Study on the Metabolic Basis of the Color Formation of Two Color-Presenting Types of Jujube Fruits.

Jujube is a plant of the genus Ziziphus in the family Rhamnaceae; its fruit has high nutritional value, and it is rich in polyphenols, flavonoids, and other secondary metabolites. The color of its peel is an important indicator for evaluating the appearance of the fruit. However, the mechanism of the difference in color presentation between the seedling offspring of the 'Red Fruit' (TLHH) and the 'Green Fruit' (TLHL) of the fresh jujube cultivar 'Tailihong' is not clear. Therefore, this study used targeted metabolomics techniques to accurately and quantitatively analyze the metabolic pathways of carotenoid and anthocyanin metabolites during the ripening process of two color-presenting types of jujube fruits. Through the analysis of the dynamic changes in the pigment content of the jujube peel, it was found that 30 DAP (days after pollination), 80 DAP, and 110 DAP were the key periods for the development of the color of the peel of 'TLHL' and 'TLHH' jujube and that the substances responsible for the main differences were chlorophyll, carotenoids, and anthocyanins. Furthermore, we used an LC-MS/MS metabolic analysis to compare the differences in the carotenoids and anthocyanin metabolites between the two color-presenting types of jujube peels at the key periods of 30 DAP, 80 DAP, and 110 DAP. We detected 32 carotene metabolites and 75 anthocyanin metabolites, respectively, among which lutein had the highest content of carotenoids; it reached the maximum value (93.05 µg/g) and was higher than that of 'TLHH' (74.14 µg/g) at 30 DAP of 'TLHL'. Both showed a decreasing trend with fruit ripening. The anthocyanin with the highest content was cyanidin-3-O-(tartaryl)rhamnoside-5-O-glucoside, which reached the maximum value (258.32 µg/g) at 30 DAP of 'TLHH' and was 51.6 times that of 'TLHL'; similarly, both showed a decreasing trend with fruit ripening. These results elucidate the main metabolites of carotenoids and anthocyanins in the two types of jujube peel and their accumulation characteristics, suggesting that the key metabolites of the difference in color between 'TLHL' and 'TLHH' jujube fruits were lutein and cyanidin-3-O-(tartaryl)rhamnoside-5-O-glucoside, increasing the understanding of the color mechanism of jujube peel and providing a reference for targeted genetic breeding of jujube peel color.

Pernicious anemia is a common cause of cobalamin deficiency-caused megaloblastic anemia in Hainan, China.

BACKGROUND: Pernicious anemia (PA) is believed to be highly prevalent in Western countries but has rarely been reported in China. The study explores whether PA, an autoimmune disease, is an uncommon cause of cobalamin (vitamin B12) deficiency anemia in China. METHODS: Clinical and hematological data were collected from 90 cobalamin deficiency-caused megaloblastic anemia (MA) patients between July 2014 and December 2021. Through anti-intrinsic factor antibody (IFA) and anti-parietal cell antibody (PCA) testing, PA was distinguished from other causes of cobalamin deficiency leading to MA. Meanwhile, 30 healthy controls (HCs) were included to estimate the positive rates of IFA and PCA. RESULTS: Of the 30 HCs, only one tested positive for IFA, and all 30 tested negative for PCA. Among the 90 patients with cobalamin deficiency-caused MA, 76.7% were positive for IFA, and 47.8% were positive for PCA; a total of 76 patients (84.4%) were diagnosed with PA. The mean follow-up time was 41.0 ± 16.3 months. During the follow-up period, no case relapsed among the continuous cobalamin-supply treatment patients, while 24.4% of patients relapsed due to the interruption of maintenance cobalamin-supplement therapy (the median recurrence time was 54.0 ± 17.7 months). CONCLUSIONS: The proportion of PA in cobalamin deficiency-caused MA patients in Hainan province was higher than 80%, which was more common than expected. Therefore, screening for IFA, PCA, endoscopic biopsy, and thyroid-related parameters are recommended for all cobalamin deficiency-caused MA patients. Furthermore, maintenance cobalamin-supplement therapy is important for PA patients.

This research examines pernicious anemia (PA), a type of anemia caused by vitamin B12 deficiency, which has been widely reported in Western countries but is less known in China. The study focuses on determining if PA is also a significant cause of this deficiency in Hainan, China. Researchers gathered data from patients with megaloblastic anemia (a blood disorder) due to lack of vitamin B12, comparing them with healthy individuals to see how common PA is. The findings reveal that a very high percentage of the patients studied have PA, much higher than expected. This suggests that PA is not as rare in this region of China as previously thought. The study also highlights the importance of continuous treatment with vitamin B12 to prevent the recurrence of the anemia. Based on these results, the researchers recommend that all patients with vitamin B12 deficiency should be tested for PA and continuously receive vitamin B12 supplements to maintain their health once diagnosed with PA. This strategic insight is of paramount importance to medical practitioners in China, potentially paving the way for enhanced clinical management protocols for individuals afflicted by this ailment.

GSH exhaustion via inhibition of xCT-GSH-GPX4 pathway synergistically enhanced DSF/Cu-induced cuproptosis in myelodysplastic syndromes.

The clinical application of the therapeutic approach in myelodysplastic syndromes (MDS) remains an insurmountable challenge for the high propensity for progressing to acute myeloid leukemia and predominantly affecting elderly individuals. Thus, the discovery of molecular mechanisms underlying the regulatory network of different programmed cell death holds great promise for the identification of therapeutic targets and provides insights into new therapeutic avenues. Herein, we found that disulfiram/copper (DSF/Cu) significantly repressed the cell viability, increased reactive oxygen species (ROS) accumulation, destroyed mitochondrial morphology, and altered oxygen consumption rate. Further studies verified that DSF/Cu induces cuproptosis, as evidenced by the depletion of glutathione (GSH), aggregation of lipoylated DLAT, and induced loss of Fe-S cluster-containing proteins, which could be rescued by tetrathiomolybdate and knockdown of ferredoxin 1 (FDX1). Additionally, GSH contributed to the tolerance of DSF/Cu-mediated cuproptosis, while pharmacological chelation of GSH triggered ROS accumulation and sensitized cell death. The xCT-GSH-GPX4 axis is the ideal downstream component of ferroptosis that exerts a powerful protective mechanism. Notably, classical xCT inhibitors were capable of leading to the catastrophic accumulation of ROS and exerting synergistic cell death, while xCT overexpression restored these phenomena. Simvastatin, an inhibitor of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase, has beneficial effects in repurposing for inhibiting GPX4. Similarly, the combination treatment of DSF/Cu and simvastatin dramatically decreased the expression of GPX4 and Fe-S proteins, ultimately accelerating cell death. Moreover, we identified that the combination treatment of DSF/Cu and simvastatin also had a synergistic antitumor effect in the MDS mouse model, with the reduced GPX4, increased COX-2 and accumulated lipid peroxides. Overall, our study provided insight into developing a novel synergistic strategy to sensitize MDS therapy by targeting ferroptosis and cuproptosis.

Biological Characteristics and Functional Analysis of the Linoleic Acid Synthase Gene ZjFAD2 in Jujube.

Jujube fruit is rich in linoleic acid and other bioactive components and has great potential to be used for the development of functional foods. However, the roles of FAD2 genes in linoleic acid biosynthesis in jujube fruit remain unclear. Here, we identified 15 major components in jujube and found that linoleic acid was the main unsaturated fatty acid; major differences in the content and distribution of linoleic acid in the pulp and seeds were observed, and levels of linoleic acid decreased during fruit maturation. Analysis of the fatty acid metabolome, genome, and gene expression patterns of cultivated and wild-type jujube revealed five ZjFAD2 family members highly related to linoleic acid biosynthesis. The heterologous expression of these five ZjFAD2 family members in tobacco revealed that all five of these genes increased the content of linoleic acid. Additionally, transient expression of these genes in jujube fruit and the virus-induced gene silencing (VIGS) test further confirmed the key roles of ZjFAD2-11 and ZjFAD2-1 in the biosynthesis of linoleic acid. The results of this research provide valuable insights into the molecular mechanism underlying linoleic acid synthesis in jujube and will aid the development of quality-oriented breeding strategies.

Five machine learning-based radiomics models for preoperative prediction of histological grade in hepatocellular carcinoma.

PURPOSE: To compare the efficacy of radiomics models via five machine learning algorithms in predicting the histological grade of hepatocellular carcinoma (HCC) before surgery and to develop the most stable model to classify high-risk HCC patients. METHODS: Contrast-enhanced computed tomography (CECT) images of 175 HCC patients before surgery were analysed, and radiomics features were extracted from CECT images (including arterial and portal phases). Five machine learning models, including Bayes, random forest (RF), k-nearest neighbors (KNN), logistic regression (LR), and support vector machine (SVM), were applied to establish the model. The stability of the five models was weighed by the relative standard deviation (RSD), and the lowest RSD value was chosen as the most stable model to predict the histological grade of HCC. The area under the curve (AUC) and Delong tests were devoted to assessing the predictive efficacy of the models. RESULTS: High-grade HCC accounted for 28.57% (50/175) of the 175 patients. The RSD value of AUC via the RF machine learning model was the lowest (2.3%), followed by Bayes (3.2%), KNN (6.4%), SVM (8.7%) and LR (31.3%). In addition, the RF model (AUC = 0.995) was better than the other four models in the training set (p < 0.05), as well as obtained good predictive performance in the test set (AUC = 0.837). CONCLUSION: Among the five machine learning models, the RF-based radiomics model was the most stable and performed excellently in identifying high histological grade of HCC.

Methyl Jasmonate- and Salicylic Acid-Induced Transcription Factor ZjWRKY18 Regulates Triterpenoid Accumulation and Salt Stress Tolerance in Jujube.

Triterpenoids are important, pharmacologically active substances in jujube (Ziziphus jujuba Mill.), and play an important role in the plant's resistance to abiotic stress. However, regulation of their biosynthesis, and the underlying mechanism of their balance with stress resistance, remain poorly understood. In this study, we screened and functionally characterized the ZjWRKY18 transcription factor, which is associated with triterpenoid accumulation. The transcription factor is induced by methyl jasmonate and salicylic acid, and its activity was observed by gene overexpression and silencing experiments, combined with analyses of transcripts and metabolites. ZjWRKY18 gene silencing decreased the transcription of triterpenoid synthesis pathway genes and the corresponding triterpenoid content. Overexpression of the gene promoted the biosynthesis of jujube triterpenoids, as well as triterpenoids in tobacco and Arabidopsis thaliana. In addition, ZjWRKY18 binds to W-box sequences to activate promoters of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and farnesyl pyrophosphate synthase, suggesting that ZjWRKY18 positively regulates the triterpenoid synthesis pathway. Overexpression of ZjWRKY18 also increased tolerance to salt stress in tobacco and Arabidopsis thaliana. These results highlight the potential use of ZjWRKY18 to improve triterpenoid biosynthesis and salt stress tolerance in plants, and provide a strong basis for metabolic engineering to improve the content of triterpenoids and breeding of jujube varieties that are resistant to stress.

Preoperative Prediction of Microsatellite Instability in Rectal Cancer Using Five Machine Learning Algorithms Based on Multiparametric MRI Radiomics.

Objectives: To establish and verify radiomics models based on multiparametric MRI for preoperatively identifying the microsatellite instability (MSI) status of rectal cancer (RC) by comparing different machine learning algorithms. Methods: This retrospective study enrolled 383 (training set, 268; test set, 115) RC patients between January 2017 and June 2022. A total of 4148 radiomics features were extracted from multiparametric MRI, including T2-weighted imaging, T1-weighted imaging, apparent diffusion coefficient, and contrast-enhanced T1-weighted imaging. The analysis of variance, correlation test, univariate logistic analysis, and a gradient-boosting decision tree were used for the dimension reduction. Logistic regression, Bayes, support vector machine (SVM), K-nearest neighbor (KNN), and tree machine learning algorithms were used to build different radiomics models. The relative standard deviation (RSD) and bootstrap method were used to quantify the stability of these five algorithms. Then, predictive performances of different models were assessed using area under curves (AUCs). The performance of the best radiomics model was evaluated using calibration and discrimination. Results: Among these 383 patients, the prevalence of MSI was 14.62% (56/383). The RSD value of logistic regression algorithm was the lowest (4.64%), followed by Bayes (5.44%) and KNN (5.45%), which was significantly better than that of SVM (19.11%) and tree (11.94%) algorithms. The radiomics model based on logistic regression algorithm performed best, with AUCs of 0.827 and 0.739 in the training and test sets, respectively. Conclusions: We developed a radiomics model based on the logistic regression algorithm, which could potentially be used to facilitate the individualized prediction of MSI status in RC patients.

Continuous Psychological Nursing Based on Grey Clustering Algorithm in Patients after Transurethral Resection of Prostate.

Objective: To explore the effect of continuous psychological nursing based on the grey clustering algorithm on erectile function, bad psychological emotion, and complications in patients after transurethral resection of prostate (TURP). Methods: 98 patients who underwent TURP were randomly divided into observation and control groups (routine nursing). The observation group first used the grey clustering algorithm to evaluate the psychological intelligence, found patients with abnormal psychological behavior, and then implemented continuous psychological nursing combined with pelvic floor muscle exercise. The patients were followed up for 4 months. The International Index of Erectile Function-5 (IIEF-5), the incidence of complications, the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) scores, and the nursing satisfaction were analyzed and compared between these two groups. Results: The grey clustering algorithm can accurately reflect the characteristics of patients' psychological changes. After targeted nursing, compared with the control group, the IIEF-5 in the observation group was higher [(24.87 ± 1.85) vs. (22.24 ± 1.47), P < 0.05], the incidence of total complications was lower (10.20% vs. 26.53%, P < 0.05), the score of HAMA was lower [(6.11 ± 2.57) vs. (10.98 ± 2.29), P < 0.05], the score of HAMD was lower [(6.97 ± 2.85) vs. (11.35 ± 2.19), P < 0.05], and the nursing satisfaction was higher (100% vs. 85.71%, P < 0.05). Conclusion: Mental intelligence evaluation based on the grey clustering algorithm combined with pelvic floor muscle exercise can significantly improve the rehabilitation effect of erectile function in patients after TURP, reduce the incidence of postoperative complications, and alleviate patients' anxiety and depression.

Preoperative Prediction of Lymph Node Metastasis of Pancreatic Ductal Adenocarcinoma Based on a Radiomics Nomogram of Dual-Parametric MRI Imaging.

Purpose: This study aims to uncover and validate an MRI-based radiomics nomogram for detecting lymph node metastasis (LNM) in pancreatic ductal adenocarcinoma (PDAC) patients prior to surgery. Materials and Methods: We retrospectively collected 141 patients with pathologically confirmed PDAC who underwent preoperative T2-weighted imaging (T2WI) and portal venous phase (PVP) contrast-enhanced T1-weighted imaging (T1WI) scans between January 2017 and December 2021. The patients were randomly divided into training (n = 98) and validation (n = 43) cohorts at a ratio of 7:3. For each sequence, 1037 radiomics features were extracted and analyzed. After applying the gradient-boosting decision tree (GBDT), the key MRI radiomics features were selected. Three radiomics scores (rad-score 1 for PVP, rad-score 2 for T2WI, and rad-score 3 for T2WI combined with PVP) were calculated. Rad-score 3 and clinical independent risk factors were combined to construct a nomogram for the prediction of LNM of PDAC by multivariable logistic regression analysis. The predictive performances of the rad-scores and the nomogram were assessed by the area under the operating characteristic curve (AUC), and the clinical utility of the radiomics nomogram was assessed by decision curve analysis (DCA). Results: Six radiomics features of T2WI, eight radiomics features of PVP and ten radiomics features of T2WI combined with PVP were found to be associated with LNM. Multivariate logistic regression analysis showed that rad-score 3 and MRI-reported LN status were independent predictors. In the training and validation cohorts, the AUCs of rad-score 1, rad-score 2 and rad-score 3 were 0.769 and 0.751, 0.807 and 0.784, and 0.834 and 0.807, respectively. The predictive value of rad-score 3 was similar to that of rad-score 1 and rad-score 2 in both the training and validation cohorts (P > 0.05). The radiomics nomogram constructed by rad-score 3 and MRI-reported LN status showed encouraging clinical benefit, with an AUC of 0.845 for the training cohort and 0.816 for the validation cohort. Conclusions: The radiomics nomogram derived from the rad-score based on MRI features and MRI-reported lymph status showed outstanding performance for the preoperative prediction of LNM of PDAC.

CT-Based Radiomics Nomogram Improves Risk Stratification and Prediction of Early Recurrence in Hepatocellular Carcinoma After Partial Hepatectomy.

Objectives: To develop and validate an intuitive computed tomography (CT)-based radiomics nomogram for the prediction and risk stratification of early recurrence (ER) in hepatocellular carcinoma (HCC) patients after partial hepatectomy. Methods: A total of 132 HCC patients treated with partial hepatectomy were retrospectively enrolled and assigned to training and test sets. Least absolute shrinkage and selection operator and gradient boosting decision tree were used to extract quantitative radiomics features from preoperative contrast-enhanced CT images of the HCC patients. The radiomics features with predictive value for ER were used, either alone or in combination with other predictive features, to construct predictive models. The best performing model was then selected to develop an intuitive, simple-to-use nomogram, and its performance in the prediction and risk stratification of ER was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: The radiomics model based on the radiomics score (Rad-score) achieved AUCs of 0.870 and 0.890 in the training and test sets, respectively. Among the six predictive models, the combined model based on the Rad-score, Edmondson grade, and tumor size had the highest AUCs of 0.907 in the training set and 0.948 in the test set and was used to develop an intuitive nomogram. Notably, the calibration curve and DCA for the nomogram showed good calibration and clinical application. Moreover, the risk of ER was significantly different between the high- and low-risk groups stratified by the nomogram (p <0.001). Conclusions: The CT-based radiomics nomogram developed in this study exhibits outstanding performance for ER prediction and risk stratification. As such, this intuitive nomogram holds promise as a more effective and user-friendly tool in predicting ER for HCC patients after partial hepatectomy.

Nomogram Based on CT Radiomics Features Combined With Clinical Factors to Predict Ki-67 Expression in Hepatocellular Carcinoma.

Objectives: The study developed and validated a radiomics nomogram based on a combination of computed tomography (CT) radiomics signature and clinical factors and explored the ability of radiomics for individualized prediction of Ki-67 expression in hepatocellular carcinoma (HCC). Methods: First-order, second-order, and high-order radiomics features were extracted from preoperative enhanced CT images of 172 HCC patients, and the radiomics features with predictive value for high Ki-67 expression were extracted to construct the radiomic signature prediction model. Based on the training group, the radiomics nomogram was constructed based on a combination of radiomic signature and clinical factors that showed an independent association with Ki-67 expression. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to verify the performance of the nomogram. Results: Sixteen higher-order radiomic features that were associated with Ki-67 expression were used to construct the radiomics signature (AUC: training group, 0.854; validation group, 0.744). In multivariate logistic regression, alfa-fetoprotein (AFP) and Edmondson grades were identified as independent predictors of Ki-67 expression. Thus, the radiomics signature was combined with AFP and Edmondson grades to construct the radiomics nomogram (AUC: training group, 0.884; validation group, 0.819). The calibration curve and DCA showed good clinical application of the nomogram. Conclusion: The radiomics nomogram developed in this study based on the high-order features of CT images can accurately predict high Ki-67 expression and provide individualized guidance for the treatment and clinical monitoring of HCC patients.

Comparative transcriptome analysis of candidate genes involved in chlorogenic acid biosynthesis during fruit development in three pear varieties of Xinjiang Uygur Autonomous Region.

Pear is one of the main fruits with thousands of years of cultivation history in China. There are more than 2000 varieties of pear cultivars around the world, including more than 1200 varieties or cultivars in China (Legrand et al., 2016). Xinjiang Uygur Autonomous Region is an important pear production region in China with 30 of varieties or cultivars. Pyrus sinkiangensis is the most popular variety, which is mainly distributed in Xinjiang (Zhou et al., 2018). Chlorogenic acid (CGA), p-coumaric acid, and arbutin are the main polyphenols in pear fruit, and their levels show great differences among different varieties (Li et al., 2014). CGA is a potential chemo-preventive agent, which possesses many important bioactivities including antioxidant, diabetes attenuating, and anti-obesity (Wang et al., 2021). Therefore, the specific CGA content of a variety is considered the embodiment of the functional nutritional value of pears.

Physicochemical and antioxidant activity of fruit harvested from eight jujube (Ziziphus jujuba Mill.) cultivars at different development stages.

Jujube is a crop highly resistant to drought and salinity, making it one of the main fruit trees in Xinjiang. The present study evaluated the changes in the physicochemical and antioxidant activities of jujube fruit of eight different cultivars from Xinjiang, China. The developmental stages were selected according to the days after full bloom and fruit peel colour during ripening; these stages included young (S1), fruit core-hardening (S2), green ripening (S3), half-red maturity (S4) and complete red. In present study, different cultivars of jujube fruit showed similar chemical profiles, but their amounts showed great variation. HZ had the highest content of sugars, and JY had the highest content of cAMP and cGMP, while relatively higher levels of ascorbic acid, catechin, epicatechin, rutin, proanthocyanidin and antioxidant activity were found in 'FS' than in other cultivars, indicating that 'FS' could be used as a potential natural antioxidant. Regarding the development stages of jujube fruit, the moisture, ascorbic acid, total polyphenol, catechin, epicatechin, proanthocyanidin and rutin contents decreased during the development of all jujube cultivars, while the fructose, glucose, sucrose, cAMP, and cGMP contents greatly increased. The antioxidant activity determined by DPPH and ABTS radical scavenging decreased as the fruits matured. Therefore, the results suggest that green jujube (S1) could be used for natural antioxidants (catechin, epicatechin, proanthocyanidin) and that the advanced ripening stage(S5) is the proper picking period for fresh fruit and commercial processing.

Development of a prognostic gene signature for hepatocellular carcinoma.

Accurate prediction of overall survival is important for prognosis and the assignment of appropriate personalized clinical treatment in hepatocellular carcinoma (HCC) patients. The aim of the present study was to establish an optimal gene model for the independent prediction of prognosis associated with common clinical patterns. Gene expression profiles and the corresponding clinical information of the LIHC cohort were obtained from The Cancer Genome Atlas. Differentially expressed genes were found using the R package "limma". Subsequently, a prognostic gene signature was developed using the LASSO Cox regression model. Kaplan-Meier, log-rank, and receiver operating characteristic (ROC) analyses were performed to verify the predictive accuracy of the prognostic model. Finally, a nomogram and calibration plot were created using the "rms" package. Differentially expressed genes were screened with threshold criteria (FDR < 0.01 and |log FC|>3) and 563 differentially expressed genes were obtained, including 448 downregulated and 115 upregulated genes. Using the LASSO Cox regression model, a prognostic gene signature was developed based on nine genes, IQGAP3, BIRC5, PTTG1, STC2, CDKN3, PBK, EXO1, NEIL3, and HOXD9, the expression levels of which were quantitated using RT-qPCR. According to the risk scores, patients were separated into high-risk and low-risk groups. In conclusion, the prognostic gene signature can be used as a combined biomarker for the independent prediction of overall survival in HCC patients. Moreover, we created a nomogram that can be used to infer prognosis and aid individualized decisions regarding treatment and surveillance.

The Analysis of Phenolic Compounds in Walnut Husk and Pellicle by UPLC-Q-Orbitrap HRMS and HPLC.

Husk and pellicle as the agri-food waste in the walnut-product industry are in soaring demand because of their rich polyphenol content. This study investigated the differential compounds related to walnut polyphenol between husk and pellicle during fruit development stage. By using ultra-high performance liquid chromatography-quadrupole-orbitrap (UHPLC-Q-Orbitrap), a total of 110 bioactive components, including hydrolysable tannins, flavonoids, phenolic acids and quinones, were tentatively identified, 33 of which were different between husk and pellicle. The trend of dynamic content of 16 polyphenols was clarified during walnut development stage by high-performance liquid chromatography (HPLC). This is the first time to comprehensive identification of phenolic compounds in walnut husk and pellicle, and our results indicated that the pellicle is a rich resource of polyphenols. The dynamic trend of some polyphenols was consistent with total phenols. The comprehensive characterization of walnut polyphenol and quantification of main phenolic compounds will be beneficial for understanding the potential application value of walnut and for exploiting its metabolism pathway.

Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma via Multi-Parametric MRI Radiomics.

OBJECTIVES: To systematically evaluate and compare the predictive capability for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients based on radiomics from multi-parametric MRI (mp-MRI) including six sequences when used individually or combined, and to establish and validate the optimal combined model. METHODS: A total of 195 patients confirmed HCC were divided into training (n = 136) and validation (n = 59) datasets. All volumes of interest of tumors were respectively segmented on T2-weighted imaging, diffusion-weighted imaging, apparent diffusion coefficient, artery phase, portal venous phase, and delay phase sequences, from which quantitative radiomics features were extracted and analyzed individually or combined. Multivariate logistic regression analyses were undertaken to construct clinical model, respective single-sequence radiomics models, fusion radiomics models based on different sequences and combined model. The accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were calculated to evaluate the performance of different models. RESULTS: Among nine radiomics models, the model from all sequences performed best with AUCs 0.889 and 0.822 in the training and validation datasets, respectively. The combined model incorporating radiomics from all sequences and effective clinical features achieved satisfactory preoperative prediction of MVI with AUCs 0.901 and 0.840, respectively, and could identify the higher risk population of MVI (P < 0.001). The Delong test manifested significant differences with P < 0.001 in the training dataset and P = 0.005 in the validation dataset between the combined model and clinical model. CONCLUSIONS: The combined model can preoperatively and noninvasively predict MVI in HCC patients and may act as a usefully clinical tool to guide subsequent individualized treatment.

Chloroquine increases the anti-cancer activity of epirubicin in A549 lung cancer cells.

The present study investigated whether the autophagy inhibitor chloroquine (CQ) can improve the sensitivity of the A549 lung cancer cell line to epirubicin (EPI). The Cell Counting Kit 8 (CCK8) assay was used to determine the EPI IC50 in A549 cells treated for 72 h. A549 cells were treated with Western blot analysis was performed to detect the expression level of the autophagy-associated protein, microtubule associated protein 1 light chain 3 ß (LC3B), and apoptosis-associated proteins such as cleaved caspase-9 and cleaved caspase-3. CCK8, colony formation, wound healing and Transwell assays were performed to analyze cell proliferation, migration and invasion capacity. Reverse transcription-quantitative PCR (RT-qPCR) was used to analyze the mRNA expression levels of LC3B and beclin-1, and the apoptosis rate was analyzed by flow cytometry. The IC50 of EPI was 0.03 µg/ml. The CCK8 results demonstrated that the cell survival rate was lower in CQ + EPI-treated cells when compared with the individual treatment groups. The colony formation results revealed that the number of clones in the EPI + CQ-treated group was reduced compared with EPI or CQ treatment alone. The wound healing assay revealed that migration was reduced in the EPI + CQ-treated group compared with the other treatment groups, and the Transwell results indicated that the number of cells passing through the Matrigel and membrane was lowest in the CQ + EPI treatment group. The mRNA expression levels of LC3B and beclin-1 were increased in the CQ + EPI group by 51.5 and 61.2%, respectively, when compared with the control group. The results indicated that LC3B protein expression was enhanced by EPI in a concentration-dependent manner, and the protein levels of cleaved caspase-3 and cleaved caspase-9 were higher in the combination group than in the EPI alone group. The flow cytometry results demonstrated that the apoptosis rate was highest in the EPI + CQ group. In conclusion, the autophagy inhibitor CQ increased the sensitivity of A549 cells to EPI, and the underlying mechanism of action may be associated with the activation of apoptosis.

Screening miRNAs associated with resistance gemcitabine from exosomes in A549 lung cancer cells.

PURPOSE: To establish a gemcitabine-resistant lung adenocarcinoma cell line, A549/G+, and to screen the differences of miRNA expression in exosomes from A549 and A549/G+ cells. METHODS: A549 cells were exposed in gemcitabine until they were resistant to gemcitabine, and extracted exosomes from A549 and A549/G+. The RNAs from exosomes were subjected to miRNA expression microarray experiments. RESULTS: After 39 weeks of continuous induction, we induced drug resistance in A549 cells. The resistance index was 6. Via GeneChip miRNA 4.0 analysis, there were 446 differential miRNAs between A549 and A549/G+. Target gene prediction and pathway analysis discovered the microRNAs in the intersections may participate in drug resistance. CONCLUSION: These differential miRNAs help to do in-depth research to elucidate the mechanism of resistance to gemcitabine in non-small cell lung cancer.

Alveolar soft part sarcoma of lung: report of a unique case with emphasis on diagnostic utility of molecular genetic analysis for TFE3 gene rearrangement and immunohistochemistry for TFE3 antigen expression.

Alveolar soft part sarcoma (ASPS) is a rare, malignant mesenchymal tumor of distinctive clinical, morphologic, ultrastructural, and cytogenetical characteristics. It typically arises in the extremities of adolescents and young adults, but has also been documented in a number of unusual sites, thus causing diagnostic confusions both clinically and morphologically. The molecular signature of ASPS is a specific der(17)t(X;17)(p11.2;q25) translocation, which results in the fusion of TFE3 transcription factor gene at Xp11.2 with ASPL at 17q25. Recent studies have shown that the ASPL-TFE3 fusion transcript can be identified by reverse-transcriptase polymerase chain reaction analysis and TFE3 gene rearragement can be detected using a dual-color, break apart fluorescence in situ hybridization assay in paraffin-embedded tissue, and the resultant fusion protein can be detected immunohistochemically with antibody directed to the carboxy terminal portion of TFE3. Herein, we report a unique case of ASPS presenting as an asymptomatic mass in the lung of a 48 year-old woman without evidence of a primary soft tissue tumor elsewhere at the time of initial diagnosis. To the best of our knowledge, this is the third report of such cases appearing in the English language literature to date. We emphasize the differential diagnoses engendered by ASPS including a series of tumors involving the lung that have nested and alveolar growth patterns, and both clear and eosinophilic cytoplasm, and demonstrate the utility of molecular genetic analysis for TFE3 rearrangement and immunohistochemistry for TFE3 antigen expression for arriving at accurate diagnosis.

Tubulocystic oncocytoma of the kidney: a case study and review of literature with focus on implications for differential diagnosis.

Renal oncocytoma (RO) can rarely present with a multilocular or tubulocystic growth pattern that may cause significant diagnostic difficulties with a variety of cystic renal cell carcinomas (RCC). Distinguishing these RO variants from their many RCC mimickers is critical because of its typical benign clinical course. Herein, we report a case of RO with extensive tubulocystic architectures on a 42-year-old female patient and discuss the clinicopathologic characterizations of this unusual RO variant with an emphasis on the wide spectrum of differential diagnoses of a variety of primary or secondary renal tumors that are featuring of both oncocytic cell changes and tubulocystic growth patterns.