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BackgroundDietary polyphenols, polypeptides, and oligosaccharides modulate inflammation and immunity by altering the composition of gut microbiota. The polyphenols and polypeptides in Chinese rice wine have protective effects against cardiovascular disease. In this study, we hypothesized that the polyphenols, polypeptides, and oligosaccharides in Chinese rice wine can ameliorate diabetic cardiomyopathy (DCM) by altering gut microbiota and metabolites.MethodsMice with DCM and high glucose cells were treated with rice wine polyphenols (RWPH), rice wine polypeptides (RWPE), and rice wine oligosaccharides. Cardiac function was evaluated by echocardiography and detection of myocardial injury markers. We observed the pathological structures using hematoxylin and eosin staining, Masson's trichrome staining, and transmission electron microscopy. The expression levels of autophagy-related proteins and stubRFP-sensGFP-LC3 fluorescence were measured to evaluate autophagy. We performed TUNEL staining and measured the levels of Bax, Bcl-2, and p53 to assess apoptosis. To analyze the effects of the rice wine functional components on the gut microbiota and metabolites of DCM mice, we performed fecal 16S-rDNA gene sequencing and serum untargeted metabolomics.ResultsOur results showed an increase in cardiac and mitochondrial function, promotion of autophagy, and inhibition of cardiomyocyte apoptosis, which indicates that RWPH and RWPE can ameliorate DCM. The abundance of Akkermansia and Desulfovibrio were reduced by the presence of RWPH and RWPE. The growth of the Lachnospiraceae_NK4A136_group and Clostridiales-unclassified were promoted by the presence of RWPH. Tryptophan metabolism-associated metabolites were increased and phenylalanine levels were reduced by the presence of RWPH and RWPE. The biosynthesis of primary bile acids was enhanced by the presence of RWPH.ConclusionBoth RWPH and RWPE provided a protective effect against DCM by promoting autophagy, inhibiting apoptosis, and reversing both gut microbiota dysbiosis and metabolic dysregulation.

BackgroundThe high prevalence of patent foramen ovale (PFO) in cryptogenic stroke suggested a stroke-causing role for PFO. As risk factors for recurrence of such stroke are not recognized, clinicians cannot sufficiently identify, treat, and follow-up high-risk patients. Therefore, this study aimed to establish a prediction model for PFO-related stroke recurrence.MethodsThis study included 392 patients with PFO-related stroke in a training set and 164 patients with PFO-related stroke in an independent validation set. In the training set, independent risk factors for recurrence identified using forward stepwise Cox regression were included in nomogram 1, and those identified using least absolute shrinkage and selection operator(LASSO)regression were included in nomogram 2. Nomogram performance and discrimination were assessed using the concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analyses (DCA). The results were also validated in the validation set.ResultsNomogram 1 was based on homocysteine (Hcy), high-sensitivity C-reactive protein (hsCRP), and albumin (ALB), and nomogram 2 was based on age, diabetes, hypertension, right-to-left shunt, ALB, prealbumin, hsCRP, and Hcy. The C-index of nomogram 1 was 0.861, which was not significantly different from that of nomogram 2 (0.893). The 2- and 5-year AUCs of nomogram 1 were 0.863 and 0.777, respectively. In the validation set, nomogram 1 still had good discrimination (C-index, 0.862; 2-year AUC, 0.839; 5-year AUC, 0.990). The calibration curve showed good homogeneity between the prediction by nomogram 1 and the actual observation. DCA demonstrated that nomogram 1 was clinically useful. Moreover, patients were successfully divided into two distinct risk groups (low and high risk) for recurrence rate by nomogram 1.ConclusionsNomogram 1, based on Hcy, hsCRP, and ALB levels, provided a more clinically realistic prognostic prediction for patients with PFO-related stroke. This model could help patients with PFO-related stroke to facilitate personalized prognostic evaluations.