Aim To observe the effects of promethazine on the analgesia,hypnosis,amnesia and therapeutic index of isoflurane.Methods The experiments were designed to study promethazine on the analgesic effect of isoflurane by hot-plate test and writhing test,and to study the effect of promethazine on the sleeping time of isoflurane by the method of righting reflex,and the amnesia of isoflurane by Morris water maze,and the ED_(50),LD_(50) by sequential method in mice.Results The result of hot-plate test and writhing test indicated that promethazine could enhance the analgesic effect of isoflurane(P＜0.05 or P＜0.01);through the experiment of righting reflex, sleeping time of isoflurane in mice was extended by promethazine(P＜0.01);in Morris water maze experiment, the average latency in the combination of promethazine and isoflurane was longer than that of the promethazine group or isoflurane group(P＜0.05 or P＜0.01), while aiming to the residence time, the combination of the two was shorter than that in the third quadrant(P＜0.01 or P＜0.05),the TCPP of the group of isoflurance was more than that of the combination group;promethazine could decrease the ED_(50) of isoflurance(P＜0.01),but it did not obviously affect its LD_(50)(P＞0.05).Conclusion Promethazine can not only reinforce the effect of isoflurance on analgesia,hypnosis and amnesia, but also boost the therapeutic index of isoflurance.

BACKGROUND:Recent studies have shown that the occurrence and prevention of osteoporosis often focus on the cellular molecular level,and the mechanism of related signaling pathways is an important way to further understand osteoporosis.At present,traditional Chinese medicine has been proved to play a significant role in alleviating osteoporosis.Kaempferol as an emerging Chinese herbal extract has become the focus of clinical and basic research due to its anti-osteoporosis effectiveness and mechanism of action. OBJECTIVE:To further understand the mechanism underlying the anti-osteoporosis effect of kaempferol active monomer through regulation of related signaling pathways by analyzing and collating domestic and foreign literature. METHODS:"Kaempferol,osteoporosis,osteoblasts,osteoclasts,bone marrow mesenchymal stem cells,signaling pathways"were used as Chinese and English search terms to search CNKI,WanFang,VIP,PubMed,Web of Science and Embase databases for relevant literature published from database inception to February 2023. RESULTS AND CONCLUSION:Kaempferol affects the occurrence and progression of osteoporosis to varying degrees by participating in the regulation of differentiation,proliferation and apoptosis of bone marrow mesenchymal stem cells,osteoblasts and osteoclasts.Kaempferol can prevent and treat osteoporosis by regulating various signaling pathways.Kaempferol can promote the proliferation and differentiation of osteoblasts and inhibit the formation of osteoclasts by interfering with the Wnt/β-catenin signaling pathway to regulate β-catenin protein counting and the formation of β-catenin-TCf/LEF complex.Kaempferol interferes with the RANK/RANKL pathway to maintain the dynamic balance of osteoclasts and bone homeostasis.Kaempferol can promote bone formation by intervening with the PI3K/Akt signaling pathway to upregulate the levels of related osteogenic factors Runx2 and Osterix and promote bone cell calcification.Kaempferol interferes with osteoclast differentiation and inhibits reactive oxygen species activity by regulating the ER/ERK pathway.Kaempferol inhibits the expression of ERK,JNK,p38/MAPK and decreases reactive oxygen species production by interfering with the MAPK pathway,thus protecting osteogenesis.Kaempferol enhances the expression of osteogenic factors,bone morphogenetic protein-2,p-Smad1/5/8,β-catenin and Runx2,inhibits the expression of Peroxisome proliferation-activated receptor,and promotes the differentiation and proliferation of osteoblasts through the BMP/Smad pathway.

Glycolysis is an important biological event in the metabolic reprogramming process of primary liver cancer.Its is mainly regulated by key rate-limiting enzymes in the glycolysis pathway,including hexokinase(HK),pyruvate kinase(PK),phosphofructokinase(PFK),and lactate dehydrogenase(LDH).Moreover,it can also be regulated by multiple mechanisms such as glucose transporters(GLUTS),monocarboxylic acid transporters(MCT),PI3K/AKT/mTORC signaling pathway and hypoxia induction factor(HIF).More and more studies have proved that key glycolytic enzymes and regulatory factors play important roles in hepatocellular carcinoma(HCC)cell proliferation,invasion,metastasis,immune escape,and drug resistance.Currently,with the continuous in-depth research on the mechanism of glycolysis,clinical therapies targeting glycolysis has become a new therapeutic strategy for HCC treatment.This article aims to summarize the research progress of key glycolytic enzymes and regulatory factors in the occurrence and development of primary liver cancer,hoping to provide help for the prevention and treatment of liver cancer.