Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Objective:To investigate the clinical characteristics and possible causes of transient spontaneous remission of childhood acute leukemia.Methods:The data of 3 children with acute leukemia who had transient spontaneous remission before standardized chemotherapy in Sun Yat-sen Memorial Hospital of Sun Yat-sen University in July 2018, May 2019 and October 2020 were collected. Moreover, the related influencing factors of spontaneous remission in leukemia were discussed by review of the literature.Results:All 3 children had fever at the onset of the disease, and they achieved transient spontaneous remission after anti-infection therapy. Case 1 obtained partial remission after the initial diagnosis of acute B lymphocytic leukemia (B-ALL), leukemia gene test showed E2A-PBX1 fusion, and relapsed after 12 days. Case 2 obtained spontaneous remission after the initial diagnosis of B-ALL, leukemia gene test showed p16 gene deletion and NRAS and EP300 genes mutation, and relapsed after 20 days. Case 3 obtained spontaneous remission after the initial diagnosis of acute monocytic leukemia, leukemia gene test showed MLL-ENL fusion and NRAS gene mutation, and relapsed after 30 days. A review of the literature showed that the main influencing factors of spontaneous remission in leukemia were Down syndrome, infection and blood transfusion. Other influencing factors included leukemia-related genes, termination of pregnancy and application of drugs.Conclusions:Transient spontaneous remission of childhood acute leukemia is rare in clinical practice, and the possible mechanism is related to infection-induced immune abnormalities. It is recommended that leukemia patients with spontaneous remission should be closely monitored for minimal residual disease.

Objective:To evaluate the efficacy and safety of eltrombopag for children with thrombocytopenia after hematopoietic stem cell transplantation (HSCT).Methods:Clinical data of 24 patients with thrombocytopenia after HSCT,who were treated with eltrombopag in the Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from August 1, 2018 to April 1, 2019 were analyzed retrospectively. The response rate and adverse reactions of eltrombopag were evaluated. Patients were divided into groups by source of hematopoietic stem cells (umbilical cord blood group and peripheral stem cell group) and type of disease (malignant and non-malignant disease group) and the clinical outcomes between groups were compared. Rank Sum test was used for comparisons between groups.Results:Among 24 cases, 15 were males and 9 females, the age of starting eltrombopag was 7.7 (2.6-13.7) years, the time of eltrombopag treatment after HSCT was 27.5 (8.0-125.0) days, the time from treatment to complete response (CR) was 23.5 (6.0-83.0) days, with the treatment course 36.5 (8.0-90.0) days. The total dose of eltrombopag was 1 400(200-5 900) mg. Complete response rate was 92% (22/24),without eltrombopag related adverse reactions. Comparing with peripheral stem cell group ( n=8), the course and total dose of eltrombopag in umbilical cord blood group ( n=16) were significantly reduced(24.5 (8.0-81.0) vs. 65.5 (35.0-90.0) d, Z=-3.004, P=0.002; 900.0 (200.0-3 850.0) vs. 2 862.5 (1 175.0-5 900.0) mg, Z=-2.604, P=0.007), but no significant differences were found in the time from treatment to complete response, platelet count after 2 weeks of eltrombopag withdrawal or platelet count at the end point of follow-up (all P>0.05). Comparing malignant patients ( n=12) and non-malignant patients ( n=12), no significant differences were found in the time from treatment to complete response, course, total dose, platelet count after 2 weeks of eltrombopag withdrawal, and platelet count at the end point of follow-up in non-malignant patients (all P>0.05). Conclusion:Eltrombopag is safe and maybe effective for thrombocytopenia after HSCT, especially for umbilical cord blood transplantation.

Objective:To establish a method for determining mercury in blood with direct mercury analyzer.Methods:After the whole blood sample was extracted by solvent and removed by nitric acid, it was then measured by direct mercury analyzer.Results:After optimizing the conditions of the instrument, the linear range was 0.3-60.0 μg/L and the curve correlation coefficient was higher than 0.999. The lower limit of quantitations was 0.3 μg/L and the minimum quantitative concentration was 3.0 μg/L. The recovery and relative standard deviations ( RSD) was 95.2%-97.6% and 1.4%-3.3%. Conclusion:The method is stable, reliable, easy to operate and has high sensitive. It can be used to determine mercury in blood.

Objective:To explore the clinical characteristics and management of childhood acute lymphoblastic leukemia (ALL) complicated with cerebral venous thrombosis (CVT).Methods:The clinical data of 14 ALL children complicated with CVT who were admitted to Department of Pediatrics of Sun Yat-sen Memorial Hospital and underwent chemotherapy from January 2011 to October 2019 were collected retrospectively. The clinical manifestations, coagulation function, imaging findings, treatment plan and prognosis of patients were analyzed.Results:CVT was diagnosed in 14 (2.8%, 14/505) cases, with a median age of 10 (3-14) years at onset, 11 cases occurred in the stage of induction remission, and the acute onsets were mainly characterized by convulsions (9 cases), consciousness disorders (6 cases) and headache (4 cases). Coagulation function test showed that, before the CVT, antithrombin Ⅲ activity was lower than 60% in 8 cases, D-dimer elevated on the day of onset in 8 cases. Arteriovenous angiography showed filling defects in single (9 cases) or multiple (5 cases) venous sinuses. The most common site of venous sinus enlargement was superior sagittal sinus (10 cases). Secondary cerebral hemorrhage was found in 5 cases. Anticoagulation therapy included combination of low-molecular-weight heparin (LMWH) and warfarin in 9 cases, sequential application of LMWH and warfarin in 2 cases, and LMWH alone in 3 cases. Patients accepted further asparaginase and no CVT recurrence or progression was found.Conclusions:The secondary coagulation dysfunction during induction remission chemotherapy is the major risk factor for CVT in ALL, which needs active monitoring and early prevention. Arteriovenous angiography can diagnose accurately, and the prognosis of anticoagulant therapy with LMWH and warfarin is optimistic.

Objective:To establish a method for determining mercury in blood with direct mercury analyzer.Methods:After the whole blood sample was extracted by solvent and removed by nitric acid, it was then measured by direct mercury analyzer.Results:After optimizing the conditions of the instrument, the linear range was 0.3-60.0 μg/L and the curve correlation coefficient was higher than 0.999. The lower limit of quantitations was 0.3 μg/L and the minimum quantitative concentration was 3.0 μg/L. The recovery and relative standard deviations ( RSD) was 95.2%-97.6% and 1.4%-3.3%. Conclusion:The method is stable, reliable, easy to operate and has high sensitive. It can be used to determine mercury in blood.

Objective: To establish a solvent desorption gas chromatographic method for determination of Sevoflurane, Isoflurane and Enflurane in the air of the Workplace. Methods: Sevoflurane, Isoflurane and Enflurane were collected with activated carbon tube and desorbed with dichloromethane, separated with DB-1 capillary columns, and then detected with flame ionization detector. Results: The linearity ranges were 1.9-304.8 μg/ml for Sevoflurane, 2.1-300.4 μg/ml for Isoflurane and 1.7-305.2 μg/ml for Enflurane, The correlation coefficient was both >0.999. Their limits of detection were 0.6 μg/ml, 0.6 μg/ml and 0.5 μg/ml, and Their limits of quatification were 1.9 μg/ml, 2.1 μg/ml and 1.7 μg/ml, and their minimum detectable concentrations were 0.1、0.2 and 0.1 mg/m³ per 4.5 L of air. Their relative standard deviations (RSD) were 2.5%-3.0%, 2.3%-3.1% and 2.2%-3.0%. The average desorption efficiencies were 101.1%-103.3%, 100.7%-102.7% and 101.0%-102.9%. The sampling efficiency was both 100%. The breakthrough volume of 100 mg actived carbon was 3.7 mg, 3.4 mg and 3.4 mg. Sevoflurane, Isoflurane and Enflurane in activated carbon tube could be kept at least 10 days at room temperature without significant losses. Conclusion The method shows lower detection limit, high accuracy and precision. It is feasible for determination of Sevoflurane, Isoflurane and Enflurane in the air of workplace.

Objective: To establish a method for determination of lead and istope ratios in the blood by ISIS-ICP-MS. Methods: After wet digestion, the blood sample was on-line addition of thallium as internal standard and analyzed by ISIS-ICP-MS. Results: The limit of detection was 0.03 μg/L and the lower limit of quantification was 0.08 μg/L. The detection concentration was 0.45 μg/L and the minimum quantitative concentration was 1.49 μg/L. The relative standard deviations (RSD) were 0.3%~1.7%. The recovery was between 91.0% and 103.4%. The precision of the major lead isotope ratios was better than 0.3%. The calibrated isotope ratios of the standard liquid are close to the certificate. Conclusion The method has a low detection limit, good precision and high accuracy, it is feasible for determination of lead concentration and isotope ratios in the bloune.

Objective: To establish a method for determination of acetone, dichloromethane, hexane, 1, 1, 1-trichloroethane, 1, 2-dichloroethane, benzene, toluene, ethylbenzene etc organic compounds in urine by headspace gas chromatography-mass spectrometry (GC-MS) . Methods: Headspace gases of urine samples were injected into GC and determined by mass. Results: Determination of urine components were in a good linear range in their concentration range of this method. The correlation coefficients were between 0.996 and 1.000 with the detection limits between 0.1 μg/L and 4.5 μg/L, the precisions were between 1.3% and 4.6%, the recovery rates were between 86.2% and 97.4%. Conclusion This method has the advantages of low detection limits, high accuracy, high precision and simple pretreatment, which is suitable for the determination of the content of various volatile organic compounds in urine.

Objective: To establish a method for the determination of manganese in urine by graphite furnace atomic absorption spectrometry (AAS) without the use of matrix modifier. Methods: The urine samples were 5 times diluted with 1% nitric acid then directly determined by AAS. Zeeman was used for background correction. Results: The linear range for determination of manganese in urine was 5~60 μg/L (urine) . The correlation coefficient was greater than 0.995 with the detection limit of 1.5 μg/L and with the lower limit of quantification of 5.0 μg/L. The relative standard deviations (RSDs) of within-run precision was between 1.1%~4.3%, the RSDs of between-run precision was between 3.3%~7.0%. The average recovery was 102.6%. The samples can be stored for 14 days at room temperature, 4℃, -8 ℃ and -35 ℃. Conclusion The method is feasible for determination of manganese in urine.