1.Proteome-wide Mendelian randomization analysis of plasma proteins identifies biomarkers for anxiety disorders
Xuelian LI ; Min DENG ; Rongting RAN ; Yuqian HE ; Geman WANG ; Yujie LI ; Zhili ZOU
Sichuan Mental Health 2026;39(1):63-69
BackgroundAnxiety disorder is a common mental disorder, with its prevalence showing a continuous upward trend, significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice, the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases, however, the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders, and to elucidate the associated biological pathways, in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus (pQTL) data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database, and the genome-wide association studies (GWAS) data of 50 486 patients with anxiety disorders and 330 460 healthy controls, the inverse-variance weighted (IVW) method was used as the main analysis method, supplemented by MR-Egger method, weighted median method, simple model method, and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test, MR-Egger intercept test, MR-PRESSO test, and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these, SPATA9 (OR=0.856, 95% CI: 0.784–0.934, P<0.01) and PDE5A (OR=0.911, 95% CI: 0.864–0.961, P<0.01) were identified as protective factors, while CRYGD (OR=1.209, 95% CI: 1.095–1.334, P<0.01), BTN3A3 (OR=1.045, 95% CI: 1.018–1.073, P<0.01), SERPINB13 (OR=1.102, 95% CI: 1.040–1.168, P<0.01), ERBB4 (OR=1.283, 95% CI: 1.109–1.484, P<0.01), LSAMP (OR=1.096, 95% CI: 1.037–1.158, P<0.01), ICOSLG (OR=1.283, 95% CI: 1.104–1.490, P<0.01), DNAJB11 (OR=1.172, 95% CI: 1.076–1.277, P<0.01), and TREML1 (OR=1.115, 95% CI: 1.054–1.179, P<0.01) were identified as risk factors. The sensitivity analysis showed that the results were robust, with no heterogeneity (Cochran's Q test P>0.05) or pleiotropy (MR-Egger intercept test P>0.05). Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction, lymphocyte proliferation, cell membrane structure and synaptic function, as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.
2.Research progress of terahertz spectroscopy in oral microbial detection
HE Tingjuan ; LEI Lei ; HU Tao ; CHENG Ran
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(5):483-493
Microorganisms are closely associated with human health, and their pathogenicity is a key factor in various infectious diseases, particularly in dentistry, where they contribute to common conditions such as dental caries, periodontitis, and oral mucosal diseases. Accurate and rapid microbial detection is crucial for early diagnosis, targeted therapy, and disease prevention. Conventional methods, including bacterial culture and molecular biological assays, offer specificity but are limited by long detection cycles, complex procedures, and dependence on laboratory conditions. Terahertz (THz) spectroscopy has emerged as a promising tool in microbial detection due to its non-ionizing nature, high sensitivity, and specific responses to water molecules and biomacromolecules. Integrating THz time-domain spectroscopy, near-field imaging, and metamaterial-enhanced techniques, studies have demonstrated the ability of this approach to effectively distinguish bacteria, fungi, and yeast, differentiate gram-positive and gram-negative bacteria, and even assess bacterial viability. Machine learning has further enhanced feature extraction and classification accuracy, and THz-based methods have shown notable advantages in multi-class microbial identification, detection of antibiotic-resistant strains, and quantitative analysis of microbial concentrations. However, current THz technologies are still constrained by strong water absorption, limited penetration depth, and the lack of standardized spectral databases. Future efforts should focus on mitigating water background interference, improving detection in complex samples, and establishing unified microbial spectral standards. This review systematically summarizes the latest advances of THz technologies in microbial detection, analyzes their mechanisms, advantages, and translational challenges, and proposes directions for future research.
3.Analysis of soil-borne nematode infection status among rural communities in Yubei, Chongqing
Dan JIANG ; Yong-dong HAO ; Sen-ping YANG ; Xiao-yuan SU ; Hua-jun BAI ; Bo LYU ; Ya-ling RAN ; He-yi GUAN ; Ling HU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):85-89
Objective To analyze the infection status and epidemic trends of soil-borne nematode infections in Yubei, Chongqing City, in 2010,2021, and 2022. Methods The local populations from four survey sites of four towns in 2010 and five sites of five towns in 2021 and 2022 were surveyed regarding their basic information using a unified form. Fecal samples of the participants were collected and tested for soil-borne nematode infections using the modified Kato-Katz thick smear method. Results In 2010, 2 049 participants were surveyed, followed by 1 000 participants in 2021 and 2022. The overall prevalence of parasitic infections declined significantly from 3.86% to 0.20%. In 2010, soil-transmitted nematode included hookworms(3.81%) and roundworms(0.29%). In 2021, the infection rates of roundworms and hookworms were 1.70% and 0.10% respectively. Notably, only Ascaris was identified in 2022(0.20%). The≥60 age group consistently exhibited the highest infection rates across all surveys, followed by the 40-59 age group. The infection rates of males in the three surveys were 3.31%,1.92%, and 0.20% respectively, and those of females were 4.37%, 1.46%, and 0.20% respectively. There was no statistically significant difference in the infection rates between males and females. Educational attainment was inversely associated with infection; in 2010, the highest prevalence was observed among those with primary education or below, whereas in 2021, illiterate or semi-literate individuals showed the highest susceptibility. The occupational distribution of infections in 2010 indicated that retirees (8.33%), farmers(4.86%), and homemakers or unemployed individuals(3.45%)were the most affected. However, in 2021 and 2022, farmers emerged as the predominant occupational group with soil-transmitted nematode infections. Conclusions The infection rate of soil-borne nematodes showed a decreasing trend in Yubei, and the infection species changed from hookworms in 2010 to Ascaris in 2022. Farmers, the elderly, and people with low education levels should continue to be the focus of preventive and control efforts.
4.Study on the brain functional network and structural-functional coupling in children with drug-resistant epilepsy
Xuhong LI ; Jianhui XIAO ; Heng LIU ; Yulun HE ; Haifeng RAN ; Yuxin XIE ; Guiqin CHEN ; Qian′e YU ; Zhen ZENG ; Wenfu LI ; Tijiang ZHANG
Chinese Journal of Radiology 2025;59(2):184-191
Objective:To investigate the changes in brain functional network and structural-functional network coupling in children with drug-resistant epilepsy (DRE), and to analyze their correlation with cognitive function, disease duration, and age of onset.Methods:This study was a cross-sectional study. Clinical and imaging data of 19 children with DRE who received consultation and treatment at the Affiliated Hospital of Zunyi Medical University from August 2021 to August 2023 (DRE group) were prospectively included. Another 27 age-and sex-matched healthy children were collected as the healthy control group. All subjects had 3D-T 1WI, T 2 fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) scans and Wechsler Intelligence Scale assessments. Independent sample t-test and Mann-Whitney U test were used to analyze the global and local topological attributes, as well as the structural-functional coupling (SFC) values at the whole brain and modular levels in two groups. Correlations between abnormal resting state brain functional network indicators and the Wechsler Intelligence Scale score [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ)], disease duration and age of onset was evaluated using a Spearman or Pearson correlation analysis. Results:Compared to the healthy control group, DRE group exhibited decreased VCI, PRI, WMI, PSI, FSIQ and the differences were all statistically significant (all P<0.05). Both brain functional networks had small world attributes. There was a statistically significant difference in the area under the curve of sparsity of degree centrality (DC) in the left pallidum between the DRE group and healthy control group (2.998±0.942, 4.992±1.945, t=-4.07, FDR corrected P<0.05). Compared with the control group, the DRE group had decreased SFC within the limbic network (LN) ( P<0.05), increased SFC within the sensorimotor (SMN) ( P<0.05), decreased SFC between the default mode network-LN ( P<0.05), and increased SFC between the SMN-attentional network (AN) ( P<0.05). There was no statistically significant difference in SFC at the whole brain level between the two groups. Correlation analysis indicated that DC in left pallidum in DRE group negatively correlated with the PSI ( r=-0.537, P=0.018), and SFC between the SMN and AN demonstrated a negative correlation with age of onset ( r=-0.537, P=0.018). Conclusion:The altered DC in left pallidum may be related to cognitive impairment in children with DRE, providing biomarker information for the study of neural mechanisms in children with DRE.
5.Predictive value of different comorbidity indices for hospitalization due to acute exacerbations in chronic obstructive pulmonary disease patients with comorbidities
Qinglin CHEN ; Ruoyan ZHANG ; Xiaofang LIU ; Xiujuan YAO ; Yanyun HE ; Ran LI ; Xichun ZHANG
Chinese Journal of General Practitioners 2025;24(7):823-833
Objective:To evaluate the predictive efficacy of different comorbidity indices for hospitalization due to acute exacerbations in chronic obstructive pulmonary disease (COPD) patients with comorbidities (CO-COPD).Methods:This retrospective cohort study included 259 stable COPD patients with comorbidities from Beijing Tongren Hospital, Capital Medical University, between October 2021 and September 2023, all with ≥1-year follow-up. Patients were categorized into hospitalized ( n=75) and non-hospitalized ( n=184) groups based on acute exacerbation events. Clinical characteristics, comorbidities, and comorbidity indices, including Charlson Comorbidity Index (CCI), COPD-specific Comorbidity Test (COTE), and comorbidities in chronic obstructive lung disease index (COMCOLD) were compared between two goups. Risk facors of hospitalization due to acute exacerbations were analyzed by Cox regression. Modified indices were developed by incorporating additional respiratory comorbidities (asthma, bronchiectasis, lung cancer) weighted by hazard ratios (HRs) from Cox reguression. The predictive performance of different comorbidity indices for hospitalization was assessed by receiver operating characteristic (ROC) curves. Results:Hospitalized patients exhibited lower BMI, FEV 1% predicted, and FEV 1/FVC (all P<0.05), alongside higher modified British Medical Research Coucil (mMRC) scores and COPD assessment test (CAT) scores, eosinophil counts, and Global Initiative for Chronic Obstructive Lung Disease, (GOLD)severity ( t=3.73, Z=-3.43, Z=-2.43, Z=-11.10, Z=-11.32, Z=-1.80, χ2=17.62, all P<0.05); and also higher use rates of inhaled corticosteroid (ICS) and systemic oral corticosteroid (OCS) ( χ2=5.48, 7.15, all P<0.05). The comorbidities of asthma, bronchiectasis, lung cancer, hypertension, coronary atherosclerotic heart disease, anxiety and depression in hospitalized group were significantly higher ( χ2=22.49, 18.30, 15.63, 5.10, 4.68, 7.46, 5.16, all P<0.05), along with the increased CCI and COTE index ( P<0.05). Comorbid asthma, bronchiectasis, and lung cancer were independent risk factors for hospitalization ( HR=1.841, 2.924, and 2.076, respectively; all P<0.05). Original CCI and COTE showed moderate predictive value ( AUC=0.609 and 0.655), while modified CCI, COTE, and COMCOLD demonstrated improved performance ( AUC=0.730, 0.760, and 0.713, respectively). At optimal cutoffs (modified CCI>3.5, COTE>4.5, COMCOLD>6.5), sensitivities were 61.3%, 76.0%, and 58.7%, with specificities of 70.1%, 61.4%, and 72.3%. Age-stratified analysis revealed enhanced predictive utility of modified indices across age groups. Conclusions:CCI, COTE, and COMCOLD provide modest predictive value for hospitalization in CO-COPD. Modified indices incorporating respiratory comorbidities significantly improve risk stratification, offering clinical utility for identifying high-risk patients in primary care settings.
6.Association of serum exosomal miR-122-5p with the prognosis of hepatic confluent necrosis and fibrosis in patients with chronic hepatitis B
Quanwei HE ; Ran XU ; Wei HAN ; Sihao WANG ; Yan CHEN ; Yongping YANG
Journal of Clinical Hepatology 2025;42(5):888-899
Objective To investigate the association of serum exosomal microRNAs(miRNAs)with hepatic inflammatory injury and histological outcomes in patients with chronic hepatitis B(CHB).Methods Peripheral serum samples were collected from six healthy adults and six patients with CHB,and size exclusion chromatography was used to extract exosomes.Small RNA sequencing and transcriptomic analysis were used to identify the serum exosomal miRNAs associated with liver inflammatory injury and fibrosis,and quantitative real-time PCR was used for validation in a mouse model of acute liver injury induced by lipopolysaccharide/D-galactosamine,a rat model of liver fibrosis induced by carbon tetrachloride,and 84 CHB patients undergoing liver biopsy twice before and after treatment.The independent-samples t test was used for comparison of normally distributed continuous data between two groups;an analysis of variance was used for comparison between multiple groups,and the Tukey test was used for further comparison between two groups.The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the Kruskal-Wallis H test was used for comparison between multiple groups,and the Dunn test was used for further comparison between two groups.The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.The univariate and multivariate Logistic regression analyses were used to investigate influencing factors.Results Abnormal expression of serum exosomal miR-122-5p was observed in patients with CHB,and it was downregulated in patients with confluent necrosis and advanced fibrosis.In the mouse model of acute liver injury and the rat model of liver fibrosis,compared with the control group,the model group had a significant reduction in the expression level of miR-122-5p in the liver(P=0.048 and 0.014),and compared with the patients with mild liver injury,the patients with severe confluent necrosis and advanced fibrosis showed a significant reduction in the expression level of miR-122-5p in liver tissue(P<0.05).Among the 84 CHB patients,the patients with severe hepatic confluent necrosis or advanced liver fibrosis had a significantly lower expression level of serum exosomal miR-122-5p than those with mild liver injury(P<0.001 and P=0.003).The multivariate Logistic regression analysis showed that the expression level of miR-122-5p was an independent influencing factor for confluent necrosis(odds ratio[OR]=0.001,95%confidence interval[CI]:0.000-0.037,P=0.005)and liver fibrosis degree(OR=0.568,95%CI:0.331-0.856,P=0.019).In addition,compared with the patients with low expression of miR-122-5p,the patients with high expression of miR-122-5p before treatment had a significantly higher reversal rate of liver fibrosis after 72 weeks of antiviral therapy(64.3%vs 38.1%,P=0.029).Conclusion Serum exosomal miR-122-5p in CHB patients is closely associated with the progression of hepatic confluent necrosis and fibrosis,and the reduction in the expression level of miR-122-5p may aggravate hepatic confluent necrosis,promote the progression of fibrosis,and affect the histological outcome of CHB patients after antiviral therapy.
7.Influence of different ratios of CA to saline on CCTA image quality in dual-flow injection technique
Yuan YUAN ; Hao LU ; Yi HE ; Ran LI ; Zhaohui ZHONG
China Medical Equipment 2025;22(8):29-35
Objective:To investigate the influence of different ratios of contrast agent(CA)to saline on image quality of coronary computed tomography angiography(CCTA)in dual-flow injection technique.Methods:A prospective study included 102 patients who were clinically diagnosed as suspected coronary heart disease(CHD)to undergo CCTA scan at Beijing Friendship Hospital,Capital Medical University,between March 2024 and October 2024.Ultimately,90 patients were enrolled,who adopted CA injection protocol of dual-flow injection technique.Patients were randomly divided into three groups using a random number table,with 30 patients in each group.The different ratios of CA to saline were adopted,which were respectively Group A(1:9),Group B(2:8),and Group C(3:7).For the reconstructed images,the computed tomography(CT)values of heart-related anatomical structures,which included superior vena cava,right atrium,right ventricle,left atrium,left ventricle,interventricular septum and each segment of the coronary artery,were measured respectively.At the same time,two radiologists,who possessed over 10 years of diagnostic experience of CCTA examination,conducted subjective evaluations for image quality.For the cases of disagreement,the consensus between them was reached through discussion.Results:In three groups,the total CA doses were respectively(42.75±5.22)ml,(47.08±5.83)ml and(50.64±6.29)ml,and the differences of that among the three groups was statistically significant(F=13.964,P<0.05).The differences of CT values of superior vena cava,right atrium,right ventricle,left atrium,left ventricle and aorta among three groups were significant(F=29.141,24.194,39.308,9.643,8.178,6.881,P<0.05).There were significant differences in the CT values of the proximal,mid,and distal segments of the left anterior descending(LAD),and the proximal and mid segments of the left circumflex(LCx)and right coronary artery(RCA)among three groups(F=7.114,9.106,3.851,6.075,4.025,7.349,5.756,P<0.05).However,there was not statistically significant difference was found among the three groups in the CT value of the distal segments of the LCx and RCA(P>0.05).There were significant differences in the subjective scores for the superior vena cava,right atrium and right ventricle among the three groups(H=8.939,29.105,32.180,P<0.05).The number of cases with 3-4 points at the superior vena cava,right atrium and right ventricle were respectively 25(83.3%),29(96.7%)and 30(100%)in group B,there was no case with 1 point.In addition,the imaging quality of right heart in group B was better than that in group A and C.There were no significant differences at left atrium,left ventricle,and each segment of coronary artery among three groups(P>0.05).Conclusion:For patients with clinically non-extreme body weight,the selection of the ratio(2:8)of CA to saline can effectively show relevantly anatomic structures of heart,and coronary artery vessels,including the right heart system,which belongs to the optimal solution.
8.Construction of a risk prediction model for premature delivery after transvaginal cervical cerclage
Ran HUANG ; He LI ; Xiaoyang ZHAO ; Xiaolin DENG ; Hong LI
China Modern Doctor 2025;63(32):37-40
Objective To explore the risk factors for premature delivery after transvaginal cervical cerclage,construct and validate a predictive model.Methods A total of 209 single-tonsus cervicitis patients who underwent McDonald cervical ring ligation at the Third Affiliated Hospital of Zhengzhou University from January 2022 to December 2024 were selected as subjects,and they were divided into preterm group(n=86)and full-term group(n=123)according to the postoperative pregnancy outcomes.LASSO regression analysis was used to screen variables,and the prediction model was constructed by multivariate Logistic regression.The performance of the model was evaluated by receiver operating characteristic curve,calibration curve and decision curve.Results Body mass index,amniotic sac protrusion,preoperative white blood cell,and cervical length before cerclage<25mm were identified as independent risk factors for preterm birth(P<0.05).The prediction model demonstrated an area under the curve of 0.823(95%CI:0.765-0.881),with sensitivity of 77.91%and specificity of 77.24%.Both the calibration curve and decision analysis confirmed the model's strong consistency and clinical net benefit.Conclusion The predictive model constructed in this study has a good predictive effect and can be used as a reference for the stratification of preterm risk after cervical cerclage.
9.Immunological features of a patient with CHARGE syndrome caused by the CHD7 gene c.5122C>T nonsense mutation
Chenlin LI ; Xin CHEN ; Qing LIU ; Ran CHEN ; Wenli HE ; Lin TONG ; Yulin LI ; Zhengxia PAN ; Yunfei AN ; Lu ZHAO
Immunological Journal 2025;41(2):97-102,122
Objective To analyze the clinical and immunological characteristics of a rare case of CHARGE syndrome,we summarize the genotype and phenotype in the Chinese patient population,and explore the underlying immunopathogenic mechanisms.Methods Clinical data from a pediatric patient with CHARGE syndrome were collected and analyzed.A comprehensive analysis of the Chinese patient population was conducted.Gene analysis and immunological characterization were performed using flow cytometry,deep sequencing,and quantitative PCR.Results The proband was a premature female infant whose primary clinical manifestations included congenital heart disease,recurrent respiratory infections,respiratory failure,airway dysplasia,hearing impairment,and bilateral choroidal coloboma.Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the CHD7 gene,c.5122C>T(p.Gln1708Ter),classified as pathogenic according to ACMG criteria.Immunological studies indicated impaired thymic output of T cells,significant alterations in the number and proportion of CD8+T cell subsets,increased apoptosis,and defective activation and production of key effector cytokines such as IFN-γ by CD8+T cells.However,no significant abnormalities were observed in peripheral lymphocyte proliferation.Conclusion CHARGE syndrome is a rare autosomal dominant genetic disorder primarily caused by mutations in the CHD7 gene.The main clinical features include ocular defects,cardiac disease,choanal atresia/cleft lip and palate,growth retardation,gonadal hypoplasia,and ear anomalies.This case study suggests that CHARGE syndrome is associated with abnormalities in the development,apoptosis,and effector functions of immune cells.
10.Analysis of transcriptome and chromatin accessibility changes during the differentiation of human embryonic stem cells into neural progenitor cells
Linying LI ; Xiaodong CAI ; Ran TONG ; Chen YANG ; Zhiming WANG ; Xiaoyu HE ; Ziyue MA ; Feng ZHANG ; Lingjie LI ; Junmei ZHOU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(4):387-403
Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.


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