[Clinical characteristics and genetic analysis of children and adolescents with monogenic diabetes].

OBJECTIVE: To explore the clinical characteristics and molecular basis for children and adolescents with monogenic diabetes. METHODS: A retrospective analysis was carried out for the clinical manifestations and laboratory data of 116 children and adolescents diagnosed with diabetes at Ningbo Women and Children's Hospital from January 2020 to March 2023. Whole exome sequencing and mitochondrial gene sequencing were carried out on 21 children with suspected monogenic diabetes. RESULTS: A total of 10 cases of monogenic diabetes were diagnosed, all of which were Maturity-onset Diabetes Of the Young (MODY). Six cases of MODY2 were due to GCK gene mutations, 1 case of MODY3 was due to HNF1A gene mutation, 2 cases of MODY12 were due to ABCC8 gene mutations, and 1 case of MODY13 was due to KCNJ11 gene mutation. Nine of the 10 patients with MODY had no typical symptoms of diabetes. A family history of diabetes was significantly more common in the MODY group compared with the T1DM and T2DM groups (P < 0.05). The BMI of the MODY group was higher than that of the T1DM group (P < 0.05). The initial blood glucose level was lower than that of the T1DM group (P < 0.05), and there was no significant difference compared with the T2DM group. The fasting C-peptide level of the MODY group was higher than that of the T1DM group (P < 0.05), and there was no significant difference compared with the T2DM group. Glycosylated hemoglobin of the MODY group was lower than both the T1DM and T2DM groups (P < 0.05). CONCLUSION: In this study, MODY has accounted for the majority of monogenic diabetes among children and adolescents, and the common mutations were those of the GCK gene in association with MODY2. Blood glucose and glycosylated hemoglobin of children with MODY were slightly increased, whilst the islet cell function had remained, and the clinical manifestations and laboratory tests had overlapped with those of type 2 diabetes. WES and mitochondrial gene sequencing can clarify the etiology of monogenic diabetes and facilitate precise treatment.

Predictive Care Improves Recovery Status and Complications after Ureteral Calculi Surgery: A Retrospective Study.

OBJECTIVE: Predictive care in patients undergoing ureteroscopic stone surgery has emerged as a promising approach. Thus, this study aims to enhance personalised nursing plans and reduce the risk of complications by conducting predictive analysis of possible risks early in the treatment and nursing process. METHODS: Clinical data were collected from 108 patients who underwent ureteroscopic stone surgery and were admitted to our hospital between January 2020 and January 2023. Patients were divided into a control group (conventional nursing, n = 53) and an observation group (predictive care, n = 55) based on the nursing method, and various clinical indicators were compared between the two groups of surgical patients. RESULTS: No significant difference in general data was found between the two groups (p > 0.05). Compared with the control group, the first time to exhaust gas (p < 0.05), the first time to get out of bed (p < 0.05), the time to exhaust stone (p < 0.05), the first time to defecate (p < 0.05) and the length of hospital stay (p < 0.05) in the observation group were shorter; 1 day after surgery, no significant differences in all dimensions of the general comfort questionnaire (GCQ) score were found; 2 days after surgery, the GCQ score in all dimensions of the observation group was significantly higher than that of the control group (p < 0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group (p < 0.05). CONCLUSIONS: Predictive nursing can effectively improve the patients with ureteral calculi, accelerate the process of postoperative recovery and reduce the occurrence of complications; Thus, this process is worthy of widespread clinical promotion.

Case Report: Identification of a novel PRR12 variant in a Chinese boy with developmental delay and short stature.

Proline Rich 12 (PRR12) protein is primarily expressed in the brain and localized in the nucleus. The variants in the PRR12 gene were reported to be related to neuroocular syndrome. Patients with PRR12 gene presented with intellectual disability (ID), neuropsychiatric disorders, some congenital anomalies, and with or without eye abnormalities. Here, we report an 11-year-old boy with a novel PRR12 variant c.1549_1568del, p.(Pro517Alafs*35). He was the first PRR12 deficiency patient in China and presented with ID, short stature, and mild scoliosis. He could not concentrate on his studies and was diagnosed with attention deficit hyperactivity disorder (ADHD). The insulin-like growth factor 1 (IGH-1) was low in our patient, which may be the cause of his short stature. Patients with neuroocular syndrome are rare, and further exploration is needed to understand the reason for neurodevelopmental abnormalities caused by PRR12 variants. Our study further expands on the PRR12 variants and presents a new case involving PPR12 variants.

Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity.

This study investigated how Metformin (Met) combined with L-carnitine (L-car) modulates brown adipose tissue (BAT) to affect obesity. High-fat-induced obese rats received daily oral gavage with Met and/or L-car, followed by serum biochemical analysis, histopathological observation on adipose tissues, and immunochemistry test for the abdominal expression of BAT-specific uncoupling protein 1 (UCP1). Mouse-embryonic-fibroblast cells were induced into adipocytes, during which Met plus L-car was added with/without saturated fatty acid (SFA). The role of nuclear factor erythroid 2-related factor 2 (Nrf2) in adipocyte browning was investigated by gene silencing. Mitochondria biogenesis in adipocytes was inspected by Mitotracker staining. Nrf2/heme oxygenase-1 (HO-1)/BAT-related genes/proinflammatory marker expressions in adipose tissues and/or adipocytes were analyzed by Western blot, qRT-PCR, and/or immunofluorescence test. Met or L-car improved metabolic disorders, reduced adipocyte vacuolization and swelling, upregulated levels of BAT-related genes including UCP1 and downregulated proinflammatory marker expressions, and activated the Nrf2/HO-1 pathway in adipose tissues of obese rats. Met and L-car functioned more strongly than alone. In adipocytes, Met plus L-car upregulated BAT-related gene levels and protected against SFA-caused inflammation promotion and mitochondria degeneration, which yet was attenuated by Nrf2 silencing. Met plus L-car enhances BAT activity and white adipose tissue browning via the Nrf2/HO-1 pathway to reduce lipid accumulation and inflammation in obese rats.

Whole paternal uniparental disomy of chromosome 4 with a novel homozygous IDUA splicing variant, c.159-9T>A, in a Chinese patient with mucopolysaccharidosis type I.

BACKGROUND: Mucopolysaccharidosis type I (MPS-I) is a rare autosomal recessive genetic lysosomal storage disorder that is caused by pathogenic variants of the α-L-iduronidase (IDUA) gene. This study aimed to identify the genetic causes of MPS-I in a Chinese patient and construct a minigene of IDUA to analyze its variants upon splicing. METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the potential causative variants. Single-nucleotide polymorphism (SNP) array was subsequently performed to confirm uniparental disomy (UPD). Minigene assay was performed to analyze the effect on splicing of mRNA. We meanwhile explored the conservative analysis and protein homology simulation. RESULTS: A novel homozygous splicing mutation of IDUA, c.159-9T>A, was identified in an individual presenting with overlapping features of MPS-I. Interestingly, only the father and sisters, but not the mother, carried the variant in a heterozygous state. WES and SNP array analyses validated paternal UPD on chromosome 4. Minigene splicing revealed two aberrant splicing events: exon 2 skipping and intron 1 retention. Moreover, the specific structure of the mutant protein obviously changed according to the results of the homologous model. CONCLUSIONS: This study describes a rare autosomal recessive disorder with paternal UPD of chromosome 4 leading to the homozygosity of the IDUA splicing variant in patients with MPS-I for the first time. This study expands the variant spectrum of IDUA and provides insights into the splicing system, facilitating its enhanced diagnosis and treatment.

The significance of machine learning in neonatal screening for inherited metabolic diseases.

Background: Neonatal screening for inherited metabolic diseases (IMDs) has been revolutionized by tandem mass spectrometry (MS/MS). This study aimed to enhance neonatal screening for IMDs using machine learning (ML) techniques. Methods: The study involved the analysis of a comprehensive dataset comprising 309,102 neonatal screening records collected in the Ningbo region, China. An advanced ML system model, encompassing nine distinct algorithms, was employed for the purpose of predicting the presence of 31 different IMDs. The model was compared with traditional cutoff schemes to assess its diagnostic efficacy. Additionally, 180 suspected positive cases underwent further evaluation. Results: The ML system exhibited a significantly reduced positive rate, from 1.17% to 0.33%, compared to cutoff schemes in the initial screening, minimizing unnecessary recalls and associated stress. In suspected positive cases, the ML system identified 142 true positives with high sensitivity (93.42%) and improved specificity (78.57%) compared to the cutoff scheme. While false negatives emerged, particularly in heterozygous carriers, our study revealed the potential of the ML system to detect asymptomatic cases. Conclusion: This research provides valuable insights into the potential of ML in pediatric medicine for IMD diagnosis through neonatal screening, emphasizing the need for accurate carrier detection and further research in this domain.