Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Objective:To investigate the effect of combined treatment of hyperforin(HPF) and amlexanox(AM) on obesity and metabolic disorders.Methods:ob/ob mice were used as an obese mice model and treated with HPF alone(2.5 mg/kg intraperitoneal injection) or combined with AM(50 mg/kg, gavage administration) for 4 weeks. Their body weight and food intake were monitored, glucose tolerance test and insulin tolerance test were performed, serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels were detected. Nuclear magnetic resonance was used to detect the body composition and metabolic cage was used to detect the energy consumption. After sampling, HE staining was used to observed the pathological change of fat and liver tissues, Western blotting and enzyme-linked immunosorbent assay(ELISA) were used to detect the cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA) signaling pathway.Results:Compared to the vehicle-treated mice(54.07 g), HPF-treated mice showed attenuated body weight gain(51.33 g, P=0.042) and reduced total fat mass( P=0.011); while administration of HPF in combination with AM(HPF/AM) further reduced the body weight(47.61 g, P=0.041). HE staining analysis showed that HPF alone or HPF/AM treatment both decreased the diameters of adipocytes and infiltration of white fat( P=0.014, P=0.032) in brown adipose tissues, which resulted in a trend of browning. However, HPF/AM-treatment didn′t further diminish adipocytes or reduce lipid accumulation in brown adipose tissues compared to HPF-treated mice. In addition, the basal oxygen consumption rate(VO 2, P<0.001) and(VCO 2, P=0.002) of HPF-treated mice were mainly elevated in the light phase relative to that of control mice; while HPF/AM-treatment further promote the energy consumption both in the dark phase and light phase. Notably, cAMP-PKA signaling pathway was obviously activated under HPF/AM-treatment in inguinal white adipose tissue. Moreover, HPF/AM-treatment showed beneficial effects on glucose metabolism and fatty liver, as indicated by improved insulin resistance, reduced liver steatosis( P=0.049) and the serum ALT levels( P=0.008). Conclusion:Combined administration of HPF and AM is an effective strategy in the treatment of obesity, improvement of metabolic disorders and alleviation of catecholamine resistance.

Objective: To compare bioelectrical impedance analysis (BIA) and dual energy X ray absorptiometry (DXA) for measuring body mineral content (BMC) of children and adolescents, and to provide a basis for BIA to accurately measure BMC in children and adolescents. Methods: By using the convenience sampling method, among 1 469 children and adolescents aged 7-17 were recruited in Guangzhou from April to May 2019, the BMC was measured by DXA and BIA. The intraclass correlation coefficient ( ICC ) and Bland Altman analysis were used to evaluate the agreement between BIA and DXA. Bland Altman analysis was performed on log transformed data. The BMC was categorized into age and specific tertiles, and the agreement between methods was evaluated based on the kappa coefficients. Treating the BMC with DXA as the dependent variable, a prediction model was constructed for correcting the BIA measure. Results: The ICC s were 0.93 and 0.94 for boys and girls, respectively. In Bland Altman analysis, the limits of agreements for the BIA to DXA ratio were wide in boys and girls, ranging from 0.27-0.76 and 0.17-0.72, respectively. The kappa coefficients for categorized BMC levels were 0.57 and 0.45 for boys and girls, respectively, showing a fair to good degree of agreement. When sub grouped by BMI, the kappa coefficients for all BMI groups of boys and overweight girls were all >0.75 , with an excellent agreement. The prediction models for boys and girls were as follows: BMC DXA =-0.51+0.44× BMC BIA + 0.06× Age +0.02× BMI ; and BMC DXA =-0.55+0.43× BMC BIA +0.06× Age +0.02× BMI , respectively. The R 2 for models of boys and girls were 0.87 and 0.87, respectively. Conclusion The agreement between BIA and DXA was poor for measuring BMC, but acceptable when evaluating the categorized BMC levels, suggesting the BIA may be applied in assessment of the BMC levels when compared to the age and gender specific population. Additionally, the prediction model for correcting BMC by BIA fis well to the measurement by DXA.

Objective:To evaluate the consistency between bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) in the measurement of body composition in children and adolescents aged 7-17 years.Methods:Fat-free mass (FFM) and fat mass (FM) were measured by both BIA and DXA in 1 431 children. The consistency between the methods was evaluated by intra-class correlation coefficients (ICCs) and Bland-Altman analysis. Logarithmic transformation of both measurements was performed before Bland-Altman analysis.Results:The ICCs for FFM were 0.986 and 0.974 and ICCs for FM were 0.854 and 0.926 in boys and girls respectively. In boys, the mean ratio of FFMs by BIA and DXA was 1.04, with limits of Agreement (LoA) of 0.95-1.14, and in girls, the mean ratio of FFMs by BIA and DXA was 1.02, with the LoA of 0.90-1.15. The LoA of FFM became narrower with age in both boys and girls. Both boys and girls had the wide LoAs for FM (0.40-1.27 and 0.48-1.48, respectively). Additionally, the LoA ranges for FFM and FM narrowed with the increase of BMI level in both boys and girls.Conclusion:For all children, BIA showed good consistency with DXA for FFM, whereas significant errors occurred in FM measurement. The consistency between BIA and DXA was better for obese children than for underweight or normal-weight children.

Objective:To provide the risk stratification method of hepatoblastoma (HB) suitable for implementation in China and explore the new treatment method for high-risk HB patients.Methods:A total of 100 cases of children and adolescents under 18 years old with newly diagnosed HB in Sun Yat-sen University Cancer Center and Sun Yat-sen University First Affiliated Hospital from September 2014 to September 2018 were included. According to the clinical stage, AFP level, pathological subtype and other factors, patients were stratified into four groups: extremely low-, low-, intermediate- and high-risk. The patients at very low risk were treated with surgery only and followed-up. The patients at very low risk were treated with C5V(Cisplatin+ 5-Fluroracil+ Vincristine) regimen for 4 courses. The patients at intermediate risk were treated with C5VD(Cisplatin+ 5-Fluroracil+ Vincristine+ Doxorubicin)regimen before and after surgery for 6-8 courses. The patients at high risk were treated with C5VD and IIV (ifoshamide+ irinotecan+ vincristine) alternately before and after surgery for 8 courses.Results:One hundred patients were stratified into extremely low-risk, low-risk, medium-risk and high-risk groups for 2, 10, 51 and 37 cases, respectively. Eighty three cases had evaluable lesions before chemotherapy. Among them, 65 patients achieved partial remission, stable disease and progressive disease were observed in 10, and 8 cases, respectively, with a response rate of 78.3%. During a median follow-up of 20 months, 30 patients experienced tumor relapse or progression, and 27 of them died. The 2-years progression-free survival (PFS) and overall survival (OS) rates were 69.2% and 72.0%, respectively. The 2-years PFS rates of patients with extremely low risk, low risk, medium risk and high risk were 100%, 88.9%, 75.3% and 43.2%, respectively. The 2-years OS rates were 100%, 100%, 81.0% and 44.8%, respectively.Conclusions:The novel HB risk classification is simple and feasible. With active comprehensive treatment, patients at extremely low-, low- and medium-risk have excellent outcomes. The survival rate of high-risk HB patients remains to be improved, and new treatment strategies need to be explored.

Objective:To provide the risk stratification method of hepatoblastoma (HB) suitable for implementation in China and explore the new treatment method for high-risk HB patients.Methods:A total of 100 cases of children and adolescents under 18 years old with newly diagnosed HB in Sun Yat-sen University Cancer Center and Sun Yat-sen University First Affiliated Hospital from September 2014 to September 2018 were included. According to the clinical stage, AFP level, pathological subtype and other factors, patients were stratified into four groups: extremely low-, low-, intermediate- and high-risk. The patients at very low risk were treated with surgery only and followed-up. The patients at very low risk were treated with C5V(Cisplatin+ 5-Fluroracil+ Vincristine) regimen for 4 courses. The patients at intermediate risk were treated with C5VD(Cisplatin+ 5-Fluroracil+ Vincristine+ Doxorubicin)regimen before and after surgery for 6-8 courses. The patients at high risk were treated with C5VD and IIV (ifoshamide+ irinotecan+ vincristine) alternately before and after surgery for 8 courses.Results:One hundred patients were stratified into extremely low-risk, low-risk, medium-risk and high-risk groups for 2, 10, 51 and 37 cases, respectively. Eighty three cases had evaluable lesions before chemotherapy. Among them, 65 patients achieved partial remission, stable disease and progressive disease were observed in 10, and 8 cases, respectively, with a response rate of 78.3%. During a median follow-up of 20 months, 30 patients experienced tumor relapse or progression, and 27 of them died. The 2-years progression-free survival (PFS) and overall survival (OS) rates were 69.2% and 72.0%, respectively. The 2-years PFS rates of patients with extremely low risk, low risk, medium risk and high risk were 100%, 88.9%, 75.3% and 43.2%, respectively. The 2-years OS rates were 100%, 100%, 81.0% and 44.8%, respectively.Conclusions:The novel HB risk classification is simple and feasible. With active comprehensive treatment, patients at extremely low-, low- and medium-risk have excellent outcomes. The survival rate of high-risk HB patients remains to be improved, and new treatment strategies need to be explored.

Objective:To explore the effect of preoperative visit with Child Life mode in the management of preschool children′s anxiety.Methods:A total of 80 cases of children of pre-school age who were operated from September 2018 to February 2019 were selected by cluster sampling method. The children from September to November 2018 who were given the traditional mode of preoperative visit were set as the control group. Children from December 2018 to February 2019 who were given preoperative visit with Child Life mode were set as the experimental group. The Modified Yale Perioperative Anxiety Scale (m-YPAS) scores, Induction Compliance Checklist (ICC) scores and Pediatric Anesthesia Emergence Delirium (PAED) scores were compared between the two groups at 4 different perioperative time points (6 hours after admission, waiting for surgery, induction of anesthesia, and 6 hours after surgery).Results:Totally three patients were suspended from the study due to surgery. A total of 77 children were studied, 38 in the experimental group and 39 in the control group. The score of m-YPAS in the experimental group was significantly lower than that of the control group(17.57±16.64 vs. 42.04±27.46, t value was 3.85, P<0.01) while waiting for surgery. The score of m-YPAS in the experimental group was significantly lower than control group (31.64±27.95 vs. 62.22±25.13, t value was 4.26, P<0.01) at the anesthesia induction. Compare with the control group, the score of m-YPAS in the experimental group showed no significant difference at both time of 6 hours after admission (18.19±17.83 vs.19.85±17.92, t value was 0.87, P>0.05) and 6 hours after surgery(35.61±15.70 vs. 41.81±17.97, t value was 1.37, P>0.05). Compare with the control group the score of ICC in the experimental group was significantly decreased (1.40±1.39 vs. 3.78±2.60, t value was 4.88, P<0.01) at the anesthesia induction. The score of PEAD in the experimental group and control group, there was no significant difference between the two groups (7.18±2.45 vs. 7.85±3.05, t value was 0.91, P>0.05). Conclusions:Compared with the traditional preoperative visit mode, the preoperative visit mode of Child Life can effectively relieve the anxiety of preschool children undergoing general anesthesia surgery while they are waiting for surgery and during anesthesia induction, and can improve the degree of cooperation during anesthesia induction.

Objective:To summarize the efficiency and long-term outcomes of limited-stage Hodgkin lymphoma in children and adolescents with ABVD therapy and determined whether omitting radiotherapy for a low-risk patient enabled the achievement of complete response (CR) after chemotherapy.Methods:We retrospectively analyzed data from 13 y (2004-2016) from patients aged ≤18 y with limited-stage HL admitted to the Sun Yat-sen University Cancer Center. Patients received treatment with ABVD chemotherapy alone or ABVD chemotherapy followed by low-dose involved field radiotherapy.Results:Total 85 subjects were eligible for study inclusion; the median age was 12 (3-18) y; 66 (77.6%) were men, 80 (94.1%) had stage-II disease, 56 (65.9%) were at low-risk, and the median follow-up duration was 72 (8-196) months; 12 relapsed, 2 had secondary neoplasm, and 2 died. The 5-year event free survival (EFS) was (85.6±3.8) %, and the overall survival (OS) was 100%. The 5-year EFS and OS was (89.1±4.2) % and 100%, respectively, for the low-risk cohort and (79.3±7.5) % and 100%, respectively for the intermediate-risk cohort. Among the 39 low-risk patients who achieved CR after chemotherapy, 15 received treatment with chemotherapy followed by LD-IFRT. In the exploratory subset analysis, the low-risk cohort who achieved CR after chemotherapy, the 5-year EFS for comparing ABVD alone with chemotherapy followed by LD-IFRT was (87.0±7.0) % versus 100% ( P=0.506) , and the OS was 100% for both the groups. Conclusions:Our retrospective analysis showed excellent survival of limited-stage HL patients with ABVD therapy. For patients who achieving CR after chemotherapy with low-risk HL, received chemotherapy followed by LD-IFRT does not improve 5-year OS and EFS. The use of risk- and response-based stratification may facilitate the development of effective and less toxic protocols.

Objective: To investigate the impact of intensified maintenance therapy on the prognosis of children and adolescents with advanced lymphoblastic lymphoma (LBL) . Methods: Retrospective analysis on the treatment results of children and adolescents with stage Ⅲ and stage Ⅳ LBL who underwent BFM-NHL-90/-95 regimen without prophylactic radiotherapy. The intensified therapy group included the patients admitted from 1998 to 2005, while others were classified as the non-intensified therapy group. Patients in the intensified therapy group were intravenously treated with "etoposide phosphate plus cytrarabine" and high-dose methotrexate alternately per 2.5-3 months in addition to the oral chemotherapy with 6-mercaptopurine and methotrexate during the maintenance phase. Results: A total of 187 LBL patients were enrolled. The rates of 5-year event free survival were (76.9 ± 5.8) % and (77.9 ± 4.3) % (χ²=0.249, P=0.617) respectively, in the intensified therapy (n=52) and the non-intensified therapy groups (n=135) , while the rates of 5-year overall survival of them were (78.8 ± 5.7) % and (79.8±4.1) % (χ²=0.353, P=0.552) , respectively. Stratified by stage, immunological type as well as risk stratification, the rates of long-term survival were similar between the two groups. During the maintenance phase, the rates of grade Ⅲ and Ⅳ myelosuppression in the intensified therapy and the non-intensified maintenance groups were 55.8% and 18.5%, respectively (χ²=25.363, P<0.05) . Conclusion Intensified maintenance therapy failed to improve the prognosis of patients with advanced LBL.