OBJECTIVETo explore the expression and significance of NLR family, pyrin domain containing 3 (NLRP3), apoptosis associated speck like protein containing a CRAD (ASC) and absent in melanoma 2 (AIM2) of patients with acute leukemia.

METHODSThe petipheral blood samples of 19 patients with ALL and 41 patients with ANLL as the AL group (each 20 cases of newly diagnosed, relapsed and complete remission group) and 20 cases of non-hematologic malignancies as the control group were collected from July 2013 to July 2014 in the First Affiliated Hospital of Gannan Medical University. The expression levels of NLRP3, ASC and AIM2 in peripheral blood plasma were determined by ELISA.

RESULTSThe expression levels of NLRP3, ASC and AIM2 in plasma of control and AL complete remission groups were significantly higher than those in newly diagnosed and relapsed groups, and were with statistical significance (P < 0.05), but there were no statistical signifirance between ALL and ANLL groups (P > 0.05).

CONCLUSIONThe expression of NLRP3, ASC and AIM2 is down-regulated in the patients with acute leukemia, which maybe play a role of anti-leukemia, and provide a laboratory evidence for diagnosis and treatment of patients with acute leukemia.

Acute Disease ; CARD Signaling Adaptor Proteins ; Carrier Proteins ; blood ; genetics ; Case-Control Studies ; Cytoskeletal Proteins ; blood ; genetics ; DNA-Binding Proteins ; blood ; genetics ; Humans ; Leukemia ; blood ; genetics ; Leukemia, Myeloid, Acute ; blood ; genetics ; NLR Family, Pyrin Domain-Containing 3 Protein

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations in the VPS33B or VIPAS39 gene. The aim of this study was to investigate the clinical features and VPS33B gene mutations of an infant with ARC syndrome. A 47-day-old female infant was referred to the hospital with the complaint of jaundiced skin and sclera for 45 days and abnormal liver function for 39 days. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined diagnosis. Physical examination showed jaundice of the skin and sclera. Systemic skin was dry with desquamation in the limbs and trunk. There were no positive signs on cardiopulmonary examination. The liver was palpable 2.0 cm under the right subcostal margin. The hips and knees were flexed, and the extension was limited, with low muscular tone in the four limbs. Biochemical analysis demonstrated raised serum total bile acids, bilirubin (predominantly conjugated bilirubin) and transaminases, but the γ-glutamyl transpeptidase level was normal. Routine urine test revealed increased glucose as well as red and white blood cells. On genetic analysis, the infant was proved to be homologous for a VPS33B mutation c.1594C>T(p.R532X). She was definitely diagnosed to have ARC syndrome. Symptomatic and supportive therapy was given, but no improvement was observed, and the infant finally died at 3 months and 29 days of life.
Arthrogryposis ; blood ; genetics ; Bile Acids and Salts ; blood ; Bilirubin ; blood ; Cholestasis ; blood ; genetics ; Humans ; Mutation ; Renal Insufficiency ; blood ; genetics ; Vesicular Transport Proteins ; genetics

OBJECTIVETo investigate the relationship between the expression of murine double minute 2 (MDM2) oncogene and non-Hodgkin lymphoma (NHL) in childhood.

METHODSThirty-one cases of NHL were enrolled in this study as patient group and 8 cases of lymphadenitis as control group. (1) Immunohistochemistry ultrasensitive S-P assay was used to detect the expression of MDM2 protein in pathological tissues in all cases. Positive cells were dyed yellow or brown in nuclei. MDM2 positive cell was defined as >/= 10% of the tumor cells were positive, which was overexpression of MDM2 protein. (2) RT-PCR (reverse transcription-polymerase chain reaction) was performed to value the overexpression of MDM2 mRNA in the pathological tissues and mononuclear cells in peripheral blood. While the ratio of MDM2/beta-actin was >16% was defined as overexpression of MDM2 mRNA.

RESULTS(1) Rates of overexpression of MDM2 protein and MDM2 mRNA were 64.5% and 61.3%, respectively, which were significantly different as compared to that of control group (P < 0.05 and P < 0.01, respectively). (2) The relationship analysis among subgroups in the experiment group showed that the overexpression of MDM2 protein did not correlate with classifications of working formulation, cellular origin, sex, clinical stage and involved extranodal sites (P > 0.05), but significantly correlated with classifications of B status and the increased serum LDH level (P < 0.05). It was shown that the overexpression of MDM2 mRNA did not correlate with classifications of working formulation, cellular origin, sex and clinical stage (P > 0.05), significantly correlated with B status (P < 0.05), and was remarkably significantly correlated with the involved extranodal sites and the increased serum LDH level (P < 0.01). (3) It was demonstrated that the overexpression of MDM2 mRNA in the pathological tissues was similar to the overexpression of MDM2 protein in the pathological tissues and MDM2 mRNA in peripheral blood (P > 0.05, kappa = 0.655 and 0.571), and the overexpression of MDM2 protein in the pathological tissues was similar to that of MDM2 mRNA in peripheral blood (P > 0.05, kappa = 0.609).

CONCLUSIONS(1) The rate of MDM2 oncogene overexpression was quite high. (2) The overexpression of MDM2 protein in pathological tissues determined by using immunohistochemistry ultrasensitive S-P assay was similar to that of MDM2 mRNA in pathological tissues detected by using RT-PCR method. Both methods might be used to detect the overexpression of MDM2 oncogene in the cases of childhood NHL. (3) The overexpression of MDM2 oncogene related to the poor status and poor prognosis of patients with childhood NHL.

Biomarkers, Tumor ; analysis ; blood ; Child ; Humans ; Immunohistochemistry ; Lymphoma, Non-Hodgkin ; blood ; genetics ; metabolism ; Neoplasm Proteins ; blood ; genetics ; Oncogenes ; Proto-Oncogene Proteins c-mdm2 ; blood ; genetics ; metabolism ; RNA, Messenger

OBJECTIVETo detect cholesteryl ester transfer protein (CETP) levels, frequencies of CETP D442G and I 14A mutations and characteristics of abnormal lipids in patients with cardio-cerebro vascular diseases.

METHODSNinety-four myocardial infarction (MI) patients, 110 stroke patients and 335 healthy controls were selected. The CETP concentration was determined using ELISA. The CETP activity was measured using a substrate of (14)C-radiolabeled discoidal bilayer particles. The CETP gene mutations were detected by PCR-RFLP.

RESULTSThe CETP concentrations in the MI and stroke group, were higher than those in the controls. The gene mutation frequencies of D442G in the MI, stroke and control group were 3.5%, 3.6% and 5%, respectively, and the frequencies of I 14A were 1.05%, 0.91% and 1%, respectively. One case of D442G homozygote was detected in the healthy group. The frequency of two CETP gene mutations showed no significant difference among the patients and controls. The CETP concentration and activity in subjects with CETP mutations were one-third of those in the control group. The level of HDL-C, apo-A1 increased in the mutation subjects, while the TG level decreased.

CONCLUSIONSThe CETP level increased significantly in patients with cardio-cerebrovascular diseases. The carriers of CETP deficiency had CETP and lipid abnormalities.

Carrier Proteins ; blood ; genetics ; Cholesterol Ester Transfer Proteins ; Glycoproteins ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Mutation ; Myocardial Infarction ; blood ; genetics ; Stroke ; blood ; genetics

OBJECTIVE: To screening coagulation and anticoagulation genes and mutations in Chinese patients with venous thromboembolism suspected of inhered thrombophilia. METHODS: Patients with venous thromboembolism caused by inherited thrombophilia were collected from the second Affiliated Hospital, Zhejiang University School of Medicine during June 2015 and December 2017. Gene sequencing was conducted to screen the anticoagulant-related genes and coagulation-related genes . The thousands of human genome database, ESP6500 database, Genoma database, HGMD mutation database were used to compare the mutation sites, and the pathogenic mutation sites were predicted according to SIFT, Polyphen, MutationTaster and CADD databases. RESULTS: Among 25 patients screened, eight patients with mutations, two patients with mutations, three patients with mutations; one patient with mutation, one patient with mutation, one patient with mutation, two patient with mutations, and one patient with mutation. CONCLUSIONS The second generation gene sequencing helps to diagnose inherited thrombophilia and guide the decision of anticoagulation duration.
Blood Proteins ; genetics ; China ; Genome, Human ; genetics ; Humans ; Mutation ; Thrombophilia ; diagnosis ; genetics

The Proto-oncogene c-myc and c-myb has been shown to be crucial in the development of the hematopoietic system. The changes in the expression of c-myc are concerned the cell proliferation and differentiation, the expression products of which play an important regulatory role in cell growth, differentiation or malignant transformation. The c-myb involves in transcription and affects cell proliferation, differentiation, apoptosis. More recently, the researches on proto-oncogene c-myc, c-myb in hematopoietic regulation have gradually increased along with development of molecular biology, molecular immunology and cell biology. Scientists point out that the directive differentiation of erythroid and megakaryocytic progenitors, and platelet abnormalities all relate to the level of their expressions. The most common thrombocytopathy includes thrombocytopenia, thrombocytosis and so on. The etiology and the mechanism of these diseases are unknown. This article reviews the structure, function and the expression of c-myc and c-myb in platelet diseases and their significance.
Blood Platelet Disorders ; genetics ; metabolism ; Humans ; Proto-Oncogene Proteins c-myb ; genetics ; metabolism ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism

OBJECTIVETo explore the relationship between IL-3 gene polymorphism and the levels of serum IL-3 and eosinophil cation protein (ECP) for understanding the role of IL-3 gene polymorphism in the mechanism of childhood asthma.

METHODSThe method of restriction fragment length polymorphism (RFLP) was adopted in detecting +1923 site polymorphism of IL-13 gene in intron 3 region, ELISA was employed in detecting the level of serum IL-13, and fluorescent enzyme-linked immunoassay was used to detect the level of serum ECP.

RESULTSThe frequency distribution of TT, TC genotypes of IL-13 Intron 3+1923 site in asthmatic children was higher than that of CC genotype in normal control (P<0.05), and the levels of serum IL-13 and ECP of TT, TC genotypes were significantly higher than those of CC genotype respectively (P<0.01).

CONCLUSIONThe close relationship of IL-3 gene polymorphism with the levels of serum IL-13 and ECP suggests that IL-3 gene polymorphism may play an important role in the mechanism of childhood asthma.

Asthma ; blood ; genetics ; Blood Proteins ; Child ; Child, Preschool ; Eosinophil Granule Proteins ; Female ; Genotype ; Humans ; Infant ; Interleukin-13 ; blood ; genetics ; Male ; Polymorphism, Genetic ; Ribonucleases ; blood

OBJECTIVETo study the association of ORMDL3 single nucleotide polymorphisms (SNP) with lysophosphatidylcholine (LysoPC) and apolipoprotein B (apoB) levels.

METHODSA total of 300 children diagnosed with bronchial asthma between January 2010 and December 2012 were selected for the asthma group, and 298 children diagnosed with upper respiratory tract infection in the same period were selected for the control group. Serum LysoPC and apoB levels were measured using enzyme-linked immunosorbent assay. Genotype analysis was performed using the TaqMan probe.

RESULTSLysoPC and apoB levels were significantly higher in the asthma group than in the control group (P<0.01). Among children with various genotypes of ORMDL3 gene at locus rs12603332, the asthma group had significantly higher LysoPC and apoB levels than the control group (P<0.01). Among the children with asthma, those with CC genotype had significantly higher LysoPC and apoB levels than those with CT and TT genotypes (P<0.01).

CONCLUSIONSLysoPC and apoB may intervene in the pathological process of asthma. Pro-inflammatory gene ORMDL3 SNP rs12603332 may be associated with high LysoPC and apoB levels, which leads to the occurrence of childhood asthma.

Apolipoproteins B ; blood ; Asthma ; blood ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Lysophosphatidylcholines ; blood ; Male ; Membrane Proteins ; genetics ; Polymorphism, Single Nucleotide

Human metapneumovirus (hMPV) is associated with acute respiratory tract infections (ARTI) in all age groups. However, there is limited information of genetic analysis of hMPV circulating in Beijing. To learn the characteristics of structural protein genes of human metapneumovirus circulating in children in Beijing, sequence analysis of matrix (M), small hydrophobic (SH) and attachment (G) proteins of hMPV from 2006 to 2010 was performed. Phylogenetic analysis of nucleotide sequences of 42 full length M genes, 49 SH gene and 55 G gene revealed that the hMPVs from pediatric patients were divided into sub-genotypes A2, B1 and B. There were highly conserved identities among M gene, with 7 conserved mutations of amino acids between A and B genotypes which were fairly conserved in the same genotype A or B. The amino acid identities of SH were 60.7% to 64.4% between different genotypes, 93.3% - 100% among same sub-genotype and 84.7% - 88.7% between different sub-genotypes. Use of alternative transcription-termination codon, nucleotide deletion and insertion resulted in variable length of nucleotide and deduced amino acid of G protein. Amino acid identities within same genotype ranged from 81.5% - 100%, whereas sequence identities between two genotypes ranged from 34.0% - 38.6% at the amino acid level. A new cluster of G genes in sub-genotype B2 appeared due to the same mutations and insertion of two amino acids in G protein encoding genes amplified from specimens collected from 2008 to 2010. Prediction of antigen sites of SH and G protein indicated that the variation of antigen sites between different sub-genotypes existed.
Child ; China ; epidemiology ; Genetic Variation ; Genotype ; Humans ; Metapneumovirus ; genetics ; Paramyxoviridae Infections ; blood ; epidemiology ; virology ; Phylogeny ; Retroviridae Proteins, Oncogenic ; blood ; genetics ; Viral Envelope Proteins ; blood ; genetics ; Viral Matrix Proteins ; blood ; genetics

Citrin is a liver-type mitochondrial aspartate-glutamate carrier encoded by the SLC25A13 gene, and its deficiency causes adult-onset type II citrullinemia and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). Here, the authors investigated clinical findings in Korean infants with NICCD and performed mutation analysis on the SLC25A13 gene. Of 47 patients with neonatal cholestasis, three infants had multiple aminoacidemia (involving citrulline, methionine, and arginine) and galactosemia, and thus were diagnosed as having NICCD. Two of these three showed failure to thrive. The laboratory findings showed hypoproteinemia and hyperammonemia, and liver biopsies revealed micro-macrovesicular fatty liver and cholestasis. The three patients each harbored compound heterozygous 1,638-1,660 dup/ S225X mutation, compound heterozygous 851del4/S225X mutation, and heterozygous 1,638-1,660 dup mutation, respectively. With nutritional manipulation, liver functions were normalized and catch-up growth was achieved. NICCD should be considered in the differential diagnosis of cholestatic jaundice in Korean infants.
Amino Acids/blood ; Calcium-Binding Proteins/*deficiency ; Cholestasis, Intrahepatic/*etiology/genetics ; Citrullinemia/genetics ; Humans ; Infant ; Membrane Transport Proteins/genetics ; Mitochondrial Proteins/genetics ; Mutation ; Organic Anion Transporters/*deficiency