Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

[Transrectal ultrasonography of intravesical prostatic protrusion and the detection rate of clinically significant prostate cancer].

OBJECTIVE: To investigate the value of transrectal ultrasonography (TRUS) in the detection of clinically significant prostate cancer (CsPCa) in patients with intravesical prostatic protrusion (IPP). METHODS: We retrospectively analyzed the data on 128 patients undergoing TRUS-guided prostate biopsy in the General Hospital of Eastern Theater Command and Jiangsu Province Hospital from January 2019 to December 2022. We measured the size of and graded IPP, compared the clinicopathological and ultrasonographic features of the patients in the CsPCa group (Gleason score ≥7) and those in the control group (Gleason score <7), and analyzed the correlation of the IPP grades with the detection rate of CsPCa by multivariate logistic regression analysis. RESULTS: The prostate volume was significantly higher in the CsPCa group than in the control (ï¼»51.3±12.1ï¼½ vs ï¼»43.5±11.3ï¼½ ml, P< 0.05), while the PSA density (PSAD) remarkably lower in the former than in the latter (ï¼»0.45±1.92ï¼½ vs ï¼»0.59±2.14ï¼½ ng/ml, P< 0.05) and so was the detection rate of CsPCa in the patients with IPP grade 3 than in those with IPP grades 0, 1 and 2 (56.0% vs 85.4%, 87.1% and 80.6%, P< 0.05). Spearman correlation analysis showed that the Gleason score was correlated positively with the prostate volume (r = 0.612) but negatively with PSAD (r = －0.735) and the IPP grade (r = －0.619) (P< 0.05). Logistic regression analysis indicated that IPP grade 3 (OR: 0.690, 95% CI: 0.380－0.995, P = 0.032) was an independent protective factor for CsPCa. CONCLUSION: CsPCa is significantly correlated with the IPP grade, and the detection rate of CsPCa by TRUS-guided biopsy is lower in patients with IPP grade 3 than in those with IPP grades 0－2. Therefore, special attention should be paid to false negative probability in case of high-grade IPP.

Stiffness-Transformable Nanoplatforms Responsive to the Tumor Microenvironment for Enhanced Tumor Therapeutic Efficacy.

Herein, we report, for the first time, a unique stiffness-transformable manganese oxide hybridized mesoporous organosilica nanoplatform (MMON) for enhancing tumor therapeutic efficacy. The prepared MMONs had a quasi-spherical morphology and were completely transformed into soft bowl-like nanocapsules in the simulated tumor microenvironment through the breakage of Mn-O bonds, which decreased their Young's modulus from 165.7 to 84.5 MPa. Due to their unique stiffness transformation properties, the MMONs had reduced macrophage internalization, improved tumor cell uptake, and enhanced penetration of multicellular spheroids. In addition, in vivo experiments showed that the MMONs displayed a 3.79- and 2.90-fold decrease in non-specific liver distribution and a 2.87- and 1.83-fold increase in tumor accumulation compared to their soft and stiff counterparts, respectively. Furthermore, chlorin e6 (Ce6) modified MMONs had significantly improved photodynamic therapeutic effect.

[Value of nomogram based on the ultrasonographic features of prostatic calcification and varicocele and serological indicators in differential diagnosis of prostate cancer].

OBJECTIVE: To explore the diagnostic performance of the nomogram based on the transabdominal ultrasonographic features of prostatic calcification and varicocele (VC) and serological indicators in differentiating PCa with BPH from simple BPH. METHODS: This retrospective study included 108 cases of PCa with BPH and 317 cases of simple BPH, all pathologically confirmed after surgery from January 2014 to December 2021. Using t test or χ2/Fisher test, we compared the clinicopathologic data, transabdominal ultrasonographic features of prostatic calcification, VC severity and serological indicators between the two groups of patients. We identified the significant independent factors for differentiating PCa with BPH from simple BPH by multivariate logistic regression analysis and constructed a nomogram for visualizing the differential diagnostic performance. RESULTS: There were significant differences in the types and diameters of prostatic calcification, PSA density (PSAD), total PSA (tPSA), VC severity, and serum testosterone level between the two groups (P < 0.05). The types of calcification, PSAD and VC severity were identified as independent factors for differentiating PCa with BPH from simple BPH. Nomogram analysis of the above factors showed a good predicting performance, with an AUC of 0.805, a sensitivity of 83.28% and a specificity of 70.37%. CONCLUSION: Transabdominal ultrasonographic features and types of prostatic calcification, PSAD and VC severity are correlated with the development and progression of PCa. Nomogram analysis of the above factors contributes to the differentiation of PCa with BPH from simple BPH.

Combined use of the automated breast volume scanner and the US elastography for the differentiation of benign from malignant lesions of the breast.

BACKGROUND: Automated breast volume scanner (ABVS) and US elastography (UE) have been useful for the differentiation of benign and malignant lesions. However, combining these two methods applied in diagnosis of breast lesions has not yet been reported. The aim of this study is to analyze the inter-examiner reliability of ABVS and UE, and compare diagnostic performance among ABVS, UE, and the combination of these two methods. METHODS: Forty-one patients (forty-six lesions) underwent both ABVS and UE examinations. ABVS images were acquired by medial and lateral scans for each breast and classified a BI-RADS category based on the distribution, size, shape, echogenicity and microcalcification of the lesions. UE images were assigned an elasticity score according to the distribution of strain induced by light compression. Kappa statistics was used to examine the reproducibility between examiners with ABVS and UE, and the concordance between pathology and ABVS, UE, and the combination of these two methods. χ2 test was used to compare diagnostic performance among these three methods.Two examiners blinded to the patients' history evaluated the results of breast imaging independently. RESULTS: Inter-examiner reliability with ABVS (κ = 0.62, 95% confidence interval (CI): 0.44-0.80) and UE (κ = 0.65, 95% CI: 0.48-0.82) was substantial. With respect to the pathology results, the inter-rater coefficient of concordance was κ = 0.81 (95% CI: 0.64-0.98) for ABVS, κ = 0.77 (95% CI: 0.58-0.96) for UE, and κ = 0.90 (95% CI: 0.77-1.00) for combination of ABVS and UE. Examiner variability was reduced from UE to ABVS, and to the combination of ABVS with UE.The diagnostic accuracy, sensitivity, and specificity for the combination of ABVS and UE were 95.7% (95%CI: 84.0-99.2), 100% (95% CI: 85.9-100), and 87.5% (95% CI: 60.4-97.8), respectively. When comparing, the diagnostic performance of ABVS combined with UE was better than, or at least equal to, that of ABVS (accuracy 91.3% (95% CI: 78.3-97.2), sensitivity 100% (95% CI: 85.0-1.00), specificity 77.8% (95% CI: 51.9-92.6)) or UE (accuracy 89.1% (95% CI: 75.6-95.9), sensitivity 96.4% (95% CI: 79.8-99.8), specificity 77.8% (95% CI: 51.9-92.6)) alone, though the improvement was no statistically significance. CONCLUSIONS: Both ABVS and UE demonstrated substantial inter-examiner reliability. With high diagnostic performance for differentiation of benign and malignant lesions in the breast, the combination of ABVS and UE are useful to improve the diagnostic accuracy and specificity.

Risk Factors for Early Recurrence After Radical Resection of Hepatocellular Carcinoma Based on Preoperative Contrast-Enhanced Ultrasound and Clinical Features.

OBJECTIVES: To investigate risk factors for the early recurrence (ER) of hepatocellular carcinoma (HCC) after radical resection based on preoperative contrast-enhanced ultrasound (CEUS) and clinical features to provide guidance for clinical treatment. METHODS: The retrospective analysis selected 130 HCC patients who underwent radical tumor resection from October 2019 to November 2021. All patients underwent preoperative routine ultrasound examination and CEUS, and the pathology was confirmed as HCC after surgery. The patients were divided into two groups based on whether there is an ER, namely the ER group and the non-ER group. The general clinical, routine and CEUS data of patients were collected, and the factors were selected by using the least absolute shrinkage and selection operator (LASSO) regression. Multivariate logistic regression was used to screen the independent influencing factors of ER. Then a nomogram model was established to predict the risk of ER, and the application value of nomogram through internal validation was evaluated. RESULTS: Multivariate logistic regression identified several independent factors influencing ER after radical HCC resection. Significant factors included early wash-out phase (95%CI = 0.003-0.206, P = 0.001), liver cirrhosis (95%CI = 2.835-221.224, P = 0.004), incomplete envelope (95%CI = 5.247-1056.130,P = 0.001), multiple lesions (95%CI = 1.110-135.424,P = 0.041), Albumin <40 g/L (95%CI = 2.496-127.223,P = 0.004), and Golgi Protein 73 (GP73) ≥ 85 ng/mL (95%CI = 1.594-30.002, P = 0.010), with all P-values <0.05. The nomogram prediction model constructed based on the results of multivariate logistic regression, demonstrated a ROC curve AUC of 0.879, a sensitivity of 93.5%, a specificity of 66.7%, and a C-index of 0.602, indicating superior diagnostic efficiency compared to independent influencing factors. The ER nomogram prediction model confirmed good discrimination and calibration in internal validation. CONCLUSION: The CEUS-Clinical combined model effectively monitors the risk of ER in high-risk populations following radical resection of HCC, timely interventions to improve patient prognosis.

Comparative analysis of the molecular response characteristics in Platycodon grandiflorus irradiated with heavy ion beams and X-rays.

The response of plants to radiation is an essential topic in both space plant cultivation and mutation breeding by radiation. In this study, heavy ion beams (HIB) generated by the ground accelerator and X-rays (XR) were used as models of high linear energy transfer (LET) and low LET radiation to study the molecular response mechanism of Platycodon grandiflorus (P. grandiflorus) seedlings after irradiation. The gene and protein expression profiles of P. grandiflorus after 15 Gy HIB and 20 Gy XR radiation were analyzed by transcriptome and proteome. The results showed that the number of differentially expressed genes (DEGs) induced by HIB radiation was less than that of XR group, but HIB radiation induced more differentially expressed proteins (DEPs). Both HIB and XR radiation activated genes of RNA silencing, double-strand break repair and cell catabolic process. DNA replication and cell cycle related genes were down-regulated. The genes of cell wall and external encapsulating structure were up-regulated after HIB radiation. The gene expression of protein folding and glucan biosynthesis increased after XR radiation. Protein enrichment analysis indicated that HIB radiation resulted in differential protein enriched in photosynthesis and secondary metabolite biosynthesis pathways, while XR radiation induced differential protein of glyoxylate and dicarboxylate metabolism and carbon metabolism. After HIB and XR radiation, the genes of antioxidant system and terpenoid and polyketide metabolic pathways presented different expression patterns. HIB radiation led to the enrichment of non-homologous end-joining pathway. The results will contribute to understanding the biological effects of plants under space radiation.

Ultrasound-based Radiomics for Predicting Metastasis in the Lymph Nodes Posterior to the Right Recurrent Laryngeal Nerve in Patients with Papillary Thyroid Cancer.

BACKGROUND: Dissection of the lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLNs) in papillary thyroid cancer (PTC) remains controversial. OBJECTIVE: This study aimed to determine the capability of ultrasonography (US)-based radiomics for presurgical prediction of metastasis in LN-prRLNs in PTC. METHODS: Patients were retrospectively enrolled and pathologically confirmed as LN-prRLN metastasis with PTC after surgery. Radiomic analysis based on preoperative US images with manual segmentation of targets was used to develop a radiomics model. US features described in ACR TI-RADS were collected to construct a clinical model. The Radiomics model, a combined model integrating radiomics and clinical model, was also developed for the presurgical prediction of metastasis in LN-prRLNs. RESULTS: A total of 570 patients, including 488 patients with non-LN-prRLN metastasis and 82 with LN-prRLN metastasis, were assessed. The 15 topperforming features finally remained significant for constructing the radiomics model. The combined model showed that US measured tumor size (OR: 1.036, P = 0.044), US suspected lateral lymph node metastasis (OR: 2.247, P = 0.009), multifocality (OR: 1.920, P = 0.021), Delphian lymph node metastasis (DLNM) (OR: 2.300, P = 0.039), VIa compartment metastasis (OR: 5.357, P = 0.000), the radiomics score (OR: 1.003, P = 0.001) were significant risk factors for predicting LN-prRLN metastasis. The combined model achieved a higher AUC of 0.849 than that of the clinical model (AUC: 0.759) and radiomics model (AUC: 0.826). CONCLUSION: The US-based radiomics combined model can more effectively predict LN-prRLN metastasis in PTCs patients preoperatively. This approach had the potential to assist surgeons indecision-making regarding LN-prRLN dissection.

Preoperative US Integrated Random Forest Model for Predicting Delphian Lymph Node Metastasis in Patients with Papillary Thyroid Cancer.

BACKGROUND: Delphian lymph node (DLN) has been considered to be a gate that predicts widespread lymph node involvement, higher recurrence and mortality rates of head and neck cancer. OBJECTIVE: This study aimed to establish a preoperative ultrasonography integrated machine learning prediction model to predict Delphian lymph node metastasis (DLNM) in patients with diagnosed papillary thyroid carcinoma (PTC). METHODS: Ultrasonographic and clinicopathologic variables of PTC patients from 2014 to 2021 were retrospectively analyzed. The risk factors associated with DLNM were identified and validated through a developed random forest (RF) algorithm model based on machine learning and a logistic regression (LR) model. RESULTS: A total of 316 patients with 402 thyroid lesions were enrolled for the training dataset and 280 patients with 341 lesions for the validation dataset, with 170 (28.52%) patients developed DLNM. The elastography score of ultrasonography, central lymph node metastasis, lateral lymph node metastasis, and serum calcitonin were predictive factors for DLNM in both models. The RF model has better predictive performance in the training dataset and validation dataset (AUC: 0.957 vs. 0.890) than that in the LR model (AUC: 0.908 vs. 0.833). CONCLUSION: The preoperative ultrasonography integrated RF model constructed in this study could accurately predict DLNM in PTC patients, which may provide clinicians with more personalized clinical decision-making recommendations preoperatively. Machine learning technology has the potential to improve the development of DLNM prediction models in PTC patients.

Multi-generation study of heavy ion beam-induced mutations and agronomic trait variations to accelerate rice breeding.

Heavy ion beam (HIB) is an effective physical mutagen that has been widely used in plant mutational breeding. Systemic knowledge of the effects caused by different HIB doses at developmental and genomic levels will facilitate efficient breeding for crops. Here we examined the effects of HIB systematically. Kitaake rice seeds were irradiated by ten doses of carbon ion beams (CIB, 25 - 300 Gy), which is the most widely used HIB. We initially examined the growth, development and photosynthetic parameters of the M1 population and found that doses exceeding 125 Gy caused significant physiological damages to rice. Subsequently, we analyzed the genomic variations in 179 M2 individuals from six treatments (25 - 150 Gy) via whole-genome sequencing (WGS). The mutation rate peaks at 100 Gy (2.66×10-7/bp). Importantly, we found that mutations shared among different panicles of the same M1 individual are at low ratios, validating the hypothesis that different panicles may be derived from different progenitor cells. Furthermore, we isolated 129 mutants with distinct phenotypic variations, including changes in agronomic traits, from 11,720 M2 plants, accounting for a 1.1% mutation rate. Among them, about 50% possess stable inheritance in M3. WGS data of 11 stable M4 mutants, including three lines with higher yields, reveal their genomic mutational profiles and candidate genes. Our results demonstrate that HIB is an effective tool that facilitates breeding, that the optimal dose range for rice is 67 - 90% median lethal dose (LD50), and that the mutants isolated here can be further used for functional genomic research, genetic analysis, and breeding.

Subchorionic Hematoma Volume Measured by Virtual Organ Computer-Aided Analysis in the Prediction of First-Trimester Pregnancy Outcome.

ABSTRACT: This study aimed to assess the association of subchorionic hematoma (SCH) size measured by virtual organ computer-aided analysis (VOCAL) with the first-trimester pregnancy outcome. A total of 139 first-trimester pregnancies from 6 to 12 weeks of gestational age with SCH were included. The circumference, area, and volume of the SCH (Cs, As, and 3DVs) and gestational sac (Cg, Ag, and 3DVg) were automatically calculated by VOCAL. Interobserver agreement was assessed with the intraclass correlation coefficient and Bland-Altman plot. Odds ratios for the clinical and ultrasound characteristics of adverse pregnancy outcomes were estimated by univariate or multivariable logistic regression. There was high interobserver agreement in VOCAL measurements of the SCH and gestational sac (intraclass correlation coefficients, >0.900). By univariate regression analysis, women with adverse pregnancy outcomes were more likely to have vaginal bleeding, a larger As and 3DVs, and higher Cs/Cg, As/Ag, and 3DVs/3DVg ratios (all P < 0.05). In the multivariable regression analysis, a higher 3DVs/3DVg ratio of SCH (odds ratio, 1.034; 95% confidence interval [CI], 1.015-1.053; P = 0.000) and vaginal heavy bleeding had a significant positive relationship with the risk of adverse pregnancy outcomes (odds ratio, 7.846; 95% CI, 1.104-55.737; P = 0.039) remained associated with an increased risk of adverse pregnancy outcomes. With 11.87% as the cutoff, the receiver operating characteristic curve yielded a good predictive performance (area under the curve, 0.713) and high sensitivity (91.18%). The measurements of SCH by VOCAL provide high reliability for estimating the total hematoma burden in first-trimester pregnant patients. A greater volume proportion (3DVs/3DVg) of SCH worsens the pregnancy outcome, and a greater risk of adverse pregnancy outcome also associated with the severity of vaginal bleeding.

Flexible CuS-embedded human serum albumin hollow nanocapsules with peroxidase-like activity for synergistic sonodynamic and photothermal cancer therapy.

Nanoparticle flexibility is an important parameter in determining cell uptake and tumor accumulation, thus modulating therapeutic efficiency in cancer treatment. Herein, we successfully prepared CuS-embedded human serum albumin hollow nanocapsules (denoted CuS/HSA) by a hard-core-assisted layer-by-layer coating approach. This approach afforded CuS/HSA hollow nanocapsules with controllable shell thickness, tunable flexibility, uniform size (272.9 nm), a large hollow cavity, peroxidase-like activity, excellent photothermal conversion ability, and a high tetra-(4-aminophenyl) porphyrin (TAPP) loading capacity (27.3 wt%). The peroxidase-like activity of the CuS nanoparticles enabled them to overcome tumor hypoxia and augment the sonodynamic therapeutic (SDT) effects and photothermal conversion ability for photothermal therapy (PTT). In vitro experiments showed that the CuS/HSA-TAPP hollow nanocapsules efficiently induced cancer cell apoptosis under US irradiation and cancer cell ablation under laser irradiation, thus facilitating synergistic SDT and PTT. Importantly, the flexibility of the CuS/HSA hollow nanocapsules resulted in significantly enhanced cellular internalization and a longer mean residence time (131.3 h) than their solid counterparts (21.0 h). In a breast tumor model, the flexible CuS/HSA hollow nanocapsules exhibited high tumor accumulation of up to 27.1%. In vivo experiments demonstrated that the flexible CuS/HSA-TAPP hollow nanocapsules effectively eliminated breast tumors via the synergistic effect of SDT and PTT.

Ultrasound Assisted a Peroxisome Proliferator-Activated Receptor (PPAR)γ Agonist-Loaded Nanoparticle-Microbubble Complex to Attenuate Renal Interstitial Fibrosis.

OBJECTIVE: To investigate the antifibrotic effect of the combination of a PPARγ agonist-loaded nanoparticle-microbubble complex with ultrasound (US) exposure on renal interstitial fibrosis (RIF). MATERIALS AND METHODS: Polylactide-co-glycolide (PLGA) nanoparticles were used to load PPARγ agonist (rosiglitazone, RSG) and prepare PLGA-RSG nanoparticles (PLNPs-RSG); then, a novel complex between PLNPs-RSG and SonoVue microbubbles (MBs) (PLNPs-RSG-MBs) was prepared. The size distribution, zeta potentials, RSG-loading capacity and entrapment efficiency were measured, and the release of RSG was assessed using a UV-vis spectrophotometer. The in vitro cytotoxicity and in vivo systemic toxicity assays were performed. The cellular uptake assessment was performed using a confocal laser scanning microscope (CLSM). The in vivo biodistribution assessment was performed using fluorescence imaging with a near-infrared (NIR) imaging system. Furthermore, this complex was administered to a unilateral ureteral obstruction (UUO) rat model with the assistance of US exposure to investigate the antifibrotic effect. RESULTS: This PLNPs-RSG-MBs complex had a size of 2199.5± 988.1 nm and a drug-loading efficiency of 28.5%. In vitro cytotoxicity and in vivo systemic toxicity assays indicated that the PLNPs-RSG-MBs complex displayed excellent biocompatibility. In addition, the complex showed high cellular uptake efficiency in vitro and kidney-targeting ability in vivo. In a UUO rat model, the combination of the PLNPs-RSG-MBs complex with US exposure significantly reduced collagen deposition and successfully attenuated renal fibrosis. CONCLUSION: The combination of the PLNPs-RSG-MBs complex with US exposure may be a promising approach for the treatment of RIF.

Disulfiram-gold-nanorod integrate for effective tumor targeting and photothermal-chemical synergistic therapy.

Herein, we successfully constructed a combination therapeutic nanoplatform with high tumor targeting for cancer treatment by integrating gold nanorods with disulfiram (denoted Au-DSF). The Au-DSF integrates possess a uniform length (70 nm), excellent photothermal conversion ability and a high DSF loading content (23.2%), and the loaded DSFs show glutathione-, acid-, and laser-responsive release properties. The Au-DSF integrates show significantly enhanced cellular uptake efficiency in breast cancer cells due to the ability of DSF to chelate to the intracellular copper (Cu) which is present at high concentrations. Furthermore, the Au-DSF exhibits improved circulation time (mean residence time = 28.4 h) and increased tumor accumulation (12.0%), due to the targeting of DSF to the abundant Cu ions at the tumor site. Moreover, the DSF/Cu complexes potently elevate reactive oxygen species, which effectively induce cancer cell apoptosis. In vivo experiments show that the Au-DSF integrates dramatically decrease tumor size via photothermal therapy and chemotherapy. Hematoxylin-eosin and TUNEL staining show that the Au-DSF integrates induce necrosis and apoptosis in cancer cells. The high therapeutic efficiency of the Au-DSF integrates for breast cancer is further demonstrated by the reduced elasticity seen in ultrasound elastography, and the absence of perfusion of the contrast agent in contrast-enhanced ultrasound imaging in tumors.

Smart Bacterial Magnetic Nanoparticles for Tumor-Targeting Magnetic Resonance Imaging of HER2-Positive Breast Cancers.

Supersensitive magnetic resonance (MR) imaging requires contrast with extremely high r2 values. However, synthesized magnetic nanoparticles generally have a relatively low r2 relaxivity. Magnetosomes with high saturation magnetization and good biocompatibility have shown potential values as MR imaging contrast agents. Magnetosomes that target human epidermal growth factor receptor-2 (HER2) were prepared using genetic technology and low-frequency sonication. Anti-HER2 affibody of the ability to target HER2 was displayed on the membrane surface of the magnetosomes through the anchor protein MamC, allowing the bacterial nanoparticles to target tumors overexpressing HER2. The prepared nanoparticles exhibited a very high relaxivity of 599.74 mM-1 s-1 and better dispersion, and their ability to target HER2 was demonstrated both in vitro and in vivo. Also, the HER2-targeting magnetosomes significantly enhanced the MR imaging of orthotopic breast cancer models with or without HER2 expression using a 7.0 T scanner. In particular, tumors overexpressing HER2 demonstrated better MR imaging than HER2-negative tumors after intravenous administration of HER2-targeting magnetosomes, and the MR signals of the augmented contrast could be detected from 3 to 24 h. The magnetosomes did not cause any notable pathogenic effect in the animals. Therefore, we expect that noninvasive imaging of tumors using HER2-targeting magnetosomes has potential for clinical applications in the near future.

Contrast-enhanced ultrasound for differentiating benign from malignant solid small renal masses: comparison with contrast-enhanced CT.

PURPOSE: The study aimed to compare the diagnostic efficiency of contrast-enhanced ultrasound (CEUS) with that of contrast-enhanced computed tomography (CECT) in the evaluation of benign and malignant small renal masses (SRMs) (<4 cm) confirmed by pathology. METHODS: A total of 118 patients with 118 renal masses smaller than 4 cm diagnosed by both CEUS and CECT were enrolled in this study, including 25 benign lesions and 93 malignant lesions. All lesions were confirmed by histopathologic diagnosis after surgical resection. The diagnostic imaging studies of the patients were retrospectively reviewed by two independent ultrasonologists and two independent radiologists blinded to the CT or ultrasound findings and final histological results. All lesions on both CEUS and CECT were independently scored on a 3-point scale (1: benign, 2: equivocal, and 3: malignant). The concordance between interobserver agreement was interpreted using a weighted kappa statistic. The diagnostic efficiency of the evaluation of benign and malignant lesions was compared between CEUS and CECT. RESULTS: All the 118 included lesions were detected by both CEUS and CECT. In CEUS and CECT imaging evaluation of the 118 lesions, the weighted kappa value interpreting the concordance between interobserver agreement was 0.89 (95% CI 0.79-0.98) and 0.93 (95% CI 0.87-0.99), respectively. Both CEUS and CECT demonstrated good diagnostic performance in differential diagnosis of benign and malignant SRMs with sensitivity of 93.5% and 89.2%, specificity of 68% and 76%, PPV of 91.6% and 93.3%, NPV of 73.9% and 65.5%, and AUC of 0.808 and 0.826, respectively. There was no statistically significant difference in any of the diagnostic performance indices between these two methods (P > 0.05). However, the qualitative diagnosis of small papillary renal cell carcinoma (RCC) by CEUS was significantly better than that by CECT (P < 0.05), while there was no significant difference in qualitative diagnostic accuracy on other histotypes of SRMs between CEUS and CECT (P > 0.05). CONCLUSIONS: Both CEUS and CECT imaging modalities are effective for the differential diagnosis of benign and malignant SRMs. Furthermore, CEUS may be more effective than CECT for the qualitative diagnosis of small papillary RCC.

GABA and GABA receptors alterations in the primary visual cortex of concave lens-induced myopic model.

Until recently most researches on myopia mechanisms have mainly been focused on the eye ball and few investigations were explored on the upper visual pathway, such as the visual cortex. The roles of gamma-aminobutyric acid (GABA) in the retinal and in the upper visual pathway are inter-correlated. As the retinal glutamate decarboxylase (GAD), GABA, and the mRNA levels of GABA receptors increased during the concave lens induced myopia formation, however, whether GABA alterations also occurred in the visual cortex during the concave lens induction is still unknown. In the present study, using HPLC, Enzyme-Linked Immunosorbent Assay (ELISA) and Real-Time Quantitative-PCR (RT-PCR) methods, we observed the changing trends of GABA, glutamate decarboxylase (GAD), and GABA receptors in the visual cortex of concave lens-induced myopic guinea pigs. Similar to the changing patterns of retinal GABA, the concentrations of GAD, GABA and the mRNA levels of GABA receptors in the visual cortex also increased. These results indicate that the exploration on myopia mechanisms should possibly be investigated on the whole visual pathway and the detailed significance of cortical GABA alterations needs further investigation.

Tumor Acidic Microenvironment Targeted Drug Delivery Based on pHLIP-Modified Mesoporous Organosilica Nanoparticles.

Enhancing the tumor-targeting delivery of chemotherapeutic drugs is important yet challenging for improving therapeutic efficacy and reducing the side effects. Here, we first construct a drug delivery system for targeting tumor acidic microenvironment by modification of pH (low) insertion peptide (pHLIP) on mesoporous organosilica nanoparticles (MONs). The MONs has thioether-bridged framework, uniform diameter (60 nm), good biocompatibility, and high doxorubicin (DOX) loading capacity (334 mg/g). The DOX loaded in the pHLIP modified MONs can be released responsive to glutathione and low pH circumstance, ensuring the chemotherapeutic drug exerts higher cytotoxic effects to cancer cells than normal cells because of high intracellular GSH of tumor cells and low pH of tumor microenvironment. Moreover, the engineered MONs exhibit higher cellular uptake in pH 6.5 medium by MDA-MB-231 and MCF-7 cells than the particles decorated with polyethylene glycol (PEG). Importantly, the pHLIP-mosaic MONs with DOX displays better cytotoxic effects against the breast cancer cells in pH 6.5 medium than pH 7.4 medium. The in vivo experiments demonstrate that the pHLIP modified MONs are accumulated in the orthotopic breast cancer via targeting to acidic tumor microenvironment while no serious pathogenic effects was observed. After loading DOX, the pHLIP-modified MONs display better therapeutic effects than the control groups on the growth of MCF-7 breast cancers, showing promise for enhancing chemotherapy.

Three-Dimensional Assessment of Automated Breast Volume Scanner Compared with Handheld Ultrasound in Pre-Operative Breast Invasive Ductal Carcinomas: A Pilot Study of 51 Cases.

The aim of the work described here was to compare the accuracy of conventional handheld ultrasound (HHUS) with that of an automated breast volume scanner (ABVS) in 3-D assessment of pre-operative invasive ductal carcinomas. HHUS and ABVS were used in 51 patients to obtain the largest tumor diameter, tumor volume and tumor surface area. The volumetric measurement was also obtained from ABVS data with medical software. With tumor size and volume on pathology as the gold standard, Bland-Altman analysis was used to compare variability. Correlation coefficients and receiver operating characteristic curves were established for all measurements for T2 classification. The correlation coefficients of all ABVS measurements were stronger than those of HHUS measurements, with the ABVS volumetric measurement significantly different with a higher accuracy of 88.24% (45/51) and predicting T-classification with higher area under the receiver operating characteristic curves (0.936). Therefore, 3-D measurements provide stronger correlations with pathology in tumor size measurement. However, more clinical trials are needed to confirm our findings.