Authors: Hu, Ying | Guo, Geyang | Li, Junjun | Chen, Jie | Tan, Pingqing
Article Type: Research Article
Abstract: BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common type of cancer around the world. The aim of this study was to seek the long non-coding RNAs (lncRNAs) acting as diagnostic and prognostic biomarker of HNSCC. METHODS: Base on TCGA dataset, the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified between HNSCC and normal tissue. The machine learning and survival analysis were performed to estimate the potential diagnostic and prognostic value of lncRNAs for HNSCC. We also build the co-expression network and functional annotation. The expression of selected candidate mRNAs and lncRNAs were validated by …Quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: A total of 3363 DEmRNAs (1822 down-regulated and 1541 up-regulated mRNAs) and 32 DElncRNAs (13 down-regulated and 19 up-regulated lncRNAs) between HNSCC and normal tissue were obtained. A total of 13 lncRNAs (IL12A.AS1, RP11.159F24.6, RP11.863P13.3, LINC00941, FOXCUT, RNF144A.AS1, RP11.218E20.3, HCG22, HAGLROS, LINC01615, RP11.351J23.1, AC024592.9 and MIR9.3HG) were defined as optimal diagnostic lncRNAs biomarkers for HNSCC. The area under curve (AUC) of the support vector machine (SVM) model, decision tree model and random forests model and were 0.983, 0.842 and 0.983, and the specificity and sensitivity of the three model were 95.5% and 96.2%, 77.3% and 97.6% and 93.2% and 97.8%, respectively. Among them, AC024592.9, LINC00941, LINC01615 and MIR9-3HG was not only an optimal diagnostic lncRNAs biomarkers, but also related to survival time. The focal adhesion, ECM-receptor interaction, pathways in cancer and cytokine-cytokine receptor interaction were four significantly enriched pathways in DEmRNAs co-expressed with the identified optimal diagnostic lncRNAs. But for most of the selected DEmRNAs and DElncRNAs, the expression was consistent with our integrated analysis results, including LINC00941, LINC01615, FOXCUT, TGA6 and MMP13. CONCLUSION: AC024592.9, LINC00941, LINC01615 and MIR9-3HG was not only an optimal diagnostic lncRNAs biomarkers, but also were a prognostic lncRNAs biomarkers. Show more
Keywords: Head and neck squamous cell carcinoma, diagnostic, prognostic, machine learning
DOI: 10.3233/CBM-190694
Citation: Cancer Biomarkers, vol. 27, no. 2, pp. 195-206, 2020
Authors: Li, Hui | Hu, Ying | Gan, Lin | Wang, YiXuan
Article Type: Research Article
Abstract: BACKGROUND: An osteoporotic fracture (OPF) can significantly affect patients’ activities of daily living (ADLs). OBJECTIVE: This study observed the effects of evidence-based nursing (EBN) on the occurrence of postoperative complications and ADLs in patients with a vertebral OPF. METHODS: A total of 90 patients with vertebral OPF were divided into two groups. The conventional orthopedic nursing method was conducted for the control group, and the EBN model was delivered for the observation group. RESULTS: Differences in the Barthel index (BI) score on the first day of admission were not statistically significant between the two groups. The BI scores on the …day before discharge, compared with the day of admission, had improved in both groups. The BI score on the day before discharge was 83.67 ± 6.94 in the observation group, and the difference was statistically significant (P < 0.05) compared with the control group (76.56 ± 6.89). The rate of satisfaction with nursing in the observation group (100.0%) was significantly higher than in the control group (82.2%) (P < 0.05). The incidence of postoperative complications in the observation group (2.2%) was significantly lower than in the control group (24.4%) (P < 0.05). CONCLUSIONS: The implementation of EBN in patients with vertebral OPF improved the postoperative ADLs, reduced the incidence of postoperative complications, and improved the patients’ satisfaction with nursing. Show more
Keywords: Osteoporotic fracture, evidence-based nursing, activities of daily living, postoperative complication, observation of clinical effectiveness
DOI: 10.3233/BMR-220161
Citation: Journal of Back and Musculoskeletal Rehabilitation, vol. 36, no. 2, pp. 517-523, 2023
Authors: Hu, Ying | Yang, Yifeng | Hou, Xuewen | Zhou, Yan | Nie, Shengdong
Article Type: Research Article
Abstract: OBJECTIVE: To investigate relationships between the severity of white matter hyperintensities (WMH), functional brain activity, and cognition in cerebral small vessel disease (CSVD) based on resting-state functional magnetic resonance imaging (rs-fMRI) data. METHODS: A total of 103 subjects with CSVD were included. The amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo), functional connectivity (FC) and their graph properties were applied to explore the influence of WMH burden on functional brain activity. We also investigated whether there are correlations between different functional brain characteristics and cognitive assessments. Finally, we selected disease-related rs-fMRI features in combination with ensemble learning to classify …CSVD patients with low WMH load and with high WMH load. RESULTS: The high WMH load group demonstrated significantly abnormal functional brain activity based on rs-MRI data, relative to the low WMH load group. ALFF and graph properties in specific brain regions were significantly correlated with patients’ cognitive assessments in CSVD. Moreover, altered rs-fMRI signal can help predict the severity of WMH in CSVD patients with an overall accuracy of 92.23%. CONCLUSIONS: This study provided a comprehensive analysis and evidence for a pattern of altered functional brain activity under different WMH load in CSVD based on rs-fMRI data, enabling accurately individual prediction of status of WMH. Show more
Keywords: Cerebral small vessel disease, white matter hyperintensities, rs-fMRI, cognition, aging
DOI: 10.3233/XST-221218
Citation: Journal of X-Ray Science and Technology, vol. 30, no. 6, pp. 1213-1227, 2022
Authors: Drummond, Eleanor S. | Rodger, Jennifer | Penrose, Marissa | Robertson, Donald | Hu, Ying | Harvey, Alan R.
Article Type: Research Article
Abstract: Purpose: In adult rats, intravitreal injections of the Rho-GTPase inhibitor C3 transferase (BA-210), or a cocktail of recombinant ciliary neurotrophic factor (CNTF) and a cyclic AMP analogue (CPTcAMP), increase retinal ganglion cell (RGC) survival and axonal regeneration. Here we examined whether these treatments also affect the dendritic architecture of regrowing RGCs. Methods: In Fischer F344 rats, one optic nerve was cut and an autologous peripheral nerve graft was sutured onto it. Rats then received intravitreal injections (4 μl) of saline, BA-210 or CNTF + CPTcAMP four and eleven days after the PN graft surgery. After 5 weeks, regenerating RGCs were …retrogradely labelled with fluorogold (FG) and in living wholemounts the dendritic trees of FG labelled RGCs were visualised by intracellular injection of 2% Lucifer Yellow. Results: Injection of BA-210 or CNTF + CPTcAMP resulted in significantly more regenerating RGCs with abnormal dendritic morphologies, including abnormally long looping processes. Compared to saline-injected regenerating controls, RGCs in BA-210 injected eyes had significantly smaller dendritic field areas and sparser dendrites, while in CNTF + CPTcAMP injected eyes there was increased branching of more distal dendrites. Conclusions: While both intraocular treatments enhance RGC axonal regrowth, they also induce significant changes in RGC dendritic morphology. It remains to be determined if such changes alter the function of the regenerating neuronal population. Show more
Keywords: Optic nerve injury, retina, regeneration, C3 transferase, peripheral nerve graft
DOI: 10.3233/RNN-130360
Citation: Restorative Neurology and Neuroscience, vol. 32, no. 3, pp. 391-402, 2014
Authors: Li, Song | Bhatia, Sangeeta | Hu, Ying‐Li | Shiu, Yan‐Ting | Li, Yi‐Shuan | Usami, Shunichi | Chien, Shu
Article Type: Research Article
Abstract: The migration of vascular endothelial cells (ECs) plays an important role in vascular remodeling. Here we studied the effects of cell morphology on the migration of bovine aortic ECs by culturing cells on micropatterned strips of collagen matrix (60‐, 30‐, and 15‐μm wide). The spreading areas of the cells on 15‐ and 30‐μm wide strips were 30% lower than those on 60‐ μm wide strips and unpatterned collagen. The cells on 15‐μm wide strips completely aligned in the direction of the strip, and had significantly lower shape index than those in all other groups. On strips of all widths, ECs …tended to migrate in the direction of strips. ECs on 15‐μm wide strips had highest speed, particularly in the direction of the strip. Vinculin staining showed that the leading edge of ECs on 15‐μm wide strips had focal adhesions that were oriented with their lamellipodial protrusion and the direction of cell migration; this arrangement of the focal adhesions may promote EC migration. The present study provides direct evidence on the role of cell morphology in EC migration, and will help us to understand the mechanisms of EC migration during angiogenesis and wound healing. Show more
Keywords: Cell morphology, endothelial cell migration, extracellular matrix, micropattern
Citation: Biorheology, vol. 38, no. 2-3, pp. 101-108, 2001
Authors: Chen, Yi-Chen | Hu, Kuang-Hu | Li, Fang-Zhen | Li, Shu-Yu | Su, Wan-Fang | Huang, Zhi-Ying | Hu, Ying-Xiong
Article Type: Research Article
Abstract: Recognition of lung cancer cells is very important to the clinical diagnosis of lung cancer. In this paper we present a novel method to extract the structure characteristics of lung cancer cells and automatically recognize their types. Firstly soft mathematical morphology methods are used to enhance the grayscale image, to improve the definition of images, and to eliminate most of disturbance, noise and information of subordinate images, so the contour of target lung cancer cell and biological shape characteristic parameters can be extracted accurately. Then the minimum distance classifier is introduced to realize the automatic recognition of different types of …lung cancer cells. A software system named “CANCER.LUNG” is established to demonstrate the efficiency of this method. The clinical experiments show that this method can accurately and objectively recognize the type of lung cancer cells, which can significantly improve the pathology research on the pathological changes of lung cancer and clinical assistant diagnoses. Show more
Keywords: Lung cancer cells, mathematical morphology, classification and recognition, clinical assistant diagnoses
Citation: Bio-Medical Materials and Engineering, vol. 16, no. 2, pp. 119-128, 2006
Authors: Hu, Ying | Mohassel, Payam | Donkervoort, Sandra | Yun, Pomi | Bolduc, Véronique | Ezzo, Daniel | Dastgir, Jahannaz | Marshall, Jamie L. | Lek, Monkol | MacArthur, Daniel G. | Foley, A. Reghan | Bönnemann, Carsten G.
Article Type: Research Article
Abstract: Calpainopathy, also known as limb girdle muscular dystrophy (LGMD) type 2A (LGMD2A) or LGMD R1 Calpain3-related, is one of the most common genetically characterized forms of limb-girdle muscular dystrophy with a wide range of phenotypic severity. We evaluated a consanguineous family with a clinical phenotype consistent with calpainopathy in whom conventional sequencing did not detect any mutations in the CAPN3 gene. Using whole exome sequencing paired with haplotype analysis, we identified a homozygous deep intronic single base pair deletion in CAPN 3 (c.946-29delT). Familial segregation studies were consistent with recessive inheritance. Immunoblotting of muscle tissue from the patient showed complete …absence of calpain 3. In silico analysis predicted the deletion to disrupt the branch point and subsequently alter splicing of exon 7. Studies of patient fibroblasts and muscle tissue confirmed altered splicing, resulting in an inclusion of a 389-bp intronic sequence upstream of exon 7, originating from a cryptic splice acceptor site in intron 6. This out-of-frame insertion results in a premature stop codon, leading to an apparent absence of protein likely due to degradation of the transcript via nonsense-mediated decay. We then designed phosphorodiamidate morpholino oligomers (PMOs) as splice modulators to block the new splice acceptor site. This approach successfully prevented the aberrant splicing – reverting the majority of the splice to the wildtype transcript. These results confirm the pathogenicity of this novel deep intronic mutation and provide a mutation-specific therapeutic strategy. Thus, deep intronic mutations in CAPN3 may be pathogenic and should be considered in the appropriate clinical setting. The identification of mutations which may be missed by traditional Sanger sequencing is essential as they may be excellent targets for individualized therapeutic strategies using RNA-directed splice modulation. Show more
Keywords: Calpainopathy, LGMD2A, deep intronic mutation, phosphorodiamidate morpholino oligomer (PMO)
DOI: 10.3233/JND-190414
Citation: Journal of Neuromuscular Diseases, vol. 6, no. 4, pp. 475-483, 2019
Authors: Villar-Quiles, Rocío N. | Donkervoort, Sandra | de Becdelièvre, Alix | Gartioux, Corine | Jobic, Valérie | Foley, A. Reghan | McCarty, Riley M. | Hu, Ying | Menassa, Rita | Michel, Laurence | Gousse, Gaelle | Lacour, Arnaud | Petiot, Philippe | Streichenberger, Nathalie | Choumert, Ariane | Declerck, Léa | Urtizberea, J.A. | Sole, Guilhem | Furby, Alain | Cérino, Matthieu | Krahn, Martin | Campana- Salort, Emmanuelle | Ferreiro, Ana | Eymard, Bruno | Bönnemann, Carsten G. | Bharucha-Goebel, Diana | Sumner, Charlotte J. | Connolly, Anne M. | Richard, Pascale | Allamand, Valérie | Métay, Corinne | Stojkovic, Tanya
Article Type: Research Article
Abstract: Background: Dominant and recessive autosomal pathogenic variants in the three major genes (COL6A1-A2-A3 ) encoding the extracellular matrix protein collagen VI underlie a group of myopathies ranging from early-onset severe conditions (Ullrich congenital muscular dystrophy) to milder forms maintaining independent ambulation (Bethlem myopathy). Diagnosis is based on the combination of clinical presentation, muscle MRI, muscle biopsy, analysis of collagen VI secretion, and COL6A1-A2-A3 genetic analysis, the interpretation of which can be challenging. Objective: To refine the phenotypical spectrum associated with the frequent COL6A3 missense variant c.7447A>G (p.Lys2483Glu). Methods: We report the clinical and molecular findings in 16 patients: 12 patients …carrying this variant in compound heterozygosity with another COL6A3 variant, and four homozygous patients. Results: Patients carrying this variant in compound heterozygosity with a truncating COL6A3 variant exhibit a phenotype consistent with COL6-related myopathies (COL6-RM), with joint contractures, proximal weakness and skin abnormalities. All remain ambulant in adulthood and only three have mild respiratory involvement. Most show typical muscle MRI findings. In five patients, reduced collagen VI secretion was observed in skin fibroblasts cultures. All tested parents were unaffected heterozygous carriers. Conversely, two out of four homozygous patients did not present with the classical COL6-RM clinical and imaging findings. Collagen VI immunolabelling on cultured fibroblasts revealed rather normal secretion in one and reduced secretion in another. Muscle biopsy from one homozygous patient showed myofibrillar disorganization and rimmed vacuoles. Conclusions: In light of our results, we postulate that the COL6A3 variant c.7447A>G may act as a modulator of the clinical phenotype. Thus, in patients with a typical COL6-RM phenotype, a second variant must be thoroughly searched for, while for patients with atypical phenotypes further investigations should be conducted to exclude alternative causes. This works expands the clinical and molecular spectrum of COLVI-related myopathies. Show more
Keywords: Collagen VI-related myopathies, COL6A3, collagen type VI, neuromuscular disorders, limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy (CMD), muscular MRI, NGS
DOI: 10.3233/JND-200577
Citation: Journal of Neuromuscular Diseases, vol. 8, no. 4, pp. 633-645, 2021