Clinical characteristics and genetic analysis of six children with carnitine palmitoyltransferase 2 deficiency. / å ­ä¾‹è‚‰ç¢±æ£•æ¦ˆé °è½¬ç§»é ¶2ç¼ºä¹ç—‡æ‚£å„¿ä¸´åºŠç‰¹å¾åŠåŸºå› å˜å¼‚åˆ†æž.

OBJECTIVES: To investigate the clinical characteristic and genetic variants of children with carnitine palmitoyltransferase 2 (CPT2) deficiency. METHODS: The clinical and genetic data of 6 children with CPT2 deficiency were retrospectively analyzed. The blood acylcarnitines and genetic variants were detected with tandem mass spectrometry and whole-exon gene sequencing, respectively. RESULTS: There were 4 males and 2 females and the mean age at diagnosis was 32 months (15 d~9 y). One case was asymptomatic, 2 had delayed onset, and 3 were of infantile type. Three cases were diagnosed at neonatal screening, and 3 cases presented with clinical manifestations of fever, muscle weakness, and increased muscle enzymes. Five children presented with decreased free carnitine and elevated levels of palmitoyl and octadecenoyl carnitines. CPT2 gene variants were detected at 8 loci in 6 children (4 harboring biallelic mutations and 2 harboring single locus mutations), including 3 known variants (p.R631C, p.T589M, and p.D255G) and 5 newly reported variants (p.F352L, p.R498L, p.F434S, p.A515P, and c.153-2A>G). It was predicted by PolyPhen2 and SIFT software that c.153-2A>G and p.F352L were suspected pathogenic variants, and p.R498L, p.F434S and p.A515P were variants of unknown clinical significance. CONCLUSIONS: The clinical phenotypes of CPT2 deficiency are diverse. The early diagnosis can be facilitated by neonatal blood tandem mass spectrometry screening and genetic testing, and most of them have good prognosis after timely diagnosis and treatment.

Clinical phenotype of a Kallmann syndrome patient with IL17RD and CPEB4 variants.

Background: This study aimed to characterize the clinical phenotype and genetic variations in patients with Kallmann syndrome (KS). Methods: This study involved the collection and analysis of clinical data from an individual with sporadic KS. Following this, peripheral blood samples were obtained from the patient and his parents. Genomic deoxyribonucleic acid was extracted and subjected to whole-exome sequencing and genomic copy number variation (CNV) detection. Finally, Sanger sequencing was performed to validate the suspected pathogenic variants. Results: Whole-exome sequencing confirmed that the child carried both the IL17RD variant (c.2101G>A, p.Gly701Ser) inherited from the mother and the new CPEB4 variant (c.1414C>T, p.Arg472*). No pathogenic CNVs were identified in CNV testing. Conclusion: Bioinformatics analysis shows that the IL17RD protein undergoing Gly701Ser mutation and is speculated to be phosphorylated and modified, thereby disrupting fibroblast growth factor signaling. This study also suggested that the CPEB4 might play a crucial role in the key signaling process affecting olfactory bulb morphogenesis. Overall, the findings of this study broaden the gene expression profile of KS-related pathogenic genes. This offers a new avenue for exploring the pathogenic mechanism of KS and provides valuable insights for precise clinical diagnosis and treatment strategies for this condition.

[Clinical and genetic analysis of a child with early-onset severe obesity].

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity. METHODS: A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic. CONCLUSION: The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.

The effect of virtual reality technology in children after surgery for concomitant strabismus.

Purpose: This study aimed to investigate the effect of virtual reality (VR) technology in children after surgery for concomitant strabismus. Methods: A total of 200 children with concomitant exotropia or concomitant esotropia were randomly divided into a training group and a control group according to the single even number random method (100 cases in each group). Patients in the training group received VR intervention training within 1 week after surgery. Patients in the control group did not receive any training. Results: Six months after the surgery, the orthophoria (the far or near strabismus degree was ≤8Δ) rate was significantly higher in the training group than in the control group (P = 0.001), while the eye position regression rate (compared to the strabismus degree within 1 week after the surgery, the amount of regression >10Δ) was significantly lower in the training group than in the control group (P = 0.001). Six months after the surgery, the number of children with simultaneous vision and remote stereovision was significantly higher in the training group than in the control group (P = 0.017 and 0.002, respectively). The differences in the number of patients with peripheral stereopsis, macular stereopsis, and stereopsis in macular fovea centralis at 1, 3, and 6 months after the surgery between the training and the control groups were not statistically significant (P = 0.916, 0.274, and 0.302, respectively). Conclusion: The intervention of VR technology after strabismus correction effectively improved children's visual function and maintained their eye position.

Global pathways: new evidence on the international graduate school choice of Chinese outbound students.

China serves as an indispensable recruitment market for higher education institutions across the globe. Using large-scale administrative and survey data from one of China's pipeline provinces for sending students abroad, we provide new evidence on the factors influencing Chinese students' graduate school choices internationally. We model international student mobility as a function of schooling-constrained, international migration, and consumption values. Descriptive results from nested logit model and multinomial logit model support the model predictions. We also construct counterfactual policy simulations by examining what would have happened under different potential scenarios in both China and destination countries. The simulation results show that the changes in Chinese college quality and family income are likely to affect the number of Chinese students studying abroad but not their distribution patterns among destination countries. In the meanwhile, factors including scholarship opportunities, work visa policies, and recruitment efforts in the destination countries would substantially shift Chinese students' choice of destination country and therefore the specific graduate school location. Supplementary Information: The online version contains supplementary material available at 10.1007/s10734-022-00979-6.

The Clinical and Genetic Characteristics in Children with Idiopathic Hypogonadotropin Hypogonadism.

Background: Idiopathic hypogonadotropin hypogonadism (IHH) is caused by hypothalamic-pituitary-gonadal axis dysfunction. This is divided into Kallmann syndrome which has an impaired sense of smell and hypogonadotropin hypogonadism with normal olfactory (nIHH sense. Approximately 60% of patients are associated with Kallmann syndrome, whereas there are approximately 40% with hypogonadotropin hypogonadism (nIHH). This disease is associated with various variants in genes along with different phenotypic characteristics, and even those gene variations could also lead to the cancer formation in patients. So, current study has been designed to investigate and to better understand the characteristics of various IHH-associated genes and the correlation between IHH genes and phenotype. Methods: The cohort included 14 children with IHH (6 patients of KS and 8 patients of IHH), including 13 boys and 1 girl. Exclusion criteria are as follows: diagnosis of secondary hypogonadotropin hypogonadism due to tumor, trauma, drugs, or other systemic diseases. Clinical data and genetic results were analyzed. Results: Almost all male patients showed micropenis (12/13, 92.3%), and few of them had cryptorchidism (5/13, 41.7%). A total of 6 genes, CHD7, PROKR2, ANOS1, FGFR1, SEMA3A, and NDNF, were detected. CHD7 was the most common (11/17, 64.7%), and the main mutation type was missense mutation (14/16, 87.5%). Six reported variants and 10 new variants (5 genes, including entire ANSO1 duplicates) were found. Neonatal variation was detected in 3 patients with IHH. Eight patients inherited the variation from their father, while five patients inherited it from their mother. One patient had both FGFR1 and SEMA3A gene variants, while the other had two different CHD7 gene variants and entire ANSO1 repeats. According to ACMG criteria, 4 variants were pathogenic (P), 2 were possibly pathogenic (LP), and 8 had uncertain significance (US). In patients with P or LP (5/6, 83.3%), we found that extragonadal symptoms were more common. Conclusions: It was concluded that variations in the studied genes could lead to the IHH. Ten new variants have been reported which may lead to different symptoms of IHH. For CHD7 variants, the rare sequencing variants (RSVs) of P or LP showed commonly associated with CHARGE syndrome. Findings of the current study may help for the better diagnosis and treatment of IHH.

Effect of Vitamin D Combined with Recombinant Human Growth Hormone in Children with Growth Hormone Deficiency.

Objective: Growth hormone deficiency (GHD) refers to the complete or partial lack of pituitary growth hormone synthesis and secretion. This study is aimed at investigating the efficacy of vitamin D and recombinant human growth hormone (rhGH) in children with GHD. Methods: A total of 100 children with GHD at our hospital were included between 1st January 2018 and 31st October 2020. The patients were divided into a study group (n = 70, received vitamin D combined with rhGH) and a control group (n = 30, received rhGH). The growth and development (bone age, growth rate, and height), bone metabolism (bone alkaline phosphatase (BAP), ß-collagen degradation product (ß-CTX), osteocalcin (OC), and amino-terminal propeptide type I procollagen (PINP)), insulin-like growth factor 1 (IGF-1), ghrelin, and adverse reactions in the two groups were measured before and 12 months after treatment. Results: There were no significant differences in the bone age, growth rate, and height between the two groups before treatment. After 12 months of treatment, the bone age, growth rate, and height of the study group were significantly higher than those of the control group. After 12 months of treatment, the levels of serum BAP, PINP, and OC in the study group were significantly higher than those in the control group, while the levels of ß-CTX in the study group were significantly lower than those in the control group. The serum IGF-1 level in the study group was significantly higher than that in the control group, while the ghrelin level in the study group was lower. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusion: Combined rhGH and vitamin D treatment can promote growth and development, improve bone metabolism, and regulate IGF-1 and ghrelin levels.

Tumor microenvironment triggered biodegradation of inorganic nanoparticles for enhanced tumor theranostics.

Inorganic nanoparticles (NPs)-mediated tumor theranostics have attracted widespread attention due to their unique physicochemical properties, such as optical, electrical, magnetic, and thermal properties. In the past decade, great advancements have been made in inorganic NPs-associated drug delivery, multimodal tumor imaging, and tumor therapy. However, the potential toxicity of inorganic NPs due to their low biodegradability, background signals interference and treatment side effects limit their clinical application. Therefore, developing biodegradable and intelligent NPs is beneficial to avoid excessive metal ions deposition, specific tumor imaging and treatment. In this review, we summarize the recent advances in tumor microenvironment (TME)-triggered biodegradation of inorganic NPs accompanied by imaging signal amplification and the released ions-mediated tumor therapy. First, the feature characteristics of the TME are introduced, including mild acidity, hypoxia, overexpressed reactive oxygen species (ROS), glutathione (GSH), and enzymes et al.; then, the biodegradation of NPs in a TME-induced activation of imaging signals, such as magnetic resonance (MR) imaging and fluorescence imaging is described; furthermore, tumor therapies through "Fenton", "Fenton-like" reactions, and interference of biological effects in cells is presented. Finally, the challenges and outlook for improving the degradation efficiency, imaging, specificity and efficiency of tumor imaging and treatment are discussed.

Prevalence of and factors associated with myopia in primary school students in the Chaoyang District of Beijing, China.

PURPOSE: To determine the prevalence of and risk factors for myopia in primary school children in Chaoyang District, Beijing. METHODS: This cross-sectional prevalence survey was conducted in September to October 2011 in 4 schools randomly chosen from among the 126 primary schools in Chaoyang District. Students were assessed with autorefractometry under cycloplegia and checked with retinoscopy for accuracy. Questionnaires were completed by the students' parents. RESULTS: Myopia was present in 36.7 ± 0.7% of 4249 students aged 5-14 years old. The prevalence of myopia in girls (38.6 ± 1.1%) was significantly higher than in boys (35.0 ± 1.0 %) (p = 0.015) and increased with age (p < 0.001), with the highest prevalence observed in children aged ≥11 years (67.5 ± 1.8%). After adjustment, having a myopic parent (aOR 3.10; 95% CI 2.49-3.86), incorrect reading posture (aOR 2.09; 95% CI 1.75-2.50), reading a book at a distance of <20 cm (aOR 1.60; 95% CI 1.16-2.21), studying at home for >3 h daily (aOR 1.50; 95% CI 1.12-2.01), studying for >1 h continuously (aOR 1.21; 95% CI 1.02-1.45), and reading extracurricular books that utilize a font larger than that used in textbooks (aOR 0.74; 95% CI 0.59-0.94) were all significantly associated with myopia. CONCLUSIONS: The prevalence of myopia among primary school children in Beijing increased with age, and was significantly higher in girls ≥10 years old. Myopia was significantly associated with parental myopia, reading posture, distance between the eyes and the book being read, font size used in extracurricular reading material, time spent studying at home, and the duration of continuous study time.