Objectives: This study investigated the clinical efficacy and safety of metformin hydrochloride sustained-release (SR) tablet (II) produced by Dulening and the original metformin hydrochloride tablet produced by Glucophage in the treatment of type 2 diabetes mellitus (T2DM). Methods: This randomized, open and parallel controlled clinical trial consecutively recruited a total of 886 patients with T2DM in 40 clinical centers between May 2016 and December 2018. These patients were randomly assigned to the Dulening group (n=446), in which patients were treated with Dulening metformin SR tablets, and the Glucophage group (n=440), in which patients were treated with Glucophage metformin tablets, for 16 weeks. The changes in the levels of glycated hemoglobin (HbAc1) and fasting blood glucose (FBG) as well as weight loss were compared between these two groups. Also, the overall incidence of adverse drug reactions (ADRs) and the incidence of ADR of the gastrointestinal system observed in patients of these two groups were also compared. Results: There were no significant differences in demographic and basal clinical characteristics between these two groups. The Dulening and Glucophage groups showed comparable levels of decrease in HbA1c levels, FBG and weight loss after 12-week treatment (all p>0.05). The Dulening group had a significantly lower overall incidence of ADRs as well as gastrointestinal ADR than the Glucophage group. Conclusions: Metformin SR tablets (II) and the original metformin tablets exhibit similar therapeutic efficacy in the treatment of T2DM, but metformin SR tablets (II) has the significantly lower incidence of ADRs than the original metformin tablets.

Objective: Statins are clinically used for protection against cardiovascular disease with lipid-lowering and anti-inflammatory properties. These properties tip the balance of macrophage polarization, which is an essential process in the development and progression of atherosclerosis. This study aimed to investigate the effect of pravastatin on atherosclerosis of the aorta in apolipoprotein E knockout (apoE-KO) mice without high lipid feeding. Methods: Six 8-week-old apoE-KO male mice were randomly divided into two groups: a control group and a pravastatin (40 mg·kg⁻¹·day⁻¹)-treated group. At 35 weeks, the mice were sacrificed and the size of plaques on the aorta was assessed by Oil Red O staining. M1 and M2 macrophages were identified by inducible nitric oxide synthase and arginase-I, respectively, using immunohistochemistry. Results: Pravastatin increased the size of atherosclerotic plaques in apoE-KO mice without high lipid feeding. The ratio of M1/M2 macrophages increased in atherosclerotic plaques, which might slow the process of atherosclerosis, while blood cholesterol levels were elevated. Conclusion: Our study suggests that pravastatin polarizes the phenotype of macrophages toward M2 in atherosclerotic lesions, despite an increase in serum cholesterol levels in ApoE-KO mice.

The accumulation of free cholesterol in macrophage lysosomes significantly enhances atherogenesis. Our recent study demonstrated that the cluster of differentiation 38 (CD38)/nicotinic acid adenine dinucleotide phosphate (NAADP)/Ca²⁺ signaling pathway plays a critical role in the efflux of lysosomal free cholesterol from macrophages in atherosclerosis. Niacin, known as nicotinic acid, is one of the oldest lipid-lowering medications showing unique anti-atherosclerotic activity. However, it is unknown whether this anti-atherosclerosis activity is associated with the efflux of lysosomal compartmentalized cholesterol in macrophages. In this study, we investigated the anti-atherosclerotic effects of niacin on the reduction of lysosomal free cholesterol via CD38/NAADP signaling in macrophages derived from low-density lipoprotein receptor (LDLr^−/−) mice. Fluorescent filipin and Nile red labeling coupled with confocal microscopy demonstrated that niacin reduced free cholesterol accumulation in lysosomes in a concentration-dependent manner. Transmission electron microscopy also showed that niacin markedly decreased cholesterol crystal formation in lysosomes in oxidized LDL-containing LDLr^−/− bone marrow–derived macrophages. Enzyme-linked immunosorbent assays showed that niacin increased NAADP production in a concentration-dependent manner, which was inhibited by small interfering RNA interference of CD38. Therefore, niacin may promote the efflux of lysosomal cholesterol from macrophages via the CD38/NAADP signaling pathway.

Increasing attention has been directed to the study of the automatic emotion recognition in human speech recently. This paper presents an approach for recognizing negative emotions in spoken dialogs at the utterance level. Our approach mainly includes two parts. First, in addition to the traditional acoustic features, linguistic features based on distributed representation are extracted from the text transcribed by an automatic speech recognition (ASR) system. Second, we propose a novel deep learning model, multi-feature stacked denoising autoencoders (MSDA), which can fuse the high-level representations of the acoustic and linguistic features along with contexts to classify emotions. Experimental results demonstrate that our proposed method yields an absolute improvement over the traditional method by 5.2 %.

Tubercidin, known for its antimicrobial, antiparasitic, and anticancer effects, faces clinical limitations due to adverse effects, especially cardiotoxicity risks for those with ischemic cardiomyopathy. This study aims to clarify the molecular pathways of Tubercidin-induced cardiotoxicity, focusing on nuclear speckles (NSs) disruption in cardiomyocytes under serum deprivation and/or hypoxia. To simulate ischemic cardiomyopathy in vitro, we utilized FMC84 and HL-1 murine cardiomyocyte cell lines, exposing them to conditions of serum limitation and/or hypoxia to evaluate the cardiotoxic impact of Tubercidin and the contributing mechanisms. Apoptosis was quantified using flow cytometry, NSs condensation was visualized via immunofluorescence with an anti-SC35 antibody, and the expression levels of key apoptotic transcripts (RFFL, RIF1, and RNF144B) were analyzed by RT-PCR. Our findings revealed that Tubercidin significantly increased apoptosis in both HL-1 and FMC84 cell lines under conditions mimicking serum deprivation (21% O2 with 1% FBS), hypoxia (1% O2 with 10% FBS), or a combination of both. Furthermore, Tubercidin treatment led to a pronounced enlargement of NSs, as detected by immunofluorescence. Concurrently, we documented significant alterations in the expression of critical apoptotic regulatory genes, implying that Tubercidin may modulate the apoptotic pathway in stressed cardiomyocytes. It is hypothesized that Tubercidin induces NSs condensation, affecting alternative splicing of cell death genes, potentially worsening ischemic cardiomyocytes' damage. Therefore, a cautious clinical use of Tubercidin for ischemic cardiomyopathy patients is advised to reduce cardiotoxicity risks.

Objective: The performance of blood glucose prediction and hypoglycemia warning based on the LSTM-GRU (Long Short Term Memory - Gated Recurrent Unit) model was evaluated. Methods: The research objects were 100 patients with Diabetes Mellitus (DM) who were chosen from Henan Provincial People’s Hospital. Their continuous blood glucose curves of 72 hours were acquired by a Continuous Glucose Monitoring System (CGMS). The blood glucose levels were predicted based on the LSTM, GRU and LSTM-GRU models, respectively. Analyses of the best predictive model were performed using Root Mean Square Error (RMSE), Mean Absolute Percentage Error (MAPE), Mean Absolute Error (MAE) and correlation analysis between the prediction blood glucose level and the original blood glucose level acquired by CGMS and Clark Error Grid Analysis (EGA). Repeated-measures analysis of variance (ANOVA) was used to analyze whether the RMSE values of the three models were statistically significant. 60 patients who had experienced hypoglycemia among 100 cases were selected for hypoglycemia warning. The sensitivity, false-positive rate and false-negative rate were used to evaluate the hypoglycemia warning performance of the LSTM-GRU model. This paper explored the changing relationship of the hypoglycemia warning performance of the model over time. Results: The predicted blood glucose levels of the three models were strongly correlated with the blood glucose levels acquired by CGMS (p < 0.001). The correlation coefficient (R-value) of the LSTM-GRU model remained sover time (R = 0.995), nevertheless, a reduction in the R-value of the LSTM and GRU models when the Prediction Horizon (PH) was 30 min or longer. When PH was 15min, 30min, 45min and 60min, the mean RMSE values of the LSTM-GRU model were 0.259, 0.272, 0.275 and 0.278 (mmol/l), respectively, which were lower than the LSTM and GRU models and the RMSE values were statistically significant (p < 0.001). The EGA results showed the LSTM-GRU model had the highest proportion in zones A and B, as the PH extended. When PH was 30min or longer, the sensitivity and false-negative rate of the hypoglycemia warning of the LSTM-GRU model had subtle changes and the false-positive rate remained sover time. Conclusions: The LSTM-GRU model demonstrated good performance in blood glucose prediction and hypoglycemia warning.