The Epidemiological Characteristics of Pulmonary Tuberculosis - Kashgar Prefecture, Xinjiang Uygur Autonomous Region, China, 2011-2020.

Introduction: National Notifiable Disease Reporting System (NNDRS) plays an important role in the early detection and control of tuberculosis (TB) in China. This study analyzed the epidemiological characteristics of pulmonary tuberculosis (PTB) in Kashgar Prefecture, Xinjiang Uygur Autnomous Region, China from 2011 to 2020 to provide a scientific basis for developing TB control strategies and measures in Kashgar.Methods:The data were collected from the NNDRS, which included the geographical distribution, age, sex, occupation, and pathogenic classification of reported PTB cases in 12 counties/cities of Kashgar Prefecture from 2011 to 2020. Descriptive statistics were used to describe the characteristic of PTB epidemic in Kashgar.Results: There were 189,416 PTB cases reported during 2011-2020, with a mean annual PTB case notification rate (CNR) of 451.29/100,000. A rising trend in the rate of reported PTB between 2011 and 2017 (χ 2 trend=26.09, P<0.01) and a declining trend between 2018 and 2020 (χ 2 trend=314.44, P<0.01) were observed. The months with the highest reported number of PTB cases were March to May and November to December. The mean annual rate of reported PTB was 451.88/100,000 for males and 450.67/100,000 for females. In addition, 19.76% of patients were bacteriologically-confirmed (Bac+) cases (37,425/189,416), and the mean annual Bac+ CNR was 89.17/100,000, rising from 64.76/100,000 in 2011 to 139.12/100,000 in 2020 (χ 2 trend=74.44, P<0.01).Conclusions: The CNR of reported PTB in Kashgar showed a significant declining trend in the past three years. Males, elderly population, winter and spring, and farmers as an occupation were the main factors associated with high incidence of tuberculosis in Kashgar. Targeted prevention and treatment of TB should be strengthened in key groups in this region.

EXPath 2.0: An Updated Database for Integrating High-Throughput Gene Expression Data with Biological Pathways.

Co-expressed genes tend to have regulatory relationships and participate in similar biological processes. Construction of gene correlation networks from microarray or RNA-seq expression data has been widely applied to study transcriptional regulatory mechanisms and metabolic pathways under specific conditions. Furthermore, since transcription factors (TFs) are critical regulators of gene expression, it is worth investigating TFs on the promoters of co-expressed genes. Although co-expressed genes and their related metabolic pathways can be easily identified from previous resources, such as EXPath and EXPath Tool, this information is not simultaneously available to identify their regulatory TFs. EXPath 2.0 is an updated database for the investigation of regulatory mechanisms in various plant metabolic pathways with 1,881 microarray and 978 RNA-seq samples. There are six significant improvements in EXPath 2.0: (i) the number of species has been extended from three to six to include Arabidopsis, rice, maize, Medicago, soybean and tomato; (ii) gene expression at various developmental stages have been added; (iii) construction of correlation networks according to a group of genes is available; (iv) hierarchical figures of the enriched Gene Ontology (GO) terms are accessible; (v) promoter analysis of genes in a metabolic pathway or correlation network is provided; and (vi) user's gene expression data can be uploaded and analyzed. Thus, EXPath 2.0 is an updated platform for investigating gene expression profiles and metabolic pathways under specific conditions. It facilitates users to access the regulatory mechanisms of plant biological processes. The new version is available at http://EXPath.itps.ncku.edu.tw.

A Long Intergenic Non-coding RNA, LINC01426, Promotes Cancer Progression via AZGP1 and Predicts Poor Prognosis in Patients with LUAD.

Various long non-coding RNAs (lncRNAs) are closely associated with lung adenocarcinoma (LUAD), playing oncogenic or anti-oncogenic roles in tumorigenesis and progression. Herein, we report a novel lncRNA-long intergenic non-protein coding RNA 1426 (LINC01426)-that has not yet been characterized in LUAD. We note that LINC01426 expression was markedly upregulated in LUAD tissues, and that functional assays verified that LINC01426 knockdown markedly inhibited cell proliferation, migration, and invasion in vitro. Xenografts derived from A549 cells knocked down of LINC01426 had evidently lower tumor weights and smaller tumor volumes. Our study also found that LINC01426 bound to hsa-miR-30b-3p as a competitive endogenous RNA in LUAD. Moreover, LINC01426 affected LUAD wound healing by interacting and combining with AZGP1, and LINC01426 expression was significantly associated with tumor-node-metastasis (TNM) staging and prognosis in patients with LUAD. To summarize, our study elucidates the oncogenic roles of LINC01426 in LUAD tumorigenesis and progression. We think that LINC01426 can serve as a potential diagnostic biomarker and therapeutic target in patients with LUAD.

PlantPAN3.0: a new and updated resource for reconstructing transcriptional regulatory networks from ChIP-seq experiments in plants.

The Plant Promoter Analysis Navigator (PlantPAN; http://PlantPAN.itps.ncku.edu.tw/) is an effective resource for predicting regulatory elements and reconstructing transcriptional regulatory networks for plant genes. In this release (PlantPAN 3.0), 17 230 TFs were collected from 78 plant species. To explore regulatory landscapes, genomic locations of TFBSs have been captured from 662 public ChIP-seq samples using standard data processing. A total of 1 233 999 regulatory linkages were identified from 99 regulatory factors (TFs, histones and other DNA-binding proteins) and their target genes across seven species. Additionally, this new version added 2449 matrices extracted from ChIP-seq peaks for cis-regulatory element prediction. In addition to integrated ChIP-seq data, four major improvements were provided for more comprehensive information of TF binding events, including (i) 1107 experimentally verified TF matrices from the literature, (ii) gene regulation network comparison between two species, (iii) 3D structures of TFs and TF-DNA complexes and (iv) condition-specific co-expression networks of TFs and their target genes extended to four species. The PlantPAN 3.0 can not only be efficiently used to investigate critical cis- and trans-regulatory elements in plant promoters, but also to reconstruct high-confidence relationships among TF-targets under specific conditions.

microRPM: a microRNA prediction model based only on plant small RNA sequencing data.

Motivation: MicroRNAs (miRNAs) are endogenous non-coding small RNAs (of about 22 nucleotides), which play an important role in the post-transcriptional regulation of gene expression via either mRNA cleavage or translation inhibition. Several machine learning-based approaches have been developed to identify novel miRNAs from next generation sequencing (NGS) data. Typically, precursor/genomic sequences are required as references for most methods. However, the non-availability of genomic sequences is often a limitation in miRNA discovery in non-model plants. A systematic approach to determine novel miRNAs without reference sequences is thus necessary. Results: In this study, an effective method was developed to identify miRNAs from non-model plants based only on NGS datasets. The miRNA prediction model was trained with several duplex structure-related features of mature miRNAs and their passenger strands using a support vector machine algorithm. The accuracy of the independent test reached 96.61% and 93.04% for dicots (Arabidopsis) and monocots (rice), respectively. Furthermore, true small RNA sequencing data from orchids was tested in this study. Twenty-one predicted orchid miRNAs were selected and experimentally validated. Significantly, 18 of them were confirmed in the qRT-PCR experiment. This novel approach was also compiled as a user-friendly program called microRPM (miRNA Prediction Model). Availability and implementation: This resource is freely available at http://microRPM.itps.ncku.edu.tw. Contact: nslin@sinica.edu.tw or sarah321@mail.ncku.edu.tw. Supplementary information: Supplementary data are available at Bioinformatics online.

EXPath tool-a system for comprehensively analyzing regulatory pathways and coexpression networks from high-throughput transcriptome data.

Next generation sequencing (NGS) has become the mainstream approach for monitoring gene expression levels in parallel with various experimental treatments. Unfortunately, there is no systematical webserver to comprehensively perform further analysis based on the huge amount of preliminary data that is obtained after finishing the process of gene annotation. Therefore, a user-friendly and effective system is required to mine important genes and regulatory pathways under specific conditions from high-throughput transcriptome data. EXPath Tool (available at: http://expathtool.itps.ncku.edu.tw/) was developed for the pathway annotation and comparative analysis of user-customized gene expression profiles derived from microarray or NGS platforms under various conditions to infer metabolic pathways for all organisms in the KEGG database. EXPath Tool contains several functions: access the gene expression patterns and the candidates of co-expression genes; dissect differentially expressed genes (DEGs) between two conditions (DEGs search), functional grouping with pathway and GO (Pathway/GO enrichment analysis), and correlation networks (co-expression analysis), and view the expression patterns of genes involved in specific pathways to infer the effects of the treatment. Additionally, the effectively of EXPath Tool has been performed by a case study on IAA-responsive genes. The results demonstrated that critical hub genes under IAA treatment could be efficiently identified.

Overexpression of the metastasis-associated gene MTA3 correlates with tumor progression and poor prognosis in hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers in the world. However, there remains a lack of effective diagnostic and treatment markers. We aimed to explore metastasis-associated protein 3 (MTA3) expression and function in HCC and its relationship with clinicopathological factors. METHODS: We investigated the expression pattern and clinicopathological significance of MTA3 in 90 patients with HCC via immunohistochemistry and explored MTA3 function via gene knockdown of MTA3. RESULTS: MTA3 was overexpressed in HCC cell nuclei and downregulated in HCC cell cytoplasm. The former finding correlated with metastasis (P = 0.010) and poor prognosis (P = 0.018). In addition, deleting MTA3 inhibited HCC cell growth, invasion, and metastasis in vitro, as shown in the colony formation, migration, and wound-healing assays. CONCLUSIONS: These results indicate that MTA3 is an oncogene of HCC, predicts poor prognosis of HCC, and may be a future marker of HCC treatment.

The long noncoding RNAs PVT1 and uc002mbe.2 in sera provide a new supplementary method for hepatocellular carcinoma diagnosis.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver in adults worldwide. Several studies have demonstrated that long noncoding RNAs (lncRNAs) are involved in the development of various types of cancer, including HCC. These findings prompted us to examine the detectability of lncRNAs in blood samples from patients with HCC. In this study, we explored the expression levels of 31 cancer-related lncRNAs in sera from 71 HCC patients and 64 healthy individuals by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). We found that 25 lncRNAs could be detected in the serum and that 7 had significantly different expression levels. A 2-lncRNA signature (PVT1 and uc002mbe.2) identified by stepwise regression showed potential as a diagnostic marker for HCC. The area under the receiver operating characteristic (ROC) curve was 0.764 (95% CI: 0.684-0.833). The sensitivity and specificity values of this serum 2-lncRNA signature for distinguishing HCC patients from the healthy group were 60.56% and 90.62%, respectively. The diagnostic ability of the combination of the serum 2-lncRNA signature with alpha-fetoprotein (AFP) was much greater than that of AFP alone. The expression levels of the 2 lncRNAs were associated with clinical parameters including tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and serum bilirubin.

Comprehensive Circular RNA Profiling Reveals That hsa_circ_0005075, a New Circular RNA Biomarker, Is Involved in Hepatocellular Crcinoma Development.

There is increasing evidence that circular RNAs (circRNAs) are involved in cancer development; however, their role in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to determine the circRNA expression profile in HCC, and investigate relevant mechanisms for cancer progression. The global circRNA expression profile between HCC (n = 3) and adjacent normal liver (n = 3) tissue was significantly different. Three circRNAs (hsa_circ_0000520, hsa_circ_0005075, and hsa_circ_0066444) showed significantly different expression levels in HCC tissues, which were further validated in 60 matched tissue samples using real-time qRT-PCR. Only hsa_circ_0005075 exhibited significant difference in expression (P <0.001) between HCC and normal tissues. Hsa_circ_0005075 expression correlated with HCC tumor size (P = 0.042), and showed good diagnostic potential (AUROC = 0.94). Finally, we constructed a network of hsa_circ_0005075-targeted miRNA-gene interactions, including miR-23b-5p, miR-93-3p, miR-581, miR-23a-5p, and their corresponding mRNAs. Gene oncology analysis revealed that hsa_circ_0005075 could participate in cell adhesion during HCC development. In summary, we identified hsa_circ_0005075 as a potential HCC biomarker; however, further studies are required to confirm the role of this circRNA, and others, in HCC development.

Systematic tracking of dysregulated modules identifies disrupted pathways in narcolepsy.

OBJECTIVE: The objective of this work is to identify disrupted pathways in narcolepsy according to systematically tracking the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. Here, we performed systematic identification and comparison of modules across normal and narcolepsy conditions by integrating PPI and gene-expression data. METHODS: Firstly, normal and narcolepsy PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, modules in PPI network were explored by clique-merging algorithm and we identified altered modules using a maximum weight bipartite matching and in non-increasing order. Finally, pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test to illuminate the biological pathways in narcolepsy. RESULTS: Our analyses revealed that 235 altered modules were identified by comparing modules in normal and narcolepsy PPI network. Pathway functional enrichment analysis of disrupted module genes showed 59 disrupted pathways within threshold P < 0.001. The most significant five disrupted pathways were: oxidative phosphorylation, T cell receptor signaling pathway, cell cycle, Alzheimer's disease and focal adhesion. CONCLUSIONS: We successfully identified disrupted pathways and these pathways might be potential biological processes for treatment and etiology mechanism in narcolepsy.

The comparison of outcomes between hypofractionated and conventional 3D-CRT regimens used in combination with TACE as first-line treatment of advanced hepatocellular carcinoma.

Treatment of primary hepatocellular carcinoma (HCC) with transcatheter hepatic arterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (3D-CRT) achieves good short-term but poor long-term survival. We retrospectively assessed whether outcomes differ between hypofractionated and conventional 3D-CRT regimens. Patients were treated in our institution between June 2005 and October 2009. All patients received two cycles of TACE followed by either hypofractionated 3D-CRT (6-8 Gy fractions for 3-4 weeks to 48-64 Gy) or conventional 3D-CRT (2 Gy fractions for 6-7 weeks to 60-70 Gy) 4 weeks later. We assessed data from 110 patients (55 in each 3D-CRT group). Overall response rates were similar in the two groups. Acute adverse event rates were not significantly higher in the hypofractionated 3D-CRT group than in the conventional 3D-CRT group; two patients and one patient, respectively, died of late radiation-induced liver failure. Overall survival at 1 year was 83.6 % in the hypofractionated 3D-CRT group versus 68.8 % in the conventional 3D-CRT group (P = 0.019), and at 3 years, it was 31.7 versus 13.9 % (P = 0.004). Median survival was 27.97 versus 16.13 months (P = 0.002). Hypofractionated 3D-CRT seemed to provide better overall survival than conventional 3D-CRT regimens combined with TACE as a first-line treatment for advanced HCC.

Reproducibility of quantitative real-time PCR assay in microRNA expression profiling and comparison with microarray analysis in narcolepsy.

MicroRNAs (miRNAs) have been shown in the pathogenesis of human neurological disorders. The study aims to identify the involvement of miRNAs in the pathophysiology of narcolepsy. Here, we conducted three independent high-throughput analysis of miRNA (miRNA microarray) in peripheral blood from 20 narcolepsy patients who fulfilled the criteria compared to 20 healthy controls with validation experiment using quantitative real-time polymerase chain reaction (real-time PCR) panels. By analyzing 2805 miRNAs in peripheral blood with microarray we identified 128 miRNAs (105 high expression and 23 low expression) that were different in patients with narcolepsy in comparison with healthy control. Then we chose six high expression candidates and six low expression candidates of at least twofold difference and p value < 0.05 to validate the changes in three independent experiments in vitro using real-time PCR. The validation test showed that levels of hsa-mir-1267, hsa-miR-4309, hsa-miR-554, hsa-miR-1272, hsa-miR-4501, hsa-miR-182-3p were higher, whereas the level of hsa-miR-625-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-197-3p, hsa-miR-4522, hsa-miR-493-5p was lower in narcolepsy patients than healthy controls. The levels of 12 miRNAs differed significantly in peripheral blood from narcolepsy patients which suggested that alterations of miRNAs expression may be involved in the pathophysiology of narcolepsy.

Diagnostic utility of N-terminal-proBNP in differentiating acute pulmonary embolism from heart failure in patients with acute dyspnea.

BACKGROUND: The plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level is frequently elevated in dyspnoeic patients and increasingly used in emergency departments to assess the cause of acute dyspnea. In this study we prospectively tested NT-proBNP levels in patients with congestive heart failure (CHF) and/or acute pulmonary embolism (APE) and determined the utility of NT-proBNP for discriminating APE from CHF. METHODS: A cohort of 177 dyspnoeic patients with a diagnosis of APE and/or CHF was prospectively studied between June 2010 and March 2013. NT-proBNP was measured by the electrochemiluminescence immunoassay (ECLIA). All patients were evaluated with transthoracic echocardiography (TTE). APE was diagnosed in the presence of thrombi signs in the pulmonary arteries with computed tomographic pulmonary angiography (CTPA) or a high-probability lung ventilation/perfusion scan. Risk stratification was based on the evaluation on admission according to the ESC guidelines from 2008. The diagnosis of CHF was based on the guidelines of the American College of Cardiology/American Heart Association and the European Society of Cardiology. Two physicians independently reviewed the records to determine the final diagnosis. RESULTS: Fifty-nine patients met the criteria for dyspnea caused by APE, and 113 patients were diagnosed with CHF. Most of the APE patients (41, 69.5%) were intermediate-risk. The symptoms and signs, such as orthopnea, paroxysmal nocturnal dyspnea and rales in the lungs, were more common in patients with CHF than in patients with APE (P < 0.01). Median NT-proBNP was significantly lower in patients with APE compared to those in patients with CHF (2 855.9 pg/ml vs. 6 911.4 pg/ml, P < 0.01). We constructed the receiver operating characteristics (ROC) curve in predicting the diagnosis of APE. At a cut point = 1 582.750 pg/ml, NT-proBNP provided a specificity of 93% and a true positive rate (sensitivity) of 17% for the diagnosis. At a cut point = 3 390.000 pg/ml, NT-proBNP had a specificity of 83% and a sensitivity of 84% for the diagnosis of APE. At a cut point = 6 486.500 pg/ml, they were 54% and 93% respectively. CONCLUSIONS: NT-proBNP can assist in excluding CHF patients from those admitted to the emergency department with acute dyspnea and identifying patients with a high probability of APE, which would reduce the missed diagnosis of APE. Larger studies are necessary to validate these findings.