The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

OBJECTIVE: To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia. METHODS: A retrospective study was conducted on 7 patients diagnosed by Yangjiang People's Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People's Hospital of Yangjiang (Ethics No: 20240001). RESULTS: For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A2, whilst another had significantly decreased Hb A and Hb A2, in addition with the appearance of a Hb H band. The content of Hb Bart's in four neonates was ≥ 0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c.2delT, HBA2: c.1A>G, HBA2: c.1A>T, and HBA1: c.2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c.427T>C (Hb CS) and HBA2: c.2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c.1A>G and Southeast Asian type deletion. CONCLUSION Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c.1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.
Humans ; Phenotype ; Codon, Initiator/genetics* ; Female ; Male ; Retrospective Studies ; alpha-Globins/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobin A/genetics* ; Adult ; Mutation

OBJECTIVE: To explore the clinical features of a child with Lamb-Shaffer syndrome (LAMSHF) due to a variant of SOX5 gene. METHODS: A child who was admitted to Children's Hospital Affiliated to Zhengzhou University in July 2022 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing (WES) was carried out on peripheral blood samples from the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-100). RESULTS: The child, an one-year-and-seven-month-old male, has manifested delayed development in speech and language, intelligence and movement, in addition with mild facial deformities and eye signs. Whole exome sequencing revealed that he has harbored a heterozygous c.1828_1829insGACT (p.Y610fs*1) frameshifting variant of the SOX5 gene. Sanger sequencing confirmed the variant to be de novo in origin. The variant was also unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_supporting). CONCLUSION The c.1828_1829insGACT (p.Y610fs*1) variant of the SOX5 gene probably underlay the pathogenesis of LAMSHF in this child. For children with delayed mental, language, intellectual, and motor development, genetic testing should be conducted to facilitate early diagnosis. Above finding has enriched the mutational spectrum of the SOX5 gene.
Humans ; SOXD Transcription Factors/genetics* ; Male ; Infant ; Exome Sequencing ; Genetic Testing ; Mutation

Objective:To explore the trend of Out-of-Pocket as a proportion of total health expenditure in Heilongjiang Province from 2013 to 2022,assessing the medical economic burden on residents and the equitable distribution of health resources.Methods:It employs statistical description and comparative research methods,collecting data on total health expenditure and Out-of-Pocketfor medical care in Heilongjiang Province from 2013 to 2022.A horizontal comparative analysis is conducted,comparing these trends with other provinces in the Northeast region and at the national level.Results:The Out-of-Pocket proportion in total health expenditure in Heilongjiang Province decreased from 41.56％in 2013 to 28.88％in 2022,indicating a downward trend;however,it remains higher than the national average during the same period.Additionally,the proportion of government health expenditure and social health expenditure has gradually increased,reflecting greater investment in the health sector by both the government and society.Conclusion:Although the Out-of-Pocket proportion in total health expenditure in Heilongjiang Province has decreased,the medical economic pressure on residents remains significant.It is recommended that the government continue to enhance health investment,optimize the health financing model,improve the efficiency of health services,reduce the burden of personal health expenditure,and achieve a more equitable distribution of health resources.

Objective:To explore the trend of Out-of-Pocket as a proportion of total health expenditure in Heilongjiang Province from 2013 to 2022,assessing the medical economic burden on residents and the equitable distribution of health resources.Methods:It employs statistical description and comparative research methods,collecting data on total health expenditure and Out-of-Pocketfor medical care in Heilongjiang Province from 2013 to 2022.A horizontal comparative analysis is conducted,comparing these trends with other provinces in the Northeast region and at the national level.Results:The Out-of-Pocket proportion in total health expenditure in Heilongjiang Province decreased from 41.56％in 2013 to 28.88％in 2022,indicating a downward trend;however,it remains higher than the national average during the same period.Additionally,the proportion of government health expenditure and social health expenditure has gradually increased,reflecting greater investment in the health sector by both the government and society.Conclusion:Although the Out-of-Pocket proportion in total health expenditure in Heilongjiang Province has decreased,the medical economic pressure on residents remains significant.It is recommended that the government continue to enhance health investment,optimize the health financing model,improve the efficiency of health services,reduce the burden of personal health expenditure,and achieve a more equitable distribution of health resources.

Objective:To explore the trend of Out-of-Pocket as a proportion of total health expenditure in Heilongjiang Province from 2013 to 2022,assessing the medical economic burden on residents and the equitable distribution of health resources.Methods:It employs statistical description and comparative research methods,collecting data on total health expenditure and Out-of-Pocketfor medical care in Heilongjiang Province from 2013 to 2022.A horizontal comparative analysis is conducted,comparing these trends with other provinces in the Northeast region and at the national level.Results:The Out-of-Pocket proportion in total health expenditure in Heilongjiang Province decreased from 41.56％in 2013 to 28.88％in 2022,indicating a downward trend;however,it remains higher than the national average during the same period.Additionally,the proportion of government health expenditure and social health expenditure has gradually increased,reflecting greater investment in the health sector by both the government and society.Conclusion:Although the Out-of-Pocket proportion in total health expenditure in Heilongjiang Province has decreased,the medical economic pressure on residents remains significant.It is recommended that the government continue to enhance health investment,optimize the health financing model,improve the efficiency of health services,reduce the burden of personal health expenditure,and achieve a more equitable distribution of health resources.

Objective:To explore the hematological phenotype and genotypic characteristics of five Chinese individuals with a rare thalassemia mutation HBB: c. 93-21G>A. Methods:A retrospective study was carried out on five individuals identified by the People′s Hospital of Yangjiang and Guangzhou Hybribio Co., Ltd. from May 2018 to September 2022. Routine blood test and hemoglobin electrophoresis were performed, and the genotypes of five subjects were determined by using PCR combined with reverse dot blotting (RDB), nested PCR, Gap-PCR and Sanger sequencing. This study was approved by Medical Ethics Cornmittee of the People′s Hospital of Yangjiang (Ethics No. 20240001).Results:Among the five individuals, hematological data of one was unavailable, and the remaining four had presented with microcytosis and hypochromia. The results of hemoglobin electrophoresis indicated that all of them had a HbA 2 level of ≥4.7%. Genetic analysis showed that one case had harbored compound heterozygous mutations of ααα anti3.7 triplet and HBB: c. 93-21G>A, one had compound heterozygous mutations of -α 3.7 and HBB: c. 93-21G>A, whilst the remaining three were heterozygous for the HBB: c. 93-21G>A mutation. Conclusion:The hematological phenotype of β-thalassemia carriers ( HBB: c. 93-21G>A) is similar to that of other β + thalassemia heterozygotes with mild β-thalassemia characteristics.

Objective:To explore the trend of Out-of-Pocket as a proportion of total health expenditure in Heilongjiang Province from 2013 to 2022,assessing the medical economic burden on residents and the equitable distribution of health resources.Methods:It employs statistical description and comparative research methods,collecting data on total health expenditure and Out-of-Pocketfor medical care in Heilongjiang Province from 2013 to 2022.A horizontal comparative analysis is conducted,comparing these trends with other provinces in the Northeast region and at the national level.Results:The Out-of-Pocket proportion in total health expenditure in Heilongjiang Province decreased from 41.56％in 2013 to 28.88％in 2022,indicating a downward trend;however,it remains higher than the national average during the same period.Additionally,the proportion of government health expenditure and social health expenditure has gradually increased,reflecting greater investment in the health sector by both the government and society.Conclusion:Although the Out-of-Pocket proportion in total health expenditure in Heilongjiang Province has decreased,the medical economic pressure on residents remains significant.It is recommended that the government continue to enhance health investment,optimize the health financing model,improve the efficiency of health services,reduce the burden of personal health expenditure,and achieve a more equitable distribution of health resources.

Objective:To explore the trend of Out-of-Pocket as a proportion of total health expenditure in Heilongjiang Province from 2013 to 2022,assessing the medical economic burden on residents and the equitable distribution of health resources.Methods:It employs statistical description and comparative research methods,collecting data on total health expenditure and Out-of-Pocketfor medical care in Heilongjiang Province from 2013 to 2022.A horizontal comparative analysis is conducted,comparing these trends with other provinces in the Northeast region and at the national level.Results:The Out-of-Pocket proportion in total health expenditure in Heilongjiang Province decreased from 41.56％in 2013 to 28.88％in 2022,indicating a downward trend;however,it remains higher than the national average during the same period.Additionally,the proportion of government health expenditure and social health expenditure has gradually increased,reflecting greater investment in the health sector by both the government and society.Conclusion:Although the Out-of-Pocket proportion in total health expenditure in Heilongjiang Province has decreased,the medical economic pressure on residents remains significant.It is recommended that the government continue to enhance health investment,optimize the health financing model,improve the efficiency of health services,reduce the burden of personal health expenditure,and achieve a more equitable distribution of health resources.

Objective:To explore the trend of Out-of-Pocket as a proportion of total health expenditure in Heilongjiang Province from 2013 to 2022,assessing the medical economic burden on residents and the equitable distribution of health resources.Methods:It employs statistical description and comparative research methods,collecting data on total health expenditure and Out-of-Pocketfor medical care in Heilongjiang Province from 2013 to 2022.A horizontal comparative analysis is conducted,comparing these trends with other provinces in the Northeast region and at the national level.Results:The Out-of-Pocket proportion in total health expenditure in Heilongjiang Province decreased from 41.56％in 2013 to 28.88％in 2022,indicating a downward trend;however,it remains higher than the national average during the same period.Additionally,the proportion of government health expenditure and social health expenditure has gradually increased,reflecting greater investment in the health sector by both the government and society.Conclusion:Although the Out-of-Pocket proportion in total health expenditure in Heilongjiang Province has decreased,the medical economic pressure on residents remains significant.It is recommended that the government continue to enhance health investment,optimize the health financing model,improve the efficiency of health services,reduce the burden of personal health expenditure,and achieve a more equitable distribution of health resources.