Exosome-mediated delivery of artificial circular RNAs for gene therapy of bladder cancer.

Bladder cancer (BCa) is one of the most common malignancies affecting men. Oncogenic transcription factors function as an important regulator in the progression of human cancer. In our study, we aimed to construct artificial circular non-coding RNAs (acircRNAs) consisting of three functional units that mimic the CRISPR-Cas system and elucidate its therapeutic role in bladder cancer. Additionally, the compare of the efficiency in regulating gene expression between acircRNA and CRISPR-dCas systems was performed. We connected the cDNA sequences of TFs aptamer and constructed a circRNA. To demonstrate the platform's practicality, ß-catenin and NF-κB were chosen as functional targets, while T24 and 5637 cell lines served as test models. Real-time Quantitative PCR (qPCR), double luciferase assay and related phenotype assay were used to detect the expression of related genes and the therapeutic effect. To elucidate the functionality of acircRNAs, luciferase vectors capable of detecting ß-catenin and NF-κB expression were employed to assess the inhibitory impact of acircRNA on ß-catenin and NF-κB. Consequently, the optimal combination involving acircRNA-3 was determined. Next, qPCR assay was employed to assess the relative expression levels of target downstream genes following acircRNA treatment. The expression of c-myc and cyclin D1 were used to determine the function of ß-catenin, while Bcl-XL and TRAF1 were used to determine that of NF-κB. The acircRNAs inhibited the ß-catenin and NF-κB related signaling in BCa cells specifically. CD63-HuR fusion protein was used to loading acircRNA into exosomes. The results showed that acircRNA could inhibit the activity of the target transcription factors, and the inhibitory effect was better than that of CRIPSR-dCas9-KRAB. Furthermore, functional experiments demonstrated that the transfection of acircRNA in bladder cells resulted in decreased proliferation, enhanced apoptosis, and suppressed migration. In conclusion, our synthetic gene device exhibited anti-tumor regulatory capabilities and showed greater efficiency in tumor suppression compared to the CRISPR-dCas9-KRAB system. Therefore, our device provides a new strategy for cancer treatment and could be a useful strategy for cancer cells.

Ultrasound tissue scatterer distribution imaging: An adjunctive diagnostic tool for shear wave elastography in characterizing focal liver lesions.

OBJECTIVES: Focal liver lesion (FLL) is a prevalent finding in cross-sectional imaging, and distinguishing between benign and malignant FLLs is crucial for liver health management. While shear wave elastography (SWE) serves as a conventional quantitative ultrasound tool for evaluating FLLs, ultrasound tissue scatterer distribution imaging (TSI) emerges as a novel technique, employing the Nakagami statistical distribution parameter to estimate backscattered statistics for tissue characterization. In this prospective study, we explored the potential of TSI in characterizing FLLs and evaluated its diagnostic efficacy with that of SWE. METHODS: A total of 235 participants (265 FLLs; the study group) were enrolled to undergo abdominal examinations, which included data acquisition from B-mode, SWE, and raw radiofrequency data for TSI construction. The area under the receiver operating characteristic curve (AUROC) was used to evaluate performance. A dataset of 20 patients (20 FLLs; the validation group) was additionally acquired to further evaluate the efficacy of the TSI cutoff value in FLL characterization. RESULTS: In the study group, our findings revealed that while SWE achieved a success rate of 49.43 % in FLL measurements, TSI boasted a success rate of 100 %. In cases where SWE was effectively implemented, the AUROCs for characterizing FLLs using SWE and TSI stood at 0.84 and 0.83, respectively. For instances where SWE imaging failed, TSI achieved an AUROC of 0.78. Considering all cases, TSI presented an overall AUROC of 0.81. There was no statistically significant difference in AUROC values between TSI and SWE (p > 0.05). In the validation group, using a TSI cutoff value of 0.67, the AUROC for characterizing FLLs was 0.80. CONCLUSIONS: In conclusion, ultrasound TSI holds promise as a supplementary diagnostic tool to SWE for characterizing FLLs.

Contrast-enhanced mammography-guided biopsy: technique and initial outcomes.

Contrast-enhanced mammography-guided biopsy (CEM-Bx), a novel technique for diagnosing suspicious enhanced lesions, was commercialized for clinical application in 2021; however, there are only a few publications documenting this technique in the existing literature. The aim of this study was to evaluate the procedural performance and preliminary outcomes of CEM-Bx performed in our hospital between from September 2021 to June 2022. We reviewed data of 12 women who underwent CEM-Bx during the study period, including their demographic and procedural characteristics, biopsy success rate, histopathological diagnosis, and average glandular dose (AGD). All women (mean age ± standard deviation: 54±6 years) showed enhanced breast lesions on CEM and underwent CEM-Bx within one week. The success rate of CEM-Bx was 100%. The vertical needle approach was used in a decubitus position (N=7, 58%), while the horizontal needle approach was used in an upright sitting position (N=5, 42%). The mean procedure time for the CEM-Bx was 17±6.3 min. The mean AGD was 14.3±12.3 mGy. Histopathologic examination revealed a malignancy rate of 66.7%. In summary, CEM-Bx is a feasible technique, with a high success rate of diagnosing contract-enhanced lesions.

Changes in Serum CRP and PCT Levels in Patients with Acute Simple Lower Urinary Tract Infection and Evaluation of the Efficacy of Treatment with Shuangdong Capsules.

Objective: The aim of this study is to investigate the changes and significance of serum C-reactive protein (CRP) and procalcitonin (PCT) levels in patients with acute simple lower urinary tract infection (ALUTI) and to analyze the efficacy of treatment with Shuangdong capsules, so as to provide a basis for the rational clinical application of drugs. Methods: 92 patients with ALUTI (observation group) were randomly divided into 46 cases each in group A and group B. Group A was treated with basic anti-infective drugs, while group B was treated with Shuangdong capsules, and the duration of treatment in both groups was 14 days. The curative effect of the two groups was analyzed, and the changes in serum PCT and CRP levels were compared before and after treatment and compared with 40 healthy people in the control group. Results: The serum PCT and CRP levels, the number of urinary leukocyte count (LEU), and the number of urinary bacterial count (BACT) were significantly higher in Group A and Group B than in the healthy control group before treatment (P < 0.05). After treatment, the total clinical efficiency of patients in group B (97.83%) was significantly higher than that in group A (78.26%) (P < 0.05). The serum PCT and CRP levels, the number of urinary LEU, and the number of urinary BACT decreased in both groups after treatment compared with those before treatment, and all of them were significantly lower in group B than in group A (P < 0.05). The area under the curve (AUC) values of serum PCT and CRP levels for the diagnosis of acute simple lower urinary tract infection were 0.747 (95% CI 0.633-0.860) and 0.926 (95% CI 0.870∼0.982), both with high sensitivity and specificity. Conclusion: The Shuangdong capsule combined with conventional antibacterial drugs has better clinical efficacy in the treatment of acute simple lower urinary tract infection; serum CRP and PCT levels in patients with acute simple lower urinary tract infection can be used as indicators for diagnosis and efficacy determination of the infection.

A case report of breast cancer in silicone-injected breasts diagnosed by an emerging technique of contrast-enhanced mammography-guided biopsy.

Background: Breast cancer in silicone-injected breasts is often obscured in conventional mammography and sonography. Contrast-enhanced magnetic resonance imaging (CE-MRI) is an optimal modality for cancer detection. This case report demonstrates the use of contrast-enhanced spectral mammography (CESM) and CESM-guided biopsy (CESM-Bx) to diagnose breast cancer in silicone-injected breasts. However, there is no relevant report in the literature. Case Presentation: A 59-year-old woman who received a liquid silicone injection for breast augmentation 30 years ago was transferred to our hospital for a CE-MRI-guided biopsy due to a suspicion of cancer in her right breast. The CE-MRI showed a 3.1-cm irregular enhanced mass and a 1.1-cm circumscribe mass in the upper outer quadrant of the right breast. Unfortunately, the CE-MRI-guided biopsy had to wait for 1 month due to a busy schedule. The CESM revealed two masses that were consistent with CE-MRI findings. CESM-Bx was performed, and the patient was diagnosed with invasive lobular carcinoma with an irregular mass and fibroadenoma of the circumscribed mass. The patient underwent substantial surgery. Conclusions: CESM-Bx is a simple emerging technique that can be used feasibly to obtain tissue proof on the concerned enhanced lesion on CESM. In such cases of silicone-injected breasts, the CESM-Bx can be used as an alternative to MRI-guided biopsy for cancer diagnosis.

Hepatic Steatosis Assessment as a New Strategy for the Metabolic and Nutritional Management of Duchenne Muscular Dystrophy.

Growing evidence suggests that patients with Duchenne muscular dystrophy (DMD) have an increased risk of obesity and metabolic syndrome (MetS). The aim of this study was to investigate the potential risk factors for MetS and hepatic steatosis in patients with different stages of DMD. A total of 48 patients with DMD were enrolled and classified into three stages according to ambulatory status. Body mass index (BMI), serum fasting glucose, insulin, and lipid profiles including triglycerides (TG) and high-density lipoprotein were measured, and the homeostatic model assessment for insulin resistance (HOMA-IR) index was evaluated. Ultrasound examinations of the liver were performed to assess hepatic steatosis using the Nakagami parameter index (NPI). The results showed that BMI, TG, HOMA-IR, and ultrasound NPI differed significantly among DMD stages (p < 0.05). In contrast to the low rates of conventional MetS indices, including disturbed glucose metabolism (0%), dyslipidemia (14.28%), and insulin resistance (4.76%), a high proportion (40.48%) of the patients had significant hepatic steatosis. The ultrasound NPI increased with DMD progression, and two thirds of the non-ambulatory patients had moderate to severe hepatic steatosis. Steroid treatment was a risk factor for hepatic steatosis in ambulatory patients (p < 0.05). We recommend that DMD patients should undergo ultrasound evaluations for hepatic steatosis for better metabolic and nutritional management.

Ultrasound Detection of Liver Fibrosis in Individuals with Hepatic Steatosis Using the Homodyned K Distribution.

Acoustic structure quantification (ASQ) based on the analysis of ultrasound backscattered statistics has been reported to detect liver fibrosis without significant hepatic steatosis. This study proposed using ultrasound parametric imaging based on the parameter α of the homodyned K (HK) distribution for staging liver fibrosis in patients with significant hepatic steatosis. Raw ultrasound image data were acquired from patients (n = 237) to construct B-mode and HK α parametric images, which were compared with the focal disturbance (FD) ratio obtained from ASQ on the basis of histologic evidence (METAVIR fibrosis score and hepatic steatosis severity). The data were divided into group I (n = 173; normal to mild hepatic steatosis) and group II (n = 64; with moderate to severe hepatic steatosis) for statistical analysis through one-way analysis of variance and receiver operating characteristic (ROC) curve analysis. The results showed that the HK α parameter monotonically decreased as the liver fibrosis stage increased (p < .05); concurrently, the FD ratio increased (p < .05). For group I, the areas under the ROC (AUROCs) obtained using the FD ratio and the α parameter (AUROCFD and AUROCα) were, respectively, 0.56 and 0.55, 0.68 and 0.68, 0.64 and 0.64 and 0.62 and 0.62 for diagnosing liver fibrosis ≥F1, ≥F2, ≥F3 and ≥F4. The values of AUROCFD and AUROCα for group II were, respectively, 0.88 and 0.91, 0.81 and 0.81, 0.77 and 0.76 and 0.78 and 0.73 for diagnosing liver fibrosis ≥F1, ≥F2, ≥F3 and ≥F4. As opposed to previous studies, ASQ was found to fail in characterizing liver fibrosis in group I; however, it was workable for identifying liver fibrosis in patients with significant hepatic steatosis (group II). Compared with ASQ, HK imaging provided improved diagnostic performance in the early detection of liver fibrosis coexisting with moderate to severe hepatic steatosis. Ultrasound HK imaging is recommended as a strategy to evaluate early fibrosis risk in patients with significant hepatic steatosis.

Adaptive Iterative Dose Reduction 3D Integrated with Automatic Tube Current Modulation for CT Coronary Artery Calcium Quantification: Comparison to Traditional Filtered Back Projection in an Anthropomorphic Phantom and Patients.

RATIONALE AND OBJECTIVES: We aimed to evaluate integrated adaptive iterative dose reduction 3D (AIDR 3D) algorithm in automatic tube current modulation (ATCM) for the quantification of coronary artery calcium score (CACS) and cardiac risk stratification. MATERIALS AND METHODS: A thoracic phantom with calcium inserts of known densities was scanned with filtered back projection (FBP) and AIDR 3D algorithms in small- and medium-sized phantoms. Twenty-four patients underwent two consecutive scans of CACS with FBP and AIDR 3D algorithms. The absolute Agatston score, Agatston score risk, volume score, and Agatston score percentile-based risk were compared, and concordance coefficients and agreement plots were made. RESULTS: Agatston and volume scores were significantly different between the phantom sizes (P < .01). There were no significant differences in the Agatston scores between FBP and AIDR 3D for the medium phantoms (P = .25). In the patients, there were no significant differences in Agatston and volume scores between FBP and AIDR 3D (P = .06 and P = .09, respectively). The correlation coefficients of Agatston and volume scores with AIDR 3D were excellent compared to those of FBP. There were no significant differences in Agatston score risk and Agatston score percentile-based risk between FBP and AIDR 3D (P = .74 and P = 1, respectively). There was mean dose reduction of 57.8% ± 18.6% for AIDR 3D. CONCLUSION: The absolute Agatston score differed between FBP and AIDR 3D reconstructions. However, the cardiac risk categorizations of the two methods were comparable. An integrated AIDR 3D algorithm with automatic tube current modulation enables radiation dose savings at a consistent noise level without sacrificing CACS.

MiRNA-200a induce cell apoptosis in renal cell carcinoma by directly targeting SIRT1.

Accumulating evidence indicates that microRNAs are implicated in tumor initiation and progression through negatively regulating oncogenes or tumor suppressor genes. In the present study, we report that the expression of miR-200a was significantly lower in renal cell carcinoma (RCC) specimens and RCC cell lines. Restoration of miR-200a suppressed cell growth, arrested cell cycle progression, and promoted cell apoptosis in RCC cell lines. We next used qRT-PCR array technology to identify Sirtuin 1 (SIRT1) as one of the downregulated proteins during miR-200a overexpression in 786-O cells. Following a further assay by luciferase reporter system, SIRT1 was validated as a direct target of miR-200a. Moreover, siRNA-mediated knockdown of SIRT1 could partially phenocopy the effects of miR-200a overexpression. In contrast, overexpression of truncated SIRT1 (without an endogenous 3'-UTR) could rescue the effect of miR-200a overexpression on 786-O cells, which suggested that SIRT1 3'-UTR is targeted by miR-200a specifically. These observations provide further evidence for a critical tumor-suppressive role of the miR-200a in RCC in addition to identifying a novel regulatory mechanism, which may contribute to SIRT1 upregulation in RCC.