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.
Child ; Family ; Humans ; Kidney Neoplasms/therapy* ; Progression-Free Survival ; Retrospective Studies

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.
Child ; Humans ; Infant ; Infant, Newborn ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neuroblastoma ; Phosphopyruvate Hydratase ; Retrospective Studies ; Survival Rate

Background: The detection of glutamic acid decarboxylase 65 (GAD65) autoantibodies is essential for the prediction and diagnosis of latent autoimmune diabetes in adults (LADA). The aim of the current study was to compare a newly developed electrochemiluminescence (ECL)-GAD65 antibody assay with the established radiobinding assay, and to explore whether the new assay could be used to define LADA more precisely. Methods: Serum samples were harvested from 141 patients with LADA, 95 with type 1 diabetes mellitus, and 99 with type 2 diabetes mellitus, and tested for GAD65 autoantibodies using both the radiobinding assay and ECL assay. A glutamic acid decarboxylase antibodies (GADA) competition assay was also performed to assess antibody affinity. Furthermore, the clinical features of these patients were compared. Results: Eighty-eight out of 141 serum samples (62.4%) from LADA patients were GAD65 antibody-positive by ECL assay. Compared with ECL-GAD65 antibody-negative patients, ECL-GAD65 antibody-positive patients were leaner (P<0.0001), had poorer β-cell function (P<0.05), and were more likely to have other diabetes-associated autoantibodies. The β-cell function of ECLGAD65 antibody-positive patients was similar to that of type 1 diabetes mellitus patients, whereas ECL-GAD65 antibody-negative patients were more similar to type 2 diabetes mellitus patients. Conclusion Patients with ECL-GAD65 antibody-negative share a similar phenotype with type 2 diabetes mellitus patients, whereas patients with ECL-GAD65 antibody-positive resemble those with type 1 diabetes mellitus. Thus, the detection of GADA using ECL may help to identify the subtype of LADA.

Sirtuin 1 (SIRT1) is a protein deacetylase, which regulates various physiological activities by deacetylating different protein substrates. An increasing number of studies have revealed critical roles of SIRT1 in different aspects of cancers including metabolism, proliferation, genomic instability, and chemotherapy resistance. Depending on the protein targets in a certain oncogenic context, SIRT1 may play a unique role in each individual blood cancer subtype. Our previous work showed that activation of SIRT1 in primitive leukemia cells of acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) promotes disease maintenance. On the other hand, an SIRT1 agonist was shown to disrupt maintenance of myelodysplastic syndrome (MDS) stem cells and holds promise as a potential therapeutic approach. Herein, we present a concise summary of the different functions of SIRT1 in hematologic malignancies.

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.
Ankyrins ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Spectrin ; genetics ; Spherocytosis, Hereditary ; genetics

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.
Adolescent ; Child ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelomonocytic, Juvenile ; genetics ; Leukocytes, Mononuclear ; Male ; Mutation ; Prognosis

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.
Facies ; Female ; GTP-Binding Protein gamma Subunits ; Humans ; Hypertriglyceridemia ; Infant ; Lipodystrophy, Congenital Generalized

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.
Animals ; Cryptococcus neoformans ; Female ; Male ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity

OBJECTIVETo study the difference in expression of TOPK/PBK in lymph nodes between children with malignant lymphoma and those with reactive lymphoid hyperplasia.

METHODSEighty 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.

RESULTSThe 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.

CONCLUSIONSThe 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.

Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Lymph Nodes ; enzymology ; Lymphoma ; enzymology ; Mitogen-Activated Protein Kinase Kinases ; analysis ; Pseudolymphoma ; enzymology

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.
Child, Preschool ; Female ; Gilbert Disease ; diagnosis ; Glucuronosyltransferase ; genetics ; Humans ; Mutation ; Sclera ; pathology ; Skin ; pathology