[Management of transition growth hormone deficiency]. / è¿‡æ¸¡æœŸç”Ÿé•¿æ¿€ç´ ç¼ºä¹ç—‡çš„ç®¡ç†.

With an increasing understanding of growth hormone deficiency, there has been a growing emphasis on the management of transition growth hormone deficiency (TGHD) in clinical practice. The inadequate diagnosis and treatment of TGHD have been a major clinical concern, leading to the development of relevant guidelines and consensus internationally. This article summarizes the evaluation, diagnosis, treatment, and clinical challenges of TGHD based on these guidelines, consensus, and existing clinical studies, aiming to optimize and further improve the clinical diagnosis, treatment, and management of TGHD.

Short stature and melanocytic nevi in a girl with ARID1B-related Coffin-Siris syndrome: a case report.

BACKGROUND: Coffin-Siris syndrome (CSS) is a rare autosomal dominant disorder characterized by intellectual disability, developmental delay, and characteristic facial features. Few patients with cutaneous phenotype in this rare syndrome have been reported. CASE PRESENTATION: Herein, we describe a 12-year-old Chinese girl diagnosed with CSS, who was referred to our hospital because of intellectual disability and short stature. Prominent characteristics of the cutaneous system were observed: (1) A congenital giant nevus from the left frontal and temporal regions to the entire left scalp; and (2) multiple melanocytic nevi on the face and trunk. Whole exome sequencing revealed a novel heterozygous variant in the ARID1B gene. Recombinant human growth hormone (rhGH) was given for short stature, and resulted in significantly improved height. No enlargement or malignant transformation of nevi occurred within 4 years of follow-up. CONCLUSION: The symptoms in cutaneous system is noteworthy,which may be a neglected phenotype in CSS.The therapeutic response of growth hormone is effective in this patient and no tumor related signs were found.

[Clinical features and FGFR3 mutations of children with achondroplasia]. / è½¯éª¨å‘è‚²ä¸å ¨æ‚£å„¿çš„ä¸´åºŠç‰¹å¾åŠFGFR3åŸºå› å˜å¼‚åˆ†æž.

OBJECTIVES: To study the clinical features and fibroblast growth factor receptor 3 (FGFR3) gene mutations of children with achondroplasia (ACH) through an analysis of 17 cases. METHODS: A retrospective analysis was performed on the clinical data and FGFR3 gene detection results of 17 children with ACH who were diagnosed from January 2009 to October 2021. RESULTS: Of the 17 children with ACH, common clinical manifestations included disproportionate short stature (100%, 17/17), macrocephaly (100%, 17/17), trident hand (82%, 14/17), and genu varum (88%, 15/17). The common imaging findings were rhizomelic shortening of the long bones (100%, 17/17) and narrowing of the lumbar intervertebral space (88%, 15/17). Major complications included skeletal dysplasia (100%, 17/17), middle ear dysfunction (82%, 14/17), motor/language developmental delay (88%, 15/17), chronic pain (59%, 10/17), sleep apnea (53%, 9/17), obesity (41%, 7/17), foramen magnum stenosis (35%, 6/17), and hydrocephalus (24%, 4/17). All 17 children (100%) had FGFR3 mutations, among whom 13 had c.1138G>A hotspot mutations of the FGFR3 gene, 2 had c.1138G>C mutations of the FGFR3 gene, and 2 had unreported mutations, with c.1252C>T mutations of the FGFR3 gene in one child and c.445+2_445+5delTAGG mutations of the FGFR3 gene in the other child. CONCLUSIONS: This study identifies the unreported mutation sites of the FGFR3 gene, which extends the gene mutation spectrum of ACH. ACH is a progressive disease requiring lifelong management through multidisciplinary collaboration.

[A predictive analysis of the association between clinical phenotypes and genotypes in children with Becker muscular dystrophy/Duchenne muscular dystrophy].

OBJECTIVE: To study the association between clinical phenotypes and genotypes in children with Becker muscular dystrophy (BMD)/Duchenne muscular dystrophy (DMD) so as to provide a theoretical basis for disease management, gene therapy, and prenatal diagnosis. METHODS: A retrospective analysis was performed for the clinical data and gene detection results of 52 children with BMD/DMD. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the DMD gene. The children with negative results of MLPA were further screened by exon chip capture combined with next-generation sequencing (NGS). The mothers of 20 probands were validated by sequencing. RESULTS: The pathogenic genes for BMD/DMD were detected in 50 children by MLPA and NGS, with a detection rate of 96%. Among the 52 children, 36 (69%) had gene deletion, 7 (13%) had duplication, and 7 (13%) had micromutation. Among the 43 children with deletion/duplication, 32 had DMD and 11 had BMD; 37 children (86%) met the reading frame rule, among whom 27 (96%) had DMD and 10 (67%) had BMD. All 7 children with micromutation had DMD. CONCLUSIONS: The reading frame rule has an extremely high predictive value for DMD but a limited predictive value for BMD.

[Improvement in cardiac morphology and function in young rats with dilated cardiomyopathy by recombinant human growth hormone].

OBJECTIVE: To investigate the effects of recombinant human growth hormone (rhGH) on the morphology and function of the left cardiac ventricle in young rats with dilated cardiomyopathy (DCM), and to evaluate the efficacy and safety of rhGH in the treatment of DCM. METHODS: Sixty male Sprague-Dawley rats were randomly and equally assigned to control group, DCM group, and rhGH group. Furazolidone (0.25 mg/g) was given by gavage for 12 weeks to prepare the DCM model. Rats in the rhGH group received an intraperitoneal injection of rhGH (0.15 U/kg) once per day for 12 weeks, while rats in the DCM group received an equal volume of normal saline instead. Rats in the control group did not receive any treatment. Cardiac indices, serum biochemical parameters, hemodynamic indices, cardiac histopathological changes, and levels of myocardial collagen fibrils in each group were determined using Doppler echocardiography, enzyme-linked immunosorbent assay, multi-channel physiological recorder, light and electron microscopy, and picrosirius red staining plus polarization microscopy, respectively. RESULTS: Compared with the control group, rats in the DCM group had significantly increased cardiac chamber size, significantly reduced ventricular wall thickness, and significantly decreased fractional shortening (FS) and ejection fraction (EF) (P<0.05). Rats in the rhGH group had significantly improved cardiac chamber size, ventricular wall thickness, FS, and EF compared with the DCM group (P<0.05). Those indices in the rhGH group were similar to those in the control group (P>0.05). There were significant differences in serum biochemical parameters and hemodynamic indices between the DCM and control groups (P<0.05). Compared with the DCM group, the rhGH group had significantly improved serum biochemical parameters and hemodynamic indices (P<0.05). Those indices in the rhGH group were similar to those in the control group (P>0.05), except for the levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. The DCM group had a significantly higher collagen type I/collagen type III (Col I/Col III) ratio in the myocardium than the control group (P<0.05), and there was no significant difference in the Col I/Col III ratio between the control and rhGH groups (P>0.05). CONCLUSIONS: rhGH plays a certain role in improvement in the morphology and function of the left cardiac ventricle in young rats with DCM.

[Clinical and pathological features in children with progressive muscular dystrophy].

OBJECTIVE: To investigate the clinical and pathological features of progressive muscular dystrophy (PMD) in children and to provide help for the early and accurate diagnosis of PMD. METHODS: Retrospective analysis was performed on the clinical data of 99 hospitalized children with PMD, including clinical manifestations, age of onset, family history, creatase, electromyogram (EMG) and pathological changes of muscles. RESULTS: Of the 99 children with PMD, the age of onset was 0.5-14.5 (4.7 ± 3.1) years. Eleven cases (11%) had a family history of PMD. Twenty-six (26%) were misdiagnosed as other diseases. All patients presented with muscle weakness when seeing the doctor, and 66 (67%) of them had muscle atrophy and/or hypertrophy. All patients had elevated creatine kinase (CK) levels. The 2-7-year-old group (n=51) had a mean CK level of 9965 ± 8876 U/L, and the 7-15-year-old group (n=48) had a mean CK level of 5110 ± 4498 U/L, with a significant difference between the two groups (P<0.01). The EMG examination performed on 66 patients showed that 54 cases (82%) had myogenic damage and 10 cases (15%) had neurogenic damage. Light microscopy revealed coexistence of atrophy and hypertrophy of muscle fibers, hyaline degeneration and granular degeneration. Electron microscopy showed that muscle fibers were different in thickness, some atrophic or hypertrophic; muscle cell nuclei moved inwardly, myofilaments dissolved and disappeared mildly under the sarcolemma, there were scattered melting lesions within muscle fibers, the numbers of glycogen granules and mitochondria increased, mild hyperplasia and expansion of sarcoplasmic reticulum were seen, and a small number of muscle fibers had necrosis. CONCLUSIONS: Weakness of both lower extremities remains the main reason for PMD patients seeing the doctor. CK is the main laboratory indicator for diagnosis of PMD. PMD is mainly manifested as myogenic damage in the early stage and may be accompanied by neurogenic damage in the late stage, according to the EMG examination. With a high misdiagnosis rate, PMD may be misdiagnosed as many other diseases. Pathological examination under light microscope and electron microscope is the main means for confirming a PMD diagnosis.

[Clinical significance of skin prick test for inhalant allergens in 3085 children with allergic diseases].

OBJECTIVE: To investigate the main inhalant allergens and their distribution patterns in children with allergic diseases from Xi'an and the surrounding area and to provide evidence for the prevention and treatment of allergic diseases in children. METHODS: Skin prick test was performed using liquid with 13 standardized allergens (ALK-ABELL, Denmark) on 3085 children from Xi'an and the surrounding area who were treated for allergic diseases between July 2006 and July 2011, to detect inhalant allergens. RESULTS: Of the 3085 patients, 1368 (44.34%) had positive SPT results, with the most prevalent inhalant allergen being Dermatophagoides pteronyssinus (804 cases, 26.06%), followed by Dermatophagoides farinae (793 cases, 25.71%), Blomia tropicalis (440 cases, 14.26%), mugwort (282 cases, 9.14%), and cat hair (204 cases, 6.61%). The positive rates were 28.66% in the <4 years group, 41.85% in the 4-6 years group, and 58.61% in the 7-15 years group (P<0.01). Males had a significantly higher SPT positive rate than females (47.78% vs 38.50%；P<0.05). The SPT positive rate was highest in children with allergic rhinitis (72.41%), followed by bronchial asthma (62-25%), allergic dermatosis (45.83%), and allergic purpura (36.28%). CONCLUSIONS: In children from Xi'an and the surrounding area, the main inhalant allergens for allergic diseases include Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis, mugwort and cat hair. The SPT positive rate increases with age. Male children have a higher SPT positive rate than female children. The SPT positive rate is highest in children with allergic rhinitis.

[Therapeutic effects of erythropoietin on hypoxic-ischemic encephalopathy in neonates].

OBJECTIVE: To study the efficacy of erythropoietinin (EPO) in the treatment of moderate or severe hypoxic-ischemic encephalopathy (HIE) in neonates. METHODS: Seventy neonates with moderate or severe HIE were randomly assigned to two groups: EPO treatment and control (n=35 each). The EPO treatment group included 22 cases of moderate HIE and 13 cases of severe HIE. The control group included 24 cases of moderate HIE and 11 cases of severe HIE. Thirty-five healthy full-term infants served as normal group. The control group received a conventional treatment. Beside the conventional treatment, the EPO treatment group was intravenously injected with EPO of 200 IU/kg•d, 3 times weekly. Routine blood test was performed every 6 days. EPO dose was adjusted based on the results of the routine blood test. The course of EPO treatment was 2 to 4 weeks. Neonatal Behavioral Neurological Assessment (NBNA) was performed at age of 28 days. The infant development test of Child Development Centre of China (CDCC) was performed at ages of 3 months and 6 months. RESULTS: The percentage of normal NBNA scores in the EPO treatment group was significantly higher than that in the control group at age of 28 days (P<0.05), but was significantly lower than that in the normal group (P<0.01). The CDCC test including physical development index (PDI) and physical development index (MDI) showed the percentage of normal results in the EPO treatment group was significantly higher than in the control group at age of 3 months (P<0.05), but was significantly lower than in the normal group (P<0.01). The CDCC test including PDI and MDI showed that the percentage of normal results in the EPO treatment group was significantly higher than in the control group at age of 6 months. The MDI test results in the EPO treatment group were not significantly different from those in the normal group at age of 6 months, but the percentage of normal results in the PDI test in the EPO treatment group was still significantly lower than that in the normal group (P<0.05). CONCLUSIONS: EPO treatment has neuroprotective effects against moderate or severe HIE and improves long-term behavioral neurological developments in neonates.

[Analysis and follow-up study on 8 children with combined congenital heart disease treated with simultaneous trans-catheter therapy].

OBJECTIVE: Interventional treatment for childhood combined congenital heart disease (CHD) has developed very quickly and more new types of occluders have emerged in recent years. The aim of this study is to investigate the efficiency and safety of interventional treatment for combined CHD in children. METHODS: Eight children with combined CHD (4 boys and 4 girls), aged 6.1+/-2.9 years, underwent simultaneous transcatheter therapy. Of the 8 children with CHD, 1 case had atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), 1 case had ASD, PDA and pulmonary stenosis (PS), 1 case had ASD and PDA, 1 case had patent foramen ovale (PFO) and PS, and 4 cases had ASD and PS. The methods of transcatheter intervention for these patients were as follows: in patients with ASD,VSD and PDA, the occlusion of VSD was performed first, followed by PDA and ASD occlusions; in patients with ASD, PDA and PS, the occlusion of percutaneous balloon pulmonary valvuloplasty (PBPV) was performed first, followed by PDA and ASD occlusions; in patients with PFO and PS, the occlusion of PBPV was performed first, and PFO occlusion followed; in patients with ASD and PS, the occlusion of PBPV was performed first, and ASD occlusion followed. RESULTS: The intervention operation was successfully performed in all of the 8 patients. No serious adverse events occurred during the operation. No residual shunt was found and all the occlusion devices were in the suitable sites shown by transthoracic echocardiography (TTE) and X-ray right after the operation. In the 6 patients with PS, the systolic pressure across the pulmonary valve decreased from 75.3+/-15.6 mmHg (before operation) to 14.0+/-5.6 mmHg after operation (P<0.05).A 3.4+/-1.2 years follow-up demonstrated that no residual shunt occurred and gradients across valve or coarctation sites were within the limit of satisfactory results. No complications were observed during the follow-up. CONCLUSIONS: Transcatheter interventional therapy for childhood combined CHD can obtain satisfactory results by proper procedures.

[Cloning and subcellular localization of apr-1--a new gene of tumor specific antigen family].

BACKGROUND & OBJECTIVE: apr-1 was cloned by improved polymerase chain reaction (PCR)-based subtractive hybridization from all-trans retinoic acid (ATRA)-induced apoptotic leukemia HL-60 cells in 1999. Preliminary results showed that apr-1 might be an apoptosis-related gene (GenBank ID: NM_014061). This study was to explore the background of apr-1 through gene cloning, bioinformatic analysis, and subcellular locating. METHODS: The cDNA encoding Apr-1 was amplified by reverse transcription-PCR (RT-PCR), and sequenced. Open reading frame (ORF) of apr-1 was analyzed with ORF finder software. Chromosome locus was defined by genome blast software. Conserved domains of amino acids were analyzed by protein blast software. Align (Cluster W) software in Vector NTI software package was used to analyze homogeneous genes (or proteins), and to draw the Phylogenetic Tree. Subcellular localization of apr-1 was performed. RESULTS: apr-1 was mapped to chromosome Xp11.22 with the ORF locating in 1 exon. Two MAGE conserved domains were found in Apr-1. Apr-1 shared homology with MAGE-A1, MAGE-B1, MAGE-C1, MAGE-D1, and Necdin. Phylogenetic analysis showed that Apr-1 was more closely related to MAGE-D1 and Necdin. Gene products of apr-1 were located in the nuclei of eukaryocytes. CONCLUSIONS: apr-1 is a member of MAGE family, and might belong to type II MAGE genes.

Knockdown of survivin gene expression by RNAi induces apoptosis in human hepatocellular carcinoma cell line SMMC-7721.

AIM: To investigate the survivin gene expression in human hepatocellular carcinoma cell line SMMC-7721 and the effects of survivin gene RNA interference (RNAi) on cell apoptosis and biological behaviors of SMMC-7721 cells. METHODS: Eukaryotic expression vector of survivin gene RNAi and recombinant plasmid pSuppressorNeo-survivin (pSuNeo-SVV), were constructed by ligating into the vector, pSuppressorNeo (pSuNeo) digested with restriction enzymes Xba I and Sal I and the designed double-chain RNAi primers. A cell model of SMMC-7721 after treatment with RNAi was prepared by transfecting SMMC-7721 cells with the lipofectin transfection method. Strept-avidin-biotin-complex (SABC) immunohistochemical staining and RT-PCR were used to detect survivin gene expressions in SMMC-7721 cells. Flow cytometry was used for the cell cycle analysis. Transmission electron microscopy was performed to determine whether RNAi induced cell apoptosis, and the method of measuring the cell growth curve was utilized to study the growth of SMMC-7721 cells before and after treatment with RNAi. RESULTS: The eukaryotic expression vector of survivin gene RNAi and pSuNeo-SVV, were constructed successfully. The expression level of survivin gene in SMMC-7721 cells was observed. After the treatment of RNAi, the expression of survivin gene in SMMC-7721 cells was almost absent, apoptosis index was increased by 15.6%, and the number of cells was decreased in G2/M phase and the cell growth was inhibited. CONCLUSION: RNAi can exert a knockdown of survivin gene expression in SMMC-7721 cells, and induce apoptosis and inhibit the growth of carcinoma cells.