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 investigate the status quo and its influencing factors of nurses'organizational silence in 3 Grade A general hospitals.Methods Convenient sampling method was used to investigate clinical nurses in 3 Grade A general hospitals in Xi'an from April to August 2023 by general data questionnaire,nurses'organizational silence questionnaire and hospital magnetic factor scale.Multiple linear regression was used to analyze the influencing factors of organizational silence.Results A total of 855 nurses completed the study.The total silence score of nurses was(56.33±8.55);The total score of hospital magnetic level was(107.63±12.85).There was a negative correlation between nurse tissue silence and hospital magnetic level(r=-0.318,P<0.01).Hospital magnetic level,age,job title and working time were the influential factors of nurses'organizational silence(all P<0.001),which together explained 62.60%of the variation.Conclusions The silence of nurses'tissue and the level of hospital magnetism are in the low-medium level.Nurses are younger in age,lower in professional title,shorter in nursing age and lower in hospital magnetism level,the higher the tissue age level is,the nursing managers can reduce the tissue silence of nurses by improving the hospital magnetism level.

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:The clinical and molecular genetic characteristics of 46, XY disorders of sex development caused by NR5A1 gene variants in 15 cases were analyzed to improve the understanding of this disease. Methods:The clinical data of children with NR5A1 gene variants diagnosed at the Children′s Hospital Affiliated to Zhengzhou University from March 2016 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed to confirm the candidate sites, and Sanger sequencing was performed for validation. The patients were treated and followed up according to their disease characteristics. Results:At the initial diagnosis, 5 of the 15 cases were raised as females and 10 as males. The gonadal tissue was testis without residual Müllerian or ooticular structure, and all had various degrees of genital abnormalities. The average EMS masculinity score was 4.8 (1~9), including micropenis (100.0%), hypospadia (86.7%), unfused scrotum (46.7%), and abnormal testicular position (60.0%), in which the hypospadias was Ⅱ°~Ⅳ°. There was no skin pigmentation in 5 patients with growth retardation. Chromosomol karyotypes were 46, XY, adrenocorticotropin and cortisol levels were normal, electrolyte levels were normal, HCG stimulation test in 5 cases had normal response, 9 cases had low response. Anti-Müllerian hormone and statin B had decreased abnormally with age. A total of 14 NR5A1 variants were detected in the 15 children, most of which occurred in exon 4, of which 9 variant loci were not included in the HGMD database as of December 2022. Conclusion:The clinical phenotype of 46, XY abnormal sexual development caused by NR5A1 gene variants is extensive, with the external genitals showing varying degrees of insufficient masculinization. Adrenal involvement is rare.

Most of the current research on depression focuses on neuronal regulation,while the astrocytic mechanism of depression is far from explored.Astrocytes are the most numerous and widely distributed glial cells in the central nervous system.With a complex structural morphology,astrocytes play an important role in a variety of neuropsychiatric disorders by interacting with neuronal synapses,vasculature and other glial cells.Recent studies have shown that astrocytes may be involved in depression by regulating monoamine transmitters,glutamate cycle,synaptic plasticity,energy metabo-lism,and neuroinflammation.This review is intended to inspire new ideas for the treatment of depres-sion and the development of novel drugs based on astrocyte regulation.

Objective:To evaluate the role of ferroptosis in lung injury in a rat model of autologous orthotopic liver transplantation.Methods:Twenty-four healthy adult SPF-grade male rats, aged 8-10 weeks, weighing 230-270 g, were divided into 3 groups ( n=8 each) using the random number table method: sham operation group (S group), autologous in situ liver transplantation group (LT group) and ferroptosis inhibitor Ferrostain-1 group (LT+ Fer-1 group). In LT group and LT+ Fer-1 group, an autologous in situ liver transplantation model was developed in anesthetized animals, and Ferrostain-1 5 mg/kg was intraperitoneally injected at 30 min before surgery in LT+ Fer-1 group. The inferior vena cava blood samples were obtained at 6 h of reperfusion, then animals were sacrificed, and lung tissues were obtained. The morphology of lung tissues was examined, and the lung injury was scored. The serum malondialdehyde (MDA) concentration and contents of MDA, reduced glutathione (GSH), glutathione peroxidase4 (GPX4), and Fe 2+ in lung tissues were measured by enzyme-linked immunosorbent assay. The expression of ferritin heavy chain 1 (FTH1) and solute carrier family 7 member 11 recombinant protein (SLC7A11) was determined by Western blot. Results:Compared with S group, the lung injury, serum MDA concentration, and contents of MDA and Fe 2+ were significantly increased, the contents of GSH and GPX4 were decreased, and the expression of FTH1 and SLC7A11 was down-regulated in LT group ( P<0.05). Compared with LT group, the lung injury, serum MDA concentration, and contents of MDA and Fe 2+ were significantly decreased, the contents of GSH and GPX4 were increased, and the expression of FTH1 and SLC7A11 was up-regulated in LT+ Fer-1 group ( P< 0.05). Conclusions:Ferroptosis is involved in the pathophysiology of lung injury in a rat model of autologous orthotopic liver transplantation.

Objective:To explore the feasibility and clinical efficacy of oblique lateral interbody fusion (OLIF) in the treatment of adjacent segment disease (ASDis).Methods:Retrospective analysis was conducted on the data of 31 patients with ASDis treated by OLIF in four medical centers from June 2015 to December 2018. There were 17 males and 14 females. The average age was (65.7±3.4) years (range, 59 to 75 years). 19 cases received single-segment fixed fusion, 11 cases received double-segment fixed fusion and 1 case received three-segment fixed fusion. Original fixed fusion site: 1 case of L 1, 2, 3 cases of L 3, 4, 11 cases of L 4, 5, 4 cases of L 5S 1, 6 cases of L 3-L 5, 5 cases of L 4-S 1, and 1 case of L 3-S 1. The time from the initial fixation and fusion to this admission was 82.5±45.5 months (rang, 24 to 180 months). ASDis occurred at the proximal end of the fixed fusion segment in 28 cases and at the distal end in 3 cases. The types of ASDis: degenerative disc disease in 11 cases, lumbar spinal stenosis in 15 cases, degenerative spondylolisthesis in 2 cases, and degenerative scoliosis in 3 cases. The location of ASDis: 6 cases of L 2, 3, 12 cases of L 3, 4, 6 cases of L 4, 5, 3 cases of L 1-L 3, 1 case of L 2-L 4, and 3 cases of L 1-L 4. At admission, 3 cases of lumbar internal fixation had been removed and 28 cases of internal fixation remained. Stand-alone OLIF was performed in 19 cases, OLIF combined with pedicle screw fixation in 8 cases, and OLIF combined with cortical screw fixation in 4 cases. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate the low back pain and lumbar function before operation and at the last follow-up, and the imaging results and complications were observed. Results:All patients were followed up. The follow-up time was 23.6±9.6 months (range, 12 to 60 months). The operation time was 73.8±25.3 mins (range, 40 to 180 min), and the intraoperative blood loss was 86.2±67.4 ml (range, 20 to 310 ml). The average blood loss in each segment was 24.8 ml. During the operation, there were 1 case of segmental vein injury, 7 cases of endplate injury, 2 cases of transient iliopsoas muscle weakness, 1 case of thigh pain and numbness, and 1 case of incomplete intestinal obstruction. There was no incision necrosis and infection. The VAS score of low back pain decreased from 5.9±1.9 before operation to 1.4±0.6 at the last follow-up, with a statistically significant difference ( t=8.47, P<0.001). The ODI index recovered from 45.2%±5.7% before operation to 13.8%±4.7% at the last follow-up, with a statistically significant difference ( t=7.92, P<0.001). The height of intervertebral space increased from 8.7±1.6 mm before operation to 11.4±1.9 mm after operation and 9.9±1.8 mm at the last follow-up. There was a statistically significant difference between postoperative and preoperative height of intervertebral space ( F=4.15, P=0.007). There was a statistically significant difference between the last follow-up and postoperative height of intervertebral space ( P=0.011). During the follow-up, there were 13 cases of fusion cage subsidence, 1 case of fusion cage displacement, and no case of internal fixation loosening or fracture. The intervertebral fusion rate was 94%(29/31) and the complication rate was 42%(13/31). Conclusion:ASDis is a common complication after lumbar fixation and fusion, and requires surgical treatment. OLIF is a reliable method to treat ASDis as it has advantages of small trauma, high fusion rate and low complication rate.

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with congenital isolated adrenocorticotropic hormone deficiency (IAD). METHODS: Clinical characteristics of the patient was reviewed. Genomic DNA of the child was subjected to whole exome sequencing. RESULTS: Genetic testing has confirmed the diagnosis of congenital IAD by identification of compound heterozygous variants of the TBX19 gene, which included a pathogenic nonsense c.535C>T (p.R179X) variant inherited from his father and a novel missense c.298C>T (p.R100C) variant inherited from his mother. CONCLUSION Congenital IAD due to variants of the TBX19 gene is a rare autosomal recessive disease. It is characterized by low plasma adrenocorticotropic hormone and cortisol levels but normal levels of other pituitary hormones. Delayed diagnosis may lead to severe early-onset adrenal failure and wrong treatment which may result in neonatal mortality. Hydrocortisone replacement is effective. Detection of pathogenic variant of TBX19 gene is the key to diagnosis.
Adrenal Insufficiency/genetics* ; Child ; Homeodomain Proteins/genetics* ; Humans ; T-Box Domain Proteins/genetics*