Clinical effect of multicenter multidisciplinary treatment in children with renal malignant tumors / 中国当代儿科杂志

OBJECTIVE@#To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors.@*METHODS@#A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children.@*RESULTS@#Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%.@*CONCLUSIONS@#Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.

Clinical features of neuroblastoma: an analysis of 44 children / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of neuroblastoma (NB) and the factors influencing survival rate.@*METHODS@#A total of 44 children with NB who were admitted from April 2016 to February 2020 were enrolled as research subjects. A retrospective analysis was performed on their medical data and follow-up data.@*RESULTS@#The common clinical symptoms of these 44 children were fever (10/44, 23%), mass (9/44, 20%), abdominal pain (8/44, 18%), cough (7/44, 16%), pale complexion (3/44, 7%), claudication (2/44, 5%), and abnormal activity (2/44, 5%). According to the INSS stage, 2 children (4%) had stage I NB, 5 children (11%) had stage II NB, 5 children (11%) had stage III NB, and 32 children (73%) had stage IV NB. The mean follow-up time was (15.3±1.5) months, with a recurrence rate of 20% and an overall survival rate of 82%. Among the 44 children, 29 (66%) achieved event-free survival and 7 (16%) had survival with tumor. The univariate analysis showed that a pathological type of NB and an increase in serum neuron-specific enolase (NSE) decreased the overall survival rate of children with NB (P<0.05).@*CONCLUSIONS@#The clinical symptoms of children with NB are not specific at the first visit. Fever, abdominal pain, and mass are common symptoms, and there is a high proportion of children in the advanced stage. The pathological type of NB and an increase in serum NSE may be associated with a reduction in the overall survival rate of children with NB.

Clinical and genetic analyses of juvenile myelomonocytic leukemia / 中国当代儿科杂志

OBJECTIVE@#To study the clinical and genetic features of juvenile myelomonocytic leukemia (JMML) and the association between genotype and prognosis. Methods The clinical data of 15 children who were diagnosed with JMML were collected. Next-generation sequencing was used to detect common gene mutations of JMML.@*RESULTS@#The male/female ratio was 6.5:1, and the age of onset was 19 months (range 2-67 months). Of the 15 children, 11 (73%) experienced disease onset before the age of 4 years, with abdominal distension and pyrexia as initial symptoms. All children had hepatosplenomegaly and superficial lymphadenectasis, with a number of peripheral blood mononuclear cells of >1.0×10/L and a percentage of juvenile cells of 1%-7% in peripheral blood smear. The percentage of bone marrow blasts + juvenile cells was <20%, and the percentage of monoblasts + promonocytes was 1%-10%. Of the 15 children, 10 (67%) had a higher level of hemoglobin F than the normal level at the corresponding age, with the highest level of 62.5%. All 15 children had the absence of Philadelphia chromosome, and one child had chromosome 7 deletion. All 15 children had a negative result of BCR/ABL fusion gene detection. PTPN11 gene mutation was found in 5 children (33%), NF1 mutation in 4 children (27%), CBL mutation in 3 children (20%), and RAS mutation in 3 children (20%). No children received regular chemotherapy, and one child underwent hematopoietic stem cell transplantation. The median follow-up time of 15 children was 18 months (range 1-48 months). Among the 15 children, 8 died (among whom 4 had PTPN11 gene mutation, 3 had NF1 mutation, and 1 had RAS mutation) and 7 survived. The children with PTPN11 mutation had the worst prognosis and the highest mortality rate, and those with CBL or NRAS mutation had a relatively good prognosis. The level of hemoglobin F was negatively correlated with survival time (r=-7.21, P=0.002).@*CONCLUSIONS@#In children with JMML, the type of gene mutation is associated with prognosis. The children with PTPN11 mutation often have a poor prognosis, and those with CBL or NRAS mutation have a relatively good prognosis.

Clinical characteristics and genetic analysis of hereditary spherocytosis caused by mutations of ANK1 and SPTB genes / 中国当代儿科杂志

This study analyzed the clinical features of 5 children with hereditary spherocytosis (HS) and the characteristics of ANK1 and SPTB gene mutations. All 5 children were confirmed with HS by peripheral blood genetic detection. Anemia, jaundice and splenomegaly were observed in all 5 children. Three children had an increase in erythrocyte osmotic fragility. All 5 children had negative results of the Coombs test, glucose 6 phosphate dehydrogenase test, sucrose hemolysis test, acidified-serum hemolysis test and thalassemia gene test. Peripheral blood smear showed an increase in spherocyte count in one child. High-throughput sequencing revealed ANK1 gene mutations in patients 1 to 3, namely c.3398(exon29)delA, c.4306C>T and c.957(exon9)_c.961(exon9)delAATCT, among which c.3398(exon29)delA had not been reported before. Patient 4 had c.318delGExon3 mutation in the SPTB gene. Patient 5 had mutations in the SPTB and SLC4A1 genes, among which c.3484delC in the SPTB gene was a spontaneous mutation; the mutation site of the SLCA4A1 gene was inherited from the father and was a non-pathogenic gene. This study suggests that anemia, jaundice and splenomegaly are major clinical manifestations of HS children. Most children with HS do not have the typical spherocytic changes. Genetic detection may help with the accurate diagnosis of HS.

Unusual facies and recurrent high triglycerides for more than one year in a girl / 中国当代儿科杂志

A girl, aged 1 year and 9 months, was found to have hypertriglyceridemia in the neonatal period, with unusual facies and signs of dark skin all over the body, disappearance of subcutaneous adipose, acanthosis nigricans of the neck, excessive and thick hair, empty cheeks, muscle hypertrophy of the extremities, hepatomegaly, and neutrophil deficiency. Whole exome sequencing of monogenic disorder revealed a homozygote mutation in the BSCL2 gene, c.974 (exon 7)_c.975 (exon 7) insG. Her parents were heterozygotes for this locus. The girl was diagnosed with congenital generalized lipodystrophy (CGL), but the association between CGL and neutrophil deficiency remained unclear. Triglyceride was maintained at a normal level after the treatment with a low-fat and high-carbohydrate diet, and there were no obvious changes in signs. CGL is a rare autosomal recessive systemic disease manifested as disappearance of systemic subcutaneous adipose, muscle hypertrophy of the extremities, and metabolic disorders in the neonatal period, such as high triglycerides, hyperinsulinemia, and hyperglycemia. About 95% of CGL cases are caused by mutations in the AGPAT2 or BSCL2 gene.

Comparision of Different Detection Methods for Blood Flow Infection with Cryptococcus Neoformans / 中国实验血液学杂志

OBJECTIVE@#To compare the sensitivity and specificity of real-time fluorescent quanttative PCR(FQ-PCR), blood culture and serum capsular antigen test for the detection of blood flow infection with cryptococcus reoformans, so as to provide the experimental evidence for use of FQ-PCR to detect the blood flow infection with cryptococcus neoformans.@*METHODS@#Sixty male Sprague-Dawley (SD) rats were randomly divided into group A (immune suppression plus infection), group B (immune normal plus infection), group C (immune suppression plus non infection) and group D (normal control). The rats in group A were injected intraperitoneally with cyclophosphamide at D1 of experiment and were injected with suspension of cryptococcus neoformans by tail vein at D4 of experiment; the rats in group B were injected intraperitoneally with saline at D1 and were injected with suspension of cryprococcus neoformans by tail vein at D4; the rats in group C were injected intraperitoneally with cyclophosphamide at D1 and were injected with saline by tail vein at D4; the rats in group D were injected intaperitoneally with saline at D1 and were injected with saline by tail vein at D4.At D 4 after successful extablishment of rat model with infection, the blood samples were collected from ocular veneous plexus at 0, 6, 12, 24, 48 and 72 hours by parity number respectively, then the plasma was extracted, and the blood samples infected at different time were detected by FQ-PCR, and at the same time, the blood culture and serum capsular antigen test were performed. The detected results obtained from above-mentioned 3 kinds of detection methods were compared.@*RESULTS@#The FQ-PCR detection of cryptococcus neoformoms showed that the positive rate detected after 12 hours in A group significantly increased (P<0.05), as compared with B, C and D groups. For the blood samples, the positive rate detected by FQ-PCR was significantly higher than that detected by the blood culture and serum capsular antigen test, moreover the detected results could be quantified, and difference was statistically significant (P<0.05).@*CONCLUSION@#The FQ-PCR system for detection of cryptococcus neoformant can detect the pathogens in blood of infected rats, and its sensitivity is superior to the blood culture and serum capsular antigen test; the FQ-PCR can detect the pathogens in blood of infected rats much more early, as compared with the blood culture and serum capsular antigen test.

Expression of TOPK/PBK in children with malignant lymphoma or reactive lymphoid hyperplasia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the difference in expression of TOPK/PBK in lymph nodes between children with malignant lymphoma and those with reactive lymphoid hyperplasia.</p><p><b>METHODS</b>Eighty children with malignant lymphoma and twenty children with reactive lymphoid hyperplasia were enrolled as subjects. Immunohistochemistry was used to determine the expression of TOPK/PBK in all the subjects. The expression of TOPK/PBK was compared between the two groups.</p><p><b>RESULTS</b>The TOPK/PBK-positivity rate was significantly higher in children with malignant lymphoma than in those with reactive lymphoid hyperplasia (P<0.05). There was no significant difference in the TOPK/PBK-positivity rate between the children with Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL). There were significant differences in the TOPK/PBK-positivity rate among children with different pathological types of NHL (P<0.05): the children with lymphoblastic lymphoma showed the highest TOPK/PBK-positivity rate and those with mature B-cell lymphoma and mature T/NK-cell lymphoma had a similar TOPK/PBK-positivity rate.</p><p><b>CONCLUSIONS</b>The expression of TOPK/PBK is up-regulated in the lymph nodes of children with malignant lymphoma. The expression level of TOPK/PBK may be related to the pathological type of NHL.</p>

Repeated yellowing of the skin and sclera for 2 years / 中国当代儿科杂志

A two-year-old girl was admitted due to repeated yellowing of the skin and sclera for 2 years and had no other specific symptoms or signs. The use of phenobarbital could relieve the symptoms of jaundice. Multiple examinations showed increased indirect bilirubin levels, and the results of aminotransferases and liver imaging were normal. There was no evidence of hemolysis. The analysis of UGT1A1 gene in her family found that this child had double homozygous mutation of c.211G>A(G71R) and c.1456T>G(Y486D), which had been reported as the pathogenic mutation for Gilbert syndrome. Her parents carried double heterozygous mutation of G71R and Y486D and had no symptom of jaundice. The child was diagnosed as having Gilbert syndrome. It is concluded that as for patients with unconjugated hyperbilirubinemia which cannot be explained by liver damage and hemolysis, their family history should be investigated in detail and gene analysis should be performed as early as possible, in order to identify congenital bilirubin metabolic disorders.

Influence of thymidylate synthase gene polymorphisms on high-dose methotrexate-related toxicities in childhood acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the influence of thymidylate synthase (TS) gene polymorphisms on high-dose methotrexate (HD-MTX)-related toxicities in childhood acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>A total of 73 children who were diagnosed with ALL between March 2011 and March 2013 were included into this study. Genomic DNAs were extracted from their peripheral blood. And then the genotypes of TS 5'-UTR were determined by direct DNA sequencing after PCR. The toxicity response of 73 patients receiving HD-MTX chemotherapy were observed and recorded, and plasma MTX concentrations at 42-48 hours after chemotherapy were measured.</p><p><b>RESULTS</b>The main HD-MTX-related toxicities of 73 patients receiving HD-MTX chemotherapy were neutropenia, decreased hemoglobin level, thrombocytopenia, liver toxicity, mucosal damage, and gastrointestinal reactions. There were no significant differences in the incidence rate of HD-MTX-related toxicities between children with different TS 5'-UTR genotypes after chemotherapy (P>0.05). TS 5'-UTR genotype was not significantly correlated with plasma MTX concentrations at 42-48 hours after chemotherapy (P>0.05).</p><p><b>CONCLUSIONS</b>TS gene polymorphisms have no influence on the incidence of HD-MTX-related toxicities in childhood ALL.</p>

Roles of platelet and its regulating factors in immune vasculitis in young rabbits / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the roles of platelet (PLT) and its regulating factors, megakaryocyte, thrombopoietin (TPO) and transforming growth factor beta1 (TGF-beta1), in immune vasculitis in young rabbits.</p><p><b>METHODS</b>An experimental model of Kawasaki disease (KD) of weanling rabbits was reproduced by bovine serum. PLT count, total number and differentiating count of megakaryocyte, and serum TPO and TGF-beta1 levels were measured 0, 4, 8, 12, 16, 20, 24 and 28 days after KD induction. Pathological analysis of coronary artery, liver, spleen, kidney and brain was performed 17 and 28 days after KD induction.</p><p><b>RESULTS</b>In the KD group, PLT count, the total number of megakaryocyte, and the middle board megakaryocyte percentage increased 12, 16, 20, 24 and 28 days; serum TPO level increased 8, 12, 16, 20, 24 and 28 days; serum TGF-beta1 level increased 16, 20, 24 and 28 days after KD induction compared with those in the normal control group (p<0.05). The pathological examinations of coronary artery, liver, spleen, kidney and brain showed severe inflammatory injuries of tiny arteries and small/medium-sized arteries 17 and 28 days after KD induction, respectively in the KD group. The aortas were showed as mild inflammatory injuries.</p><p><b>CONCLUSIONS</b>PLT, megakaryocyte, TPO and TGF-beta1 participate in the pathogenesis of KD, and they may play an important role in the injuries of immune vasculitis. This suggests that they may serve as markers for the assessment of severity in KD.</p>