Endocrine and metabolic features of female children with Prader-Willi syndrome: an analysis of 4 cases / 中国当代儿科杂志

This article reports the clinical features and endocrine and metabolic features of 4 children with Prader-Willi syndrome (PWS). All the patients were female and aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity, unusual facies, developmental retardation, and intellectual disability. Genetic detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region, one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of endocrine and metabolic disorders: 2 patients had short stature, among whom one had delayed appearance of secondary sex characteristics and the other one had type 2 diabetes; one patient had insulin resistance and no mammary gland development; one patient had a body height of P-Pand precocious puberty. Patients with PWS have various endocrine disorders, so long-term endocrine follow-up and management is very important.

Reversible cataract as the presenting sign of diabetes mellitus: report of two cases and literature review

Type 1 diabetes mellitus [T1DM] is the most common form of diabetes in young children. Serious optic complications, e.g. diabetic retinopathy and diabetic cataract involvement, are not usually detected in T1DM patients at the onset of the disease. Two girls aged 11 years and 9 years were hospitalized in our unit in 2008 and 2009. They presented cataracts 1 and 6 months before the diagnosis of T1DM, respectively. After blood glucose level was controlled by insulin therapy, the cataract was resolved, totally in one and partly in the other girl. Meanwhile, visual acuity of both cases recovered, closely associated with fluctuation of plasma glucose level. In this study, we describe the symptoms, probable mechanism and treatment of diabetic cataract. Early antihyperglycemic therapy and maintenance of stable blood glucose level may reverse acute diabetic cataract or prevent it from getting worse

Detection of thyroid antibodies in children with type 1 diabetes mellitus / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of positive thyroid antibodies in children with type 1 diabetes mellitus (T1DM) and its influencing factors.</p><p><b>METHODS</b>The clinical data of T1DM children who were treated in the Children's Hospital of Zhejiang University from May 2005 to April 2011 were retrospectively studied. The relationships of thyroid globulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) with cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ were evaluated, and the percentages of CD3+, CD4+ and CD8+ T-lymphocytes in peripheral blood were examined.</p><p><b>RESULTS</b>A total of 186 T1DM children with complete data of both TGAb and TPOAb were included in the study, among whom 143 with normal TGAb and TPOAb levels and 43 (23.1%) presented with positive thyroid antibody (including 21 cases with both positive TGAb and positive TPOAb). Eighteen cases (9.7%) were diagnosed as autoimmune polyglandular syndrome type 3 variant (APS3v). Significantly more patients in the positive thyroid antibody group had a family history of diabetes than in the negative thyroid antibody group (27.9% vs 14.7%; P<0.05). The average age of the positive thyroid antibody group was 10.1±3.2 years, which was significantly greater than that in the negative thyroid antibody group (8.1±4.0 years) (P<0.05). The IL-2 level (4.48 ±1.27 pg/mL vs 2.82 ±0.84 pg/mL, P<0.05) and the percentage of peripheral CD3+ T-lymphocyte[(61±11)% vs (66±11)%; P<0.05] were also different between the positive and negative thyroid antibody groups.</p><p><b>CONCLUSIONS</b>Genetic background and abnormal function of T-lymphocytes (especially higher IL-2 level) may be involved in the elevated prevalence of positive thyroid antibody in T1DM children.</p>

The prevalence of type 2 diabetes mellitus and prediabetes in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the incident and prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in obese children in the last ten years.</p><p><b>METHODS</b>The clinical data of hospitalized children with newly diagnosed diabetes mellitus (DM) or obesity between October 2000 and September 2011 were retrospectively studied.</p><p><b>RESULTS</b>A total of 503 newly onset cases were diagnosed as DM in the past ten years, of which 31 were diagnosed as T2DM. The prevalence of T2DM in the second five-year duration increased significantly compared with that in the first five-year duration (0.18‰ vs 0.05‰; P<0.01). The number of cases of type 1 diabetes mellitus (T1DM) and T2DM increased by 1.35 fold and 4.20 fold, respectively in the second five-year duration. A total of 1301 obese patients received oral glucose tolerance tests, and 29 cases were diagnosed with T2DM and 255 cases with prediabetes. Of the 255 cases of prediabetes, 133 had dyslipidemia, 138 had non-alcoholic fatty liver disease and 53 had hypertension.</p><p><b>CONCLUSIONS</b>The prevalence rates of T1DM and T2DM increased significantly in the last 5 years. The prevalence of T2DM increased more significantly than T1DM. There was a higher prevalence of prediabetes in obese children. Childhood obesity predicts a higher risk of T2DM and cardiovascular disease in the future.</p>

Genetic mutation analysis of a kindred with a patient suffering from 17 alpha-hydroxylase/17, 20-lyase deficiency / 中华儿科杂志

<p><b>OBJECTIVE</b>To detect CYP17A1 gene mutation in a patient with 17 alpha-hydroxylase/17, 20-lyase deficiency and her family members.</p><p><b>METHOD</b>Genomic DNA was extracted from the blood of the patient, her parents and twin sister. The 8 exons of CYP17A1 gene were amplified with polymerase chain reaction (PCR) and screened for mutations by sequencing.</p><p><b>RESULT</b>The analysis revealed that the patient was a compound heterozygote carrying two different inherited point mutations on CYP17A1 gene. They were nt186delC on exon 1 and nt1085G > A on exon 6. This type of mutation could induce 17OHD because of complete loss of 17 alpha-hydroxylase activities. And her parents and the twin sister were carriers on CYP17A1 gene. In addition, the mutation nt186delC was a novel point mutation and it was not discovered in normal children.</p><p><b>CONCLUSION</b>A new compound heterozygote carrying two different inherited point mutations on CYP17A1 gene was found, and her parents and twin sister were carriers. This is probably the first report in the world of a twin sisters of whom one is a patient with 17OHD and the other is a carrier of CYP17A1 gene mutation.</p>

Age-dependent alteration of insulin and ghrelin expression in pancreatic islets of intrauterine growth-retarded rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the age-dependent alteration of insulin and ghrelin expression in the pancreatic islets of intrauterine growth-retarded (IUGR) rats during development and to identify the role of ghrelin in insulin resistance induced by IUGR.</p><p><b>METHODS</b>Neonatal SD rats were divided into normal birth weight group (N group) and intrauterine growth-retarded group (I group). Plasma glucose, ghrelin and serum insulin were analyzed at day 1, 3, 7 and 10 and at week 2, 3, 4,8 and 12 after birth.Entire pancreas samples were collected for determination of ghrelin and insulin mRNA. Immunohistochemical double-staining and confocal microscopy was performed on rat pancreas.</p><p><b>RESULT</b>Plasma insulin levels of I group were lower than those of N group at day 1, 3 and 7 (P <0.05). The homeostasis model assessment-insulin resistance index (HOMA-IR) of I group was higher than that of N group at day 1, 3 and 7 (P<0.05). Plasma glucose levels, insulin, HOMA-IR and ghrelin concentrations decreased in an age-dependent manner (F = 4.12 to approximately 125.97, P <0.001) in both groups. Plasma ghrelin level was correlated with HOMA-IR in I group(r=0.553, P=0.000). Pancreatic ghrelin contents, pancreatic ghrelin mRNA expression, the percentage of insulin (+) cells and ghrelin (+) cells in both groups decreased in an age-dependent manner (F = -49.29 to approximately 427.28, P<0.001). There were differences in the above indexes between N and I group (F = -69.98 to approximately 169.22, P<0.05). Insulin secretion was negatively correlated with ghrelin contents in both groups (r=-0.895, P=0.000; r=-0.458, P=0.002). Percentage of insulin(+) cells was negatively correlated with the percentage of ghrelin (+) cells in pancreatic islets in both groups (r=-0.810,P=0.000; r=-0.714, P=0.000). The distributions of ghrelin (+) cells in pancreatic islets of I group were different from those of N group.</p><p><b>CONCLUSION</b>The effects of IUGR on weight, plasma ghrelin levels and insulin secretion of pups rats persist after birth and ghrelin may be involved in the process of insulin resistance in IUGR rats.</p>

Expression of ghrelin and calcium channels in pancreas of neonatal rats with different birth weight / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of the intrauterine environment on pancreas ghrelin and L-type calcium channels of islet like cell clusters (ICCs) in neonatal rats.</p><p><b>METHODS</b>Different birth weight neonatal rat models were established. The samples of entire pancreas or ICCs were collected at the first day after birth. Ghrelin, Cav1.2, Cav1.3 mRNAs and proteins were determined using real-time RT-PCR and immunohistochemistry respectively.</p><p><b>RESULT</b>The real-time RT-PCR revealed that ghrelin mRNA in SGA group were significantly higher than that of the AGA group (P <0.05). Cav1.2 mRNA of SGA group and LGA group was significantly lower than that of the AGA group; Cav1.3 mRNA of SGA group was significantly lower than that of the AGA group (P <0.05). The results of integral OD value of immunohistochemistry were consistent with those of real-time RT-PCR.</p><p><b>CONCLUSION</b>Intrauterine nutritional status may affect pancreatic endocrine cells differentiation and maturity, resulting in the difference of expression ghrelin and calcium channels in ICCs.</p>

Identification of a novel missense mutation of the DAX-1 gene in a Chinese pedigree with X-linked adrenal hypoplasia congenita / 中华儿科杂志

<p><b>OBJECTIVE</b>Inactivating mutations of DAX-1 give rise to the X-linked form of adrenal hypoplasia congenita (AHC). Affected individuals are at risk of early postnatal Addisonian crisis, but the variable phenotypic expression of DAX-1 insufficiency renders this diagnosis challenging. This study aimed to understand the clinical features and identify DAX-1 gene mutation of the affected individuals and their relatives in a Chinese adrenal hypoplasia congenita kindred.</p><p><b>METHODS</b>The proband was diagnosed as adrenal insufficiency shortly after birth and his elder cousin was also diagnosed as having this disease at the age of about 8 years. Clinical data were obtained from 2 affected individuals when they were hospitalized into the department of pediatrics, Ruijin Hospital in 2006; 20 peripheral blood samples were obtained from the affected individuals and their relatives; exons in DAX-1 gene were amplified, and PCR product was purified and sequenced directly for analyzing mutation.</p><p><b>RESULTS</b>A novel hemizygous mutation (T785C) was found in DAX-1 gene in both patients. Some clinical features such as the age of onset were different although these 2 patients carried the same mutation. There were 5 carriers of this mutation in the patients' maternal pedigree.</p><p><b>CONCLUSION</b>The results suggested that adrenal hypoplasia congenita in this kindred was caused by a novel mutation (T785C) in DAX-1 gene, and the same mutation can give rise to the variable phenotype.</p>

Research on secretion expression in Pichia pastoris and function of the HC-pro gene of watermelon mosaic virus / 生物工程学报

HC-pro gene of Watermelon Mosaic virus was obtained by RT-PCR was 1371bp in length. It was cloned into pPI(9K, then the eucaryotic recombinant expression plasmid pPIC9K-WHC was constructed. After being linearized with restriction endonuclease Sal I , the recombinant plasmid was transformed into Pichia pastoris GS115 by electroporation. The high copy transformants with Mut+ /His+ phenotype were selected by RT-PCR and screening on G418, MD and MM medium. Induced by methanol for 5 days, the culture supernatant was analyzed by SDS-PAGE, the results showed that a specific protein with a molecular weight of about 66 kD was expressed. Western blot analysis proved that the expression protein could specifically bind to HC-Pro polyclonal antibody. Far western blot analysis proved that the expression protein could bind to coat protein, given support to "bridge" hypothesis that HC-Pro help aphid transmission of non-persistent viruses.

Metformin hydrochloride ameliorates adiponectin levels and insulin sensitivity in adolescents with metabolic syndrome / 中华儿科杂志

<p><b>OBJECTIVES</b>Metabolic syndrome (MS) in adolescents was reported to be closely associated with cardiovascular diseases in adulthood. However, no unified treatment measure for MS in adolescents is currently available. The aim of this study was to measure the changes of serum adiponectin levels, insulin sensitivity and other biochemical markers after metformin therapy in adolescents with MS, which might provide some information for set up a unified therapeutic measure for MS in adolescents.</p><p><b>METHODS</b>In this study, 348 moderately or severely obese adolescents and 24 non-obese healthy adolescents matched in age and sex were enrolled. The obese group included 208 males and 140 females aged from 7 to 16 years (11.5 +/- 2.1 years). Oral glucose tolerance test and biochemical markers measurement were done to all these subjects. Whole body insulin sensitivity index (WBISI), homeostasis model assessment-insulin resistance (HOMA-IR) and fasting serum adiponectin were compared among 36 adolescents with MS (who had two or three abnormalities of hyperglycosemia, hypertension or dyslipidemia), 61 simple obese subjects without abnormality of biochemical markers and 24 healthy controls. Moreover, the changes of WBISI, HOMA-IR and adiponectin levels in 20 cases with MS after metformin therapy for 3 months were measured.</p><p><b>RESULTS</b>(1) HOMA-IR in control group (1.3), simple obese group (2.3) and MS group (4.9) increased by turns (F = 54.08, P < 0.001). WBISI and serum adiponectin in control group, simple obese group and MS group decreased by turns with significant difference [89.6, 22.8 and 10.7, F = 30.06; (7.1 +/- 2.6), (5.9 +/- 1.9), (2.8 +/- 0.9) mg/L, F = 64.93; P < 0.01 for all]. (2) HOMA-IR after metformin therapy decreased [5.7 (1.9-12.4) vs. 2.9 (0.9-7.4), t = 5.05, P < 0.01]; while the serum adiponectin levels increased with significant differences [(3.0 +/- 0.9) mg/L vs. (6.1 +/- 1.9) mg/L, t = 6.19, P < 0.01]. Systolic blood pressure [(132.4 +/- 7.5) mm Hg vs. (116.6 +/- 9.1) mm Hg, t = 8.36, P < 0.01], 2-hour glucose [(8.2 +/- 2.9) mmol/L vs. (5.3 +/- 1.0) mmol/L, t = 3.96, P < 0.01], triglyceride [(2.8 +/- 1.2) mmol/L vs. (1.3 +/- 0.9) mmol/L, t = 4.22, P < 0.01], total cholesterol [(4.9 +/- 0.6) mmol/L vs. (4.0 +/- 0.6) mmol/L, t = 4.72, P < 0.01], alanine aminotransferase [80.5 (29.0-286.0) U/L vs. 56.0 (23.0-163.0) U/L, t = 3.80, P < 0.01].</p><p><b>CONCLUSION</b>Insulin sensitivity in adolescents with MS was lower than that of simple obese group. Metformin can improve or ameliorate adiponectin levels, insulin sensitivity and some clinical markers.</p>

Effect of recombinant human growth hormone on glucose metabolism in children with growth hormone deficiency / 中华儿科杂志

<p><b>OBJECTIVE</b>Numerous studies in children with growth hormone deficiency (GHD) show that recombinant human growth hormone (rhGH) treatment results in significant catch-up growth, but some papers reported that the children who underwent rhGH therapy might be at increased risk of diabetes. The aim of this study was to investigate the effects of rhGH treatment on blood glucose and insulin metabolism in children with GHD and the relationship between growth hormone (GH) and glucose homeostasis.</p><p><b>METHODS</b>In this study, 44 children with GHD treated with rhGH [0.1 U/(kgxd)] and age- and sex-matched 20 healthy children were enrolled. The GHD group included 28 males and 16 females aged from 4.5 to 16.5 years (mean 10.4 +/- 2.6 years), including 18 cases of complete GHD and 26 cases of partial GHD. The sexual development stage of all subjects was in Tanner I. Oral glucose tolerance tests (OGTT) were done, and body mass index (BMI), serum insulin-like growth factor-1 (IGF-1) level and insulin resistance by homeostasis model (HOMA-IR) were measured at the time of diagnosis and every 3 months after rhGH therapy. Continuous glucose monitoring system (CGMS) was applied for two cases with hyperglycemia.</p><p><b>RESULTS</b>(1) Fasting glucose and IGF-1 levels increased since 3 months of treatment and did not decrease since then. The levels of fasting glucose and IGF-1 at every time points of rhGH therapy were higher than the levels at the time of diagnosis (F = 6.81, P < 0.01; F = 7.31, P < 0.01, respectively). HOMA-IR and fasting insulin levels were increased since 3 and 9 months of treatment (P = 0.001 and P = 0.021, respectively). They decreased after 12 months of therapy and the levels at 18 months of therapy were similar to that at diagnosis. (2) Pearson correlation analysis showed that HOMA-IR was positively correlated with BMI, IGF-1 and the duration of treatment (r = 0.251, 0.437, 0.281, P < 0.01, respectively). The curve between HOMA-IR and duration of therapy was similar with parabola and the quadratic equation obtained was as follows: HOMA-IR = 1.5048 + 0.2177 x duration of therapy (months)-0.0103 x duration of therapy (months)(2) (r(2) = 0.147, F = 14.16, P < 0.01). (3) Two cases had transitory hyperglycemia. Their fasting glucose levels were all higher than 7.1 mmol/L. The glucose levels returned to normal after 1 month and 5 days respectively. OGTT and CGMS showed that their plasma glucose levels were normal after rhGH therapy was applied again.</p><p><b>CONCLUSION</b>The children who underwent rhGH therapy may be at increased risk of insulin resistance (especially during the first year) and the therapy may even induce transitory glucose metabolic disorder in a very small proportion of patients. Circulating IGF-1 may participate in the control of insulin sensitivity and play an important role in the hormonal balance between GH and insulin. It may be necessary to monitor glucose metabolism and IGF-1 for all children who are treated with rhGH therapy.</p>

Expression of P53 and Bax in rat liver induced by microcystin LR in vivo / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To examine the expression of P53, Bcl-2 and Bax proteins in rat liver after exposed to microcystin LR.</p><p><b>METHODS</b>SD rats received microsystin LR by gastric perfusion. The expression of P53, Bax and Bcl-2 in liver was detected by Western blot.</p><p><b>RESULTS</b>The expression of P53 and Bax in each treatment group increased significantly compared with that in control group(P<0.05), with the exception of 0.1 microg/kg LR exposure group. Moreover, with exposure levels increasing the expression of P53 and Bax increased gradually; while no changes of the expression of Bcl-2 were observed.</p><p><b>CONCLUSION</b>P53 and Bax may play important roles in microcystin LR induced apoptosis, but Bcl-2 seems not be involved in this process.</p>

Effects of China-made recombinant human growth hormone on the treatment of growth hormone deficiency / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of China-made recombinant human growth hormone (r-hGH) in children with growth hormone deficiency (GHD) and to investigate the utilities of various biochemical parameters in GHD diagnosis and treatment.</p><p><b>METHODS</b>Our study comprises of 30 normal children and 71 GHD children treated with China-made r-hGH substitution therapy 0.1 IU x kg(-1) x d(-1) for 6 months. Serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), bone turnover markers (Ost, ICTP), and anti-growth hormone antibody (GHAb) were detected before and after r-hGH treatment.</p><p><b>RESULTS</b>After the first 3 and 6 months of treatment, growth velocities of GHD children were significantly increased (13.1 +/- 3.7 and 12.6 +/- 3.6 cm/year) compared with pretreatment values (2.9 +/- 0.8 cm/year, P < 0.01). GHD Children had obviously reduced serum levels of IGF-1, IGFBP-3, and bone turnover markers (Ost, ICTP) compared with normal controls (P < 0.01), and these biochemical parameters improved significantly after treatment (P < 0.01). Growth hormone antibodies were positive in 17 of 45 cases after treatment by binding capacity detection. The binding percentage of growth hormone antibody which was increased more than 30% after the treatment showed a negative correlation with growth velocity (P < 0.01).</p><p><b>CONCLUSIONS</b>(1) The growth stimulating effect and safety were confirmed in using China-made r-hGH in the treatment of GHD children for 6 months. (2) The measurements of serum IGF-1 and IGFBP-3 may serve as useful parameters in the diagnosis of GHD. (3) Serum Ost and ICTP are useful laboratory criteria for evaluating the effect of r-hGH therapy in the early stage. (4) It is necessary to monitor serum levels of GHAb during r-hGH therapy.</p>

Value of Different Indexes in Evaluating Insulin Resistance in Obese Children / 实用儿科临床杂志

Objective To explore the effect of different indexes on evaluating insulin resistance in obese children. Methods Oral glucose tolerance test (OGTT) was performed in obese children (n= 61) and age - matched normal volunteers( n= 23) Serum glucose and insulin levels were determined at 0,30,60,120,180 min after OGTT, insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). Indexes such as the ratio of area under the curve of glucose(AUCG)/area under the curve of insulin(AUCI), the ratio of fasting blood sugar(FBG) and fasting blood insulin (FINS) were meanwhile calculated. Results The level of serum FINS was significantly higher in obese children(P