The Impact of Emergency Department Arrival Time on Door-to-Balloon Time in Patients with ST-Segment Elevation Myocardial Infarction Receiving Primary Percutaneous Coronary Intervention.

Door-to-balloon (DTB) time significantly affects the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). The effects of temporal differences in emergency department (ED) arrival time on DTB time and on different segments of DTB time remain inconclusive. Therefore, we performed a retrospective study in a tertiary hospital between January 2013 and December 2021 and investigated the relationship between a patient's arrival time and both their DTB time and different segments of their DTB time. Of 732 STEMI patients, 327 arrived during the daytime (08:01-16:00), 268 during the evening (16:01-24:00), and 137 at night (00:01-08:00). Significantly higher odds of delay in DTB time were observed during the nighttime (adjusted odds ratio (aOR): 2.87; 95% confidence interval (CI): 1.50-5.51, p = 0.002) than during the daytime. This delay was mainly attributed to a delay in cardiac catheterization laboratory (cath lab) activation-to-arrival time (aOR: 6.25; 95% CI: 3.75-10.40, p < 0.001), particularly during the 00:00-04:00 time range. Age, sex, triage level, and whether patients arrived during the COVID-19 pandemic also had independent effects on different segments of DTB time. Further studies are required to investigate the root causes of delay in DTB time and to develop specific strategies for improvement.

Nuclear-targeted carbon quantum dot mediated CRISPR/Cas9 delivery for fluorescence visualization and efficient editing.

Nuclear targeted delivery has great potential in improving the efficiency of non-viral carrier mediated genome editing. However, direct and efficient delivery of CRISPR/Cas9 plasmid into the nucleus remains a challenge. In this study, a nuclear targeted gene delivery platform based on fluorescent carbon quantum dots (CQDs) was developed. Polyethylenimine (PEI) and polyethylene glycol (PEG) synergistically passivated the surface of CQDs, providing an excitation-independent green-emitting fluorescent CQDs-PEI-PEG conjugate (CQDs-PP) with an ultra-small size and positive surface charge. Here we show that CQDs-PP could bind CRISPR/Cas9 plasmid to form a nano-complex by electrostatic attraction, which can bypass lysosomes and enter the nucleus by passive diffusion, and thereby improve the transfection efficiency. Also, CQDs-PP could deliver CRISPR/Cas9 plasmid into HeLa cells, resulting in the insertion/deletion mutation of the target EFHD1 gene. More importantly, CQDs-PP exhibited a considerably higher gene editing efficiency as well as comparable or lower cytotoxicity relative to Lipo2000 and PEI-passivated CQDs-PEI (CQDs-P). Thus, the nuclear-targeted CQDs-PP is expected to constitute an efficient CRISPR/Cas9 delivery carrier in vitro with imaging-trackable ability.

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway.

Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive. Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot. Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells. Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.