EFFECT OF ANESTHESIA DURATION ON INTRAVITREAL INJECTION PAIN: A double-blinded, randomized, comparative study.

PURPOSE: To determine the effect of different durations of topical anesthesia on intravitreal injection (IVI) pain. METHODS: This was a double-blinded, randomized, comparative study . Three hundred and twelve sequential eyes undergoing IVI were randomized to one of six groups according to the duration of topical anesthesia (from 1 to 30 minutes, one group for every 5-minute range, Groups 1-6). Topical anesthesia before IVI was standardized. Patients graded their pain using the visual analog scale and the Wong-Baker FACES scale at 15 minutes after the procedure. RESULTS: The pain scores among the six groups were significantly different for the visual analog scale ( P = 0.013) and Wong-Baker FACES scale ( P = 0.024). The mean pain scores for Group 4 were 1.97 ± 1.04 (visual analog scale) and 2.02 ± 1.08 (Wong-Baker FACES scale) and were significantly lower than those of Group 1, 2, 5, or 6. CONCLUSION: The duration of topical anesthesia significantly correlated with IVI pain. Preoperative 0.5% proparacaine hydrochloride drops were most effective in relieving IVI pain 11 to 20 minutes after topical administration.

Network Pharmacology-Based Analysis of the Potential Biological Mechanisms of Coix Seed against Colorectal Cancer.

Objective: The aim of this study was to explore the potential biological mechanisms of coix seed in the treatment of colorectal cancer (CRC) based on network pharmacology analysis. Methods: The active components of coix seed and their potential action targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The disease targets related to CRC were obtained from the DisGeNET database. The intersection targets of the drug targets and disease targets were selected, and a component-target-disease network was built using Cytoscape 3.8.0 tool. A global network of the core target protein interactions was constructed using String database. Biological function analysis and pathway enrichment analysis of core targets were conducted to explore the potential. Results: A total of nine active components were obtained from the TCMSP database corresponding to 37 targets. Further analysis showed that 18 overlapping targets were associated with CRC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted based on the 18 targets and 11 significantly enriched signaling pathways implicated in CRC were identified. Conclusion: The multicomponent and multitarget characteristics of coix seed are preliminarily verified, and the potential biological mechanisms of coix seed in the treatment of CRC are predicted, which provides a theoretical basis for the experimental research.

Astragaloside IV ameliorates diet-induced hepatic steatosis in obese mice by inhibiting intestinal FXR via intestinal flora remodeling.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major clinical and public health burden worldwide with no established pharmacological therapy. Changes in the intestinal flora and associated metabolite bile acids (BAs) have been described in NAFLD. Astragaloside IV (AS-IV) is a low drug permeability saponin with protective effects against multiple diseases. However, the specific mechanism underlying the involvement of AS-IV in the regulation of NAFLD is yet to be clarified. PURPOSE: This study aimed to investigate the effect of AS-IV on NAFLD and explore whether intestinal flora was involved. METHODS: The effect of AS-IV was evaluated on high-fat diet-fed mice. Real-time PCR, immunohistochemistry, immunofluorescence, and biochemical analyses were performed. 16S rRNA gene sequencing and UPLC-TQMS were used to determine the alterations in the intestinal flora and concentration of BAs. Fecal microbiota transplantation (FMT) and intestine-specific farnesoid X receptor (FXR) knockout were also performed. RESULTS: AS-IV treatment alleviated diet-induced metabolic impairments, particularly hepatic steatosis. These changes occurred in the setting of decreased intestinal bile salt hydrolase (BSH)-expressing flora. Further analysis showed that the reduced BSH activity increased intestinal tauro-ß-muricholic acid levels, an inhibitor of intestinal FXR. Inhibition of intestinal FXR signaling by AS-IV was accompanied by decreased expression of intestinal fibroblast growth factor 15 and subsequent hepatic FXR activation as well as increased glucagon-like peptide-1 and decreased ceramide production, all of which contribute to the inhibition of sterol regulatory element-binding protein-1c-mediated hepatic steatosis. Furthermore, intestine-specific Fxr knockout and FMT further demonstrated an FXR- and intestinal flora-dependent preventive effect of AS-IV on hepatic steatosis. CONCLUSION: These results show that the changes in intestinal flora and BAs serve an essential role in the remission of hepatic steatosis by AS-IV, thereby suggesting that AS-IV may be used as a prebiotic agent to provide viable treatment for NAFLD.

Cloning of Two Acetylcholinesterase Genes and Analysis of Point Mutations Putatively Associated with Triazophos Resistance in Chilo auricilius (Lepidoptera: Pyralidae).

Acetylcholinesterase (AChE) is the target of organophosphate (OP) and carbamate insecticides. Mutations in the AChE gene (ace) leading to decreased insecticide susceptibility is the main resistance mechanism in insects. In this study, two Chilo auricilius acetylcholinesterase genes, designated as Caace1 and Caace2, were cloned using RT-PCR and RACE. Caace1 cDNA is 2534 bp, with ORF of 2082 bp, and it encodes an acetylcholinesterase 1 (CaAChE1) protein comprising a calculated 693 amino acid (aa) residues. Caace2 cDNA contains 2280 bp, with a full-length ORF of 1917 bp, encoding acetylcholinesterase 2 (CaAChE2) comprising a calculated 638 aa residues. At the aa level, CaAChE1 displays the highest similarity (97%) with the Chilo suppressalis AChE1, and CaAChE2 shows the highest similarity with the C. suppressalis AChE2 (99%). From the restriction fragment length polymorphism (RFLP) PCR (RFLP-PCR) analysis, one mutation in Caace1, similar to the ace1 mutation associated with triazophos resistance in C. suppressalis, was detected. Detailed examination of field populations of C. auricilius indicated this resistance mutation in C. auricilius is still quite infrequent. Based on the assay of AChE activity and RFLP-PCR testing, an individual that contains resistance mutation has lower AChE activities, while the individual that does not contain the resistance mutation has higher AChE activities. This study provides a basis for future investigations into the mechanism of OP resistance in C. auricilius, as well as a guidance for C. auricilius control with reasonable choice of pesticides.