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Accumulating evidence indicates that the onset of myocardial infarction (MI) shows obvious circadian rhythmicity. Clinical studies have shown that MIs that occur in the early morning have a poor prognosis, but the mechanisms involved are still unknown. In this study, we showed that the expression level of Period 2 (per2) in the heart of mice is lower in the early morning than at noon and that increasing the expression of per2 in H9C2 cells and rat cardiomyocytes increases autophagy levels. Further studies indicated that overexpression of per2 after an MI improved cardiac function by increasing autophagy. In summary, this study has shown that the circadian clock protein, per2, may be a regulator of MI.

Ulcerative colitis (UC), one forms of chronic inflammatory bowel disease (IBD), is characterized by recurrent inflammation, and Renshen Baidu Powder (RSBDP) is often used as a traditional Chinese medicine prescription for treating of UC, but the pharmacological mechanisms remains unclear. This research aims to explore the mechanisms of RSBDP in the treatment of UC based on network pharmacology. Through multiple databases collected the compounds and targets, and constructed the network. The crossover genes enrichment analysis were performed by protein-protein interaction (PPI) construction and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, 181 compounds and 266 targets were obtained. Potential candidate ingredients mainly include phytosterols, flavonoids, and coumarins, all of which have anti-inflammatory activities. GO and KEGG enrichment analysis suggested that RSBDP have anti-inflammatory and immunomodulatory effects. The effect of RSBDP on UC might be achieved by regulating the balance of cytokines (i.e., IL-6, TNF, IL-1) and the downstream mediators (i.e., STAT1, STAT3) in the immune system. And inflammation-, immune- and hypoxic-related pathways, like TNF, Toll-like receptors and HIF-1 signaling pathway. These results provide a theoretical basis for studying the effective substances of RSBDP in the treatment of UC and their mechanism of action for further research.

Background Although switching between ticagrelor and clopidogrel is common in clinical practice, the efficacy and safety of this de-escalation remain controversial. Hypothesis We assessed the occurrences, reasons, and outcomes of switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing successful primary percutaneous coronary intervention (PCI). Methods A total of 653 patients with STEMI were randomly assigned to receive loading dose of ticagrelor or clopidogrel before PCI and then received maintenance dose, respectively, for 12 months follow-up. The primary outcome was major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome included unexpected rehospitalization for angina, coronary revascularization, and stent thrombosis. The safety outcome was bleeding described by the Bleeding Academic Research Consortium (BARC) criteria. Results A total of 602 participants completed the study. The rate of switching from ticagrelor to clopidogrel was 48.6% and the main reason was financial burden. The rate of secondary ischemic events in the de-escalation group was higher than that in the ticagrelor group (15.1% vs 5.6%, P = 0.008), but lower than that in the clopidogrel group (15.1% vs 24.6%, P = 0.03), while there were no significant differences in MACE among the three groups (P = 0.16). De-escalation, ticagrelor, and clopidogrel did not cause significant differences in the rates of major bleeding among the three groups (BARC ≥ 2, P = 0.34). Conclusion Switching from ticagrelor to clopidogrel is very common in patients with STEMI in China. De-escalation might be safe but associated with high risk of ischemic events as compared to ticagrelor.

Homeobox A10 (HOXA10) is a well-known transcription factor that plays an important role in directing endometrial differentiation and establishing the conditions required for implantation. Interestingly, the expression level of HOXA10 may be associated with litter size. To study the effects of the porcine HOXA10 promoter fragment on the expression of HOXA10 gene in vivo, we generated a transgenic mouse model using pronuclear microinjection, and measured the expression of HOXA10 in the endometrium. There was no difference in the expression level of HOXA10 between transgenic and wild-type mice in the absence of hormone stimulation. However, following treatment with progesterone and estradiol benzoate, the expression level of HOXA10 was significantly increased in transgenic mice compared with that of wild-type mice. Furthermore, the litter size of transgenic females was larger than that of wild-type females (7.02±1.73 vs. 6.48±1.85; P=0.14). Moreover, the difference of litter size was greater in the later parities (7.33±1.62 vs. 6.37±2.02; P=0.08) compared with the first parity (6.76±1.81 vs. 6.61±1.67; P=0.77) between transgenic and wild-type mice. Therefore, our transgenic mouse model provides exciting insights regarding the actions of HOXA10 and its hormone-inducible promoter in vivo. The present study offers valuable proof of principle to develop transgenic pigs with a hormone-inducible promoter regulating HOXA10 to alter litter size.