Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

Objective : To study the expression of QSOX1 in osteosarcoma tissues and cells and its role in prolifera- tion，migration and invasion． Methods : Western blot and immunohistochemistry were used to verify the expression of QSOX1 in osteosarcoma tissues and cells，and the cell line MG63 with the highest expression was selected．Slow virus knocked down and selected stable strains shQSOX1 group and shCtrl group．Western blot was used to detect the expression level of QSOX1 protein in MG63 after transfection．CCK-8 assay was used to detect the level of cell proliferation．Scratch test verified the level of cell migration．Transwell test was used to detect the invasion ability of cells ; Western blot was used to detect the mRNA expression level of NF-κB signal pathway in shCtrl group and shQ- SOX1 group. Results : Western blot and immunohistochemistry showed that QSOX1 was low expressed in human osteoblast line hFOB1. 19 and adjacent tissues，but high expressed in osteosarcoma tissue and osteosarcoma cells(P < 0. 001) ．CCK-8 experiment showed that the proliferation ability of shQSOX1 group was inhibited compared with shCtrl group (P＜0. 05) ; In the scratch test，the migration ability of shQSOX1 group decreased (P＜0. 001) ; Transwell proved that the invasive ability of shQSOX1 group was affected (P＜0. 001) ; NF-κB was highly expressed in shCtrl group and low expressed in shQSOX1 group (P＜0. 001) ． Conclusion QSOX1 is highly expressed in osteo- sarcoma．Knockout of QSOX1 gene can inhibit the proliferation，migration and invasion of osteosarcoma．Knockout of QSOX1 makes NF-κB signal pathway is deactivated.

Objective : To investigate the expression of milk fat globule epidermal growth factor 8 protein(MFGE8) in osteosarcoma cell lines and its effects on the proliferation，apoptosis，invasion and migration ability of osteosarco- ma cells(U2OS) ． Methods : The expression of MFGE8 protein in normal osteoblasts and osteosarcoma cell lines was examined by Western blot method．The relationship between MFGE8 mRNA expression and prognosis of osteo- sarcoma patients was analyzed by GEO database．The effects of down-regulation of MFGE8 on proliferation，apopto- sis，migration and invasion of U2OS cells were examined. Results : Western blot method showed that the expres- sion of MFGE8 protein was higher in osteosarcoma cells than that in normal osteoblasts and its was negatively corre- lated with the prognosis of osteosarcoma patients ( all P ＜0. 05) ; compared with sh-Ctrl ( U2OS cells transfected with the null group) group，the U2OS cells in sh-MFGE8 (U2OS cells transfected with sh-MFGE8) group had de- creased healing rate and invasion number while increased proliferation inhibition rate and apoptosis rate ，and all differences were statistically significant (P＜0. 05) ． Conclusion MFGE8 is highly expressed in U2OS ofosteosar- coma cells，and down-regulation of MFGE8 can inhibit the proliferation，invasion and migration of U2OS and in- duce their apoptosis.

Objective: To investigate the effect of modified hyaluronic acid(HA) hydrogel-controlled release brain-derived neurotrophic factor(BDNF) on the growth, differentiation, and apoptosis of rat embryonic neural stem cells(rFNSCs). Methods: The experiment took rat embryonic stem cells as the research object. The experiments were divided into three groups, blank control group [rFNSCs co-cultured with poly(lactic-co-glycolic acid)(PLGA)and HA],conditional control group(rFNSCs co-cultured with BDNF-PLGA and HA), and experimental group(rFNSCs co-cultured with BDNF-PLGA and modified hyaluronic acid hydrogel that is Dex-HA). ELISA was used for detecting the release curve of BDNF in the controlled-release scaffold. The Live/Dead assay detected the apoptosis of rFNSCs in each group, CCK-8 experiment was used to test the cell proliferation activity of rFNSCs after coculture with hydrogel. The differentiation ratios of rFNSCs in different groups were detected by immunocytochemical staining. Results: ELISA result showed that the controlled-release scaffold could release BDNF for 14 days.Live/Dead result showed the number of rFNSCs apoptotic in experimental group was less than blank control group and conditional control group. CCK-8 experiment result showed that the cell proliferation activity of rFNSCs in the experimental group was showed stronger survivability than blank control group and conditional control group. The difference was statistically significant(P<0. 05). Moreover, immunocytochemical staining showed that the experimental group hydrogel could promote the neuronal differentiation of rFNSCs and reduce their differentiation into astrocytes in vitro compared with the blank control group and the conditional control group. The difference was statistically significant(P<0. 05). Conclusion modified hyaluronic acid hydrogel controlled release brain-derived neurotrophic factor can promote the growth and differentiation of rFNSCs and reduce their apoptosis.