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 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 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 analyze the relationship between serum microRNA(miR)-204 and miR-200b lev-els and clinical efficacy in patients with oral submucosal fibrosis(OSF).Methods A total of 110 patients with OSF who visited Affiliated Hospital of Hebei Engineering University from December 2021 to December 2022 were collected as the study group,another 50 healthy people who underwent physical examination during the same period were collected as the control group.The quantitative real-time PCR(qRT-PCR)method was ap-plied to detect and compare the serum levels of miR-204 and miR-200b in the study group and the control group.The study group was divided into miR-204 high expression group and low expression group,and miR-200b high expression group and low expression group.The clinical efficacy,transforming growth factor β1(TGF-β1),interleukin-6(IL-6),clinical pathological features,and visual analogue scale(VAS)of patients with different levels of serum miR-204 and miR-200b were compared,and Spearman and Pearson methods were applied to analyze the correlation between serum miR-204 and miR-200b levels and various indicators in the study group.Results The serum level of miR-204 and miR-200b in the study group was obviously lower than those in the control group,and the difference was statistically significant(P＜0.05).The total effective rates of patients in the high expression group of miR-204 and the high expression group of miR-200b were both 100.00％,which were higher than the total effective rates of the low expression group of miR-204 and the low expression group of miR-200b(86.79％and 88.89％)respectively,and the differences were statisti-cally significant(P＜0.05).The results of univariate analysis showed that the serum levels of miR-204 and miR-200b in OSF patients with chewing betel nut,mouth opening degree≤28 mm,oral mucosal lesion area＞4 cm2,and VAS score＞3 points were obviously lower than those with non chewing betel nut,mouth opening degree＞28 mm,oral mucosal lesion area≤4 cm2,and VAS score≤3 points,and the differences were statis-tically significant(P＜0.05).The levels of TGF-β1 and IL-6 in patients with high expression of miR-204 and miR-200b were obviously lower than those in patients with low expression of miR-204 and miR-200b,and the differences were statistically significant(P＜0.05).The correlation analysis results showed that the serum levels of miR-204 and miR-200b in patients with OSF were negatively correlated with oral mucosal lesion are-a,VAS score,TGF-β1,IL-6(P＜0.05),and positively correlated with mouth opening degree(P＜0.05).Conclusion The serum levels of miR-204 and miR-200b in patients with OSF are closely related to clinical ef-ficacy,and when the serum levels of miR-204 and miR-200b increase,OSF patients have better clinical efficacy.

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.