MrGPS: an m6A-related gene pair signature to predict the prognosis and immunological impact of glioma patients.

N6-methyladenosine (m6A) RNA methylation is the predominant epigenetic modification for mRNAs that regulates various cancer-related pathways. However, the prognostic significance of m6A modification regulators remains unclear in glioma. By integrating the TCGA lower-grade glioma (LGG) and glioblastoma multiforme (GBM) gene expression data, we demonstrated that both the m6A regulators and m6A-target genes were associated with glioma prognosis and activated various cancer-related pathways. Then, we paired m6A regulators and their target genes as m6A-related gene pairs (MGPs) using the iPAGE algorithm, among which 122 MGPs were significantly reversed in expression between LGG and GBM. Subsequently, we employed LASSO Cox regression analysis to construct an MGP signature (MrGPS) to evaluate glioma prognosis. MrGPS was independently validated in CGGA and GEO glioma cohorts with high accuracy in predicting overall survival. The average area under the receiver operating characteristic curve (AUC) at 1-, 3- and 5-year intervals were 0.752, 0.853 and 0.831, respectively. Combining clinical factors of age and radiotherapy, the AUC of MrGPS was much improved to around 0.90. Furthermore, CIBERSORT and TIDE algorithms revealed that MrGPS is indicative for the immune infiltration level and the response to immune checkpoint inhibitor therapy in glioma patients. In conclusion, our study demonstrated that m6A methylation is a prognostic factor for glioma and the developed prognostic model MrGPS holds potential as a valuable tool for enhancing patient management and facilitating accurate prognosis assessment in cases of glioma.

GPGPS: a robust prognostic gene pair signature of glioma ensembling IDH mutation and 1p/19q co-deletion.

MOTIVATION: Many studies have shown that IDH mutation and 1p/19q co-deletion can serve as prognostic signatures of glioma. Although these genetic variations affect the expression of one or more genes, the prognostic value of gene expression related to IDH and 1p/19q status is still unclear. RESULTS: We constructed an ensemble gene pair signature for the risk evaluation and survival prediction of glioma based on the prior knowledge of the IDH and 1p/19q status. First, we separately built two gene pair signatures IDH-GPS and 1p/19q-GPS and elucidated that they were useful transcriptome markers projecting from corresponding genome variations. Then, the gene pairs in these two models were assembled to develop an integrated model named Glioma Prognostic Gene Pair Signature (GPGPS), which demonstrated high area under the curves (AUCs) to predict 1-, 3- and 5-year overall survival (0.92, 0.88 and 0.80) of glioma. GPGPS was superior to the single GPSs and other existing prognostic signatures (avg AUC = 0.70, concordance index = 0.74). In conclusion, the ensemble prognostic signature with 10 gene pairs could serve as an independent predictor for risk stratification and survival prediction in glioma. This study shed light on transferring knowledge from genetic alterations to expression changes to facilitate prognostic studies. AVAILABILITY AND IMPLEMENTATION: Codes are available at https://github.com/Kimxbzheng/GPGPS.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

bvnGPS: a generalizable diagnostic model for acute bacterial and viral infection using integrative host transcriptomics and pretrained neural networks.

MOTIVATION: The confusion of acute inflammation infected by virus and bacteria or noninfectious inflammation will lead to missing the best therapy occasion resulting in poor prognoses. The diagnostic model based on host gene expression has been widely used to diagnose acute infections, but the clinical usage was hindered by the capability across different samples and cohorts due to the small sample size for signature training and discovery. RESULTS: Here, we construct a large-scale dataset integrating multiple host transcriptomic data and analyze it using a sophisticated strategy which removes batch effect and extracts the common information from different cohorts based on the relative expression alteration of gene pairs. We assemble 2680 samples across 16 cohorts and separately build gene pair signature (GPS) for bacterial, viral, and noninfected patients. The three GPSs are further assembled into an antibiotic decision model (bacterial-viral-noninfected GPS, bvnGPS) using multiclass neural networks, which is able to determine whether a patient is bacterial infected, viral infected, or noninfected. bvnGPS can distinguish bacterial infection with area under the receiver operating characteristic curve (AUC) of 0.953 (95% confidence interval, 0.948-0.958) and viral infection with AUC of 0.956 (0.951-0.961) in the test set (N = 760). In the validation set (N = 147), bvnGPS also shows strong performance by attaining an AUC of 0.988 (0.978-0.998) on bacterial-versus-other and an AUC of 0.994 (0.984-1.000) on viral-versus-other. bvnGPS has the potential to be used in clinical practice and the proposed procedure provides insight into data integration, feature selection and multiclass classification for host transcriptomics data. AVAILABILITY AND IMPLEMENTATION: The codes implementing bvnGPS are available at https://github.com/Ritchiegit/bvnGPS. The construction of iPAGE algorithm and the training of neural network was conducted on Python 3.7 with Scikit-learn 0.24.1 and PyTorch 1.7. The visualization of the results was implemented on R 4.2, Python 3.7, and Matplotlib 3.3.4.

A Comprehensive Assessment of the Chinese Version of the Duke Activity Status Index in Patients with Cardiovascular Diseases.

Background: Exercise capacity serves as a direct representation of cardiac function. The Duke Activity Status Index (DASI), a self-administered 12-item questionnaire, covers aspects of daily living, household tasks, sexual function, and physical activity. Although widely used to evaluate exercise capacity, its validation in Chinese cardiovascular disease (CVD) patients has not been thoroughly explored. Considering the significant cultural and lifestyle differences between China and Western countries, which may influence Chinese patients' comprehension and responses to DASI, our objective is to culturally adapt DASI for Chinese patients with CVD to ensure its precision in assessing exercise capacity. Methods: The cultural adaptation of the original DASI questionnaire into Chinese followed a rigorous process to ensure its validity, reliability, and sensitivity to Chinese CVD patients. The study included 107 outpatients diagnosed with CVD who completed the DASI and cardiopulmonary exercise testing (CPET). Cronbach's alpha, Spearman correlation, and factor analysis were utilized to test reliability and validity. Receiver operating characteristic (ROC) curve analysis was employed to assess the prognostic utility of the DASI. Results: Participants had a mean DASI score of 39.40 ± 10.75 and a peak oxygen uptake (Peak VO 2 ) of 19.53 ± 5.89 mL/min/kg. The Chinese version of the DASI exhibited satisfactory reliability and validity in CVD patients, with a Chronbach's alpha coefficient of 0.706. The DASI score demonstrated a moderate correlation with Peak VO 2 measured by CPET (r = 0.67, p < 0.001). Factor analysis yielded three factors, accounting for 56.76% of the total variance, with factor 1 contributing to 26.38% of the variance. ROC curve analysis demonstrated that the DASI exhibited discriminative utility in the identification of patients with improved long-term prognosis (p < 0.001). The ROC curve had an area of 0.788 [95% confidence interval (CI) = 0.704-0.871]. The DASI score ≥ 36.85 served as the optimal threshold for enhanced long-term prognosis, exhibiting a sensitivity of 0.80 and a specificity of 0.69. Conclusions: The culturally adapted DASI questionnaire is a straightforward and efficient tool for reasonably evaluating exercise capacity in Chinese CVD patients.

Rewiring of 3D Chromatin Topology Orchestrates Transcriptional Reprogramming and the Development of Human Dilated Cardiomyopathy.

BACKGROUND: Transcriptional reconfiguration is central to heart failure, the most common cause of which is dilated cardiomyopathy (DCM). The effect of 3-dimensional chromatin topology on transcriptional dysregulation and pathogenesis in human DCM remains elusive. METHODS: We generated a compendium of 3-dimensional epigenome and transcriptome maps from 101 biobanked human DCM and nonfailing heart tissues through highly integrative chromatin immunoprecipitation (H3K27ac [acetylation of lysine 27 on histone H3]), in situ high-throughput chromosome conformation capture, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin using sequencing, and RNA sequencing. We used human induced pluripotent stem cell-derived cardiomyocytes and mouse models to interrogate the key transcription factor implicated in 3-dimensional chromatin organization and transcriptional regulation in DCM pathogenesis. RESULTS: We discovered that the active regulatory elements (H3K27ac peaks) and their connectome (H3K27ac loops) were extensively reprogrammed in DCM hearts and contributed to transcriptional dysregulation implicated in DCM development. For example, we identified that nontranscribing NPPA-AS1 (natriuretic peptide A antisense RNA 1) promoter functions as an enhancer and physically interacts with the NPPA (natriuretic peptide A) and NPPB (natriuretic peptide B) promoters, leading to the cotranscription of NPPA and NPPB in DCM hearts. We revealed that DCM-enriched H3K27ac loops largely resided in conserved high-order chromatin architectures (compartments, topologically associating domains) and their anchors unexpectedly had equivalent chromatin accessibility. We discovered that the DCM-enriched H3K27ac loop anchors exhibited a strong enrichment for HAND1 (heart and neural crest derivatives expressed 1), a key transcription factor involved in early cardiogenesis. In line with this, its protein expression was upregulated in human DCM and mouse failing hearts. To further validate whether HAND1 is a causal driver for the reprogramming of enhancer-promoter connectome in DCM hearts, we performed comprehensive 3-dimensional epigenome mappings in human induced pluripotent stem cell-derived cardiomyocytes. We found that forced overexpression of HAND1 in human induced pluripotent stem cell-derived cardiomyocytes induced a distinct gain of enhancer-promoter connectivity and correspondingly increased the expression of their connected genes implicated in DCM pathogenesis, thus recapitulating the transcriptional signature in human DCM hearts. Electrophysiology analysis demonstrated that forced overexpression of HAND1 in human induced pluripotent stem cell-derived cardiomyocytes induced abnormal calcium handling. Furthermore, cardiomyocyte-specific overexpression of Hand1 in the mouse hearts resulted in dilated cardiac remodeling with impaired contractility/Ca2+ handling in cardiomyocytes, increased ratio of heart weight/body weight, and compromised cardiac function, which were ascribed to recapitulation of transcriptional reprogramming in DCM. CONCLUSIONS: This study provided novel chromatin topology insights into DCM pathogenesis and illustrated a model whereby a single transcription factor (HAND1) reprograms the genome-wide enhancer-promoter connectome to drive DCM pathogenesis.

Association between sleep duration and metabolic syndrome: linear and nonlinear Mendelian randomization analyses.

BACKGROUND: Observational studies have found that both short and long sleep duration are associated with increased risk of metabolic syndrome (MetS). This study aimed to examine the associations of genetically determined sleep durations with MetS and its five components (i.e., central obesity, high blood pressure, dyslipidemia, hypertriglyceridemia, and hyperglycemia) among a group of elderly population. METHODS: In 335,727 participants of White British from the UK Biobank, linear Mendelian randomization (MR) methods were first employed to examine the causal association of genetically predicted continuous sleep duration with MetS and its each component. Nonlinear MR analyses were performed to determine the nonlinearity of these associations. The causal associations of short and long sleep duration with MetS and its components were further assessed by using genetic variants that associated with short (≤ 6 h) and long sleep (≥ 9 h) durations. RESULTS: Linear MR analyses demonstrated that genetically predicted 1-h longer sleep duration was associated with a 13% lower risk of MetS, a 30% lower risk of central obesity, and a 26% lower risk of hyperglycemia. Non-linear MR analyses provided evidence for non-linear associations of genetically predicted sleep duration with MetS and its five components (all P values < 0.008). Genetically predicted short sleep duration was moderately associated with MetS and its four components, including central obesity, dyslipidemia, hypertriglyceridemia, and hyperglycemia (all P values < 0.002), whereas genetically long sleep duration was not associated with MetS and any of its components. CONCLUSIONS: Genetically predicted short sleep duration, but not genetically predicted long sleep duration, is a potentially causal risk factor for MetS.

Photothermal Nanozymatic Nanoparticles Induce Ferroptosis and Apoptosis through Tumor Microenvironment Manipulation for Cancer Therapy.

It is highly desirable to design a single modality that can simultaneously trigger apoptosis and ferroptosis to efficiently eliminate tumor progression. Herein, a nanosystem based on the intrinsic properties of tumor microenvironment (TME) is designed to achieve tumor control through the simultaneous induction of ferroptosis and apoptosis. CuCP molecules are encapsulated in a liposome-based nanosystem to assemble into biocompatible and stable CuCP nanoparticles (CuCP Lipo NPs). This nanosystem intrinsically possesses nanozymatic activity and photothermal characteristics due to the property of Cu atoms and the structure of CuCP Lipo NPs. It is demonstrated that the synergistic strategy increases the intracellular lipid-reactive oxides species, induces the occurrence of ferroptosis and apoptosis, and completely eradicates the tumors in vivo. Proteomics analysis further discloses the key involved proteins (including Tp53, HMOX1, Ptgs2, Tfrc, Slc11a2, Mgst2, Sod1, and several GST family members) and pathways (including apoptosis, ferroptosis, and ROS synthesis). Conclusively, this work develops a strategy based on one nanosystem to synergistically induce ferroptosis and apoptosis in vivo for tumor suppression, which holds great potential in the clinical translation for tumor therapy.

Effect of pharmacological treatment on outcomes of heart failure with preserved ejection fraction: an updated systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Optimal treatment strategies for patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. The goal of this study was to compare the treatment effects of different therapeutic agents for patients with HFpEF. METHODS: Randomized controlled trials (RCTs) published before June 2022 were searched from PubMed, Clinical Trials gov, and the Cochrane Central Register databases. Combined odds ratios (ORs) with 95% confidence intervals (CI) were calculated for the primary and secondary outcomes. All-cause death was the primary endpoint and cardiac death, hospitalization for HF, and worsening HF (WHF) events were secondary endpoints in this meta-analysis. RESULTS: Fifteen RCTs including 31,608 patients were included in this meta-analysis. All-cause and cardiac death were not significantly correlated between drug treatments and placebo. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduced HF hospitalizations [odds ratio (OR) = 0.64, (95% confidence interval (95%CI 0.43 - 0.96), OR = 0.73, (95%CI 0.61 - 0.86), and OR = 0.74, (95%CI 0.66 - 0.83), respectively] without heterogeneity among studies. Only SGLT2 inhibitors significantly reduced WHF events [OR = 0.75, (95%CI 0.67 - 0.83)]. CONCLUSIONS: No treatments were effective in reducing mortality, but ARNIs, ACEIs or SGLT2 inhibitors reduced HF hospitalizations and only SGLT2 inhibitors reduced WHF events for patients with HFpEF.

Systemic immune-inflammation index predicted the clinical outcome in patients with type-B aortic dissection undergoing thoracic endovascular repair.

BACKGROUND: The systemic immune-inflammation index (SII) has been reported to have prognostic ability in various cardiovascular diseases; however, it has not been studied in type-B aortic dissection (TBAD). We aimed to explore the relation of SII with short-term and long-term outcomes in TBAD patients undergoing thoracic endovascular repair (TEVAR). METHODS: We performed a retrospective analysis of a prospectively maintained database from 2010 to 2017. The patients were divided into two groups (high SII and low SII) as per the optimal cut-off value determined using the receiver operating characteristic curve. Multivariate logistic and Cox regression analyses were performed to analyse the relationship between the SII and the short-term and long-term outcomes. RESULTS: A total of 805 TBAD patients who underwent TEVAR were enrolled. Twenty-six (3.2%) patients died during hospitalisation. At the end of a median follow-up duration of 48.80 mon, 70 (9.8%) patients had died. The patients were divided into the high-SII group [n = 333 (41.4%%)] and the low-SII group [n = 472 (58.6%)] as per the optimal cut-off value of 1,062. Multivariable logistic analyses showed that a high-SII score was independently associated with major adverse cardiovascular events (MACEs) in-hospital (odd ratio [OR], 1.67; 95% confidence interval [CI], 1.13-2.47; p = .01). In addition, multivariable Cox analyses showed that a high-SII score could be an independent indicator for follow-up adverse events (hazard ratio [HR], 1.70; 95% CI, 1.14-2.56, p = .01). CONCLUSIONS: Systemic immune-inflammation index is associated with both in-hospital and long-term outcomes in patients with TBAD undergoing TEVAR. Therefore, SII may serve as valuable tool for risk stratification before intervention.

Long-Term Trends in Risk Factor Management in Respondents with Chronic Kidney Disease in the USA.

INTRODUCTION: Unhealthy lifestyle factors are known to increase the risk of chronic kidney disease (CKD) and its complications. The long-term trends in these factors are unclear. METHODS: The aim of the study was to assess temporal trends in the prevalence of risk factors in adults with CKD in the USA and identify sociodemographic subgroups at most risk. Subanalysis of data was carried out from a stratified, complex, multistage probability-based cross-sectional and nationally representative survey. We examined participants from National Health and Nutritional Examination Survey (NHANES) respondents aged ≥20 years with CKD from 1999 to 2018. CKD was defined as estimated glomerular filtration rate of 15-59 mL/min/1.73 m2. Evaluated risk factors included uncontrolled blood pressure, blood glucose, blood lipids, excessive sodium intake, excessive protein intake, poor diet, obesity, smoking, depression, physical inactivity, and sedentary behavior. Sociodemographic variables included age, sex, race/ethnicity, marital status, education level, family income, and employment status. RESULTS: Blood pressure control among respondents with CKD (n = 4,342) was poor but significantly improved from the 1999-2000 (82% uncontrolled) to 2017-2018 surveys (66%; p for linear trend = 0.02). Prevalence of uncontrolled blood glucose (15-22%; p < 0.01), excessive sodium intake (72-78%; p = 0.04), and obesity (32-51%; p < 0.01) significantly increased over this time. The proportion of respondents with uncontrolled blood lipids, depression, smoking, excessive protein intake, poor diet, physical inactivity, or sedentary behavior showed no significant change over the 10-year period. Older people were more likely to have high blood pressure, high blood glucose, and high blood lipids but healthier lifestyle habits than younger people. And respondents of males, non-Hispanic blacks, Hispanics, low income, low education, widowed/divorced/separated, and employed had worse risk factor control compared to reference groups. DISCUSSION/CONCLUSION: Although the control of several risk factors in US NHANES respondents with CKD improved from 1999 to 2018, further reductions remain of value.

The psychological impact of COVID-19 pandemic on medical staff in Guangdong, China: a cross-sectional study.

BACKGROUND: During previous pandemic outbreaks, medical staff have reported high levels of psychological distress. The aim of the current study was to report a snapshot of the psychological impact of the coronavirus disease 2019 (COVID-19) pandemic and its correlated factors on medical staff in Guangdong, China. METHODS: On the 2nd and 3rd February 2020, soon after the start of the COVID-19 pandemic, we surveyed medical staff at four hospitals in Guangdong, China, to collect demographic characteristics, Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS-14), and Insomnia Severity Index (ISI) scores. RESULTS: Complete responses were received from 1045 medical staff. Respondents were divided into high- and low-risk groups according to their working environment of contacting with potential or confirmed COVID-19 cases. The proportion of staff with anxiety (55.4% v. 43.0%, p < 0.001) or depression (43.6% v. 36.8%, p = 0.028) was significantly higher in the high-risk group than the low-risk group. The percentage of staff with severe anxiety was similar in the two groups. Doctors were more susceptible to moderate-to-severe depressive symptoms. The high-risk group had higher levels of clinical insomnia (13.5% v. 8.5%, p = 0.011) and were more likely to be in the upper quartile for stress symptoms (24.7% v. 19.3%, p = 0.037) than the low-risk group. Additionally, work experience negatively correlated with insomnia symptoms. CONCLUSIONS: It is important for hospitals and authorities to protect both the physical and psychological health of medical staff during times of pandemic, even those with a low exposure risk.

Management and Outcomes of Non-A Non-B Aortic Dissection.

OBJECTIVE: The results of best medical treatment (BMT), endovascular based treatment (EBT), and total arch replacement (TAR) with frozen elephant trunk (FET) treatment in a single centre experience were reported in non-A non-B aortic dissection patients. METHODS: From January 2016 to May 2020, 215 consecutive patients with acute or subacute non-A non-B aortic dissection were enrolled. The primary endpoints were all cause death. Secondary endpoints included follow up adverse aortic event (AE), a composite of the outcomes of dissection related death, rupture, retrograde type A aortic dissection, stent graft induced new entry tear, secondary endoleak, and follow up re-intervention. Kaplan-Meier curves were used to evaluate associations between different treatments and outcomes. RESULTS: Among the 215 dissection patients, 127 (59.1%) received EBT, 42 (19.5%) received TAR + FET, and the remaining 46 (21.4%) received BMT. Thirty day mortality was higher in patients receiving TAR + FET (7.1%) than in those treated with EBT (1.6%) or BMT (2.2%) (p = .12). However, after a median follow up of 39.1 (27.0 - 50.7) months, no additional death was recorded in the TAR + FET group, while nine (7.3%) patients died in the EBT group and 14 (31.8%) died in the BMT group (p < .001). Specifically, EBT and TAR + FET showed no significant difference in midterm mortality rate, follow up AE, and re-intervention for complicated or uncomplicated dissection patients involving zone 2. For patients with uncomplicated non-A non-B aortic dissection involving zone 2, EBT could profoundly decrease the mortality rate, follow up AE and re-intervention when compared with BMT (p < .010 for all), although this difference was not statistically significant between TAR + FET and BMT. No statistical comparison was performed in patients with zone 1 involvement because of the limited number of patients. CONCLUSION: It was demonstrated that EBT or TAR + FET might be a viable strategy for non-A non-B aortic dissection patients.

Adherence to prescribed antihypertensive medication among patients with depression in the United States.

BACKGROUND: Hypertensive patients with depression have a higher mortality rate and a worse prognosis compared with hypertensive only. Depression may reduce medication adherence in hypertension patients. METHODS: This study includes respondents in the National Health and Nutritional Examination Survey (NHANES) database from 2005 to 2018 who had previously been diagnosed with hypertension. Medication adherence was defined as taking medication as recommended by a physician. The depressive state was assessed using the patient health questionnaire (PHQ)-9. RESULTS: Nine thousand one hundred eighty-six respondents were included in the analysis. Medication adherence was associated with depression (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.26 to1.75) and depression score (OR: 1.04 per each point increase, 1.03 to 1.05) in the unadjusted analyses. After adjusting for clinical and socioeconomic/demographic factors, there were significant statistical correlations between depression score and medication adherence (aOR: 1.02 per each point increase, 1.00 to 1.03, p < 0.05), but there was no significant statistical correlation between depression and medication adherence (p > 0.05). It was still statistically significant relationships between sex, age, body mass index (BMI), race, marital status, and health insurance with medication adherence after adjusted socioeconomic/demographic factors. CONCLUSION: Depression was marginally associated with poor medication adherence in hypertensive patients, and the correlation increased with depression degree. Moreover, socioeconomic/demographic factors have an independent impact on medication adherence including sex, age, BMI, race, marital status, and health insurance.

New genetic variants associated with major adverse cardiovascular events in patients with acute coronary syndromes and treated with clopidogrel and aspirin.

Although a few studies have reported the effects of several polymorphisms on major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI), these genotypes account for only a small fraction of the variation and evidence is insufficient. This study aims to identify new genetic variants associated with MACE end point during the 18-month follow-up period by a two-stage large-scale sequencing data, including high-depth whole exome sequencing of 168 patients in the discovery cohort and high-depth targeted sequencing of 1793 patients in the replication cohort. We discovered eight new genotypes and their genes associated with MACE in patients with ACS, including MYOM2 (rs17064642), WDR24 (rs11640115), NECAB1 (rs74569896), EFR3A (rs4736529), AGAP3 (rs75750968), ZDHHC3 (rs3749187), ECHS1 (rs140410716), and KRTAP10-4 (rs201441480). Notably, the expressions of MYOM2 and ECHS1 are downregulated in both animal models and patients with phenotypes related to MACE. Importantly, we developed the first superior classifier for predicting 18-month MACE and achieved high predictive performance (AUC ranged between 0.92 and 0.94 for three machine-learning methods). Our findings shed light on the pathogenesis of cardiovascular outcomes and may help the clinician to make a decision on the therapeutic intervention for ACS patients.

Omega-3 fatty acid protects cardiomyocytes against hypoxia-induced injury through targeting MiR-210-3p/CASP8AP2 axis.

MicroRNAs (miRs) regulate diverse biological functions in both normal and pathological cellular conditions by post-transcriptional regulation of various genes expression. Nevertheless, the role of miRs in regulating the protective functions of omega-3 fatty acid in relation to hypoxia in cardiomyocytes remains unknown. The aim of this study was to investigate the effects of omega-3 fatty acid supplementation on cardiomyocyte apoptosis and further delineate the mechanisms underlying microRNA-210 (miRNA-210)-induced cardiomyocyte apoptosis in vitro. H9C2 cultured cells were first subjected to hypoxia followed by a subsequent treatment with main component of the Omega-3 fatty acid, Docosahexaenoic Acid (DHA). Cell apoptosis were detected by flow cytometry and the expression of miR-210-3p were detected by RT-qPCR and caspase-8-associated protein 2 (CASP8AP2) at protein levels by immunoblotting. Dual luciferase assay was used to verify the mutual effect between miR-210-3p and the 3'-untranslated region (UTR) of CASP8AP2 gene. DHA was shown to reduce apoptosis in H9C2 cells subjected to hypoxia. While DHA caused a significant increase in the expression of miR-210-3p, there was a marked reduction in the protein expression of CASP8AP2. MiR-210-3p and CASP8AP2 were significantly increased in H9C2 cardiomyocyte subjected to hypoxia. Overexpression of miR-210-3p could ameliorate hypoxia-induced apoptosis in H9C2 cells. MiR-210-3p negatively regulated CASP8AP2 expression at the transcriptional level. Both miR-210-3p mimic and CASP8AP2 siRNA could efficiently inhibit apoptosis in H9C2 cardiomyocyte subjected to hypoxia. We provide strong evidence showing that Omega-3 fatty acids can attenuate apoptosis in cardiomyocyte under hypoxic conditions via the up-regulation of miR-210-3p and targeting CASP8AP2 signaling pathway.

Prognostic dynamic nomogram integrated with metabolic acidosis for in-hospital mortality and organ malperfusion in acute type B aortic dissection patients undergoing thoracic endovascular aortic repair.

BACKGROUND: Organ malperfusion is a lethal complication in acute type B aortic dissection (ATBAD). The aim of present study is to develop a nomogram integrated with metabolic acidosis to predict in-hospital mortality and organ malperfusion in patients with ATBAD undergoing thoracic endovascular aortic repair (TEVAR). METHODS: The nomogram was derived from a retrospectively study of 286 ATBAD patients who underwent TEVAR from 2010 to 2017 at a single medical center. Model performance was evaluated from discrimination and calibration capacities, as well as clinical effectiveness. The results were validated using a prospective study on 77 patients from 2018 to 2019 at the same center. RESULTS: In the multivariate analysis of the derivation cohort, the independent predictors of in-hospital mortality and organ malperfusion identified were base excess, maximum aortic diameter ≥ 5.5 cm, renal dysfunction, D-dimer level ≥ 5.44 µg/mL and albumin amount ≤ 30 g/L. The penalized model was internally validated by bootstrapping and showed excellent discriminatory (bias-corrected c-statistic, 0.85) and calibration capacities (Hosmer-Lemeshow P value, 0.471; Brier Score, 0.072; Calibration intercept, - 0.02; Slope, 0.98). After being applied to the external validation cohort, the model yielded a c-statistic of 0.86 and Brier Score of 0.097. The model had high negative predictive values (0.93-0.94) and moderate positive predictive values (0.60-0.71) for in-hospital mortality and organ malperfusion in both cohorts. CONCLUSIONS: A predictive nomogram combined with base excess has been established that can be used to identify high risk ATBAD patients of developing in-hospital mortality or organ malperfusion when undergoing TEVAR.

Comorbidity of depression and anxiety leads to a poor prognosis following angina pectoris patients: a prospective study.

BACKGROUND: Depression and anxiety are two common mood problems among patients with cardiovascular disease (CVD) and are associated with poor cardiac prognoses. The comorbidity of depression and anxiety is considered to be a more severe psychological status than non-comorbid mood disorders. However, little is known about the relationship between depression or anxiety and noncardiac readmission. We conducted a prospective study on the prognostic impact of depression, anxiety, and the comorbidity of the two among angina pectoris (AP) patients. METHOD: In this prospective study, 443 patients with AP were included in the analysis. Follow-up assessments were performed 1 year, and 2 years after patient discharges. Clinical outcomes of interest included noncardiac readmission, major adverse cardiovascular events (MACEs), and composite events. Depression and anxiety symptom scores derived from the patient health questionnaire-9 (PHQ-9) and generalised anxiety disorder-7 (GAD-7) questionnaire were used to assess mood symptoms at baseline. Participants with symptom scores of ≥10 on both the depression and anxiety questionnaires formed the clinical comorbidity subgroup. We used multivariable Cox proportional hazards models to evaluate the impact of individual mood symptom and comorbidity on clinical outcomes. RESULTS: Among all the AP patients, 172 (38. 9%) were determined to have depression symptoms, 127 (28.7%) patients had anxiety symptoms and 71 (16.0%) patients suffered from their comorbidity. After controlling covariates, we found that patients who endured clinical depression (hazard ratio [HR] = 2.38, 95% confidence interval [CI] 1.06-5.33, p = 0.035) and anxiety ([HR] 2.85, 95% [CI] 1.10-7.45, p = 0.032) had a high risk of noncardiac readmission. Compared to participants with no mood symptoms, those with clinical comorbidity of depression and anxiety presented a greater risk of noncardiac readmission ([HR] 2.91, 95% [CI] 1.03-8.18, p = 0.043) MACEs ([HR] 2.38, 95% [CI] 1.11-5.10, p = 0.025) and composite event ([HR] 2.52, 95% [CI] 1.35-4.69, p = 0.004). CONCLUSION: Depression and anxiety were found to have predictive value for noncardiac readmission among patients with AP. Furthermore, prognoses were found to be worse for patients with comorbidity of depression and anxiety than those with single mood symptom. Additional attention needs to be focused on the initial identification and long-term monitoring of mood symptom comorbidity.

GenCLiP 3: mining human genes' functions and regulatory networks from PubMed based on co-occurrences and natural language processing.

SUMMARY: We present a web server, GenCLiP 3, which is an updated version of GenCLiP 2.0 to enhance analysis of human gene functions and regulatory networks, with the following improvements: i) accurate recognition of molecular interactions with polarity and directionality from the entire PubMed database; ii) support for Boolean search to customize multiple-term search and to quickly retrieve function related genes; iii) strengthened association between gene and keyword by a new scoring method; and iv) daily updates following literature release at PubMed FTP. AVAILABILITY: The server is freely available for academic use at: http://ci.smu.edu.cn/genclip3/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Left atrial volume index is superior to left atrial diameter index in relation to coronary heart disease in hypertension patients with preserved left ventricular ejection fraction.

Objective: Research hypothesis is that left atrial (LA) volume index is superior to LA diameter index for coronary heart disease and LA volume index is important to refine risk stratification.Methods: We retrospectively enrolled 222 asymptomatic non-ischemic patients with hypertension who had stored digital images in 2012. Patients were followed up for coronary heart disease over a median of 3.2 years. The Area under receiver operating characteristic curve for LA parameters with coronary heart disease was evaluated. Cox regression was used to assess the association between left atrial parameters and coronary heart disease.Results: The mean age of patients was 62 years, 45% were men, and mean left atrial diameter, mean left atrial volume, mean LA diameter index, mean LA volume index was 32 mm, 43 ml, 21 mm/m2, 27 ml/m2, respectively. After 3.2 years follow up, 10 patients experienced coronary heart disease. Compared with patients without coronary heart disease, LA diameter index and LA volume index increased in coronary heart disease group (P < 0.05). Multivariate cox regression analysis showed, adjusted for age, sex, smoking, cholesterol, fasting plasma glucose, diabetes, systolic blood pressure, left ventricular mass index, and E/e' ratio, a unit rise in LA volume index was associated with a 15% increase in the risk of coronary heart disease. (HR:1.155; 95% CI 1.002-1.332). Compared with LA diameter index, the area under receiver operating characteristic curve values for predicting coronary heart disease were higher for LA volume index (0.797).Conclusions: Our study showed that LA volume index was superior to LA diameter index. LA volume index had independent prognostic implications in terms of coronary heart disease prediction in hypertension patients with preserved left ventricular ejection fraction.

Predictive value of 18F-FDG PET/CT in patients with acute type B aortic intramural hematoma.

BACKGROUND: The clinical course and predictors of adverse aortic events (AAE) in patients with acute Stanford type B intramural hematoma (IMH) remain controversial. This study aimed to investigate whether 18F-FDG PET/CT can predict risk in patients with acute type B IMH. METHODS AND RESULTS: This study included 34 patients with acute type B IMH who underwent PET/CT within 14 days from the onset of symptoms. The maximal standardized uptake values (SUVmax) of 18F-FDG uptake was significantly different between patients with or without AAE (4.3 ± 0.6 vs 3.7 ± 1.0, P = 0.020), but not the target to blood ratio (TBR, SUVmax divided by SUV in the superior vena cava) (1.6 ± 0.2 vs 1.5 ± 0.5, P = 0.064). In patients with initial ulcer-like projection (ULP), a blood-filled pouch protruding into the IMH, which was seen in 25 patients(74%), both the SUVmax and TBR were significantly higher in patients who developed AAE, (4.3 ± 0.6 vs 3.3 ± 0.5, P = 0.001; 1.6 ± 0.2 vs 1.4 ± 0.2, P = 0.01); the TBR >1.5, which is determined from receiver-operating-characteristic curve, had a sensitivity of 73% and a specificity of 80% in predicting AAE. CONCLUSION: Patients with ULP and high 18F-FDG uptake were more likely to develop AAE and may require closer surveillance with serial imaging.