Qualitative and quantitative MRI analysis of alveolar soft part sarcoma: correlation with histological grade and Ki-67 expression.

OBJECTIVE: To investigate the correlation between MRI findings and histological features for preoperative prediction of histological grading and Ki-67 expression level in alveolar soft part sarcoma (ASPS). METHODS: A retrospective analysis was conducted on 63 ASPS patients (Jan 2017-May 2023). All patients underwent 3.0-T MRI examinations, including conventional sequences, dynamic contrast-enhanced scans with time-intensity curve analysis, and diffusion-weighted imaging with apparent diffusion coefficient (ADC) measurements. Patients were divided into low-grade (histological Grade I) and high-grade (histological Grade II/III) groups based on pathology. Immunohistochemistry was used to assess Ki-67 expression levels in ASPS. Statistical analysis included chi-square tests, Wilcoxon rank-sum test, binary logistic regression analysis, Spearman correlation analysis, and receiver operating characteristic curve analysis of various observational data. RESULTS: There were 29 low-grade and 34 high-grade patients (26 males and 37 females) and a wide age range (5-68 years). Distant metastasis, tumor enhancement characteristics, and ADC values were independent predictors of high-grade ASPS. High-grade ASPS had lower ADC values (p = 0.002), with an area under the curve (AUC), sensitivity, and specificity of 0.723, 79.4%, and 58.6%, respectively, for high-grade prediction. There was a negative correlation between ADC values and Ki-67 expression (r = -0.526; p < 0.001). When the cut-off value of ADC was 0.997 × 10-3 mm²/s, the AUC, sensitivity, and specificity for predicting high Ki-67 expression were 0.805, 65.6%, and 83.9%, respectively. CONCLUSION: Qualitative and quantitative MRI parameters are valuable for predicting histological grading and Ki-67 expression levels in ASPS. CRITICAL RELEVANCE STATEMENT: This study will help provide a more nuanced understanding of ASPS and guide personalized treatment strategies. KEY POINTS: There is limited research on assessing ASPS prognosis through MRI. Metastasis, enhancement, and ADC correlated with histological grade; ADC related to Ki-67 expression. MRI provides clinicians with valuable information on ASPS grading and proliferation activity.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations.

BACKGROUND: The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus (T2DM) is currently controversial. It is unknown whether this association can be gene realized across different populations. AIM: To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, Medline, Baidu Academic, China National Knowledge Infrastructure, China Biomedical Liter-ature Database, and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12, 2022. Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature. RESULTS: Twelve case-control studies (including 11273 cases and 11654 controls) met our inclusion criteria. In the full population, allelic model [odds ratio (OR): 1.19; 95% confidence interval (95%CI): 1.09-1.29; P < 0.0001], recessive model (OR: 1.20; 95%CI: 1.11-1.29; P < 0.0001), dominant model (OR: 1.27. 95%CI: 1.14-1.42; P < 0.0001), and codominant model (OR: 1.36; 95%CI: 1.15-1.60; P = 0.0003) (OR: 1.22; 95%CI: 1.10-1.36; P = 0.0002) indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM. In stratified analysis, this association was confirmed in Asian populations: allelic model (OR: 1.25; 95%CI: 1.13-1.37; P < 0.0001), recessive model (OR: 1.29; 95%CI: 1.11-1.49; P = 0.0007), dominant model (OR: 1.35; 95%CI: 1.20-1.52; P < 0.0001), codominant model (OR: 1.49; 95%CI: 1.22-1.81; P < 0.0001) (OR: 1.26; 95%CI: 1.16-1.36; P < 0.0001). In non-Asian populations, this association was not significant: Allelic model (OR: 1.06, 95%CI: 0.98-1.14; P = 0.12), recessive model (OR: 1.04; 95%CI: 0.75-1.42; P = 0.83), dominant model (OR: 1.06; 95%CI: 0.98-1.15; P = 0.15), codominant model (OR: 1.08; 95%CI: 0.82-1.42; P = 0.60. OR: 1.15; 95%CI: 0.95-1.39; P = 0.14). CONCLUSION: KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population. Carriers of the C allele had a higher risk of T2DM. This association was not significant in non-Asian populations.

Mitochondrial-Targeted Metal-Phenolic Nanoparticles to Attenuate Intervertebral Disc Degeneration: Alleviating Oxidative Stress and Mitochondrial Dysfunction.

As intervertebral disc degeneration (IVDD) proceeds, the dysfunctional mitochondria disrupt the viability of nucleus pulposus cells, initiating the degradation of the extracellular matrix. To date, there is a lack of effective therapies targeting the mitochondria of nucleus pulposus cells. Here, we synthesized polygallic acid-manganese (PGA-Mn) nanoparticles via self-assembly polymerization of gallic acid in an aqueous medium and introduced a mitochondrial targeting peptide (TP04) onto the nanoparticles using a Schiff base linkage, resulting in PGA-Mn-TP04 nanoparticles. With a size smaller than 50 nm, PGA-Mn-TP04 possesses pH-buffering capacity, avoiding lysosomal confinement and selectively accumulating within mitochondria through electrostatic interactions. The rapid electron exchange between manganese ions and gallic acid enhances the redox capability of PGA-Mn-TP04, effectively reducing mitochondrial damage caused by mitochondrial reactive oxygen species. Moreover, PGA-Mn-TP04 restores mitochondrial function by facilitating the fusion of mitochondria and minimizing their fission, thereby sustaining the vitality of nucleus pulposus cells. In the rat IVDD model, PGA-Mn-TP04 maintained intervertebral disc height and nucleus pulposus tissue hydration. It offers a nonoperative treatment approach for IVDD and other skeletal muscle diseases resulting from mitochondrial dysfunction, presenting an alternative to traditional surgical interventions.

Smart Enzyme-Like Polyphenol-Copper Spray for Enhanced Bacteria-Infected Diabetic Wound Healing.

Developing functional medical materials is urgent to treat diabetic wounds with a high risk of bacterial infections, high glucose levels and oxidative stress. Here, a smart copper-based nanocomposite acidic spray has been specifically designed to address this challenge. This copper-based nanocomposite is pH-responsive and has multienzyme-like properties. It enables the spray to effectively eliminate bacteria and alleviate tissue oxidative pressure, thereby accelerating the healing of infected diabetic wounds. The spray works by generating hydroxyl radicals through catalysing H2O2, which has a high sterilization efficiency of 97.1%. As alkaline micro-vessel leakage neutralizes the acidic spray, this copper-based nanocomposite modifies its enzyme-like activity to eliminate radicals. This reduces the level of reactive oxygen species in diabetic wounds by 45.3%, leading to a similar wound-healing effect between M1 diabetic mice and non-diabetic ones by day 8. This smart nanocomposite spray provides a responsive and regulated microenvironment for treating infected diabetic wounds. It also offers a convenient and novel approach to address the challenges associated with diabetic wound healing.

Interface Chirality: From Biological Effects to Biomedical Applications.

Chiral surface is a critical mediator that significantly impacts interaction with biological systems on regulating cell behavior. To better understand how the properties of interfacial Chirality affect cell behavior and address the limitations of chiral materials for biomedical applications, in this review, we mainly focus on the recent developments of chiral bio-interfaces for the controllable and accurate guidance of chiral biomedical phenomena. In particular, we will discuss how cells or organisms sense and respond to the chiral stimulus, as well as the chirality mediating cell fate, tissue repair, and organism immune response will be reviewed. In addition, the biological applications of chirality, such as drug delivery, antibacterial, antivirus and antitumor activities, and biological signal detection, will also be reviewed. Finally, the challenges of chiral bio-interfaces for controlling biological response and the further application of interface chirality materials for biomedical will be discussed.

Absorbable Thioether Grafted Hyaluronic Acid Nanofibrous Hydrogel for Synergistic Modulation of Inflammation Microenvironment to Accelerate Chronic Diabetic Wound Healing.

Current standard of care dressings are unsatisfactorily inefficacious for the treatment of chronic wounds. Chronic inflammation is the primary cause of the long-term incurable nature of chronic wounds. Herein, an absorbable nanofibrous hydrogel is developed for synergistic modulation of the inflammation microenvironment to accelerate chronic diabetic wound healing. The electrospun thioether grafted hyaluronic acid nanofibers (FHHA-S/Fe) are able to form a nanofibrous hydrogel in situ on the wound bed. This hydrogel degrades and is absorbed gradually within 3 days. The grafted thioethers on HHA can scavenge the reactive oxygen species quickly in the early inflammation phase to relieve the inflammation reactions. Additionally, the HHA itself is able to promote the transformation of the gathered M1 macrophages to the M2 phenotype, thus synergistically accelerating the wound healing phase transition from inflammation to proliferation and remodeling. On the chronic diabetic wound model, the average remaining wound area after FHHA-S/Fe treatment is much smaller than both that of FHHA/Fe without grafted thioethers and the control group, especially in the early wound healing stage. Therefore, this facile dressing strategy with intrinsic dual modulation mechanisms of the wound inflammation microenvironment may act as an effective and safe treatment strategy for chronic wound management.

A Multi-Functional Silicon Nanoparticle Designed for Enhanced Osteoblast Calcification and Related Combination Therapy.

Implant materials applied in bone defect commonly focus on the inducement of bone regeneration and neglect to cure complications including bacterial infection and inflammation, which may result in delayed unions or even amputation. In this study, a microporous silica nanoparticle-poly(N-isopropylacrylamide-b-(2-(dimethylamino)ethyl methacrylate) is synthesized for loading DXMS and the ECM-derived peptide (Sequence: Succinic acid-GTPGPQGIAGQRGVV) in order to enhance the osteoblast calcification and relieve related symptoms. Positively charged PDMA blocks endow the nanoparticle with the antimicrobial property. Moreover, the combination of DXMS makes it have the ability of anti-inflammation and promoting calcification formation. Furthermore, incorporation of the peptide leads to a significant improvement of mineralization and alkaline phosphatase expression in the preosteoblast. After intramuscular implantation in mice for four weeks, the results indicate the composite nanoparticle can promote ectopic bone formation. These combined properties make the composite silicon nanoparticle a promising osteogenic drug appropriate for further study in bone repair and related combination therapy.

Amino-Modified Polymer Nanoparticles as Adjuvants to Activate the Complement System and to Improve Vaccine Efficacy in Vivo.

Subunit vaccines are safer but often poorly immunogenic in comparison to traditional vaccines, and thus, adjuvants and delivery vehicles are needed to enhance the immune response. The complement system is a part of the innate immune system, which plays an important role in innate and adaptive immunity. Therefore, the activation of the complement system could be utilized as a potential strategy for vaccine applications. Herein, cysteamine hydrochloride was grafted onto a methoxy poly(ethylene glycol)-block-poly (allyl glycidyl ether)-block-poly(ε-caprolactone) copolymer to synthesize a triblock polymer mPEG5k-PAGE15(NH2)-PCL5k(TPCAH) with amino groups on the side chain. The positive charge of the amino groups could bind with the negatively charged protein (like ovalbumin (OVA)) to form a stable complex by electrostatic interaction. The triblock copolymer TPCAH we designed can easily self-assemble into polymer nanomicelles, and the size of the nanoparticles is similar to that of the pathogens, which was beneficial to the uptake by lymphocytes. Furthermore, the amino groups modified on the side chain can not only integrate with proteins but also activate the complement system, thereby enhancing the immune response of subunit vaccines. The results showed that the complex TPCAH@OVA could efficiently promote powerful anti-OVA-specific antibody production, enhance CD4+ T- and CD8+ T-cell activation, improve the lymphocyte proliferation efficiency, and increase the secretion of different cytokines. In addition, the abundant amino groups on the surface of TPCAH@OVA could effectively activate the complement system to further enhance adaptive immunity. Overall, these results indicated that the triblock copolymer TPCAH as an adjuvant and carrier can effectively improve the ability of innate and adaptive immune responses to resist pathogens, making it a potential candidate for vaccine applications.

Added value of apparent diffusion coefficient in distinguishing between serous and mucin-producing pancreatic cystic neoplasms.

OBJECTIVES: To evaluate the added value of diffusion-weighted imaging (DWI) on MRI in differentiating serous from mucin-producing pancreatic cystic neoplasms (PCNs). METHODS: One hundred seventeen patients with PCN measuring ≥ 10 mm were included. Three readers independently evaluated MRI with and without the use of apparent diffusion coefficient (ADC). Logistic regression was used to analyze whether confidence scores were different with the use of different image sets. Diagnostic performance with and without ADC was compared. RESULTS: DWI/ADC improved confidence in 44.8%, 73.6%, and 78.2% of patients by the three readers in distinguishing serous from mucin-producing PCNs. The use of ADC increased the probability of a higher confidence in the differentiation as compared to morphological imaging for all three readers (p < 0.001). Odds ratio for increase in the diagnostic confidence with the use of ADC for the three readers with decreasing years of experience were 5.8, 6.8, and 12.7. The diagnostic accuracy of morphological MRI with ADC was higher than that without ADC for two of three readers with lesser experience (87.2% vs. 80.8%; 91.5% vs. 80.8%). CONCLUSION: DWI may have added value as a complementary tool to conventional morphological MRI in differentiating between serous and mucin-producing PCNs with possibly greater value for readers with less experience in reading abdominal MRI. KEY POINTS: • Optimal management of PCNs requires differentiation of serous from mucin-producing PCNs. • ADC measurements allow increased confidence in differentiating serous from mucin-producing PCNs. • ADC measurements increase the accuracy in diagnosing serous versus mucin-producing PCNs.

Photostability Highly Improved Nanoparticles Based on IR-780 and Negative Charged Copolymer for Enhanced Photothermal Therapy.

The development of near-infrared (NIR) dyes with desirable photophysical characteristics for tumor therapy is highly expected at present. In this report, IR-780 iodide was loaded by the mercaptopropionic acid grafted poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(allyl glycidyl ether) [mPEG5K-PCL10K-PAGE6 (MPA)] copolymer to form nanomicelles (IR-780@TBMPA) in aqueous solution. On account of the hydrophobic and electrostatic interaction between mPEG5K-PCL10K-PAGE6 (MPA) and IR-780, the IR-780@TBMPA micelle was structurally stable with improved solubility, light stability and biocompatibility. The encapsulation of IR-780 indicated no influence on its original physicochemical property, showing good optical and thermal characteristics. The drug-loaded micelles had appropriate microscopic size for endocytosis, displaying significant cytotoxicity to HeLa cells under NIR laser irradiation. In addition, the phototoxicity generated by photothermal and photodynamic effect of IR-780@TBMPA under 808 nm laser irradiation was also investigated by reactive oxygen species (ROS) detection and flow cytometry. Furthermore, the superior accumulation of IR-780@TBMPA in tumor tissues provided sufficient hyperthermia to kill tumor cells, indicating its potential in cancer clinical therapy.

Development of Organic/Inorganic Compatible and Sustainably Bioactive Composites for Effective Bone Regeneration.

In this paper, we demonstrate a strategy of covalently bonding bioactive molecules onto inorganic hydroxyapatite (HAp) to improve the compatibility between organic and inorganic components and endow the bone composites with sustainable bioactivity. Bone morphogenetic protein-2 (BMP-2) peptide covalently immobilized nano-hydroxyapatite (nHAp-BMP-2) is developed to preserve the bioactivity and slow the release of the BMP-2 peptide. Then nHAp-BMP-2 was further incorporated into an ultraviolet-curable mixture of gelatin methacrylamide (GelMA) and four-armed PEG methacrylamide (four-armed PEGMA) to form a Gel/(nHAp-BMP-2) composite. The hydrogen bonding between gelatin and BMP-2 on nHAp-BMP-2 enhanced the compatibility between inorganic and organic components. The Gel/(nHAp-BMP-2) composite exhibited superior biocompatibility caused by gelatin and nHAp-BMP-2, except in a two-dimensional cell culture, the hydrogel was also capable of a three-dimensional cell culture. In addition, the introduction of nHAp-BMP-2 had a positive influence on bone marrow mesenchymal stem cell proliferation, differentiation, and the subsequent calcification on the composite. After treatment of a rat calvarial defect model for 12 weeks, the Gel/(nHAp-BMP-2) group showed the largest new bone volume and the highest ratio of new bone (50.54 ± 13.51 mm3 and 64.38 ± 17.22%, respectively) compared to those of the other groups. These results demonstrate that this way of controlling BMP-2 release is effective and the Gel/(nHAp-BMP-2) composite has great potential in bone regeneration therapy.

Utility of volumetric contrast-enhanced and diffusion-weighted MRI in differentiating between common primary hypervascular liver tumors.

BACKGROUND: Differentiating between hepatocellular carcinoma (HCC), focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) is usually achievable by MRI. However, in some cases with atypical imaging findings accurate diagnosis may be difficult. PURPOSE: To assess the diagnostic value of volumetric contrast-enhanced (CE) and volumetric diffusion-weighted imaging (DWI) in differentiating between HCC, FNH, and HCA. STUDY TYPE: Retrospective. SUBJECTS: In all, 143 patients (206 lesions): 42 HCA (81 lesions), 51 FNH (65 lesions), and 50 HCC (60 lesions). FIELD STRENGTH/SEQUENCE: 1.5T MRI, T1 -T2 WI, DWI. ASSESSMENT: Patients underwent CE-MRI and DWI (b = 0, 750 mm2 /s). Volumetric assessment of lesions' contrast enhancement and apparent diffusion coefficient (ADC) was performed with semiautomatic software after 3D image registration and segmentation by an observer and compared between three lesion groups. The diagnosis of lesions was based on histopathology, typical MRI findings, and/or follow-up. STATISTICAL TESTS: Independent t-test was used to compare parameters between two groups, one-way analysis of variance (ANOVA) between three groups, and receiver operator characteristic curve (ROC) analysis to define under-curve area and optimal cutoff. RESULTS: Mean values (±standard deviation) for HCC, FNH, and HCA, respectively, were: 1) arterial enhancement (%), 40.5 ± 13.2, 88.6 ± 32.6, 69.6 ± 25.1; 2) venous enhancement (%) 72.4 ± 22.1, 95.2 ± 30.9, 80.7 ± 30.6; and 3) ADC (10-6 mm2 /s) 1404.5 ± 168.1, 1413.4 ± 232.1, 1070.1 ± 232.1. ADC was the best differentiator of HCA from FNH (at 1211 × 10-6 mm2 /s; sensitivity 80.4%, specificity 71.7%) and arterial enhancement was the best differentiator of HCC from both HCA (at 48%; sensitivity 80.0%, specificity 80.5%) and FNH (at 52%; sensitivity 85.7%, specificity 85.4%). A combination of arterial enhancement and ADC (at 50% and 1227 × 10-6 mm2 /s) differentiated three types of tumors with high specificity (87.9%). DATA CONCLUSION: Volumetric CE-MRI and volumetric DWI can help to differentiate between HCC, FNH, and HCA. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1080-1090.

Unresectable Intrahepatic Cholangiocarcinoma: Multiparametric MR Imaging to Predict Patient Survival.

Purpose To determine the performance of magnetic resonance (MR) imaging-based tumor metrics for evaluation of response to transarterial chemoembolization (TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICCA). Materials and Methods Ninety-four patients with unresectable ICCA underwent baseline and follow-up MR imaging after TACE and were followed up until death or end of study duration. Lesions were analyzed for anatomic (Response Evaluation Criteria in Solid Tumors [RECIST] and tumor volume) and functional (viable tumor volume, viable tumor burden, and apparent diffusion coefficient [ADC]) volumetric MR parameters by using semiautomatic software. Response was assessed by using changes in viable tumor volume by using modified RECIST (mRECIST)-derived thresholds (three-dimensional mRECIST), viable tumor burden, and ADC. Overall survival was the primary endpoint. Cox-regression and Kaplan-Meier survival analysis were used. Results Tumor volume did not change after TACE (P = .07) whereas RECIST diameter showed a small change (-2.6%; P = .02). There was an increase in ADC (20.7%) and a decrease in viable tumor volume (-29.3%) and viable tumor burden (-29.1%; P < .001 for all). Higher overall survival was noted among responders by using thresholds of 25% increase in ADC, 66% decrease in viable tumor volume, and 50% decrease in viable tumor burden (log-rank test, P < .05). Hazard ratio for nonresponders by using ADC, three-dimensional mRECIST, and viable tumor burden at multivariable analysis was 2.9 (P = .004), 4.1 (P = .009), and 4.0 (P = .002), respectively. Survival differences were noted for patients who showed response by using all three parameters (ADC, three-dimensional mRECIST, and viable tumor burden) versus those who showed response by using either one or two of these parameters versus those who showed no response (P < .001). Conclusion Changes in volumetric ADC, viable tumor volume, and viable tumor burden at MR imaging provide prognostic information among patients with unresectable ICCA who undergo TACE. © RSNA, 2018 Online supplemental material is available for this article.

Are pancreatic IPMN volumes measured on MRI images more reproducible than diameters? An assessment in a large single-institution cohort.

OBJECTIVES: To assess reproducibility of volume and diameter measurement of intraductal papillary mucinous neoplasms (IPMNs) on MRI images. METHODS: Three readers measured the diameters and volumes of 164 IPMNs on axial T2-weighted images and coronal thin-slice navigator heavily T2-weighted images using manual and semiautomatic techniques. Interobserver reproducibility and variability were assessed. RESULTS: Interobserver intraclass correlation coefficients (ICCs) for the largest diameter measured using manual and semiautomatic techniques were 0.979 and 0.909 in the axial plane, and 0.969 and 0.961 in the coronal plane, respectively. Interobserver ICCs for the volume measurements were 0.973 and 0.970 in axial and coronal planes, respectively. The highest intraobserver reproducibility was noted for coronal manual measurements (ICC 0.981) followed by axial manual measurements (ICC 0.969). For the diameter measurements, Bland-Altman analysis revealed the lowest interobserver variability for manual axial measurements with an average range of 95% limits of agreement (LOA) of 0.68 cm. Axial and coronal volume measurements showed similar 95% LOA ranges (8.9 cm3 and 9.4 cm3, respectively). CONCLUSIONS: Volume and diameter measurements on axial and coronal images show good interobserver and intraobserver reproducibility. The single largest diameter measured manually on axial images showed the highest reproducibility and lowest variability. The 95% LOA may help define reproducible size changes in these lesions using measurements from different readers. KEY POINTS: • MRI measurements by different radiologists can be used for IPMN follow-up. • Both diameter and volume measurements demonstrate excellent interobserver and intraobserver reproducibility. • Manual axial measurements show the highest interobserver reproducibility in determining size. • Axial and coronal volume measurements show similar limits of agreement. • Manual axial measurements show the lowest variability in agreement range.

Prediction of post-TACE necrosis of hepatocellular carcinoma usingvolumetric enhancement on MRI and volumetric oil deposition on CT, with pathological correlation.

OBJECTIVE: To investigate whether volumetric enhancement on baseline MRI and volumetric oil deposition on unenhanced CT would predict HCC necrosis and response post-TACE. METHOD: Of 115 retrospective HCC patients (173 lesions) who underwent cTACE, a subset of 53 HCC patients underwent liver transplant (LT). Semiautomatic volumetric segmentation of target lesions was performed on dual imaging to assess the accuracy of predicting tumour necrosis after TACE in the whole cohort and at pathology in the LT group. Predicted percentage tumour necrosis is defined as 100 % - (%baseline MRI enhancement - %CT oil deposition). RESULTS: Mean predicted tumour necrosis by dual imaging modalities was 61.5 % ± 31.6%; mean percentage tumour necrosis on follow-up MRI was 63.8 % ± 31.5 %. In the LT group, mean predicted tumour necrosis by dual imaging modalities was 77.6 % ± 27.2 %; mean percentage necrosis at pathology was 78.7 % ± 31.5 %. There was a strong significant correlation between predicted tumour necrosis and volumetric necrosis on MRI follow-up (r = 0.889, p<0.001) and between predicted tumour necrosis and pathological necrosis (r = 0.871, p<0.001). CONCLUSION: Volumetric pre-TACE enhancement on MRI and post-TACE oil deposition in CT may accurately predict necrosis in treated HCC lesions. KEY POINTS: • Imaging-based tumour response can assist in therapeutic decisions. • Lipiodol retention as carrier agent in cTACE is a tumour necrosis biomarker. • Predicting tumour necrosis with dual imaging potentially obviates immediate post-treatment MRI. • Predicting tumour necrosis would facilitate further therapeutic decisions in HCC post-cTACE. • Pre-TACE MRI and post-TACE CT predict necrosis in treated HCC.

Predicting Parametrial Invasion in Cervical Carcinoma (Stages IB1, IB2, and IIA): Diagnostic Accuracy of T2-Weighted Imaging Combined With DWI at 3 T.

OBJECTIVE: The objective of our study was to retrospectively evaluate the efficacy of combined analysis of T2-weighted imaging and DWI in the diagnosis of parametrial invasion (PMI) in cervical carcinoma. MATERIALS AND METHODS: The clinical records of 192 patients with cervical carcinoma who met the study requirements were reviewed for this retrospective study. The signal intensities of suspicious PMI tissue were assessed on T2-weighted images, DW images, and apparent diffusion coefficient maps independently by two experienced radiologists. The radiologist observers predicted the presence of PMI by scoring T2-weighted imaging alone and then by scoring T2-weighted imaging and DWI combined. The results were compared with histopathologic findings. RESULTS: Histopathologic findings revealed PMI in 24 of 192 study subjects. In positively predicting the presence of PMI, T2-weighted imaging and DWI combined scored significantly better than T2-weighted imaging alone, as proven by high sensitivity (T2-weighted imaging alone vs T2-weighted imaging and DWI combined: observer 1, 75.0% vs 83.3% [p = 0.477]; observer 2, 66.7% vs 91.7% [p < 0.05]), high specificity (T2-weighted imaging alone vs T2-weighted imaging and DWI combined: observer 1, 84.5% vs 98.8% [p < 0.001]; observer 2, 85.7% vs 98.8% [p < 0.001]), and high accuracy (T2-weighted imaging alone vs T2-weighted imaging and DWI combined: observer 1, 83.3% vs 96.9% [p < 0.001]; observer 2, 83.3% vs 97.9% [p < 0.001]). The area under the ROC curve was also significantly higher for T2-weighted imaging and DWI combined (observer 1, 0.911; observer 2, 0.952) than for T2-weighted imaging alone (observer 1, 0.798; observer 2, 0.762). Although the interobserver agreement was good for T2-weighted imaging (κ = 0.695) and excellent for T2-weighted imaging and DWI combined (κ = 0.753), the improvement failed to achieve statistical significance (p = 0.28). CONCLUSION: Combined analysis of T2-weighted imaging and DWI enhances the accuracy of diagnosing PMI in patients with cervical cancer compared with T2-weighted imaging alone.

Accuracy of apparent diffusion coefficient in differentiating pancreatic neuroendocrine tumour from intrapancreatic accessory spleen.

OBJECTIVES: To evaluate and compare the accuracy of absolute apparent diffusion coefficient (ADC) and normalised ADC (lesion-to-spleen ADC ratio) in differentiating pancreatic neuroendocrine tumour (NET) from intrapancreatic accessory spleen (IPAS). METHODS: Study included 62 patients with the diagnosis of pancreatic NET (n=51) or IPAS (n=11). Two independent reviewers measured ADC on all lesions and spleen. Receiver operating characteristics (ROC) analysis to differentiate NET from IPAS was performed and compared for absolute and normalised ADC. Inter-reader reliability for the two methods was assessed. RESULTS: Pancreatic NET had significantly higher absolute ADC (1.431x10-3 vs 0.967x10-3 mm2/s; P<0.0001) and normalised ADC (1.59 vs 1.09; P<0.0001) compared to IPAS. An ADC value of ≥1.206x10-3 mm2/s was 70.6% sensitive and 90.9% specific for the diagnosis of NET vs. IPAS. Lesion to spleen ADC ratio of ≥1.25 was 80.4% sensitive, and 81.8% specific while ratio of ≥1.29 was 74.5% sensitive and 100% specific in the differentiation. The area under the curve (AUCs) for two methods were similar (88.2% vs. 88.8%; P=0.899). Both methods demonstrated excellent inter-reader reliability with ICCs for absolute ADC and ADC ratio being 0.957 and 0.927, respectively. CONCLUSION: Both absolute and normalised ADC allow clinically relevant differentiation of pancreatic NET and IPAS. KEY POINTS: • Imaging overlaps between IPASs and pancreatic-NETs lead to unnecessary procedures including pancreatectomy. • Uniquely low ADC of spleen allows differentiating IPASs from pancreatic NETs. • Both absolute-ADC and normalised-ADC (lesion-to-spleen ADC-ratio) demonstrate high accuracy in differentiating IPASs from NETs. • Both methods demonstrate excellent inter-reader reliability.

CO2 Stimuli-Responsive, Injectable Block Copolymer Hydrogels Cross-Linked by Discrete Organoplatinum(II) Metallacycles via Stepwise Post-Assembly Polymerization.

Supramolecular polymeric gels cross-linked by well-defined, discrete metal-organic macrocycles (MOMs) or metal-organic cages have become a prevailing topic within the field of supramolecular self-assembly. However, the realization of supramolecular polymeric hydrogels cross-linked by discrete organometallic architectures with good biocompatibility is still a great challenge. Herein, we present the successful preparation of CO2 stimuli-responsive, injectable block copolymer hydrogels cross-linked by discrete organoplatinum(II) metallacycles. Through the combination of coordination-driven self-assembly and stepwise post-assembly polymerization, star block copolymers (SBCPs) containing well-defined hexagonal metallacycles as cores were successfully prepared, which featured CO2 stimuli-responsive properties including CO2-triggered morphology transition and CO2-induced thermoresponsive behavior. Interestingly, the resultant SBCPs were capable of forming supramolecular hydrogels with MOMs as junctions near physiological temperature, which allowed the realization of a reversible gel-to-sol transformation through the removal and addition of CO2. More importantly, the resultant supramolecular hydrogels presented good cytocompatibility in vitro. Therefore, this study provides a new strategy for the construction of new "smart" supramolecular hydrogels with promising applications as biological materials.

Increased kinetic growth rate during late phase liver regeneration impacts the risk of tumor recurrence after colorectal liver metastases resection.

BACKGROUND: Although experimental data strongly support the pro-tumorigenic role of postoperative liver regeneration, this hypothesis has not been clinically investigated. We aimed to examine the impact of liver regeneration determined by volumetric imaging on recurrence following resection of colorectal liver metastasis (CRLM). METHODS: Resected liver volume was subtracted from total liver volume (TLV) to define postoperative remnant liver volume (RLVp). Early and late kinetic growth rates (KGR) were defined as the postoperative increases in liver volume within 2-3 and 8-10 months from surgery, respectively, divided by the corresponding time interval. RESULTS: Median early and late KGR was 2.6%/month (IQR: -0.9 to 12.3) and 1.0%/month (IQR: -0.64 to 2.91), respectively. Late KGR predicted intrahepatic recurrence after 1 year from surgery (AUC 0.677, P = 0.011). Specifically, patients with a late KGR ≥1% had a higher cumulative risk of recurrence compared with patients with a KGR <1% (P = 0.038). In multivariate analysis, KGR ≥1% independently predicted recurrence (P = 0.027). DISCUSSION: A KGR ≥1% during the late regeneration phase was associated with increased risk of intrahepatic recurrence. These data may inform the timing of adjuvant therapy administration and focus surveillance strategies for high-risk patients.

Effect of microRNA-101 on proliferation and apoptosis of human osteosarcoma cells by targeting mTOR.

Studies have proved that microRNA-101 (miR-101) functions as a tumor suppressor and is associated with growth and apoptosis of various human cancers. However, the role of miR-101 in osteosarcoma and the possible mechanism by which miR-101 affects the tumor growth and apoptosis have not been fully elucidated. In this study, we found that the expression of miR-101 was down-regulated in osteosarcoma tissues and Saos-2 cell line as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. To better characterize the role of miR-101 in osteosarcoma, we used a gain-of-function analysis by transfecting human osteosarcoma cell line Saos-2 with chemically synthesized miR-101 mimics. The results showed that overexpression of miR-101 inhibited the proliferation and promoted the apoptosis of Saos-2 cells. Meanwhile, bioinformatic analysis demonstrated that mTOR gene was a direct target of miR-101. Overexpression of miR-101 significantly decreased the expression of mTOR at both mRNA and protein levels in Saos-2 cells, consequently inhibiting Saos-2 cells proliferation and promoting cells apoptosis in an mTOR-dependent manner. Taken together, these data suggest that miR-101 may act as a tumor suppressor, which is commonly downregulated in both osteosarcoma tissues and cells. mTOR plays an important role in mediating miR-101 dependent biological functions in osteosarcoma. Reintroduction of miR-101 may be a novel therapeutic strategy by down-regulating mTOR expression.