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).

Objective:To study the role of a novel brain-derived peptide hypoxic-ischemic brain damage associated peptide (HIBDAP) in regulating pyroptosis of oxygen-glucose deprived (OGD) microglia.Methods:The sequence of HIBDAP was coupled with the sequence of cell-penetrating peptide transactivator of transcription (TAT) to form TAT-HIBDAP. Fluorescein isothiocyanate (FITC) labeled TAT-HIBDAP was added to microglia cells and observed under fluorescence microscope. Microglia cells were treated with different concentrations of TAT-HIBDAP (1, 5, 10, 20 μmol/L) and then OGD process. Cell pyroptosis was analyzed using lactate dehydrogenase (LDH) assay. The concentration of TAT-HIBDAP with the most prominent inhibiting effects was determined and selected for subsequent experiments. The pyroptosis morphology of the control group, the OGD group and the HIBDAP group (5 μmol/L TAT-HIBDAP+OGD) was observed using transmission electron microscope. The mRNA and protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes were examined using real-time quantitative PCR and Western Blot analysis.Results:Fluorescence microscope showed FITC-labeled TAT-HIBDAP could successfully enter microglia cells. Compared with the OGD group, low concentrations of TAT-HIBDAP (1, 5, 10 μmol/L) could significantly reduce microglia pyroptosis and the concentration of 5 μmol/L showed the most prominent effects. Compared with the control group, OGD group showed typical pyroptosis morphology and HIBDAP group showed significantly improved morphology. The mRNA and protein expression of NLRP3 inflammasomes in the OGD group were significantly higher than the control group and also the HIBDAP group.Conclusions:The novel brain-derived peptide HIBDAP may reduce the expression of NLRP3 inflammasomes and inhibit the pyroptosis of OGD microglia.

Objective:To explore the application value of single source dual energy CT (DECT) scanning technique in improving the image quality of the pancreas.Methods:Imaging data of 21 patients with normal pancreas and 36 patients with pancreas related diseases in the First Affiliated Hospital of Naval Medical University from July 2021 to August 2021 were collected. All the patients first underwent multi-slice CT (MDCT) scan with no-contrast, and then dynamic enhanced MDCT scan. And the DECT scan was used in the delay period. Virtual single energy images (VMI, 40~100keV) of normal pancreas and mixed energy images of pancreatic lesions (PI, 80 and 140kVp) were obtained. The regions of interest (ROI) of fat on abdominal wall, normal pancreas and abdominal aorta were delineated, the CT values and standard deviation (SD) of each ROI were measured and recorded, and the pancreatic signal-to-noise ratio (SNR) and contrast-to-noise ratio (SNR) of each energy image were calculated. The objective index and subjective score of VMI(40-100keV) and PI (80kVp and 140kVp) with iodine (water) base map and VMI best CNR were compared between groups. The correlation between VMI(40-100keV) and PI(80, 140kVp) with iodine (water) base map and VMIbest CNR was analyzed by univariate regression.Results:In VMI(40-100keV) of normal pancreas, the highest SNR value was VMI best CNR and iodine (water) base map, and the highest CNR values were VMI 60keV and iodine (water) base map. There were significant differences on SNR and CNR values between different energy VMI and iodine (water) base map ( P<0.05). Among the four images of PI 80kVp, PI 140kVp, VMI best CNR and iodine (water) base map for pancreatic lesions, the SNR and CNR values of iodine (water) base map were the highest. The SNR and CNR values of VMI best CNR were higher than those of PI 80kVp, and the differences were statistically significant ( P<0.05). The lesion significance and edge sharpness score of iodine (water) base map was the highest, which was better than other groups; the lesion significance and edge sharpness score of VMI best CNR was better than PI 140kVp, and the differences were statistically significant ( P<0.05). The results of univariate regression analysis showed that the SNR values of PI 80kVp, PI 140kVp and VMI best CNR for pancreatic lesions were positively correlated with those of the iodine (water) base map ( P<0.05), the CNR values of PI 140kVp and VMI best CNR images were positively correlated with the iodine (water) base map ( P<0.05), and the SNR and CNR values of PI 140kVp were positively correlated with VMI best CNR ( P<0.05). Conclusions:VMI with different energy and iodine (water) base maps can be obtained by single source DECT enhanced scanning of pancreas related diseases. The VMI best CNR was the best among all VMIs, while the SNR and CNR values of iodine (water) base maps were the highest in all images. The VMI best CNR and iodine (water) base maps can improve the image quality of pancreas related diseases.

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 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.

ObjectiveTo compare the clinical efficacies between bloodletting cupping plus acupuncture and acupuncture alone in treating hypertension.MethodSixty patients with primary hypertension were randomized into a treatment group and acontrol group, 30 cases in each group. The treatment group was intervened by bloodletting cupping plus acupuncture, while the controlgroup was by acupuncture. The clinical symptoms, blood pressure, and hemorheological parameters were observed before and after intervention.ResultThe clinical symptoms were improved in both groups after intervention, and the total effective rate was 76.7%in the treatment group versus 63.3% in the control group; the blood pressure dropped in both groups, and the differences were statistically significant between the two groups (P<0.05); the treatment group was superior to the control group in improving the whole blood viscosity and erythrocyte sedimentation rate(P<0.01).ConclusionBloodletting cupping is effective in treating primary hypertension; regarding the short-term therapeutic efficacy, bloodletting cupping plus acupuncture can produce a more significant effect than acupuncture alone in improving the blood pressure, whole blood viscosity, and erythrocyte sedimentation rate in primary hypertension patients.

Objective: To investigate the effect of gross total resection on the local control and survival of patients with stage IV neuroblastoma (NB) and analyze the extent of surgical resection of primary tumors that affects patient survival. Methods: A total of 96 patients with stage Ⅳ NB who were admitted to the Sun Yat-Sen University Cancer Center between January 2000 and December 2011 were analyzed. The patients were treated with combined-modality therapy, including chemotherapy, surgery, and/or radiotherapy. The patients were divided according to the extent of surgical resection of primary tumor into the following groups: group A, biopsy or tumor removal of less than 50% of the primary lesion; group B, incomplete resection of more than 50% but less than 90% of the lesion; group C, removal of more than 90% of the lesion; and group D, complete resection with or without macroscopic residual tumors. The survival rates of each group were analyzed. Results: The median age of the 96 patients was 4.4 years, ranging from 1.2-18.8 years. The overall 3-year progression-free survival (PFS) and overall survival (OS) of the total patients were 32.8% and 36.7%, respectively. A total of 24 cases were assigned in group A, 10 in group B, 23 in group C, and 39 in group D. Subgroup analysis revealed that the 3-year PFS rate was 17.5% for group A, 20.0% for group B, 45.1% for group C, and 40.5% for group D. The PFS rates were not statistically significant-ly different between groups A and B (P=0.352) and between groups C and D (P = 0.792). However, the OS was higher in groups C and D than that in groups A and B. The 3-year PFS rates were 42.2% and 17.8% for groups C and D (P<0.001), respectively. Conclu-sion: Resection extension of more than 90% of the primary tumor combined with chemotherapy and (or) radiation therapy can improve the survival of patients with stage Ⅳ NB. However, this treatment modality does not affect the treatment outcomes for minimal gross tu-mor residuals.

OBJECTIVETo evaluate the long-term survival of children and adolescents with lymphoblastic lymphoma (LBL) treated by a modified NHL-BFM-90 protocol.

METHODSFrom March 1998 to November 2010, 107 untreated patients with LBL (age <18 years) were enrolled and stratified into three groups (R1, R2 and R3), according to the stage of disease and response to induction chemotherapy. All patients received different intensive chemotherapy regimens based on a modified NHL-BFM-90 protocol. Total treatment duration was 2 years.

RESULTSOf the 107 patients, 79 were boys and 28 were girls, with a median age of 10 years (range 2.5-18 years). Six patients (5.6%) were stage I/II, 101 (94.4%) stage III/IV. The R1, R2 and R3 groups accounted for 5.6%, 71.0% and 23.4%, respectively. 75.7% of the patients had T-LBL, and 24.3% was B-LBL. At a median follow-up duration of 60 months (range 1-186 months), 24 patients died. The 5-year event-free survival (EFS) and overall survival (OS) were 75.5% and 77.8 % for all patients, 100.0% and 100.0% for group R1, 84.5% and 87.5 % for R2, 44.0% and 44.0% for R3, 72% and 73.5% for T-LBL, 86.4% and 88.5% for B-LBL, respectively. Myleosuppression was the major toxicity and need aggressive management.

CONCLUSIONThe modified NHL-BFM-90 protocol is an effective therapy for children and adolescents with LBL in low and intermediate risk. T-LBL had the similar outcomes as B-LBL did. The patients in high-risk group had a poor survival and new protocols are needed.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; Asparaginase ; Child ; Child, Preschool ; Daunorubicin ; Disease-Free Survival ; Female ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prednisone ; Treatment Outcome ; Vincristine