Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. Methods:A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072).Results:The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c. 2384G>T (p.Gly795Val) and c. 2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+ PM3+ PP3+ PP4; PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.

OBJECTIVE: To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. METHODS: A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072). RESULTS: The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c.2384G>T (p.Gly795Val) and c.2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+PM3+PP3+PP4; PM1+PM2_Supporting+PP3+PP4). CONCLUSION The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.
Humans ; Male ; Child ; ATP-Binding Cassette Transporters/genetics* ; Stargardt Disease/genetics* ; Heterozygote ; Mutation ; Exome Sequencing ; Macular Degeneration/congenital*

Objective:To analyze the data changes of tertiary hospitals,secondary hospitals and primary healthcare institutions in Shandong before and after the reform of Dignosis Related Group(DRG)/Diagnosis-Intervention Packet(DIP)payment method,and to explore the impact of the reform of DRG/DIP payment method on the effect of hierarchical diagnosis and treatment.Methods:Data were collected from 16 cities in Shandong Province for a total of 18 quarters in the first half of 2019-2023,including the percentage of expenditure of the health insurance fund,the percentage of discharges,and the sub-average hospitalization cost.Spatial panel models were constructed to conduct σ-convergence and absolute β-convergence analyses.Results:The convergence analysis showed that the inter-regional differences in the percentage of discharges,the percentage of fund expenditure and the average hospitalization cost of tertiary medical institutions were reduced;the regression coefficients of the three indicators in the absolute convergence analysis were significantly negative(β＜0,P＜0.01),indicating that the level of hierarchical diagnosis and treatment in various cities and regions has been equalized.Conclusion:The reform of DRG/DIP payment method reform has effectively optimized the allocation of medical resources in Shandong and reduced regional differences.It is needed to strengthen the effect of the payment method reform,reinforced the incentive of primary care and construct a full-cycle health management-oriented health insurance system in the future.

Objective:To analyze the data changes of tertiary hospitals,secondary hospitals and primary healthcare institutions in Shandong before and after the reform of Dignosis Related Group(DRG)/Diagnosis-Intervention Packet(DIP)payment method,and to explore the impact of the reform of DRG/DIP payment method on the effect of hierarchical diagnosis and treatment.Methods:Data were collected from 16 cities in Shandong Province for a total of 18 quarters in the first half of 2019-2023,including the percentage of expenditure of the health insurance fund,the percentage of discharges,and the sub-average hospitalization cost.Spatial panel models were constructed to conduct σ-convergence and absolute β-convergence analyses.Results:The convergence analysis showed that the inter-regional differences in the percentage of discharges,the percentage of fund expenditure and the average hospitalization cost of tertiary medical institutions were reduced;the regression coefficients of the three indicators in the absolute convergence analysis were significantly negative(β＜0,P＜0.01),indicating that the level of hierarchical diagnosis and treatment in various cities and regions has been equalized.Conclusion:The reform of DRG/DIP payment method reform has effectively optimized the allocation of medical resources in Shandong and reduced regional differences.It is needed to strengthen the effect of the payment method reform,reinforced the incentive of primary care and construct a full-cycle health management-oriented health insurance system in the future.

Objective:To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. Methods:A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072).Results:The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c. 2384G>T (p.Gly795Val) and c. 2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+ PM3+ PP3+ PP4; PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.

Lung cancer is a major cause of cancer-related mortality worldwide. Among patients with non-small cell lung cancer (NSCLC), approximately 3%-7% harbor anaplastic lymphoma kinase (ALK) gene fusions. In recent years, multiple tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with metastatic ALK-positive NSCLC. However, disease progression due to resistance remains a challenge. This article retrospectively analyzes a case of advanced lung adenocarcinoma with the echinoderm microtubule associated protein like 4 (EML4)-ALK fusion variant 3 (V3). The patient developed resistance to Lorlatinib treatment accompanied by mesenchymal-epithelial transition factor (MET) amplification. Effective tumor control was achieved with the combined use of Crizotinib and Lorlatinib, providing a valuable reference for further exploration of treatment strategies following resistance to ALK-TKIs in clinical practice.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/genetics* ; Aminopyridines/therapeutic use* ; Crizotinib/therapeutic use* ; Drug Resistance, Neoplasm/drug effects* ; Lactams/therapeutic use* ; Lung Neoplasms/genetics* ; Oncogene Proteins, Fusion/metabolism* ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-met/metabolism* ; Pyrazoles/therapeutic use*

Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors. In contrast, chemogenetic or optogenetic activation of spinal astrocytes triggers pain hypersensitivity, implying that bone cancer-induced astrocytic activation is involved in the development of bone cancer pain. IL-17A expression predominantly in spinal astrocytes, whereas its receptor IL-17 receptor A (IL-17RA) was mainly detected in neurons expressing VGLUT2 and PAX2, and a few in astrocytes expressing GFAP. Specific knockdown of IL-17A in spinal astrocytes blocked and delayed the development of bone cancer pain. IL-17A overexpression in spinal astrocytes directly induced thermal hyperalgesia and mechanical allodynia, which could be rescued by CaMKIIα inhibitor. Moreover, selective knockdown IL-17RA in spinal Vglut2 ⁺ or Vgat ⁺neurons, but not in astrocytes, significantly blocked the bone cancer-induced hyperalgesia. Together, our findings provide evidence for the crucial role of sex-independent astrocytic signaling in bone cancer pain. Targeting spinal astrocytes and IL-17A/IL-17RA-CaMKIIα signaling may offer new gender-inclusive therapeutic strategies for managing bone cancer pain.

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Objective To discuss the clinical value of systemic immune-inflammation index(SII)in predicting the prognosis of patients with extrahepatic cholangiocarcinoma(ECCA)treated with biliary stenting combined with 125I seeds implantation.Methods A total of 128 patients with unresectable ECCA,who received biliary stenting combined with 125I seeds implantation at the Interventional Department of the Affiliated Hospital of Xuzhou Medical University of China between August 2018 and August 2021,were enrolled in this study.The peripheral blood routine testing was performed within 3 days before operation,based on which the SII was calculated.Receiver operating characteristic(ROC)curve was applied to determine the optimal cut-off value of SII,based on which the patients were divided into high-SII group and low-SII group.Cox regression model was used to analyze the independent factors affecting patient prognosis.The Kaplan-Meier curve was plotted to analyze the one-year survival.Results The optimal cut-off value of SII was 1 050,the sensitivity was 66.0％,the specificity was 69.3％,and the area under ROC curve of SII was 0.676.The one-year survival rate of patients with ECCA in the high-SII group was significantly lower than that in the low-SII group(P＜0.05).Univariate Cox regression analysis indicated that vascular invasion,T stage,adjuvant chemotherapy,CA19-9,and preoperative SII were the important factors affecting the prognosis of patients with ECCA.Multivariate Cox regression analysis revealed that T stage,CA19-9,and preoperative SII were the independent risk factors for patient prognosis,while adjuvant chemotherapy was a protective factor.The Kaplan-Meier curves showed that the one-year survival rate in high-SII group was remarkably lower than that in the low-SII group.Conclusion Preoperative SII has an important value in evaluating the prognosis of patients with ECCA who are treated with biliary stenting combined with 125I seed implantation.(J Intervent Radiol,2023,32:1221-1225)