eccDB: a comprehensive repository for eccDNA-mediated chromatin contacts in multi-species.

SUMMARY: We developed the eccDB database to integrate available resources for extrachromosomal circular DNA (eccDNA) data. eccDB is a comprehensive repository for storing, browsing, searching, and analyzing eccDNAs from multispecies. The database provides regulatory and epigenetic information on eccDNAs, with a focus on analyzing intrachromosomal and interchromosomal interactions to predict their transcriptional regulatory functions. Moreover, eccDB identifies eccDNAs from unknown DNA sequences and analyzes the functional and evolutionary relationships of eccDNAs among different species. Overall, eccDB offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher the molecular regulatory mechanisms of eccDNAs. AVAILABILITY AND IMPLEMENTATION: eccDB is freely available at http://www.xiejjlab.bio/eccDB.

Relativistic baryonic jets from an ultraluminous supersoft X-ray source.

The formation of relativistic jets by an accreting compact object is one of the fundamental mysteries of astrophysics. Although the theory is poorly understood, observations of relativistic jets from systems known as microquasars (compact binary stars) have led to a well established phenomenology. Relativistic jets are not expected to be produced by sources with soft or supersoft X-ray spectra, although two such systems are known to produce relatively low-velocity bipolar outflows. Here we report the optical spectra of an ultraluminous supersoft X-ray source (ULS) in the nearby galaxy M81 (M81 ULS-1; refs 9, 10). Unexpectedly, the spectra show blueshifted, broad Hα emission lines, characteristic of baryonic jets with relativistic speeds. These time-variable emission lines have projected velocities of about 17 per cent of the speed of light, and seem to be similar to those from the prototype microquasar SS 433 (refs 11, 12). Such relativistic jets are not expected to be launched from white dwarfs, and an origin from a black hole or a neutron star is hard to reconcile with the persistence of M81 ULS-1's soft X-rays. Thus the unexpected presence of relativistic jets in a ULS challenges canonical theories of jet formation, but might be explained by a long-speculated, supercritically accreting black hole with optically thick outflows.

CNIT: a fast and accurate web tool for identifying protein-coding and long non-coding transcripts based on intrinsic sequence composition.

As more and more high-throughput data has been produced by next-generation sequencing, it is still a challenge to classify RNA transcripts into protein-coding or non-coding, especially for poorly annotated species. We upgraded our original coding potential calculator, CNCI (Coding-Non-Coding Index), to CNIT (Coding-Non-Coding Identifying Tool), which provides faster and more accurate evaluation of the coding ability of RNA transcripts. CNIT runs âˆ¼200 times faster than CNCI and exhibits more accuracy compared with CNCI (0.98 versus 0.94 for human, 0.95 versus 0.93 for mouse, 0.93 versus 0.92 for zebrafish, 0.93 versus 0.92 for fruit fly, 0.92 versus 0.88 for worm, and 0.98 versus 0.85 for Arabidopsis transcripts). Moreover, the AUC values of 11 animal species and 27 plant species showed that CNIT was capable of obtaining relatively accurate identification results for almost all eukaryotic transcripts. In addition, a mobile-friendly web server is now freely available at http://cnit.noncode.org/CNIT.

SEanalysis: a web tool for super-enhancer associated regulatory analysis.

Super-enhancers (SEs) have prominent roles in biological and pathological processes through their unique transcriptional regulatory capability. To date, several SE databases have been developed by us and others. However, these existing databases do not provide downstream or upstream regulatory analyses of SEs. Pathways, transcription factors (TFs), SEs, and SE-associated genes form complex regulatory networks. Therefore, we designed a novel web server, SEanalysis, which provides comprehensive SE-associated regulatory network analyses. SEanalysis characterizes SE-associated genes, TFs binding to target SEs, and their upstream pathways. The current version of SEanalysis contains more than 330 000 SEs from more than 540 types of cells/tissues, 5042 TF ChIP-seq data generated from these cells/tissues, DNA-binding sequence motifs for ∼700 human TFs and 2880 pathways from 10 databases. SEanalysis supports searching by either SEs, samples, TFs, pathways or genes. The complex regulatory networks formed by these factors can be interactively visualized. In addition, we developed a customizable genome browser containing >6000 customizable tracks for visualization. The server is freely available at http://licpathway.net/SEanalysis.

A P53-related microRNA model for predicting the prognosis of hepatocellular carcinoma patients.

Studies have shown that microRNAs (miRNAs) play a vital role in tumor progression and patients' prognosis. Therefore, we aimed to construct a miRNA model for forecasting the survival of hepatocellular carcinoma (HCC) patients. The gene expression data of 433 patients with HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus public databases were remined by survival analysis and receptor manipulation characteristic curve (ROC). A prognostic model including six miRNAs (hsa-mir-26a-1-3p, hsa-mir-188-5p, hsa-mir-212-5p, hsa-mir-149-5p, hsa-mir-105-5p, and hsa-mir-132-5p) were constructed in the training dataset (TCGA, n = 333). HCC patients were stratified into a high-risk group and a low-risk group with significantly different survival (median: 2.75 vs. 8.93 years, log-rank test p < .001). Then we proved its performance of stratification in another independent dataset (GSE116182, median: 2.55 vs 6.96 years, log-rank test p = .008). Cox regression analysis showed that the prognostic model was an independent prognostic indicator for HCC patients. Then time-dependent ROC analyses were performed to test the prognostic ability of the model with that of TNM staging, we found the model had a better performance, especially at 5 years (AUC = 0.76). Functional prediction showed that the genes targeted by the six prognostic miRNAs in the prognostic model were highly expressed in the P53-related pathway. In conclusion, we constructed a prognostic miRNA model that could indicate the survival of HCC patients.

A robust two-gene signature for glioblastoma survival prediction.

Glioblastoma multiforme (GBM) is a highly malignant brain tumor. We explored the prognostic gene signature in 443 GBM samples by systematic bioinformatics analysis, using GSE16011 with microarray expression and corresponding clinical data from Gene Expression Omnibus as the training set. Meanwhile, patients from The Chinese Glioma Genome Atlas database (CGGA) were used as the test set and The Cancer Genome Atlas database (TCGA) as the validation set. Through Cox regression analysis, Kaplan-Meier analysis, t-distributed Stochastic Neighbor Embedding algorithm, clustering, and receiver operating characteristic analysis, a two-gene signature (GRIA2 and RYR3) associated with survival was selected in the GSE16011 dataset. The GRIA2-RYR3 signature divided patients into two risk groups with significantly different survival in the GSE16011 dataset (median: 0.72, 95% confidence interval [CI]: 0.64-0.98, vs median: 0.98, 95% CI: 0.65-1.61 years, logrank test P < .001), the CGGA dataset (median: 0.84, 95% CI: 0.70-1.18, vs median: 1.21, 95% CI: 0.95-2.94 years, logrank test P = .0017), and the TCGA dataset (median: 1.03, 95% CI: 0.86-1.24, vs median: 1.23, 95% CI: 1.04-1.85 years, logrank test P = .0064), validating the predictive value of the signature. And the survival predictive potency of the signature was independent from clinicopathological prognostic features in multivariable Cox analysis. We found that after transfection of U87 cells with small interfering RNA, GRIA2 and RYR3 influenced the biological behaviors of proliferation, migration, and invasion of glioblastoma cells. In conclusion, the two-gene signature was a robust prognostic model to predict GBM survival.

The interaction of lncRNA EZR-AS1 with SMYD3 maintains overexpression of EZR in ESCC cells.

EZR, a member of the ezrin-radixin-moesin (ERM) family, is involved in multiple aspects of cell migration and cancer. SMYD3, a histone H3-lysine 4 (H3-K4)-specific methyltransferase, regulates EZR gene transcription, but the molecular mechanisms of epigenetic regulation remain ill-defined. Here, we show that antisense lncRNA EZR-AS1 was positively correlated with EZR expression in both human esophageal squamous cell carcinoma (ESCC) tissues and cell lines. Both in vivo and in vitro studies revealed that EZR-AS1 promoted cell migration through up-regulation of EZR expression. Mechanistically, antisense lncRNA EZR-AS1 formed a complex with RNA polymerase II to activate the transcription of EZR. Moreover, EZR-AS1 could recruit SMYD3 to a binding site, present in a GC-rich region downstream of the EZR promoter, causing the binding of SMYD3 and local enrichment of H3K4me3. Finally, the interaction of EZR-AS1 with SMYD3 further enhanced EZR transcription and expression. Our findings suggest that antisense lncRNA EZR-AS1, as a member of an RNA polymerase complex and through enhanced SMYD3-dependent H3K4 methylation, plays an important role in enhancing transcription of the EZR gene to promote the mobility and invasiveness of human cancer cells.

A novel multidimensional signature predicts prognosis in hepatocellular carcinoma patients.

The abnormal expression of microRNAs (miRNAs) or protein-coding genes (PCGs) have been found to be associated with the prognosis of hepatocellular carcinoma (HCC) patients. Using bioinformatics analysis methods including Cox's proportional hazards regression analysis, the random survival forest algorithm, Kaplan-Meier, and receiver operating characteristic (ROC) curve analysis, we mined the gene expression profiles of 469 HCC patients from The Cancer Genome Atlas (n = 379) and Gene Expression Omnibus (GSE14520; n = 90) public database. We selected a signature comprising one protein-coding gene (PCG; DNA polymerase µ) and three miRNAs (hsa-miR-149-5p, hsa-miR-424-5p, hsa-miR-579-5p) with highest accurate prediction (area under the ROC curve [AUC] = 0.72; n = 189) from the training data set. The signature stratified patients into high- and low-risk groups with significantly different survival (median 27.9 vs. 55.2 months, log-rank test, p < 0.001) in the training data set, and its risk stratification ability were validated in the test data set (median 47.4 vs. 84.4 months, log-rank test, p = 0.03) and an independent data set (median 31.0 vs. 46.0 months, log-rank test, p = 0.01). Multivariable Cox regression analysis showed that the signature was an independent prognostic factor. And the signature was proved to have a better survival prediction power than tumor-node-metastasis (TNM) stage (AUC signature = 0.72/0.64/0.62 vs. AUC TNM = 0.65/0.61/0.61; p < 0.05). Moreover, we validated the expression of these prognostic genes from the PCG-miRNA signature in Huh-7 cell by real-time polymerase chain reaction. In conclusion, we found a signature that can predict survival of HCC patients and serve as a prognostic marker for HCC.

Long-term efficacy of implantable cardiac resynchronization therapy plus defibrillator for primary prevention of sudden cardiac death in patients with mild heart failure: an updated meta-analysis.

Previous studies of implantable cardiac resynchronization therapy plus defibrillator (CRT-D) therapy used for primary prevention of sudden cardiac death have suggested that CRT-D therapy is less effective in patients with mild heart failure and a wide QRS complex. However, the long-term benefits are variable. We performed a meta-analysis of randomized trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Three studies (3858 patients) with a mean follow-up of 66 months were included. Overall, CRT-D therapy was associated with significantly lower all-cause mortality than was implantable cardioverter defibrillator (ICD) therapy (OR, 0.78; 95 % CI, 0.63-0.96; P = 0.02; I (2) = 19 %). However, the risk of cardiac mortality was comparable between two groups (OR, 0.74; 95 % CI, 0.53-1.01; P = 0.06). CRT-D treatment was associated with a significantly lower risk of hospitalization for heart failure (OR, 0.67; 95 % CI, 0.50-0.89; P = 0.005; I (2) = 55 %). The composite outcome of all-cause mortality and hospitalization for heart failure was also markedly lower with CRT-D therapy than with ICD treatment alone (OR, 0.67; 95 % CI, 0.57-0.77; P < 0.0001; I (2) = 0 %). CRT-D therapy decreased the long-term risk of mortality and heart failure events in patients with mild heart failure with a wide QRS complex. However, long-term risk of cardiac mortality was similar between two groups. More randomized studies are needed to confirm these findings, especially in patients with NYHA class I heart failure or patients without LBBB.

Genetic evidence reveals a causal relationship between rheumatoid arthritis and interstitial lung disease.

Background/purpose: Previous epidemiological studies have associated interstitial lung disease (ILD) with rheumatoid arthritis (RA), yet the causality of this relationship remains uncertain. This study aimed to investigate the genetic causal link between ILD and RA. Methods: Genome-wide association study (GWAS) statistics for ILD and RA were collected from public datasets. Relevant single-nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship between the two conditions. The MR analysis primarily used the inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression methods. Sensitivity analyses, including MR-Egger, leave-one-out, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), were conducted to evaluate the heterogeneity and pleiotropy. Replication analyses using Asian datasets were also conducted to enhance the robustness of our findings. Results: In the European population, RA was found to increase the risk of ILD by 9.6% (OR: 1.096, 95% CI: 1.023-1.174, p = 0.009). Conversely, ILD was associated with a 12.8% increased risk of RA (OR: 1.128, 95% CI: 1.013-1.256, p = 0.029). Replication analyses from Asian GWAS further supported these findings, particularly the increased risk of ILD attributable to RA (OR: 1.33, 95% CI: 1.18-1.49, p-value <0.001). Conclusion: Our findings underscore the clinical importance of screening for ILD in RA patients and suggest that effective management of RA could significantly benefit ILD patients. The potential applicability of novel RA treatments to ILD warrants further exploration. Additionally, racial disparities in the manifestation of these diseases should not be overlooked, as they may offer new perspectives for targeted therapies in diverse populations.

[The prospective register study of domestic tirofiban for clinical application in acute coronary syndrome].

OBJECTIVE: To evaluate the current clinical application of domestic tirofiban in patients with acute coronary syndrome (ACS) and to explore its safety profile focused on the common causes and correlation factors for the hemorrhagic events. METHODS: The patients diagnosed as ST-elevation myocardial infarction (STEMI) and medium to high risk non-ST-elevation myocardial infarction (NSTEMI)/unstable angina(UA) in 15 hospitals from September 2009 to December 2011 and given domestic tirofiban, were enrolled in this study. The following data were carefully collected: demographic data, comorbidities, concomitant medications, laboratory data, interventional treatment, application of tirofiban, hemorrhagic events and major adverse cardiac events(MACE) in hospital and at day 30 after discharge. RESULTS: (1) A total of 927 patients were enrolled in the study. The domestic tirofiban was given to 241 subjects (26.0%) before the intervention, 567 subjects (61.2%) during the intervention and 89 subjects (9.6%) after the intervention. The standardized application was performed in 737 subjects (79.5%) with the loading dose of 10 µg/kg and the maintenance dose of 0.15 µg·kg(-1)·min(-1). In all the subjects, the average maintenance time was (30.4 ± 14.2) hours with the average dose of (339.3 ± 182.9)ml. (2)During hospitalization, major bleeding happened in 4 cases (0.4%) and major adverse cardiac events (MACE) in 37 cases (4.0%). (3)At day 30 after discharge, 1 cases (0.1%) was reported with major bleeding and 9 cases (1.0%) with MACE. (3)The least MACE was showed in the preoperative tirofiban group (2.5%) and followed by the intraoperative group (4.1%) and the postoperative group (9.0%). Compared with the non-standardized application group, MACE was significantly decreased in the standardized application group (2.44% vs 10.00%, P < 0.05). CONCLUSIONS: The standardized application of the domestic tirofiban could decrease the incidence of MACE. Taken into account the combination therapy of clopidogrel and aspirin in the vast majority of patients, the domestic tirofiban exhibits a good safety profile with a relatively lower incidence of bleeding than the similar clinical studies.

Drug screening and biomarker gene investigation in cancer therapy through the human transcriptional regulatory network.

A complex and vast biological network regulates all biological functions in the human body in a sophisticated manner, and abnormalities in this network can lead to disease and even cancer. The construction of a high-quality human molecular interaction network is possible with the development of experimental techniques that facilitate the interpretation of the mechanisms of drug treatment for cancer. We collected 11 molecular interaction databases based on experimental sources and constructed a human protein-protein interaction (PPI) network and a human transcriptional regulatory network (HTRN). A random walk-based graph embedding method was used to calculate the diffusion profiles of drugs and cancers, and a pipeline was constructed by using five similarity comparison metrics combined with a rank aggregation algorithm, which can be implemented for drug screening and biomarker gene prediction. Taking NSCLC as an example, curcumin was identified as a potentially promising anticancer drug from 5450 natural small molecules, and combined with differentially expressed genes, survival analysis, and topological ranking, we obtained BIRC5 (survivin), which is both a biomarker for NSCLC and a key target for curcumin. Finally, the binding mode of curcumin and survivin was explored using molecular docking. This work has a guiding significance for antitumor drug screening and the identification of tumor markers.

The hypoxia-associated genes in immune infiltration and treatment options of lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a common lung cancer with a poor prognosis under standard chemotherapy. Hypoxia is a crucial factor in the development of solid tumors, and hypoxia-related genes (HRGs) are closely associated with the proliferation of LUAD cells. Methods: In this study, LUAD HRGs were screened, and bioinformatics analysis and experimental validation were conducted. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to gather LUAD RNA-seq data and accompanying clinical information. LUAD subtypes were identified by unsupervised cluster analysis, and immune infiltration analysis of subtypes was conducted by GSVA and ssGSEA. Cox regression and LASSO regression analyses were used to obtain prognosis-related HRGs. Prognostic analysis was used to evaluate HRGs. Differences in enrichment pathways and immunotherapy were observed between risk groups based on GSEA and the TIDE method. Finally, RT-PCR and in vitro experiments were used to confirm prognosis-related HRG expression in LUAD cells. Results: Two hypoxia-associated subtypes of LUAD were distinguished, demonstrating significant differences in prognostic analysis and immunological characteristics between subtypes. A prognostic model based on six HRGs (HK1, PDK3, PFKL, SLC2A1, STC1, and XPNPEP1) was developed for LUAD. HK1, SLC2A1, STC1, and XPNPEP1 were found to be risk factors for LUAD. PDK3 and PFKL were protective factors in LUAD patients. Conclusion: This study demonstrates the effect of hypoxia-associated genes on immune infiltration in LUAD and provides options for immunotherapy and therapeutic strategies in LUAD.

Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS: In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

[Cause of in-hospital death among acute myocardial infarction patients undergoing primary percutaneous coronary intervention in Beijing].

OBJECTIVE: To analyze the cause of in-hospital death among acute myocardial infarction patients undergoing primary percutaneous coronary intervention (PPCI) in Beijing area to evoke better individualized preventive approach. METHODS: In-hospital mortality and causes were analyzed based on database from Beijing percutaneous coronary intervention registry study (BJPCI Registry) in 2010. RESULTS: A total of 4660 PPCI patients from 48 hospitals were included. In-hospital mortality was 2.4% (n = 110). Cardiogenic shock (39.1%, 43/110), mechanical complications (28.2%, 31/110) and intervention-related complications [28.2%, 31/110: procedure related (n = 28), drug related (n = 3)] were the leading causes of in-hospital death. Five deaths was attributed to comorbidity related reason (4.5%, 5/110). The in-hospital mortality had no significant difference among hospitals of different grade or total annual PCI (all P > 0.05). In-hospital mortality was slightly higher in hospital with annual PPCI < 300 than in hospitals with annual PPCI ≥ 300 (2.9% vs. 1.8%, P < 0.05). CONCLUSION: Cardiogenic shock, mechanical complications and intervention-related complications are the main causes of in-hospital death among acute myocardial infarction patients receiving PPCI.

Use of oral anticoagulants and its associated factors among nonvalvular atrial fibrillation patients with new-onset acute ischemic stroke: A report from the China Atrial Fibrillation Registry study.

BACKGROUND: The adherence of oral anticoagulant (OAC) therapy among nonvalvular atrial fibrillation (NVAF) patients with acute ischemic stroke (AIS) in China during recent years was unclear, and the possible factors that influenced the initiation and persistent use of OAC were needed to be explored. METHODS: A total of 1085 NVAF patients, who experienced new-onset and nonfatal AIS from August 2011 to December 2020 during follow-ups in the China Atrial Fibrillation Registry (China-AF), were enrolled. Information including patients' demographic characteristics, medical history, medication usage, which were collected before and after the index stroke, were used in the analysis. RESULTS: OAC was initiated in 40% (434/1085) NVAF patients within 3 months after new-onset AIS. High-reimbursement-rate insurance coverage (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.03-2.22, p = .036), 3-month-peri-stroke AF episodes (OR: 2.63, 95% CI: 1.88-3.69, p < .001), and pre-stroke OAC usage (OR: 8.92, 95% CI: 6.01-13.23, p < .001), were positively associated with initiation of OAC within 3 months after new-onset AIS, while age (OR: 0.98, 95% CI: 0.96-1.00, p = .024), female (OR: 0.63, 95% CI: 0.44-0.90, p = .012) and higher modified HASBLED score (OR: 0.45, 95% CI: 0.37-0.55, p < .001) were negatively associated with it. Among 3-month-post-stroke OAC users, history of radiofrequency ablation (hazard ratio: 1.65, 95% CI: 1.16-2.35; p = .006) was positively associated with non-persistence of OAC usage. CONCLUSIONS: In China, the proportion of NVAF patients who initiated OAC therapy since new-onset AIS was still low. More efforts are needed on improving patients' adherence to anticoagulant therapy.

A Study on Weak Edge Detection of COVID-19's CT Images Based on Histogram Equalization and Improved Canny Algorithm.

The coronavirus disease 2019 (COVID-19) is a substantial threat to people's lives and health due to its high infectivity and rapid spread. Computed tomography (CT) scan is one of the important auxiliary methods for the clinical diagnosis of COVID-19. However, CT image lesion edge is normally affected by pixels with uneven grayscale and isolated noise, which makes weak edge detection of the COVID-19 lesion more complicated. In order to solve this problem, an edge detection method is proposed, which combines the histogram equalization and the improved Canny algorithm. Specifically, the histogram equalization is applied to enhance image contrast. In the improved Canny algorithm, the median filter, instead of the Gaussian filter, is used to remove the isolated noise points. The K-means algorithm is applied to separate the image background and edge. And the Canny algorithm is improved continuously by combining the mathematical morphology and the maximum between class variance method (OTSU). On selecting four types of lesion images from COVID-CT date set, MSE, MAE, SNR, and the running time are applied to evaluate the performance of the proposed method. The average values of these evaluation indicators are 1.7322, 7.9010, 57.1241, and 5.4887, respectively. Compared with other three methods, these values indicate that the proposed method achieves better result. The experimental results prove that the proposed algorithm can effectively detect the weak edge of the lesion, which is helpful for the diagnosis of COVID-19.

Prognostic Value of an Autophagy-Related Five-Gene Signature for Lower-Grade Glioma Patients.

Background: Molecular characteristics can be good indicators of tumor prognosis and have been introduced into the classification of gliomas. The prognosis of patients with newly classified lower-grade gliomas (LGGs, including grade 2 and grade 3 gliomas) is highly heterogeneous, and new molecular markers are urgently needed. Methods: Autophagy related genes (ATGs) were obtained from Human Autophagy Database (HADb). From the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), gene expression profiles including ATG expression information and patient clinical data were downloaded. Cox regression analysis, receiver operating characteristic (ROC) analysis, Kaplan-Meier analysis, random survival forest algorithm (RSFVH) and stratification analysis were performed. Results: Through univariate Cox regression analysis, we found a total of 127 ATGs associated with the prognosis of LGG patients from TCGA dataset and a total of 131 survival-related ATGs from CGGA dataset. Using TCGA dataset as the training group (n = 524), we constructed a five-ATG signature (including BAG1, BID, MAP1LC3C, NRG3, PTK6), which could divide LGG patients into two risk groups with significantly different overall survival (Log Rank P < 0.001). Then we confirmed in the independent CGGA dataset that the five-ATG signature had the ability to predict prognosis (n = 431, Log Rank P < 0.001). We further discovered that the predictive ability of the five-ATG signature was better than the existing clinical indicators and IDH mutation status. In addition, the five-ATG signature could further classify patients after receiving radiotherapy or chemotherapy into groups with different prognosis. Conclusions: We identified a five-ATG signature that could be a reliable prognostic marker and might be therapeutic targets for autophagy therapy for LGG patients.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study).

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Identification of key genes by integrating DNA methylation and next-generation transcriptome sequencing for esophageal squamous cell carcinoma.

Aberrant DNA methylation leads to abnormal gene expression, making it a significant regulator in the progression of cancer and leading to the requirement for integration of gene expression with DNA methylation. Here, we identified 120 genes demonstrating an inverse correlation between DNA methylation and mRNA expression in esophageal squamous cell carcinoma (ESCC). Sixteen key genes, such as SIX4, CRABP2, and EHD3, were obtained by filtering 10 datasets and verified in paired ESCC samples by qRT-PCR. 5-Aza-dC as a DNA methyltransferase (DNMT) inhibitor could recover their expression and inhibit clonal growth of cancer cells in seven ESCC cell lines. Furthermore, 11 of the 16 genes were correlated with OS (overall survival) and DFS (disease-free survival) in 125 ESCC patients. ChIP-Seq data and WGBS data showed that DNA methylation and H3K27ac histone modification of these key genes displayed inverse trends, suggesting that there was collaboration between DNA methylation and histone modification in ESCC. Our findings illustrate that the integrated multi-omics data (transcriptome and epigenomics) can accurately obtain potential prognostic biomarkers, which may provide important insight for the effective treatment of cancers.