A 64-year-old male patient with gastric adenocarcinoma received chemotherapy with oxaliplatin (250 mg intravenous infusion on day 1) and tegafur gimeracil oteracil potassium (60 mg orally twice daily on day 1 to day 14, 21 days as a cycle). One month later, he was given nivolumab immunotherapy (240 mg intravenous infusion on day 1, 14 days as a cycle). On the 2nd day of the 4th cycle of nivolumab treatment (the 44th day after the first dose), the patient developed diarrhea with watery stools, 3 to 4 times a day, accompanied by mild abdominal pain; 3 days later, the diarrhea worsened, showing dark red bloody stools, covered with pus moss, up to 10 times a day, accompanied by obvious abdominal pain. According to colonoscopy and histological examination results, ulcerative colitis (initial onset, total colon, active stage, and severe) was diagnosed, which was considered as a grade 3 immune-related colitis induced by nivolumab. After suspension of chemotherapy and immunotherapy, and administration of glucocorticoids and octreotide, the patient′s abdominal pain and diarrhea were gradually improved. On the 45th day of nivolumab withdrawal, the patient received chemotherapy with oxaliplatin and tegafur gimeracil oteracil potassium again, and colitis did not recur.

A 64-year-old male patient with gastric adenocarcinoma received chemotherapy with oxaliplatin (250 mg intravenous infusion on day 1) and tegafur gimeracil oteracil potassium (60 mg orally twice daily on day 1 to day 14, 21 days as a cycle). One month later, he was given nivolumab immunotherapy (240 mg intravenous infusion on day 1, 14 days as a cycle). On the 2nd day of the 4th cycle of nivolumab treatment (the 44th day after the first dose), the patient developed diarrhea with watery stools, 3 to 4 times a day, accompanied by mild abdominal pain; 3 days later, the diarrhea worsened, showing dark red bloody stools, covered with pus moss, up to 10 times a day, accompanied by obvious abdominal pain. According to colonoscopy and histological examination results, ulcerative colitis (initial onset, total colon, active stage, and severe) was diagnosed, which was considered as a grade 3 immune-related colitis induced by nivolumab. After suspension of chemotherapy and immunotherapy, and administration of glucocorticoids and octreotide, the patient′s abdominal pain and diarrhea were gradually improved. On the 45th day of nivolumab withdrawal, the patient received chemotherapy with oxaliplatin and tegafur gimeracil oteracil potassium again, and colitis did not recur.

OBJECTIVE：To explo re the potential molecular mechanism of ursolic acid in the treatment of osteoporosis （OP）. METHODS：TCMSP，PubMed database and UniProt database were used to screen potential targets of monomer compound ursolic acid. OP related target genes were searched with GeneCards database. The common target genes of component-disease were obtained by Venny 2.1 online mapping tool. The protein-protein interaction （PPI）network of component-disease common target genes was constructed by using STRING database ，and topological analysis was carried out ；the core target genes ，whose degree value was greater than the average degree value ，were screened. GO functional annotation and KEGG pathway enrichment analysis of component-disease common target genes were carried out by DAVID database. AutoDock Vina 1.1.2 software was used for molecular docking ，using protein encoded by the core target gene as receptor and ursolic acid as ligand. RESULTS ：A total of 55 ursolic acid related target genes and 4 273 OP related target genes were excavated ，with a total of 44 common target genes. PPI network with above common target genes included 44 nodes and 513 edges，with an average node degree of 23.3. There were 24 core target genes ，including VEGFA，TP53，IL6，CASP3. There were 340 GO functional items were enriched （corrected P＜ 0.05），including 263 biological processes （negative regulation of apoptosis ，etc.），25 molecular functions （protein binding ，etc.） and 52 cell components （cytosol，etc.）. There were 90 KEGG signaling pathways （corrected P＜0.05），such as tumor pathway ， hepatitis B pathway ，TNF signaling pathway ，viral carcinogenesis and phosphatidylinositol 3 kinase/protein kinase B （PI3K-Akt） signaling pathway. The binding energy between ursolic acid and 6 proteins encoded by core target genes such as TP53 was lower than －5 kcal/mol，which had strong binding activity. CONCLUSIONS ：The therapeutic effect of ursolic acid on OP may be achieved by regulating VEGFA，TP53，IL6，CASP3，JUN and other core target genes and acting on multiple key pathways such as cancer pathway ， hepatitis B and TNF signaling