In recent years,traditional English teaching has been greatly affected by network platform.As SMMU has been trying to perfect the Online English Writing Course,the questionnaire completed by the students taking the course shows that the course designs have proved effective in the improvement of research-based learning.

Objective To explore the Csx/Nkx 2.5 gene expression in the heart during the embryonic period and its mutation in subjects with congenital heart disease(CHD). Methods Immunohistochemistry was used to reveal the Csx/Nkx 2.5 gene expression, and PCR-SSCP-silver staining and DNA sequencing for mutation. Sixty-three embryos or fetus, 126 children with congenital heart diseases and 30 normal controls were included in the study. Results Elevated expression of Csx/Nkx 2.5 gene was found in atrium and trabecular of ventricle. After 16 weeks of gestation, the expression in atrium was stable, while slightly reduced in the trabecular. The expression in the ventricle was lower than that in the atrium in early embryonic stage followed by continuous increase which was most remarkable in 13~16 weeks and kept stable after 16 weeks. No expression of Csx/Nkx 2.5 was detected in epicardium. Three different kinds of gene polymorphisms in the third base of the 21st amino acid codon were found in all subjects:A,G,A/G. Conclusions Gene Csx/Nkx 2.5 plays an important role during the fetal heart development and its expression varies in different parts of the heart during different period in fetal development. Neither the sporadic nor the CHD cases showed any mutations in this study.

[Summary] Microcephalic or Majewski's osteodysplastic primordial dwarfism type Ⅱ ( MOPD Ⅱ) is an extremely rare genetic disease mainly caused by pericentrin ( PCNT) gene mutations. This paper reported one 13-year-old boy, who was admitted because of the slow growth for more than 13 years and deepened skin color over six months. He was diagnosed as MOPD Ⅱ associated with a combination of growth hormone deficiency, type 2 diabetes, hypertension, acanthosis nigricans, multiple café-au-lait spots. On magnetic resonance imaging of brain, no vascular malformations such as aneurysms were shown. There were novel compound heterozygous mutations of PCNT gene in the patient, with the nonsense mutations of c. 502C > T ( p. Gln168 * heterozygous variation) and c. 3103C > T (p. Arg1035* heterozygous variation). His father carried a nonsense mutation c. 3103C > T ( p. Arg1035 *heterozygous variation ) and his mother had a nonsense mutation c. 502C > T ( p. Gln168 * heterozygous variation). After treatment with metformin for three months, his blood glucose returned to normal, and acanthosis nigricans was improved. It seems critical to evaluate the abnormal condition of blood vessels regularly for MOPD Ⅱpatients with PCNT gene mutations.

[Objective] The present study aimed to determine the protective role of Melatonin (MT) against Acrylamide (AA)-induced testicular toxicity and the potential molecular mechanism.[Methods] The animals were randomly divided into three groups,the control group (n =12),the AA group (n =12) and the AA+MT group (n =12).The rats in the AA and AA + MT group were gavaged with AA at a dose of 15 mg/(kg · day) for 4 consecutive weeks.After 3 weeks of AA treatment,MT was intraperitoneally injected 30 minutes before AA treatment at 10 mg/(kg· day) for 1 week in the AA + MT rats.Subsequently,the mitochondrial membrane potential measurement,TUNEL assay,Western blot and electron microscopic techniques were applied in the present study.[Results] The results showed that AA could decrease the testis mitochondrial membrane potential (P ＜ 0.05) which could be recovered by MT (P ＜ 0.05).Moreover,MT induced down-regulation of Bax expression and up-regulation of Bcl-2 expression in the testis,compared with AA rats.The amelioration of testicular apoptosis was further confirmed by the TUNEL labeling.Western blot results suggested that the decreased ratios of Bcl-2/Bax and Bcl-xL/Bak in the AA group (both P ＜ 0.05) could be recovered by MT treatment (both P ＜ 0.05).The levels of Cyt-c,Casp-3,p53 and NF-κB in AA group were markedly elevated compared with the control (all P ＜ 0.05),and reduced in MT treatment group (all P ＜ 0.05).MT could relieve abnormal mitochondrial structures in the seminiferous tubule in the electron microscopic level.[Conclusion] MT may exert productive effect through its anti-apoptotic properties associated with mitochondria.

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 analyze the clinical feature, diagnosis and treatment of Alstrom syndrome. Method The clinical data of a case of Alstrom syndrome and the result of her ALMS1 sequencing by the two generation sequencing were retrospectively reviewed. Results The 12 year and 10 month old female suffered from dilated cardiomyopathy, obesity, optic nerve diseases, sensorineural hearing loss, high blood glucose and irregular menstruation since one month of birth. Laboratory examination showed she had high testosterone level, hyperglycemia, hyperlipidemia and fatty liver. High-throughput sequencing confirmed there was ALMS1 gene mutation which includes hybrid frameshift mutations of c.5418delC and p.Y1807Tfs*23, and heterozygous nonsense mutation of c.10549C>T and p.Q3517*, and c.5418delC was a new variation reported for the first time. Conclusion Alstrom syndrome is an autosomal recessive genetic disease, which is characterized by multiple organ dysfunction and metabolic syndrome, and can be diagnosed by gene detection.

Objective To explore the clinical manifestation and gene mutation of primary renal glucosuria (PRG). Methods The clinical data and gene detection results of a child with PRG were analyzed. Results A girl aged 2 years and 10 mouths had glucose ++++ by urine dipstick analysis and 22.4 g of the 24 h urine glucose. Her father was urine glucose positive. Genome DNA was extracted from peripheral blood of the girl and her parents, SLC5A2 gene were amplified by PCR for sequencing, including exons and splicing areas. The results showed a homozygous point mutation (c.127-16C>A) in girl, and both of her patents had the same heterozygous mutation. This mutation had been classified to pathogenic mutations by ClinVar data base. Conclusions The diagnosis of PRG is confirmed in this child and SLC5A2 gene mutation is the cause.

The clinical data of a case of diabetic ketoacidosis with FOXP3 mutation identified by genetic test were collected and summarized. The follow-up results and clinical characteristics of 18 months after hematopoietic stem cell transplantation were analyzed. The male patient was 3 years and 5 months old. At the age of 5 months, the patient was diagnosed as diabetic ketoacidosis due to mental malaise and vomiting, followed by severe diarrhea, repeated eczema, and nephrotic syndrome, which was confirmed as IPEX syndrome due to FOXP3 gene mutation by genetic test. In August 2018, hematopoietic stem cell transplantation was carried out in the Hematology Department of our hospital. During 18 months of follow-up, the patients′ autoimmune status was ameliorated, no new autoimmune diseases appeared, the blood glucose control was significantly improved, and the insulin dosage was significantly reduced.

Objective: To expand the knowledge of the clinical and molecular characteristics of the children with Bloom syndrome. Methods: Clinical data of two siblings with classic Bloom syndrome of Shanghai Children's Medical Center from January 2009 to June 2017 were obtained and analyzed. The DNA of peripheral blood was collected from two Bloom syndrome siblings and their parents during 2015. The mutations were detected with high-throughput sequencing by Illumina sequencing platform. Results: The two siblings (probands) visited our department for short stature and growth retardation, they had full-term normal delivery after normal pregnancy of their mother. Both cases presented with feeding difficulties, malnutrition, microcephaly and mental retardation, repeated infection, symmetrical short stature and special faces. At first, the proband was an 8-year-3-month old girl, her height was 99.7 cm, body mass index (BMI) 12.07 kg/m², head circumference was 45.5 cm, and birth weight was 1.6 kg. Her younger brother was 3-year-11-month old, his height was 86.6 cm, BMI was 14 kg/m², birth weight was 1.95 kg, and the head circumference reached 36 cm at 16 months. No evidence of cancer and characteristic rash was detected at 8-year follow-up. Pathogenic complex heterozygous mutations c.772_773delCT, p.Leu258Glufs*7 and c.959+ 2T>A in BLM gene were detected in both siblings, which were separately inherited from their unaffected parents. Besides , c.959 + 2T>A has not been reported previously. Conclusions Children with Bloom syndrome are characterized by short stature, microcephaly, special faces, feeding difficulties, and immunodeficiency. And butterfly erythematous rash may be absent. The c.959+2T>A mutation detected in our patients maybe a novel pathogenic mutation.

OBJECTIVETo analyze clinical manifestations and genetic mutation in a child with severe short stature and other malformations.

METHODSThe child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples of the proband and her family members. Candidate genes were captured with Agilent SureSelect and sequenced on an Illumina platform. Suspected mutation was verified by Sanger sequencing.

RESULTSThe patient, a six-year-and-10-month old girl, presented with non-symmetrical short stature, dysmorphism, abnormalities of limbs and spine, amblyopia of left eye, and cataract of right eye, in addition with frequent respiratory infection and micturition. Laboratory testing suggested 25-hydroxy vitamin D deficiency (18.9 ng/mL). Spine X-ray showed multiple malformations with centrums. Her mother also featured short stature (138 cm). Her aunt had short stature (130 cm) and limb-length discrepancy. Her little brother was 2.5 years old, and his height was 81 cm (-3.4 SD). Exome sequencing revealed a heterozygous mutation c.184C to T (p.Arg62Trp) in the proband and her mother. The same mutation was not found in her father and brother.

CONCLUSIONThe patient was diagnosed with X-linked chondrodysplasia punctata 2. Mutation of the EBP gene probably underlied the disease in this family.