Objective To retrospectively analyze the efficacy and safety of combined hetrombopag in the treatment of cancer therapy induced thrombocytopenia(CTIT)after chemotherapy for germ cell tumors.Methods The data of patients with CTIT ≥ grade Ⅲcombined with chemotherapy for intracranial germ cell tumors admitted from January 2021 to March 2024 were collected and analyzed,and 33 patients met the enrollment criteria.The patients in the study group were treated with oral hetrombopag combined with subcutaneous injections of recombinant human thrombopoietin(rhTPO)or interleukin-11(IL-11),and those in the control group were treated with subcutaneous injections of rhTPO or IL-11.The differences of the two groups of patients in platelet counts,platelet-raising response rate,mean onset of action time,and prolongation of the next cycle of treatment before and after the treatment were compared to each other,and the adverse reactions of the two groups were also counted.Results The platelet counts of patients in both groups were improved post-treatment,with no statistical significance between the two groups for platelet count elevation on days d1,d2,and d3 of the medication(P＞0.05).The platelet elevation counts of the study group were significantly elevated on day d(7±3)after the medication compared with the control group,with a statistically significant difference(P＜0.05),and the rate of platelet elevation response increased with time prolongation.The mean time to onset of drug administration was 3(3,5)in the study group and 4(3,7)in the control group,with no statistically significant difference(P＞0.05).The incidence of prolongation of the time to the next cycle of treatment was 54.5％in the study group and 81.8％in the control group,and the difference between the two groups was not statistically significant(P＞0.05).Two patients in the study group developed mild reversible liver function abnormalities.Conclusion The efficacy of hetrombopag combined with subcutaneous injection of t rhTPO or IL-11 in the treatment of thrombocytopenia after chemotherapy for intracranial germ cell tumors is reliable,and it can significantly elevate platelet counts with tolerable adverse effects.

Objective To retrospectively analyze the efficacy and safety of combined hetrombopag in the treatment of cancer therapy induced thrombocytopenia(CTIT)after chemotherapy for germ cell tumors.Methods The data of patients with CTIT ≥ grade Ⅲcombined with chemotherapy for intracranial germ cell tumors admitted from January 2021 to March 2024 were collected and analyzed,and 33 patients met the enrollment criteria.The patients in the study group were treated with oral hetrombopag combined with subcutaneous injections of recombinant human thrombopoietin(rhTPO)or interleukin-11(IL-11),and those in the control group were treated with subcutaneous injections of rhTPO or IL-11.The differences of the two groups of patients in platelet counts,platelet-raising response rate,mean onset of action time,and prolongation of the next cycle of treatment before and after the treatment were compared to each other,and the adverse reactions of the two groups were also counted.Results The platelet counts of patients in both groups were improved post-treatment,with no statistical significance between the two groups for platelet count elevation on days d1,d2,and d3 of the medication(P＞0.05).The platelet elevation counts of the study group were significantly elevated on day d(7±3)after the medication compared with the control group,with a statistically significant difference(P＜0.05),and the rate of platelet elevation response increased with time prolongation.The mean time to onset of drug administration was 3(3,5)in the study group and 4(3,7)in the control group,with no statistically significant difference(P＞0.05).The incidence of prolongation of the time to the next cycle of treatment was 54.5％in the study group and 81.8％in the control group,and the difference between the two groups was not statistically significant(P＞0.05).Two patients in the study group developed mild reversible liver function abnormalities.Conclusion The efficacy of hetrombopag combined with subcutaneous injection of t rhTPO or IL-11 in the treatment of thrombocytopenia after chemotherapy for intracranial germ cell tumors is reliable,and it can significantly elevate platelet counts with tolerable adverse effects.

OBJECTIVE: To investigate the regulatory effects of miR-26a-5p on the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) by regulating cAMP response element binding protein 1 (CREB1). METHODS: The adipose tissues of four 3-4 weeks old female C57BL/6 mice were collected and the cells were isolated and cultured by digestion separation method. After morphological observation and identification by flow cytometry, the 3rd-generation cells were subjected to osteogenic differentiation induction. At 0, 3, 7, and 14 days after osteogenic differentiation induction, the calcium deposition was observed by alizarin red staining, ALP activity was detected, miR- 26a-5p and CREB1 mRNA expressions were examined by real-time fluorescence quantitative PCR, and CREB1 protein and its phosphorylation (phospho-CREB1, p-CREB1) level were measured by Western blot. After the binding sites between miR-26a-5p and CREB1 was predicted by the starBase database, HEK-293T cells were used to conduct a dual-luciferase reporter gene experiment to verify the targeting relationship (represented as luciferase activity after 48 hours of culture). Finally, miR-26a-p inhibitor (experimental group) and the corresponding negative control (control group) were transfected into ADSCs. Alizarin red staining, ALP activity, real-time fluorescent quantitative PCR (miR-26a-5p) and Western blot [CREB1, p-CREB1, Runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN)] were performed at 7 and 14 days after osteogenic induction culture. RESULTS: The cultured cells were identified as ADSCs. With the prolongation of osteogenic induction culture, the number of calcified nodules and ALP activity significantly increased ( P<0.05). The relative expression of miR-26a-5p in the cells gradually decreased, while the relative expressions of CREB1 mRNA and protein, as well as the relative expression of p-CREB1 protein were increased. The differences were significant between 7, 14 days and 0 day ( P<0.05). There was no significant difference in p-CREB1/CREB1 between different time points ( P>0.05). The starBase database predicted that miR-26a-5p and CREB1 had targeted binding sequences, and the dual-luciferase reporter gene experiment revealed that overexpression of miR-26a-5p significantly suppressed CREB1 wild-type luciferase activity ( P<0.05). After 7 and 14 days of osteogenic induction, compared with the control group, the number of calcified nodules, ALP activity, and relative expressions of CREB1, p-CREB1, OCN, and RUNX2 proteins in the experimental group significantly increased ( P<0.05). There was no significant difference in p-CREB1/CREB1 between the two groups ( P>0.05). CONCLUSION Knocking down miR-26a-5p promoted the osteogenic differentiation of ADSCs by up-regulating CREB1 and its phosphorylation.
Animals ; Female ; Mice ; Cell Differentiation ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Mesenchymal Stem Cells ; Mice, Inbred C57BL ; MicroRNAs/metabolism* ; Osteocalcin/metabolism* ; Osteogenesis/genetics* ; RNA, Messenger/genetics*