multivariate model was evaluated via receiver operating characteristic (ROC) curve and area under ROC curve (AUC). RESULTS: Significant differences were found in clinical parameters (age, gender, disease duration, smoking), conventional image features (site, maximum diameter, time-density curve, peripheral vessels sign) and textural IBMs (mean, uniformity, energy, entropy) between PA group and WT group (P<0.05). ROC analysis showed that clinical parameter (age) and quantitative textural IBMs (mean, energy, entropy) were able to categorize the patients into PA group and WT group, with the AUC of 0.784, 0.902, 0.910, 0.805, respectively. When IBMs were added in clinical model, the multivariate models including age-mean and age-energy performed significantly better than the univariate models with the improved AUC of 0.940, 0.944, respectively (P<0.001). CONCLUSIONS: Both clinical parameter and CT textural IBMs can be used for the preoperative, noninvasive diagnosis of parotid PA and WT. The diagnostic performance of textural IBM model was obviously better than that of clinical model and conventional image model in this study. While the multivariate model consisted of clinical parameter and textural IBM had the optimal diagnostic performance, which would contribute to the better selection of individualized surgery program.

Abnormal Baseline Brain Activity in Neuromyelitis Optica Patients Without Brain Lesion Detected by Resting-State Functional Magnetic Resonance Imaging.

OBJECTIVE: To investigate the baseline brain activity in neuromyelitis optica patients without brain lesion using the regional amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuation (fALFF) as indexes. MATERIALS AND METHODS: Forty-two patients of NMO with normal performance in conventional MRI and 42 healthy controls, matched in gender and age, were enrolled in this study. Resting-state functional magnetic resonance imaging (rs-fMRI) data acquired using the rs-fMRI Data Analysis Toolkit. The relationships between expanded disability states scale (EDSS) scores, abnormal baseline brain activity and disease duration were explored. RESULTS: The left inferior temporal, left cerebellum_4_5, bilateral superior temporal pole, left caudate, right superior temporal, left middle frontal and left superior occipital showed significantly increased ALFF in the NMO. Regions of abnormal fALFF were similar to those of ALFF except that increased fALFF were also indicated in the right cerebellum crus2, right hippocampus, left parahippocampal gyrus and left supplementary motor area. Furthermore, a significant correlation between EDSS scores and ALFF/fALFF was noted in the left inferior temporal gyrus. CONCLUSION: Results confirmed the disturbances in NMO-related neural networks, which probably be related to spinal cord damage.

The features of cerebral permeability and perfusion detected by dynamic contrast-enhanced magnetic resonance imaging with Patlak model in relapsing-remitting multiple sclerosis.

OBJECTIVE: To investigate the features of cerebral permeability and perfusion detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with Patlak model in relapsing-remitting multiple sclerosis (RRMS) and their correlations with Expanded Disability Status Scale (EDSS) scores and disease duration. PATIENTS AND METHODS: Twenty-seven RRMS patients underwent conventional MRI and DCE-MRI with 3.0 T magnetic resonance scanner were enrolled in the study. A Patlak model was used to quantitatively measure MRI biomarkers, including volume transfer constant (Ktrans), fractional plasma volume (Vp), cerebral blood flow (CBF), and cerebral blood volume (CBV). The correlations of MRI biomarkers with EDSS scores and disease duration were analyzed. RESULTS: The MRI biomarkers Ktrans, Vp, CBF, and CBV of contrast-enhancing (CE) lesions were significantly higher (P<0.05) than those of non-enhancing (NE) lesions and normal-appearing white matter (NAWM) regions. The skewness and kurtosis of Ktrans values in CE lesions were significantly higher (P<0.05) than that of NE lesions. No significant correlation was found among the biomarkers with EDSS scores and disease duration (P>0.05). CONCLUSION: Our study demonstrated the abnormalities of permeability and perfusion characteristics in multiple sclerosis (MS) lesions and NAWM regions by DCE-MRI with Patlak model. The Ktrans, Vp, CBF, and CBV of CE lesions were significantly higher than that of NE lesions, but these MRI biomarkers did not associate with the severity and duration of the disease. The skewness and kurtosis of Ktrans value in CE lesions were significantly higher than that in NE lesions, indicating that these parameters of Ktrans histogram can be used to distinguish the pathology of MS lesions.

Tuberculosis of the parotid lymph nodes: clinical and imaging features.

OBJECTIVES: To characterize clinical, computed tomography (CT) and magnetic resonance imaging (MRI) features of tuberculosis (TB) of the parotid nodes. MATERIALS AND METHODS: CT (n=21) and MR (n=7) images, and clinical data from 25 patients with TB of the parotid nodes were retrospectively analyzed by two experienced radiologists who reached consensus. RESULTS: Younger patients (aged <50 years) accounted for 72%. Eighty percent of patients were asymptomatic, and had no history of TB exposure. According to clinical and imaging findings, 64% and 60% patients were misdiagnosed as having tumors, respectively. A total of 43 lesions were identified. Thirty-eight (88.4%) lesions involved the superficial lobe. Fourteen (56%) cases had multiple lesions. There were four types of changes in the parotid fascia: local thickening (40%, n=10); local rupture with thickened adjacent skin (28%, n=7); focal bulge (20%, n=5); and no changes (12%, n=3). Cervical lymphadenopathy was seen in 14 out of 25 cases (56%). The lesions were contrast-enhanced in four patterns on CT images: homogeneous enhancement (37.1%, n=13), irregular cyst-like enhancement (37.1%, n=13), thick-walled ring enhancement (14.2%, n=5), and garland-like enhancement (11.4%, n=4). On MRI, the signal intensity of lesions was isointense on T1-weighted image, hyperintense on T2-weighted image, markedly hyperintense on diffusion-weighted imaging, and low on the apparent diffusion coefficient map. The surrounding parotid parenchymal edema was identified clearly on coronal MR images. CONCLUSION: TB of the parotid nodes tend to simulate tumors clinically and radiologically. Their preferential sites are the superficial lobe. In young patients with positive purified protein derivative skin test and lesions accompanied by cervical lymphadenopathy, changes in the parotid fascia and parotid parenchymal edema adjacent to the lesions on CT and MRI may be helpful in the diagnosis and to facilitate differential diagnosis.

Differential diagnostic value of 64-slice spiral computed tomography in solitary pulmonary nodule.

The present study aimed to evaluate the diagnostic value of 64-slice spiral multivariate computed tomography (CT) combined with dynamic contrast-enhanced scanning for benign and malignant solitary pulmonary nodules (SPNs). A total of 93 patients with SPN as diagnosed by CT were included. All these patients were subjected to routine and dynamic enhancement CT scanning. After reconstruction, the morphological characteristics following dynamic enhancement were analyzed, and compared for the benign and malignant SPN cases. The incidences of lobulation, spicular sign, pleural indentation and vacuole sign in the malignant SPN group were significantly higher compared with the benign SPN group. During the dynamic enhancement scanning, the CT values at all the time points for the inflammatory and malignant SPN groups were significantly higher than the benign SPN group. No significant differences were observed in the dynamic enhancement CT values at 30, 60, 90 and 120 sec between the inflammatory, and malignant SPN groups. However, in the inflammatory SPN group, the dynamic enhancement CT values at 300 and 540 sec were significantly lower than the malignant SPN group. Notably, the diagnostic accordance rate for the morphological signs combined with dynamic enhancement diagnosis was significantly higher than the morphological signs alone. The 64-slice spiral CT morphological signs combined with dynamic enhancement detection can be more effective for the differential diagnosis of benign and malignant SPN, which may provide potent evidence for the early clinical treatment.

Establishment and evaluation of the VX2 orthotopic lung cancer rabbit model: a ultra-minimal invasive percutaneous puncture inoculation method.

The purpose of the present work is to establish an ultra-minimal invasive percutaneous puncture inoculation method for a VX2 orthotopic lung cancer rabbit model with fewer technical difficulties, lower mortality of rabbits, a higher success rate and a shorter operation time, to evaluate the growth, metastasis and apoptosis of tumor by CT scans, necropsy, histological examination, flow cytometry and immunohistochemistry. The average inoculation time was 10-15 min per rabbit. The tumor-bearing rate was 100%. More than 90% of the tumor-bearing rabbits showed local solitary tumor with 2-10 mm diameters after two weeks post-inoculation, and the rate of chest seeding was only 8.3% (2/24). The tumors diameters increased to 4-16 mm, and irregularly short thorns were observed 3 weeks after inoculation. Five weeks post-inoculation, the liquefaction necrosis and a cavity developed, and the size of tumor grew further. Before natural death, the CT images showed that the tumors spread to the chest. The flow cytometry and immunohistochemistry indicated that there was less apoptosis in VX2 orthotopic lung cancer rabbit model compared to chemotherapy drug treatment group. Minimal invasive percutaneous puncture inoculation is an easy, fast and accurate method to establish the VX2 orthotopic lung cancer rabbit model, an ideal in situ tumor model similar to human malignant tumor growth.

[Risk factors of portal vein thrombosis after surgery for advanced schistosomiasis portal hypertension].

OBJECTIVE: To explore the risk factors of portal vein thrombosis (PVT) after splenectomy and esophagogastric devascularization for advanced schistosomiasis portal hypertension. METHODS: The clinical data were collected retrospectively from 211 advanced schistosomiasis portal hypertension patients after splenectomy and esophagogastric devascularization from August, 2004 to March 2014, and all the data were analyzed statistically for the risk factors of PVT after the surgery by single factor analysis and Logistic regression analysis. RESULTS: Totally 59 patients were found with PVT and the incidence was 27.96% (59/211). The single factor analysis showed that 8 factors were related to PVT after surgery, including the history of upper gastrointestinal hemorrhage, the diameter of portal vein, the diameter of splenic vein, esophageal varices, ascites, portal hypertension gastropathy, gastric varices , and blood ammonia level. The Logistic regression analysis showed that the independent risk factors of PVT were broadening of the diameter of portal vein (OR = 1.763 , P = 0.000) and portal hypertension gastropathy (OR = 1.089, P = 0.037). CONCLUSIONS: The incidence of PVT after surgery for advanced schistosomiasis is high, and the independent risk factors are broadening of diameter of portal vein and portal hypertension gastropathy.

Imaging Misdiagnosis Analysis of a Rare Case of Renal Subcapsular Hematoma Located in the Renal Hilum and Collecting Area.

We report a rare case of renal subcapsular hematoma, which was located in the renal hilum and collecting area. Preoperative ultrasonography, retrograde urethrography, and computed tomographic examinations misdiagnosed the patient with simple hydronephrosis, without finding a lesion causing the hydronephrosis. We retrospectively summarized the imaging features and analyzed the reasons leading to the misdiagnosis.