Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.

Objective To summarize the clinical features and prognosis of children suffered from malignant solid tumors of head and neck.Methods The clinical data of children with primary malignant solid tumors located in the head and neck was retrospectively analyzed from January 2007 to December 2021 in the Department of Oncology,Beijing Children's Hospital,Capital Medical University,and the clinical features,prognostic factors were summarized.Results A total of 234 children with malignant solid tumors of head and neck were included,with a male to female ratio of 1∶0.7,aged from 3 months to 17 years and 6 months(median age 51 months).173 cases(73.9％)were treated with local painless masses.Other symptoms included snoring and facial paralysis.The proportion of rhabdomyosarcoma(RMS)was the highest(145 cases,62.0％),followed by neuroblastoma(NB)(25 cases,10.7％),Ewing sarcoma(19 cases,8.1％),etc.A total of 47 cases(20.1％)had distant metastasis.The patients received surgery,chemotherapy and radiotherapy under the mode of multidisciplinary treatment(MDT).The 3-year and 5-year overall survival(OS)were 80.8％and 75.8％,respectively,and the 3-year and 5-year progression free survival(PFS)were 64.0％and 58.9％,respectively.Tumor survivors had abnormal appearance or facial motor function(49 cases,41.2％),developmental problems or abnormal tooth loss(18 cases,15.1％),and other long-term complications that may be related to the tumor or treatment.Conclusion There are various pathologic types of pediatric head and neck malignant solid tumors,RMS and NB are the most common.Local painless mass was the most common complaint.Distant metastasis is an independent risk factor for the prognosis of head and neck malignant solid tumors.Under the MDT model,the prognosis of malignant solid tumors of the head and neck in our center was generally good.In the treatment of the tumors,the side effects and sequelae should be controlled as small as possible under the premise of long-term survival.

Objective:To investigate the effect of the antioxidant Tempol on the skin depigmentation of a vitiligo-like mouse model induced by the combination of the endogenous reactive oxygen species (ROS) producer AAPH and tyrosinase-related protein 2 (TRP2) -180 nonapeptide.Methods:A vitiligo-like skin depigmentation model was established by immunizing mice with injections of a TRP2-180 nonapeptide mixture into the foot pads twice and into the tails twice, with the injection interval being 1 week. After the first injection, 12 immune-induced mouse models of vitiligo were randomly divided into 4 groups (3 mice per group) : a model group, an AAPH group, a Tempol group, and a combined treatment group; additionally, 3 untreated mice injected with an ovalbumin (OVA) 257-264 peptide served as a sham control group. Mice in the AAPH group, the Tempol group, and the combined treatment group were subcutaneously injected with AAPH into the tails, intraperitoneally injected with Tempol, and received the above both treatments, respectively, while mice in the model group and the sham control group received phosphate-buffered saline injections into the tail and/or abdomen. Drug interventions were carried out 3 times per week for 3 consecutive weeks. Six weeks after the last immunization, mice were sacrificed. The area of depigmented macules on the tail was measured using a point-counting method, X-gal staining and double immunofluorescence staining were performed to assess the distribution and number of melanocytes, mast cells, and CD8 + T cells in depigmented macules on the tail. HaCaT cells were in vitro co-cultured with AAPH and/or Tempol, and a conventional culture group served as the control. Cellular ROS levels were measured by dichlorofluorescin diacetate labeling and flow cytometry; Western blot analysis was performed to determine the expression of matrix metalloproteinase 9 (MMP9) and stem cell factor (SCF) in cell lysates, and to detect soluble SCF levels in the culture supernatant. Comparisons among multiple groups were conducted using one-way analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:Depigmented macules were observed on the tails of mice in all groups except the sham control group. The area of depigmented macules was significantly larger in the AAPH group (7.27 ± 0.31 cm 2) than in the model group and combined treatment group (3.53 ± 0.21 cm 2, 4.07 ± 0.40 cm 2; t = 13.48, 11.56, respectively, both P < 0.001), while there was no significant difference between the Tempol group (3.30 ± 0.40 cm 2) and the model group ( P = 0.424). X-gal staining and double immunofluorescence staining showed that the number of melanocytes in the normal skin around the depigmented macules was significantly lower in the AAPH group and the combined treatment group than in the model group ( t = 6.31, 5.16, respectively, both P < 0.001), and no significant difference was observed between the AAPH group and the combined treatment group ( P = 0.516). The numbers of CD8 + T cells and mast cells were significantly higher in the AAPH group than in the model group and the combined treatment group (all P < 0.001). The numbers of the 3 types of cells mentioned above in the Tempol group did not differ from those in the model group (all P > 0.05). The ROS levels in HaCaT cells in the AAPH group were the highest, and significantly higher than those in the control group and the combined treatment group (both P < 0.001). Western blot analysis showed that the MMP9 level in the cell lysates and soluble SCF level in the culture supernatant were significantly higher in the AAPH group than in the control group and the combined treatment group (all P < 0.05) ; no significant difference was observed in the membrane-bound SCF level in cell lysates among the groups ( F = 0.06, P = 0.977) . Conclusion:The antioxidant Tempol could inhibit the formation of skin depigmented macules in vitiligo-like mouse models under AAPH-induced oxidative stress.

Objective:To investigate the effect of the antioxidant Tempol on the skin depigmentation of a vitiligo-like mouse model induced by the combination of the endogenous reactive oxygen species (ROS) producer AAPH and tyrosinase-related protein 2 (TRP2) -180 nonapeptide.Methods:A vitiligo-like skin depigmentation model was established by immunizing mice with injections of a TRP2-180 nonapeptide mixture into the foot pads twice and into the tails twice, with the injection interval being 1 week. After the first injection, 12 immune-induced mouse models of vitiligo were randomly divided into 4 groups (3 mice per group) : a model group, an AAPH group, a Tempol group, and a combined treatment group; additionally, 3 untreated mice injected with an ovalbumin (OVA) 257-264 peptide served as a sham control group. Mice in the AAPH group, the Tempol group, and the combined treatment group were subcutaneously injected with AAPH into the tails, intraperitoneally injected with Tempol, and received the above both treatments, respectively, while mice in the model group and the sham control group received phosphate-buffered saline injections into the tail and/or abdomen. Drug interventions were carried out 3 times per week for 3 consecutive weeks. Six weeks after the last immunization, mice were sacrificed. The area of depigmented macules on the tail was measured using a point-counting method, X-gal staining and double immunofluorescence staining were performed to assess the distribution and number of melanocytes, mast cells, and CD8 + T cells in depigmented macules on the tail. HaCaT cells were in vitro co-cultured with AAPH and/or Tempol, and a conventional culture group served as the control. Cellular ROS levels were measured by dichlorofluorescin diacetate labeling and flow cytometry; Western blot analysis was performed to determine the expression of matrix metalloproteinase 9 (MMP9) and stem cell factor (SCF) in cell lysates, and to detect soluble SCF levels in the culture supernatant. Comparisons among multiple groups were conducted using one-way analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:Depigmented macules were observed on the tails of mice in all groups except the sham control group. The area of depigmented macules was significantly larger in the AAPH group (7.27 ± 0.31 cm 2) than in the model group and combined treatment group (3.53 ± 0.21 cm 2, 4.07 ± 0.40 cm 2; t = 13.48, 11.56, respectively, both P < 0.001), while there was no significant difference between the Tempol group (3.30 ± 0.40 cm 2) and the model group ( P = 0.424). X-gal staining and double immunofluorescence staining showed that the number of melanocytes in the normal skin around the depigmented macules was significantly lower in the AAPH group and the combined treatment group than in the model group ( t = 6.31, 5.16, respectively, both P < 0.001), and no significant difference was observed between the AAPH group and the combined treatment group ( P = 0.516). The numbers of CD8 + T cells and mast cells were significantly higher in the AAPH group than in the model group and the combined treatment group (all P < 0.001). The numbers of the 3 types of cells mentioned above in the Tempol group did not differ from those in the model group (all P > 0.05). The ROS levels in HaCaT cells in the AAPH group were the highest, and significantly higher than those in the control group and the combined treatment group (both P < 0.001). Western blot analysis showed that the MMP9 level in the cell lysates and soluble SCF level in the culture supernatant were significantly higher in the AAPH group than in the control group and the combined treatment group (all P < 0.05) ; no significant difference was observed in the membrane-bound SCF level in cell lysates among the groups ( F = 0.06, P = 0.977) . Conclusion:The antioxidant Tempol could inhibit the formation of skin depigmented macules in vitiligo-like mouse models under AAPH-induced oxidative stress.

Objective To summarize the clinical features and prognosis of children suffered from malignant solid tumors of head and neck.Methods The clinical data of children with primary malignant solid tumors located in the head and neck was retrospectively analyzed from January 2007 to December 2021 in the Department of Oncology,Beijing Children's Hospital,Capital Medical University,and the clinical features,prognostic factors were summarized.Results A total of 234 children with malignant solid tumors of head and neck were included,with a male to female ratio of 1∶0.7,aged from 3 months to 17 years and 6 months(median age 51 months).173 cases(73.9％)were treated with local painless masses.Other symptoms included snoring and facial paralysis.The proportion of rhabdomyosarcoma(RMS)was the highest(145 cases,62.0％),followed by neuroblastoma(NB)(25 cases,10.7％),Ewing sarcoma(19 cases,8.1％),etc.A total of 47 cases(20.1％)had distant metastasis.The patients received surgery,chemotherapy and radiotherapy under the mode of multidisciplinary treatment(MDT).The 3-year and 5-year overall survival(OS)were 80.8％and 75.8％,respectively,and the 3-year and 5-year progression free survival(PFS)were 64.0％and 58.9％,respectively.Tumor survivors had abnormal appearance or facial motor function(49 cases,41.2％),developmental problems or abnormal tooth loss(18 cases,15.1％),and other long-term complications that may be related to the tumor or treatment.Conclusion There are various pathologic types of pediatric head and neck malignant solid tumors,RMS and NB are the most common.Local painless mass was the most common complaint.Distant metastasis is an independent risk factor for the prognosis of head and neck malignant solid tumors.Under the MDT model,the prognosis of malignant solid tumors of the head and neck in our center was generally good.In the treatment of the tumors,the side effects and sequelae should be controlled as small as possible under the premise of long-term survival.

OBJECTIVE: To compare the effects of ~(56)Fe~(17+),~(12)C~(6+)ion beams and~(60)Co γ rays on chromosome aberration in human lymphoblastoid cells. METHODS: The human lymphoblastoid cells were divided into 0. 1,0. 3,0. 5,0. 7,1. 0,2. 0 Gy irradiated groups and 0. 0 Gy control group. They were separately exposed to ~(56)Fe~(17+)ion beams( linear energy transfer was 400. 0 ke V/μm),~(12)C~(6+)ion beams( linear energy transfer was 26. 0 ke V/μm) and~(60)C γ rays. Chromosome specimens were harvested 48 hours after irradiation. The effects of different radiation on dicentric plus centric ring( “d + r”) aberration rate and chromosome aberration in human lymphoblastoid cells were detected by light microscope with artificial counting. RESULTS: The “d + r”aberration rates induced by 0. 3-2. 0 Gy ~(12)C~(6+)ion beams were significantly higher than those of ~(56)Fe~(17+)ion beams and~(60)Co γ rays at the same dose( P < 0. 017). Chromosome aberration cell rates of 0. 1-2. 0 Gy ~(12)C~(6+)ion beams were significantly higher than those of ~(56)Fe~(17+)ion beams and~(60)C γ rays at the same dose( P < 0. 017). At the dose range of 0. 0-2. 0 Gy,chromosome aberration effects of three kinds of radiations were gradually increased( P < 0. 01). The relative biological effectiveness of ~(56)Fe~(17+)ion beams was lower than that of ~(12)C~(6+)ion beams.CONCLUSION: The chromosome aberration induced by ~(12)C~(6+)ion beams was more serious than that of~(60)Co γ rays and ~(56)Fe~(17+)ion beams.

Objective To investigate the changes of proteomics in serum of Sprague-Dawley(SD) rats after accumulated irradiation with 137Cs γ-rays.Methods A total of thirty mature SD rats were randomly divided into three groups:0.2 Gy group,2 Gy group and healthy control group.Rats were irradiated at a dose rate of 0.336 mGy/min for 10 d and 20 d continuously.Isobaric tags for relative and absolute quantitation (iTRAQ) was used to analyze the different protein expression in serum of irradiated rats.Gene Ontology,KEGG pathway and protein-protein interaction network analysis were conducted using softwares.Results In total,363 protein spots were identified.Twenty nine proteins were differentially expressed in both groups compared with control,of which 10 proteins were up-regulated and 19 proteins were down-regulated.Based on the information of GO categories,these differentially expressed proteins were mainly located in the cytoplasm and membrane concerning the function of binding and catalytic activity.Analysis with the PAJEK software demonstrated that 16 differentially expressed proteins could form a complicated interaction network where glutathione S-transferase P1 (GSTP1),phosphoglycerate kinase 1 (PGK1) and protein disulfide-isomerase (PDI) might be key nodes.Conclusions Accumulated irradiation can induce differentially expressed proteins in serum of irradiated rats.Analysis on functional roles of the screened proteins GSTP1,PGK1 and PDI may provide insight into further mechanistic investigations and underlying molecular biomarkers induced by accumulated irradiation.

Objective To explore the effects of accumulated 60CD,γ-ray irradiation on small molecular metabolites in rats urine.Methods Ten healthy male SD rats were irradiated by 60Co γ-rays in 5 days and the accumulated doses were 0,0.2,0.4,0.6,0.8,1.0 Gy,respectively.The metabolites in urine of different groups were measured with 1 H-NMR combined with principal components analysis (PCA) and partial least square discriminate analysis (PLS-DA). Results The metabolites in rat urine were obviously changed after irradiation. Compared with control group,the amount of acetoacetate decreased after irradiation(t =29.7 -30.7,P ＜ 0.05 ),but its relative level was stable when the dose increased ( P ＞ 0.05 ).Meanwhile,the relative level of hippuric acid increased ( t =4.4 - 21.6,P ＜ 0.05 ) especially when the accumulated dose was higher than 1 Gy (t =21.6,P＜0.05). The relative level of proline,taurine and trimethylamine-N-oxide increased after irradiation with the same trend( t =3.5 - 13.4,4.7 - 11.5,2.9- 12.7,P＜0.05). Conclusions The acetoacetate,hippuric acid,proline,taurine,and trimethylamine-N-oxide may be applicable for biomarkers of accumulative irradiation on rat.