Objective To screen the mutation of KATP channel mutations in Chinese pedigrees with infantile onset type 1 diabetes mellitus (T1DM) and neonatal diabetes mellitus.Methods A cohort of 12 children of infant onset T1DM and neonatal diabetes mellitus admitted into Beijing Children's Hospital between March 2004 and June 2013 were selected.PCR amplification and direct sequencing were used to analyze the 39 exons of ABCC8 gene and one exon of KCNJ11.And the mutational sites of the parents of the probands was sequenced in order to identify the inheritance.Results Analysis revealed ABCC8 mutation in 25％ (3/12 cases) of the patients,a case of transient neonatal diabetes (TNDM),a case of permanent neonatal diabetes mellitus (PNDM) and a case of infant onset T1DM.All positive patients showed a known heterozygosis mutation in the ABCC8 gene(R1182Q,c.3545G ＞ A,D209E,c.627C ＞ G,E208K c.622G ＞ A).The residue R1182Q,which was located at a position involved in joining transmembrane domain 2 to nucleotide binding domain 2,the mutations E208K and D209E were located in the intracellular region that links the transmembrane domain with the gatekeeper module.All the three mutations were located throughout the cytoplasm part of SUR1 protein.The TNDM successfully transferred from insulin to oral sulfonylureas therapy.Conclusions There is a complex genetic pathogenesis in neonatal and infant-onset diabetes.The KATP channel activating mutations is one of the main causes of neonatal diabetes mellitus and may cause T1DM in infants in China.Oral Glibenclamide therapy seems highly effective for some patients with the KATP channel activating mutations.

Objectives To evaluate final adult height(FAH), lipid profile, sexual development, and quality of life in individuals with childhood-onset growth hormone deficiency (CO-GHD) during the transition from childhood to adulthood, to reassess the function of GH-IGF-I axis, and to explore effective managements for different types of GHD in each period. Methods Totally 80 CO-GHD patients were divided into 2 groups; 22 patients with isolated growth hormone deficiency ( IGHD) and 58 patients with multiple pituitary hormone deficiencies (MPHD); 62 male (age ≥18 years) and 18 female ( age ≥ 16 years) patients. The clinical and biochemical parameters, education and occupation, rhGH, and other hormones therapy in the past were followed up. Results rhGH replacement improved FAH of patients with GHD. The incidences of either hyperlipidemia (39.0% , 47.4%) or fatty liver disease (26.8%, 31.6%) showed no statistically significant changes between 2 groups with and without rhGH replacement. Mean value of IGF-I SDS was significantly higher in IGHD group than that in MPHD group (-1.43±0. 31,-3. 01 ±0. 66) ,and also IGFBP3(-2. 10±0. 33,-3. 17±0. 19,all P< 0.05 ). Patients with IGHD had normal sexual development, but the incidence of sexual dysfunction accounted for 79.7% in MPHD group. Conclusions rhGH improves FAH of individuals with CO-GHD. Patients with CO-GHD should be followed during the transition period; GHD patients carry a high risk of metabolic abnormalities in the adulthood; IGHD female can give birth to offsprings; patients with MPHD have gonadotrophin deficiency of varying degrees.

Objective To explore the value of amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in evaluating the efficacy of therapy with recombinant human growth hormone ( rhGH ) in patients with idiopathic short stature (ISS) and isolated growth hormone deficiency ( IGHD ).Methods Forty-eight prepubertal children( IGHD n=25,ISS n=23 ) treated for at least 1 year with rhGH were included.Serum insulin-like growth factor- Ⅰ ( IGF- Ⅰ ) and NTproCNP levels were measured before starting treatment and 6 months later.Twelve months after starting treatment,all patients were assessed and annual growth velocity ( GV ),height standard deviation score ( HTSDS),and gained HTSDS (△HTSDS) were recorded.Results In GHD group,positive relationships between GV and change of IGF- ISDS( △IGF- ISDS ),GV and change of NTproCNP concentrations(△NTproCNP) were found( r=0.407,P=0.044 ;r=0.490,P=0.013 ).GH peak value was also positively associated with IGF- ISDS and NTproCNP before therapy ( r =0.558,P =0.004; r =0.630,P =0.001 ).△IGF- ISDS and △NTproCNP were positively associated after therapy ( r =0.466,P =0.019 ).In ISS group,GV was associated with △NTproCNP ( r=0.845,P＜ 0.01 ).Conclusions NTproCNP is a novel biomarker of growth as its level increases during growth-promoting treatment.Furthermore,IGF- Ⅰ is also valuable in evaluating the efficacy of rhGH therapy in short stature patients.

Objective To investigate the clinical characteristics and molecular pathological mechanism of McCune-Albright syndrome ( MAS) in order to provide a guidance for the precision medicine of MAS. Method The clinical data and genetic findings of 41 patients with MAS were analyzed retrospectively. Results (1) MAS girls had the phenotype of peripheral precocious puberty with premature sexual development and high estradiol, low LH and FSH, and the increased volume of uterus and ovary. ( 2 ) In 41 MAS cases, there were 17 cases with GNAS1 gene mutation, and the total positive rate was 41. 5%, of which the classic triad was 66. 7%, two signs 56. 3%, and 12. 5% in only one classic sign. GNAS1 gene mutation was found in 78. 6% of patients with polyostotic fibrous dysplasia of bone, while only 55. 0% in patients with cafe au lait skin spots. Children with precocious puberty and fibrous dysplasia of bone is an important basis for clinical diagnosis of MAS, but cafe au lait skin spots does not seem to be the specifical manifestation of MAS. Conclusion Clinically MAS was lack of typical clinical manifestations, and the most important clinical weight factor for the diagnosis of MAS was peripheral precocious puberty with fibrous dysplasia of bone. GNAS1 gene screening may be helpful to improve the clinical accurate diagnosis of MAS.

Histone deacetylases are involved in many biological processes and have roles in regulating cell behaviors such as cell cycle entry, cell proliferation and apoptosis. However, the effect of histone deacetylases on the development of hair cells (HCs) has not been fully elucidated. In this study, we examined the influence of histone deacetylases on the early development of neuromasts in the lateral line of zebrafish. Hair cell development was evaluated by fluorescent immunostaining in the absence or presence of histone deacetylase inhibitors. Our results suggested that pharmacological inhibition of histone deacetylases with inhibitors, including trichostatin A, valproic acid and MS-275, reduced the numbers of both HCs and supporting cells in neuromasts. We also found that the treatment of zebrafish larvae with inhibitors caused accumulation of histone acetylation and suppressed proliferation of neuromast cells. Real-time PCR results showed that the expression of both p21 and p27 mRNA was increased following trichostatin A treatment and the increase in p53 mRNA was modest under the same conditions. However, the expression of p53 mRNA was significantly increased by treatment with a high concentration of trichostatin A. A high concentration of trichostatin A also led to increased cell death in neuromasts as detected in a TUNEL assay. Moreover, the nuclei of most of these pyknotic cells were immunohistochemically positive for cleaved caspase-3. These results suggest that histone deacetylase activity is involved in lateral line development in the zebrafish and might have a role in neuromast formation by altering cell proliferation through the expression of cell cycle regulatory proteins.
Animals ; Apoptosis ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor Proteins/genetics/metabolism ; Histone Deacetylase Inhibitors/*pharmacology ; Histone Deacetylases/*metabolism ; Histones/metabolism ; Larva/growth & development/metabolism ; Lateral Line System/cytology/*growth & development/metabolism ; Mechanoreceptors/drug effects/*metabolism/physiology ; RNA, Messenger/genetics/metabolism ; Zebrafish ; Zebrafish Proteins/*metabolism

Objective To explore the etiology and clinical characteristics of short stature. Method Clinical data of 2075 children with short stature treated from May 1995 to July 2017 were retrospectively analyzed. The etiology and morbidity of pathological short stature and normal variant short stature were analyzed. The clinical characteristics of growth hormone deficiency (GHD) , idiopathic short stature (ISS) , constitutional delay in growth (CDG) and familial short stature (FSS) were analyzed. The etiological differences between severe short stature [height standard deviation score (SDS) ≤-3] and general short stature (height SDS＞-3) were analyzed. Results Among 2075 children diagnosed with short stature, 1719 (82.84％) were pathological short stature, among which GHD (38.60％) and ISS (22.02％) were more common. Normal variant short stature was found in 356 children (17.16％) , with FSS and CDG accounting for 10.70％ and 6.46％ respectively. There were statistically significant differences in the sex ratio, age at initial diagnosis, height SDS, body mass index (BMI) , bone age and bone age delay among children with four common childhood short stature (GHD, ISS, CDG and FSS) (all P＜0.01) . Boys were more than girls in four kinds of childhood short stature. The height SDS was the lowest in GHD group and the highest in CDG group; BMI was highest in GHD group, but lower in CDG and ISS group. Bone age delay was highest in GHD group and lowest in CDG group. In severe short stature group, the rates of complete GHD, multiple pituitary hormone deficiency, small for gestational age infant, Turner syndrome, hypothyroidism and Russell-Silver syndrome were higher than those in general short stature group, but the rates of partial GHD, ISS, FSS and CDG was lower than those in general short stature group. Conclusion The etiology of short stature is complex. Analysis of the etiology and clinical features is helpful for clinical diagnosis and treatment.

Objective: To investigate the long-term effects of GnRHa treatment on final height gain, gonadal function, and body mass index(BMI) in children with central precocious puberty(CPP) or early and fast puberty(EFP), and to explore the influencing factors of height gain and early predictors. Methods: Fifty patients with CPP and 44 patients with EFP who were treated with GnRHa for more than 2 years were enrolled(80 females and 14 males). Body height, bone age, BMI, gonads hormone, uterus and ovarian volumes(female), testicular volume(male), and other parameters before and after treatment were measured. Results: (1)For girls: GnRHa plus GH treatment gained more final height compared with GnRHa treatment [(10.69±5.73) cm vs (7.42±5.76) cm, P<0.05]. Height lost >5cm at the initial treatment benefited much more for the final height compared with height lost<5cm [(10.65±3.32) cm vs (6.51±3.40) cm, P<0.01]. The proportion of overweight/obesity decreased when reaching the final height compared with the initial treatment and stopping the treatment. Serum LH level, uterine and ovarian volume were significantly decreased after stopping treatment compared with before treatment, and increased half a year to 1 year after stopping treatment.100% of girls had menarche and 95% reached the regular cycle 3 years after stopping treatment.(2)For boys: GnRHa plus GH treatment and GnRHa treatment gained height by(8.78±5.2) and(7.99±4.82) cm, respectively. Serum LH level and testicular volume were significantly decreased after stopping treatment as compared with those before treatment, and increased for half a year to 1 year after stopping treatment. Conclusion GnRHa treatment can significantly improve the final height for girls with CPP and EFP. The patients with more height lost could gain more height, which can be used as a predictor of height gain.

Objective: Based on the application and funding of Otorhinolaryngology Head and Neck Surgery (H13) funded by the Nature Science Foundation of China (NSFC), we analyzed the basic research status of the field of Otorhinolaryngology Head and Neck Surgery, and provided the references for developing the discipline development plan, optimizing the discipline strategic layout and promoting the discipline progress. Method: The data of both applied and funded grants of Otorhinolaryngology Head and Neck Surgery in NSFC from 2009 to 2019 were collected for further analysis. Results: From 2009 to 2019, H13 received 5 103 applications, accounting for 1.00% of the total number of applications in the department of health science, and 922 applications were funded (mainly from the General Projects and the Youth Science Fund Projects), with a funding rate of 18.07% and a funding amount of 445.509 million yuan, accounting for 1.02% of the total funding amount of the department of health science. Among the seven sub-categories of H13, H1304 (Hearing abnormal and balance disorders) received 1 845 applications, and 352 were funded. H1301 (Disease of smell, nose and anterior skull base) received 1 217 applications, and 248 were founded, H1303 (Ear and lateral skull base disease) and H1305 (Otorhinolaryngology and developmental related diseases) received 498 and 488 applications,and 83 and 112 were founded respectively. The National Science Fund for Distinguished Young Scholars received 33 applications, and 5 were founded, with a funding rate of 15.15%. Clinicians accounted for 81% of the General Projects principals, and researchers and technicians accounted for 19%. Clinicians accounted for 72% of the Youth Science Fund Projects principals, and researchers and technicians accounted for 24%. Conclusion The basic research of Otorhinolaryngology Head and Neck Surgery in China has some shortcomings, such as small volume, uneven development of various disciplines, less leading academic leaders, less training of young leading talents, less major projects, more clinicians instead of researchers engaged in the basic scientific research.

As a type of prebiotics and dietary fiber, inulin performs plenty of significant physiological functions and is applied in food and pharmaceutical fields. Inulosucrase from microorganisms can use sucrose as the substrate to synthesize inulin possessing higher molecular weight than that from plants. In this work, a hypothetical gene coding inulosucrase was selected from the GenBank database. The catalytic domain was remained by N- and C- truncation strategies, constructing the recombinant plasmid. The recombinant plasmid was expressed in E. coli expression system, and after purifying the crude enzyme by Ni²⁺ affinity chromatography, a recombinant enzyme with a molecular weight of approximately 65 kDa was obtained. The optimal pH and temperature of the recombinant enzyme were 5.5 and 45 °C, respectively, when sucrose was used as the sole substrate. The activity of this enzyme was inhibited by various metal ions at different degrees. After purifying the produced polysaccharide, nuclear magnetic resonance analysis was used to determine that the polysaccharide was inulin connected by β-(2,1) linkages. Finally, the conditions for the production of inulin were optimized. The results showed that the inulin production reached the maximum, approximately 287 g/L after 7 h, when sucrose concentration and enzyme dosage were 700 g/L and 4 U/mL, respectively. The conversion rate from sucrose to inulin was approximately 41%.
Escherichia coli/genetics* ; Hexosyltransferases/genetics* ; Inulin ; Oligosaccharides ; Sucrose

Objective: To summarize the clinical characteristics of 6 children with Hutchinson-Gilford progeria syndrome, and to analyze the pathogenic genes carried by some patients. Methods: The clinical data of 6 patients were summarized. The pathogenic genes of 4 families were analyzed. Genomic DNA was extracted from 3ml of the subject′s blood with EDTA anticoagulation. The first-generation sequencing technology was used to analyze the sequence of Lamin A/C(LMNA) gene and to identify the pathogenic mutation sites by comparing with normal sequencing results. Results: All the children had typical clinical manifestations of the disease which has been previously reported in the literature, such as severe growth retardation, special skin manifestations, and distinctive craniofacial manifestations.Gene sequencing results revealed that 2 patients carried classical heterozygous mutation of LMNA c. 1824C>T(p.G608G). The other two patients carried atypical mutations of LMNA IVS8-4 C>A and c. 1968+ 2T>C, among which the mutation of IVS8-4 C>A has not been reported. Conclusions In Chinese children, both classical and non-classical mutations in LMNA gene lead to the occurrence of premature aging. It is easy to make a diagnosis based on clinical manifestations. Finding of the pathogenic gene may further confirm the diagnosis.