Objective To analyze the etiology of diabetes ketoacidosis(DKA) in children with type 1 diabetes.Methods Totally 850 person-time of type 1 diabetes children in recent 20 years in our hospital were selected as studied subjects. Two hundred and twenty-five person-time of them were hospitalized because of DKA.Fifty-six cases (131 person-time) were due to recurrent DKA.These patients were classified into 2 groups according to onset time: group 1(diagnosed from 1982 to 1991) and group 2(diagnosed from 1992 to 2001).Results The analysis of recurrent DKA suggested that 71.8 % of them was due to infection, 20.4 % of them did not obey diabetic diet and 9.2 % of them discontinued insulin injection. The etiology of DKA showed no difference in two groups. The number of recurrent DKA in two groups was significantly different (P

Objective To evaluate the associations of human leukocyte antigen(HLA)-DQ gene with autoimmune polyglandular syndrome(APS),type 1 diabetic mellitus(T1DM) and autoimmune thyroid disease(AITD).Methods Fifteen cases of APS,29 cases of T1DM and 40 cases of AITD were selected as research subjects,while 27 healthy children were selected as controls.The DQA1 and DQB1 alleles were determined by polymerase chain reaction(PCR) and sequence-based typing method.The difference of their frequency in children and adolescents was analyzed.Results Compared with controls,APS and T1DM patients had increased frequency of subjects with DQA1*0301,0501(all P

OBJECTIVEHLA-DMA and DMB are non-classical genes whose product (DM molecules) plays an important role in antigen presentation. Our present study was designed to investigate the relationship between human leukocyte antigen-DMA, -DMB and clinical status heterogeneity of type 1 diabetes.

METHODSA total of 80 children (male 36, female 44) with type 1 diabetes were selected as research subjects. Diagnosis of type 1 diabetes was made according to WHO criteria. The range of age at onset of type 1 diabetes was 2.5 - 14 years. Ninety-one healthy adult blood donors were selected as normal controls. Polymerase chain reaction and dot blot hybridization techniques were used to classify DMA and DMB alleles. Patients with type 1 diabetes were classified into different groups according to different clinical status, including sex, age of onset, ketosis onset situation on diagnosis, remained function of islet beta cell, etc. Then distribution of DM susceptive alleles and heterodimer in different clinical groups were studied.

RESULTSThe frequencies of DMA * 0103 and DMB * 0103 alleles in patients were significantly increased (50% vs. 8%, 43% vs. 22%, respectively), these two alleles confer susceptibility to type 1 diabetes in Chinese. The frequencies of DMA * 0103/DMB * 0102, DMA * 0103/DMB * 0103 and DMA * 0103/DMB * 0101 heterodimers were also increased in the patients. The above heterodimers confer predisposition to type 1 diabetes. Both DMB * 0103 allele and DM susceptive heterodimers are related to islet beta cell function on diagnosis. The patients with DMB * 0103 allele or DM susceptive heterodimers were significantly increased in the patients with lower C-peptide level on diagnosis (56% vs. 29%; 58% vs. 34% respectively). DM heterodimes were also related to onset age and ketosis-onset-situations of the patients. The patients carrying DM susceptive heterodimers had higher probability to suffer type 1 diabetes before 10 years of age and had the predisposition to ketosis or ketoacidosis on diagnosis.

CONCLUSIONHLA- class II non-classical alleles-DMA and DMB may play an important role in pathogenesis of type 1 diabetes, and clinical status heterogeneity of type 1 diabetes may be related to genetic mechanism.

Adolescent ; Alleles ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1 ; genetics ; pathology ; Female ; Gene Frequency ; HLA-D Antigens ; genetics ; Humans ; Male ; Polymerase Chain Reaction

Objective To study the relationship between cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway and glutamine-stimulated insulin secretion.Methods In the prerequisite of the existence of glucose(0.25 mmol/L),the insulin secretion of βHC9 cells was stimulated with different concentrations of glutamine (0.0,0.5,1.0,2.0,5.0 mmol/L),then culture liquids were extracted and centrifugalized,and the insulin levels in the cell culture liquids and the cAMP levels in βHC9 cells were determined,so as to study the effects of glutamine stimulation on the insulin level in cell culture liquids and cAMP levels in βHC9 cells were assayed.Results In the prerequisite of the glucose existence,with the increasing of the concentrations of glutamine(0.0,0.5,1.0,2.0,5.0 mmol/L),the insulin levels[0.0 ng/(mL · million),19.1 ng/(mL · million),29.1 ng/(mL · million),30.1 ng/(mL · million),33.9 ng/(mL · million)] in cell culture liquids and the cAMP levels (0.0 pmol/million,40.0 pmol/million,51.5 pmol/million,52.5 pmol/million,61.3 pmoL/million) in βHC9 cells increased accordingly.Conclusion Glutamine has amplifying effect on glucose stimulated insulin secretion,such amplifying effect needs the existence of cAMP to be prerequisite.

Objective To reveal the clinical features of children with transient neonatal diabetes mellitus (TNDM) in order to provide a basis for the TNDM treatment strategy formulation.Methods Four patients diagnosed as TNDM hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University from Dec.2008 to Dec.2010 were chosen as research subjects.Their clinical data were analyzed retrospectively.Results The 4 patients diagnosed as TNDM started insulin therapy.Two cases of the 4 patients transferred from insulin to oral Sulfonylureas for 2-3 weeks after their conditions became steady.One patient was treated with Sulfonylureas successfully and the other one was partially effective with this therapy.After 2 to 3 years follow-up,3 cases remitted in 1 month after birth with no other severe complications,one case lost.Conclusions Infants with TNDM had unique clinical features.The patients develop diabetes in the first few weeks of life but go into remission in a few months.So the follow-up for those TNDM patient is very essential for clinical classification.Oral glibenclamide therapy seems highly effective and safe for some TNDM patients.

OBJECTIVETo investigate the glutamate dehydrogenase 1 (GLUD1) gene mutation of three patients diagnosed as glutamate dehydrogenase congenital hyperinsulinism (GDH-HI).

METHODSThree patients diagnosed as GDH-HI and their parents were involved in the study. PCR-DNA direct sequencing was used to analyze the exons 6,7,10,11 and 12 of the GLUD1 gene.

RESULTSIn the first case, an R269H heterozygous mutation was found in the GLUD1 gene, with autosomal dominant inheritance. In the second case, there was a de novo S445L heterozygous mutation of the GLUD1 gene. No mutation was detected in the third case.

CONCLUSIONIn Chinese, R269H, S445L heterozygous mutation of the GLUD1 gene can lead to GDH-HI. Genetic analysis is necessary in making genetic diagnosis of congenital hyperinsulinsm.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Congenital Hyperinsulinism ; enzymology ; genetics ; DNA Mutational Analysis ; Exons ; Female ; Glutamate Dehydrogenase (NADP+) ; genetics ; Humans ; Infant ; Male ; Molecular Sequence Data ; Mutation, Missense

Congenital Hyperinsulinism ; drug therapy ; Humans ; Infant ; Male ; Octreotide ; adverse effects ; therapeutic use

Diabetes Mellitus ; drug therapy ; genetics ; Female ; Follow-Up Studies ; Humans ; Infant, Newborn ; Insulin ; therapeutic use ; Male

OBJECTIVETo explore the effect of microRNA (miRNA)-mediated p65 gene knockdown on the proliferation and apoptosis of human breast cancer MDA-MB-231 cells.

METHODSp65-targeted miRNA plasmid was constructed and transfected into MDA-MB-231 cells via lipofectamine(TM)2000. The expression of p65 gene in the transfected cells at the mRNA and protein levels were detected by RT-PCR and Western blotting, respectively. The cell proliferation and apoptosis were measured by MTT assay and flow cytometry (FCM), respectively. The expressions of apoptosis-related proteins were detected by Western blotting in the transfected cells.

RESULTSCompared with the negative control group, the expressions of p65 mRNA and protein in p65miRNA-trasnfected cells were significantly down-regulated (P<0.05). MTT assay showed significantly lowered viability of MDA-MB-231 cells after the transfection (P<0.05). FCM showed an increased cell apoptosis rate in p65miRNA group compared with that in the negative control group (P<0.05). Caspase-3 and PARP were both cleaved into their active forms and the expression of these active forms was increased in p65miRNA group.

CONCLUSIONThe miRNA targeting p65 gene can inhibit the proliferation and induce apoptosis of breast cancer cells, and p65 gene might become a new target in gene therapy for human breast cancer.

Apoptosis ; genetics ; Breast Neoplasms ; genetics ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gene Knockdown Techniques ; Gene Silencing ; Humans ; MicroRNAs ; genetics ; RNA, Messenger ; genetics ; metabolism ; Transcription Factor RelA ; genetics ; metabolism ; Transfection

Objective To investigate the clinical features of these children with congenital hyperinsulinism (CHI) who had no response to diazoxide and provide a theoretical foundation for the formulation of CHI treatment strategy.Methods Eighteen patients with CHI who had no response to diazoxide hospitalized in Beijing Children's Hospital from 2008 to 2012 were chosen as research subjects.Their clinical data were analyzed retrospectively.Results There were 18 patients with persistent hypoglycemia after using diazoxide,which indicated that they had no response to diazoxide.Twelve patients of them were born as macrosomia and their onset age was less than 6 months.Half of the children(9/18 cases) even had hypoglycemia in neonatal period.All the manifestations were conformed to the clinical characteristics of ATP-sensitive potassium channel CHI.Four children who were unresponsive to diazoxide received octreotide treatment,and it was effective on them.Four patients had a near-total pancreatectomy.After a long-term followup study,their blood sugar maintained a normal level,and they did not appear serious postoperative complications.Conclusions Children with CHI who have no response to diazoxide are characterized by coming earlier and higher birth weight.Octreotide is proposed in case of non-response to diazoxide.When medical treatment is not efficient in prevention of hypoglycemia,a subtotal pancreatectomy has to be considered as a last resort.