Clinical efficacy of subthreshold micropulse laser combined with anti-VEGF drugs in the treatment of diabetic macular edema: A meta-analysis.

BACKGROUND: To systematically evaluate the efficacy and safety of subthreshold micropulse laser (SML) combined with anti-vascular endothelial growth factor (VEGF) drugs for the treatment of diabetic macular edema (DME). METHODS: The randomized controlled trials on SML combined with anti-VEGF drugs for DME were retrieved from China National Knowledge Infrastructure, Wan Fang Data, VIP Data, Sino Med (China Biomedical Literature Database), PubMed, Web of Science, The Cochrane Library, and Embase by computer from inception to April 19, 2022. The observation group was treated with SML combined with anti-VEGF drugs, while the control group was treated with anti-VEGF agents alone or SML. And the references of the included literature were manually searched. The Meta-analysis was performed using Revman 5.4 and STATA SE 15. RESULTS: This study finally included 15 randomized controlled trials involving 891 eyes for Meta-analysis. The results showed that there was no statistically significant difference between the 2 groups in best-corrected visual acuity at 1, 3, 6, 9, and 12 months after treatment. There was no statistical difference between the 2 groups in central macular thickness (CMT) at 1, 3, and 6 months after treatment (P > .05). CMT in the observation group was lower than that in the control group at 9 and 12 months (P < .05). There was no statistical difference between the 2 groups in total macular volume at 3, 6, 9, and 12 months in CMT (P > .05). The number of anti-VEGF drugs injections in the observation was lower than that in the control group (P < .05). The occurrence of complications between the 2 groups was not statistically significant difference (P > .05). CONCLUSION: SML in combination with anti-VEGF drugs in patients with DME are comparable in reducing the number of anti-VEGF drugs injections and CMT, thereby reducing the financial burden on patients. It does not differ in best-corrected visual acuity and total macular volume.

Development of an m6A-Related lncRNAs Signature Predicts Tumor Stemness and Prognosis for Low-Grade Glioma Patients.

Background: Growing evidence has revealed that m6A modification of long noncoding RNAs (lncRNAs) dynamically controls tumor stemness and tumorigenesis-related processes. However, the prognostic significance of m6A-related lncRNAs and their associations with stemness in low-grade glioma (LGG) remain to be clarified. Methods: A multicenter transcriptome analysis of lncRNA expression in 1,247 LGG samples was performed in this study. The stemness landscape of LGG tumors was presented and associations with clinical features were revealed. The m6A-related lncRNAs were identified between stemness groups and were further prioritized via least absolute shrinkage and selection operator Cox regression analysis. A risk score model based on m6A-related lncRNAs was constructed and validated in external LGG datasets. Results: Based on the expression of LINC02984, PFKP-DT, and CRNDE, a risk model and nomogram were constructed; they successfully predicted the survival of patients and were extended to external datasets. Significant correlations were observed between the risk score and tumor stemness. Moreover, patients in different risk groups exhibited distinct tumor immune microenvironments and immune signatures. We finally provided several potential compounds suitable for specific risk groups, which may aid in LGG treatment. Conclusions: This novel signature presents noteworthy value in the prediction of prognosis and stemness status for LGG patients and will foster future research on the development of clinical regimens.

Mapping enhancer and chromatin accessibility landscapes charts the regulatory network of Alzheimer's disease.

BACKGROUND: Enhancers are regulatory elements that target and modulate gene expression and play a role in human health and disease. However, the roles of enhancer regulatory circuit abnormalities driven by epigenetic alterations in Alzheimer's disease (AD) are unclear. METHODS: In this study, a multiomic integrative analysis was performed to map enhancer and chromatin accessibility landscapes and identify regulatory network abnormalities in AD. We identified differentially methylated enhancers and constructed regulatory networks across brain regions using AD brain tissue samples. Through the integration of snATAC-seq and snRNA-seq datasets, we mapped enhancers with DNA methylation alterations (DMA) and chromatin accessibility landscapes. Core regulatory triplets that contributed to AD neuropathology in specific cell types were further prioritized. RESULTS: We revealed widespread DNA methylation alterations (DMA) in the enhancers of AD patients across different brain regions. In addition, the genome-wide transcription factor (TF) binding profiles showed that enhancers with DMA are pervasively regulated by TFs. The TF-enhancer-gene regulatory network analysis identified core regulatory triplets that are associated with brain and immune cell proportions and play important roles in AD pathogenesis. Enhancer regulatory circuits with DMA exhibited distinct chromatin accessibility patterns, which were further characterized at single-cell resolutions. CONCLUSIONS: Our study comprehensively investigated DNA methylation-mediated regulatory circuit abnormalities and provided novel insights into the potential pathogenesis of AD.

Chromosome-scale genome of the human blood fluke Schistosoma mekongi and its implications for public health.

BACKGROUND: Schistosoma mekongi is a human blood fluke causing schistosomiasis that threatens approximately 1.5 million humans in the world. Nonetheless, the limited available S. mekongi genomic resources have hindered understanding of its biology and parasite-host interactions for disease management and pathogen control. The aim of our study was to integrate multiple technologies to construct a high-quality chromosome-level assembly of the S. mekongi genome. METHODS: The reference genome for S. mekongi was generated through integrating Illumina, PacBio sequencing, 10 × Genomics linked-read sequencing, and high-throughput chromosome conformation capture (Hi-C) methods. In this study, we conducted de novo assembly, alignment, and gene prediction to assemble and annotate the genome. Comparative genomics allowed us to compare genomes across different species, shedding light on conserved regions and evolutionary relationships. Additionally, our transcriptomic analysis focused on genes associated with parasite-snail interactions in S. mekongi infection. We employed gene ontology (GO) enrichment analysis for functional annotation of these genes. RESULTS: In the present study, the S. mekongi genome was both assembled into 8 pseudochromosomes with a length of 404 Mb, with contig N50 and scaffold N50 lengths of 1168 kb and 46,759 kb, respectively. We detected that 43% of the genome consists of repeat sequences and predicted 9103 protein-coding genes. We also focused on proteases, particularly leishmanolysin-like metalloproteases (M8), which are crucial in the invasion of hosts by 12 flatworm species. Through phylogenetic analysis, it was discovered that the M8 gene exhibits lineage-specific amplification among the genus Schistosoma. Lineage-specific expansion of M8 was observed in blood flukes. Additionally, the results of the RNA-seq revealed that a mass of genes related to metabolic and biosynthetic processes were up-regulated, which might be beneficial for cercaria production. CONCLUSIONS: This study delivers a high-quality, chromosome-scale reference genome of S. mekongi, enhancing our understanding of the divergence and evolution of Schistosoma. The molecular research conducted here also plays a pivotal role in drug discovery and vaccine development. Furthermore, our work greatly advances the understanding of host-parasite interactions, providing crucial insights for schistosomiasis intervention strategies.

Pan-cancer analyses reveal multi-omic signatures and clinical implementations of the forkhead-box gene family.

BACKGROUND: Forkhead box (FOX) proteins belong to one of the largest transcription factor families and play crucial roles in the initiation and progression of cancer. Prior research has linked several FOX genes, such as FOXA1 and FOXM1, to the crucial process of carcinogenesis. However, the overall picture of FOX gene family across human cancers is far from clear. METHODS: To investigate the broad molecular signatures of the FOX gene family, we conducted study on multi-omics data (including genomics, epigenomics and transcriptomics) from over 11,000 patients with 33 different types of human cancers. RESULTS: Pan-cancer analysis reveals that FOX gene mutations were found in 17.4% of tumor patients with a substantial cancer type-dependent pattern. Additionally, high expression heterogeneity of FOX genes across cancer types was discovered, which can be partially attributed to the genomic or epigenomic alteration. Co-expression network analysis reveals that FOX genes may exert functions by regulating the expression of both their own and target genes. For a clinical standpoint, we provided 103 FOX gene-drug target-drug predictions and found FOX gene expression have potential survival predictive value. All of the results have been included in the FOX2Cancer database, which is freely accessible at http://hainmu-biobigdata.com/FOX2Cancer. CONCLUSION: Our findings may provide a better understanding of roles FOX genes played in the development of tumors, and help to offer new avenues for uncovering tumorigenesis and unprecedented therapeutic targets.

Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas.

Background: Glioblastomas are the most common and malignant central nervous system (CNS) tumors that occupied a highly heterogeneous tumor microenvironment (TIME). Long noncoding RNAs (lncRNAs), whose expression can be modified by DNA methylation, are emerging as critical regulators in the immune system. However, knowledge about the epigenetic changes in lncRNAs and their contribution to the immune heterogeneity of glioma is still lacking. Methods: In this study, we integrated paired methylome and transcriptome datasets of glioblastomas and identified 2 robust immune subtypes based on lncRNA methylation features. The immune characteristics of glioma subtypes were compared. Furthermore, immune-related lncRNAs were identified and their relationships with immune evasion were evaluated. Results: Glioma immunophenotypes exhibited distinct immune-related characteristics as well as clinical and epigenetic features. 149 epigenetically regulated (ER) lncRNAs were recognized that possessed inverse variation in epigenetic and transcriptional levels between glioma subtypes. Immune-related lncRNAs were further identified through the investigation of their correlation with immune cell infiltrations and immune-related pathways. In particular, the 'Hot' glioma subtype with higher immunoactivity while a worse survival outcome was found to character immune evasion features. We finally prioritized candidate ER lncRNAs associated with immune evasion markers and response to glioma immunotherapy. Among them, CD109-AS1 and LINC02447 were validated as novel immunoevasive biomarkers for glioma through in vitro experiments. Conclusion: In summary, our study systematically reveals the crosstalk among DNA methylation, lncRNA, and immune regulation in glioblastomas, and will facilitate the development of epigenetic immunotherapy approaches.

Enhanced insulin-regulated phagocytic activities support extreme health span and longevity in multiple populations.

The immune system plays a central role in many processes of age-related disorders and it remains unclear if the innate immune system may play roles in shaping extreme longevity. By an integrated analysis with multiple bulk and single cell transcriptomic, so as DNA methylomic datasets of white blood cells, a previously unappreciated yet commonly activated status of the innate monocyte phagocytic activities is identified. Detailed analyses revealed that the life cycle of these monocytes is enhanced and primed to a M2-like macrophage phenotype. Functional characterization unexpectedly revealed an insulin-driven immunometabolic network which supports multiple aspects of phagocytosis. Such reprogramming is associated to a skewed trend of DNA demethylation at the promoter regions of multiple phagocytic genes, so as a direct transcriptional effect induced by nuclear-localized insulin receptor. Together, these highlighted that preservation of insulin sensitivity is a key to healthy lifespan and extended longevity, via boosting the function of innate immune system in advanced ages.

Identification and functional analysis of N6-methyladenine (m6 A)-related lncRNA across 33 cancer types.

BACKGROUND: N6-methyladenosine (m6 A) plays an essential role in tumorigenesis and cancer progression. Long noncoding RNAs (lncRNAs) are discovered to be important targets of m6 A modification, and they play fundamental roles in diverse biological processes. However, there is still a lack of knowledge with regards to the association between m6 A and lncRNAs in human tumors. METHODS: The relationship between lncRNAs and 21 m6 A regulators was comprehensively explored, through the integration of multi-omics data from M6A2Target, m6A-Atlas, and TCGA (The Cancer Genome Atlas). In order to explore the potential roles of m6A-related lncRNAs in human tumors, three applicable methods were introduced, which include the construction of ceRNA networks, drug sensitivity estimation, and survival analysis. RESULTS: A substantial number of positive correlation events across 33 cancer types were found. Moreover, cancer-specific lncRNAs were associated with tissue specificity, and cancer-common lncRNAs were conserved in cancer-related biological function. In particular, the m6 A-related lncRNA FGD5-AS1 was found to be associated with cancer treatment, through its influence on cisplatin resistance in breast cancer patients. Finally, a user-friendly interface Lnc2m6A, which is enriched with various browsing sections resource for the exhibition of relationships and putative biogenesis between lncRNAs and m6 A modifications, is offered in http://hainmu-biobigdata.com/Lnc2m6A. CONCLUSIONS: In summary, the results from this paper will provide a valuable resource that guides both mechanistic and therapeutic roles of m6 A-related lncRNAs in human tumors.

The synergistic interaction landscape of chromatin regulators reveals their epigenetic regulation mechanisms across five cancer cell lines.

Chromatin regulators (CRs) regulate the gene transcription process through combinatorial patterns, which currently remain obscure for pan-cancer. This study identified the interaction of CRs and constructed CR-CR interaction networks across five tumor cell lines. The global interaction analysis revealed that CRs tend to function in synergistically. In addition, common and specific CRs in interaction networks were identified, and the epigenetic processes of these CRs in regulating gene transcription were analyzed. Common CRs have conserved binding sites but cooperate with different partners in multiple tumor cell lines. They also participate in gene transcription regulation, through mediation of different histone modifications (HMs). Specific CRs, ATF2 and PRDM10 were found to distinguish liver cancer samples with different prognosis. PRDM10 participates in gene transcription regulation, by exertion of influence on the DNA methylation level of liver cancer. Through analysis of the edges in the CR-CR interaction networks, it was found EP300-TAF1 has genome-wide distinct signaling patterns, which exhibit different effects on downstream targets. This analysis provides novel insights for the understanding of synergistic mechanism of CRs function, as controllers of gene transcription across cancer types.

Pediatric Pan-Central Nervous System Tumor Methylome Analyses Reveal Immune-Related LncRNAs.

Pediatric central nervous system (CNS) tumors are the second most common cancer diagnosis among children. Long noncoding RNAs (lncRNAs) emerge as critical regulators of gene expression, and they play fundamental roles in immune regulation. However, knowledge on epigenetic changes in lncRNAs in diverse types of pediatric CNS tumors is lacking. Here, we integrated the DNA methylation profiles of 2,257 pediatric CNS tumors across 61 subtypes with lncRNA annotations and presented the epigenetically regulated landscape of lncRNAs. We revealed the prevalent lncRNA methylation heterogeneity across pediatric pan-CNS tumors. Based on lncRNA methylation profiles, we refined 14 lncRNA methylation clusters with distinct immune microenvironment patterns. Moreover, we found that lncRNA methylations were significantly correlated with immune cell infiltrations in diverse tumor subtypes. Immune-related lncRNAs were further identified by investigating their correlation with immune cell infiltrations and potentially regulated target genes. LncRNA with methylation perturbations potentially regulate the genes in immune-related pathways. We finally identified several candidate immune-related lncRNA biomarkers (i.e., SSTR5-AS1, CNTN4-AS1, and OSTM1-AS1) in pediatric cancer for further functional validation. In summary, our study represents a comprehensive repertoire of epigenetically regulated immune-related lncRNAs in pediatric pan-CNS tumors, and will facilitate the development of immunotherapeutic targets.

Comprehensive Analysis of the Carcinogenic Process, Tumor Microenvironment, and Drug Response in HPV-Positive Cancers.

Human papillomavirus (HPV) is a common virus, and about 5% of all cancers worldwide is caused by persistent high-risk HPV infections. Here, we reported a comprehensive analysis of the molecular features for HPV-related cancer types using TCGA (The Cancer Genome Atlas) data with HPV status. We found that the HPV-positive cancer patients had a unique oncogenic process, tumor microenvironment, and drug response compared with HPV-negative patients. In addition, HPV improved overall survival for the four cancer types, namely, cervical squamous cell carcinoma (CESC), head and neck squamous cell carcinoma (HNSC), stomach adenocarcinoma (STAD), and uterine corpus endometrial carcinoma (UCEC). The stronger activity of cell-cycle pathways and lower driver gene mutation rates were observed in HPV-positive patients, which implied the different carcinogenic processes between HPV-positive and HPV-negative groups. The increased activities of immune cells and differences in metabolic pathways helped explain the heterogeneity of prognosis between the two groups. Furthermore, we constructed HPV prediction models for different cancers by the virus infection score (VIS) which was linearly correlated with HPV load and found that VIS was associated with drug response. Altogether, our study reveals that HPV-positive cancer patients have unique molecular characteristics which help the development of precision medicine in HPV-positive cancers.

Prognostic Implications and Immune Infiltration Characteristics of Chromosomal Instability-Related Dysregulated CeRNA in Lung Adenocarcinoma.

An accumulating body of research indicates that long-noncoding RNAs (lncRNAs) regulate the target genes and act as competitive endogenous RNAs (ceRNAs) playing an indispensable role in lung adenocarcinoma (LUAD). LUAD is frequently accompanied by the feature of chromosomal instability (CIN); however, CIN-related ceRNAs have not been investigated yet. We systematically analyzed and integrated CIN-related dysregulated ceRNAs characteristics in LUAD samples for the first time. In TCGA LUAD cohort, CIN in tumor samples was significantly higher than that in those of adjacent, and patients with high CIN risk tended to have worse clinical outcomes. We constructed a double-weighted CIN-related dysregulated ceRNA network, in which edge weight and node weight represented the disorder extent of ceRNA and the correlation of RNA expression level and prognosis, respectively. After module mining and analysis, a potential prognostic biomarker composed of 12 RNAs (8 mRNAs and 4 lncRNAs) named CIN-related dysregulated ceRNAs (CRDC) was obtained. The CRDC risk score had a positive relation with clinical stage and CIN, and patients with high CRDC risk scores exhibited poor prognosis. Moreover, CRDC tended to be an independent risk factor with high robustness to overcome the effect of multicollinearity among other explanatory variables for disease-specific survival (DSS) in TCGA and two GEO cohorts. The result of functional analysis indicated that CRDC was involved in multiple cancer progresses, especially immune-related pathways. The patients with lower CRDC risk had higher B cell, T cell CD4+, T cell CD8+, neutrophil, macrophage, and myeloid dendritic cell infiltration than the patients with higher CRDC risk. Meanwhile, patients with lower CRDC risk could get more benefits from immunological therapy. The results suggested that the CRDC could be a potential prognostic biomarker and an immunotherapy predictor for lung adenocarcinoma.

Pars plana vitrectomy assisted by intravitreal injection of conbercept enhances the therapeutic effect and quality of life in patients with severe proliferative diabetic retinopathy.

OBJECTIVE: To explore the application value of intravitreal injection of Conbercept (IVC)-assisted pars plana vitrectomy (PPV) in patients with severe proliferative diabetic retinopathy (PDR). METHODS: Forty-eight patients with severe PDR who underwent surgical treatment in Chongqing Aier Eye Hospital between October 2019 and June 2021 were retrospectively enrolled, and their clinical data were analyzed. Of them, 22 patients receiving PPV alone were assigned to the PPV group, and the remaining 26 patients treated with IVC-assisted PPV were included in the PPV+IVC group. The intra-operative indicators, postoperative complication rate, visual acuity (VA) improvement, and postoperative quality of life (QoL) were compared between the two groups. The levels of vascular endothelial growth factor (VEGF), placental growth factor (PIGF), and basic fibroblast growth factor (bFGF) in aqueous humor (AH) as well as serum contents of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were determined by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: Compared to the PPV group, the operation time of the PPV+IVC group was significantly shorter, and the incidence of severe intraoperative blood loss (IBL), bipolar electrocoagulation hemostasis, iatrogenic retinal breaks (IRBs), postoperative silicone oil tamponade (SOT), and overall complications were significantly reduced. After surgery, the central macular thickness (CMT) was lower and the best corrected visual acuity (BCVA) assessed by the standard visual acuity chart and VA were significantly more improved in the PPV+IVC group versus the PPV group. After the use of Conbercept, the AH levels of VEGF, PIGF, and bFGF in the PPV+IVC group decreased and were significantly lower than those in the PPV group. The PPV+IVC group also showed lower serum levels of TNF-α, IL-6, and IL-1ß than the PPV group. CONCLUSIONS: IVC-assisted PPV can effectively reduce the difficulty of surgical treatment for PDR, better improve the postoperative VA of patients, and reduce inflammation with fewer complications.

A Pan-Cancer Analysis of Cystatin E/M Reveals Its Dual Functional Effects and Positive Regulation of Epithelial Cell in Human Tumors.

Cystatin E/M (CST6), a representative cysteine protease inhibitor, plays both tumor-promoting and tumor-suppressing functions and is pursued as an epigenetically therapeutic target in special cancer types. However, a comprehensive and systematic analysis for CST6 in pan-cancer level is still lacking. In the present study, we explored the expression pattern of CST6 in multiple cancer types across ∼10,000 samples from TCGA (The Cancer Genome Atlas) and ∼8,000 samples from MMDs (Merged Microarray-acquired Datasets). We found that the dynamic expression alteration of CST6 was consistent with dual function in different types of cancer. In addition, we observed that the expression of CST6 was globally regulated by the DNA methylation in its promoter region. CST6 expression was positively correlated with the epithelial cell infiltration involved in epithelial-to-mesenchymal transition (EMT) and proliferation. The relationship between CST6 and tumor microenvironment was also explored. In particular, we found that CST6 serves a protective function in the process of melanoma metastasis. Finally, the clinical association analysis further revealed the dual function of CST6 in cancer, and a combination of the epithelial cell infiltration and CST6 expression could predict the prognosis for SKCM patients. In summary, this first CST6 pan-cancer study improves the understanding of the dual functional effects on CST6 in different types of human cancer.

Whole Blood Transcriptome Analysis Reveals the Correlation between Specific Immune Cells and Septicemic Melioidosis.

Melioidosis is a serious infectious disease caused by the environmental Gram-negative bacillus Burkholderia pseudomallei. It has been shown that the host immune system, mainly comprising various types of immune cells, fights against the disease. The present study was to specify correlation between septicemic melioidosis and the levels of multiple immune cells. First, the genes with differential expression patterns between patients with septicemic melioidosis (B. pseudomallei) and health donors (control/healthy) were identified. These genes being related to cytokine binding, cell adhesion molecule binding, and MHC relevant proteins may influence immune response. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed 23 enriched immune response pathways. We further leveraged the microarray data to investigate the relationship between immune response and septicemic melioidosis, using the CIBERSORT analysis. Comparison of the percentages of 22 immune cell types in B. pseudomallei vs. control/healthy revealed that those of CD4 memory resting cells, CD8+ T cells, B memory cells, and CD4 memory activated cells were low, whereas those of M0 macrophages, neutrophils, and gamma delta T cells were high. The multivariate logistic regression analysis further revealed that CD8+ T cells, M0 macrophages, neutrophils, and naive CD4+ cells were strongly associated with the onset of septicemic melioidosis, and M2 macrophages and neutrophils were associated with the survival in septicemic melioidosis. Taken together, these data point to a complex role of immune cells on the development and progression of melioidosis.

The Functional Characterization of Epigenetically Related lncRNAs Involved in Dysregulated CeRNA-CeRNA Networks Across Eight Cancer Types.

Numerous studies have demonstrated that lncRNAs could compete with other RNAs to bind miRNAs, as competing endogenous RNAs (ceRNAs), to regulate each other. On the other hand, ceRNAs were found to be recurrently dysregulated in cancer status. However, limited studies considered the upstream epigenetic regulatory factors that disrupted the normal competing mechanism. In the present study, we constructed the lncRNA-associated dysregulated ceRNA networks across eight cancer types. lncRNAs in the individual dysregulated network and pan-cancer core dysregulated ceRNA subnetwork were found to play more important roles than mRNAs. Integrating lncRNA methylation profiles, we identified 49 epigenetically related (ER) lncRNAs involved in the dysregulated ceRNA networks, including 18 epigenetically activated (EA) lncRNAs, 18 epigenetically silenced (ES) lncRNAs, and 13 rewired ER lncRNAs across eight cancer types. Furthermore, we evaluated the epigenetic regulating patterns of these lncRNAs and screened nine pan-cancer ER lncRNAs (six EA and three ES lncRNAs). The nine lncRNAs were found to regulate the cancer hallmarks by competing with mRNAs. Moreover, we found that integrating the expression and methylation profiles of the nine lncRNAs could predict cancer incidence in eight cancer types robustly and the cancer outcome of several cancer types. These results provide an improved understanding of methylation regulation to ceRNA and offer novel potential molecular therapeutic targets for the diagnosis and prognosis across different cancer types.

Quantitative Evaluation of Rotator Cuff Tears Based on Non-linear Statistical Analysis of Ultrasound Radiofrequency Signals.

There is increasing clinical requirement for early and accurate ultrasound diagnosis of rotator cuff tears (RCTs). A method based on non-linear statistical analysis was proposed for the detection of RCTs using ultrasound radiofrequency (RF) signals. One hundred fifty-two patients with shoulder pain were first examined with ultrasound and then diagnosed with magnetic resonance imaging (MRI) as the ground truth. By comparison of the region of interest (ROI) with a part of the supraspinatus with no pathologic change part in the same RF signal frame, the relative Pks value (viz., rPks value) was evaluated to quantify the pathophysiologic changes. The results indicated that the rPks values of all RCTs are <0.7, and the accuracy, sensitivity and specificity of the proposed method can reach 97.5%, 100% and 91.4%, respectively. This computer-aided method was found to perform better diagnostic than the results reported by an experienced radiologist (accuracy = 75.7%, sensitivity = 72.6%, and specificity = 85.7%). The high sensitivity advantage of this method indicates that the prospects for its application in the computer-aided diagnosis of RCTs are good.

Contributions of Gene Modules Regulated by Essential Noncoding RNA in Colon Adenocarcinoma Progression.

Noncoding RNAs (ncRNAs), especially microRNA (miRNA) and long noncoding RNA (lncRNA), have an impact on a variety of important biological processes during colon adenocarcinoma (COAD) progression. This includes chromatin organization, transcriptional and posttranscriptional regulation, and cell-cell signaling. The aim of this study is to identify the ncRNA-regulated modules that accompany the progression of COAD and to analyze their mechanisms, in order to screen the potential prognostic biomarkers for COAD. An integrative molecular analysis was carried out to identify the crosstalks of gene modules between different COAD stages, as well as the essential ncRNAs in the posttranscriptional regulation of these modules. 31 ncRNA regulatory modules were found to be significantly associated with overall survival in COAD patients. 17 out of the 31 modules (in which ncRNAs played essential roles) had improved the predictive ability for COAD patient survival compared to only the mRNAs of those modules, which were enriched in the core cancer hallmark pathways with closer interactions. These suggest that the ncRNAs' regulatory modules not only exhibit close relation to COAD progression but also reflect the dynamic significant crosstalk of genes in the modules to the different malignant extent of COAD.

Identifying autophagy gene-associated module biomarkers through construction and analysis of an autophagy-mediated ceRNA­ceRNA interaction network in colorectal cancer.

Autophagy is crucial in cellular homeostasis and has been implicated in the development of malignant tumors. However, the regulatory function of autophagy in cancer remains to be fully elucidated. In the present study, the autophagy-mediated competing endogenous RNA (ceRNA)­ceRNA interaction networks in colorectal cancer (CRC) were constructed by integrating systematically expression profiles of long non­coding RNAs and mRNAs. It was found that a large proportion of autophagy genes were inclined to target hub nodes, including a fraction of autophagy genes, by comparing with other genes within ceRNA networks, and showed preferential interaction with themselves. The present study also revealed that autophagy genes may be used as prognostic markers for cancer therapy. A risk score model based on multivariable Cox regression analysis was then used to capture novel biomarkers in connection with lncRNA for the prognosis of CRC. These biomarkers were confirmed in the test dataset and an additional independent dataset. Furthermore, the prognostic value of biomarkers is independent of conventional clinical factors. These results provide improved understanding of autophagy-mediated ceRNA regulatory mechanisms in CRC and provide novel potential molecular therapeutic targets for the diagnosis and treatment of CRC.

Detection of dysregulated competing endogenous RNA modules associated with clear cell kidney carcinoma.

Recent evidence has suggested that competitive endogenous RNAs (ceRNAs) are important regulatory molecules in clear cell kidney carcinoma (KIRC) and their dysregulation may contribute to cancer pathogenesis. However, the critical roles of dysregulated ceRNAs in KIRC remain unknown. In the present study, a KIRC dysregulated ceRNA­ceRNA network (KDCCNet) was constructed based on the 'ceRNA hypothesis' by integrating microRNA regulation and expression profiles in cancerous and normal tissues. Two dysregulated patterns of ceRNAs interaction (gain and loss) exist in KDCCNet. The two modules, which are 95% loss interactions and 97% gain interactions, were demonstrated to be able to distinguish normal samples from cancer samples. Two long non­coding (lnc)­RNAs (glucuronidase ß pseudogene 11 and LIFR antisense RNA 1) demonstrated significant associations with KIRC prognosis. The present study of the KDCCNet revealed a novel biological mechanism for KIRC and provides novel lncRNAs as candidate prognostic biomarkers.