The Molecular Mechanism of Radix Paeoniae Rubra.-Cortex Moutan. Herb Pair in the Treatment of Atherosclerosis: A Work Based on Network Pharmacology and In Vitro Experiments.

Radix Paeoniae Rubra. (Chishao, RPR) and Cortex Moutan. (Mudanpi, CM) are a pair of traditional Chinese medicines that play an important role in the treatment of atherosclerosis (AS). The main objective of this study was to identify potential synergetic function and underlying mechanisms of RPR-CM in the treatment of AS. The main active ingredients, targets of RPR-CM and AS-related genes were obtained from public databases. A Venn diagram was utilized to screen the common targets of RPR-CM in treating AS. The protein-protein interaction network was established based on STRING database. Biological functions and pathways of potential targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Cytoscape was used to construct the drug-compound-target-signal pathway network. Molecular docking was performed to verify the binding ability of the bioactive ingredients and the target proteins. The endothelial inflammation model was constructed with human umbilical vein endothelial cells stimulated with ox-LDL, and the function of RPR-CM in treating AS was verified by CCK-8 assay, enzyme-linked immunosorbent assay, and qPCR. In this study, 12 active components and 401 potential target genes of RPR-CM were identified, among which quercetin, kaempferol and baicalein were considered to be the main active components. A total of 1903 AS-related genes were identified through public databases and four GEO datasets (GSE57691, GSE72633, GSE6088 and GSE199819). There are 113 common target genes of RPR-CM in treating AS. PPI network analysis identified 17 genes in cluster 1 as the core targets. Bioinformatics analysis showed that RPR-CM in AS treatment was associated with multiple downstream biological processes and signal pathways. PTGS2, JUN, CASP3, TNF, IL1B, IL6, FOS, STAT1 were identified as the core targets of RPR-CM, and molecular docking showed that the main bioactive components of RPR-CM had good binding ability with the core targets. RPR-CM extract significantly inhibited the levels of inflammatory factors TNF-α, IL-6, IL-1ß, MCP-1, VCAM-1 and ICAM-1 in HUVECs, and inhibited endothelial inflammation. This study revealed the active ingredients of RPR-CM, and identified the key downstream targets and signaling pathways in the treatment of AS, providing theoretical basis for the application of RPR-CM in prevention and treatment of AS.

Regiodivergent and Stereoselective Synthesis of Highly Substituted 1,3-Dienes via Arylative Acyloxy Migration of Propargyl Esters.

We report the first catalyst-controlled regiodivergent method that enables the synthesis of structurally diverse 1,2,3,4-tetrasubstituted conjugated dienes with excellent regio- and stereochemical outcomes from the same set of readily available propargyl esters and diaryliodonium salts. In this diene chemistry, the in situ generated, highly electrophilic aryl-CuIII complex serves not only as a π-Lewis acid catalyst for alkyne activation/acyloxy migration but also as an aryl electrophile equivalent. The competitive arylative 1,2- and 1,3-acyloxy migration patterns are exquisitely dictated by Cu and Au/Cu relay catalyses, respectively, providing a modular and attractive approach to traditionally inaccessible tetrasubstituted 1,3-dienes in a regiodivergent manner. Finally, the synthetic utility of this method is demonstrated by further synthetic derivatization of 1,3-dienes into an array of useful compounds.

The effect of a simple simulator on the application of laparoscopic common bile duct exploration in a low volume center.

BACKGROUND: The purpose of this study was to investigate the effect of a simple laparoscopic common bile duct exploration (LCBDE) simulator and corresponding practicing program on the application of performing LCBDE in a low volume center. METHODS: A retrospective review was performed by analyzing data from the electronic medical record for 4118 patients with choledocholithiasis in Changxing County Hospital (Huzhou, Zhejiang, China) between January 2013 and December 2018. From January 2016, we have developed a simple LCBDE-specific simulator and corresponding practicing program in our hospital. The percentage of patients with choledocholithiasis managed by LCBDE before and after the introduction of a simple LCBDE-specific simulator and corresponding practicing program was compared. RESULTS: There were 8.9% (367/4118) patients with a diagnosis of choledocholithiasis confirmed by MRCP. Single-stage management with LC+LCBDE was performed in 23.7% (87/367) patients. Among them, 23 cases were performed between January 2013 and December 2015, and 64 cases were performed between January 2016 and December 2018. The introduction of simulator-enhanced practicing program in January 2016 has resulted in an increase in the percentage of performed LCBDE, from 12.9% to 33.9%. In addition, there was an 29.5% reduction in the mean operating time (from 193 min to 136 min) needed for LCBDE with T-tube when compared these two periods. CONCLUSIONS: LCBDE simulator can improve the application in a low volume center, and help to increase the utilization of this effective, one stage treatment for choledocholithiasis and reduce the need for costlier ERCP.