[Early diagnosis and intervention for prepubertal short stature children]. / å ³æ³¨é’æ˜¥æœŸå‰çŸ®èº«æå„¿ç«¥çš„æ—©æœŸè¯Šæ–­åŠå¹²é¢„.

The prevalence of short stature among prepubertal children in China is relatively high. Early identification of the cause and timely intervention can bring greater benefits to children with short stature. This paper provides an overview of early diagnosis, intervention measures, and personalized medication dosage for prepubertal short stature children, aiming to provide references for clinical doctors.

[Screening results and genetic features of glucose-6-phosphate dehydrogenase deficiency in 54 025 preterm infants in Chengdu, China].

OBJECTIVE: To analyze the screening results of glucose-6-phosphate dehydrogenase (G6PD) deficiency and gene mutation distribution of G6PD deficiency in preterm infants in Chengdu, China, in order to provide a basis for the improvement of G6PD screening process in preterm infants. METHODS: Fluorescent spot test for G6PD deficiency using dried blood spots was used for G6PD screening of 54 025 preterm infants born from January 1, 2015 to December 31, 2019 in Chengdu, and G6PD enzymology and gene detection were used for the diagnosis of 213 infants with positive screening results. RESULTS: Among the 54 025 preterm infants, 192 were diagnosed with G6PD deficiency, with an incidence rate of 3.55‰. The incidence rate of G6PD deficiency in preterm infants was higher than that in full-term infants in the same period of time and tended to increase year by year. Birth in summer, gestational age <32 weeks, and birth weight <2 500 g were influencing factors for the increase in false positive rate of screening (P < 0.05). The diagnostic accordance rate of genetic tests was significantly higher than that of enzyme activity assay in female infants (P < 0.05). Nine gene mutations were detected in Chengdu, without compound heterozygous mutation. Homozygous mutation was not detected in female infants. In the 80 infants with gene mutations, the top three gene mutations were c.1388G>A in 26 infants (32%), c.1376G>T in 21 infants (26%), and c.1024C>T in 13 infants (16%), accounting for 75%. There was a significant difference in pathogenicity grading among the three gene mutations (P < 0.001). The pairwise comparison showed that c.1024C>T had a significantly lower pathogenicity grade than c.1376G>T and c.1388G>A (P < 0.0167), suggesting that c.1376G>T and c.1388G>A had greater influence on enzyme activity than c.1024C>T. CONCLUSIONS: Screening for G6PD deficiency in preterm infants should be taken seriously. It is recommended to apply cold-chain transportation of samples in summer to reduce the false positive rate of primary screening for G6PD deficiency. Genetic tests should be promoted in girls with positive screening results to improve the detection rate of G6PD deficiency in preterm female infants. There are various types of gene mutations in preterm infants with G6PD deficiency in Chengdu, and infants with c.1024C>T mutation tend to have mild conditions.

An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. METHODS: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. FINDINGS: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. CONCLUSIONS: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. FUNDING: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).

Clinical and genetic characteristics of two cases with Williams-Beuren syndrome.

Herein, we describe 2 cases of Williams-Beuren syndrome (WBS). In both cases, the patients exhibited mental retardation, characteristic facial features, and indirect inguinal hernia. Case 1, a girl aged 2 years and 5 months old, presented with hypercalcemia, and in case 2, a boy aged 4 years and 11 months old, the disorder manifested as infantile spasms, supravalvular aortic stenosis, and pulmonary stenosis. Brain MRI revealed no abnormalities in either case. The electroencephalogram of case 2 showed hypsarrhythmia. Case 1 was treated with bisphosphonates and somatropin for hypercalcemia and short stature. Case 2 received antiepileptic drug and ketogenic diet therapy. In both cases, a 7q11.23 deletion including fragment deletion of the GTF21 gene was found, which may be associated with mental retardation. Notably, in case 2, a 921.1kb deletion in Yq11.23 was detected, which has not been reported in WBS before. The deletion of Yq11.23 is located in the AZFc region, which is an important factor in male infertility with primary azoospermia and oligozoospermia. The occurrence of hypercalcemia in case 1 may be related to the deletion of BAZ1B, while the supravalvular aortic stenosis and pulmonary stenosis were associated with deletion of the ELN gene. We explored the clinical and genetic characteristics of WBS to better understand disease.

Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism.

BACKGROUND: Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. METHODS: Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). RESULTS: Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ±â€Š2.3 mL and 4.1 ±â€Š1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ±â€Š1.8 cm and 5.1 ±â€Š1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ±â€Š0.5 cm and 2.0 ±â€Š0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. CONCLUSIONS: The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Nanomolar-Potency Small Molecule Inhibitor of STAT5 Protein.

We herein report the design and synthesis of the first nanomolar binding inhibitor of STAT5 protein. Lead compound 13a, possessing a phosphotyrosyl-mimicking salicylic acid group, potently and selectively binds to STAT5 over STAT3, inhibits STAT5-SH2 domain complexation events in vitro, silences activated STAT5 in leukemic cells, as well as STAT5's downstream transcriptional targets, including MYC and MCL1, and, as a result, leads to apoptosis. We believe 13a represents a useful probe for interrogating STAT5 function in cells as well as being a potential candidate for advanced preclinical trials.

Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma.

The STAT3 gene is abnormally active in glioblastoma (GBM) and is a critically important mediator of tumor growth and therapeutic resistance in GBM. Thus, for poorly treated brain cancers such as gliomas, astrocytomas, and glioblastomas, which harbor constitutively activated STAT3, a STAT3-targeting therapeutic will be of significant importance. Herein, we report a most potent, small molecule, nonphosphorylated STAT3 inhibitor, 31 (SH-4-54) that strongly binds to STAT3 protein (K D = 300 nM). Inhibitor 31 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. Moreover, in vivo, 31 exhibited blood-brain barrier permeability, potently controlled glioma tumor growth, and inhibited pSTAT3 in vivo. This work, for the first time, demonstrates the power of STAT3 inhibitors for the treatment of BTSCs and validates the therapeutic efficacy of a STAT3 inhibitor for GBM clinical application.

Reflection spectroscopy for the determination of Au nanostructure formation on carbon surfaces.

Au electrodeposition has been performed on carbon electrodes to fabricate Au nanostructures on the working electrode of screen-printed carbon chips. The amount of Au deposited was characterized using the raw reflection spectra obtained by detecting UV-Vis spectrum reflected from the electrode surface. SEM images at different deposition time points provided evidence for the growth of Au nanostructures. The increase in deposition time led to an increase in the intensity of the spectrum obtained for both chips. The acquired optical properties of the carbon chips provide a promising platform for simultaneous optical and electrochemical measurements.