ABLE-SCORE, a simplified risk score for major adverse cardiovascular outcomes in left ventricular hypertrabeculation: a multicenter longitudinal cohort study.

BACKGROUND: Left ventricular hypertrabeculation (LVHT) is a heterogeneous entity with life-threatening complications and variable prognosis. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVHT is comparatively complex for clinical practice. This study aimed to develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVHT. METHODS: This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVHT patients between January 2009 and December 2020 at Fuwai Hospital (derivation cohort, n = 300; internal validation cohort, n = 129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort, n = 95). The derivation/internal validation cohorts and the external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors in the multivariable Cox regression predictive model for MACE, and underwent both internal and external validations to confirm its discrimination, calibration, and clinical applicability. RESULTS: A total of 524 LVHT patients (43.5 ± 16.6 years, 65.8% male) were included in the study. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement, and left ventricular ejection fraction ≤ 40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell's C-index of 0.821 [95% confidence interval (CI), 0.772-0.869], 0.786 (95%CI, 0.703-0.869), and 0.750 (95%CI, 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVHT. According to decision curve analysis, the ABLE-SCORE displayed greater net benefits than the existing risk score for LVHT, indicating its strength in clinical applicability. CONCLUSIONS: A simplified and efficient risk score for MACE was developed and validated using a large LVHT cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVHT.

Prognostic value of cardiac deceleration capacity in patients with atrial fibrillation after catheter ablation: A systematic review and meta-analysis.

INTRODUCTION: Cather ablation (CA) is a well-recognized treatment alternative for atrial fibrillation (AF) patients despite more than 20% ablation-treated patients suffering from AF recurrence. The underlying mechanism of AF recurrence postablation is probably associated with high cardiac parasympathetic activity, which can be assessed with deceleration capacity (DC) of heart rate. Given that the relationship between DC and AF recurrence is still controversial, this systematic review and meta-analysis was performed to investigate the characteristics of DC in patients with and without AF recurrence, evaluating the prognostic value of DC in AF patients after CA. METHODS: A literature search was systematically performed in the Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases until October 01, 2023. The observational studies reporting either the pre- and postablation DC in both recurrence and non-recurrence groups or the ratios based on DC for predicting AF recurrence were mainly included. Weighted mean differences (WMD) or odds ratios (OR) based on DC would be calculated with a random-effect model, if heterogeneity estimated with the I2 index and Q statistic was significant (I2 > 50% or p < .05); otherwise, a fixed-effect model would be utilized. RESULTS: A total of eight observational studies involving 914 AF patients treated with radiofrequency or cryoballoon ablation were included in this study. Ablation-treated patients with AF recurrence had the higher DC postablation in relation to those without recurrence (WMD, 1.00; 95% confidence interval [CI], 0.33-1.67; p < .01), which was present up to 3 months of follow-up (WMD, 1.54; 95% CI, 1.11-1.96; p < .01), whereas there was no statistical significance in DC before ablation between recurrence and non-recurrence groups (WMD, 0.34; 95% CI, -0.12 to 0.79; p = .15). The high DC postablation was a risk factor for AF recurrence in ablation-treated patients (OR, 2.17; 95% CI, 1.44-3.25; p < .01). CONCLUSION: The high DC postablation was associated with the risk of AF recurrence, suggesting that DC may act as a prognostic indicator in AF patients treated with CA.

Association of serum vitamin D status with gestational diabetes mellitus and other laboratory parameters in early pregnant women.

BACKGROUND: The association between serum 25-hydroxy vitamin D (25(OH)D) status and gestational diabetes mellitus (GDM) gained attention in recent years, however the conclusion is still controversial due to many interfering factors, such as region of living, environment, lifestyle, and food supplements. Other metabolites (laboratory parameters) are also important in reflecting gestational states. This study aimed to investigate the association of serum 25(OH)D status in early pregnancy with GDM and other laboratory parameters in pregnant women. METHODS: A total of 1516 pregnant women whose blood glucose were normal before pregnancy in the city of Foshan in Guangdong, China were enrolled in this study. GDM was diagnosed between 24 to 28 weeks of pregnancy following the guidelines from the American Diabetes Association. Maternal serum 25(OH)D and other laboratory parameters-including hematology, coagulation, chemistry, and bone density-were measured utilizing various analytical methods in clinical laboratory at gestational weeks 11 to 14. RESULTS: The average 25(OH)D concentration was 59.1 ± 12.6 nmol/L. None of the study subjects had 25(OH)D < 25 nmol/L; 434 (28.6%) women had 25(OH)D deficiency (< 50 nmol/L), 882 women (58.2%) had 25(OH)D insufficiency (50-74 mmol/L) and 200 women (13.2%) had 25(OH)D sufficiency (≥ 75 nmol/L). There were 264 (17.4%) women diagnosed with GDM. There was not, however, an association between serum 25(OH)D in early pregnancy and GDM. Interestingly, women with more parity and high serum alkaline phosphatase levels had higher serum 25(OH)D levels. There was a possible positive association between serum 25(OH)D and pre-albumin, and a possible negative association between serum 25(OH)D, creatinine, and thrombin time. This study did not find an association between serum 25(OH)D and bone density. CONCLUSIONS: There were no associations between maternal serum 25(OH)D concentration in early pregnancy and the risk of GDM or bone density. There were, however, correlations between serum 25(OH)D and parity, seasoning at sampling, serum alkaline phosphatase, creatinine, pre-albumin, and coagulation factor thrombin time, which need further study to explain their pathophysiology and clinical significance.

Efficacy and safety of laser combination therapy and laser alone therapy for keloid: a systematic review and meta-analysis.

To evaluate the efficacy and safety of laser alone therapy and laser combination therapy (mainly combined with other kinds of laser or steroids) for keloid.PubMed, Embase and Web of Science were searched for relevant articles from inception to June 2020. Comprehensive Meta-Analysis software 2.0 (CMA) was used to perform the meta-analysis.A total of 29 articles were included in this meta-analysis. During the mean follow-up of 14 (1-84) months, the overall improvement rates of baseline Vancouver scar scale (VSS) score and itch were 0.454 (95%CI 0.351-0.561, I2 = 0) and 0.786 (95%CI 0.613-0.895, I2 = 0) in the laser combination therapy group. The improvement rates of scar height and flexibility in the laser combination therapy group were 0.629 (95%CI 0.519-0.727, I2 = 52.089) and 0.784 (95%CI 0.251-0.975, I2 = 89.420). The average improvement rate of the scar score in laser combination therapy was 0.338 (0.201-0.510); however, there were insufficient data for laser alone therapy comparison. The laser combination therapy had a greater pain improvement rate, 0.580 (0.389-0.750) versus 0.420 (0.224-0.645), compared to laser alone therapy, and a greater degree of good or excellent (> 50%) improvement in the overall scar, 0.636 (95%CI 0.347-0.852) versus 0.149 (95%CI 0.032-0.482), with laser alone therapy. Moreover, a lower regrowth rate of 0.187 (0.129-0.263) versus 0.249 (0.060-0.631), a lower post-treatment pigmentation rate of 0.125 (0.091-0.169) versus 0.135 (0.058-0.282), and a lower infection rate of 0.047 (0.009-0.209) versus 0.076 (0.012-0.351) were observed in the laser combination therapy compared with those rates in the laser alone therapy.The overall effect of laser combination therapy was better than that of laser alone therapy, and the incidence of adverse reactions was lower in laser combination therapy than in laser alone therapy.

Identification of Human Global, Tissue and Within-Tissue Cell-Specific Stably Expressed Genes at Single-Cell Resolution.

Stably Expressed Genes (SEGs) are a set of genes with invariant expression. Identification of SEGs, especially among both healthy and diseased tissues, is of clinical relevance to enable more accurate data integration, gene expression comparison and biomarker detection. However, it remains unclear how many global SEGs there are, whether there are development-, tissue- or cell-specific SEGs, and whether diseases can influence their expression. In this research, we systematically investigate human SEGs at single-cell level and observe their development-, tissue- and cell-specificity, and expression stability under various diseased states. A hierarchical strategy is proposed to identify a list of 408 spatial-temporal SEGs. Development-specific SEGs are also identified, with adult tissue-specific SEGs enriched with the function of immune processes and fetal tissue-specific SEGs enriched in RNA splicing activities. Cells of the same type within different tissues tend to show similar SEG composition profiles. Diseases or stresses do not show influence on the expression stableness of SEGs in various tissues. In addition to serving as markers and internal references for data normalization and integration, we examine another possible application of SEGs, i.e., being applied for cell decomposition. The deconvolution model could accurately predict the fractions of major immune cells in multiple independent testing datasets of peripheral blood samples. The study provides a reliable list of human SEGs at the single-cell level, facilitates the understanding on the property of SEGs, and extends their possible applications.

Effectiveness of cardioneuroablation in different subtypes of vasovagal syncope.

BACKGROUND: Cardioneuroablation (CNA) has shown encouraging results in patients with vasovagal syncope (VVS). However, data on different subtypes was scarce. METHODS: This observational study retrospectively enrolled 141 patients [mean age: 40 ± 18 years, 51 males (36.2%)] with the diagnosis of VVS. The characteristics among different types of VVS and the outcomes after CNA were analyzed. RESULTS: After a mean follow-up of 4.3 ± 1.5 years, 41 patients (29.1%) experienced syncope/pre-syncope events after CNA. Syncope/pre-syncope recurrence significantly differed in each subtype (P = 0.04). The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure (n = 6, 16.7%), followed by mixed (n = 26, 30.6%) and vasodepressive (n = 9, 45.0%). Additionally, a significant difference was observed in the analyses of the Kaplan-Meier survival curve (P = 0.02). Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type (P < 0.01). Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity (DC) level than those without (7.4 ± 1.0 ms vs. 9.0 ± 1.6 ms, P = 0.01). Patients with DC < 8.4 ms had an 8.1 (HR = 8.1, 95% CI: 2.2-30.0, P = 0.02) times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC ≥ 8.4 ms, and this association still existed after adjusting for age and sex (HR = 8.1, 95% CI: 2.2-30.1, P = 0.02). CONCLUSIONS: Different subtypes exhibit different event-free rates. The vasodepressive type exhibited the lowest event-free rate, but those patients with DC ≥ 8.4 ms might benefit from CNA.

Fucosterol exhibits selective antitumor anticancer activity against HeLa human cervical cell line by inducing mitochondrial mediated apoptosis, cell cycle migration inhibition and downregulation of m-TOR/PI3K/Akt signalling pathway.

[This retracts the article DOI: 10.3892/ol.2018.7769.].

A Multi-Gene Model Effectively Predicts the Overall Prognosis of Stomach Adenocarcinomas With Large Genetic Heterogeneity Using Somatic Mutation Features.

BACKGROUND: Stomach adenocarcinoma (STAD) is one of the most common malignancies worldwide with poor prognosis. It remains unclear whether the prognosis is associated with somatic gene mutations. METHODS: In this research, we collected two independent STAD cohorts with both genetic profiling and clinical follow-up data, systematically investigated the association between the prognosis and somatic mutations, and analyzed the influence of heterogeneity on the prognosis-genetics association. RESULTS: Typical association was identified between somatic mutations and overall prognosis for individual cohorts. In The Cancer Genome Atlas (TCGA) cohort, a list of 24 genes was also identified that tended to mutate within cases of the poorest prognosis. The association showed apparent heterogeneity between different cohorts, although common signatures could be identified. A machine-learning model was trained with 20 common genes that showed a similar mutation rate difference between prognostic groups in the two cohorts, and it classified the cases in each cohort into two groups with significantly different prognosis. The model outperformed both single-gene models and TNM-based staging system significantly. CONCLUSION: The study made a systematic analysis on the association between STAD prognosis and somatic mutations, identified signature genes that showed mutation preference in different prognostic groups, and developed an effective multi-gene model that can effectively predict the overall prognosis of STAD in different cohorts.

Medical Image Fusion Based on Sparse Representation and PCNN in NSCT Domain.

The clinical assistant diagnosis has a high requirement for the visual effect of medical images. However, the low frequency subband coefficients obtained by the NSCT decomposition are not sparse, which is not conducive to maintaining the details of the source image. To solve these problems, a medical image fusion algorithm combined with sparse representation and pulse coupling neural network is proposed. First, the source image is decomposed into low and high frequency subband coefficients by NSCT transform. Secondly, the K singular value decomposition (K-SVD) method is used to train the low frequency subband coefficients to get the overcomplete dictionary D, and the orthogonal matching pursuit (OMP) algorithm is used to sparse the low frequency subband coefficients to complete the fusion of the low frequency subband sparse coefficients. Then, the pulse coupling neural network (PCNN) is excited by the spatial frequency of the high frequency subband coefficients, and the fusion coefficients of the high frequency subband coefficients are selected according to the number of ignition times. Finally, the fusion medical image is reconstructed by NSCT inverter. The experimental results and analysis show that the algorithm of gray and color image fusion is about 34% and 10% higher than the contrast algorithm in the edge information transfer factor QAB/F index, and the performance of the fusion result is better than the existing algorithm.

LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation.

OBJECTIVE: Long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is involved in various kinds of cancer. However, the role of lncGAS5 in the development of ovarian cancer remains unclear. In the current study, we explored the cellular mechanism and clinical value of lncRNA GAS5 in ovarian cancer. METHODS: Quantitative real-time PCR was used to detect mRNA level of LncRNA GAS5 in 20 ovarian cancer tissues. The effect of lncRNA GAS5 on cell proliferation was performed using CCK-8 assay. Cell apoptosis was evaluated by flow cytometry. Western blotting was used to detect the protein level of lncRNA GAS5 potential target. Standard sandwich ELISA was used to quantify the level of inflammatory cytokines. The cells with stable expression of lncRNA GAS5 were injected into nude mice to study the effect of lncRNA GAS5 on tumorigenesis in vivo. Results: The expression of lncRNA GAS5 was significantly decreased in ovarian cancer tissues. Decrease in lncRNA GAS5 expression resulted in increased cell proliferation and colony formation and reduced ovarian cancer cell apoptosis. In contrast, exogenous overexpression of lncRNA GAS5 in ovarian cancer cells inhibited proliferation, colony formation and apoptosis in ovarian cancer cells. In addition, the role of lncRNA GAS5 in ovarian cancer was associated with inflammasome formation and pyroptosis. CONCLUSION: These results suggested that lncRNA GAS5 acts as tumor suppressor and could be used as a potential treatment target for diagnosis and therapy of ovarian cancer.

Fucosterol exhibits selective antitumor anticancer activity against HeLa human cervical cell line by inducing mitochondrial mediated apoptosis, cell cycle migration inhibition and downregulation of m-TOR/PI3K/Akt signalling pathway.

Cervical cancer greatly contributes to cancer-associated mortalities worldwide. The growing incidence of cervical cancer is of primary concern, and has signaled the need for multiple treatment options. Despite preliminary responses to chemotherapy and/or surgical interventions, the tumors consistently relapse. Previously, natural products gained attention for their diverse bioactivities, which include however are not limited to, neuroprotective, antimicrobial and anticancer effects. The present study evaluated the anticancer activity of fucosterol against a panel of human cancer cell lines. Results indicated that fucosterol exhibited selective inhibitory activity against human HeLa cervical cancer cell line with an IC50 of 40 µM. Fucosterol also induced apoptosis in HeLa cells and prompted reactive oxygen species mediated alterations in mitochondrial membrane potential. It triggered cell cycle arrest of HeLa cells at G2/M check point and exerted inhibitory effects on cell migration. The activation of the phosphoinositide-3-kinase (PI3K)/AKT Serine/Threonine Kinase 1 (AKT)/mechanistic target of Rapamycin (mTOR) pathway is important in cancer tumorigenesis, progression and chemotherapy resistance. The results demonstrated that fucosterol significantly inhibited the expression levels of key proteins of the PI3K/Akt/mTOR signaling pathway. Overall, the results of the present study suggest that fucosterol may prove beneficial in the management of cervical cancer.