Neonatal diabetes mellitus(NDM)occurs within the first 6 months of life. Depending on clinical outcomes,it is classified into transient neonatal diabetes mellitus(TNDM)and permanent neonatal diabetes mellitus (PNDM). TNDM,which accounts for 50% of NDM goes into remission after treatment for an average period of 12 weeks,but relapse in puberty and early adulthood. PNDM,on the other hand,is a lifelong disease without remission. The clinical features of TNDM and PNDM overlap,and the typing is based on clinical remission on follow - up. More than 20 pathogenic genes have been identified in PNDM,of which the most common are KCNJII and ABCC8 encoding the Kir6. 2 and SUR1 subunits of KATP channel accounting for 50% . TNDM is caused by defects associated with overexpres-sion of paternally expressed genes in the imprinted region of chromosome 6q24 in 70% cases. About 26% of the defects contain mutations in KCNJII,ABCC8,INS or HNFIB. In vitro and clinical studies suggest that treatment with oral sul-fonylurea can close KATP channel and improve glycemic control and neuropsychological development. However,10% of patients with KCNJII and 15% ABCC8 mutations fail to achieve glycemic control when insulin therapy is switched to o-ral sulfonylureas. Therefore,molecular diagnosis is vital not only in accurate typing but also for better prognostication.

At present, Pediatrics textbook for international students is still in the exploring stage in China. It is necessary to make an attempt to write pediatric English textbooks by ourselves for the purpose of minimizing the gap between English original textbook and Chinese spectrum of disease, and being in accordance with teaching programs. Pediatrics English textbook should be written with excellent original English textbooks as important implications for professional resources, and adopting readable writing styles as well as multifaceted language support. Quality assurance of the textbook relies on the evaluations, and then the concrete improvement measures focusing on the significant parts of the difficulties such as author's selection, compiling style and language of textbook.

Objective To inverstigate the effect and safety of refractory intrahepatic and extrahepatic bile duct stones treated by choledochoscope holmium laser combined with electrohydraulic lithotripsy.Methods The cllnical data of 67 cases of postoperative intrahepatic and extrahepatic bile duct stones treated with combined endoscopic holmium laser and electrohydraulic lithotripsy were analysed retrospectively.Results After 1 to 7 times of biliary endoscopic holmium laser electrohydraulic lithotripsy treatment,65 patients had complete removal of all residual stones with the success rate of 97%,and without complications.Conclusions After holmium laser combined with electrohydraulic lithotripsy,the effect of choledochoscopic removal of intrahepatic and extrahepatic bile duct residual stones can be greatly improved It is a safe method for treatment of refractory intra-and extra-hepatic bile duct stones.

Objective The report was focused on polycystic ovary syndrome(PCOS) in female adolescents related to homosexual precocious puberty,and the new awareness of its influence on long-term health of homosexual precocious girls.Methods A girl with idiopathic central precocious puberty (ICPP) but diagnosed as PCOS in adolescence was reported and the data were reviewed.Results A girl was diagnosed as ICPP when she was near 8 years old with obesity,but without hyperinsulinemia,then she received the treatment of a 3.75 mg dose gonadotropin hormone analogues (GnRHa) every 28 days.Her gonads development was under control while her growth was arrested.Growth hormone(GH) injection started at 13 months.She stopped all medications when finished GH and GnRHa treatment for 12 months and 25 months.She went to see doctors again because of no menarche after discontinuing medication for nearly 2 years.She appeared obese and acne,hirsutism,athanens negricans and purple purple striae on the skin.Hyperinsulinemia and hypertestosterone were demonstrated.Pelvic B ultrasonography showed polycystic ovary,and she was diagnosed as PCOS.She was ordered to lose weight and to take metformin.And adrenocorticotropic hormone stimulating test was done,and B ultrasonography again ruled out atypical congenital adrenal hyperplasia and tumor of adrenal gland.She got her menarche 1 month later.Twelve months after the PCOS diagnosis and treatment,she had 4 menses,her insulin level decreased,glucose tolerance and her serum testosterone level turned normal.At the same time,the form of ovarian and follicular was significantly reduced.After taking mefformin for 20 months,her height and weight did not change,her menstrual was regular every 35-40 days,each time lasting about 7 days.She was followed up.We also reviewed literatures and learnt that precocious puberty might not be a benign situation and it might have an intrinsic relation to obesity,precocious puberty and PCOS.It might be the cofactors for causing PP and PCOS that accessed luteinizing hormone(LH) secretion and disorder of hypothalamus pituitary gonad(HPG) axis except obesity with hyperinsulinemia.Reported pubertas praecox in childhood developed to PCOS at 30％ with high prevalence of obesity.GnRHa suppressive therapy might relate to PCOS and had disputation for improving final height.There were fewer investigations on adolescent PCOS,and no consensus guideline on it in China.Conclusions Girls with ICPP may develop to PCOS some time later.The clinical features of the reported girl and the knowledge from literatures support the hypothesis that inner relationship between the CPP and the PCOS.The LH high secretion and disorder of HPG axis may be the causes of them; LH treatment on suppressing obesity should be cautious during treatment.The benefit and risk from GnRHa treatment should be evaluated thoroughly.Further clinical research should be conducted on adolescent PCOS.

Objective To analyze the clinical features of 35 patients with Silver-Russell syndrome (SRS) in Beijing Children's Hospital in recent 6 years,and to recognize the clinical manifestations and improve the diagnosis of the disease.Methods The diagnostic criteria of SRS were studied retrospectively,the differences among 3 different diagnostic criteria were compared.Results Thirty-five SRS patients were diagnosed by means of 3 criteria,over a period from 2006 to 2012.There were 23 males and 12 females,with age range 0.08 ～ 12.15 yr.77 ％ of cases met the three criteria,97％ met two of the three criteria.There were dwarfism in 33 cases (94.2％),genital abnormalities in 1 case (2.9％),and asymmetry of limbs in 1 case (2.9％).The clinical characteristics with the frequencies accounting for over 80％ included short stature (average height-3.61 SDS),leanness (body mass index ＜-2.11SDS),bone dysmorphism including triangular face,irregular teeth,asymmetry of limbs,clinodactyly of fifth finger,and bone age obviously lagged behind.60％ of the cases showed bone age lagging behind more than 1 year.Height lagging behind was more obviously then bone age.Conclusions The diagnosis of SRS is mainly based on Clinical manifestation,laboratory and biochemical examinations are of no avail.There is a high coincidence with the 3 different diagnostic criteria.Clinical features in more than 80％ patients with SRS are short stature,craniofacial triangular dysmorphism,irregular teeth,limbs asymmetry and fifth finger clinodactyly,and mild lagging behind of bone age.

Objective To investigate the incidence of newly-onset type 1 diabetes mellitus ( T1DM ) complicated with ketoacidosis(DKA) and its relevant factors in pediatrics. Methods Hospital records of 317 T1DM children below 18 years of age, diagnosed from 2010 to 2012 were reviewed. By using retrospectively analyzed data of inpatients with newly-diagnosed T1DM, the incidence of DKA was calculated. In this study, the influential factors of DKA included gender, age, residence, family history of diabetes mellitus, duration of symptoms, misdiagnosis or missed diagnosis, and delayed treatment. Patients were divided into two groups:group 1, aged<5 year and group 2, aged>5 year. Results Of all patients diagnosed with T1DM, 175 ( 55. 2%) presented with DKA, and mild, moderate, and severe DKA accounted for 26. 5%, 23. 9%, 49. 6%, respectively. The incidences of DKA in group 1 andgroup2were67.5% and48.0% (P=0.001),withthehighestfrequency(70.3%)inpatientsaged<2 years. The proportion of severe DKA in group 1 was significantly higher than that of group 2 (60. 0% vs 41. 3%, P=0. 048). The rates of misdiagnosis and missed diagnosis in the two groups were respectively 27. 4% and 12. 0%(P=0. 001), being 37. 8% in children<2 years. The HbA1C level of group 1 was lower than group 2 (11. 50% vs 12.54%,P=0.001). Intheacutemetabolicandhoneymoonperiod,Cpeptidelevelsofgroup1werebothlowerthan those of group 2 [(0. 36 vs 0. 55) ng/ml, P=0. 001;(0. 40 vs 0. 61) ng/ml, P=0. 02]. The DKA incidence of patients with misdiagnosis or missed diagnosis was significantly increased(83. 9% vs 49. 0%, P=0. 000). Compared with those without DKA, C peptide level of patients with DKA was lower in the acute metabolic period[(0. 56 vs 0.40)ng/ml,P<0. 01], but no difference in honeymoon period[(0. 67 vs 0. 59)ng/ml,P=0. 22]. Logistic regression showed that age, misdiagnosis or missed diagnosis were associated with the presence of DKA. The possibility of the occurrence of DKA in patients aged>5 years was half of patients aged<5 years ( OR=0. 448, P=0. 003), and the risk of DKA in patients with misdiagnosis or missed diagnosis was higher (OR=5. 640, P=0. 005). Conclusion DKA in patients with newly-onset T1DM is frequent and often severe. Multivariate analysis revealed that patients aged <5 years and those with misdiagnosis or missed diagnosis are encountered high risk of DKA.

The characteristics of thyroid nodules in children are significantly different from those in adults,and the assessment and treatment of thyroid nodules in children are also different from those in adults.The key step to evaluate thyroid nodules is to differentiate benign from malignant nodules.Early identification of risk factors,definite diagnosis based on medical history,laboratory and related instruments,reasonable treatment and avoidance of overdiagnosis and treatment are helpful to improve the prognosis of children with thyroid nodules,especially children with malignant tumors,and reduce complications.

Resistance to the thyroid hormone is a rare and hereditary thyroid disease,the signs and symptoms are diverse and the onset is hidden.It is often misdiagnosed as a common thyroid disease and given inappropriate diagnosis and treatment.Improper diagnosis and treatment would cause adverse effect on growth and development of sick children.It is necessary to improve awareness,understanding and mastery of this disease,so as to improve the level of clinical diagnosis and treatment.

A 2-month-and-20-day-old girl was hospitalized because of slow weight gain for 20 days.The patient was diagnosed as anemia,pneumonia and neutrophils firstly,and showed no improvement during anti-infective therapy,blood transfusion,and leukopenia drugs.The urinary organic acid spectrum of the patient showed increased methylmalonic acid slightly,but the normal value was found by 4 tests,which was inconsistent with the typical methylmalonic aciduria.By analyzing clinical manifestations and plasma homocysteine,folic acid and vitamin B12 levels,she was considered to have intracellular cobalamin metabolic disorder.Then,normal diet,intramuscular injection of vitamin B12,and feeding calcium,betaine,and L-carnitine were given,and the girl's symptoms were improved significantly.Latter gene analysis further showed that the patient had methylmalonic aciduria CblC type.Clinical manifestations of methylmalonic aciduria are complex and individually various,different therapies showed be applied to different causes.The value of urinary methylmalonic acid level alone cannot judge etiology;diagnosis should be based on blood amino acids and carnitine spectrum,homocysteine level and vitamin B12 level.

Objective: To analyze the effect of the use of antibiotics intervened by clinical pharmacist in diabetic ketoacidosis (DKA) patients. Method: This was a prospective clinical study with a historical control group.The group 1 was the control group which was not intervened for antibiotics use from January 2010 to November 2012. The group 2 was the intervention group treated from December 2012 to June 2016. Group 1 was divided into group 1a which included newly-onset diabetes patients and group 1b which included long standing diabetes patients. Group 2 was divided into the similar group 2a and group 2b.Clinical pharmacist supervised the implementation of terms to restrict the use of antibiotics.Changes of the rate of antibiotics use, the length of time of antibiotics use, hospital stay, the cost of antibiotics, etc.were compared. Result: In group 1a and group 2a, the rate of antibiotics use was 85%(107/126) and 31%(58/190)(χ²=25.787), the length of time of antibiotics use was 11(7-18)d and 6(4-10)d (U=1 507), the hospital stay was 23(18-27)and 20(6-24)d(U=8 177) , the cost of antibiotics was 1 615(1 000-2 970)and 1 080(504-1 932) yuan ( U=1 783), the differences had statistical significance(P<0.05). In group 1b and group 2b, the rate of antibiotics use was 97% (33/34) and 48% (23/48)(χ²=14.222), the length of time of antibiotics use was 8(6-12)d and 5(4-7)d (U=180), the hospital stay was 15(10-21)and 12(8-16)d (U=580), the cost of antibiotics was 2 200(1 356-3 100)and 1 600(705-2 200) yuan (U=223), the differences had statistical significance(P<0.05). Conclusion Clinical pharmacist intervened use of antibiotics was effective in reducing the use of antibiotics and financial burden.