Incremental value of radiomics-based heterogeneity to the existing risk criteria in predicting recurrence of hepatocellular carcinoma after liver transplantation.

OBJECTIVES: The aim of the study was to evaluate the association between the radiomics-based intratumoral heterogeneity (ITH) and the recurrence risk in hepatocellular carcinoma (HCC) patients after liver transplantation (LT), and to assess its incremental to the Milan, University of California San Francisco (UCSF), Metro-Ticket 2.0, and Hangzhou criteria. METHODS: A multicenter cohort of 196 HCC patients were investigated. The endpoint was recurrence-free survival (RFS) after LT. A CT-based radiomics signature (RS) was constructed and assessed in the whole cohort and in the subgroups stratified by the Milan, UCSF, Metro-Ticket 2.0, and Hangzhou criteria. The R-Milan, R-UCSF, R-Metro-Ticket 2.0, and R-Hangzhou nomograms which combined RS and the four existing risk criteria were developed respectively. The incremental value of RS to the four existing risk criteria in RFS prediction was evaluated. RESULTS: RS was significantly associated with RFS in the training and test cohorts as well as in the subgroups stratified by the existing risk criteria. The four combined nomograms showed better predictive capability than the existing risk criteria did with higher C-indices (R-Milan [training/test] vs. Milan, 0.745/0.765 vs. 0.677; R-USCF vs. USCF, 0.748/0.767 vs. 0.675; R-Metro-Ticket 2.0 vs. Metro-Ticket 2.0, 0.756/0.783 vs. 0.670; R-Hangzhou vs. Hangzhou, 0.751/0.760 vs. 0.691) and higher clinical net benefit. CONCLUSIONS: The radiomics-based ITH can predict outcomes and provide incremental value to the existing risk criteria in HCC patients after LT. Incorporating radiomics-based ITH in HCC risk criteria may facilitate candidate selection, surveillance, and adjuvant trial design. KEY POINTS: • Milan, USCF, Metro-Ticket 2.0, and Hangzhou criteria may be insufficient for outcome prediction in HCC after LT. • Radiomics allows for the characterization of tumor heterogeneity. • Radiomics adds incremental value to the existing criteria in outcome prediction.

Computed Tomography-Based Radiomics Analysis for Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

PURPOSE: Previous studies have pointed out that magnetic resonance- and fluorodeoxyglucose positron emission tomography-based radiomics had a high predictive value for the response of the neoadjuvant chemotherapy (NAC) in breast cancer by respectively characterizing tumor heterogeneity of the relaxation time and the glucose metabolism. However, it is unclear whether computed tomography (CT)-based radiomics based on density heterogeneity can predict the response of NAC. This study aimed to develop and validate a CT-based radiomics nomogram to predict the response of NAC in breast cancer. METHODS: A total of 162 breast cancer patients (110 in the training cohort and 52 in the validation cohort) who underwent CT scans before receiving NAC and had pathological response results were retrospectively enrolled. Grades 4 to 5 cases were classified as response to NAC. According to the Miller-Payne grading system, grades 1 to 3 cases were classified as nonresponse to NAC. Radiomics features were extracted, and the optimal radiomics features were obtained to construct a radiomics signature. Multivariate logistic regression was used to develop the clinical prediction model and the radiomics nomogram that incorporated clinical characteristics and radiomics score. We assessed the performance of different models, including calibration and clinical usefulness. RESULTS: Eight optimal radiomics features were obtained. Human epidermal growth factor receptor 2 status and molecular subtype showed statistical differences between the response group and the nonresponse group. The radiomics nomogram had more favorable predictive efficacy than the clinical prediction model (areas under the curve, 0.82 vs 0.70 in the training cohort; 0.79 vs 0.71 in the validation cohort). The Delong test showed that there are statistical differences between the clinical prediction model and the radiomics nomogram ( z = 2.811, P = 0.005 in the training cohort). The decision curve analysis showed that the radiomics nomogram had higher overall net benefit than the clinical prediction model. CONCLUSION: The radiomics nomogram based on CT radiomics signature and clinical characteristics has favorable predictive efficacy for the response of NAC in breast cancer.

LncRNA ZFAS1 promotes laryngeal cancer progression through RBFOX2-mediated MENA alternative splicing.

Laryngeal cancer (LC) is the most common aggressive malignancy of the head and neck. LncRNA ZNFX1 antisense RNA 1 (ZFAS1) displays oncogenic properties in head and neck squamous cell carcinoma, but its regulatory role in laryngeal cancer progression remains obscure. Here, we found that ZFAS1 expression in laryngeal cancer tissues and cells was higher than that in adjacent normal tissues and normal nasopharyngeal epithelial cells. Highly expressed ZFAS1 was associated with advanced lymph node metastasis stages and clinical stages. ZFAS1 overexpression promoted LC cell proliferation, invasion, and N-cadherin and Vimentin expression, and suppressed E-cadherin expression. While ZFAS1 knockdown played an opposite role. Mechanistically, ZFAS1 stabilized RNA binding fox-1 homolog 2 (RBFOX2) protein expression by binding to RBFOX2, and RBFOX2 overexpression reversed the effect of ZFAS1 silence on cell functions. Moreover, highly expressed RBFOX2 led to skipping of MENA exon 11a and generating a pro-invasive isoform (MENAINV ). MENAINV overexpression effectively abolished the inhibitory effect of RBFOX2 knockdown on cell malignant progression. Furthermore, Hep2 cells infected with lentivirus-mediated ZFAS1 shRNA or negative control shRNA were subcutaneously injected into mice to assess the role of ZFAS1 in tumor growth. And the data showed that silencing ZFAS1 in vivo hindered xenograft tumor growth. In conclusion, silencing ZFAS1 alleviated malignant progression of laryngeal cancer cells and mouse xenograft tumor growth by regulating RBFOX2-mediated alternative splicing of MENA.

An FDG PET/CT metabolic parameter-based nomogram for predicting the early recurrence of hepatocellular carcinoma after liver transplantation.

PURPOSE: To construct an FDG PET/CT metabolic parameter-based model to predict early recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: A total of 62 patients with HCC after LT were enrolled with a follow-up period of 1 year. Basic clinical, pathology, and laboratory data, CT features (CPLC), and PET metabolic parameters (CPLCP) were collected for model construction. A CPLC nomogram without metabolic parameters and a CPLCP nomogram with metabolic parameters were established. The net reclassification index (NRI) and integrated discrimination improvement (IDI) of the two models were calculated. The constructed model was compared with Milan criteria and University of California San Francisco (UCSF) criteria. The time-dependent area under the receiver operating characteristic curve (time-AUC) was used to compare the efficiency of the models, and the bootstrap method was used to for verification. Harrell's concordance index (C-index) was used to evaluate the performance of these models. Decision curve analysis (DCA) was used to evaluate the clinical practicability of each model. RESULTS: Thirty out of 62 patients experienced a recurrence during the 1-year follow-up. BCLC stage (P = 0.009), MVI (P = 0.032), AFP (P = 0.004), CTdmax (P = 0.033), and MTV (P = 0.039) were the independent predictors. The CPLC nomogram and the CPLCP nomogram were established. Compared with the CPLC nomogram, the NRI of the CPLCP nomogram increased by 38.98% (95% CI = -18.77-60.43%) and the IDI increased by 4.40% (95% CI = -1.00-16.62%). The AUC value of the CPLCP nomogram was higher than those of Milan criteria and UCSF criteria in the time-AUC curve. Moreover, the CPLCP nomogram had a higher C-index (0.774) than other models. Finally, the DCA curve showed that clinical practicability of the CPLCP nomogram outperformed the Milan criteria and UCSF criteria. CONCLUSIONS: The CPLCP nomogram combining basic clinical data, pathology data, laboratory data, CT features, and PET metabolic parameters showed good efficacy and high clinical practicability in predicting the early recurrence of HCC after LT.

Additional value of metabolic parameters to PET/CT-based radiomics nomogram in predicting lymphovascular invasion and outcome in lung adenocarcinoma.

PURPOSE: Lymphovascular invasion (LVI) impairs surgical outcomes in lung adenocarcinoma (LAC) patients. Preoperative prediction of LVI is challenging by using traditional clinical and imaging parameters. The purpose of this study was to investigate the value of the radiomics nomogram integrating clinical factors, CT features, and maximum standardized uptake value (SUVmax) to predict LVI and outcome in LAC and to evaluate the additional value of the SUVmax to the PET/CT-based radiomics nomogram. METHODS: A total of 272 LAC patients (87 LVI-present LACs and 185 LVI-absent LACs) with PET/CT scans were retrospectively enrolled, and 160 patients with SUVmax ≥ 2.5 of them were used for PET radiomics analysis. Clinical data and CT features were analyzed to select independent LVI predictors. The performance of the independent LVI predictors and SUVmax was evaluated. Two-dimensional (2D) and three-dimensional (3D) CT radiomics signatures (RSs) and PET-RS were constructed with the least absolute shrinkage and selection operator algorithm and radiomics scores (Rad-scores) were calculated. The radiomics nomograms, incorporating Rad-score and independent clinical and CT factors, with SUVmax (RNWS) or without SUVmax (RNWOS) were built. The performance of the models was assessed with respect to calibration, discrimination, and clinical usefulness. All the clinical, PET/CT, pathologic, therapeutic, and radiomics parameters were assessed to identify independent predictors of progression-free survival (PFS). RESULTS: CT morphology was the independent LVI predictor. SUVmax provided better discrimination capability compared with CT morphology in the training set (P < 0.001) and test set (P = 0.042). A total of 1409 CT and PET radiomics features were extracted and reduced to 8, 8, and 10 features to build the 2D CT-RS, 3D CT-RS, and the PET-RS, respectively. There was no significant difference in AUC between the 2D-RS and 3D-RS (P > 0.05), and 2D CT-RS showed a relatively higher AUC than 3D CT-RS. The CT-RS, the CT-RNWOS, and the CT-RNWS showed good discrimination in the training set (AUC [area under the curve], 0.799, 0.796, and 0.851, respectively) and the test set (AUC, 0.818, 0.822, and 0.838, respectively). There was significant difference in AUC between the CT-RNWS and CT-RNWOS (P = 0.044) in the training set. Decision curve analysis (DCA) demonstrated the CT-RNWS outperformed the CT-RS and the CT-RNWOS in terms of clinical usefulness. Furthermore, DCA showed the PETCT-RNWS provided the highest net benefit compared with the PET-RNWS and CT-RNWS. PFS was significantly different between the pathologic and RNWS-predicted LVI-present and LVI-absent patients (P < 0.001). Carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), pathologic LVI, histologic subtype, and SUVmax were independent predictors of PFS in the 244 CT-RNWS-predicted cohort; and CA125, NSE, pathologic LVI, and SUVmax were the independent predictors of PFS in the 141 PETCT-RNWS-predicted cohort. CONCLUSIONS: The radiomics nomogram, incorporating Rad-score, clinical and PET/CT parameters, shows favorable predictive efficacy for LVI status in LAC. Pathologic LVI and SUVmax are associated with LAC prognosis.

Improved Cellular Delivery of Antisense Oligonucleotide for miRNA-21 Imaging In Vivo Using Cell-Penetrating Peptide-Based Nanoprobes.

Most oligonucleotides fail to enter a cell and cannot escape from endosomes after endocytosis because of their negative charge and large molecular weight. More efficient cellular delivery of oligonucleotides should be developed for the widespread implementation of antisense imaging. The purpose of this study was to construct a novel antisense nanoprobe, 99mTc-labeled anti-miRNA oligonucleotides/cell-penetrating peptide PepFect6 (99mTc-AMO/PF6), and to evaluate its efficacy for imaging the miRNA-21 expression in A549 lung adenocarcinoma xenografts. Naked AMO and commercial Lipofectamine 2000-based nanoparticles (AMO/LIP) were used for comparison. The cellular delivery efficiency of AMO/PF6 was first investigated by laser confocal scanning microscopy using Cy5.5-labeled probes and further validated by in vivo fluorescence imaging. Then, the probes were labeled with 99mTc via hydrazinonicotinamide (HYNIC). The cytotoxicity assay, cellular uptake, and retention kinetics of the probes were evaluated in vitro. The biodistribution of the probes was investigated in A549 lung cancer xenografts, and SPECT imaging was performed in vivo. AMO/PF6 showed lower cytotoxicity than AMO/LIP (P < 0.05) but showed no significant difference with naked AMO. Fluorescence microscopy demonstrated more extensive and scattered signal distribution inside the A549 cells by AMO/PF6 than AMO/LIP. The labeling efficiency of 99mTc-AMO/PF6 was 72.6 ± 1.42%, and the specific activity was 11.6 ± 0.13 MBq/ng. The cellular uptake of 99mTc-PF6/AMO peaked at 12 h, with the uptake of 11.24 ± 0.12 mol/cell × 10-16, and the cellular retention of 99mTc-AMO/PF6 was 3.92 ± 0.15 mol/cell × 10-16 at 12 h after interrupted incubation. AMO/PF6 showed higher cellular uptake and retention than naked AMO and AMO/LIP. The biodistribution study showed that the tumor had the highest radioactivity accumulation, with the uptake ratio of tumor/muscle (T/M) increasing from 14.59 ± 0.67 to 21.76 ± 0.98 between 1 and 6 h after injection, followed by the uptake in the kidneys and the liver. The results of in vivo fluorescence and SPECT imaging were consistent with the results of the biodistribution. The tumor was visualized at 6 h after injection of AMO/PF6 with the highest T/M ratio among these probes (P < 0.05). PF6 improves cellular delivery of antisense oligonucleotides via noncovalent nanoparticles. 99mTc-AMO/PF6 shows favorable imaging properties and is promising for miRNAs imaging in vivo.

A CT-based radiomics nomogram for differentiation of renal angiomyolipoma without visible fat from homogeneous clear cell renal cell carcinoma.

OBJECTIVES: To develop and validate a radiomics nomogram for preoperative differentiating renal angiomyolipoma without visible fat (AML.wovf) from homogeneous clear cell renal cell carcinoma (hm-ccRCC). METHODS: Ninety-nine patients with AML.wovf (n = 36) and hm-ccRCC (n = 63) were divided into a training set (n = 80) and a validation set (n = 19). Radiomics features were extracted from corticomedullary phase and nephrographic phase CT images. A radiomics signature was constructed and a radiomics score (Rad-score) was calculated. Demographics and CT findings were assessed to build a clinical factors model. Combined with the Rad-score and independent clinical factors, a radiomics nomogram was constructed. Nomogram performance was assessed with respect to calibration, discrimination, and clinical usefulness. RESULTS: Fourteen features were used to build the radiomics signature. The radiomics signature showed good discrimination in the training set (AUC [area under the curve], 0.879; 95%; confidence interval [CI], 0.793-0.966) and the validation set (AUC, 0.846; 95% CI, 0.643-1.000). The radiomics nomogram showed good calibration and discrimination in the training set (AUC, 0.896; 95% CI, 0.810-0.983) and the validation set (AUC, 0.949; 95% CI, 0.856-1.000) and showed better discrimination capability (p < 0.05) compared with the clinical factor model (AUC, 0.788; 95% CI, 0.683-0.893) in the training set. Decision curve analysis demonstrated the nomogram outperformed the clinical factors model and radiomics signature in terms of clinical usefulness. CONCLUSIONS: The CT-based radiomics nomogram, a noninvasive preoperative prediction tool that incorporates the Rad-score and clinical factors, shows favorable predictive efficacy for differentiating AML.wovf from hm-ccRCC, which might assist clinicians in tailoring precise therapy. KEY POINTS: • Differential diagnosis between AML.wovf and hm-ccRCC is rather difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, demographics, and CT findings facilitates differentiation of AML.wovf from hm-ccRCC with improved diagnostic efficacy. • The CT-based radiomics nomogram might spare unnecessary surgery for AML.wovf.

Prevalence of reduced visual acuity among school-aged children and adolescents in 6 districts of Changsha city: a population-based survey.

BACKGROUND: To calculate and evaluate the prevalence of reduced uncorrected distant visual acuity (UCDVA) in primary, middle and high schools in 6 districts of Changsha, Hunan, China. METHODS: A population-based retrospective study was conducted in 239 schools in 6 districts of Changsha. After routine eye examination to rule out diseases that can affect refraction, 250,980 eligible students from primary, middle and high schools were enrolled in the survey. Then the uncorrected distant and near visual acuity of each eye were measured. Categories of schools, districts, grades, eye exercises and sports time were also documented and analyzed. RESULTS: The overall prevalence of reduced UCDVA was 51.8% (95% confidence interval [CI]: 51.6-52.0%) in 6 districts of Changsha. Results of individual districts were as follows: Furong district 59.9%(95% CI: 57.9-61.8%), Tianxin district 62.3%(95% CI: 60.5-64.0%), Wangcheng district 47.8%(95% CI: 46.8-48.8%), Kaifu district 58.5%(95% CI: 58.0-58.9%), Yuhua district 47.0%(95% CI: 46.7-47.4%) and Yuelu district 52.6%(95% CI: 52.3-52.9%). The proportion of normal VA is seen to decrease from primary grade 3. The proportion of mildly reduced UCDVA is higher in primary grade 1 and 2. The proportion of moderately reduced UCDVA remains similar during 12 grades. The proportion of severely reduced UCDVA increases with grades. Multivariate analysis shows that the prevalence of reduced UCDVA is higher in key schools (risk ratio [RR] = 1.47, 95% CI 1.44-1.50) than non-key schools. CONCLUSIONS: According to the existing data analysis results, the prevalence of reduced UCDVA among primary, middle and high school students in Changsha is very high. Some effective measures need to be taken to prevent it.

Contrast-Enhanced CT Texture Analysis for Distinguishing Fat-Poor Renal Angiomyolipoma From Chromophobe Renal Cell Carcinoma.

OBJECTIVE: To evaluate the value of 2-dimensional (2D) and 3-dimensional (3D) computed tomography texture analysis (CTTA) models in distinguishing fat-poor angiomyolipoma (fpAML) from chromophobe renal cell carcinoma (chRCC). METHODS: We retrospectively enrolled 32 fpAMLs and 24 chRCCs. Texture features were extracted from 2D and 3D regions of interest in triphasic CT images. The 2D and 3D CTTA models were constructed with the least absolute shrinkage and selection operator algorithm and texture scores were calculated. The diagnostic performance of the 2D and 3D CTTA models was evaluated with respect to calibration, discrimination, and clinical usefulness. RESULTS: Of the 177 and 183 texture features extracted from 2D and 3D regions of interest, respectively, 5 2D features and 8 3D features were selected to build 2D and 3D CTTA models. The 2D CTTA model (area under the curve [AUC], 0.811; 95% confidence interval [CI], 0.695-0.927) and the 3D CTTA model (AUC, 0.915; 95% CI, 0.838-0.993) showed good discrimination and calibration (P > .05). There was no significant difference in AUC between the 2 models (P = .093). Decision curve analysis showed the 3D model outperformed the 2D model in terms of clinical usefulness. CONCLUSIONS: The CTTA models based on contrast-enhanced CT images had a high value in differentiating fpAML from chRCC.

MTA1 promotes viability and motility in nasopharyngeal carcinoma by modulating IQGAP1 expression.

Nasopharyngeal carcinoma (NPC) is frequently seen in Chinese, especially the population that resides in southeast China. Metastasis-associated protein 1 (MTA1) is a chromatin modifier and plays a role in tumor cell metastasis. IQGAP1 is a ubiquitously expressed protein that contributes to cytoskeleton remodeling. This study aimed to investigate the role of MTA1 and IQGAP1 in NPC malignant transformation. MTA1 and IQGAP1 expression in NPC (n = 43) and control tissues (n = 31) were detected using qRT-PCR, immunoblot, and immunohistochemistry. MTA1 was overexpressed in CNE-1 and CNE-2 cell line by pcDNA3.1/MTA1 transfection. Dominant-negative p53 was transfected to inhibit p53 activity. si-IQGAP1 or dominant-negative IQGAP1 (IQGAP1ΔGRD) was used to suppress IQGAP1 activity. Cell proliferation was measured by CKK-8 assay. Cell migration was evaluated by Transwell assay. The results showed that MTA1 and IQGAP1 were highly expressed in NPC tissues compared with the controls. Forced expression of MTA1 accelerated cell proliferation and migration and upregulated IQGAP1 expression in a p53-independent way. Knockdown of IQGAP1 or transfection of dominant-negative IQGAP1 impeded tumor cell proliferation and migration as well as PI3K/Akt signaling induced by MTA1. In conclusion, MTA1 participates in NPC malignant transformation via regulating IQGAP1 expression and PI3K/Akt signaling pathway.

EZH2 promotes cell proliferation by regulating the expression of RUNX3 in laryngeal carcinoma.

Enhancer of zeste homolog 2 (EZH2) is a highly conserved histone methyltransferase, which is overexpressed in different types of cancers such as breast and prostate cancer. It is reported that EZH2 can directly down-regulate RUNX3 by increasing histone H3 methylation. However, the role of EZH2 in the development and progression of laryngeal carcinoma has not yet been investigated, and the relationship between EZH2 and RUNX3 in laryngeal carcinoma is rarely reported. The current study aims to determine the role of EZH2 in the progression of laryngeal carcinoma, and investigate the interaction between EZH2 and the tumor suppressor RUNX3. Our study found that EZH2 is overexpressed in laryngeal carcinoma patients, and silencing EZH2 by EZH2 siRNA significantly inhibited the proliferation of laryngeal carcinoma cells. Besides, we also found that RUNX3 is repressed in laryngeal carcinoma patients. Moreover, RUNX3 as a downstream target protein of EZH2 is up-regulated by EZH2 siRNA accompanied by a decrease in the trimethylation modification pattern of H3K27. RUNX3 siRNA inhibits the decreased proliferation induced by EZH2 siRNA. Furthermore, ß-catenin protein expression is down-regulated by EZH2 siRNA and up-regulated by RUNX3 siRNA, and RUNX3 siRNA inhibits the down-regulation effect of EZH2 siRNA on ß-catenin protein expression. Additionally, the Wnt/ß-catenin activator BIO reverses the inhibitory effect of EZH2 siRNA on Hep-2 cell proliferation. Taken together, our results suggest that EZH2 regulates cell proliferation potentially by targeting RUNX3 through the Wnt/ß-catenin signaling pathway in laryngeal carcinoma.

MicroRNA-26a inhibits proliferation and tumorigenesis via targeting CKS2 in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck cancers, with high mortality and incidence. MicroRNA-26a (miR-26a) is involved in the development and progression of several tumours. However, the roles of miR-26a and its target CKS2 in LSCC progression are not yet clear. The mRNA and protein expression was determined using RT-PCR and Western blotting assay, respectively. Cell proliferation was detected using a Cell Counting kit-8 assay (CCK-8). Transwell assay was used to evaluate cell migration and invasion. Dual-luciferase reporter assay was applied to determine the relationship between miR-26a and CKS2. In addition, a tumour xenograft model in nude mice was established to further determine the effects of miR-26a on tumourigenesis. In this study, we found that miR-26a level was down-regulated in LSCC tissues and cell lines, while CKS2 expression was increased. Cell proliferation, migration, invasion and the expression of MMP2 and MMP9 was suppressed by miR-26a overexpression, but enhanced by inhibition of miR-26a. Dual-luciferase reporter assay demonstrated that CKS2 is a direct target of miR-26a in AMC-HN-8 cells. Overexpression of miR-26a caused a significant reduction in CKS2 expression, and reinforced expression of CKS2 abolished the tumour-suppressive function of miR-26a. Moreover, miR-26a inhibited tumour growth in vivo. Taken together, miR-26a inhibited proliferation and tumourigenesis of LSCC via targeting CKS2 in vitro and in vivo.

Preoperative evaluation of cochlear implantation through the round window membrane in the facial recess using high-resolution computed tomography.

PURPOSE: We evaluated the risk of cochlear implantation through the round window membrane in the facial recess through a preoperative analysis of the angle between the facial nerve-round window and the cranial midline using high-resolution temporal bone CT. METHODS: Temporal bone CT films of 176 patients with profound sensorineural hearing loss at our hospital from 2013 to 2015 were reviewed. The preoperative temporal bone CT scans of the patients were retrospectively analysed. The vertical distance (d value) from the leading edge of the facial nerve to the posterior wall of the external auditory canal and the angle (α value) between the line from the leading edge of the facial nerve to the midpoint of the round window membrane and the median sagittal line on the round window membrane plane were measured. Based on intraoperative observation, the round window membrane was divided into complete round window membrane exposure (group A), partial exposure (group B), and unexposed (group C) groups, and statistical analysis was performed. RESULTS: The α value could be effectively measured for all 176 patients (62.60 ± 7.12), and the d value could be effectively measured for 95 cases (5.53 ± 1.00). An analysis of the correlation between the α and d values of these 95 cases found a negative correlation. Of the 176 cases, one-way analysis of variance (ANOVA) showed that the differences among the groups were significant [P = 0.000 (< 0.05)]. CONCLUSION: The angle (α value) between the line connecting the leading edge of the facial nerve to the midpoint of the round window and the median sagittal line measured in preoperative CT scans was associated with the difficulty of intraoperatively exposing the round window membrane. When the α value was larger than a certain degree, the difficulty of exposing the round window membrane was increased. In such cases, the surgeon should fully expose the round window membrane during surgery, which could result decrease the likelihood of complications.

Gradient-Pattern Micro-Grooved Wicks Fabricated by the Ultraviolet Nanosecond Laser Method and Their Enhanced Capillary Performance.

Capillary-gradient wicks can achieve fast or directional liquid transport, but they face fabrication challenges by traditional methods in terms of precise patterns. Laser processing is a potential solution due to its high pattern accuracy, but there are a few studies on laser-processed capillary-gradient wicks. In this paper, capillary step-gradient micro-grooved wicks (CSMWs) were fabricated by an ultraviolet nanosecond pulsed laser, and their capillary performance was studied experimentally. The CSMWs could be divided into three regions with a decreasing capillary radius. The equilibrium rising height of the CSMWs was enhanced by 124% compared to the non-gradient parallel wick. Different from the classical Lucas-Washburn model describing a uniform non-gradient wick, secondary capillary acceleration was observed in the negative gradient direction of the CSMWs. With the increase in laser power and the decrease in scanning speed, the capillary performance was promoted, and the optimal laser processing parameters were 4 W-10 mm/s. The laser-enhanced capillary performance was attributed to the improved hydrophilicity and reduced capillary radius, which resulted from the increased surface roughness, protrusion morphology, and deep-narrow V-shaped grooves induced by the high energy density of the laser. Our study demonstrates that ultraviolet pulsed laser processing is a highly efficient and low-cost method for fabricating high-performance capillary gradient wicks.

The value of 18F-FDG PET/CT-based radiomics in predicting perineural invasion and outcome in non-metastatic colorectal cancer.

PURPOSE: Perineural invasion (PNI) has been recognized as an important prognosis factor in patients with colorectal cancer (CRC). The purpose of this retrospective study was to investigate the value of 18F-FDG PET/CT-based radiomics integrating clinical information, PET/CT features, and metabolic parameters for preoperatively predicting PNI and outcome in non-metastatic CRC and establish an easy-to-use nomogram. METHODS: A total of 131 patients with non-metastatic CRC who undergo PET/CT scan were retrospectively enrolled. Univariate analysis was used to compare the differences between PNI-present and PNI-absent groups. Multivariate logistic regression was performed to select the independent predictors for PNI status. Akaike information criterion (AIC) was used to select the best prediction models for PNI status. CT radiomics signatures (RSs) and PET-RSs were selected by maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) regression and radiomics scores (Rad-scores) were calculated for each patient. The prediction models with or without Rad-score were established. According to the nomogram, nomogram scores (Nomo-scores) were calculated for each patient. The performance of different models was assessed with the area under the curve (AUC), specificity, and sensitivity. The clinical usefulness was assessed by decision curve (DCA). Multivariate Cox regression was used to selected independent predictors of progression-free survival (PFS). RESULTS: Among all the clinical information, PET/CT features, and metabolic parameters, CEA, lymph node metastatic on PET/CT (N stage), and total lesion glycolysis (TLG) were independent predictors for PNI (p < 0.05). Six CT-RSs and 12 PET-RSs were selected as the most valuable factors to predict PNI. The Rad-score calculated with these RSs was significantly different between PNI-present and PNI-absent groups (p < 0.001). The AUC of the constructed model was 0.90 (95%CI: 0.83-0.97) in the training cohort and 0.80 (95%CI: 0.65-0.95) in the test cohort. The nomogram's predicting sensitivity was 0.84 and the specificity was 0.83 in the training cohort. The clinical model's predicting sensitivity and specificity were 0.66 and 0.85 in the training cohort, respectively. Besides, DCA showed that patients with non-metastatic CRC could get more benefit with our model. The results also indicated that N stage, PNI status, and the Nomo-score were independent predictors of PFS in patients with non-metastatic CRC. CONCLUSION: The nomogram, integrating clinical data, PET/CT features, metabolic parameters, and radiomics, performs well in predicting PNI status and is associated with the outcome in patients with non-metastatic CRC.

Radiomics Analysis of Contrast-Enhanced CT Predicts Survival in Clear Cell Renal Cell Carcinoma.

PURPOSE: To develop and validate the radiomics nomogram that combines clinical factors and radiomics features to estimate overall survival (OS) in patients with clear cell renal cell carcinoma (ccRCC), and assess the incremental value of radiomics for OS estimation. MATERIALS AND METHODS: One hundred ninety-four ccRCC cases were included in the training cohort and 188 ccRCC patients from another hospital as the test cohort. Three-dimensional region-of-interest segmentation was manually segmented on multiphasic contrast-enhanced abdominal CT images. Radiomics score (Rad-score) was calculated from a formula generated via least absolute shrinkage and selection operator (LASSO) Cox regression, after which the association between the Rad-score and OS was explored. The radiomics nomogram (clinical factors + Rad-score) was developed to demonstrate the incremental value of the Rad-score to the clinical nomogram for individualized OS estimation, which was then evaluated in relation to calibration and discrimination. RESULTS: Rad-score, calculated using a linear combination of the 11 screened features multiplied by their respective LASSO Cox coefficients, was significantly associated with OS. Calibration curves showed good agreement between the OS predicted by the nomograms and observed outcomes. The radiomics nomogram presented higher discrimination capability compared to clinical nomogram in the training (C-index: 0.884; 95% CI: 0.808-0.940 vs. 0.803; 95% CI: 0.705-0.899, P < 0.05) and test cohorts (C-index: 0.859; 95% CI: 0.800-0.921 vs. 0.846; 95% CI: 0.777-0.915, P < 0.05). CONCLUSIONS: The radiomics nomogram may be used for predicting OS in patients with ccRCC, and radiomics is useful to assist quantitative and personalized treatment.

Construction of an immunized rabbit phage display antibody library for screening microcystin-LR high sensitive single-chain antibody.

Microcystin-LR (MC-LR) is one of the most common biotoxin that pollutes water and agricultural products. The study aims to obtain the high sensitive anti-MC-LR single-chain antibody (scFv) for detecting MC-LR. Here, a MC-LR-immunized rabbit phage display scFv library with its capacity of 3.26×109CFU/mL was constructed and used for anti-MC-LR phage scFv particles screening. After four rounds of biopanning, 18 positives were isolated and identified successfully. The most positive scFv (RscFv3) was expressed in Escherichia coli HB2151 and purified with a concentration of 796.7µg/mL, and the purified anti-MC-LR polyclonal antibodies (PAbs) were 3.6mg/mL. The PAbs and scFv based indirect competitive enzyme linked immunosorbent assay (IC-ELISAs) were established for MC-LR and its analogues, and the results showed they all had high sensitive for MC-LR with detection limits of 0.03 and 0.05µg/L, and had strong cross-reactivity for MC-RR, MC-WR and MC-YR, respectively. The average recovery rate was 91.9% with coefficient of variation <6.8% for scFv-based IC-ELISA to detect MC-LR spiked in water samples, which met the requirement of indoor testing. The present results indicate that we have obtained a high sensitive anti-MC-LR scFv by the MC-LR-immunized phage library construction and screening, and the scFv-based IC-ELISA can be used for monitoring MC-LR in water samples.

lncRNA CASC2/miR­18a­5p axis regulates the malignant potential of nasopharyngeal carcinoma by targeting RBBP8.

Nasopharyngeal carcinoma (NPC) is a prevalent head and neck tumor which has a high mortality rate in Southeast Asia, especially in Southern China. Cancer susceptibility candidate 2 (CASC2) is a newly identified long non­coding RNA (lncRNA) that has been found to play a suppressive role in several types of tumors. However, the expression and functional role of CASC2 in NPC are still unclear. In the present study, using NPC tissues, cells and transplanted mice, we investigated the mechanism of CASC2­mediated regulation of NPC. We showed that the CASC2 level is reduced in NPC tissues and cells. CASC2 downregulation promoted proliferation and inhibited apoptotic cell death in NPC cells. In contrast, CASC2 upregulation inhibited proliferation and increased apoptosis. There were putative binding sites of microRNA (miR)­18a­5p in the promoter of CASC2. The level of miR­18a­5p was upregulated in NPC tissues and cells. We further confirmed that CASC2 could directly bind with miR­18a­5p and inhibit miR­18a­5p expression, using reporter gene and RNA immunoprecipitation assays. miR­18a­5p suppressed CASC2 upregulation­mediated decrease in proliferation and increase in apoptotic cell death. Bioinformatics predicted the putative binding site of miR­18a­5p in the 3' untranslated region of C­terminal binding protein interacting protein (CtIP)/RBBP8. It was further confirmed that miR­18a­5p could directly bind with RBBP8 and inhibit RBBP8 expression. Downregulation of RBBP8 inhibited the anti­miR­18a­5p­mediated increase in apoptosis and decrease in proliferation. Downregulation of CASC2 increased tumor growth, increased the level of miR­18a­5p and decreased RBBP8 expression in vivo. In summary, CASC2 regulates NPC malignancy through modulation of RBBP8 via sponging miR­18a­5p. Our findings highlight the CASC2/miR­18a­5p/RBBP8 axis in NPC pathogenesis and provide new biomarkers and potential targets for the therapy of NPC.

Analysis on biomass and productivity of epilithic algae and their relations to environmental factors in the Gufu River basin, Three Gorges Reservoir area, China.

The main purpose of this study conducted from August 2010 was to find biomass and productivity of epilithic algae and their relations to environmental factors and try to explore the restrictive factors affecting the growth of algae in the Gufu River, the one of the branches of Xiangxi River located in the Three Gorges Reservoir of the Yangtze River, Hubei Province, Central China. An improved method of in situ primary productivity measurement was utilized to estimate the primary production of the epilithic algae. It was shown that in rivers, lakes, and reservoirs, algae are the main primary producers and have a central role in the ecosystem. Chlorophyll a concentration and ash-free dry mass (AFDM) were estimated for epilithic algae of the Gufu River basin in Three Gorges Reservoir area. Environmental factors in the Gufu River ecosystem highlighted differences in periphyton chlorophyll a ranging from 1.49 mg m-2 (origin) to 69.58 mg m-2 (terminal point). The minimum and maximum gross primary productivity of epilithic algae were 96.12 and 1439.89 mg C m-2 day-1, respectively. The mean net primary productivity was 290.24 mg C m-2 day-1. The mean autotrophic index (AFDM:chlorophyll a) was 407.40. The net primary productivity, community respiration ratio (P/R ratio) ranged from 0.98 to 9.25 with a mean of 2.76, showed that autotrophic productivity was dominant in the river. Relationship between physicochemical characteristics and biomass was discussed through cluster and stepwise regression analysis which indicated that altitude, total nitrogen (TN), NO3--N, and NH4+-N were significant environmental factors affecting the biomass of epilithic algae. However, a negative logarithmic relationship between altitude and the chlorophyll a of epilithic algae was high. The results also highlighted the importance of epilithic algae in maintaining the Gufu River basin ecosystems health.