Objective To investigate the correlation between the expression of long non-coding ribonucleic acid growth arrest specific 5(lncRNA GAS5),phospholysine phosphohistidine inorganic pyrophosphate phos-phatase(LHPP)and epithelial-mesenchymal transition(EMT)in cancer tissues of patients with non-small cell lung cancer(NSCLC)and its clinical significance.Methods Cancer tissues and adjacent tissues of 90 patients with NSCLC who underwent surgical resection in the First Hospital Affiliated to Hebei North College from June 2018 to January 2020 were collected.The expressions of lncRNA GAS5,LHPP and EMT-associated pro-teins[E-calmodulin(E-Cad),N-calmodulin(N-Cad),and vimentin(VIM)]were detected by real-time fluores-cence quantitative polymerase chain reaction.The relationship between lncRNA GAS5 and LHPP mRNA and clinicopathological features in cancer tissues of NSCLC patients was analyzed,and the correlation between ln-cRNA GAS5 and LHPP mRNA and EMT-associated proteins expression in cancer tissues of NSCLC patients was analyzed by Pearson correlation.Kaplan-Meier method was used to plot the survival curves of NSCLC pa-tients with different lncRNA GAS5 and LHPP mRNA expressions,and multivariate Cox regression was used to analyze the prognostic factors of NSCLC patients.Results The expressions of lncRNA GAS5,LHPP mR-NA and E-Cad mRNA in cancer tissues of NSCLC patients were lower than those in adjacent tissues,while the expressions of N-Cad mRNA and VIM mRNA were higher than those in adjacent tissues,with statistical sig-nificance(P＜0.05).Pearson correlation analysis showed that lncRNA GAS5 in cancer tissues of NSCLC pa-tients was positively correlated with E-Cad mRNA expression(r=0.724,P＜0.001),and negatively correla-ted with N-Cad mRNA and VIM mRNA expression(r=-0.699,-0.689).P＜0.001);lncRNA GAS5 was positively correlated with LHPP mRNA expression(r=0.651,P＜0.001).The mRNA expressions of ln-cRNA GAS5 and LHPP in cancer tissues of NSCLC patients with different degrees of differentiation,tumor TNM stage and lymph node metastasis were significantly different(P＜0.05).Kaplan-Meier survival curve a-nalysis showed that the 3-year overall survival rate in the lncRNA GAS5 high expression group[68.18％(30/44)]was higher than that in the lncRNA GAS5 low expression group[36.96％(17/46)].The 3-year overall survival rate in the high LHPP mRNA expression group[67.39％(31/46)]was higher than that in the lowLHPP mRNA expression group[36.36％(16/44)],and the difference was statistically significant(x2=10.274,10.322,P＜0.05).Low differentiation,TNM stage Ⅲ and lymph node metastasis were independent risk factors for death in NSCLC patients,and lncRNA GAS5≥1.32 and LHPP mRNA≥1.12 were independ-ent protective factors(P＜0.05).Conclusion The low expression of lncRNA GAS5 and LHPP mRNA in cancer tissues of patients with NSCLC is related to EMT-associated proteins expression,differentiation de-gree,tumor TNM stage,lymph node metastasis and prognosis,and may become a new target for the diagnosis and treatment of NSCLC.

Objective:To retrospectively analyze a pediatric case of X-linked hypophosphatemic rickets treated with Burosumab and improve clinicians′ awareness of the safety and effectiveness of the drug.Methods:Clinical data of the child were collected. Whole-exon genetic testing after parental consent confirmed X-linked hypophosphatemic rickets. During 18 months of Burosumab treatment, fasting blood phosphorus, alkaline phosphate, calcium, and calcium phosphate product were monitored every 11-14 days. Parathyroid hormone and 25 hydroxyvitamin D were checked every 2-6 weeks, while knee spacing, liver and kidney function, urinary calcium creatinine ratio, electrocardiogram were assessed every 3 months. Radiological imaging was performed every 6 months, with continuous follow-up of the child.Results:Whole-exon sequencing results showed a c. 1080_1081insCAATGTTA(p.T361Qfs*3) spontaneous heterozygous frameshift mutation in the PHEX gene in the child, which has not been reported previously. After the patient was treated with Burosumab for 18 months, the biochemical indexes were significantly improved, and the rickets score was reduced, without gingival abscess or other adverse events.Conclusion:The variant c. 1080_1081insCAATGTTA(p.T361Qfs*3) in the PHEX gene was identified as the cause of the patient′s condition. Burosumab, as a targeted therapeutic agent for X-linked hypophosphatemic rickets, showed significant treatment efficacy.

Objective: To discuss the clinical value of neck circumference in screening for overweight and obesity in children and adolescents, so as to provide a theoretical basis and new ideas for overweight and obesity screening. Methods: From May to July 2023, a total of 2 493 children and adolescents aged 3 to 16 were sampled from three schools by the cluster random sampling method. General data, neck circumference, body mass index (BMI), waisttoheight ratio, and other information were collected. Mann-Whitney ranksum test, Spearman correlation analysis, and receiver operating characteristic (ROC) curve analysis were used to statistically analyze the data. Results: The prevalence of overweight and obesity in children and adolescents aged 3 to 16 was 33.05%, and the prevalence of abdominal obesity was 28.33%.The neck circumferences of boys and girls in the overweight and obese group showed statistically significant differences from the normal weight group during the preschool, schoolage, and adolescence periods (Z=-16.69--4.54, P<0.05). The neck circumferences of children of different genders were moderately positively correlated with BMI (r=0.50-0.79, P<0.01). ROC curve analysis showed that neck circumference had good accuracy in assisting the screening for the occurrence of overweight and obesity in boys and girls during the preschool, schoolage, and adolescence periods [the AUC for boys:0.80(0.71-0.89), 0.89(0.86-0.91), 0.84(0.81-0.87); the AUC for girls:0.76(0.67-0.86), 0.81(0.74-0.88), 0.73(0.68-0.77), P<0.01], the optimal neck circumference cutoff values for boys were 26.95, 28.95, 33.55 cm, and for girls were 25.05, 26.55, 28.35 cm respectively. The neck circumferences of boys and girls were moderately positively correlated with the waisttoheight ratio during the schoolage and adolescence periods (r=0.41-0.70, P<0.01). ROC curves showed that neck circumferences had good accuracy in assisting the screening for the occurrence of abdominal obesity in boys and girls during the schoolage and adolescence periods [the AUC for boys:0.89(0.86-0.92), 0.82(0.78-0.85); the AUC for girls:0.84(0.75-0.93), 0.87(0.75-0.93)], the optimal cutoff values for boys were 28.95, 32.75 cm; for girls were 26.45, 31.85 cm respectively. Conclusion The neck circumference can be applied to screen for overweight and abdominal obesity in children and adolescents, and can provide new ideas for the prevention and control of overweight and obesity in children and adolescents.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Objective:To analyze the neurocognitive abnormalities and related emotional and behavioral problems in 410 adolescent patients with Turner syndrome (TS) managed in Henan Children′s Hospital in the past 5 years, and to explore the relationship between neurocognitive abnormalities and chromosome karyotype, pubertal development, hormone replacement therapy.Methods:A retrospective case series study.A total of 410 adolescent patients who were diagnosed with TS by karyotype or fluorescence in situ hybridization in the outpatient or inpatient Department of Endocrinology, Genetics and Metabolism at Henan Children′s Hospital from June 2018 to June 2023 were selected and divided into 2 groups according to age: < 12 years old and 12-18 years old.Neurocognitive assessments were performed based on the results of the Wechsler Intelligence Scale (4 th edition) for children and behavior scales for children, SPSS 22.0 software was used for data processing and statistical analysis, and chi-square test was used to analyze the correlation between chromosome karyotype, intelligence development level, pubertal development status, hormone therapy status and the occurrence of neuropsychiatric diseases. Results:Among the 410 TS patients, 207 cases had the karyotype of 45, X0/46, XX, accounting for 50.49%, 94 cases had the monosomic karyotype of 45, X0, accounting for 22.93%.Forty-six patients completed the Wechsler intelligence test, with the intelligence quotient (IQ) score ranging from 70 to 105, with high verbal comprehension and perceptual reasoning scores and low processing speed and working memory scores on all assessments.Fifty-two patients completed the hyperactivity scale assessment, and 43 cases had a predisposition to attention deficit hyperactivity disorder (ADHD).There were no significant differences in total IQ, perceptual reasoning and processing speed among the children with karyotype 45, X0, chimeric, and X chromosome structural abnormalities ( H=3.161, 1.955, 5.890, all P>0.05), while there were significant differences in verbal comprehension and working memory among the three groups ( H=7.697, 9.694, all P<0.05).Among TS patients 12-18 years old, 68 cases completed the depression scale self-assessment, of which 23 cases had depressive tendencies.There was no correlation between depressive tendency and chromosome karyotype, pubertal development and hormone replacement therapy ( P>0.05). Conclusions:TS patients generally have low intelligence levels and tend to have ADHD in childhood.TS patients in the pubertal development have a high incidence of depression.Pubertal development status and hormone replacement therapy show no correlation with the occurrence of neuropsychiatric diseases in TS patients.

Objective:To explore the efficacy and safety of sirolimus in the treatment of diazoxide unresponsive congenital hyperinsulinism(CHI) and summarize the single-center experience.Methods:A retrospective analysis was conducted on the clinical data of 5 cases of CHI treated with sirolimus after ineffective treatment with diazoxide, admitted to the Children′s Hospital Affiliated to Zhengzhou University from January 2017 to December 2022. The efficacy and safety of sirolimus in the treatment of CHI were evaluated.Results:The study included 5 patients, 3 males and 2 females. The age of onset ranged from 1 to 90 days. Initial symptoms included poor mental state(2/5) and convulsions(3/5). Blood glucose levels were 1.1 to 2.3 mmol/L, and insulin levels ranged from 13.52 to 70.53 μIU/mL. Two cases were classified as diffuse type, and the histological type of 3 cases was unknown. Genetic testing confirmed the diagnosis, with whole-exome sequencing revealing an unreported novel mutation in 1 case(ABCC8 exon 25_28del). Of the five patients, three patients were treated with sirolimus after diazoxide and octreotide failed, one patient was treated after unresponsive diazoxide, and the other one was treated after diazoxide, octreotide, and even near-total pancreatectomy failed. The onset age of sirolimus therapy ranged from 1 to 20 months. The maximum dosage of sirolimus was 1.2-3.2 mg·m -2·d -1, and the duration of medication ranged from 2 to 12 months. One patient was fully responsive to sirolimus, and the other four patients were partially responsive. All patients achieved euglycemia with sirolimus alone or in combination with standard CHI treatment. During follow-up, non-infectious diarrhea, elevated carcinoembryonic antigen, elevated triglycerides, and elevated liver enzymes were observed. Conclusion:This study indicates that sirolimus has a certain degree of efficacy in CHI patients for whom diazoxide treatment is ineffective. However, the long-term efficacy and safety warrant further multicenter trials.

Objective:To analyze clinical and genetic characteristics of congenital hypogonadotropic hypogonadism(CHH) in children.Methods:Clinical data of 0-18 year old CHH patients diagnosed in the Department of Endocrinology, Genetics and Metabolism of Children′s Hospital Affiliated to Zhengzhou University from January 1, 2016 to December 31, 2023 were retrospectively analyzed, including their hormone levels and genetic test results.Results:A total of 95 patients with CHH were included. Among them, 25 were diagnosed before the age of 3, 37 between the ages of 3-14, and 33 were over 14 years old at the time of first diagnosis. The primary manifestations were micropenis(95 cases, 100%) and cryptorchidism(46 cases, 48.5%). The incidence of cryptorchidism was the lowest in the group over 14 years of age. Hormonal analysis revealed that the peak levels of LH following statin B and GnRH stimulation, the peak levels of FSH after GnRH stimulation, and testosterone levels following hCG stimulation were the highest in the infant group. Genetic analysis identified 20 CHH-related genes in 61 out of 77 cases.Double-gene mutation accounted for 7.8%(6/77) and triple-gene mutation accounted for 3.9%(3/77). The most common mutations were FGFR1(18/77, 23.4%), CHD7(12/77, 15.6%), PROKR2(11/77, 14.3%) and ANOS1(6/77, 7.8%). The incidence of cryptorchidism in these four genotypes was 50%, 75%, 45.5% and 83.3%, respectively. The incidence of testicular dysfunction was 22.2%, 16.7%, 27.3%, and 16.7%, respectively, with no statistical significance.Conclusion:The primary manifestation of CHH is micropenis and cryptorchidism. In children with CHH, the incidence of testicular Leydig cell and Sertoli cell dysfunction increased with age in CHH children. FGFR1, CHD7, PROKR2 and ANOS1 were common variants of CHH.

Objective:To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD).Methods:Two children with HMGCLD diagnosed at Henan Provincial Children′s Hospital respectively in December 2019 and June 2022 were selected as the study subjects. Clinical data and results of laboratory testing were analyzed retrospectively.Results:Both children had manifested with repeated convulsions, severe hypoglycemia, metabolic acidosis and liver dysfunction. Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine (C5OH) and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio (C5OH/C8), and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid, 3-methyl glutaric acid, 3-methyl glutacoic acid, 3-hydroxyisoglycine and 3-methylprotarylglycine. Child 1 was found to harbor homozygous c. 722C>T variants of the HMGCL gene, which was rated as uncertain significance(PM2_Supporting+ PP3). Child 2 was found to harbor homozygous c. 121C>T variants of the HMGCL gene, which was rated as pathogenic(PVS1+ PM2_Supporting+ PP4). Conclusion:Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may can facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.

Objective:To explore the clinical features and genetic variants in three children suspected for β-ketothiolase deficiency (BKTD).Methods:Clinical manifestations, laboratory examination and genetic testing of three children suspected for BKTD at Henan Children′s Hospital between January 2018 and October 2022 were collected, and their clinical and genetic variants were retrospectively analyzed.Results:The children were all males with a age from 7 to 11 months. Their clinical manifestations have included poor spirit, shortness of breath, vomiting, convulsions after traumatic stress and/or infection. All of them had severe metabolic acidosis, elevated ketone bodies in blood and urine, hypoglycemia, with increased isoprenyl-carnitine and 3-hydroxyisovalyl-carnitine in the blood, and 2-methyl-3-hydroxybutyrate and methylprotaroyl glycine in the urine. All of them were found to harbor compound heterozygous variants of the ACAT1 gene, including c. 1183G>T and a large fragment deletion (11q22.3-11q23.1) in child 1, c. 121-3C>G and c. 826+ 5_826+ 9delGTGTT in child 2, and c. 928G>C and c. 1142T>C in child 3. The variants harbored by children 2 and 3 were known to be pathogenic or likely pathogenic. The heterozygous c. 1183G>T variant in child 1 was unreported previously and rated as a variant of unknown significance (PM2_Supporting+ PP3+ PP4) based on guidelines from the American College of Medical Genetics and Genomics. The large segment deletion in 11q22.3-11q23.1 has not been included in the DGV Database and was rated as a pathogenic copy number variation. Conclusion:The variants of the ACAT1 gene probably underlay the pathogenesis of BKTD in these three children.

Objective:To explore the clinical characteristics and genetic variants in three children with late-onset Multiple acyl-Coenzyme A dehydrogenase deficiency (MADD type Ⅲ).Methods:Clinical data of three children diagnosed with late-onset MADD at the Children′s Hospital Affiliated to Zhengzhou University between March 2020 and March 2022 were retrospectively analyzed. All children were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. All children had received improved metabolic therapy and followed up for 1 ~ 3 years.Results:The children had included 2 males and 1 female, and aged from 2 months to 11 years and 7 months. Child 1 had intermittent vomiting, child 2 had weakness in lower limbs, while child 3 had no symptom except abnormal neonatal screening. Tandem mass spectrometry of the three children showed elevation of multiple acylcarnitines with short, medium and long chains. Children 1 and 2 showed increased glutaric acid and multiple dicarboxylic acids by urine Gas chromatography-mass spectrometry (GC-MS) analysis. All children were found to harbor compound heterozygous variants of the ETFDH gene, including a paternal c. 1211T>C (p.M404T) and a maternal c. 488-22T>G variant in child 1, a paternal c. 1717C>T (p.Q573X) and a maternal c. 250G>A (p.A84T) variant in child 2, and a paternal c. 1285+ 1G>A and maternal c. 629A>G (p.S210N) variant in child 3. As for the treatment, high-dose vitamin B2, levocarnitine and coenzyme Q 10 were given to improve the metabolism, in addition with a low fat, hypoproteinic and high carbohydrate diet. All children showed a stable condition with normal growth and development during the follow-up. Conclusion:The compound heterozygous variants of the ETFDH gene probably underlay the muscle weakness, remittent vomiting, elevated short, medium, and long chain acylcarnitine, as well as elevated glutaric acid and various dicarboxylic acids in the three children with type Ⅲ MADD.