Observation on the therapeutic efficacy and survival rate of oral Etoposide in children with disseminated medulloblastoma after the standard treatment plan / 中华实用儿科临床杂志

Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.

Clinical feature analysis of medulloblastoma with extraneural metastasis in children / 中华实用儿科临床杂志

Objective:Summarizing the clinical characteristics of extraneural metastasis in childhood medulloblastoma.Methods:A total of 616 cases with medulloblastoma treated in Beijing Shijitan Hospital from April 2010 to April 2019 were analyzed retrospectively, among which 11 cases developed extraneural metastasis.The age of onset, location and time of extraneural metastasis, pathological and molecular typing, treatment and prognosis were descriptively analyzed.The differences of blood biochemical indexes between medulloblastoma cases with and without extraneural metastasis were statistically analyzed by t test. Results:As of February 2020, the median follow-up period was 16 months (ranging from 3 to 69 months). Eleven cases, including 8 males and 3 females, were diagnosed with extraneural metastasis, with the incidence being about 1.8%.The median age of medulloblastoma was 6 years (2-10 years), and the median age at presentation of extraneural metastasis was 7 years (2-12 years). Extraneural metastasis occurred from 0.5 months to 38.0 months after the operation, and the affected location includes bone (6 cases), bone marrow (3 cases), lung (3 cases), pelvis (2 cases) and abdominal cavity (1 case). In these patients, the range of lactic dehydrogenase (LDH) was (2 298.00±1 570.70) U/L and neuron-specific enolase (NSE) was (201.00±68.34) μg/L, which were significantly higher than those in patients without extraneural metastasis [(249.50±46.28) U/L and (22.80±7.12) μg/L, all P<0.05]. Partial patients were treated with chemotherapy, while the majority of them were treated with palliative treatment in the terminal stage, with the survival period mostly less than 10 months. Conclusions:Although there is a low incidence of extraneural metastasis in medulloblastoma pediatric patients, the prognosis of these patients with extraneural metastasis is poor and most of them would die within one year.The most common sites include bone, followed by bone marrow and lungs, which may be related to the spread of cerebrospinal fluid and the increased levels of LDH and NSE.

Effect of neutrophil-lymphocyte ratio at the initial visit on the survival of children with newly diagnosed medulloblastoma / 中华实用儿科临床杂志

Objective:To explore the effect of neutrophil-lymphocyte ratio (NLR) at the initial visit on the survival of children with newly diagnosed medulloblastoma (MB).Methods:This was a case-control study involving 61 children with newly diagnosed MB at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University from August 2018 to January 2020 .The blood cell counts, lymphocyte subsets and immunoglobulin in the periphe-ral blood were measured to calculate NLR at the initial visit.Based on the cut-off value determined by receiver opera-ting characteristic (ROC) curve, patients were divided into high NLR group (≥ 2.07, n=21) and low NLR group (<2.07, n=40). The progression-free survival (PFS) and overall survival (OS) between 2 groups were analyzed by the Kaplan-Meier method, followed by Log- rank test.The correlation between NLR at the initial visit with clinical characteristics, lymphocyte subsets and immunoglobulin of children with newly diagnosed MB was analyzed.Differences between groups were compared by the Chi- square test, Mann- Whitney U test and independent sample t test. Results:The survival analysis showed that the relapse rate (38.1% vs.10.0%, χ2=6.879, P=0.016) and mortality rate (19.0% vs.0, χ2=8.154, P=0.011) were significantly higher in high NLR group than those of low NLR group.PFS (12 months vs.19 months, χ2=9.775, P=0.002) and OS (19 months vs.20 months, χ2=8.432, P=0.004) were significantly shorter in high NLR group than those of low NLR group.No significant differences in clinical characteristics were detected between groups (all P>0.05). Compared with low NLR group, the percentage of T lymphocyte[(67.93±6.37)% vs.(73.38±8.08)%, t=2.886, df=48.865, P=0.006], T helper cells (Th)[(30.86±5.53)% vs.(34.29±7.44)%, t=2.037, df=51.981, P=0.047], and T suppressor cells (Ts)[(27.39±5.50)% vs.(30.84±6.58)%, t=2.164, df=47.581, P=0.035] were significantly lower in high NLR group.Spearman correlation analysis showed a negative correlation between NLR and T lymphocyte count ( r=-0.303, P=0.018), and Ts lymphocyte count ( r=-0.260, P=0.043). Conclusions:Children with newly diagnosed MB expressing a high level of NLR had a poor prognosis, which may be associated with T lymphocyte and Ts lymphocyte.

Analysis of clinical characteristics and risk factors associated with incomplete intestinal obstruction in children with medulloblastoma / 中华实用儿科临床杂志

Objective:To analyze the clinical characteristics of children with medulloblastoma (MB) complicated with incomplete intestinal obstruction, and to explore the possible pathogenesis of intestinal obstruction in children with MB.Methods:A total of 409 children with MB admitted to the Department of Pediatrics of Beijing Shijitan Hospital, Capital Medical University from October 2014 to January 2019 were recruited into this study, and the clinical data of children with incomplete intestinal obstruction were collected and analyzed retrospectively.A comparison was performed between these children and those without intestinal obstruction who were treated at the same time.The chi- squared test and Logistic regression analysis were adopted to explore the pathogenesis of intestinal obstruction.The overall survival (OS) rate was calculated with the Kaplan-Meier method. Results:There were 11 cases of 409 children with MB complicated with incomplete intestinal obstruction in total, with the morbidity of 2.7%, they were all over 3 years old, with the median age of 8.7 years, and a male-to-female ratio of 4.5∶1.The incomplete intestinal obstruction in all cases occurred during the first cycle of maintenance chemotherapy after radiotherapy.All these patients could be reco-vered after conservative treatment, and no incomplete intestinal obstruction occurred in the subsequent chemotherapy.The results of Logistic regression analysis showed that there was a correlation between age and the development of incomplete intestinal obstruction ( P<0.05). The 2-year OS rate of MB patients complicated with incomplete intestinal obstruction was (87.5±11.7)%, and that of patients without incomplete intestinal obstruction during the same period was (92.8±1.6)%, which showed that the difference between the two group was not statistically significant ( P>0.05). Conclusions:Incomplete intestinal obstruction would occur in all MB patients within 2 months after radiotherapy, and children more than 3 years old are more prone to suffer from this disease.Therefore, it can be supposed that gastrointestinal mucosa was damaged under the double attack of radiotherapy and Vincristine, which slowed down the intestinal peristalsis, thus inducing intestinal obstruction.

Analysis of prognostic factors and survival status of children with medulloblastoma / 中华实用儿科临床杂志

Objective@#To investigate the prognostic factors and survival status of children with medulloblastoma (MB) by using retrospective analysis.@*Methods@#From February 2011 to December 2017, 224 children with newly-diagnosed MB were enrolled in this study, which was carried out at Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University.The overall survival (OS) rate and progression-free survival (PFS) rate were calcula-ted by using Kaplan-Meier method, the difference between 2 groups was tested by Log-rank method, and prognostic factors were analyzed by COX regression.@*Results@#Until December 30, 2018, the median survival time of all these 224 children was 4.1 years, the survival rate was 74.6%, complete response (CR) rate was 60.3%, and the relapse rate was 1.7%. The 5-year PFS rate and 5- year OS rate of all patients were (58.2±3.6)% and (72.5±3.3)%, respectively. Survival rates of children in the high-risk group, with metastatic disease, aged <3 years, and with positive tumor cells in the cerebrospinal fluid(CSF) were very low. The 5-year OS rates were (54.8±5.3)%, (57.7±5.9)%, (41.6±8.7)%, and (53.0±7.3)%, respectively.Compared to others, the children with MB large-cell/anaplastic histology [5-year OS rate was (35.3±13.6)%] and MB group 3 subtype [3-year OS rate was (25.0±13.0)%] lived a miserable life.Meanwhile, the children in the stand-risk group, without metastatic disease, no large-cell/anaplastic histology, age older than 3 years, and with tumor cell negative in CSF, lived a better life. The 5-year OS rates were (87.5±3.5)%, (80.3±3.7)%, (70.6±5.5)%, (78.3±3.3)%, and (78.4±3.5)%, respectively, and all of them were over 70.0%. No WNT tumors progressed or relapsed, and 5- year OS rate was 100.0%. The survival status of SHH subgroup was inferior to that of group 4 subtype[(64.8±5.8)% vs.(83.5±3.8)%, χ2=5.417, P=0.015]. With COX analysis, age and tumor cells in CSF at the time of diagnosis were independent risk factors for OS and PFS of MB (PFS: Wald=8.485, P=0.004; Wald=11.702, P=0.001; OS: Wald=16.274, P=0.000; Wald=7.191, P=0.007).@*Conclusions@#Survival of children with MB more than 3 years old has been reached a perfectly high level.Age and tumor cells in CSF are independent risk factors for the OS and PFS. However, the prognosis of large-cell/anaplastic histology, malignancy cell positive in CSF, group 3 and children under 3 years old, is still poor, and intensive treatment is needed urgently for those patients.

Early diagnosis and treatment of secondary lung damage in children with malignant brain tumors after radiation therapy / 中华实用儿科临床杂志

Objective To investigate the early diagnosis and treatment of craniospinal irradiation(CSI)in-duced lung injury (RILI)in children with malignant brain tumors.Methods From January 2014 to January 2016,a total of 145 children with malignant brain tumors from Beijing Shijitan Hospital,Capital Medical University were enrolled in this study.All children received postoperative CSI.Ten children were diagnosed as RILI by high－resolution computed tomography (HRCT)scanning before the start of subsequent chemotherapy and 42 days after CSI.Oral Pred-nisone acetate tablets 0.5－1.0 mg/(kg·d)were given to treat RILI and compound Sulfamethoxazole to prevent sec-ondary lung inflammation.Antibiotic treatment and symptomatic support were given to 2 patients because of the com-bined infection.Then every 4 weeks HRCT was performed and the dosage of Prednisone was adjusted.Clinical charac-teristics and treatment effects were observed synthetically.Results Up to January 2018,the median follow－up time was 28 months (ranged from 26 to 48 months),only 10 patients suffered from RILI,and the morbidity was 6.9%.Eight of 10 patients had medulloblastoma,1 case with pineoblastoma,and 1 case with atypical teratoma/rhabdomyoid tumor. They were 6 boys and 4 girls,and the median age was 8 years old (ranged from 5 to 13 years old).The time points of diagnosis of lung damage were 39－52 days after the end of radiotherapy,and lesions were located in the dorsal or basal segments of lower lobe of unilateral or bilateral lung in HRCT scanning.No obvious respiratory symptoms or other dis-comfort was found except for frequent cough in 2 patients.Lung lesions were gradually reduced and disappeared within 2 to 8 months after treatment with Prednisone and compound Sulfamethoxazole.Two cases suffered severe infection be-fore or during the subsequent chemotherapy,and the condition was gradually improved after anti－infection treatment based on drug sensitivity test.Then subsequent chemotherapy underwent successfully.Conclusions RILI presents mild symptoms or asymptomatic.Routine lung imaging after radiotherapy is beneficial to the early diagnosis of lung damage, and early treatment with Prednisone and prophylaxis with compound Sulfamethoxazole has a good prognosis.

Survival of children with relapsed medulloblastoma treating with high-dose chemotherapy and intrathecal Methotrexate:a retrospective study in a single institution / 中华实用儿科临床杂志

Objective To investigate the treatment value of intensified chemotherapy combined with intrathe-cal Methotrexate(ITMTX)in the treatment of children with relapsed medulloblastoma.Methods From February 2011 to February 2014,40 relapsed patients in Beijing Shijitan Hospital,Capital Medical University,aged 10.6 years(2.7 to 17.7 years),were received 4 cycles of carboplatin and Etoposide continuously infusion for 96 h,and sequentially fo-llowed with Ifosfamide,Etoposide and Nedaplatin for 3 cycles,then administrated oral Temozolomide(TMZ)and Etopo-side for 12 cycles.All patients were divided into ITMTX group,which were performed ITMTX during every chemothera-py or every 3 weeks,and no intrathecal Methotrexate(no-ITMTX)group,which were not performed with ITMTX.Re-sponses were evaluated,and the objective response time,time to tumor progress(TTP),time to treatment failure (TTF),and recurrence-free interval(RFI)of the two groups were contrasted.The side-effects of chemotherapy and ITMTX were analyzed,overall survival was calculated using Kaplan-Meier method,and chi-square test or t test was used to compare the difference between two groups.Results Until 30thDecember 2016,the follow-up time was 29.4 months(ranging from 2 to 57 months). The 3-year overall survival(OS)rate was(53.5 ± 8.1)%,and 45.0% pa-tients were objective response,and the mean objective response time was 2 months,and the RFI was 18 months.For IT-MTX patients,the 3-year OS rate was(66.6 ± 11.5)%,the objective response ratio was 70.0%,and mean objective response time was 1.5 months,24 months free-event of TTP and TTF was 70.0% and 90.0%,respectively,and the RFI was 22.5 months.For no-ITMTX patients,the 3-year OS rate was(40.0 ± 11.0)%,objective response ratio was 20.0%,and mean objective response time was 2.5 months(1.5-4.0 months),24 months free-event of TTP and TTF was 35.0% and 50.0%,respectively,and the RFI was 5 months(0-40 months).Compared with those of no-ITMTX patients,the RFI,24 months TTP and TTF of ITMTX patients were much better,there were statistical signi-ficances(all P<0.05).The main side-effects of chemotherapy was gastrointestinal hematologic side-effects,and re-covered quickly with supportive treatment.No obvious Methotrexate induced neurotoxicity was found.Conclusion Based on high-dose chemotherapy,ITMTX can further improve the long-term survival of patients with relapsed medulloblas-toma,and it is more feasible and suitable for relapsed MB children in China.

Clinical characteristic and survival analysis of childhood supratentorial primitive neuroectoderma:a center re-trospective study / 中华实用儿科临床杂志

Objective To analyze the survival rate and adverse effect of therapy of childhood supratentorial primitive neuroectoderma (sPNET)patients in order to investigate a suitable therapy. Methods Between December 2012 and December 2014,18 children,aged from 0. 6 to 13. 6 years old,were treated with pediatric himtumor(HIT)-2000 protocol in Beijing Shijitan Hospital,Capital Medical University. All patients were performed tumor gross total re-section,and someone accepted irradiation therapy firstly. The adverse effect of radiotherapy and chemotherapy was ana-lyzed,and the 3 - year progression - free survival (PFS)rate and overall survival (OS)rate were calculated by using Kaplan - Meier method. Results Till September 2017,the mean follow - up time was 3. 0 years (0. 2 - 4. 8 years), and the survival rate was 72. 2％ (13 / 18 cases). Eleven cases(11 / 18 cases,61. 1％)were complete remission,but 7 cases (7 / 18 cases,38. 9％)relapsed during or after therapy. The 3 - year PFS and OS rates were (66. 7 ± 11. 1)％and (71. 8 ± 10. 7)％,respectively. Moreover,14 patients received craniospinal irradiation,and their 3 - year PFS and OS rates were (68. 8 ± 13. 3)％ and (85. 7 ± 9. 4)％,respectively,there was no significant difference between the overall rates(all P >0. 05). During the follow - up period,all patients were not involved radiation - reduced brain necro-sis,myelitis,and pancreatic injury. During the whole central radiotherapy,14 children had different degree of blood rou-tine abnormalities,mainly manifested in leukocytes and thrombocytopenia,and the blood routine was restored to normal after subcutaneous injection of granulocyte stimulating factor. The adverse reactions of the gastrointestinal tract were re-latively mild,mainly nausea and vomiting,and the improvement of the gastric mucosa and the protection of the gastric mucosa were all improved. The gastrointestinal tract adverse reactions caused by HIT - 2000 were mainly nausea,vomi-ting,abdominal pain,diarrhea,constipation,and so on. The incidence of hematological adverse reactions was high,up to 100％,of which 2 cases were cured by active anti infection and symptomatic treatment due to the lack of granulocytic and fever. Conclusion HIT - 2000 protocol is a feasible and efficient therapy method for sPNET of Chinese children patients,and the adverse effects are tolerable.

Effects of endogenous sulfur dioxide on the oxidative stress induced by cobalt chloride in the rat pulmonary artery smooth muscle cells / 中华实用儿科临床杂志

Objective To investigate the effects of endogenous sulfur dioxide (SO2) on the oxidative stress induced by cobalt chloride (CoCl2) in the rat pulmonary artery smooth muscle cells (PASMCs).Methods Rat PASMCs were treated with 200 μ mol/L CoCl2 to mimic the hypoxia insult.Endogenous SO2 generating enzyme aspartate aminotransferase 1 (AAT1) expression was upregulated or downregulated (AAT1 sh) by transfection with lentivirus.Rat PASMCs were randomly divided into 8 groups:vehicle group,vehicle + CoCl2 group,AAT1 group,AAT1 + CoCl2 group,scramble group,scramble + SO2 group,AAT1 sh group and AAT1 sh + SO2 group.SO2 donor Na2 SO3/NaHSO3 at concentration of 100 μ mol/L were added in scramble + SO2 group and AAT1sh + SO2 group.The expressions of AAT1,superoxide dismutase 1 (SOD1) and SOD2 in PASMCs were detected by Western blot method.In situ SO2 content in PASMCs was detected by fluorescent probe.The superoxide anions in PASMCs were labeled by dihydroethidium (DHE) probe under fluorescent microscope.Results Compared with the vehicle group,the levels of SO2 and the expressions of AAT1 (0.221 ± 0.002 vs.0.446 ± 0.004),SOD1 (0.076 ± 0.028 vs.0.171 ± 0.019) and SOD2 (0.080 ± 0.031 vs.0.196 ± 0.018) significantly decreased (all P ＜ 0.01),and superoxide anion increased in rat PASMCs of vehicle + CoCl2 group.Meanwhile,compared with vehicle + CoCl2 group,the levels of SO2 and the expressions of AAT1 (0.839 ± 0.056 vs.0.221 ± 0.002),SOD1 (0.177 ± 0.020 vs.0.076 ± 0.028) and SOD2 (0.195 ±0.018 vs.0.080-± 0.031) markedly increased (all P ＜ 0.01),and superoxide anion decreased in rat PASMCs of AAT1 + CoCl2 group.On the contrary,compared with the scramble group,the levels of SO2 and the expressions of AAT1 (0.062 ±0.017 vs.0.354 ±0.034),SOD1 (0.054 ±0.029 vs.0.157 ±0.023) and SOD2(0.180 ±0.100 vs.0.586 ± 0.176)significantly decreased (all P ＜ 0.01),and superoxide anion increased in rat PASMCs of AAT1sh group.Furthermore,compared with the AAT1 sh group,the levels of SO2 and the expressions of SOD1 (0.155 ± 0.022vs.0.054 ± 0.029) and SOD2 (0.578 ± 0.200 vs.0.180 ± 0.100) significantly increased (all P ＜ 0.01),and superoxide anion decreased in rats PASMCs of AAT1sh + SO2 group.Conclusion Endogenous SO2/AAT1 inhibits CoCl2-induced oxidative stress in rat PASMCs.

Change of endogenous hydrogen sulfide pathway in the monocrotaline-induced pulmonary hypertensive rats / 中华实用儿科临床杂志

Objective To investigate the production of hydrogen sulfide (H2S) in rats with monocrotaline (MCT)-induced pulmonary hypertension(PAH).Methods Fourteen male Wistar rats were randomly divided into 2 groups (7 cases for each group):control group and MCT group.Rats in the MCT group were intraperitoneally injected with MCT (60 mg/kg) on day 1 while rats in the control group received only the same volume of 9 g/L saline.And then the conventional breeding was given for 21 days.Mean pulmonary artery pressure (mPAP) was evaluated via right cardiac catheterization procedure.The ratio of right ventricular mass (RV) and left ventricular plus septal mass (LV + SP) [RV/(LV + SP)] was calculated.The morphological change of pulmonary artery was observed by applying hematoxylin-eosin (HE) staining on the lung tissue paraffin section by measuring relative media thickness (RMT) and relative media area (RMA) of pulmonary aetery.H2S contents in serum and lung tissue rat were detected by using free radicals detector.The expression of cystathionine-γ-lyase (CSE),a key enzyme catalyzing endogenous H2S generaion,in lung tissue was detected by using Western blot method.CSE mRNA level in lung was detected by adopting the real-time polymerase chain reaction (RT-PCR) method.Results Compared with control group,mPAP of rats in MCT group was increased significantly [(49.31 ±3.67) mmHg vs (14.31 ±2.07) mmHg(1 mm Hg =0.133 kPa),P ＜ 0.01] and the ratio of RV/(LV + SP) was increased (0.43 ± 0.03 vs 0.21 ± 0.03,P ＜ 0.01),while RMT and RMA of pulmonary artery were enlarged [(43.46 ± 1.94) μm vs (13.16 ± 1.48) μm,P ＜ 0.01;(3 321.10 ± 318.20) μm2 vs (963.40 ± 127.26) μm2,P ＜0.01].The evaluation of microstructure of pulmonary artery showed that the vessel wall of pulmonary artery in control rats was thin and no inflammatory cell was observed around artery.However,the vessel wall of pulmonary artery in rats of MCT group was thickened and there was evident infiltration of inflammatory cells in perivascular area.Compared with control group,H2S contents in serum and lung tissue of rats in MCT group were markedly decreased [(9.28 ± 0.94) μmol/L vs (14.20 ± 1.21) μmol/L,P ＜ 0.01;(0.43 ± 0.08) μmol/g protein vs (0.87 ±0.17) μmol/g protein,P ＜0.01],while CSE protein and mRNA expression in lung tissue of rats in MCT group were downregulated (0.14 ± 0.02 vs 0.28 ± 0.09,P ＜ 0.01;0.84 ± 0.06 vs 1.12 ± 0.04,P ＜ 0.01).Condusion Endogenous H2S pathway is significantly downregulated in rats with monocrotaline-induced pulmonary hypertension.

Cardioprotective effect of creatine phosphate sodium combined with compound coenzyme on myocardial injury induced by Adriamycin of children with tumor / 中华实用儿科临床杂志

Objective To explore the protective effect of creatine phosphate sodium and compound coenzyme on tumor children with Adriamycin(ADM)-induced myocardial injury.Methods From Feb.2012 to Feb.2014,there were 153 tumor children administered in Shijitan Hospital,the Capital Medical University,among which there were 112 male and 41 female,aged from 10 months to 5 years,and the median age was 2.3 years.All the cases were randomly divided into 3 groups,with the dose of ADM at 20-30 mg/(m2 · d) for 3 days,and for 3 to 6 courses of treatment.All cases were rolled in the ADM chemotherapy:group A,intravenous infusion of creatine phosphate sodium(1.0 g/d) and compound coenzyme(1 injection/d),at a total of 7 days;group B with only intravenous infusion of creatine phosphate sodium(1.0 g/d) for a total of 7 days;group C with only intravenous infusion compound coenzyme(1 injection/d) for a total of 7 days.Two days before ADM chemotherapy,creatine phosphate sodium and / or compound coenzyme were administrated to protect the musculus cardiacus.One day before chemotherapy and two days after chemotherapy,the peripheral blood was taken to determine levels of malondialdehyde (MDA),creatine kinase (CK),creatine kinase MB (CK-MB),cardiac troponin(cTnT),N terminal pro-brain natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hsCRP),electrocardiogram,echocardiogram and so on.Then the changes of all those indicators before and after the chemotherapy between the groups were compared.Results The morbidity of myocardial damage induced by ADM was increased significantly with its dose accumulation (x2 =18.462,P ＜ 0.05).Creatine phosphate sodium combined with compound coenzyme could decrease the morbidity of myocardial damage induced by ADM (x2 =4.883,5.971,all P ＜ 0.05).Compared with those before chemotherapy,the cTnT (t =2.561,P ＜ 0.05),NT-proBNP (t =6.654,P ＜ 0.01) and hsCRP(t =3.149,P ＜ 0.01) levels of group A decreased markedly.Serum levels of MDA (t =2.170,P ＜0.05),CK-MB(t =2.596,P ＜0.05) and hsCRP(t =2.604,P ＜0.05) of group B increased obviously.Serum levels of MDA (t =2.151,P ＜ 0.05) and CK-MB (t =4.109,P ＜ 0.05) of group C also increased obviously.After chemotherapy,the detection of serum indexes of all groups showed as below.Contracted with those of group A,the serum MDA(t =4.461,P ＜ 0.01),CK-MB (t =3.273,P ＜ 0.01),cTnT (t =3.476,P ＜ 0.01),NT-proBNP (t =7.081,P ＜ 0.01) and hsCRP(t =5.941,P ＜ 0.01) levels of group B increased distinctly.Meanwhile,the MDA (t =4.064,P ＜0.01),CK-MB(t =5.452,P ＜0.01),cTnT(t =2.768,P ＜0.05),NT-proBNP(t =4.806,P ＜0.01)and hsCRP(t =3.436,P ＜ 0.05) levels of group C also increased significantly.Conclusions Both creatine phosphate and compound coenzyme could reduce the myocardial damage induced by ADM.Combination of them has important clinical value for better prevention of cardiac toxicity of ADM,enhancement of the prognosis of childhood tumor,and improvement of the long-term quality life of those children.

Effects of endogenous sulfur dioxide on pulmonary vascular inflammation in rats with monocrotaline-induced pulmonary hypertension / 中华实用儿科临床杂志

Objective To investigate the effects of endogenous sulfur dioxide(SO2) on pulmonary vascular inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension.Methods Thirty-two Wistar rats were randomly divided into 4 groups(n =8 for each group):control group,MCT group,MCT + L-aspartic acid-β-hydroxamate(HDX) group,and MCT + SO2 group.Rats in the MCT group,MCT + HDX group,and MCT + SO2 group were subcutaneously injected with MCT(60 mg/kg) on the first day.For rats in MCT + HDX group,HDX(25 mg/kg,on day 0,7 and 14) was given orally after injection of MCT; and rats in MCT + SO2 group were subcutaneously injected with the SO2 donor sodium sulfite/sodium bisulfate(Na2SO3/NaHSO3,and mole ratio was adjusted to approximately 3:1) each day.Rats in the control group received only the same volume of solvent vehicle only.After 3 weeks,mean pulmonary artery pressure(mPAP) of each rat was evaluated by using a right cardiac catheterization procedure.Immunohistochemistry was used to detect the expression of inflammatory related factor intercellular adhesion molecule-1 (ICAM-1) and the key molecules of nuclear factor-κB (NF-κB) signal transduction pathway,including p65 and inhibitor of NF-κB (IκBα) in the small pulmonary artery endothelial cells.Results The differences in mPAP,expression of ICAM-1,IκBα and p65 in the small pulmonary artery endothelial cells were found among the 4 groups (mPAP:F =53.334,P ＜ 0.01 ; ICAM-1:F =183.82,P ＜ 0.01 ; IκBα:F =142.89,P ＜ 0.01 ; p65:F =105.46,P ＜0.01).The mean pulmonary artery pressure(mPAP) was significantly raised in MCT group rats as compared with that of the control group along with upregulated expressions of ICAM-1 protein and p65 protein in small pulmonary artery endothelial cells,while the expression of IκBα protein in small pulmonary artery endothelial cells was significantly low.After administration of HDX,the mPAP and the expression of ICAM-1 protein and p65 protein in small pulmonary artery endothelial cells further increased compared with those of MCT group,while the expression of IκBα protein in small pulmonary artery endothelial cells was significantly lower than that of MCT group.Whereas with treatment of SO2 derivatives,the mPAP,the expression of ICAM-1 protein and p65 protein in small pulmonary artery endothelial cells were significantly lower than those of MCT group,while the expression of IκBα protein in small pulmonary artery endothelial cells increased significantly compared with that of MCT group.Conclusions Endogenous SO2 might inhibit the activation of NF-κB pathway in the small pulmonary artery endothelial cells,attenuate the pulmonary vascular inflammation and prevent the MCT-induced pulmonary hypertension in rats.

Changes of atrial natriuretic peptide and antidiuretic hormone in children with postural tachycardia syndrome and orthostatic hypertension: a case control study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The abnormal blood volume regulation is one of the most important pathogenesis in postural tachycardia syndrome in children. This study was designed to investigate the plasma atrial natriuretic peptide and antidiuretic hormone levels in postural tachycardia syndrome children, and their associations with the changes in heart rate and blood pressure in head-up test.</p><p><b>METHODS</b>Twenty-one postural tachycardia syndrome patients ((12 ± 2) years) and 26 healthy children ((12 ± 1) years) were included. According to blood pressure changes in head-up test, the postural tachycardia syndrome patients were divided into two subgroups: postural tachycardia syndrome with orthostatic hypertension and postural tachycardia syndrome without orthostatic hypertension. The plasma atrial natriuretic peptide and antidiuretic hormone levels were measured using enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>The plasma atrial natriuretic peptide level in postural tachycardia syndrome patients was higher than the control (P = 0.004), whereas the difference in plasma antidiuretic hormone level between postural tachycardia syndrome and controls was not significant (P = 0.222). The plasma antidiuretic hormone level of patients suffering from postural tachycardia syndrome with orthostatic hypertension was much higher than that of children having postural tachycardia syndrome without orthostatic hypertension (P < 0.05). In postural tachycardia syndrome patients, the upright max heart rate was positively correlated with the plasma atrial natriuretic peptide level (r = 0.490, P < 0.05) and the upright systolic blood pressure was positively correlated with the plasma antidiuretic hormone levels (r = 0.472, P < 0.05).</p><p><b>CONCLUSIONS</b>There was a disturbance of plasma atrial natriuretic peptide and antidiuretic hormone in postural tachycardia syndrome children.</p>

Changes of sulfur dioxide, nuclear factor-κB, and interleukin-8 levels in pediatric acute lymphoblastic leukemia with bacterial inflammation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bacterial inflammation is a common complication in patients with leukemia, and sulfur dioxide (SO2) is a bioactive molecule in modulating Gram-negative bacilli infection. This study aimed to examine the changes in SO2, nuclear factor-κB (NF-κB), and interleukin-8 (IL-8) levels in pediatric acute lymphoblastic leukemia (ALL) with Gram-negative bacterial inflammation.</p><p><b>METHODS</b>Fifty-five ALL children were enrolled in this study, including 30 males and 25 females, aged 3-13 years, and the median age was 7.8 years. All these children who accepted chemotherapy for ALL were divided into the control group (before chemotherapy), the infection group (after chemotherapy with infection), and the recovery group (the infection was controlled after 1 week). The serum level of SO2 was detected using high performance liquid chromatography with fluorescence assay, and NF-κB and IL-8 levels were measured by enzyme-linked immunosorbent assay (ELISA). Human THP-1 cells were cultured, induced, and differentiated into macrophages, which were divided into five groups and each group was cultured with different stimulators: lipopolysaccharide (LPS) group, LPS+L-aspartate-β-hydroxamate (HDX) group, LPS+SO2 group, SO2, and control groups. NF-κB level and IL-8 protein contents by ELISA were examined in each group.</p><p><b>RESULTS</b>In comparison with those of the control group, levels of serum SO2, NF-κB, and IL-8 of the infection group were significantly increased (P < 0.05), while those of the recovery group were significantly decreased (P < 0.05). A positive correlation was found between levels of serum SO2 and intracellular NF-κB/IL-8, and the correlation coefficients were 0.671 and 0.798 (P < 0.05), respectively. According to the results found in human THP-1 cells, levels of NF-κB and IL-8 in LPS group were significantly increased compared with those of the control group (P < 0.05); when compared with those in LPS group, levels of NF-κB in LPS+HDX group further increased significantly (P < 0.05); however, the NF-κB levels of LPS+SO2 group decreased significantly (P < 0.05).</p><p><b>CONCLUSION</b>SO2 may play an anti-inflammatory role during the process of inflammation by inhibiting the activation and transcription of NF-κB.</p>

Immune regulation of hydrogen sulfide in children with acute lymphoblastic leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute lymphoblastic leukemia (ALL) and chemotherapy can cause immune imbalance, and gaseous molecule hydrogen sulfide (H2S) can participate in the process of immune response. This study aimed to investigate the immune regulation of H2S in pediatric ALL.</p><p><b>METHODS</b>Children (n = 78) with ALL admitted during 2010-2013 were included in this study. Two blood samples were collected in period of before chemotherapy, bone marrow remission and two days after chemotherapy, respectively. Serum contents of H2S and cytokines, including interleukin-1β (IL-1β), interleukin-2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10) and macrophage inflammatory protein-1α (MIP-1α), were detected using ELISA method. Stepwise regression was used to analyze the correlation between H2S and cytokines. Furthermore, human Jurkat cells were cultured in vitro, and nucleoprotein of Jurkat cells and peripheral blood mononuclear cells (PBMCs) were collected, contents of cystathionine γ-lyase (CSE) and certain cytokines were measured by Western blotting.</p><p><b>RESULTS</b>Serum concentrations of H2S, IL-1β, IL-6, IL-10 and MIP-1a in children with ALL were increased significantly (P < 0.01), while concentrations of IL-2, TNF-α, IFN-γ and IL-4 decreased obviously (P < 0.01). In patients after chemotherapy, concentrations of H2S and IL-10 were decreased significantly (P < 0.05), but IL-4 and IFN-γ concentrations increased markedly (P < 0.05). At remission stage, H2S, IL-1β, IL-4, IL-6, IL-10 and MIP-1α concentrations were further decreased markedly (P < 0.05), but concentrations of IL-2, TNF-α and IFN-γ increased again (P < 0.05). Protein contents of CSE, IL-10, IL-4 and IL-2 of PBMCs also increased markedly in children with ALL. Moreover, changes of CSE protein contents of PBMCs were consistent with serum H2S contents, and there were significant correlation between H2S and certain cytokines based on stepwise regression analysis. Furthermore, compared with those of PBMCs group, in vitro study indicated that Jurkat cells of H2S group expressed IFN-γ, IL-10, IL-4 and IL-2 protein increased obviously (P < 0.05), while IL-4, IL-2 and CSE expression of PPG group decreased markedly (P < 0.05).</p><p><b>CONCLUSION</b>Gaseous molecule H2S might participate in the process of immune regulation in pediatric ALL through modulating transcription and expression of cytokines.</p>

Changes in plasma nitric oxide and nitric oxide synthase activity in children with orthostatic hypotension / 中华实用儿科临床杂志

Objective To explore the changes in plasma nitric oxide (NO) and nitric oxide synthase (NOS) activity in children with orthostatic hypertension(OHT) and the relationship with blood pressure changes.Methods The OHT group included 51 children who were diagnosed OHT in in-patient and out-patient departments of Peking University First Hospital from Jun.2012 to Jun.2013.Their age range was (12 ± 2) years.At the same time,control group consisted of 28 normal children who received physical examination with their age range of(12 ± 1) years.The diagnosis of OHT was based on the clinical manifestation and head-up tests.Plasma NO was determined by using a nitrate reductase method and plasma NOS activity by a chemical colorimetric method.Results 1.There were no significant differences between OHT group and control group in age,sex ratio,height,weight and body mass index (all P ＞0.05).2.In OHT children,the upright systolic blood pressure was higher than that of the supine [(114 ± 10) mmHg vs (104 ± 9) mmHg,t =-12.853,P ＜ 0.001],and the upright diastolic blood pressure was higher than that of the supine[(73 ±7) mmHg vs(59 ± 8) mmHg,t =-21.859,P ＜0.001].3.Plasma NO level and NOS activity,however,were significantly lower in OHT group than those in the control group [NO:(28.947 ± 6.031) μmol/L vs (35.216 ±6.662) μmol/L,t =4.257,P ＜ 0.001 ; NOS activity:(14.753 ± 3.060) U/mL vs (17.560 ± 4.253) U/mL,t =3.026,P =0.006].4.There was significantly negative correlation between plasma NO and the upright systolic blood pressure(r =-0.276,P ＜ 0.05) and the systolic blood pressure change (r =-0.280,P ＜ 0.05).Conclusions Plasma NO level and NOS activity were significantly lower in OHT children than those in control group.The abnormal vascular endothelial function may play an important role in OHT in children.

Advances in study of physiologic effects of endogenous sulfur dioxide and its derivatives / 北京大学学报(医学版)

Sulfur dioxide (SO_2) is an ordinary air pollutant globally and harm to human health. L-cysteine is the major sulfur-containing amino acid and its normal metabolism can produce hydrogen sulfur (H_2S) and SO_2. It is realized that H_2S has various bioactivities and is the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO). Recently, attention has been paid to the physiologic effects of endogenous SO_2 and its derivatives (bisulfite and sulfite) in vivo, and recognized that SO_2 and its derivatives can lower blood pressure, change heart rates, participate in inflammatory reactions, and so on, suggesting that endogenous SO_2 may modulate the physiologic functions in vivo as a bioactive molecule.

Vasorelaxant effect of sulfur dioxide derivatives on isolated aortic rings of rats and its mechanisms / 北京大学学报(医学版)

6(mmol/L).) Nicardipine(1?10~(-9) mol/L) could decrease the contraction of the rings to NE,and even could inhibit the relaxation of Na_2SO_3/NaHSO_3 almost completely.The inhibition of the endogenous SO_2 production with HDX(1?10~(-4) mol/L),resulted in an increase in the contraction of rings.The contraction curve to NE shifted to the left,and IC_(50) also changed from(6.48?0.84)?10~(-7)mol/L to(3.97?(1.63))?10~(-7) mol/L(P

The effect of sulfur dioxide on blood pressure and aortic structure of spontaneously hypertensive rat / 中国药理学通报

Aim To investigate the effect of sulfur dioxide (SO2) on blood pressure and aortic structure of the spontaneous hypertensive rat(SHR).Methods Sixteen male SHRs at the age of 4 weeks were randomly divided into SHR control group and SHR+Na2SO3/NaHSO3 group,respectively.Another eight male WKY rats served as WKY control group.Five weeks later, the blood pressure was determined.The rat aortas were dyed with Hart's Method. The morphometric parameters including outer radius, lumen radius and the wall thickness were calculated by Leica workstation. The proliferative index (PI) of smooth muscle cells was detected by immunohistochemical assay.Results The blood pressure of SHR control increased compared with that of WKY control rats(P