PD-1抑制剂联合安罗替尼治疗化疗后进展的晚期食管鳞状细胞癌的回顾性研究

目的:观察程序性死亡因子受体-1(programmed death receptor 1,PD-1)抑制剂联合安罗替尼在晚期食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)患者后线治疗中的疗效及安全性。方法:经过化疗后进展的晚期ESCC患者接受PD-1抑制剂联合安罗替尼治疗,直至疾病进展或不能耐受。主要研究终点为无进展生存(progression-free survival,PFS),次要研究终点为客观缓解率(objective response rate,ORR)及总生存(overall survive,OS)。随访截止到2021年11月30日。结果:2019年3月至2021年7月郑州大学附属肿瘤医院共63例ESCC患者接受了PD-1抑制剂联合安罗替尼治疗,中位无进展生存(median progression-free survival,mPFS)为7.1个月(95%CI:4.3~9.9),ORR为14.3%,疾病控制率(disease control rate,DCR)为69.8%,中位总生存(median overall survival,mOS)尚未达到。不良反应主要为乏力31例(49.2%)、甲状腺功能减退29例(46.0%)、高血压24例(38.1%)、恶心和呕吐22例(34.9%)、手足综合征21例(33.3%)、皮疹20例(31.7%)。3级不良反应有出血及穿孔3例(4.8%)、间质性肺炎2例(3.2%)、甲状腺功能减退2例(3.2%)、免疫心肌炎1例(1.6%)、皮疹1例(1.6%)、腹泻1例(1.6%)等。未观察到4级不良反应及治疗相关死亡事件的发生。结论:PD-1抑制剂联合安罗替尼在晚期化疗后进展的ESCC治疗中显示出显著的疗效及良好的安全性,可作为ESCC患者后线治疗的选择。

Genomic analysis of intestinal flora and liver genes in mice with circadian rhythm disorders fed with flavonoids from Sedum aizoon L.

A traditional herb that is rich in active substances such as flavonoids, polyphenols and alkaloids, Sedum aizoon L . has antioxidant and preventive effects against chronic diseases. Circadian rhythm disorders are often accompanied by changes in intestinal flora, and flavonoids that can regulate intestinal flora may be an effective way to prevent and regulate circadian rhythm disorders. In this study, we established a humanized circadian rhythm mouse model to explore the regulatory mechanism of flavonoids from Sedum aizoon L .(FSAL) on circadian rhythm disorders in mice. The results after feeding FSAL for 4 weeks showed that FSAL improved the imbalance of intestinal microbial structure caused by circadian rhythm disorders, thus regulating alanine, aspartate and glutamate metabolism, histidine metabolism and other metabolites and substances related to metabolism. The analysis of liver transcriptome showed that FSAL significantly regulated retinol metabolism, peroxisome proliferator-activated receptors(PPARs) pathway, and hepatitis C pathway in mouse liver. Therefore, this study obtained the conclusion that FSAL can regulate intestinal flora, metabolites and liver genes to improve circadian rhythm disorders and maintain mouse health.

Influences of flavonoids from Sedum aizoon L. on the cell membrane of Botrytis cinerea

Botrytis cinerea is a plant pathogen,which affects the quality of fruits.However,chemical antifungal agents are extremely harmful to the environment,hence it’s critical to create a natural plant-derived antifungal agent to replace chemical antifungal agents.The study explored the antifungal mechanisms of flavonoids from Sedum aizoon L.(FSAL)against B.cinerea.In the study,cell membrane served as an important breakthrough point.The minimum inhibitory concentration(MIC)of FSAL against B.cinerea was investigated.The propidium iodide(PI)staining observation of B.cinerea was explored.The activities of crucial enzymes involved in the metabolism were studied as well as the phospholipid and fatty acid changes.The expression of genes related to the membrane lipid metabolism was also measured.The results showed that FSAL had a certain inhibitory effect on B.cinerea and the MIC was 1.500 mg/mL.FSAL disrupted the cell membrane of B.cinerea,which decreased the contents of glutathione and proline at a low level as well as the membrane phospholipids.Compared with the control group,the activities of crucial enzymes were decreased,and the expression of key genes was reduced.It indicated that FSAL inhibited B.cinerea by disrupting its cell membrane,offering the possibility of a natural plant-derived antifungal agent for the preservation of fruits.