Objective
To assess the overall diagnostic accuracy of different MR imaging sequences in the detection of the dysplastic nodule (DN).
Methods
PubMed, Cochrane Library, and Web of Science were ...systematically searched. Study selection and data extraction were conducted by two authors independently. Quality assessment of diagnostic accuracy studies (QUADAS) 2 in RevMan software was used to score the included studies and assess their methodological quality. A random-effects model was used for statistical pooling by Meta-Disc. Subgroup analysis and sensitivity analysis were used to explore potential sources of heterogeneity.
Results
Fourteen studies (335 DN lesions in total) were included in our meta-analysis. The area under the curve (AUC) of summary receiver operating characteristic (SROC) of T
2
WI was 0.87. Pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of DWI were 0.81 (95%CI, 0.73–0.87), 0.90 (95%CI, 0.86–0.93), 7.04 (95%CI, 4.49–11.04), and 0.24 (95%CI, 0.17–0.33) respectively. In the arterial phase, pooled sensitivity, specificity, PLR, and NLR were 0.89 (0.84–0.93), 0.75 (0.72–0.79), 3.72 (2.51–5.51), and 0.17 (0.12–0.25), respectively. Pooled sensitivity, specificity, PLR, and NLR of the delayed phase were 0.78 (0.72–0.83), 0.60 (0.55–0.65), 2.19 (1.55–3.10), and 0.36 (0.23–0.55) separately. Pooled sensitivity, specificity, PLR, and NLR of the hepatobiliary phase were 0.77 (0.71–0.82), 0.92 (0.89–0.94), 8.74 (5.91–12.92), and 0.24 (0.14–0.41) respectively. Pooled sensitivity, specificity, and PLR were higher on DWI and hepatobiliary phase in diagnosing LGDN than HGDN.
Conclusion
MR sequences, particularly DWI, arterial phase, and hepatobiliary phase imaging demonstrate high diagnostic accuracy for DN.
Key Points
•
MRI has dramatically improved the detection and accurate diagnosis of DNs and their differentiation from hepatocellular carcinoma.
•
Overall diagnostic accuracy of different MRI sequences in the detection of DN has not been studied before.
•
Our meta-analysis demonstrates that MRI achieves a high diagnostic value for DN, especially when using DWI, arterial phase imaging, and hepatobiliary phase imaging.
Purpose
This study aimed to evaluate the Ki-67 proliferation state in patients with gastrointestinal stromal tumors (GISTs) using radiomics prediction signatures based on contrast-enhanced computed ...tomography (CE-CT).
Materials and methods
This single-center, retrospective study involved 103 patients (48 men and 55 women, mean age 61.1 ± 10.6 years) who had pathologically confirmed GISTs after curative resection, including 63 with low Ki-67 proliferation level (Ki-67 labeling index ≤ 6%) and 40 with high Ki-67 proliferation level (Ki-67 labeling index > 6%). Radiomics features of the delineated lesions were preoperatively extracted from three-phase CE-CT images, including the arterial, venous, and delayed phases. The most relevant features were selected to construct the radiomics signatures using a logistic regression algorithm. Significant demographic characteristics and semantic features on CT were selected to develop a nomogram along with the optimal radiomics feature. We calculated the sensitivity, specificity, accuracy, F1 score, and area under the receiver operating characteristic (ROC) curve to evaluate the predictive performance of radiomics signatures.
Results
Ten quantitative radiomics features (two first-order and eight texture features) were selected to construct radiomics signatures. The radiomics signature based on the three-phase CE-CT images showed better predictive performance than that based on the single-phase CE-CT images, with an area under the curve (AUC) of 0.83 (95% CI 0.73–0.92) and F1 score of 82% in the training dataset and an AUC of 0.80 (95% CI 0.63–0.95) and F1 score of 75% in the testing dataset. The nomogram showed good calibration.
Conclusion
Radiomics signatures using CE-CT images are generalizable and could be used in clinical practice to determine the proliferation state of Ki-67 in GISTs.
Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As ...interleukin‐1β (IL‐1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL‐1β‐induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL‐6, inducible nitric oxide synthase, cyclooxygenase‐2, and tumor necrosis factor‐α (TNF‐α) in a concentration‐dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti‐inflammatory effect by inactivating the PI3K/AKT/NF‐κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.
Maslinic acid (MA) could prevent IL‐1β‐associated inflammation as well as extracellular matrix (ECM) degradation in human osteoarthritis (OA) chondrocytes. The potential mechanism involved in the protective effect of MA was that it could reverse inflammation‐related destruction via inhibiting PI3K/AKT/NF‐κB pathways activation. MA ameliorates OA progression in vivo via inhibiting the devastation of cartilage surface, cartilage calcification, and osteophytes formation.
Ligand-to-metal charge transfer (LMCT) is a mechanistic strategy that provides a powerful tool to access diverse open-shell species using earth abundant elements and has seen tremendous growth in ...recent years. However, among many reaction manifolds driven by LMCT reactivity, a general and catalytic protocol for modular difunctionalization of alkenes remains unknown. Leveraging the synergistic cooperation of iron-catalyzed ligand-to-metal charge transfer and radical ligand transfer (RLT), here we report a photocatalytic, modular difunctionalization of alkenes using inexpensive iron salts catalytically to function as both radical initiator and terminator. Additionally, strategic use of a fluorine atom transfer reagent allows for general fluorochlorination of alkenes, providing the first example of interhalogen compound formation using earth abundant element photocatalysis. Broad scope, mild conditions and versatility in converting orthogonal nucleophiles (TMSN
3
and NaCl) directly into corresponding open-shell radical species are demonstrated in this study, providing a robust means towards accessing vicinal diazides and homo-/hetero-dihalides motifs catalytically. These functionalities are important precursors/intermediates in medicinal and material chemistry. Preliminary mechanistic studies support the radical nature of these transformations, disclosing the tandem LMCT/RLT as a powerful reaction manifold in catalytic olefin difunctionalization.
Simple iron salts are able to photocatalyze the diazidation, dichlorination, and fluorochlorination of alkenes
via
the merger of ligand-to-metal charge transfer (LMCT) and either radical ligand transfer (RLT) or fluorine atom transfer (FAT).
Background Solid components of part-solid nodules (PSNs) at CT are reflective of invasive adenocarcinoma, but studies describing radiomic features of PSNs and the perinodular region are lacking. ...Purpose To develop and to validate radiomic signatures diagnosing invasive lung adenocarcinoma in PSNs compared with the Brock, clinical-semantic features, and volumetric models. Materials and Methods This retrospective multicenter study (
, NCT03872362) included 291 patients (median age, 60 years; interquartile range, 55-65 years; 191 women) from January 2013 to October 2017 with 297 PSN lung adenocarcinomas split into training (
= 229) and test (
= 68) data sets. Radiomic features were extracted from the different regions (gross tumor volume GTV, solid, ground-glass, and perinodular). Random-forest models were trained using clinical-semantic, volumetric, and radiomic features, and an online nodule calculator was used to compute the Brock model. Performances of models were evaluated using standard metrics such as area under the curve (AUC), accuracy, and calibration. The integrated discrimination improvement was applied to assess model performance changes after the addition of perinodular features. Results The radiomics model based on ground-glass and solid features yielded an AUC of 0.98 (95% confidence interval CI: 0.96, 1.00) on the test data set, which was significantly higher than the Brock (AUC, 0.83 95% CI: 0.72, 0.94;
= .007), clinical-semantic (AUC, 0.90 95% CI: 0.83, 0.98;
= .03), volumetric GTV (AUC, 0.87 95% CI: 0.78, 0.96;
= .008), and radiomics GTV (AUC, 0.88 95% CI: 0.80, 0.96;
= .01) models. It also achieved the best accuracy (93% 95% CI: 84%, 98%). Both this model and the model with added perinodular features showed good calibration, whereas adding perinodular features did not improve the performance (integrated discrimination improvement, -0.02;
= .56). Conclusion Separating ground-glass and solid CT radiomic features of part-solid nodules was useful in diagnosing the invasiveness of lung adenocarcinoma, yielding a better predictive performance than the Brock, clinical-semantic, volumetric, and radiomics gross tumor volume models.
See also the editorial by Nishino in this issue. Published under a CC BY 4.0 license.
Younger age is an independent risk factor for breast cancer (BC) prognosis, and BC in young women is often considered more aggressive. BC patients with different age and molecular subtypes have ...different metastasis patterns and survival. Herein, we aim to explore the metastasis patterns, characteristics and treatment methods of young patients with BC, and to compare them with older patients. Data of young patients (aged less than or equal to40 years old) and older patients (aged >40 years old) with BC were extracted from the Surveillance, Epidemiology, and End Results (SEER) registration database in 2010-2019 in this retrospective cohort study. Univariate and multivariate competing risk models and proportional hazard models were used to explore the association between different metastasis patterns and treatments and BC prognoses in young and older patients. Kaplan-Meier (KM) curves were drawn to reflect the survival probability of patients with BC who have different metastasis patterns. Also, we performed subgroup analysis of different metastasis patterns to explore the association between different treatments and overall survival (OS)/cancer specific survival (CSS) in patients with BC. The evaluation index was hazard ratios (HRs) with 95% confidence intervals (CIs). Totally, 5,984 patients died, and 92.56% of them died from BC. There were respectively 1,089 young patients and 9,105 older patients, and we found some differences of characteristics and metastasis patterns between them. After adjusting for covariates, young patients who had brain metastasis and multiple sites metastasis seemed to have high risk of both lower OS and CSS. Among older patients with BC, brain metastasis, liver metastasis, and multiple sites metastasis were all positively associated with both lower OS and CSS. In young and older patients, those who not receive radiotherapy or surgery, or received non-surgery combined with radiotherapy seemed to have high risk of both lower OS and CSS. Breast-conserving surgery (BCS) and surgery combined with radiotherapy were associated with higher OS and CSS in young patients, while only older patients received surgery combined with radiotherapy had higher OS and CSS. Results of subgroup analysis indicated that for patients with different metastasis patterns, developing a personalized treatment plan is necessary. Characteristics of BC between young patients and older patients were different. Clinicians should focus on different metastasis sites and choose appropriate treatments in patients with different ages, which may improve the prognoses.
Limited DNA end resection is the key to impaired homologous recombination in BRCA1-mutant cancer cells. Here, using a loss-of-function CRISPR screen, we identify DYNLL1 as an inhibitor of DNA end ...resection. The loss of DYNLL1 enables DNA end resection and restores homologous recombination in BRCA1-mutant cells, thereby inducing resistance to platinum drugs and inhibitors of poly(ADP-ribose) polymerase. Low BRCA1 expression correlates with increased chromosomal aberrations in primary ovarian carcinomas, and the junction sequences of somatic structural variants indicate diminished homologous recombination. Concurrent decreases in DYNLL1 expression in carcinomas with low BRCA1 expression reduced genomic alterations and increased homology at lesions. In cells, DYNLL1 limits nucleolytic degradation of DNA ends by associating with the DNA end-resection machinery (MRN complex, BLM helicase and DNA2 endonuclease). In vitro, DYNLL1 binds directly to MRE11 to limit its end-resection activity. Therefore, we infer that DYNLL1 is an important anti-resection factor that influences genomic stability and responses to DNA-damaging chemotherapy.
Benzodiazepines (BZDs) and Non-BZDs (NBZDs) have been widely used for patients with chronic insomnia. Long-term uses of BZDs may cause cognitive impairment and increase the risk for dementia in older ...patients. NBZD as an agonist of the GABA
receptor complex includes eszopiclone, zopiclone, zolpidem, and zaleplon, also collectively known as Z drugs. However, evaluations for an association between cognitive impairment and Z drug use have been limitedly performed. This study aimed to investigate the association between the risk of cognitive decline and exposure to Z drugs in middle-aged and older patients with chronic insomnia.
Investigations were performed on patients with chronic insomnia who visited the outpatient Department of Neurology, Beijing Friendship Hospital, and were assessed for the global cognitive function (MoCA) and memory (AVLT), executive function (TMT-B), visuospatial ability (CDT), verbal function (BNT-30), and attention (DST). Multiple regression analysis was conducted to determine the independent factors of cognition and evaluated the effect of Z drug use (zolpidem and zopiclone) on cognition.
A total of 120 subjects were identified. In our analysis, BZD exposure density (
= 0.025, OR = 1.43, 95% CI, 1.25-1.86) was an independent risk factor of cognitive impairment in middle-aged and older patients with chronic insomnia. Neither Z drug use (
= 0.103) nor Z drug exposure density (
= 0.765) correlated with global cognitive function. Moreover, there was a positive association between Z drug use and attention (
= 0.002, OR = 0.42, 95% CI, 0.24-0.73). Additionally, income level (
= 0.001, OR = 0.23, 95% CI, 0.10-0.53), severity of insomnia (
= 0.019, OR = 1.20, 95% CI, 1.03-1.40) and age (
= 0.044, OR = 1.07, 95% CI, 1.00-1.14) were also independent factors of global cognitive function.
BZD exposure density was an independent risk factor of cognitive impairment in middle-aged and older patients with chronic insomnia, but no correlation was found between Z drug use and cognitive impairment. Moreover, the use of Z drugs seemed to be associated with protection for attention. The use for prescription of BZDs, in this case, should be avoided or limited to low doses. Due to the addiction and tolerance, Z drugs should also be prescribed with great caution in middle-aged and elderly patients.
Emerging as a powerful tool for lead optimization in pharmaceutical research and development, to develop the facile, general protocols that allows the incorporation of fluorine-containing motif in ...drug candidates has accumulated enormous research interest in recent years. Among these important motifs, the incorporation of strategic motif CF
on aliphatic chain especially with the concomitant construction of trifluoromethylated alkanes bearing a CF
-substituted stereogenic carbon, is of paramount importance. Herein, we disclose an asymmetric nickel-catalyzed reductive trifluoroalkylation of alkenyl halides for enantioselective syntheses of diverse α-trifluoromethylated allylic alkanes, offering a general protocol to access the trifluoromethyl analogue to chiral α-methylated allylic alkanes, one of the most prevalent key components among natural products and pharmaceuticals. Utilities of the method including the application of the asymmetric trifluoroalkylation on multiple biologically active complex molecules, derivatization of transformable alkenyl functionality were demonstrated, providing a facile method in the diversity-oriented syntheses of CF
-containing chiral drugs and bioactive-molecules.
Purpose. Diabetic retinopathy (DR) is an ocular disease caused by diabetes and may lead to vision impairment and even blindness. Oxidative stress and inflammation are two key pathogenic factors of ...DR. Recently, regulatory roles of different microRNAs (miRNAs) in DR have been widely verified. miR-26a-5p has been confirmed to be a potential biomarker of DR. Nevertheless, the specific functions of miR-26a-5p in DR are still unclear. Methods. Primary cultured mouse retinal Müller cells in exposure to high glucose (HG) were used to establish an in vitro DR model. Müller cells were identified via morphology observation under phase contrast microscope and fluorescence staining for glutamine synthetase. The in vivo animal models for DR were constructed using streptozotocin-induced diabetic C57BL/6 mice. Western blotting was performed to quantify cytochrome c protein level in the cytoplasm and mitochondria of Müller cells and to measure protein levels of glial fibrillary acidic protein (GFAP), ubiquitin-specific peptidase 14 (USP14), as well as factors associated with NF-κB signaling (p-IκBα, IκBα, p-p65, and p65) in Müller cells or murine retinal tissues. ROS production was detected by CM-H2DCFDA staining, and the concentration of oxidative stress markers (MDA, SOD, and CAT) was estimated by using corresponding commercial kits. Quantification of mRNA expression was conducted by RT-qPCR analysis. The concentration of proinflammatory factors (TNF-α, IL-1β, and IL-6) was evaluated by ELISA. Hematoxylin-eosin staining for murine retinal tissues was performed for histopathological analysis. Immunofluorescence staining was conducted to determine NF-κB p65 nuclear translocation in Müller cells. Furthermore, the interaction between miR-26a-5p and USP14 was verified via the luciferase reporter assays. Results. HG stimulation contributed to Müller cell dysfunction by inducing inflammation, oxidative injury, and mitochondrial damage to Müller cells. miR-26a-5p was downregulated in Müller cells under HG condition, and overexpression of miR-26a-5p relieved HG-induced Müller cell dysfunction. Moreover, miR-26a-5p targeted USP14 and inversely regulated USP14 expression. Additionally, HG-evoked activation of NF-κB signaling was suppressed by USP14 knockdown or miR-26a-5p upregulation. Rescue assays showed that the protective impact of miR-26a-5p upregulation against HG-induced Müller cell dysfunction was reversed by USP14 overexpression. Furthermore, USP14 upregulation and activation of NF-κB signaling in the retinas of DR mice were detected in animal experiments. Injection with miR-26a-5p agomir improved retinal histopathological injury and weakened the concentration of proinflammatory cytokines and oxidative stress markers in the retinas of DR mice. Conclusion. miR-26a-5p inhibits oxidative stress and inflammation in DR progression by targeting USP14 and inactivating the NF-κB signaling pathway.
PDF
