A lightweight network based on multi-feature pseudo-color mapping for arrhythmia recognition.

Heartbeats classification is a crucial tool for arrhythmia diagnosis. In this study, a multi-feature pseudo-color mapping (MfPc Mapping) was proposed, and a lightweight FlexShuffleNet was designed to classify heartbeats. MfPc Mapping converts one-dimensional (1-D) electrocardiogram (ECG) recordings into corresponding two-dimensional (2-D) multi-feature RGB graphs, and it offers good excellent interpretability and data visualization. FlexShuffleNet is a lightweight network that can be adapted to classification tasks of varying complexity by tuning hyperparameters. The method has three steps. The first step is data preprocessing, which includes de-noising the raw ECG recordings, removing baseline drift, extracting heartbeats, and performing data balancing, the second step is transforming the heartbeats using MfPc Mapping. Finally, the FlexShuffleNet is employed to classify heartbeats into 14 categories. This study was evaluated on the test set of the MIT-BIH arrhythmia database (MIT/BIH DB), and it yielded the results i.e., accuracy of 99.77%, sensitivity of 94.60%, precision of 89.83% and specificity of 99.85% and F1-score of 0.9125 in 14-category classification task. Additionally, validation on Shandong Province Hospital database (SPH DB) yielded the results i.e., accuracy of 92.08%, sensitivity of 93.63%, precision of 91.25% and specificity of 99.85% and F1-score of 0.9315. The results show the satisfied performance of the proposed method.

Relationship between coagulopathy score and ICU mortality: Analysis of the MIMIC-IV database.

Objective: Coagulopathy score has been applied as a new prognostic indicator for sepsis, heart failure and acute respiratory failure. However, its ability to forecast intensive care unit (ICU) mortality in patients with an acute cerebral hemorrhage (ICH) has not been assessed. The purpose of this study was to clarify the relationship between ICU mortality and early coagulation problem score. Methods: Data from the Medical Information Mart for Intensive Care (MIMIC-IV) (v2.0) database were used in this retrospective cohort analysis. The association between the coagulation disorder score and ICU mortality was examined using multivariate logistic regression. Furthermore, the impact of additional variables on the results was investigated by a subgroup analysis. Results: 3174 patients (57.3 % male) were enrolled in total. The ICU mortality reached 18.2 %. After adjusting for potential confounders, the ICU mortality of patients rose with the increase of coagulation disorder score. The ROC curve revealed the predictive accuracy of coagulation dysfunction score to mortality in patients with ICU. The coagulation disorder score had a lower AUC value (0.601, P < 0.001) than the SAPSII(AUCs of 0.745[95 % CI, 0.730-0.761]) and the combined indicators(AUCs of 0.752[95 % CI, 0.737-0.767]), but larger than single indicators platelet, INR and APTT. In the subgroup analysis, most subgroups showed no significant interaction, but only age showed significant interaction in the adjusted model. Conclusion: The coagulopathy score and ICU mortality were found to be strongly positively correlated in this study, and its ability to predict ICU mortality was better than that of a single measure (platelet, INR, or APTT), but worse than that of the SAPSII score, GCS system.

Bipyridine Derivatives as NOP2/Sun RNA Methyltransferase 3 Inhibitors for the Treatment of Colorectal Cancer.

Based on the structure of caerulomycin A, 90 novel bipyridine derivatives were designed and synthesized. Among these, compound B19 exerted strong antitumor effects in vivo and in vitro. Importantly, NOP2/Sun RNA methyltransferase 3 (NSUN3) protein was identified as the target specific binding to B19, which inhibits oxidative phosphorylation of mitochondrial energy metabolism and enhances glycolytic activity by binding to NSUN3. Knockdown of NSUN3 inhibited both proliferation and migration of colorectal cancer (CRC) cells by activating AMPK-related signaling and inhibiting downstream STAT3 signaling to exert antiproliferative and pro-apoptotic effects. Our findings support the use of NSUN3 inhibitors as promising therapeutic strategies against CRC.

Visualized Lead Selection for Arrhythmia Classification Based on a Lead Activation Heatmap Using Multi-Lead ECGs.

Visualizing the decision-making process is a key aspect of research regarding explainable arrhythmia recognition. This study proposed a visualized lead selection method to classify arrhythmia for multi-lead ECG signals. The proposed method has several advantages, as it uses a visualized approach to select effective leads, avoiding redundant leads and invalid information. It also captures the temporal dependencies of ECG signals and the complementary information between leads. The method deployed a lead activation heatmap (LA heatmap) based on a lead-wise network to select the proper 5 leads from 12-lead ECG heartbeats extracted from the public 2018 Chinese Physiological Signal Challenge database (CPSC 2018 DB), which were then fed into a ResBiTime network combining bidirectional long short-term memory (Bi-LSTM) networks and residual connections for a classification task of nine heartbeat categories (i.e., N, AF, I-AVB, RBBB, PAC, PVC, STD, LBBB, and STE). The results indicate an average precision of 93.25%, an average recall of 93.03%, an average F1-score of 0.9313, and that the proposed method can effectively extract additional information from ECG heartbeat data.

The effect of warming ropivacaine on ultrasound-guided subgluteal sciatic nerve block: a randomized controlled trial.

BACKGROUND: There is a long latent period for the sciatic nerve block before a satisfactory block is attained. Changes in the temperature of local anesthetics may influence the characters of the peripheral nerve block. This study was designed to evaluate the effect of warming ropivacaine on the ultrasound-guided subgluteal sciatic nerve block. METHODS: Fifty-four patients for distal lower limbs surgery were randomly allocated into warming group (group W, n = 27) or room tempeture group (group R, n = 27) with the ultrasound-guided subgluteal sciatic nerve block. The group W received 30 ml of ropivacaine 0.5% at 30℃ and the group R received 30 ml of ropivacaine 0.5% at 23℃. The sensory and motor blockade were assessed every 2 min for 30 min after injection. The primary outcome was the onset time of limb sensory blockade. RESULTS: The onset time of sensory blockade was shorter in group W than in group R (16 (16,18) min vs 22 (20,23) min, p < 0.001), and the onset time of motor blockade was also shorter in group W than in group R (22 (20,24) min vs 26 (24,28) min, p < 0.001). The onset time of sensory blockade for each nerve was shorter in group W than in group R (p < 0.001). No obvious differences for the duration of sensory and motor blockade and the patient satisfaction were discovered between both groups. No complications associated with nerve block were observed 2 days after surgery. CONCLUSIONS: Warming ropivacaine 0.5% to 30℃ accelerates the onset time of sensory and motor blockade in the ultrasound-guided subgluteal sciatic nerve block and it has no influence on the duration of sensory and motor blockade. TRIAL REGISTRATION: The trial was registered on October 3, 2022 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/bin/project/edit?pid=181104 ), registration number ChiCTR2200064350 (03/10/2022).

Aquaporin-7 Facilitates Proliferation and Adipogenic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Regulating Hydrogen Peroxide Transport.

Hydrogen peroxide (H2O2) is a major form of reactive oxygen species that play an important role in the survival, proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). The regulatory mechanisms of H2O2 homeostasis in BMSCs are not fully understood. Here we demonstrate for the first time that aquaglyceroporin AQP7 is a functional peroxiporin expressed in BMSCs and remarkably upregulated upon adipodenic induction. The proliferation ability of BMSCs from AQP7-/- mice was significantly decreased, as indicated by fewer clonal formation and cell cycle arrest compared with wildtype BMSCs. AQP7 deficiency caused accumulation of intracellular generated H2O2 during BMSCs proliferation, leading to oxidative stress and inhibition of PI3K/AKT and STAT3 signaling pathways. After adipogenic induction, however, the AQP7-/- BMSCs exhibited greatly reduced adipogenic differentiation with fewer lipid droplets formation and lower cellular triglycerides content than wildtype BMSCs. In such case AQP7 deficiency was found to diminish import of extracellular H2O2 produced by plasma membrane NADPH Oxidases, resulting in altered AMPK and MAPK signaling pathways and reduced expression of lipogenic genes C/EBPα and PPARγ. Our data revealed a novel regulatory mechanism of BMSCs function through AQP7-mediated H2O2 transport across plasma membrane. AQP7 is a peroxiporin mediating H2O2 transport across the plasma membrane of BMSCs. During proliferation, AQP7 deficiency results in accumulation of intracellular generated H2O2 due to reduced export, which inhibited STAT3 and PI3K/AKT/insulin receptor signaling pathways and cell proliferation. During adipogenic differentiation, however, AQP7 deficiency blocked the uptake of extracelluar H2O2 generated through plasma membrane NOX enzymes. The reduced intracellular H2O2 level causes decreased expression of lipogenic genes C/EBPα and PPARγ due to altered AMPK and MAPK signaling pathways, leading to impaired adipogenic differentiation.

Prognostic significance of serum resolvin D1 levels in patients with acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study.

OBJECTIVE: Resolvin D1 (RvD1) has anti-inflammatory properties and may be neuroprotective. This study was designed to assess usability of serum RvD1 as a prognostic biomarker after intracerebral hemorrhage (ICH). METHODS: In this prospective, observational study of 135 patients and 135 controls, serum RvD1 levels were measured. Its relations to severity, early neurologic deterioration (END) and poststroke 6-month worse outcome (modified Rankin Scale scores of 3-6) were determined via multivariate analysis. Predictive effectiveness was evaluated based on area under receiver operating characteristic curve (AUC). RESULTS: Patients had markedly lower serum RvD1 levels than controls (median, 0.69 ng/ml versus 2.15 ng/ml). Serum RvD1 levels were independently correlated with the National Institutes of Health Stroke Scale (NIHSS) [ß, -0.036; 95 % confidence interval (CI), -0.060--0.013; VIF, 2.633; t = -3.025; P = 0.003] and hematoma volume (ß, -0.019; 95 % CI, -0.056--0.009; VIF, 1.688; t = -2.703; P = 0.008). Serum RvD1 levels substantially discriminated risks of END and worse outcome with AUCs at 0.762 (95 % CI, 0.681-0.831) and 0.783 (95 % CI, 0.704-0.850) respectively. A RvD1 cut-off value of 0.85 ng/ml was effective in predicting END with a sensitivity of 95.0 % and specificity of 48.4 % and its levels <0.77 ng/ml distinguished patients at risk of worse outcome with a sensitivity of 84.5 % and specificity of 63.6 %. Under restricted cubic spline, serum RvD1 levels were linearly related to risk of END and worse outcome (both P > 0.05). Serum RvD1 levels and NIHSS scores independently predicted END with odds ratio (OR) values of 0.082 (95 % CI, 0.010-0.687) and 1.280 (95 % CI, 1.084-1.513) respectively. Serum RvD1 levels (OR, 0.075; 95 % CI, 0.011-0.521), hematoma volume (OR, 1.084; 95 % CI, 1.035-1.135) and NIHSS scores (OR, 1.240; 95 % CI, 1.060-1.452) were independently associated with worse outcome. END prediction model containing serum RvD1 levels and NIHSS scores, and prognostic prediction model containing serum RvD1 levels, hematoma volumes and NIHSS scores displayed efficient predictive ability with AUCs at 0.828 (95 % CI, 0.754-0.888) and 0.873 (95 % CI, 0.805-0.924) respectively. Such two models were visually shown via building two nomograms. Using Hosmer-Lemeshow test, calibration curve and decision curve, the models were comparatively stable and had clinical benefit. CONCLUSION: There is a dramatical declination of serum RvD1 levels after ICH, which is tightly related to stroke severity and is independently predictive of poor clinical outcome, implying that serum RvD1 may be of clinical significance as a prognostic marker of ICH.

Prognostic significance of serum NLRC4 in patients with acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study.

Objective: Caspase activation and recruitment domain-containing protein 4 (NLRC4) is implicated in neuroinflammation. The aim of the study was to discern the potential ability of serum NLRC4 in assessment of prognosis after intracerebral hemorrhage (ICH). Methods: In this prospective, observational study, serum NLRC4 levels were quantified in 148 acute supratentorial ICH patients and 148 controls. Severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume, and poststroke 6-month functional outcome was estimated according to the modified Rankin Scale (mRS). Early neurologic deterioration (END) and 6-month poor outcome (mRS 3-6) were deemed as the two prognostic parameters. Multivariate models were established for investigating associations, and receiver operating characteristic (ROC) curves were configured to indicate predictive capability. Results: Patients had substantially higher serum NLRC4 levels than controls (median, 363.2 pg/ml vs. 74.7 pg/ml). Serum NLRC4 levels had independent correlation with NIHSS scores [ß, 0.308; 95% confidence interval (CI), 0.088-0.520], hematoma volume (ß, 0.527; 95% CI, 0.385-0.675), serum C-reactive protein levels (ß, 0.288; 95% CI, 0.109-0.341) and 6-month mRS scores (ß, 0.239; 95% CI, 0.100-0.474). Serum NLRC4 levels above 363.2 pg/ml were independently predictive of END (odds ratio, 3.148; 95% CI, 1.278-7.752) and 6-month poor outcome (odds ratio, 2.468; 95% CI, 1.036-5.878). Serum NLRC4 levels significantly distinguished END risk [area under ROC curve (AUC), 0.765; 95% CI, 0.685-0.846] and 6-month poor outcome (AUC, 0.795; 95% CI, 0.721-0.870). In terms of predictive ability for 6-month poor outcome, serum NLRC4 levels combined with NIHSS scores and hematoma volume was superior to NIHSS scores combined with hematoma volume, NIHSS scores and hematoma volume (AUC, 0.913 vs. 0.870, 0.864 and 0.835; all P < 0.05). Nomograms were built to reflect prognosis and END risk of combination models, where serum NLRC4, NIHSS scores and hematoma volume were enforced. Calibration curves confirmed stability of combination models. Conclusions: Markedly raised serum NLRC4 levels following ICH, in close relation to illness severity, are independently associated with poor prognosis. Such results are indicative of the notion that determination of serum NLRC4 may aid in severity assessment and prediction of functional outcome of ICH patients.

Discovery of unglycosylated indolocarbazoles as ROCK2 isoform-selective inhibitors for the treatment of breast cancer metastasis.

Breast cancer metastasis is a major challenge in clinical therapy because of the absence of effective treatments. Rho-associated coiled-coil kinase (ROCK), which is essential for cell invasion and migration, has recently been suggested as a potential target for the treatment of cancer metastasis. Herein, we report the structure-activity relationships (SAR) of indolocarbazoles against ROCK2 and reveal the crucial role of the C-3 hydroxyl for ROCK2 inhibition. The most potent unglycosylated aglycone THK01 was demonstrated to bind to and stabilize ROCK2 with potent anti-metastatic effects in breast cancer in vitro and in vivo with no obvious toxicities. Further mechanistic studies revealed that the anti-metastatic effect of THK01 was closely related to the suppression of STAT3Y705 activation. Moreover, THK01 exhibited excellent selectivity over the isoform protein ROCK1 (>100-fold). Taken together, with low toxicity, the ROCK2 inhibitor THK01 potently inhibited breast cancer metastasis through the ROCK2-STAT3 signaling pathway, which offers a new opportunity for the treatment of metastatic breast cancer.

Mdivi-1 ameliorates early brain injury after subarachnoid hemorrhage via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.

Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms. The endovascular perforation model of SAH was performed in adult male Sprague Dawley rats. The results indicated Mdivi-1(a selective Drp1 inhibitor) reversed the morphologic changes of mitochondria and Drp1 translocation, reduced ROS levels, ameliorated the BBB disruption and brain edema remarkably, decreased the expression of MMP-9 and prevented degradation of tight junction proteins-occludin, claudin-5 and ZO-1. Mdivi-1 administration also inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB), leading to decreased expressions of TNF-ɑ, IL-6 and IL-1ß. Moreover, Mdivi-1 treatment attenuated neuronal cell death and improved neurological outcome. To investigate the underlying mechanisms further, we determined that Mdivi-1 reduced p-PERK, p-eIF2α, CHOP, cleaved caspase-3 and Bax expression as well as increased Bcl-2 expression. Rotenone (a selective inhibitor of mitochondrial complexes I) abolished both the anti-BBB disruption and anti-apoptosis effects of Mdivi-1. In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress in SAH, and the inhibition of Drp1 by Mdivi-1 attenuated early brain injury after SAH probably via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.