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Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD.We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak V̇oThe median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇oExercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.

We present a complete representation theorem for nullnorms on bounded lattices. Explicitly, any nullnorm on a bounded lattice can be represented in terms of two order-preserving maps, a triangular conorm, a triangular norm and a conditionally associative function. As a particular case, we retrieve the known representation of nullnorms only taking values that are comparable with the annihilator (in terms of two order-preserving maps, a triangular conorm and a triangular norm). As an illustration of the representation theorem, we generate construction methods for nullnorms, especially those taking at least one value that is incomparable with the annihilator.

First, we present construction methods for interior operators on a meet semilattice. Second, under the assumption that the underlying meet semilattices constitute the range of an interior operator, we prove an ordinal sum theorem for countably many (finite or countably infinite) triangular norms on bounded meet semilattices, which unifies and generalizes two recent results: one by Dvořak and Holcapek and the other by some of the present authors. We also characterize triangular norms that are representable as the ordinal sum of countably many triangular norms on given bounded meet semilattices.

The functional roles and mechanism of the XIST in osteoarthritis and the chondrogenic differentiation of BMSCs were clarified.The expression levels of XIST, TAF15, FUT1 and YY1 were detected through quantitative RT-PCR. The protein expression of Sox9, ACAN, COL2A1 and FUT1 were detected by western blot and immunohistochemistry. The damage of cartilage tissue was detected by HE staining, and Safranin O-fast green. Alcian-Blue and Alizarin red S staining were performed to evaluate BMSCs chondrogenic differentiation. The relationship between XIST and TAF15, XIST and TAF15 were analyzed by RNA immunoprecipitation assay. Luciferase reporter assays and chromatin immunoprecipitation were performed to detect the interaction relationship between XIST and YY1. In addition, osteoarthritis mice were built to assess the function of XISTThe levels of XIST, TAF15 and FUT1 were upregulated in cartilage tissues from osteoarthritis patient. The level of XIST was decreased in BMSCs during chondrogenic differentiation. XIST overexpression inhibited the chondrogenic differentiation of BMSCs. Moreover, silencing of FUT1 reversed the effects of XIST overexpression on BMSCs chondrogenic differentiation. Mechanistically, in BMSCs, YY1 induced the expression of XIST in BMSCs, and XIST regulated FUT1 mRNA stability through targeting TAF15. Furthermore, silencing of XIST alleviated the symptoms of cartilage injury in OA mice.Taken together, these results suggested that YY1 induced XIST was closely related to the chondrogenic differentiation of BMSCs and the progression of osteoarthritis by TAF15/FUT1 axis, and may be a new OA therapeutic target.

The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved.The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH.In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia.A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients.Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

Hypothyroidism is closely associated with increased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). The thyroid gland plays an important role in this process because thyroid hormones (THs) modulate cholesterol production, transformation and clearance. Although recent evidence suggests that thyroid-stimulating hormone (TSH) itself also participates in hyperlipidemia, the underlying mechanism remains unclear. Others demonstrated that the pathologic development of hypothyroidism-related hyperlipidemia was associated with down-regulated THs and up-regulated TSH in serum. This finding suggests a role for hypothyroidism in hyperlipidemia and potentially in related cardio-metabolic disease. Multiple newly identified modulatory biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), might play a role in modulating the risk of hyperlipidemia induced by hypothyroidism. Moreover, hypothyroidism also contributes to the production of dysfunctional high-density lipoprotein (HDL) particles. In the present review, we examine the relationship between hypothyroidism with the risk and pathologic development of hyperlipidemia. We explore mechanisms by which hypothyroidism promotes hyperlipidemia in general and its contribution to cardio-metabolic disease specifically.

Lung cancer is a major cause of cancer-associated deaths worldwide, and lung adenocarcinoma (LUAD) is the most common lung cancer subtype. Micro RNAs (miRNAs) regulate the pattern of gene expression in multiple cancer types and have been explored as potential drug development targets. To develop an oncomiR-based panel, we identified miRNA candidates that show differential expression patterns and are relevant to the worse 5-year overall survival outcomes in LUAD patient samples. We further evaluated various combinations of miRNA candidates for association with 5-year overall survival and identified a four-miRNA panel: miR-9-5p, miR-1246, miR-31-3p, and miR-3136-5p. The combination of these four miRNAs outperformed any single miRNA for predicting 5-year overall survival (hazard ratio [HR]: 3.47, log-rank p-value = 0.000271). Experiments were performed on lung cancer cell lines and animal models to validate the effects of these miRNAs. The results showed that singly transfected antagomiRs largely inhibited cell growth, migration, and invasion, and the combination of all four antagomiRs considerably reduced cell numbers, which is twice as effective as any single miRNA-targeted transfected. The

There remains a lack of prognosis models for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to develop a nomogram predicting 3-, 5-, and 7-year survival in patients with CTEPH and verify the prognostic model. Patients with CTEPH diagnosed in Fuwai Hospital were enrolled consecutively between May 2013 and May 2019. Among them, 70% were randomly split into a training set and the other 30% as a validation set for external validation. Cox proportional hazards model was used to identify the potential survival-related factors which were candidate variables for the establishment of nomogram and the final model was internally validated by the bootstrap method. A total of 350 patients were included in the final analysis and the median follow-up period of the whole cohort was 51.2 months. Multivariate analysis of Cox proportional hazards regression showed body mass index, mean right atrial pressure, N-terminal pro-brain natriuretic peptide (per 500 ng/ml increase in concentration), presence of anemia, and main treatment choice were the independent risk factors of mortality. The nomogram demonstrated good discrimination with the corrected C-index of 0.82 in the training set, and the C-index of 0.80 (95% CI: 0.70 to 0.91) in the external validation set. The calibration plots also showed a good agreement between predicted and actual survival in both training and validation sets. In conclusion, we developed an easy-to-use nomogram with good apparent performance using 5 readily available variables, which may help physicians to identify CTEPH patients at high risk for poor prognosis and implement medical interventions.

We introduce three broad classes of nullnorms on a bounded lattice and lay bare the structure of their members. For that purpose, we introduce particular subsets of a bounded lattice, called upper (resp. lower) beams, and appropriate associative operations on them, called beam (resp. dual beam) operations, which conveniently generalize triangular norms (resp. triangular conorms). It is shown that nullnorms in the first (resp. second) class are characterized by a triangular conorm (resp. triangular norm) and a beam operation (resp. dual beam operation), while nullnorms in the third class are characterized by a triangular conorm and a triangular norm. We also discuss the relationships among these three classes.

Wind speed predictions are essential for wind power management and wind farm operation. However, due to the high volatility and nonstationarity of measured wind data, it is often difficult to achieve an accurate prediction. This study proposes a hybrid approach that consists of two stages, i.e., data preprocessing and wind speed predicting, to improve the accuracy of short-term wind speed prediction. A preprocessing algorithm for the transformation and standardization of hourly mean wind speed is utilized to remove the non-Gaussian distribution of wind data and diurnal nonstationarity. Several statistical models and artificial intelligence models are then adopted in the second stage of the prediction process, including a persistence model, autoregressive model, autoregressive moving average model and backpropagation neural network. The proposed approach is developed based on the weighted averaging of these models and error optimization theory. Finally, wind speed data for 12 months from two meteorological towers located in Yanan, China, are investigated to demonstrate the effectiveness and accuracy of the proposed approach for multistep wind speed predictions, and its performance is then compared with several existing prediction models. The results indicate that the prediction accuracy improves significantly after preprocessing with the proposed approach, outperforming all the existing aforementioned models.