CircNOP14 increases the radiosensitivity of hepatocellular carcinoma via inhibition of Ku70-dependent DNA damage repair.

Circular RNAs (circRNAs) are profoundly affected in hepatocellular carcinoma (HCC) through various pathways. However, the role of circRNAs in the radiosensitivity of HCC cells is yet to be explored. In this study, we identified a circRNA-hsa_circ_0006737 (circNOP14) involved in the radiosensitivity of HCC. We found that circNOP14 increased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified Ku70 as a novel and robust interacting protein of circNOP14. Mechanistically, circNOP14 interacts with Ku70 and prevents its nuclear translocation, thereby increasing irradiation-induced DNA damage. Therefore, our findings may provide a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

Contrast-enhanced ultrasound evaluation of renal perfusion before angioplasty and its predictive value for hypertension.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is a common disease in the elderly population. OBJECTIVE: The aim was to develop a contrast-enhanced ultrasound (CEUS)-based model for predicting post-angioplasty improvement in hypertension in patients with severe ARAS. METHODS: Thirty-five patients with severe ARAS (⩾ 70%) were included in this study, and 42 renal arteries received percutaneous transluminal renal arterial stenting. An optimal integral formula was developed from pre-interventional color-coded duplex sonography (CCDS) and CEUS parameters using least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic (ROC) curve analysis. A model for predicting short-term hypertension improvement was established using the integral formula and clinical risk factors. Bootstrapping was used for internal validation. RESULTS: Two integral formulas, LASSO.CCDS and LASSO.CEUS, were established. ROC curves of the two integral formulas showed that LASSO.CEUS was the better formula for predicting hypertension improvement (AUC 0.816, specificity 78.6%). Univariate and multivariate regression analyses showed that duration of hypertension (OR 0.841, P= 0.027), diabetes (OR = 0.019, P= 0.010), and LASSO.CEUS (OR 7.641, P= 0.052) were predictors of short-term hypertension improvement after interventional therapy. Using LASSO.CEUS combined with clinical risk factors, the following prediction model was established: logit (short-term improvement in hypertension) = 1.879-0.173 × hypertension duration - 3.961 × diabetes + 2.034 × LASSO.CEUS (AUC 0.939). CONCLUSIONS: The model established using CEUS parameters and clinical risk factors could predict hypertension improvement after interventional therapy, but further research and verification are needed.

Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)-derived from exons 2-6 of EYA3-facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions. METHODS: CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model. RESULTS: CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells. CONCLUSIONS: Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

Learning and Investigation of the Role of Angiotensin-Converting Enzyme in Radiotherapy for Nasopharyngeal Carcinoma.

Ionizing radiation (IR) is an important treatment for nasopharyngeal carcinoma (NPC) that mainly kills tumor cells by producing large amounts of reactive oxygen species (ROS). Intracellular ROS levels affect the sensitivity of tumor cells to IR. Recently, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-converting enzyme (ACE) have been found to affect the intracellular levels of ROS. Therefore, we performed a health informatics assessment of ACE in the TCGA database. We explored the effect of ACE in NPC cells. We found that either knockdown of ACE or inhibition of ACE by enalaprilat could decrease ROS levels in NPC cells. Furthermore, knockdown of ACE or inhibition of ACE by enalaprilat could reduce IR-induced ROS levels. ACE knockdown or inhibition reduced IR-induced DNA damage and apoptosis. ACE overexpression increased the level of ROS in NPC cells and further increased sensitivity to IR. These findings indicate that ACE influences the effect of IR by regulating the level of ROS in NPC cells.

Percutaneous ablation of liver metastases from colorectal cancer: a comparison between the outcomes of ultrasound guidance and CT guidance using propensity score matching.

PURPOSE: The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM). METHODS: This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients' initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)-free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups. RESULTS: PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040). CONCLUSION: For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.

Peritumoral abnormalities on dynamic-enhanced CT after brachytherapy for hepatic malignancies: local progression or benign changes?

OBJECTIVES: To determine if dynamic CT can differentiate local progression from radioactive seed-induced peritumoral reaction (RSIPR) after brachytherapy with iodine-125 radioactive seeds (BIRS) for advanced hepatic malignancies. METHODS: Enhanced CT images of seed-implanted lesions between 2006 and 2018 were retrospectively evaluated. Hounsfield units of peritumoral parenchyma were measured and assessed quantitatively. The classification, conversion, consequences, and serological indicators during follow-up were recorded and quantified. Statistical differences were analyzed using a Pearson χ2 test. RESULTS: RSIPR was observed in 201 of 290 (69.3%) lesions (161 patients; median age, 55 years; range, 26-79 years), while local progression occurred in 53 lesions. The low density of local progression was much lower than that of RSIPR (p < 0.001), and the former did not exhibit iso-/high density in the portal or equilibrium phase. Ring-like enhancement in progressive lesions was also quite different from RSIPR. Local progression rate was lower for lesions with RSIPR than for those without RSIPR (14.9% vs 25.8%; p = 0.03), and their doses were different (397.2 Gy vs 120.3 Gy, p < 0.001). CONCLUSIONS: Radioactive seed-induced peritumoral reaction has characteristic manifestations on CT images, which is associated with a higher dose of lesions and lower local progression rate. Notably, the enhancement pattern of local progression was distinct from RSIPR and was clearly distinguishable on dynamic-enhanced CT. KEY POINTS: • Radioactive seed-induced peritumoral reaction after brachytherapy with 125I seeds for liver malignancies has characteristic manifestations on CT images, which is associated with a higher dose of lesions (397.2 Gy vs 120.3 Gy, p < 0.001), as a focal radiation injury. • Lesions with RSIPR were less likely to develop local progression, while those without RSIPR had a higher rate of local progression (14.9% vs 25.8%; p = 0.03). • The enhancement pattern of local progression after brachytherapy was distinct from radioactive seed-induced peritumoral reaction and was clearly distinguishable on dynamic-enhanced CT.

High Levels of DEAH-Box Helicases Relate to Poor Prognosis and Reduction of DHX9 Improves Radiosensitivity of Hepatocellular Carcinoma.

Background: Liver hepatocellular carcinoma (LIHC), one of the most common primary malignancies, exhibits high levels of molecular and clinical heterogeneity. Increasing evidence has confirmed the important roles of some RNA helicase families in tumor development, but the function of the DEAH-box RNA helicase family in LIHC therapeutic strategies has not yet been clarified. Methods: The LIHC dataset was downloaded from The Cancer Genome Atlas (TCGA). Consensus clustering was applied to group the patients. Least absolute shrinkage and selection operator Cox regression and univariate and multivariate Cox regression were used to develop and validate a prognostic risk model. The Tumor Immune Estimation Resource and Tumor Immune Single Cell Hub databases were used to explore the role of DEAH-box RNA helicases in LIHC immunotherapy. In vitro experiments were performed to investigate the role of DHX9 in LIHC radiosensitivity. Results: Twelve survival-related DEAH-box RNA helicases were identified. High helicase expression levels were associated with a poor prognosis and clinical features. A prognostic model comprising six DEAH-box RNA helicases (DHX8, DHX9, DHX34, DHX35, DHX38, and DHX57) was constructed. The risk score of this model was found to be an independent prognostic indicator, and LIHC patients with different prognosis were distinguished by the model in the training and test cohorts. DNA damage repair pathways were also enriched in patients with high-risk scores. The six DEAH-box RNA helicases in the risk model were substantially related to innate immune cell infiltration and immune inhibitors. In vitro experiments showed that DHX9 knockdown improved radiosensitivity by increasing DNA damage. Conclusion: The DEAH-box RNA helicase signature can be used as a reliable prognostic biomarker for LIHC. In addition, DHX9 may be a definitive indicator and therapeutic target in radiotherapy and immunotherapy for LIHC.

USP12 positively regulates M-MDSC function to inhibit antitumour immunity through deubiquitinating and stabilizing p65.

The relative abundance of myeloid-derived suppressor cells (MDSCs) compared to cytotoxic T cells determines the outcomes of diseases and the efficacy of immunotherapy. Ubiquitin-specific peptidase 12 (USP12), a member of the USP family of deubiquitinases, targets multiple signalling pathways and regulates diverse biological processes, including cell proliferation and survival. It is well known that ubiquitylation is an important mechanism for regulating the immune response. However, it is unclear whether USP12 regulates tumour growth by influencing MDSCs. In the present study, we reported that USP12 deficiency decreased infiltration and impaired the suppressor function of monocytic (M)-MDSCs, resulting in increased CD8+ T-cell response and decelerated tumour growth. USP12-knockout M-MDSCs were less potent in inhibiting the proliferation of CD8+ T cells and their ability to secrete IFN-γ. Furthermore, USP12 deficiency inhibited the suppressor function of M-MDSCs by downregulating the negative regulatory molecules inducible nitric oxide synthase and PD-L1, through deubiquitinating and stabilizing p65. Our results suggest that USP12 is a positive regulator of M-MDSCs and may serve as a potential target for antitumor therapy.

Prediction of Split Renal Function Improvement After Renal Artery Stenting by Blood Oxygen Level-Dependent Magnetic Resonance Imaging.

Background: The discrepancy between the high technical success rate and the relatively low clinical response rate of renal artery stenting (RAS) raises the importance to identify atherosclerotic renal artery stenosis (ARAS) patients who are most likely to benefit from RAS. This study aimed to investigate the feasibility and accuracy of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) in predicting split renal function (SRF) improvement after RAS in patients with ARAS. Methods: Thirty patients with severe ARAS who were treated with RAS were enrolled. Baseline cortical and medullary R2* values of each kidney were measured by BOLD-MRI, and each patient's SRF was evaluated by nuclear renal dynamic imaging at baseline and 1-month follow-up. Results: In total, 35 severe stenotic renal arteries of the 30 patients were analyzed. At 1-month follow-up, 34 kidneys (97.1%) of severe ARAS had acquired SRF. SRF improved in 12 kidneys of 10 patients. The cortical R2* and medullary R2* values in the SRF improvement kidneys were higher than those in the non-improvement kidneys (P ≤ 0.001). The area under the curve of medullary R2* was 0.879 (95% confidence interval [CI] 0.736-1.000). A medullary R2* value ≥29.1 s-1 was noted to provide good sensitivity (0.833, 95% CI 0.552-0.970) and specificity (0.864, 95% CI 0.667-0.953) in predicting SRF improvement. Medullary R2* value was the only independent predictor of SRF improvement in multivariable analysis (P = 0.034, OR 3.017, 95%CI 1.089-8.358). Conclusion: This study showed that a BOLD-MRI medullary R2* value ≥29.1 s-1 was an excellent predictor of SRF improvement in patients with severe ARAS who underwent renal artery stenting.

Contrast-Enhanced Ultrasound Evaluation of Renal Blood Perfusion Changes After Percutaneous Transluminal Renal Angioplasty and Stenting for Severe Atherosclerotic Renal Artery Stenosis.

This study used contrast-enhanced ultrasound (CEUS) to evaluate changes in renal cortical blood perfusion after percutaneous transluminal renal angioplasty and stenting (PTRAS) for severe renal artery stenosis (RAS) (≥70%). CEUS was performed in 21 patients with 24 severe RASs that underwent PTRAS. Renal cortical perfusion was quantitatively evaluated by comparing time intensity curve (TIC) parameters for SonoVue (Bracco, Milan, Italy) contrast enhancement, including peak intensity (PI), time to peak (TTP), mean transmit time (MTT), curve ascending slope (S), area under the curve (AUC), AUC-wash-in and AUC-wash-out. The parameters PI, TTP, MTT and S differed significantly between the pre-intervention and post-intervention TIC analysis (p < 0.05). Of the 24 pre-intervention curve appearances, 58.3% (14/24) improved after operation. The PI difference correlated positively with the estimated glomerular filtration rate difference (r = 0.433, p < 0.05). In conclusion, changes in some ultrasound perfusion parameters on CEUS and the shape of the TIC can be used to quantitatively and intuitively evaluate renal cortical blood perfusion change after PTRAS.

Renal function, complications, and outcomes of a reduction in tumor size after transarterial embolization for renal angiomyolipomas: a meta-analysis.

OBJECTIVE: The present study aimed to evaluate renal function, complications, and changes in tumor size after transarterial embolization for patients with renal angiomyolipomas. METHODS: We performed a meta-analysis of transarterial embolization in patients with renal angiomyolipomas from January 1994 to April 2018. Endpoints of interest were the estimated glomerular filtration rate, serum creatinine levels, blood urea nitrogen levels, complications, and reduction of tumors. RESULTS: A total of 30 studies comprising 653 patients were included. A total of 32.0% of patients were treated by urgent transarterial embolization for spontaneous ruptured renal angiomyolipomas. Other patients sought to relieve symptoms or received embolism prophylactically. The estimated glomerular filtration rate showed no significant difference between before and after embolization. In 363 patients with data on complications, post-embolization syndrome occurred most frequently (54.0%). Only 16 (4.4%) patients had major complications. The diameter of sporadic angiomyolipomas was reduced by a mean of 2.09 cm (95% confidence interval [CI], 0.73-3.45 cm; I2 = 29.3%) and they were reduced in size by 30.0% (95% CI, 16.0%-44.0%; I2 = 27.9%). CONCLUSIONS: Transarterial embolization of renal angiomyolipomas affects renal function preservation, with a low complication rate. Transarterial embolization is useful for sporadic and tuberous sclerosis complex-related angiomyolipomas.

Successful endovascular treatment of chronic renal artery occlusion: a preliminary retrospective case series including 15 patients.

PURPOSE: To evaluate in a retrospective, single-center, case series if percutaneous transluminal renal angioplasty/stenting of chronic renal artery occlusion is beneficial to renal function and blood pressure control, which remains controversial. METHODS: Data from 15 consecutive patients with renal artery stump who underwent successful percutaneous transluminal renal angioplasty/stenting only for unilateral chronic renal artery occlusion at our center from January 2007 to February 2018 and completed follow-up were retrospectively evaluated. Of the 15 patients, 14 (93.3%) were treated with stenting and 1 with only balloon angioplasty. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula corrected for Chinese, and changes in blood pressure and need for antihypertensive medications were recorded. RESULTS: At median 1.5-year (interquartile range 0.5-5.0) follow-up, restenosis rate was 20.0%. Renal function improved or remained stable in 26.7% and 53.3% of patients, respectively, and blood pressure normalized or improved in 13.3% and 40.0% of patients, respectively. Young patients with Takayasu's arteritis or fibromuscular dysplasia appeared to benefit the most from revascularization. CONCLUSIONS: In this preliminary retrospective series of select patients with renal artery stump, endovascular treatment of chronic renal artery occlusion appeared to preserve renal function and improve blood pressure.

Quality of Life, Adverse Events, and Reintervention Outcomes after Laparoscopic Radiofrequency Ablation for Symptomatic Uterine Fibroids: A Meta-Analysis.

In this review, we assessed the short-term (3 and 6 months) and long-term (12, 24, and 36 months) symptom relief and quality of life improvement, procedure-related adverse event rate, reintervention rate, and days missed from work after laparoscopic radiofrequency ablation. Using MeSH keywords "uterine fibroid" and "ablation technique," a systematic search was performed in PubMed, Ovid, Embase, Cochrane Library, and Clinicaltrials.gov. Studies consisting of uterine fibroid symptoms and quality of life scores were considered eligible. Both comparative and noncomparative studies were included. Using a random-effects model, a meta-analysis was performed. Eight studies with a total of 581 patients were finally included in our review. Based on validated questionnaires, quality of life improved significantly until 36 months after laparoscopic radiofrequency ablation therapy, with a maximum improvement (Health-Related Quality of Life [HRQL] questionnaire score of +41.64 [95% confidence interval (CI), 38.94-44.34] and a transformed Symptom Severity Score [tSSS] of -39.37 [95% CI, 34.70-44.04]) at 12 months after laparoscopic radiofrequency ablation. All subscales of quality of life improved significantly, and most of the changes remained stable in long-term follow-up. The overall reintervention rate was 4.39% (95% CI, 1.60%-8.45%), and the median uterine volume reduction was 69.17 cm³ (95% CI, 35.87-102.46 cm³).The overall procedure-related adverse events rate was 1.78% (95% CI, 0.62%-3.53%), and patients missed an average of 4.35 days (95% CI, 2.55-6.15 days) of work. In conclusion, laparoscopic radiofrequency ablation therapy is an efficacious way to treat small-sized and nonpedunculated symptomatic uterine fibroids, providing stable long-term symptom relief and quality of life improvement with a low risk of adverse events and reintervention and just a few days of missed work.

Prophylactic selective arterial embolization for renal angiomyolipomas: efficacy and evaluation of predictive factors of significant shrinkage.

PURPOSE: To evaluate the efficacy of prophylactic selective arterial embolization (SAE) of angiomyolipomas (AMLs) and to find out predictive factors of significant shrinkage of AMLs after SAE. METHODS: Patients receiving prophylactic SAE for renal AMLs with complete medical records were included. The changes of the size, urine erythrocyte counts, and serum creatinine of all patients pre- and post-embolization were assessed. Demographic data, symptoms, the background of tuberous sclerosis complex (TSC), aneurysms, enhancement features, initial tumor sizes, and serum creatinine pre-embolization were estimated as predictive factors of significant shrinkage in size. RESULTS: Forty-five patients receiving prophylactic SAE for AMLs successfully in our center were included with median follow-up of 14.0 months (interquartile range 6.5-40.5). Mean size of AMLs decreased from 10.7 ± 6.2 to 8.3 ± 5.9 cm by 23.4% ± 20.6% at the latest follow-up (P < 0.001). Urine erythrocytes decreased significantly after SAE (11.1 [interquartile range 5.7-23.2] vs. 6.4 [interquartile range 2.7-13.4], P < 0.001). In addition, there was no significant change between the serum creatinine before and after embolization (81.8 ± 14.9 mmol/L vs. 83.6 ± 17.1 mmol/L, P = 0.224). Of the variables mentioned above, only the enhanced area of AMLs before SAE was statistically significant between the groups with and without significant shrinkage (P < 0.001). In multiv-ariate analysis, enhanced area < 25% (AOR = 0.015, 95% CI 0.001-0.367) and having the background of TSC (AOR = 0.056, 95% CI 0.004-0.799) were identified as predictive factors of significant shrinkage of the tumors. CONCLUSIONS: Prophylactic SAE is effective in reducing the size of renal AMLs and decreasing urine erythrocytes with preservation of renal function. Significant shrinkage of AMLs after SAE is modulated by the enhanced area and the background of TSC.