OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

The study explored the pathological mechanism of doxorubicin chemotherapy-induced neurotoxicity and the intervention methods of traditional Chinese medicine. BALB/c mice were selected to establish tumor-bearing mouse models by orthotopic injection of 4T1 triple-negative breast cancer cells. After randomization, the mice were treated with doxorubicin chemotherapy or doxorubicin chemotherapy + Kaixin San(KXS). The lesions in the prefrontal cortex of mice were observed by pathological examination, and the lesion information was obtained by long non-coding RNA sequencing. The occurrence of lesions was determined by Western blot and biochemical indicators. In addition, neuroblastoma cells and microglia cells were used to construct in vitro models, and drug-containing serum and p-AMPK dephosphorylation inhibitors were used to further verify the accuracy of animal experiments. Pathological results showed that KXS could alleviate doxorubicin-induced neuronal degeneration in the prefrontal cortex. The long non-coding RNA sequencing suggested that neuronal degeneration and the intervention process of KXS were related to ferroptosis, immune diseases, AMPK signaling pathway, etc. Western blot and biochemical indicators confirmed that this process was directly related to the activation of the AMPK/HIF-1α/ACSL4 signaling pathway to alleviate ferroptosis of neurons and immune response of glial cells. In conclusion, KXS could alleviate doxorubicin-induced neurotoxicity by activating the AMPK signaling pathway and reducing the ferroptosis of neurons and immune response of glial cells.
Animals ; Doxorubicin/toxicity* ; Mice ; AMP-Activated Protein Kinases/genetics* ; Signal Transduction/drug effects* ; Mice, Inbred BALB C ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Humans ; Cell Line, Tumor ; Neurotoxicity Syndromes/genetics*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objectives To evaluate the clinical characteristics,in-hospital and three-year outcome in ST-elevation myocardial Infarction (STEMI) patients receiving conservative treatment (CT),thrombolytic treatment (TT) and primary percutaneous coronary intervention (PCI) in Beijing.Methods This 12-month prospective,multicenter registry study was conducted in 19 hospitals with 808 patients with STEMI in Beijing between Jan.2006 and Dec.2006,518 (64.1％) received PCI,106 (16.1％) received TT and 184 (22.8％) received CT therapy.Patients were followed up for 3 years.Results At baseline,the age of patients in CT group [(64.5 ± 13.5) years] was significantly higher than those in TT group [(57.9 ± 11.0) years] and in PCI group [(60.4 ± 12.3) years,all P ＜ 0.01] ; and the median time from symptom onset to hospital in CT group (207 min) was significantly longer than those in TT group (130 min) and PCI group (130 min,all P ＜ O.01).Emergency Medical Service (EMS) use was significantly higher in PCI group (184/518,35.5％) than in CT group (46/184,27.3％) and TT group (29/107,25.0％,all P＜0.05).Health insurance holder was the highest in PCI group (P ＜ 0.01).PCI was performed less frequently than thrombolytic therapy [66.6％ (345/518) vs.80.2％ (85/106),P =0.02] during offhours and more frequently performed in tertiary hospitals than in secondary hospitals [66.8％ (437/654)vs.52.6％ (81/154),P ＜ 0.01)].The in-hospital mortality and the cardiovascular mortality at 3 year after hospital discharge was significantly higher in CT group [9.2％ (17/185) and 9.4％ (15/159)] than in PCI group [3.5％ (18/518),4.5％ (20/446)] and in TT group [6.6％ (7/106),2.3％ (2/86),all P＜0.01].Patients in PCI group had the highest adherence level of aspirin,β-blocker,angiotensinconverting enzyme inhibitors/angiotensin-receptor blockers or statins at 3-years follow-up (all P ＜ 0.05).Multivariable Cox proportional hazards regression analysis showed that only PCI was associated with lower risk of cardiovascular death (HR =0.40,95％ CI:0.21-0.73,P ＜0.01).Conclusions Social and clinical setting may affect the physician's decision to provide reperfusion therapy in Beijing for STEMI patients.Better adherence of secondary preventive drugs and lower cardiovascular death are observed in STEMI patients receiving PCI during the 3-years follow-up.