Association between IL-10 Gene -592(C→A) (rs1800872) SNP and GVHD after Allogeneic Hematopoietic Stem Cell Transplantation in Children / 中国实验血液学杂志

OBJECTIVE@#To study the association between IL-10 gene-592(C→A) (rs1800872) single nucleotide polymorphism (SNP) and the graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children.@*METHODS@#Ninety-seven childhood patients and seventy-one donors in the Hematology Oncology Center of Beijing Children's Hospital from Jan 2011 to Jul 2017 were enrolled in this study. The genomic DNA was extracted from peripheral blood cells and the SNP genotype was analyzed using TaqMan SNP genotyping assay.@*RESULTS@#In malignant patients with AA genotype, the incidence of Ⅱ-Ⅳ grade acute GVHD (aGVHD) was lower than that in patients with AC and CC genotype (9.1% vs 43.5%) (P＜0.01), and the gastrointestinal aGVHD rate was also lower (9.1% vs 39.1%) (P＜0.05). There's no significant association between patients' genotype and Ⅱ-Ⅳ grade aGVHD in total patients and non-malignant patients. Also, the genotype in patients did not corelate with chronic GVHD (cGVHD) and 1 year transplantation-related mortality (TRM). In cases who received HSCT of donors with AA genotype, the liver aGVHD rate was higher than that in cases who received HSCT of donors with AC and CC genotype (23.1% vs 0.0%) (P＜0.05), but the genotype in donors did not correlate with Ⅱ-Ⅳ grade aGVHD, cGVHD and 1 year TRM.@*CONCLUSION@#AA genotype in the IL-10 gene-592 (C→A) (rs1800872) single nucleotide polymorphism in patients protects pediatric malignant patients against Ⅱ-Ⅳ grade aGVHD and gastrointestinal aGVHD after allo-HSCT. AA genotype in donors is a risk factor for liver aGVHD after allo-HSCT in non-malignant disease.

Effects of Prevention and Treatment by Integrated Traditional Chinese and Western Medicine on TCM Constitutions of Community Diabetic Patients / 中国中医药信息杂志

Objective To analyze the improved the effects of prevention and treatment by integrated tradition Chinese and Western medicine on TCM constitutions and relevant indexes of community diabetic patients; To provide a reference for the comprehensive prevention and treatment of community diabetes.Methods By using cluster sampling method, 700 patients with diabetes aged 45 to 65 in healthcare service center in Minhang District in Shanghai were chosen randomly and divided into intervention group and control group, with 350 cases in each group. The control group used information platform, and was treated with standardized management and treatment of diabetes. On the basis of the treatment of the control group, the intervention group was identified TCM constitutions once a month, developed personalized community diabetes prevention and treatment of TCM norms, and gave guidance and intervention for health preserving and disease prevention for a year. The TCM constitution improvement was observed. Diabetic symptoms grading scale and anxiety self-rating scale, depression self-rating scale were assessed, and the complications were observed.Results Before intervention: TCM constitution of yin-yang harmony (51.43％) > yin asthenia (18.29％) > qi asthenia (11.71％) > yang asthenia (9.71％) > damp-heat (1.57％). After intervention: TCM constitution of yin-yang harmony (63.71％) > yin asthenia (8.71％) > qi asthenia (6.57％), yang asthenia (6.29％) > damp-heat (1.71％). There was difference in constitutions of yin-yang harmony, yang asthenia, and damp-heat before and after and through intervention and group interaction (P<0.05). There was statistical significance in diabetes symptoms curative effect index between the two groups (P=0.021). There was statistical significance in ophthalmoscopy results before and after and through intervention and group interaction (P=0.002).Conclusion The prevention and treatment by intervention of integrated traditional Chinese and Western medicine can improve the TCM constitutions of diabetic patients in community and influence the symptoms of diabetes.

Expressions of 1,25 (OH)2D3, vitamin D receptor and 24-hydroxylase in Henoch-Sch(o)nlein purpura / 中华实用儿科临床杂志

Objective To study the expressions of 1,25 (OH) 2 D3,vitamin D receptor (VDR) and 24-hydroxylase (CYP24A1) and investigate the effects of 1,25 (OH)2D3 and its related molecules in the pathogenesis of Henoch-Sch(o)nlein purpura (HSP).Methods 1.The levels in the plasma 1,25 (OH) 2 D3 of 35 HSP patients and 14 healthy children were detected by enzyme-linked immunosorbent assay (ELISA).2.Total RNA of peripheral blood were extracted and transcribed into cDNA.Sybr green dye based real-time quantitative PCR method was used to compare the expression levels (indicated as 2-△ct value) of VDR and CYP24A1 in patients with HSP and those in the controls.Results The level of 1,25 (OH)2D3 was (13.29 ± 10.12) μg/L in plasma of HSP patients,lower than that of the healthy control group[(29.51-± 23.06) μg/L] (P ＜ 0.01).Compared with healthy control group,the level of VDR mRNA was higher but CYP24A1 mRNA was lower in HSP patients (P ＜ 0.05).Conclusion The patients with HSP have lower ability to synthesize active form of vitamin D and respond to VDR-mediated vitamin D effects,enhancing the ability to degrade this hormone.

Allogeneic stem cell transplantation for 8 patients with malignant infantile osteopetrosis in China / 中华儿科杂志

<p><b>OBJECTIVE</b>Osteopetrosis is a rare genetic disorder and the malignant infantile osteopetrosis (MIOP) is the worst subtype of this disease. Seventy percent of patients die in six years of life without proper treatment. Hematopoietic stem cell transplantation (HSCT) offers the only chance of cure for MIOP.</p><p><b>METHOD</b>Retrospective analysis was performed on 8 patients with MIOP who underwent HSCT in Beijing Children's Hospital during the period from 2006 to 2011.</p><p><b>RESULT</b>Eight cases (4 male and 4 female, mean age at HSCT 13.5 months) were diagnosed as malignant infantile osteopetrosis. Conditioning regimen included fludarabine, busulfan and cyclophosphamide. All patients received cyclosporin for prophylaxis of graft vs. host disease (GvHD). A UMD recipient underwent CD34(+) cell selection. ATG/ALG, mycophenolate mofetil (MMF) and methotrexate (MTX) used for recipients with unrelated cord donor (2) and recipients with haplo-identical donors (5). Average time for neutrophil engraftment was 15.7 day (9 - 36), platelet engraftment was 43.3 day (10 - 68). The patients were followed up from 47 days to 5 years, 1 patient died of post-transplant complications. Seven cases presented better in clinical manifestation. Acute GvHD I°-II° was observed in 6 patients, III°-IV° in 2 patients. It was controlled by anti-GvHD therapy.</p><p><b>CONCLUSION</b>Non-allogenic stem cell transplantation treatment of infantile MIOP showed high survival rate and restoration of hematopoiesis in haploid transplant patients, therefore, non-allogenic HSCT may be an option to treat MIOP in children.</p>

Tolerability of 6-mercaptopurine in children with acute lymphoblastic leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>6-Mercaptopurine (6-MP) has been the backbone of maintenance chemotherapy for acute lymphoblastic leukemia (ALL), the response to 6-MP is highly variable, adverse events leading to discontinuation or dose-reduction (children intolerant) of 6-MP occur in many children with ALL. The aim of this study was to investigate the tolerability of 6-MP and to optimize thiopurine use.</p><p><b>METHODS</b>The authors evaluated in a prospective manner the tolerance of 6-MP in ALL children from Oct. 1, 2004 to Sept. 30, 2007 who were newly diagnosed in Beijing Children's Hospital, using BCH-ALL-2003 protocols, during the maintenance therapy and followed up to Sept. 30, 2008. All children had a treatment period of at least 3 months for maintenance therapy.</p><p><b>RESULTS</b>Totally 133 children including 81 boys and 52 girls at median age of 67 months (18 - 188 months), 100% of the patients went into complete remission (CR) on day 33 of induction chemotherapy, and the median time to CR was 26 months (6 - 47 months). All the children had maintenance therapy from 3 to 25 months (mean 13.5 +/- 7.4) and 72(54%) received 6-MP standard doses continuously for total courses, the median daily dose of 6-MP was 46 mg/(m(2).d) 6-MP, their WBC was (3 - 4) x 10(9)/L, ANC (1.5 - 2) x 10(9)/L, they had no severe liver toxicity. In 4 children the dose of 6-MP was increased to 125% because WBC was higher than 6 x 10(9)/L, ANC higher than 3 x 10(9)/L. Sixty one children (46%) had poor tolerability to 6-MP, they experienced adverse events that led to discontinuation (n = 19) or dose reduction (n = 42) of 6-MP, the actual mean dose for the 42 cases was 25 - 30 mg/(m(2).d) and the time to occurrence of toxic effects was 2.5 weeks. Reasons for discontinuation or dose reduction were severe myelotoxicity occurred in 48 children, hepatotoxicity in 12, and skin rash in one.</p><p><b>CONCLUSIONS</b>In this cohort of ALL children, the difference of tolerance to oral 6-MP was obvious, 54% of the children well tolerated 6-MP during the whole course at oral standard dose, and severe granulocytopenia did not occur. However, 46% developed severe granulopenia or hepatotoxicity, the dosage had to be reduced in order to decrease the probability of severe toxicity. It is suggested that standard dose of 6-MP is not always the maximum tolerant dose in some children and inadequate dose may be the cause of therapy failure.</p>

A prospective multicenter clinical control trial on treatment of refractory nephrotic syndrome with mycophenolate mofetil in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of mycophenolate mofetil (MMF) plus prednisone on refractory nephrotic syndrome (RNS) in children.</p><p><b>METHODS</b>One hundred and forty-two children with RNS from ten clinical trial centers were divided into two groups: MMF (n=87) and control (n=55). The MMF group patients were administered with oral MMF (30-40 mg/kg daily) for at least 6 months. Afterwards the patients who responded to MMF received another 6 months MMF treatment at a dosage of 10-20 mg/kg daily. The controls were treated with pulse intravenous infusion of cyclophosphamide (CTX) (10 mg/kg daily) for 2 days every 2 weeks for 3 months. Then CTX was administered at a dosage of 500 mg/m2 once a month 4, 7 and 10 months after treatment. While the patients received MMF or CTX treatment, they were treated with oral prednisone (0.5-1 mg/kg daily) for 2 to 3 months, and then the dosage of prednisone was gradually reduced. Urinary protein, liver and renal functions, and side effects of drugs were examined at regular intervals for one year.</p><p><b>RESULTS</b>Of the 87 patients, 58 achieved complete remission, 16 achieved partial remission, 9 achieved early remission and 4 had no response to treatment. In the control group, 35 achieved complete remission, 9 achieved partial remission, 1 achieved early remission and 10 had no response to treatment. The total remission rate in the MMF group (95.4%) was significantly higher than that in the control group (81.8%) (P<0.01). After treatment 67 patients (65.4%) in the MMF group had negative proteinuria compared with 36 patients (65.4%) in the control group (P>0.05). MMF was found to be more effective in reducing proteinuria, and improving hypoproteinemia, oliguria, hyperlipemia, and edema than CTX. MMF was better tolerated with lower incidences of adverse reactions than CTX.</p><p><b>CONCLUSIONS</b>The combined therapy of MMF and prednisone is more effective and tolerable than pulse intravenous infusion of CTX for treatment of RNS in children.</p>

Therapeutic Effect of Fludarabine,Cytarabine and Granulocyte Colony-Stimulating Factor Regime on Relapsed and Refractory Acute Leukemia in Children / 实用儿科临床杂志

Objective To primarily explore the efficacy and adverse effects of the combination of fiudarabine,cytarabine and granulocyte colony-stimulating factor(G-CSF)(FLAG regime)therapy for relapsed and refractory acute leukemia in children.Methods Ten children were treated with the FLAG regime for relapsed and refractory acute myeloid leukemia (AML)and acute lymphoblastic leukemia(ALL)from Feb.2007 to Mar.2010.There were 8 male and 2 female,with mean age 8 years(ranging from 4 to 12 years).AML was diagnosed in 8 children,AML-M2 in 5 cases,AML-M4 in 3 cases.ALL was diagnosed in 2 children,both were B-ALL.Six children had refractory disease,and 4 cases were in relapse.FLAG regime included:fludarabine 25 mg?m-2?d-1,days 1-5;cytarabine 2 g?m-2?d-1,days 1-5;G-CSF 150-300 ?g?d-1,from day 0 to neutrophils ≥0.5?109 L-1.Results Complete remission was obtained in 6 children(60%),partial remission was obtained in 1 child(10%),and 3 children were considered non-response(30%).The total effective rate was 70%.For 8 children with AML,6 children had achieved complete remission(75%),2 children had non-response(25%).While in children with ALL,1 child got partial remission,and the other one had non-response.Myelosuppression and infections due to neutropenia were the most frequent adverse effects,severe nonhematologic toxicity were not observed in these children.And there were no chemotherapy-related death.Conclusions The FLAG regime is effective in treatment of children with relapsed and refractory acute leukemia,especially for the children with the relapsed and refractory AML.The adverse effects from this regime were well tolerated.FLAG regime can give children with relapsed and refractory acute leukemia another chance.

Expression of Hepatocyte Growth Factor and Transforming Growth Factor-? of Renal Tissues in Children with Nephropathy / 实用儿科临床杂志

Objective To explore the expression and mutual relationship between transforming growth factor-?(TGF-?) and hepatocyte growth factor(HGF) in children's renal tissues,as well as the effect of the 2 indexes on the renal pathological change.Methods According to the severity of renal pathological change under light microscope,61 cases were divided into 3 groups:named control group(26 cases,clinically diagnosed as thin basement membrane nephropathy),test group Ⅰ [22 cases,clinically diagnosed as less evident focal segmental glomerulosclerosi(FSGS) nephropathy] and test group Ⅱ(13 cases,clinically diagnosed as evident FSGS nephropathy).Immunity class test(SP method:streptavidinbiotin peroxidase method) was used to detect the representation of HGF and TGF-?.Semi-quantitative analysis had been carried out in all cases.Film reading of cell was viewed by Olympus microscope,brown yellow from cytoplase as the positive signal,10 high power microscope visions were randomly selected from renal glomerali area and 10 from renal interstitium area.Medical image analysis software was used to determine the masculine area of HGF or TGF-? and image intensity;then the immunity class index was defined as masculine area ? image intensity.Results 1.HGF and TGF-? existed in all renal tissues;2.Expressions of HGF and TGF-? increased obviously along with FSGS pathology alteration(Pa

Changes of Transforming Growth Factor-?_1 Levels in Children with Immunoglobulin A Glomerulonephritis and Mesangial Proliferate Glomerulonephrit is / 实用儿科临床杂志

Objective To detect the levels of transforming growth factor-?_1(TGF-?_1) in plasma,serum and urinary of children with Immunoglobulin A glomerulonephritis(IgAGN) and mesangial proliferate glomerulonephritis(MsPGN) and explore the different effects of TGF-?_1 in the two diseases.Methods The plasma,serum and urinary TGF-?_1 levels were measured in 24 children with IgAGN,and 30 children with MsPGN and 30 healthy controls by enzyme-linked immunosorbent assay(ELISA).Results The TGF-?_1 levels in plasma,serum and urinary samples of IgAGN group were increased.The TGF-?_1 levels of IgAGN were significantly higher than those of MsPGN and heathy controls(P(0.05)).Conclusion It is showed that TGF-?_1 plays a diffenent role in IgAGN and MsPGN.

Adaptive Reaction of Actin Cytoskeleton in Podocyte Structure of Glomerulus / 实用儿科临床杂志

Actin cytoskeleton in podocyte is a complicated network structure,and the stability of this structure depend on many proteins which located in slit diaphragm,the apical membrane domain and the basal membrane domain with the stimulus of mechanical stress,the actin cytoskeleton can be adaptive regulated to maintain the normal function of glomerulus,and several signal pathways involve in the process,such as RhoA/Rho kinase signal pathway and TRPC6.

Clinical and Pathological Analysis of 48 Children with Focal Segmental Glomerulosclerosis / 实用儿科临床杂志

Objective To investigate the relationship between the clinical character and pathological variants as well as response to treatment of focal segmental glomerulosclerosis(FSGS) in children.Methods The clinical feature, laboratory data and histological variants of 48 children with idiopathic FSGS proven by renal biopsy were studied retrospectively. Among them,34 were boys;14 cases were girls. The age ranged from 1.75 to 16.0 years.Results Of 48 children with FSGS,nephrotic syndrome in 32(66.7%)was the predominant clinical manifestation. The pathological classification included FSGS not otherwise specified(NOS) in 29 cases(60.42%), perihilar variant in 14 cases(29.17%), tip variant 3 cases(6.25%), cellualr variant 2 cases(4.17%)and no collapsing variant. The different pathological variants had similar rate of segmental sclerosis glomeruli; perihilar variant had a higher global sclerosis glomeruli than FSGS NOS and other variants and there was a statistical significance(P 0.05).Vascular lesions were rarely seen in all kinds of histological variants of children.Conclusions Hypertension and renal insufficiency are less frequently seen in children FSGS, isolated hematuria as unique clinic presentation is common in FSGS. All pathological variants have tubular-interstitial lesions, but vascular lesions are rarely seen. Most FSGS children with nephrotic syndrome are sensitive to steroid at initial stage, and easy to develop frequent relapse gradually, immunosuppressive agent may be helpful to elevate remission rate.

Cyclosporin A Combination with Angiotensin-Converting Enzyme Inhibitor in Treatment of Alport′s Syndrome / 实用儿科临床杂志

Objective To study the possibility of medication treatment in Alport′s syndrome(AS).Methods Two boys with AS,received cyclosporin A(CyA) in combination with angiotensin-converting enzyme inhibitor(ACEI) or only ACEI,which lasted 22 months and 20 months,respectively.Results After the treatments with the medication,there was obvious effectiveness in the 2 patients with relieved symptom and almost normal serum standard,especially the permanent and obvious recession of proteinuria.There was no side effects of medication during the treatment.Conclusion Patients with AS can be treated with CyA and ACEI,with symptomatic recession,as well as suspend the progression of pathology of kidney.