Publications by authors named "Xiuying Wang"

139 Publications

Multi-parametric MRI phenotype with trustworthy machine learning for differentiating CNS demyelinating diseases.

J Transl Med 2021 09 6;19(1):377. Epub 2021 Sep 6.

Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, No.45 Changchun Street, Xuanwu District, Beijing, 100053, China.

Background: Misdiagnosis of multiple sclerosis (MS) and neuromyelitis optica (NMO) may delay the treatment, resulting in poor prognosis. However, the precise identification of these two diseases is still challenging in clinical practice. We aimed to evaluate the value of quantitative radiomic features extracted from the brain white matter lesions for differential diagnosis of MS and NMO.

Methods: We recruited 116 CNS demyelinating patients including 78 MS, and 38 NMO. Three neuroradiologists performed visual differential diagnosis based on brain MRI for comparison purpose. A multi-level scheme was designed to harness the selection of discriminative and stable radiomics features extracted from brain while mater lesions in T1-MPRAGE, T2 sequences and clinical factors. Based on the imaging phenotype composed of the selected radiomic and clinical features, Multi-parametric Multivariate Random Forest (MM-RF) model was constructed and verified with both 10-fold cross-validation and independent testing. Result interpretation was provided to build trust in diagnostic decisions.

Results: Eighty-six patients were randomly selected to form the training set while the rest 30 patients for independent testing. On the training set, our MM-RF model achieved accuracy 0.849 and AUC 0.826 in 10-fold cross-validation, which were significantly higher than clinical visual analysis (0.709 and 0.683, p < 0.05). In the independent testing, the MM-RF model achieved AUC 0.902, accuracy 0.871, sensitivity 0.873, specificity 0.869, respectively. Furthermore, age, sex and EDSS were found mildly correlated with the radiomic features (p of all < 0.05).

Conclusions: Multi-parametric radiomic features have potential as practical quantitative imaging biomarkers for differentiating MS from NMO.
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http://dx.doi.org/10.1186/s12967-021-03015-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419989PMC
September 2021

Deep Attention and Graphical Neural Network for Multiple Sclerosis Lesion Segmentation from MR Imaging Sequences.

IEEE J Biomed Health Inform 2021 Sep 1;PP. Epub 2021 Sep 1.

The segmentation of multiple sclerosis (MS) lesions from MR imaging sequences remains a challenging task, due to the characteristics of variant shapes, scattered distributions and unknown numbers of lesions. However, the current automated MS segmentation methods with deep learning models face the challenges of (1) capturing the multiple scattered lesions in multiple regions and (2) delineating the global contour of variant lesions. To address these challenges, in this paper, we propose a novel attention and graph-driven network (DAG-Net), which incorporates (1) the spatial correlations for embracing the lesions in distant regions and (2) the global context for better representing lesions of variant features in a unified architecture. Firstly, the novel local attention coherence mechanism is designed to construct dynamic and expansible graphs for the spatial correlations between pixels and their proximities. Secondly, the proposed spatial-channel attention module enhances features to optimize the global contour delineation, by aggregating relevant features. Moreover, with the dynamic graphs, the learning process of the DAG-Net is interpretable, which in turns support the reliability of segmentation results. Extensive experiments were conducted on a public ISBI2015 dataset and an in-house dataset in comparison to state-of-the-art methods, based on the geometrical and clinical metrics. The experimental results validate the effectiveness of the proposed DAG-Net on segmenting variant and scatted lesions in multiple regions.
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http://dx.doi.org/10.1109/JBHI.2021.3109119DOI Listing
September 2021

Predictive value of preoperative serum squamous cell carcinoma antigen level for lymph node metastasis in early-stage cervical squamous cell carcinoma.

Medicine (Baltimore) 2021 Aug;100(33):e26960

Department of Gynecology Oncology, Dalian Obstetrics and Gynecology Hospital Affiliated to Dalian Medical University, Dalian, Liaoning, China.

Abstract: To explore the predictive value of preoperative serum squamous cell carcinoma antigen (SCC-Ag) level for lymph node metastasis (LNM), particularly, in patients surgically treated for early-stage cervical squamous cell carcinoma.We enrolled 162 patients with cervical squamous cell carcinoma stages IB to IIA following the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification. The patients had previously undergone radical surgery. Correlation of the SCC-Ag level with clinicopathological features and the predictive value of SCC-Ag for LNM were analyzed.High preoperative SCC-Ag level was correlated with FIGO stage (P = .001), tumor diameter >4 cm (P < .001), stromal infiltration (P < .001), LNM (P < .001) and lymphovascular space invasion (LVSI), (P = .045). However, it was not correlated with age, histological differentiation, parametrial involvement, and positive vaginal margin (P > .05). Univariate analysis revealed that FIGO stage (P = .015), tumor diameter (P = .044), stromal infiltration (χ2 = 10.436, P = .005), SCC-Ag ≧ 2.75 ng/mL (χ2 = 14.339, P < .001), LVSI (χ2 = 12.866, P  < .001), parametrial involvement (χ2 = 13.784, P < .001) were correlated with LNM, but not with age, histological differentiation, and positive vaginal margin. Moreover, multivariate analysis demonstrated that SCC-Ag ≧2.75 ng/mL (P = .011, OR = 3.287) and LVSI (P = .009, OR = 7.559) were independent factors affecting LNM. The area under the receiver operator characteristic curve of SCC-Ag was 0.703 (P < .001), while 2.75 ng/mL was the best cutoff value for predicting LNM. The sensitivity and specificity of diagnosis were 69.4% and 65.9%, respectively.High SCC-Ag level was revealed to be an independent risk factor for the prognosis of squamous carcinoma of the cervix before an operation. Besides, SCC-Ag (2.75 ng/mL) can be utilized as a potential marker to predict LNM in early stage cervical cancer before an operation.
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http://dx.doi.org/10.1097/MD.0000000000026960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376392PMC
August 2021

Xylooligosaccharide attenuates lipopolysaccharide-induced intestinal injury in piglets via suppressing inflammation and modulating cecal microbial communities.

Anim Nutr 2021 Sep 22;7(3):609-620. Epub 2021 Mar 22.

Hubei Key Laboratory of Animal Nutrition and Feed Science, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University, Wuhan, 430023, China.

Xylooligosaccharide (XOS) has been considered to be an effective prebiotic, but its exact mechanisms remain unknown. This research was conducted to evaluate the effects of XOS on pig intestinal bacterial community and mucosal barrier using a lipopolysaccharide (LPS)-caused gut damage model. Twenty-four weaned pigs were assigned to 4 treatments in a 2 × 2 factorial design involving diet (with or without XOS) and immunological challenge (saline or LPS). After 21 d of feeding 0% or 0.02% commercial XOS product, piglets were treated with saline or LPS. After that, blood, small intestinal mucosa and cecal digesta were obtained. Dietary XOS enhanced intestinal mucosal integrity demonstrated by higher villus height, villus height-to-crypt depth ratio, disaccharidase activities and claudin-1 protein expression and lower crypt depth. XOS also caused down-regulation of the gene expression of toll-like receptor 4 and nucleotide-binding oligomerization domain protein signaling, accompanied with decreased pro-inflammatory cytokines and cyclooxygenase 2 contents or mRNA expression and increased heat shock protein 70 mRNA and protein expression. Additionally, increased Bacteroidetes and decreased Firmicutes relative abundance were observed in the piglets fed with XOS. At the genus level, XOS enriched the relative abundance of beneficial bacteria, e.g., , , and . Moreover, XOS enhanced short chain fatty acids contents and inhibited histone deacetylases. The correlation analysis of the combined datasets implied some potential connections between the intestinal microbiota and pro-inflammatory cytokines or cecal metabolites. These results suggest that XOS inhibits inflammatory response and beneficially modifies microbes and metabolites of the hindgut to protect the intestine from inflammation-related injury.
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http://dx.doi.org/10.1016/j.aninu.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326603PMC
September 2021

Quantitative Prediction of Microsatellite Instability in Colorectal Cancer With Preoperative PET/CT-Based Radiomics.

Front Oncol 2021 22;11:702055. Epub 2021 Jul 22.

School of Computer Science, The University of Sydney, Sydney, NSW, Australia.

Objectives: Microsatellite instability (MSI) status is an important hallmark for prognosis prediction and treatment recommendation of colorectal cancer (CRC). To address issues due to the invasiveness of clinical preoperative evaluation of microsatellite status, we investigated the value of preoperative F-FDG PET/CT radiomics with machine learning for predicting the microsatellite status of colorectal cancer patients.

Methods: A total of 173 patients that underwent F-FDG PET/CT scans before operations were retrospectively analyzed in this study. The microsatellite status for each patient was identified as microsatellite instability-high (MSI-H) or microsatellite stable (MSS), according to the test for mismatch repair gene proteins with immunohistochemical staining methods. There were 2,492 radiomic features in total extracted from F-FDG PET/CT imaging. Then, radiomic features were selected through multivariate random forest selection and univariate relevancy tests after handling the imbalanced dataset through the random under-sampling method. Based on the selected features, we constructed a BalancedBagging model based on Adaboost classifiers to identify the MSI status in patients with CRC. The model performance was evaluated by the area under the curve (AUC), sensitivity, specificity, and accuracy on the validation dataset.

Results: The ensemble model was constructed based on two radiomic features and achieved an 82.8% AUC for predicting the MSI status of colorectal cancer patients. The sensitivity, specificity, and accuracy were 83.3, 76.3, and 76.8%, respectively. The significant correlation of the selected two radiomic features with multiple effective clinical features was identified (p < 0.05).

Conclusion: F-FDG PET/CT radiomics analysis with the machine learning model provided a quantitative, efficient, and non-invasive mechanism for identifying the microsatellite status of colorectal cancer patients, which optimized the treatment decision support.
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http://dx.doi.org/10.3389/fonc.2021.702055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339969PMC
July 2021

Deciphering CT texture features of human visceral fat to evaluate metabolic disorders and surgery-induced weight loss effects.

EBioMedicine 2021 Jul 3;69:103471. Epub 2021 Jul 3.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background: Metabolic syndrome (MetS) is highly related to the excessive accumulation of visceral adipose tissue (VAT). Quantitative measurements of VAT are commonly applied in clinical practice for measurement of metabolic risks; however, it remains largely unknown whether the texture of VAT can evaluate visceral adiposity, stratify MetS and predict surgery-induced weight loss effects.

Methods: 675 Chinese adult volunteers and 63 obese patients (with bariatric surgery) were enrolled. Texture features were extracted from VATs of the computed tomography (CT) scans and machine learning was applied to identify significant imaging biomarkers associated with metabolic-related traits.

Findings: Combined with sex, ten VAT texture features achieved areas under the curve (AUCs) of 0.872, 0.888, 0.961, and 0.947 for predicting the prevalence of insulin resistance, MetS, central obesity, and visceral obesity, respectively. A novel imaging biomarker, RunEntropy, was identified to be significantly associated with major metabolic outcomes and a 3.5-year follow-up in 338 volunteers demonstrated its long-term effectiveness. More importantly, the preoperative imaging biomarkers yielded high AUCs and accuracies for estimation of surgery responses, including the percentage of excess weight loss (%EWL) (0.867 and 74.6%), postoperative BMI group (0.930 and 76.1%), postoperative insulin resistance (0.947 and 88.9%), and excess visceral fat loss (the proportion of visceral fat reduced over 50%; 0.928 and 84.1%).

Interpretation: This study shows that the texture features of VAT have significant clinical implications in evaluating metabolic disorders and predicting surgery-induced weight loss effects.

Funding: The complete list of funders can be found in the Acknowledgement section.
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http://dx.doi.org/10.1016/j.ebiom.2021.103471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264112PMC
July 2021

Correction to: Automatic identification of myopic maculopathy related imaging features in optic disc region via machine learning methods.

J Transl Med 2021 May 11;19(1):203. Epub 2021 May 11.

Department of Preventative Ophthalmology, Shanghai Eye Diseases Prevention and Treatment Center, Shanghai Eye Hospital, No. 380 Kangding Road, Shanghai, 200040, China.

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http://dx.doi.org/10.1186/s12967-021-02874-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114694PMC
May 2021

Automatic identification of myopic maculopathy related imaging features in optic disc region via machine learning methods.

J Transl Med 2021 04 26;19(1):167. Epub 2021 Apr 26.

Department of Preventative Ophthalmology, Shanghai Eye Diseases Prevention and Treatment Center, Shanghai Eye Hospital, No. 380 Kangding Road, Shanghai, 200040, China.

Background: Myopic maculopathy (MM) is the most serious and irreversible complication of pathologic myopia, which is a major cause of visual impairment and blindness. Clinic proposed limited number of factors related to MM. To explore additional features strongly related with MM from optic disc region, we employ a machine learning based radiomics analysis method, which could explore and quantify more hidden or imperceptible MM-related features to the naked eyes and contribute to a more comprehensive understanding of MM and therefore may assist to distinguish the high-risk population in an early stage.

Methods: A total of 457 eyes (313 patients) were enrolled and were divided into severe MM group and without severe MM group. Radiomics analysis was applied to depict features significantly correlated with severe MM from optic disc region. Receiver Operating Characteristic were used to evaluate these features' performance of classifying severe MM.

Results: Eight new MM-related image features were discovered from the optic disc region, which described the shapes, textural patterns and intensity distributions of optic disc region. Compared with clinically reported MM-related features, these newly discovered features exhibited better abilities on severe MM classification. And the mean values of most features were markedly changed between patients with peripapillary diffuse chorioretinal atrophy (PDCA) and macular diffuse chorioretinal atrophy (MDCA).

Conclusions: Machine learning and radiomics method are useful tools for mining more MM-related features from the optic disc region, by which complex or even hidden MM-related features can be discovered and decoded. In this paper, eight new MM-related image features were found, which would be useful for further quantitative study of MM-progression. As a nontrivial byproduct, marked changes between PDCA and MDCA was discovered by both new image features and clinic features.
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http://dx.doi.org/10.1186/s12967-021-02818-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074495PMC
April 2021

Sex modifies APOE ε4 dose effect on brain tau deposition in cognitively impaired individuals.

Brain 2021 Apr 20. Epub 2021 Apr 20.

Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.

Recent studies in cognitively unimpaired elderly individuals suggest that the APOE ε4 allele exerts a dosage-dependent effect on brain tau deposition. The aim of this study was to investigate sex differences in APOE ε4 gene dosage effects on brain tau deposition in cognitively impaired individuals using quantitative 18F-flortaucipir PET. Preprocessed 18F-flortaucipir tau PET images, T1-weighted structural MRI images, demographic information, global cortical amyloid-β burden measured by 18F-florbetapir PET, CSF total tau and phosphorylated tau measurements were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Two hundred and sixty-eight cognitively impaired individuals with 146 APOE ε4 non-carriers and 122 carriers (85 heterozygotes and 37 homozygotes) were included in the study. An iterative reblurred Van Cittert iteration partial volume correction method was applied to all downloaded PET images. MRI images were used for PET spatial normalization. Twelve regional standardized uptake value ratios relative to the cerebellum were computed in standard space. APOE ε4 dosage by sex interaction effect on 18F-flortaucipir standardized uptake value ratios was assessed using generalized linear models and sex-stratified analysis. We observed a significant APOE ε4 dosage by sex interaction effect on tau deposition in the lateral temporal, posterior cingulate, medial temporal, inferior temporal, entorhinal cortex, amygdala, parahippocampal gyrus regions after adjusting for age and education level (P < 0.05). The medial temporal, entorhinal cortex, amygdala and parahippocampal gyrus regions retained a significant APOE ε4 dosage by sex interaction effect on tau deposition after adjusting for global cortical amyloid-β (P < 0.05). In sex-stratified analysis, there was no significant difference in tau deposition between female homozygotes and heterozygotes (P > 0.05). In contrast, male homozygotes standardized uptake value ratios were significantly greater than heterozygotes or non-carriers throughout all twelve regions of interest (P < 0.05). Female heterozygotes exhibited significantly increased tau deposition compared to male heterozygotes in the orbitofrontal, posterior cingulate, lateral temporal, inferior temporal, entorhinal cortex, amygdala and parahippocampal gyrus (P < 0.05). Results from voxelwise analysis were similar to the ones obtained from regions of interest analysis. Our findings suggest that an APOE ε4 dosage effect on brain region-specific tau deposition exists in males, but not females. These results have important clinical implications towards developing sex and genotype-guided therapeutics in Alzheimer's disease and uncovers a potential explanation underlying differential apolipoprotein E ε4-associated Alzheimer's risk in males and females.
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http://dx.doi.org/10.1093/brain/awab160DOI Listing
April 2021

Necroptosis Underlies Hepatic Damage in a Piglet Model of Lipopolysaccharide-Induced Sepsis.

Front Immunol 2021 12;12:633830. Epub 2021 Mar 12.

Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, China.

Background: Necroptosis is a newly recognized form of programmed cell death with characteristics of both necrosis and apoptosis. The role of necroptosis in hepatic damage during sepsis is poorly understood. In this study, we investigated the occurrence of necroptosis in hepatic damage, and its contribution to hepatic damage in a piglet model of lipopolysaccharide (LPS)-induced sepsis.

Methods: Two animal experiments were conducted. In trial 1, piglets were challenged with LPS and sacrificed at different time points after LPS challenge. In trial 2, piglets were pretreated with necrostatin-1, a specific inhibitor of necroptosis, prior to LPS challenge. Alterations in the hepatic structure and function, pro-inflammatory cytokine expression, and the necroptosis signaling pathway were investigated. Typical ultrastructural characteristics of cell necrosis was observed in the liver of LPS-challenged piglets.

Results: Expressions of critical components of necroptosis including kinases (RIP1, RIP3, and MLKL), mitochondrial proteins (PGAM5 and DRP1), and an intracellular damage-associated molecular pattern (HMGB1) were increased in the liver in a time-dependent manner, followed by hepatic inflammation, morphological damage, and dysfunction as manifested by elevated hepatic expression of IL-1β, IL-6 and TNF-α as well as increased serum AST and AKP activities and the AST/ALT ratio. Pretreatment with necrostatin-1 significantly reduced the expression of RIP1, RIP3 and MLKL as well as PGAM5, DRP1 and HMGB1, which subsequently led to obvious attenuation of hepatic inflammation and damage.

Conclusions: Our study demonstrates that necroptosis occurs in the liver during sepsis and contributes to septic hepatic injury.
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http://dx.doi.org/10.3389/fimmu.2021.633830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994362PMC
September 2021

Deep Cognitive Gate: Resembling Human Cognition for Saliency Detection.

IEEE Trans Pattern Anal Mach Intell 2021 Mar 23;PP. Epub 2021 Mar 23.

Saliency detection by human refers to the ability to identify pertinent information using our perceptive and cognitive capabilities. While human perception is attracted by visual stimuli, our cognitive capability is derived from the inspiration of constructing concepts of reasoning. Saliency detection has gained intensive interest with the aim of resembling human perceptual system. However, saliency related to human cognition, particularly the analysis of complex salient regions (cogitating process), is yet to be fully exploited. We propose to resemble human cognition, coupled with human perception, to improve saliency detection. We recognize saliency in three phases (Seeing - Perceiving - Cogitating), mimicking human's perceptive and cognitive thinking of an image. In our method, Seeing phase is related to human perception, and we formulate the Perceiving and Cogitating phases related to the human cognition systems via deep neural networks (DNNs) to construct a new module (Cognitive Gate) that enhances the DNN features for saliency detection. To the best of our knowledge, this is the first work that established DNNs to resemble human cognition for saliency detection. In our experiments, our approach outperformed 17 benchmarking DNN methods on six well-recognized datasets, demonstrating that resembling human cognition improves saliency detection.
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http://dx.doi.org/10.1109/TPAMI.2021.3068277DOI Listing
March 2021

Lanthanide-Doped Upconversion-Linked Immunosorbent Assay for the Sensitive Detection of Carbohydrate Antigen 19-9.

Front Chem 2020 26;8:592445. Epub 2021 Feb 26.

The Education Ministry Key Laboratory of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, School of Chemistry and Materials Science, Shanghai Normal University, Shanghai, China.

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable attention in detection of biological analytes and bioimaging owing to their superior optical properties, including high photochemical stability, sharp emission bandwidth, large anti-Stokes shifts, and low toxicity. In this work, we fabricated UCNP-linked immunosorbent assay (ULISA) for the sensitive detection of carbohydrate antigen 19-9 (CA19-9). The design is based on amino-functionalized SiO-coated Gd-doped NaYF:Yb,Er upconversion nanoparticles ([email protected]) as a direct background-free luminescent reporter; a secondary anti-IgG antibody (Ab) was conjugated to the surface of [email protected] (UCNP-Ab), and UCNP-Ab was used for specific targeting of CA19-9. The UCNPs were well characterized by TEM, SEM, XRD, FT-IR, and UV-vis. The detection process was similar to enzyme-linked immunosorbent assay (ELISA). UCNPs were used as signal transducer to replace the color compounds for an enzyme-mediated signal amplification step. An anti-CA19-9 primary antibody (Ab) was fixed for capturing the CA19-9, and the fluorescence signal was obtained from the specific immunoreaction between UCNP-Ab and CA19-9. Under optimum conditions, this ULISA shows sensitive detection of CA19-9 with a dynamic range of 5-2,000 U/ml. The ULISA system shows higher detection sensitivity and wider detection range compared with the traditional ELISA for CA19-9 detection. This strategy using UCNPs as signal transducer may pave a new avenue for the exploration of rare doped UCNPs in ELISA assay for clinical applications in the future.
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http://dx.doi.org/10.3389/fchem.2020.592445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954120PMC
February 2021

PathoFusion: An Open-Source AI Framework for Recognition of Pathomorphological Features and Mapping of Immunohistochemical Data.

Cancers (Basel) 2021 Feb 4;13(4). Epub 2021 Feb 4.

Ken Parker Brain Tumour Research Laboratories, Brain and Mind Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.

We have developed a platform, termed PathoFusion, which is an integrated system for marking, training, and recognition of pathological features in whole-slide tissue sections. The platform uses a bifocal convolutional neural network (BCNN) which is designed to simultaneously capture both index and contextual feature information from shorter and longer image tiles, respectively. This is analogous to how a microscopist in pathology works, identifying a cancerous morphological feature in the tissue context using first a narrow and then a wider focus, hence bifocal. Adjacent tissue sections obtained from glioblastoma cases were processed for hematoxylin and eosin (H&E) and immunohistochemical (CD276) staining. Image tiles cropped from the digitized images based on markings made by a consultant neuropathologist were used to train the BCNN. PathoFusion demonstrated its ability to recognize malignant neuropathological features autonomously and map immunohistochemical data simultaneously. Our experiments show that PathoFusion achieved areas under the curve (AUCs) of 0.985 ± 0.011 and 0.988 ± 0.001 in patch-level recognition of six typical pathomorphological features and detection of associated immunoreactivity, respectively. On this basis, the system further correlated CD276 immunoreactivity to abnormal tumor vasculature. Corresponding feature distributions and overlaps were visualized by heatmaps, permitting high-resolution qualitative as well as quantitative morphological analyses for entire histological slides. Recognition of more user-defined pathomorphological features can be added to the system and included in future tissue analyses. Integration of PathoFusion with the day-to-day service workflow of a (neuro)pathology department is a goal. The software code for PathoFusion is made publicly available.
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http://dx.doi.org/10.3390/cancers13040617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913958PMC
February 2021

Pediatric anti-N-methyl-d-aspartate receptor encephalitis in southern China: Analysis of 111 cases.

J Neuroimmunol 2021 03 15;352:577479. Epub 2021 Jan 15.

Department of Neurology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9# Jin Sui Road, 510623 Guangzhou, Guangdong Province, PR China. Electronic address:

Objective: To study the clinical features of children diagnosed with anti-NMDAR encephalitis in southern China.

Methods: Clinical data of children diagnosed with anti-NMDAR encephalitis from October 2014 to June 2020 from one national regional medical center were analyzed. Neurological disability was assessed by modified Rankin Scale (mRS) throughout the course of disease.

Results: 111 children (M/F = 49/62; mean onset age = 6.8 y) with anti-NMDAR encephalitis were involved. Prodromal events occurred in 34.2% of patients with infectious events being the most common. Seizure was the most common initial symptom, though movement disorder served as the most common event throughout the course of disease. 9.9% of patients had overlapped with other neuronal autoantibodies. Electroencephalogram showed abnormalities with slow wave (100.0%), epileptic discharge (31.5%) and delta brush (8.1%) respectively. 41.4% of patients had abnormal brain MRI, with focal lesions being the most common. None patients had tumor. 80.9% of patients had good response to first line therapy (steroid plus immunoglobulin), while 14 patients accepted second-line therapy (Rituximab) and all had a good response. Boys were significantly more likely to need more course of steroid. 13.8% of patients relapsed. 2 male patients died. mRS score was significantly improved after treatment. 51.4% of patients had a full recovery and 81.7% had mRS score ≤ 2. The median mRS score of boys after treatment was higher than that of girls. Non-infectious prodromal event, past medical history, perivascular lesions in brain MRI, hospital stay, initial mRS score higher than 3, and RTX treatment were independent risk factors associated with poor prognosis, defined as mRS score > 2.

Conclusion: Of pediatric anti-NMDAR encephalitis in southern China: median onset age around 7 years; girls more common; boys might have poor outcome than girls; seizure or movement disorder respectively being most common onset or course symptom; a few overlapped with other neuronal autoantibodies; rare combined with tumor; most had a good response to immunotherapy and a good prognosis; relapse rate relatively high; fatality rate relatively low; some risk factors associated with poor prognosis.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577479DOI Listing
March 2021

Combination Therapy Using Kartogenin-Based Chondrogenesis and Complex Polymer Scaffold for Cartilage Defect Regeneration.

ACS Biomater Sci Eng 2020 11 13;6(11):6276-6284. Epub 2020 Oct 13.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

Articular cartilage has a highly organized structure, responsible for supporting tremendous mechanical loads. How to repair defected articular cartilage has become a great challenge as the avascular nature of cartilage limits its regenerative ability. Aiming to facilitate chondrogenic differentiation and cartilage regeneration, we recently explored a novel combination therapy using soluble poly-l-lysine/Kartogenin (L-K) nanoparticles and a poly(lactic--glycolic acid) PLGA/methacrylated hyaluronic acid (PLHA) complex scaffold. The potential use for joint cartilage reconstruction was investigated through L-K nanoparticles stimulating adipose-derived stem cells (ADSCs) on PLHA scaffolding, which ultimately differentiated into cartilage . In this study, on one hand, an effective method was established for obtaining uniform L-K nanoparticles by self-assembly. They were further proved to be biocompatible to ADSCs cytotoxicity assays and to accelerate ADSCs secreting type 2 collagen in a dose-dependent manner by immunofluorescence. On the other hand, the porous PLHA scaffold was manufactured by the combination of coprecipitation and ultraviolet (UV) cross-linking. Nanoindentation technology-verified PLHA had an appropriate stiffness close to actual cartilage tissue. Additional microscopic observation confirmed that the PLHA platform supported proliferation and chondrogenesis for ADSCs . In the presence of ADSCs, a 12-week osteochondral defect regeneration by the combination therapy showed that smooth and intact cartilage tissue successfully regenerated. Furthermore, the results of combination therapy were superior to those of phosphate-buffered saline (PBS) only, KGN, or KGN/PLHA treatment. The results of magnetic resonance imaging (MRI) and histological assessment indicated that the renascent tissue gradually regenerated while the PLHA scaffold degraded. In conclusion, we have developed a novel multidimensional combination therapy of cartilage defect repair that facilitated cartilage regeneration. This strategy has a great clinical translational potential for articular cartilage repair in the near future.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00724DOI Listing
November 2020

Sentinel lymph node mapping in high-risk endometrial cancer: a systematic review and meta-analysis.

Gland Surg 2020 Dec;9(6):2091-2105

Gynecological Oncology Ward, Dalian Maternal and Child Health Hospital Affiliated to Dalian Medical University, Dalian, China.

Background: In the staging of endometrial cancer (EC), the role of sentinel lymph node (SLN) mapping for high-risk EC is still unclear.

Methods: Two authors independently reviewed abstracts and full-text articles for inclusion and assessed study quality. English studies published in PubMed, Embase, and Cochrane Library before 20th SEP, 2019 were retrieved to perform a systematic evaluation and meta-analysis which evaluate the detection rate and diagnostic accuracy of SLN mapping in high-risk EC. Statistical analysis was conducted using stata14.0 software.

Results: A total of 12 studies were included, including 758 high-risk EC patients. The detection rate of SLN mapping was 84.8% (95% CI, 79.9-89.6%). The pooled bilateral detection rate was 67.0% (95% CI, 56.8-77.3%). The pooled para-aortic detection rate was 8.4% (95% CI, 1.8-14.9%). The pooled sensitivity was 87% (95% CI, 79-92%), and the pooled specificity was 98% (95% CI, 96-99%). Pooled negative predictive value (NPV) was 97.7% (95% CI, 96.4-99.1%), AUC =0.99 (95% CI, 0.97-0.099).

Conclusions: SLN mapping still has a high detection rate and diagnostic accuracy in high-risk EC. SLN mapping is a reliable alternative to systematic lymph node dissection, but its prognostic effect on high-risk EC is yet to be further studied and verified by large sample studies.
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http://dx.doi.org/10.21037/gs-20-807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804562PMC
December 2020

Necroptosis is active and contributes to intestinal injury in a piglet model with lipopolysaccharide challenge.

Cell Death Dis 2021 01 11;12(1):62. Epub 2021 Jan 11.

Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023, Wuhan, China.

Necroptosis, a newly discovered form of programmed cell death that combines the features of apoptosis and necrosis, is important in various physiological and pathological disorders. However, the role of necroptosis on intestinal injury during sepsis has been rarely evaluated. This study aimed to investigate the presence of necroptosis in intestinal injury, and its contribution to intestinal injury in a piglet model challenged with Escherichia coli lipopolysaccharide (LPS). Firstly, a typical cell necrotic phenomenon was observed in jejunum of LPS-challenged pigs by transmission electron microscope. Protein expression of necroptosis signals including receptor-interacting protein kinase (RIP) 1, RIP3, and phosphorylated mixed-lineage kinase domain-like protein (MLKL), mitochondrial proteins including phosphoglycerate mutase family member 5 (PGAM5) and dynamin-related protein 1 (DRP1), and cytoplasmic high-mobility group box 1 (HMGB1) were time-independently increased in jejunum of LPS-challenged piglets, which was accompanied by the impairment of jejunal morphology, and digestive and barrier function indicated by lower activities of jejunal disaccharidases and protein expression of jejunal tight junction proteins claudin-1 and occludin. Pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were also dynamically induced in serum and jejunum of piglets after LPS challenge. Moreover, pretreatment with necrostatin-1 (Nec-1), an specific inhibitor of necroptosis, inhibited necroptosis indicated by decreased necrotic ultrastructural changes and decreased protein expression of RIP1, RIP3, and phosphorylated MLKL as well as PGAM5, DRP1, and cytoplasmic HMGB1. Nec-1 pretreatment reduced jejunal morphological injury, and improved digestive and barrier function. Nec-1 pretreatment also decreased the levels of serum and jejunal pro-inflammatory cytokines and the numbers of jejunal macrophages and monocytes. These findings indicate for the first time that necroptosis is present and contributes to LPS-induced intestinal injury. Nec-1 may have a preventive effect on intestinal injury during sepsis.
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http://dx.doi.org/10.1038/s41419-020-03365-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801412PMC
January 2021

Involvement of the cytokine TWEAK in the pathogenesis of psoriasis vulgaris, pustular psoriasis, and erythrodermic psoriasis.

Cytokine 2021 02 8;138:155391. Epub 2020 Dec 8.

Department of Dermatology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China. Electronic address:

Psoriasis is a common chronic inflammatory dermatitis in which various cytokines play a detrimental role. The cytokine tumor necrosis factor-related weak inducer of apoptosis (TWEAK) is involved in the pathogenesis of multiple inflammatory disorders. However, the potential role of TWEAK in various subtypes of psoriasis has not been studied in depth. To investigate whether the levels of TWEAK are associated with clinical traits and the levels of some known psoriasis-related cytokines, such as interleukin (IL)-17A, IL-22, interferon (IFN)-γ, and IL-36γ, 20 patients with psoriasis vulgaris (PV), 8 patients with pustular psoriasis (PP), 8 patients with erythrodermic psoriasis (EP), and 20 healthy controls (HCs) were recruited into this study. The levels of serum cytokines were detected by commercial enzyme-linked immunosorbent assay kits. The average levels of TWEAK, IL-17A, IL-22, IFN-γ, and IL-36γ were significantly higher in the psoriasis groups than in the HC group. Furthermore, there was a statistically significant correlation between TWEAK and IL-17A/IFN-γ in PV and IL-36γ in EP, but there was no correlation between TWEAK and IL-22 in any subtype of psoriasis. This study suggests that TWEAK may have a role in the pathogenesis of PV, PP, and EP via synergy with IL-17A, IFN-γ, or IL-36γ, but not with IL-22.
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http://dx.doi.org/10.1016/j.cyto.2020.155391DOI Listing
February 2021

Multiple Subchondral Bone Cysts Cause Deterioration of Articular Cartilage in Medial OA of Knee: A 3D Simulation Study.

Front Bioeng Biotechnol 2020 6;8:573938. Epub 2020 Oct 6.

Institute of Translational Medicine, China Medical University, Shenyang, China.

Aims: To investigate the impact of subchondral bone cysts (SBCs) in stress-induced osseous and articular variations in cystic and non-cystic knee models using finite element analysis.

Materials And Methods: 3D knee joint models were reconstructed from computed tomography (CT) and magnetic resonance imaging (MRI). Duplicate 3D models were also created with a 3D sphere mimicking SBCs in medial tibia. Models were divided into three groups. In group A, a non-cystic knee model was used, whereas in groups B and C, SBCs of 4 and 12 mm size were simulated, respectively. Cyst groups were further divided into three sub-groups. Each of sub-group 1 was composed of a solitary SBC in the anterior half of tibia adjacent to joint line. In sub-group 2, a solitary cyst was modeled at a lower-joint location, and in sub-group 3, two SBCs were used. All models were vertically loaded with weights representing double- and single-leg stances.

Results: During single-leg stance, increase in subchondral bone stress in sub-groups B-1 and B-3 were significant ( = 0.044, = 0.026). However, in sub-group B-2, a slight increase was observed than non-cystic knee model (9.93 ± 1.94 vs. 9.35 ± 1.85; = 0.254). All the sub-groups in group C showed significantly increased articular stress ( < 0.001). Conversely, a prominent increase in peri-cystic cancellous bone stress was produced by SBCs in groups B and C ( < 0.001). Mean cartilage shear stress in sub-groups B-1 and B-2 (0.66 ± 0.56, 0.58 ± 0.54) was non-significant ( = 0.374, = 0.590) as compared to non-cystic model (0.47 ± 0.67). But paired cysts of the same size (B-3) produced a mean stress of 0.98 ± 0.49 in affected cartilage ( = 0.011). Models containing 12 mm SBCs experienced a significant increase in cartilage stress ( = 0.001, = 0.006, < 0.001) in sub-groups C-1, C-2, and C-3 (1.25 ± 0.69, 1.01 ± 0.54, and 1.26 ± 0.59), respectively.

Conclusion: The presence of large-sized SBCs produced an increased focal stress effect in articular cartilage. Multiple cysts further deteriorate the condition by increased osseous stress effect and high tendency of peripheral cyst expansion in simulated cystic knee models than non-cystic knee models.
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http://dx.doi.org/10.3389/fbioe.2020.573938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583719PMC
October 2020

LncRNA MALAT1 Regulates the Progression and Cisplatin Resistance of Ovarian Cancer Cells via Modulating miR-1271-5p/E2F5 Axis.

Cancer Manag Res 2020 12;12:9999-10010. Epub 2020 Oct 12.

Department of Gynecology, The First People's Hospital of Lianyungang, Lianyungang 222000, Peoples' Republic of China.

Background: Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were reported to be related to the development of ovarian cancer (OC). In this study, the functional mechanisms of lncRNA metastasis associated with lung adenocarcinoma transcript 1 (MALAT1) and microRNA-1271-5p (miR-1271-5p) were explored in OC.

Methods: The level of MALAT1, miR-1271-5p, or E2F transcription factor 5 (E2F5) was detected by qRT-PCR. MTT assay, flow cytometry analysis and transwell migration and invasion assays were performed to determine cell proliferation, apoptosis, migration and invasion, respectively. E2F5 protein expression was detected by Western blot. The interaction between miR-1271-5p and MALAT1 or E2F transcription factor 5 (E2F5) was confirmed by the dual-luciferase reporter assay.

Results: MALAT1 and E2F5 level were increased, while miR-1271-5p level was decreased in cisplatin (DDP)-resistant OC tissues and cells. MALAT1 knockdown or miR-1271-5p upregulation decreased IC of cisplatin, and inhibited cell proliferation, migration, invasion, and facilitated cell apoptosis in DDP-resistant OC cells. Moreover, MALAT1 sponged miR-1271-5p to upregulate E2F5 expression. Besides, MALAT1 knockdown decreased DDP resistance, inhibited cell proliferation, migration, invasion, and promoted cell apoptosis by sponging miR-1271-5p to downregulate E2F5 expression in DDP-resistant OC cell.

Conclusion: We demonstrated that MALAT1 mediated DDP-resistant OC development through miR-1271-5p/E2F5 axis, providing the theoretical basis for OC therapy.
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http://dx.doi.org/10.2147/CMAR.S261979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567574PMC
October 2020

Identification of lncRNA Signature Associated With Pan-Cancer Prognosis.

IEEE J Biomed Health Inform 2021 06 3;25(6):2317-2328. Epub 2021 Jun 3.

Long noncoding RNAs (lncRNAs) have emerged as potential prognostic markers in various human cancers as they participate in many malignant behaviors. However, the value of lncRNAs as prognostic markers among diverse human cancers is still under investigation, and a systematic signature based on these transcripts that related to pan-cancer prognosis has yet to be reported. In this study, we proposed a framework to incorporate statistical power, biological rationale, and machine learning models for pan-cancer prognosis analysis. The framework identified a 5-lncRNA signature (ENSG00000206567, PCAT29, ENSG00000257989, LOC388282, and LINC00339) from TCGA training studies (n = 1,878). The identified lncRNAs are significantly associated (all P ≤ 1.48E-11) with overall survival (OS) of the TCGA cohort (n = 4,231). The signature stratified the cohort into low- and high-risk groups with significantly distinct survival outcomes (median OS of 9.84 years versus 4.37 years, log-rank P = 1.48E-38) and achieved a time-dependent ROC/AUC of 0.66 at 5 years. After routine clinical factors involved, the signature demonstrated better performance for long-term prognostic estimation (AUC of 0.72). Moreover, the signature was further evaluated on two independent external cohorts (TARGET, n = 1,122; CPTAC, n = 391; National Cancer Institute) which yielded similar prognostic values (AUC of 0.60 and 0.75; log-rank P = 8.6E-09 and P = 2.7E-06). An indexing system was developed to map the 5-lncRNA signature to prognoses of pan-cancer patients. In silico functional analysis indicated that the lncRNAs are associated with common biological processes driving human cancers. The five lncRNAs, especially ENSG00000206567, ENSG00000257989 and LOC388282 that never reported before, may serve as viable molecular targets common among diverse cancers.
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http://dx.doi.org/10.1109/JBHI.2020.3027680DOI Listing
June 2021

Effects of a nurse-led positive psychology intervention on sexual function, depression and subjective well-being in postoperative patients with early-stage cervical cancer: A randomized controlled trial.

Int J Nurs Stud 2020 Nov 3;111:103768. Epub 2020 Sep 3.

Radiology Department, The Second Affiliated Hospital of Chongqing Medical University, No.74 Linjiang Road, Yuzhong District, Chongqing, 400010, China. Electronic address:

Background: Sexual dysfunction is a common long-term complication of cervical cancer and its treatment. However, due to traditional Chinese culture, there are few studies on interventions to improve sexual function in China.

Objectives: To evaluate the effectiveness of a nurse-led positive psychology intervention on sexual function, depression and subjective well-being amongst postoperative patients with early-stage cervical cancer.

Design: A randomized controlled trial.

Settings And Methods: Patients who had undergone radical hysterectomy for early-stage cervical cancer and were followed up in gynaecological clinics were recruited via convenience sampling from three tertiary hospitals in Chongqing, China. Patients who met the inclusion criteria and agreed to participate (N = 91) were randomly assigned to a nurse-led positive psychology intervention (intervention group, n = 46) or usual care (control group, n = 45). The Female Sexual Function Index, Self-rating Depression Scale and Index of Well-being were used to assess sexual function, depression and subjective well-being, respectively, at baseline and 3 and 6 months after the intervention. Data were analysed by the chi-square test, Mann-Whitney U test, t-test and Pearson correlation analysis.

Results: Compared with participants in the control group, participants in the intervention group showed significant improvements in sexual function (mean difference [MD]: -3.95, P = 0.005 at 3 months post-intervention; MD: -4.36, P = 0.001 at 6 months post-intervention). In addition, at 3 and 6 months after the intervention, the number of patients with improvements in their levels of depression and well-being in the intervention group was higher than that in the control group (P<0.05). The Pearson correlation analysis results showed that there was a negative correlation between sexual function and level of depression in patients (r =-0.612, P<0.001) and that sexual function was positively correlated with subjective well-being (r = 0.638, P<0.001).

Conclusion: The intervention group experienced significant improvements in sexual function, depression and subjective well-being. These findings suggest that a nurse-led positive psychology intervention should be implemented for postoperative patients with early-stage cervical cancer.
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http://dx.doi.org/10.1016/j.ijnurstu.2020.103768DOI Listing
November 2020

Impact of phosphorus fertilizer level on the yield and metabolome of goji fruit.

Sci Rep 2020 09 4;10(1):14656. Epub 2020 Sep 4.

College of Horticulture, Northwest A & F University, Yangling, 712000, Shan Xi, China.

Goji (Lycium barbarum L.) is a highly medicinal value tree species. The yield and nutritional contents of goji fruit are significant affected by fertilizer level. In this study, we analyzed the yield and nutritional contents change of goji fruit, which planted in pot (vermiculite:perlite, 1:2, v:v) in growth chamber under P0 (32.5 g/per tree), P1 (65 g/per tree), and P2 (97.5 g/per tree). Meanwhile, we utilized an integrated Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) to analysis of the response of the metabolome in goji fruit to phosphorus level. The results show that the yield of goji fruits had strongly negative correlation with phosphorus level, especially in the third harvest time. The amino acids, flavonoids, polysaccharides, and betaine contents of goji fruits in the first harvest time had obvious correlated with the level of phosphorus level. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicated that the impact of different phosphorus fertilizer levels on each group mainly involved the biosynthesis of flavonoids. The results provide new insights into the theoretical basis of the relationship between the nutritional contents of goji fruits and phosphorus fertilizer level.
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http://dx.doi.org/10.1038/s41598-020-71492-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474080PMC
September 2020

Rectifying Supporting Regions With Mixed and Active Supervision for Rib Fracture Recognition.

IEEE Trans Med Imaging 2020 12 30;39(12):3843-3854. Epub 2020 Nov 30.

Automatic rib fracture recognition from chest X-ray images is clinically important yet challenging due to weak saliency of fractures. Weakly Supervised Learning (WSL) models recognize fractures by learning from large-scale image-level labels. In WSL, Class Activation Maps (CAMs) are considered to provide spatial interpretations on classification decisions. However, the high-responding regions, namely Supporting Regions of CAMs may erroneously lock to regions irrelevant to fractures, which thereby raises concerns on the reliability of WSL models for clinical applications. Currently available Mixed Supervised Learning (MSL) models utilize object-level labels to assist fitting WSL-derived CAMs. However, as a prerequisite of MSL, the large quantity of precisely delineated labels is rarely available for rib fracture tasks. To address these problems, this paper proposes a novel MSL framework. Firstly, by embedding the adversarial classification learning into WSL frameworks, the proposed Biased Correlation Decoupling and Instance Separation Enhancing strategies guide CAMs to true fractures indirectly. The CAM guidance is insensitive to shape and size variations of object descriptions, thereby enables robust learning from bounding boxes. Secondly, to further minimize annotation cost in MSL, a CAM-based Active Learning strategy is proposed to recognize and annotate samples whose Supporting Regions cannot be confidently localized. Consequently, the quantity demand of object-level labels can be reduced without compromising the performance. Over a chest X-ray rib-fracture dataset of 10966 images, the experimental results show that our method produces rational Supporting Regions to interpret its classification decisions and outperforms competing methods at an expense of annotating 20% of the positive samples with bounding boxes.
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http://dx.doi.org/10.1109/TMI.2020.3006138DOI Listing
December 2020

Antitumor effects of aconitine in A2780 cells via estrogen receptor β‑mediated apoptosis, DNA damage and migration.

Mol Med Rep 2020 Sep 10;22(3):2318-2328. Epub 2020 Jul 10.

Department of Medical Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261041, P.R. China.

Ovarian cancer (OVCA) is the deadliest type of malignant gynecological disease, and previous studies have demonstrated that estrogen receptor β (ERβ) serves important roles in this disease. Aconitine, a toxin produced by the Aconitum plant, displays potent effects against cancers. The aim of the study was to investigate the pharmacological activities and mechanisms of aconitum on OVCA. In the present study, the activity of aconitine in the human OVCA A2780 cell line was investigated. The results revealed that aconitine suppressed cell viability, colony formation and motility. Terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling, mitochondria membrane potential and comet assays showed that aconitine induced mitochondria apoptosis and DNA damage in A2780 cells. Investigation of the mechanism revealed that a high expression of ERβ and prolyl hydroxylase 2 was detected after aconitine treatment, and aconitine significantly suppressed the expression of vascular endothelial growth factor and hypoxia‑inducible factor 1α to activate ERβ signaling. Moreover, the expression levels of p53, Bax, apoptotic peptidase activating factor 1, cytochrome C, cleaved caspase‑3/9 and cleaved poly (ADP‑ribose) polymerase were upregulated, and the expression levels of Bcl‑2, Bcl‑xl and phosphorylated ATM serine/threonine kinase were downregulated by aconitine. Interestingly, aconitine also markedly downregulated the expression of matrix metalloproteinase 2 (MMP2) and MMP9, which are associated with tumor invasion. In addition, a molecular docking assay revealed that aconitine exerted strong affinity towards ERβ mainly through hydrogen bonding and hydrophobic effects. Collectively, these results suggested that aconitine suppressed OVCA cell growth by adjusting ERβ‑mediated apoptosis, DNA damage and migration, which should be considered a potential option for the future treatment of OVCA.
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http://dx.doi.org/10.3892/mmr.2020.11322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411431PMC
September 2020

5-aminolaevulinic acid-based photodynamic therapy induces both necrosis and apoptosis of keratinocytes in plantar warts.

J Cosmet Laser Ther 2020 Apr 30;22(3):165-170. Epub 2020 Jun 30.

Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an, China.

Background: 5-aminolaevulinic acid (ALA)-based photodynamic therapy (ALA-PDT) is an effective treatment for proliferative skin diseases. Many studies revealed that ALA-PDT induces apoptosis of cancer cells. However, the mechanism of PDT in warts is not fully elucidated.

Objective: This study was designed to explore the efficacy of ALA-PDT for plantar warts and its possible mechanism.

Methods: Twenty-five patients with plantar warts underwent four rounds of ALA-PDT at weekly intervals. Therapeutic effects were observed 1 month since last treatment. The adverse reactions were also recorded during and after the procedure. To observe histological changes, 5 patients accepted tissue biopsies before and 24 h after first PDT treatment.

Results: Twenty-two patients (88%) showed a complete response. Twenty patients complained of a mild burning sensation during treatment, and four patients developed local edema immediately after red light exposure. Five patients had burns after treatment, which disappeared within 24 h. Histologically, epidermal keratinocytes demonstrated remarkable necrocytosis and apoptosis after PDT.

Conclusions: ALA-PDT is highly effective for treatment of plantar warts. The most common adverse effects observed in patients are pain and edema. ALA-PDT might eradicate plantar warts by activating both necrosis and apoptosis to trigger the death of proliferating keratinocytes.
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http://dx.doi.org/10.1080/14764172.2020.1785626DOI Listing
April 2020

Activation of the NF-B and MAPK Signaling Pathways Contributes to the Inflammatory Responses, but Not Cell Injury, in IPEC-1 Cells Challenged with Hydrogen Peroxide.

Oxid Med Cell Longev 2020 21;2020:5803639. Epub 2020 Jan 21.

Hubei Key Laboratory of Animal Nutrition and Feed Science, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University, Wuhan, China.

Oxidative stress can lead to intestinal cell injury as well as the induction of inflammation. It is not clear whether inflammation is an important factor leading to cell injury caused by oxidative stress. The purpose of this study was to investigate the role of inflammation in intestinal injury caused by hydrogen peroxide (HO). Our results revealed that HO stimulation significantly decreased the viability of intestinal porcine epithelial cells (IPEC-1), increased lactate dehydrogenase (LDH) activity, and disrupted the distribution of the tight junction protein claudin-1. HO significantly increased the mRNA expression of interleukin-6 (IL-6), IL-8, and tumor necrosis factor- (TNF-). HO stimulation also led to increased phosphorylation of p38 and jun N-terminal kinase (JNK), and p65 NF-B protein translocation into the nucleus of IPEC-1 cells. Cells treated with the NF-B inhibitor (BAY11-7082), the p38 inhibitor (SB202190), or the JNK inhibitor (PD98059) significantly decreased mRNA and protein expression of IL-6, IL-8, and TNF-. However, treatment with mitogen-activated protein kinase (MAPK) or NF-B inhibitors did not prevent the damage effect on cell viability, LDH activity, or the distribution of claudin-1 in cells challenged with HO. In summary, our data demonstrate that activation of the NF-B and MAPK signaling pathways can contribute to the inflammatory response, but not cell injury, in IPEC-1 cells challenged with HO.
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http://dx.doi.org/10.1155/2020/5803639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204152PMC
January 2021

Similar responses to EQ-5D-3L by two elicitation methods: visual analogue scale and time trade-off.

BMC Med Res Methodol 2020 05 14;20(1):118. Epub 2020 May 14.

School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.

Background: Health-related quality of life (HRQoL) is often measured using EQ-5D-3L by the elicitation methods of visual analogue scale (VAS) and time trade-off (TTO). Although many countries have constructed both national VAS and TTO value sets, the fact that VAS and TTO value sets produces different values bewilders researchers and policymakers. The aim of this study is to explore certain conditions which could yield similar value sets using VAS and TTO.

Methods: A homogeneous sample of medical school students was selected to value 18 hypothetical health states using VAS and TTO methods. The 18 hypothetical health states were produced by orthogonal design (L18, 2*3^7). The range of rescaled values was transformed into - 1 ~ 0 ~ 1. The investigations via different methods were carried out by computer-assisted personal interviewing with a wash-time interval of 72 h. Value sets for VAS and TTO were constructed using general least square regression models. Independent variables were composed of 10 dummy variables from 5 dimensions and including or omitting both constant and N3 terms.

Results: Three hundred thirteen medical students participated. The mean age was 21.03 ± 0.44 years and 56.2% were female. The four regression models (for each method with and without constant and N3 terms) were all statistically significant (P < 0.05) with high goodness-of-fit (Adj. R > 0.94 and MAE < 0.033). Differences between the coefficients of the 10 dummy variables corresponding to each model were all less than 0.059. Pearson correlation coefficients between observed means and predicted values exceeded 0.981. Fitted curves of VAS and TTO largely coincided.

Conclusions: VAS and TTO can generate similar responses under certain conditions, suggesting that the two valuation methods could be equivalent intrinsically. The VAS method appears a more valid approach for valuation in the general population due to its greater simplicity and feasibility.
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http://dx.doi.org/10.1186/s12874-020-01008-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227357PMC
May 2020

Chitosan modified FeO/KGN self-assembled nanoprobes for osteochondral MR diagnose and regeneration.

Theranostics 2020 15;10(12):5565-5577. Epub 2020 Apr 15.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, PR China.

Chondral and osteochondral defects caused by trauma or pathological changes, commonly progress into total joint degradation, even resulting in disability. The cartilage restoration is a great challenge because of its avascularity and limited proliferative ability. Additionally, precise diagnosis using non-invasive detection techniques is challenging, which increases problems associated with chondral disease treatment. To achieve a theranostic goal, we used an integrated strategy that relies on exploiting a multifunctional nanoprobe based on chitosan-modified Fe3O4 nanoparticles, which spontaneously self-assemble with the oppositely charged small molecule growth factor, kartogenin (KGN). This nanoprobe was used to obtain distinctively brighter T-weighted magnetic resonance (MR) imaging, allowing its use as a positive contrast agent, and could be applied to obtain accurate diagnosis and osteochondral regeneration therapy. This nanoprobe was first investigated using adipose tissue-derived stem cells (ADSCs), and was found to be a novel positive contrast agent that also plays a significant role in stimulating ADSCs differentiation into chondrocytes. This self-assembled probe was not only biocompatible both and , contributing to cellular internalization, but was also used to successfully make distinction of normal/damaged tissue in T-weighted MR imaging. This novel combination was systematically shown to be biosafe via the decrement of apparent MR signals and elimination of ferroferric oxide over a 12-week regeneration period. Here, we established a novel method for osteochondral disease diagnosis and reconstruction. Using the FeO-CS/KGN nanoprobe, it is easy to distinguish the defect position, and it could act as a tool for dynamic observation as well as a stem cell-based therapy for directionally chondral differentiation.
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http://dx.doi.org/10.7150/thno.43569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196312PMC
May 2021

Neuropsychological Deficits in Patients with Electrical Status Epilepticus During Sleep: A Non-invasive Analysis of Neurovascular Coupling.

Brain Topogr 2020 05 3;33(3):375-383. Epub 2020 Mar 3.

Department of Neurology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 318# Ren Min Road, Guangzhou, Guangdong, 510120, P.R. China.

To evaluate the effects of electrical status epilepticus during sleep (ESES) on cerebral blood flow (CBF) and explore the associated neuro-vascular coupling and neuropsychological deficits. 19 ESES patients were recruited to undergo real-time transcranial doppler ultrasonography (TCD) and video-EEG monitoring (vEEG). Patients were grouped based on their cognitive functions or their EEG patterns. The mean cerebral blood flow velocity (CBFV) of the unilateral middle cerebral artery was measured using TCD and was used to calculate various relevant parameters. The 19 patients participated in a total of 54 effective TCD-vEEG monitoring sessions. We found a significant effect of clinical severity for the following measurements: spike wave index (SWI), peak and average deep sleep stage (N3) CBFV, peak, average and minimum deep sleep and awake CBFV, and CBFV oscillations during deep sleep. Nevertheless, CBFV oscillations were not related to SWI. Furthermore, CBFV oscillations revealed a statistically significant difference between the near-ESES and asymmetric-ESES groups. CBFV oscillations may reflect the neuro-vascular coupling process associated with ESES disfunction. Understanding the relationship between CBFV oscillations and epileptic activity will be important for assessing the neuropsychological damage associated with ESES and for developing treatment options for this and other diseases.
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http://dx.doi.org/10.1007/s10548-020-00759-4DOI Listing
May 2020
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