Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Objective: To study the diagnostic strategy of β-thalassemia through retrospective analysis of 3 cases of β-thalassemia. Methods: Three patients were admitted to the Department of Pediatrics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2014 to June 2015. The clinical manifestations, hemoglobin electrophoresis and gene detection of these patients and their parents were analyzed, diagnostic ideas and key points were discussed when beta thalassemia gene detection did not explain clinical manifestations or hemoglobin electrophoresis. Results: Case 1, boy, 5 years old, was diagnosed as compound heterozygotes of β41-42 and IVS-Ⅱ-654 with hereditary persistence of fetal hemoglobin(HPFH) according to the clinical manifestations of mild anemia, normal size of liver and spleen, 92.8% fetal hemoglobin (HbF) and gene analysis. Case 2, girl, 3 years old, was confirmed the diagnosis of thalassemia intermedia with β41-42 heterozygote compound and ααα^anti3.7 heterozygote in accordance with the manifestations of severe anemia, hepatosplenomegaly, 8.6% HbF, 4.1% hemoglobin A₂(HbA₂) and gene analysis. Case 3, girl, 3 years old, with severe anemia, hepatosplenomegaly, 51.2% HbF and 3.7% HbA₂, was diagnosed as thalassemia major with compound heterozygotes of PolyA (T→C) and β17 by DNA sequencing. Conclusion The diagnosis of β-thalassemia should be confirmed by clinical manifestations of hemolytic anemia, hemoglobin electrophoresis, gene diagnosis and family survey.

Objective To investigate the BRAF-V600E mutation in pediatric patients with Langerhans cell histiocytosis and its clinical features. Methods A retrospective study was conducted among 27 children who were diagnosed in our hospital between August 2009 and June 2015 ,including 17 males and 10 females. BRAF-V600E was amplified from tissue samples of the 27 children with LCH by PCR and the relationship was analysed between the mutation and clinical features ,outcome. Results BRAF-V600E mutation was found in 9 cases within all 27 tested cases(33.3%). Significant difference was not found in age ,gender ,system involvement ,6-week reaction ,3-year overall survival and event-free survival between BRAF-V600E positive and negative groups. Conclusions BRAF-V600E mutation was found in Chinese pediatric LCH patients with positive rate of 33.3%, that indicates LCH might be a neoplastic disease. However ,its definite role on disease onset ,system involvement and disease progression remains unknown.

OBJECTIVETo evaluate antifungal combination strategy in children with hematologic diseases and invasive fungal disease( IFD).

METHODSA retrospective clinical study was performed based on 67 childhood patients with hematologic diseases and IFD who firstly accepted combination antifungal therapy for ≥ 7 days during January 2012 and December 2014. Of them, 11 cases received combination of echinocandin with azole, 10 cases received combination of echinocandin with amphotericin B, and 46 cases received combination of azole with amphotericin B.

RESULTSOverall response rate was 79.1%. Univariate analysis revealed that granulocyte recovery (P=0.031), status of underling disease (P=0.023) and the duration of the therapy (P=0.046) were significantly associated with efficacy. Multivariate analysis showed that the independent prognostic factor was the duration of combination antifungal therapy (OR=0.229, 95% CI 0.061- 0.863, P=0.029). The response rates of echinocandin combined with azole, echinocandin combined with amphotericin B and azole combined with amphotericin B were 81.8%, 60.0% and 82.6%, respectively (P>0.05), and 12-week survival rates were 81.8%, 80.0% and 86.5%, respectively (P>0.05). The drug- related adverse reactions occurred 59 times in 34 patients. BUN increasing, hypokalemia and abnormal liver functions were considered the main side effects.

CONCLUSIONFor IFD in children with hematologic disease, to extend the duration of treatment (≥ 14 days) could significantly improve the curative effect. Combinations of echinocandin with azole, echinocandin with amphotericin B and azole with amphotericin B can be used as a combination treatment options. Combination of Azole with amphotericin B is efficacious, safe and economic treatment option considering efficacy, survival rate, cost and dosage form.

Amphotericin B ; administration & dosage ; therapeutic use ; Antifungal Agents ; administration & dosage ; therapeutic use ; Child ; Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Hematologic Diseases ; microbiology ; Humans ; Mycoses ; drug therapy ; Retrospective Studies ; Survival Rate ; Treatment Outcome

BACKGROUND: Hemorrhagic cystitis (HC) is one of common complications in patients undergoing hematopoietic stem cell transplantation (HSCT). It is of great value for improvement in the HSCT outcome to describe the clinical characteristics of HC and risk factors. OBJECTIVE: To investigate the incidence of HC in children after HSCT, and to analyze its clinical characteristics and risk factors.DESIGN: Case analysis SETTING: Center of Hematopoietic Stem Cell Transplantation, Department of Pediatrics, Second Affiliated Hospital of Sun Yat-sen University.PARTICIPANTS: Experiments were performed at the Center of Hematopoietic Stem Cell Transplantation, Department of Pediatrics of Second Affiliated Hospital of Sun Yat-sen University from October 1998 to June 2004. Eighty-eight patients receiving umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT) were enrolled; 49 were males and 39 were females. The age ranged from 2 to 18 years with an average of 8.0 years. Guardians of child patients signed informed consents. The experimental procedures were approved by Medical Ethics Committee.METHODS: ①Conditioning regimens included combination of cyclophosphamide (CY, 120-200 mg/kg) with busulphan (BU, 14-20 mg/kg)-based chemotherapy and combination of CY with total body irradiation (TBI, 2-8 Gy) or total lymphoid irradiation (TLI, 2-8 Gy)-based radiotherapy. ②HC was defined according to the criteria proposed by references 7 and 8. The incidence, clinical characteristics, laboratory examination, treatment and outcome for HC were described. The association of various clinical factors including age, gender, human leucocyte antigen (HLA) typing, diseases for transplant, the type of stem cell, the type of transplantation, the occurrence of acute graft-versus-host disease (aGVHD) and cytomegalovirus (CMV) infection with the development of HC were examined.MAIN OUTCOME MEASURES: ①Incidence of HC, ②HC patient characteristics and laboratory examination, ③HC treatment and outcome, and ④risk factors analysis. RESULTS: All 88 patients were included in the final analysis. ①The incidence of HC: 16 patients (18.2%, 16/88) developed HC post-transplant with the severity graded as mild in 11 cases (68.7%) and severe in 5 cases (31.3%). ②HC patient characteristics and laboratory examination: All had hematuria and 8 cases (50.0%) had typical pollakisuria, urinary urgency, odynuria and gross hematuria; 10 cases (62.5%) had gross hematuria and 11 had proteinuria (+ to +++); Leucocytes were detected in 7 cases. ③Treatment and outcome: All patients recovered at a median of 13.5 days (range 2-53 days). ④Risk factors analysis: The incidence of HC was significantly higher in the group of ≥ 6 years old, presence of aGVHD and development of cytomegalo-virus (CMV) infection (P < 0.05-0.01). CONCLUSION: ①HC has its own clinical characteristics following HSCT in children but with good prognosis. ②The risk factors for HC are ≥ 6 years old, presence of aGVHD and CMV infection.

Objective To investigate the relationship between the clinical manifestations,prognosis and histopathological findings of mucormycosis.Methods The clinical data on and pathological findings from 7 cases of mucormycosis confirmed by fungal culture in the institute from 1989 to 2006 were analyzed retrospectively.Results There was 1 case of hinocerebral mucormycosis and 6 cases of cutaneous mucormycosis,among them,2 were mucormycotic necrotizing fasciitis (MNF).The condition of patients with rhinocerebral mucormycosis or MNF aggravated rapidly and all the 3 patients died from mucormycosis. Histopathological examination showed mixed infiltrates of inflammatory cells as well as necrosis and angioin vasion.On the contrary,the condition of the remaining 4 patients with cutanesus mucormycosis,who presented mainly with indurated erythematous patch,progressed slowly,and 2 patients were cured.Histologically,the lesions were characterized by granulbmatous infiltration with a few hyphae;no typical angioinva sion phenomenon was noted.There was no evidence of perineural invasion with hyphae in any of the 7 cases.ConclusionIn patients with mucormycosis,histopathological findings characterized by mixed infiltrates of inflammatory cells,numerous hyphae and typical angioinvasion phenomenon may herald a poor prognosis.

BACKGROUND: Brain-awakening nasal sprayer is composed of many herbs,such as Chuanxiong and Shichangpu, which were regarded by "Shennong Bencaojing" as having the function of "preventing stroke in the brain".OBJECTIVE: To observe the changes of free radicals and nitric oxide synthase in rat brain following focal ischemic-reperfusional injury due to brain-awakening nasal sprayer intervention and compare with that due to classical nimodipine.DESIGN: A randomized controlled study.SETTING: Department of internal medicine of a hospital affiliated to a traditional Chinese medical university.MATERIALS: Seventy adult male Wistar rats of clean grade, were randomly divided into seven groups: brain-awakening nasal sprayer of higher dosage group, moderate dosage group, lower dosage group, nimodipine intraperitoneal injection group, physical saline nasal sprayer group, menstruum nasal sprayer group, and sham operation group with 10 rats in each.METHODS: Focal brain ischemia-reperfusion model was established by blocking the left cerebral middle artery in rats of all the groups except sham operation group. Three days before model establishment and during reperfusion, rats were given different dosages of brain-awakening nasal sprayer composed of Chuanxiongqin and Shichangpu of 5.4, 2.7, 1.08 mg/(kg · d) and 1.35, 0. 54, 0.27 g/(kg· d), respectively, three times a day; which was replaced by physical saline and menstruum nasal sprayer of 0. 18 mL/ (kg · d),three times a day in physical saline nasal sprayer group and menstruum nasal sprayer group; rats in nimodipine intraperitoneal injection group received intraperitoneal injection of nimodipine by 0. 8 mg/(kg · d) twice a day. Rats in sham operation group were routinely raised. The content of prodialdehyde, superoxide dismutase and nitric oxide synthase were measured with colorimetric method.MAIN OUTCOME MEASURES: ① The changes of prodialdehyde content, superoxide dismutase and nitric oxide synthase activity in rat brain following focal ischemic-reperfusional injury in groups of different dosage of brain-awakening nasal sprayer and other groups. ② Comparison between different dosage brain-awakening nasal sprayer intervention groups and nimodipine intraperitoneal injection group.RESULTS: Eight rats died during model establishment and the other 62 rats entered the results analysis. ① Content of prodialdehyde: It was significantly lower in higher dosage group and nimodipine intraperitoneal injection group than in physical saline nasal sprayer group [ (0.92 ± 0. 32), (0. 87 ± 0. 39)vs(1.35 ±0. 34) μmol/g, P ＜ 0.05], but there was no difference between higher dosage group and nimodipine intraperitoneal injection group. ② Activity of superoxide dismutase: It was obviously higher in higher dosage group and nimodipine intraperitoneal injection group than in physical saline nasal sprayer group[ (35.64 ± 11.67), (33.88 ± 7. 15) vs(20. 70 ± 3.88) NU/mg,P ＜ 0. 05 ], but no difference could be observed between higher dosage group and nimodipine intraperitoneal injection group. ③ Activity of nitric oxide synthase and superoxide dismutase: It was found obviously higher in higher dosage group and nimodipine intraperitoneal injection group than in physical saline nasal sprayer group[ (4.64 ± 1.22), (5.00 ± 1.10) vs (3.08 ± 1.12) mkat/g, P ＜ 0.05], but no difference could be observed between higher dosage group and nimodipine intraperitoneal injection group.④ The activity of nitric oxide synthase and superoxide dismutase slightly increased while prodialdehyde slightly decreased in moderate dosage group,lower dosage group and menstruum nasal sprayer group, which did not differ significantly from physical saline nasal sprayer group.CONCLUSION: Brain-awakening nasal sprayer intervention exerts multiple effects such as preventing lipo-peroxidation following brain ischemic- reperfusional injury, in addition to suppressing prodialdehyde production, attenuating injury induced by free radicals and increasing nitric oxide synthase activity, thereby playing a similar role to nimodipine in protecting against brain ischemic-reperfusionaldamage

【Objective】To investigate the therapeutic effect of Zhuyin Capsule(ZC)for the treatment of congestive heart failure(CHF).【Methods】Fifty SD rats were randomized into five groups: A(pseudo-operation),B(model),C(treated with hydrochlorothiazide 14.29?mg?kg~(-1)?d~(-1)),D(treated with ZC 0.26?g?kg~(-1)?d~(-1))and E(treated with ZC 0.51?g?kg~(-1)?d~(-1)).Except group A,rat models of CHF were established in other groups.Thirty-five days after the modeling,groups C,D and E were treated with corresponding drugs according to the experimental design for 2 days.Cardiac function and the pathological features of heart,liver and lung were examined.【Results】The changes in group A were as follows: heart rate became fast,blood pressure decreased,left ventricular end diastolic pressure(LVEDP)increased,the maximum rate of left ventricular pressure rise(+dp/dt_(max))decreased,ventricular cavity became enlarged and the wall was thin,and there appeared myocardial fibrosis,congested liver and edema in pulmonary alveoli,indicating the success of CHF model.High-dose ZC could relieved the above changes(P0.05).【Conclusion】ZC can decrease the preload and afterload of the heart,and reduce the pathological changes of heart,liver and lung in CHF rats,which may be one of its therapeutic mechanisms.

ive] To observe the therapeutic effect of Naoxing Granule (NG) for acute ischemic stroke (AIS) and to explore its mechanism. [Methods] Single-blind controlled trial was applied. Two hundred cases of AIS were randomly allocated to Group A (n = 150, treated with NG) and Group B (n = 50, treated with nimodipine). Therapeutic effect of NG was observed and plasma free radical levels and the ratio of thromboxane A2 (TXA2) and prostaglandin 2 (PGI2) were detected. [Results] The total effective rate was 91.3%and 76.0% , and the remarkably effective rate was 62.0% and 46.0% in Group A and Group B respectively ( P

0.05) . NNS could decrease blood viscosity and hematocrit, inhibit the aggregation of erythrocytes and platelet and increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH -Px). [Conclusion] NNS has an effect on AIS, which is similar to nimodipine. Its therapeutic mechanism may be related to the relief of cerebral ischemia by improving blood rheology and cerebral blood flow and protecting brain cells from injury by eliminating free radicals.