The clinical data of a patient with Klinefelter syndrome (KS) complicated by partial androgen insensitivity syndrome (PAIS) was retrospectively analyzed.The patient, a 2-month-and-22-day-old baby, was admitted to Children′s Hospital Affiliated to Zhengzhou University due to abnormal external genitalia in October 2021.Upon birth, the patient exhibited abnormal external genitalia, manifested as clitoral hypertrophy.Hormonal examinations were consistent with those of peers, while chromosomal analysis revealed 47, XXY.Due to the severe undermasculinization, whole exome sequencing was conducted, indicating a heterozygous variant of the AR gene (c.1847G>A, p.Arg616His). The patient was diagnosed with PAIS, and her elder sister was diagnosed with complete androgen insensitivity syndrome.For further treatment, a multidisciplinary comprehensive evaluation is needed.This is a rare case of KS combined with PAIS, suggesting the possibility of AR gene mutations in KS children with severe undermasculinization.

Objective:To evaluate the effectiveness and safety of treatment with Burosumab in pediatric X-linked hypophosphatemia (XLH) patients.Methods:In this retrospective case study, 4 children with pediatric XLH, who were treated with Burosumab in Beijing Children′s Hospital, Capital Medical University and Shandong Provincial Hospital affiliated to Shandong First Medical University from July 2022 to December 2023, were selected as the study objects. We collected and analyzed their clinical characteristics, biochemical indicators, imaging results, and treatment. The children were followed up every 3 months until December 2023, and the clinical outcomes and adverse drug reactions after treatment were evaluated.Results:Of the 4 patients, 3 were males and 1 was female; they were aged 6.7, 2.9, 2.1, and 2.3 years, respectively. Three patients had previously received treatment with phosphate supplements and active vitamins, but their wadding gait and lower limb deformities did not improve significantly, neither did their imaging changes of active richets. The initial dose of Burosumab in the 4 patients was 0.8 mg/kg, administered subcutaneously every 2 weeks, with a treatment course of 0.8-1.3 years. The fasting serum phosphorus and tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) of the 4 patients before treatment were 0.72, 0.95, 0.81, 0.66 mmol/L and 0.67, 0.85, 0.87, 0.61 mmol/L, respectively. At the last follow-up, the fasting serum phosphorus and TmP/GFR levels were significantly increased (0.96, 1.09, 1.09, 0.90 mmol/L, and 0.85, 0.79, 1.03, 0.98 mmol/L, respectively). Among them, only the TmP/GFR level (1.17 mmol/L) in case 2 achieved normal values at 3 months post-therapy, while the rest did not reach the normal range for children of the same age. After treatment, the alkaline phosphatase levels of all patients gradually decreased (the values were 461, 240, 423, and 237 U/L, respectively), and the ALP levels in cases 2 and 4 returned to normal at the last visit. Case 4 showed a slight increase in parathyroid hormone (PTH) levels after 9 months of treatment, while the PTH levels in the rest 3 cases remained normal. Case 1 underwent a 6-minute walking test, and the walking distance increased from 245 m to 570 m. Abnormal gait, lower limb deformity, and the severity of rickets in the 4 patients had all improved. No adverse drug reactions such as nephrocalcinosis, local skin injection reaction, hyperphosphatemia, or vitamin D deficiency were observed.Conclusion:Burosumab can improve clinical symptoms in children with XLH with a good safety profile.

Objective To explore the effect and mechanism of Baicalein in the treatment of hyperuricemia.Methods The mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate.The effect and potential mechanism of Baicalein in the treatment of hyperuricemia were studied by biochemical indexes,pathological changes,non-target metabonomics and network pharmacology.Results Baicalein could reduce the contents of serum uric acid,creatinine and blood urea nitrogen,reduce the inflammatory injury of renal tissue,up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein.Nine disease-related targets such as BCL2,SIRT1 and XDH were screened by network pharmacology.Six key metabolic pathways including nicotinic acid and nicotinamide metabolism,caffeine metabolism and purine metabolism were screened by metabonomics analysis.Conclusions Baicalein can treat hyperuricemia and reduce renal injury,and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.

Objective To determine the blood physiological and biochemical indexes in the inbred SHANXI MU strain of spontaneous type 2 diabetes(T2DM)Chinese hamsters.Methods Chinese hamsters with spontaneously developed T2DM and normal hamsters(n=10 hamsters per group),aged 12 months,were selected for the study.Fasting blood samples were collected and 15 physiological parameters and 16 biochemical indicators were analyzed using a Sysmex XT automated hematology analyzer and Hitachi fully automatic biochemical analyzer.Results The white cell count,red cell count,platelet count,hemoglobin level,alanine transaminase,aspartate transaminase,glutamate,total cholesterol,triglycerides,and uric acid all differed significantly between the diabetic and control groups(P＜0.05).Conclusions The change of blood physiological and biochemical indexes in the Chinese hamster spontaneous T2DM model were in line with the trend in human T2DM incidence,thus providing basic data for the application of this model.

Objective To observe the value of myocardial performance index(MPI)for evaluating fetal left ventricular(LV)function in pregnant women with obstetric antiphospholipid syndrome(OAPS).Methods Totally of 41 singleton pregnancy women with OAPS(criteria-OAPS[C-OAPS]group,n=16;non-criteria OAPS[NC-OAPS]group,n=25)and 60 healthy singleton pregnancy women(control group)were prospectively enrolled.Mitral flow E velocities/A velocities,isovolumic relaxation time(IRT),isovolumic contraction time(ICT),ejection time(ET)and MPI of fetal LV were compared among 3 groups.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of MPI for predicting adverse pregnancy outcomes of pregnant woman.Results Significant differences of mitral flow E velocities/A velocities,IRT,ICT,ET and MPI of fetal LV were found among 3 groups(all P＜0.05).Results of pairwise comparison showed that among C-OAPS group,NC-OAPS group and control group,IRT and MPI of LV decreased,whereas E/A and ET of LV increased in order(all P＜0.05).ICT in C-OAPS group was higher than that in control group(P＜0.05).The sensitivity,specificity and area under the curve of MPI for predicting adverse pregnancy outcomes of pregnant woman with OAPS was 90.00％,64.45％and 0.798,respectively.Conclusion MPI could be used to evaluate fetal LV function in pregnant women with OAPS,also being helpful for predicting adverse pregnancy outcomes.

A retrospective case review was conducted of 3 cases with umbilical venous catheterization(UVC) related pericardial effusions in the Neonatal Intensive Care Unit of Zhongnan Hospital of Wuhan University from December 2020 to April 2022.All 3 cases were preterm infants with gestational ages of 33 + 4, 31 and 27 + 6 weeks, respectively.UVC was inserted routinely in 24 hours after birth.Three neonates developed tachycardia or bradycardia, dyspnea, decreased oxygen saturation and muffled heart sound at the 1 st to 4 th day after catheterization.Echocardiography indicated pericardial effusion, so the 3 neonates underwent pericardiocentesis and drainage.Among the 3 neonates, 2 cases improved and have good prognosis, 1 case died.UVC can cause pericardial effusion, which occurs mostly in the early stage after catheterization.Pericardial effusion and tamponade should be considered when patients show unexplained sudden clinical deterioration after catheterization, such as dyspnea, cyanosis, tachycardia or bradycardia, etc.Once diagnosed, umbilical vein catheter should be removed in time and pericardiocentesis and drainage should be performed for decompression.Early diagnosis and intervention can effectively improve the prognosis.

OBJECTIVE: To improve the recognition of Familial glucocorticoid deficiency type 1 (FGD1) due to variants of melanocortin 2 receptor (MC2R) gene. METHODS: Two children with FGD1 diagnosed at the Henan Children's Hospital respectively in 2019 and 2021 were selected as the study subjects. Clinical data, treatment, follow-up and results of genetic testing were collected and retrospectively analyzed. RESULTS: Whole exome sequencing revealed that both children had harbored compound heterozygous variants of the MC2R gene, including c.433C>T (p.R145C) and c.710T>C (p.L237P) in child 1, and c.145delG (p.V49Cfs*35) and c.307G>A (p.D103N) in child 2, among which c.710T>C (p.L237P) and c.145delG (p.V49Cfs*35) were unreported previously. CONCLUSION FGD1 is clinically rare, and genetic sequencing is crucial for the definite diagnosis. Discovery of the and novel variants has enriched the mutational spectrum of the FGD1 gene.
Humans ; Child ; Glucocorticoids/therapeutic use* ; Receptor, Melanocortin, Type 2/genetics* ; Retrospective Studies ; Adrenal Insufficiency/genetics* ; Mutation

Objective:To analyze the clinical and genetic features, as well as the treatment outcomes of two boys with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by gain-of-function mutations in the V2 vasopressin receptor gene (AVPR2).Methods:The clinical manifestations, genetic testing, therapeutic interventions and the outcomes of two boys with NSIAD hospitalized in the Department of Endocrinology, Beijing Children′s Hospital in April 2019 were reported. A literature search with "Nephrogenic syndrome of inappropriate antidiuresis" and "AVPR2 gene" as keywords was conducted at the China national knowledge infrastructure (CNKI), the Wanfang Data Knowledge Service Platform, PubMed and Springer Link up to May 2020. Relevant published articles were reviewed.Results:The two cases presented with chronic and severe hyponatremia with hypo-osmolality, inappropriately elevated urinary osmolality and urinary sodium levels. The onset age was 5.25-years and 2 months respectively. AVPR2 sequencing revealed a previously described hemizygous activating mutation (c.409C>T, p.R137C) in both of boys, each inherited the variant from their mother. Patient 1 limited fluid intake by himself in his daily life, intravenous and oral sodium supplementations showed no significant increase of serum sodium level. Oral furosemide increased the serum sodium level and maintained it within normal range. The serum sodium and potassium levels were in the normal range during the 1-year follow-up period with oral furosemide. The serum sodium level of Patient 2 increased with restricting fluid intake and with salt supplementation. However, after he experienced respiratory infection, the plasma sodium level decreased. Subsequently, oral anti-infection medicine and furosemide were applied. The serum sodium level increased two days later and remained at a normal range afterwards. The boy was 1 year old with normal growth. He stopped taking furosemide after 4 months while taking 1 gram of salt per day, the blood sodium level maintained at normal range. Literature search identified no reports in Chinese journals, whereas 50 publications were found in English journals. A total of 30 NSIAD probands were reported and 16 of those (53%) had childhood onset, most presented with seizures. The majority had a hotspot change at the nucleotide position of 409 in AVPR2. Nine cases had an amino acid change as R137C and five cases as R137L. Fluid restriction and oral urea intake were main treatment options, no report so far was found with oral furosemide treatment.Conclusions:NSIAD presented with hyponatremia without any other specific presentations. Genetic testing for variants in AVPR2 is helpful for early diagnosis and timely treatment. The first two cases of oral furosemide treatment were reported by the article which helped to maintain a normal serum sodium level after limiting fluid intake and supplementing sodium which showed limited effect.

Objective:To investigate the clinical and genetic features, and treatment of X-linked hypophosphatemic rickets (XLH).Methods:In this retrospective study, we reviewed the medical records of 25 pediatric patients with XLH who were admitted to Department of Endocrinology Genetics and Metabolism,Beijing Children′s Hospital from January 2010 to January 2020. The clinical characteristics, PHEX gene variants, as well as clinical outcome of the patients were summarized. To analyze the correlation between genotype and phenotype, the patients were divided into different subgroups according to the location of the variants, including N-terminal-located vs. C-terminal-located variant, and Zn-binding domain exon 17 or 19 variant vs. non-exon 17 or 19 variant. The age at onset, height standard deviation score (HtSDS), intercondylar or intermalleolar distance, fasting serum phosphorus, and HtSDS and intercondylar or intermalleolar distance at the final follow-up were compared by rank sum test or t text. Results:Among the 25 children with XLH, 8 were boys and 17 were girls. The median age of onset was 1.2 (1.0, 1.8) years, and the median age of diagnosis was 2.5 (1.5, 4.3) years. The main clinical manifestations were abnormal gait and lower limb deformity. The HtSDS was -2.0(-3.2, -0.8), and the intercondylar or intermalleolar distance was 4.5 (3.0, 6.0) cm. The fasting serum phosphorus level was 0.8 (0.7, 0.9) mmol/L, while the serum alkaline phosphatase level was (721±41) U/L and the serum calcium level was (2.5±0.1) mmol/L. Three patients (12%) had parathyroid hormone levels above the upper limit of the normal range. Twenty-five patients (100%) showed radiographic changes of active rickets. Nephrocalcinosis was found in 2 cases (9%). Twenty-four different PHEX variations were detected in 25 patients, among whom 11 (44%) had not been reported previously. No hot spot variation was found. No statistical differences (all P>0.05) were identified in clinical features and outcomes either in comparing patients with N-terminal (21 cases) and C-terminal (4 cases) variants, or in comparing patients with variant located in exon 17 or 19 (4 cases) or not (21 cases). Twenty-four cases (96%) were treated regularly with phosphate supplements and active vitamin D. After 2.7 (1.6, 5.0) years of follow-up, clinical symptoms were relieved in 96% (24/25) of the patients. The HtSDS after treatment had no significant difference compared to that before treatment (-2.0(-3.2, -0.8) vs.-2.0(-2.8, -1.1), Z =-0.156, P>0.05), while the intercondylar or intermalleolar distance after treatment was significantly reduced compared to that before treatment (4.5(3.0, 6.0) vs. 1.5(0, 3.3) cm, Z =-3.043, P<0.05). Bone X-rays were reexamined in 17 cases after treatment, and radiographic signs of rickets were improved. Eighteen cases had secondary hyperparathyroidism and 7 cases had nephrocalcinosis. Conclusions:The main clinical manifestations of XLH are abnormal gait, lower limb deformity and short stature. A high proportion of novel variations of PHEX gene but no hot spot variation neither genotype-phenotype correlation are found. Regular treatment with phosphate supplements and active vitamin D can significantly improve the symptoms except for the height. However, the rate of adverse events including secondary hyperparathyroidism and nephrocalcinosis seems to be high.

Objective To explore the clinical features and risk factors of poor prognosis in neonatal necrotizing enterocolitis(NEC).Methods A retrospective study was carried out in the infants with NEC admitted to 6 cooperative hospitals in Guangdong Province between January 2005 and December 2014.The clinical features and risk factors of poor prognosis in preterm and full-term infants diagnosed NEC,early onset and late onset NEC were analyzed.Results A total of 449 cases who met the criteria were admitted during the study time.The mortality was 23.6％ (106/449 cases),of which the preterm group was 24.6％ (58/238 cases) while the full-term group was 22.7％ (48/211 cases),the early onset group was 22.1％ (45/204 cases) while the late onset group was 24.3％ (57/235 cases).The median number of NEC onset in preterm group was 11 d after birth while the number of the full-term group was 6 d.Full-term infants who diagnosed NEC were more likely to manifest themselves as abdominal distension (52.1％ vs.42.0％,x2 =4.597,P =0.032),vomiting(36.5％ vs.17.2％,x2 =21.428,P =0.000) and bloody stool(30.3％ vs.21.4％,x2 =4.653,P =0.031);but in the onset of NEC,preterm infants more likely to have feeding intolerance (21.0％ vs.12.8％,x2=5.309,P =0.021).The early onset group of full-term NEC was much common in twins or multiplets(9.4％ vs.1.1％,x2 =6.226,P =0.013),which rate of surgical therapy was much higher (41.0％ vs.27.0％,P =0.036) and the breast-feeding rate before NEC was lower than the late onset group(14.5％ vs.32.6％,x2 =9.500,P =0.002),the differences were statistically significant.The gestational age and birth weight were bigger in the early onset group of preterm NEC[(33.8 ±2.5) weeks vs.(32.2 ±2.8) weeks,t =4.261,P =0.000;(2.1 ±0.5) kg vs.(1.7 ± 0.5) kg,t =4.735,P =0.000)],but length of stay was shorter than the late onset group (18.0 d vs.26.5 d,P =0.000).Logistic regression analysis showed that the risk factors of poor prognosis of full-term NEC were shock,peritonitis and sepsis;while risk factors of poor prognosis of preterm NEC were small for gestational age infant,pulmonary hemorrhage,shock,intestinal perforation and sepsis;the risk factors of poor prognosis of the early onset group of full-term NEC was shock;while those of the late onset group were shock and peritonitis;the risk factors of poor prognosis in the early onset group of preterm NEC were shock and sepsis,while those in the late onset group were pulmonary hemorrhage,shock,intestinal perforation and sepsis.Conclusions Compared to the preterm NEC,the onset time of full-term NEC was earlier and the clinical manifestations were more typical.Early identification and management of shock,peritonitis,intestinal perforation,sepsis and pulmonary hemorrhage can reduce the risk of poor prognosis of neonate NEC.