Genome-Wide Identification and Analysis of Enhancer-Regulated microRNAs Across 31 Human Cancers.

Enhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner, and dysregulation of target genes could lead to various diseases, such as cancer. Recent studies have shown that enhancers can regulate microRNAs (miRNAs) and participate in their biological synthesis. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer-miRNA interactions and 1,280 distal enhancer-miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited a significant cancer type-specific feature trend at the tissue level rather than at the single-cell level, and there was a noteworthy positive correlation between the expression of the miRNA and the number of enhancers regulating the same miRNA in most cancers. Furthermore, we found that there was a high correlation between the formation of enhancer-miRNA pairs and the expression of enhancer RNAs (eRNAs) whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, guanine-cytosine (GC) content, and histone modification signatures. Notably, GC content, H3K4me1, and H3K36me3 were present differently between distal and proximal regulation, suggesting that they might participate in chromosome looping of enhancer-miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391-1186507 ∼ miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on the enhancer affected the expression of the TNFRSF18 gene as a tumor suppressor.

Ultrasound-guided continuous thoracic paravertebral block alleviates postoperative delirium in elderly patients undergoing esophagectomy: A randomized controlled trial.

BACKGROUND: Delirium is a common postoperative complication in older patients undergoing thoracic surgery and presages poor outcomes. Postoperative pain is an important factor in the progression of delirium. The purpose of this study was to test whether continuous thoracic paravertebral block (PVB), a more effective approach for analgesia, could decrease the incidence of delirium in elderly patients undergoing esophagectomy. METHODS: A total of 180 geriatric patients undergoing esophagectomy were randomly divided into 2 groups and treated with PVB or patient-controlled analgesia (PCA). Perioperative plasma CRP, IL-1ß, IL-6, and TNF-α levels were detected in all patients. Pain intensity was measured by a numerical rating scale. Delirium was assessed using the confusion assessment method. RESULTS: The incidence of postoperative delirium was significantly lower in the PVB group than in the PCA group. Patients in the PVB group had lower plasma CRP, IL-1ß, IL-6, and TNF-α levels and less pain when coughing after surgery. CONCLUSIONS: Ultrasound-guided continuous thoracic paravertebral block improved analgesia, reduced the inflammatory reaction and decreased the occurrence of delirium after surgery.

Influence of exposure to nicotine during pregnancy on the learning and memory for adult offspring.

We aimed to investigate the indirect influence of exposure to nicotine during pregnancy on the learning and memory of adult offspring mice. Thirty pregnant C57 mice were randomly divided into either the control group (CON) or the nicotine group (NIC), with 15 mice each. The CON group was given access to drug-free water, and the NIC group was given 60 g/ml nicotine in drinking water. Sixteen adult mice were randomly selected from the 8 litters for Morris water maze test. The level of products of related factors in the hippocampus of mice in the NIC and the CON groups were compared using the 1H-MRS method. The escape latency time that the adult offspring mice in the NIC group took in the place navigation test was significantly longer than that of the CON group. In addition, the NIC group took longer time to arrive at the plate than the CON group (P<0.05). mRNA and protein levels of NR1 in the hippocampus of the NIC group was significantly higher than that in the CON group (P<0.05).α7nACh mRNA in the hippocampus of the NIC group was not significantly different from that of the CON group (P>0.05), while the expression levels of α7nACh protein in the hippocampus of the NIC group was significantly lower than that in the CON group (P<0.05). Detection of protein level of muscarinic receptors in the hippocampus of adult offspring mice in the NIC group showed that when compared to the CON group, the expression levels of M1, M3, M5 of the NIC group was not significantly different from that of the CON group (P>0.05). Therefore, exposure to nicotine during pregnancy can cause damage to the learning ability of adult offspring mice but do not significantly influence their working memory.

Postoperative benefits of dexmedetomidine combined with flurbiprofen axetil after thyroid surgery.

The present study determined the effect of dexmedetomidine (Dex) combined with flurbiprofen axetil (FA) on analgesia, immune response, and preservation of cognitive function in patients subjected to general anesthesia. We recruited 100 patients with thyroid surgery and randomly divided them into four groups: Dex (D), FA (F), Dex combined with FA (DF), and saline control (C). The extubation and recovery times for Groups D and DF were significantly longer than for Groups F and C. After extubation, the heart rate and mean arterial pressure for Groups F, D, and DF were significantly lower than for Group C, and data for Group DF was significantly lower than for Group F. The visual analog scale and Riker sedation agitation scores were significantly lower in Group DF than for the other three groups. T- and B-lymphocytes were significantly higher in Group DF than in the other three groups. Compared with Groups F and C, the levels of TNF-α and IL-6 in Group DF were significantly reduced, while IL-2 markedly increased. The combined use of Dex and FA significantly improved pain after general anesthesia thyroid surgery, reduced restlessness and postoperative cognitive dysfunction, enhanced immune function, and promoted wound repair.