1.Multimodal investigation of stress-induced RNA-brain covariance and its association with depression vulnerability
Yun LIU ; Xijuan XIA ; Kehan YAN ; Yang JI ; Yifeng LUO ; Zhihong CAO ; Yuefeng LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(9):790-797
Objective:To explore the RNA expression and alterations in brain structure in individuals who have experienced stressful life events (SLE), as well as the correlation patterns between them and their association with the occurrence of depression.Methods:Prospectively, a total of 80 SLE subjects were recruited from the psychiatry and psychology clinic of the Jiangsu University Affiliated Yixing Hospital between January 2021 and December 2022, with 16 normal controls (NC) enrolled concurrently. The 17 items Hamilton depression scale (HAMD-17) and social readjustment rating scale (SRRS) were used to assess depressive symptoms and stress levels. RNA sequencing information of peripheral blood and imaging data at baseline were collected. Based on whether depression occurred during the 2-year follow-up period, SLE subjects were divided into the SLE-depression group ( n=15) and the SLE-non-depression group ( n=65). Differentially expressed genes (DEGs) were screened using differential analysis and protein-protein interaction (PPI) networks. Fractional anisotropy (FA) of white matter tracts and gray matter volume (GMV) were extracted using tract-based spatial statistics and voxel-based morphometry.Using analysis of variance compared inter-group differences in gene expression, GMV and white matter FA values. Partial correlation analysis was used to explore correlations between DEGs, altered GMV and white matter microstructure. Gene set enrichment analysis (GSEA) was performed on key genes to identify potential biological pathways. Propensity score matching constructed sensitivity subgroups to verify result robustness. Results:The SLE-depression group showed significantly higher SRRS and HAMD-17 scores at baseline and at the end of follow-up compared to the SLE-non-depression group and the NC group ( H=47.773, 35.427, 41.114, all P<0.05). Expression levels of IL-10 (2.12±0.28, 2.43±0.44), EZH2 (2.11±0.43, 2.45±0.51), NCAM1 (3.60±0.30, 3.03±0.39), CD3E (4.95±0.37, 4.57±0.48), CCK (3.29±0.28, 3.02±0.42), and CX3CR1 (5.55±0.40, 5.91±0.34) were significantly different between the SLE-depression group and SLE-non-depression group( F=5.549~28.371, all P<0.05). Compared with the SLE-non-depression group, the SLE-depression group exhibited significantly lower FA values in the genu of the corpus callosum (0.29±0.04, 0.31±0.04) and the left uncinate fasciculus (0.31±0.02, 0.33±0.02), as well as significantly smaller GMV in the right hippocampus (0.29±0.07, 0.33±0.06), bilateral middle frontal gyrus (left: 0.27±0.05, 0.31±0.05; right: 0.28±0.06, 0.32±0.06), right insula (0.36±0.03, 0.38±0.04), and left precentral gyrus (0.19±0.04, 0.24±0.05) ( F=4.593-12.064, all P<0.05, FDR correction). GMV in the right anterior cingulate and paracingulate gyri was significantly larger than that in the SLE-non-depression group (0.34±0.05, 0.29±0.06) ( F=6.704, P=0.034, FDR correction). Partial correlation analysis revealed significantly stronger correlations between hub DEGs and altered brain regions in the SLE-depression group ( r=0.017-0.801) compared to the SLE-non-depression group ( r=0.002-0.382), with a statistically significant difference ( U=629, P<0.001; Cliff's Delta=0.454). GSEA indicated that the aforementioned genes were primarily involved in pathways including the ribosome, spliceosome, ribosome biogenesis in eukaryotes, and neuroactive ligand-receptor interaction. Sensitivity analysis confirmed that the above results remained statistically significant after balancing sample sizes (all P<0.05). Conclusion:The SLE-depression group showed specific RNA expression and brain structure alterations compared to the SLE-non-depression group, and the correlation between RNA and brain structure was significantly enhanced in the SLE-depression group. This suggests that the correlation between genes and brain structure in the SLE population may be related to their susceptibility to depression.
2.Clinical Features of Idiopathic Pulmonary Hypertension Patients With Cardiovascular Comorbidities
Qi WANG ; Zhihua HUANG ; Sicheng ZHANG ; Qin LUO ; Zhihong LIU
Chinese Circulation Journal 2025;40(8):762-769
Objectives:To investigate the clinical characteristics of patients with idiopathic pulmonary arterial hypertension(IPAH)with cardiovascular comorbidities.Methods:A total of 150 patients with IPAH admitted to Fuwai Hospital,Chinese Academy of Medical Sciences from October 2014 to June 2024 were enrolled in this retrospective study.The clinical variables,cardiac structure and hemodynamic characteristics were analyzed and compared between IPAH patients with or without cardiovascular comorbidities.Results:The mean age of the 150 patients was(35.9±12.5)years,73.3%of whom were female.There were 88(58.7%)IPAH patients with cardiovascular comorbidities.Compared to those without cardiovascular comorbidities(n=62),patients with cardiovascular comorbidities were older([38.9±12.3]years vs.[31.7±11.9]years,P=0.001),and N-terminal pro-B-type natriuretic peptide level was higher(1 469.0[656.8,2 615.8]pg/ml vs.923.5[304.4,1 958.8]pg/ml,P=0.006).The hemodynamic examination indicated that patients with cardiovascular comorbidities were featured with higher mean right atrial pressure(6.0[3.3,9.0]mmHg[1 mmHg=0.133 kPa]vs.4.0[3.0,6.3]mmHg,P=0.006),but lower mixed venous oxygen saturation([67.0±7.0]%vs.[70.3±6.9]%,P=0.010)and cardiac index(2.4[1.9,2.9]L/[min·m2]vs.2.8[2.3,3.8]L/[min·m2],P=0.013).Among IPAH patients with cardiovascular comorbidities,compared to patients with 1 comorbidity,patients with≥2 comorbidities were older(51.0[40.0,63.3]years vs.35.0[29.3,43.8]years,P<0.001),left atrial anteroposterior diameter([35.6±4.8]mm vs.[30.4±4.4]mm,P<0.001)and left end-diastolic anteroposterior diameter([40.8±7.5]mm vs.[35.8±5.5]mm,P=0.006)were larger.In patients with cardiovascular comorbidities,hypertension was the most common comorbidity(48.9%).Conclusions:Patients with IPAH and cardiovascular comorbidities exhibit aging characteristics.A series of cardiovascular comorbidities,including hypertension,significantly impact the clinical features,cardiac structural parameters,and hemodynamic status of IPAH.The assessment and management of comorbidities in IPAH patients should be prioritized in the future clinical practice.
3.Pulmonary Hypertension in Adult With Late-onset Glycogen Storage Disease Type Ⅱ(Pompe Disease):a Case Report
Lixing HU ; Qin LUO ; Zhihui ZHAO ; Li DENG ; Tao YANG ; Qing ZHAO ; Zhihong LIU
Chinese Circulation Journal 2025;40(8):813-815
Glycogen storage disease type Ⅱ,also known as Pompe disease,is an autosomal recessive metabolic myopathy with pulmonary hypertension as a rare complication.We reported a case of pulmonary hypertension in adult with late-onset glycogen storage disease type Ⅱ.Her arterial blood gas results indicated type Ⅱ respiratory failure,lung function indicated severe restricted ventilation dysfunction,sleep monitoring indicated severe sleep apnea hypopnea,severe nocturnal hypoxemia,echocardiography-derived systolic pulmonary pressure was 62 mmHg(1 mmHg=0.133 kPa),electromyography indicated myogenic lesion,and whole exon sequencing indicated GAA gene mutation.Supportive therapy and enzyme replacement therapy are applied in this patient.
4.Expert Consensus on the Medical Quality Control Indicator System for Pulmonary Arterial Hypertension in Chinese Adults
Chinese Circulation Journal 2025;40(8):746-751
To enhance the standardization and management of diagnosis and treatment for pulmonary arterial hypertension in Chinese adults,Working Group on Pulmonary Hypertension,National Center for Cardiovascular Quality Improvement,National Center for Cardiovascular Diseases,China Specialized Alliance of Pulmonary Hypertension and National Expert Committee for Cardiovascular Diseases,Professional Committee of Right Heart and Pulmonary Vascular Diseases established a working group.Guided by the"structure-process-outcome"theoretical framework,the group established a medical quality control indicator system for pulmonary arterial hypertension in Chinese adults through literature review,expert discussions,and Delphi expert consultation.The system ultimately comprises 32 primary indicators and 6 secondary indicators.It encompasses three categories of indicators:structure,process,and outcome,with the process indicators further covering diagnosis and risk stratification,initial treatment,and follow-up.This quality control indicator system has laid the theoretical foundation for improving the medical quality of care for Chinese adult patients with pulmonary arterial hypertension,though it still requires validation and refinement during clinical practice.
5.Effectiveness and Safety of Recombinant Human Brain Natriuretic Peptide for the Treatment of Patients With Right Heart Failure Caused by Pulmonary Arterial Hypertension
Lixing HU ; Qing ZHAO ; Zhihui ZHAO ; Qin LUO ; Li DENG ; Ping JIANG ; Zhihong LIU
Chinese Circulation Journal 2025;40(8):782-786
Objectives:To observe the effectiveness and safety of recombinant human brain natriuretic peptide(rhBNP)for the treatment of patients with right heart failure caused by pulmonary arterial hypertension(PAH).Methods:A total of 421 patients with right heart failure caused by PAH who were hospitalized in Fuwai Hospital from January 2019 to June 2024 were retrospectively included in this study.All patients were treated with rhBNP on top of conventional therapy.24 h urine volume,body weight,liver and renal function index,electrolyte,uric acid,red blood cell distribution width(RBCDW),cardiac function,blood pressure and heart rate before and after the treatment of rhBNP were compared.Clinical symptoms,signs and the occurrence of adverse events during treatment were also observed.Results:Compared with baseline,after treatment with rhBNP,the 24 h urine volume increased.The levels of body weight,transaminase,total bilirubin,direct bilirubin,uric acid,RBCDW,systolic blood pressure,heart rate,and N-terminal pro-B-type natriuretic peptide significantly decreased(all P<0.05).There were no statistically significant differences in the levels of serum creatinine,and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio(both P>0.05).Dyspnea and lower limbs edema were improved in 75.2%cases(227/302)and 66.9%cases(281/420)respectively.The incidence of adverse events and severe adverse events during rhBNP treatment were 1.2%(5/421)and 0.5%(2/421)respectively.Conclusions:Adding rhBNP on top of standard medication can effectively increase 24 h urine volume,reduce body weight,improve some prognostic indicators,improve the clinical symptoms and signs of heart failure without negatively affecting the renal function in right heart failure patients caused by PAH.Blood pressure should be closely monitored during the treatment process.
6.Pay Attention to the Management of Patients With Idiopathic Pulmonary Arterial Hypertension Complicated With Cardiopulmonary Diseases
Chinese Circulation Journal 2025;40(8):729-731
With the passage of time,the disease spectrum of comorbidities in patients with arterial pulmonary arterial hypertension has gradually become more diversified,posing significant challenges to the diagnosis,differential diagnosis,and management of the disease.This article introduces the key points of differential diagnosis and the precautions for treatment of patients with arterial pulmonary arterial hypertension complicated by cardiopulmonary diseases,aiming to further improve the individualized diagnosis and treatment of pulmonary arterial hypertension.
7.Multimodal investigation of stress-induced RNA-brain covariance and its association with depression vulnerability
Yun LIU ; Xijuan XIA ; Kehan YAN ; Yang JI ; Yifeng LUO ; Zhihong CAO ; Yuefeng LI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(9):790-797
Objective:To explore the RNA expression and alterations in brain structure in individuals who have experienced stressful life events (SLE), as well as the correlation patterns between them and their association with the occurrence of depression.Methods:Prospectively, a total of 80 SLE subjects were recruited from the psychiatry and psychology clinic of the Jiangsu University Affiliated Yixing Hospital between January 2021 and December 2022, with 16 normal controls (NC) enrolled concurrently. The 17 items Hamilton depression scale (HAMD-17) and social readjustment rating scale (SRRS) were used to assess depressive symptoms and stress levels. RNA sequencing information of peripheral blood and imaging data at baseline were collected. Based on whether depression occurred during the 2-year follow-up period, SLE subjects were divided into the SLE-depression group ( n=15) and the SLE-non-depression group ( n=65). Differentially expressed genes (DEGs) were screened using differential analysis and protein-protein interaction (PPI) networks. Fractional anisotropy (FA) of white matter tracts and gray matter volume (GMV) were extracted using tract-based spatial statistics and voxel-based morphometry.Using analysis of variance compared inter-group differences in gene expression, GMV and white matter FA values. Partial correlation analysis was used to explore correlations between DEGs, altered GMV and white matter microstructure. Gene set enrichment analysis (GSEA) was performed on key genes to identify potential biological pathways. Propensity score matching constructed sensitivity subgroups to verify result robustness. Results:The SLE-depression group showed significantly higher SRRS and HAMD-17 scores at baseline and at the end of follow-up compared to the SLE-non-depression group and the NC group ( H=47.773, 35.427, 41.114, all P<0.05). Expression levels of IL-10 (2.12±0.28, 2.43±0.44), EZH2 (2.11±0.43, 2.45±0.51), NCAM1 (3.60±0.30, 3.03±0.39), CD3E (4.95±0.37, 4.57±0.48), CCK (3.29±0.28, 3.02±0.42), and CX3CR1 (5.55±0.40, 5.91±0.34) were significantly different between the SLE-depression group and SLE-non-depression group( F=5.549~28.371, all P<0.05). Compared with the SLE-non-depression group, the SLE-depression group exhibited significantly lower FA values in the genu of the corpus callosum (0.29±0.04, 0.31±0.04) and the left uncinate fasciculus (0.31±0.02, 0.33±0.02), as well as significantly smaller GMV in the right hippocampus (0.29±0.07, 0.33±0.06), bilateral middle frontal gyrus (left: 0.27±0.05, 0.31±0.05; right: 0.28±0.06, 0.32±0.06), right insula (0.36±0.03, 0.38±0.04), and left precentral gyrus (0.19±0.04, 0.24±0.05) ( F=4.593-12.064, all P<0.05, FDR correction). GMV in the right anterior cingulate and paracingulate gyri was significantly larger than that in the SLE-non-depression group (0.34±0.05, 0.29±0.06) ( F=6.704, P=0.034, FDR correction). Partial correlation analysis revealed significantly stronger correlations between hub DEGs and altered brain regions in the SLE-depression group ( r=0.017-0.801) compared to the SLE-non-depression group ( r=0.002-0.382), with a statistically significant difference ( U=629, P<0.001; Cliff's Delta=0.454). GSEA indicated that the aforementioned genes were primarily involved in pathways including the ribosome, spliceosome, ribosome biogenesis in eukaryotes, and neuroactive ligand-receptor interaction. Sensitivity analysis confirmed that the above results remained statistically significant after balancing sample sizes (all P<0.05). Conclusion:The SLE-depression group showed specific RNA expression and brain structure alterations compared to the SLE-non-depression group, and the correlation between RNA and brain structure was significantly enhanced in the SLE-depression group. This suggests that the correlation between genes and brain structure in the SLE population may be related to their susceptibility to depression.
8.Predictive study of brain gray matter volume combined with regional homogeneity on the alleviation of post-traumatic stress disorder in bereaved parents who lost their only child
Chensi LI ; Yifeng LUO ; Zhihong CAO ; Yuefeng LI ; Jiyuan GE ; Qingyue LAN ; Rongfeng QI ; Luo'an WU ; Li ZHANG ; Guangming LU
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(10):879-884
Objective:To investigate the predictive value of multimodal magnetic resonance imaging (MRI) techniques in assessing symptom remission of post-traumatic stress disorder (PTSD) of bereaved parents who lost their only child.Methods:In this prospective study, 34 parents with PTSD resulting from the loss of the only child were followed-up for 2 years. Based on the PTSD diagnostic status at the end of the follow-up, participants were divided into the remission group and the persistent group.R 3.6.1 and SPSS 20.0 software were used for statistical analysis.Baseline clinical data and neuroimaging findings were compared between the two groups. Logistic regression and LASSO regression analyses were used to identify independent predictors of PTSD symptom remission. The predictive performance of these factors was evaluated by receiver operating characteristic (ROC) curve analysis.Results:Initial screening with univariate Logistic regression and LASSO regression revealed that regional homogeneity (ReHo) in the left middle temporal gyrus, the combined predictive value based on ReHo, and the integrated predictive value combining gray matter volume (GMV) and ReHo (GMV-ReHo predictor) were significant factors influencing symptom remission (all P<0.05). Multivariate Logistic regression further demonstrated that the GMV-ReHo predictor retained independent predictive significance ( P<0.05), with ROC curve analysis showing an area under the curve (AUC) of 0.979 (95% CI=0.935-0.996, P<0.001) for its ability to predict PTSD remission. Notably, a combined model incorporating both the scores of the clinician administered PTSD scale (CAPS) and the GMV-ReHo predictor achieved an enhanced predictive performance, yielding an AUC of 0.984 (95% CI=0.952-0.998, P<0.001). Conclusion:The GMV-ReHo predictor effectively identifies symptom remission in PTSD resulting from the loss of the only child.
9.Correlation of hippocampal subfield volumes and structural covariance network alterations with memory function in individuals with subjective cognitive decline
Chengmin ZHOU ; Ju ZHANG ; Weiyan JIA ; Jinxin WANG ; Yuefeng LI ; Zhihong CAO ; Yifeng LUO
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(6):495-502
Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network between participants with subjective cognitive decline (SCD) and healthy individuals, and to analyze the correlations of the volumes of the different subfields and altered covariance brain regions with memory function.Methods:A total of 57 SCD individuals(SCD group) and 44 normal controls(NC group) participants were assessed for memory function using composite scores from the auditory verbal learning test (AVLT) and the Wechsler memory scale visual reproduction (VR) test from June 2022 to October 2023.T1-weighted structural magnetic resonance imaging (MRI) data were collected from all participants, and hippocampal subfields, cortical regions, and subcortical nuclei were segmented using FreeSurfer to measure the gray matter volume of each structure. A structural covariance network was constructed based on the correlation of gray matter volumes across regions. Statistical analysis was performed using R 4.3.1 software. Inter-group differences in hippocampal subfield volumes were compared using multivariate analysis of covariance. Differences in structural covariance connectivity between groups were assessed using Z-test, while network topology differences were compared through permutation testing. Finally, partial correlation analysis was used to examine correlation of the volumes of the differential hippocampal subfields and covariance brain regions with memory function. Results:The SCD group exhibited significantly lower years of education, AVLT-immediate score, AVLT-delayed score, VR-immediate score, VR-delayed score, and memory function Z-score compared to the NC group ( t=2.064, 3.888, 2.622, 3.222, 4.761, 5.184, all P<0.05). The volumes of the right subiculum((387.75±55.20)mm 3, (352.70±70.25)mm 3), left presubiculum((263.12±38.52)mm 3, (239.79±46.02)mm 3), left subiculum((388.12±49.34)mm 3, (351.74±67.30)mm 3) and left CA1((571.01±80.01)mm 3, (526.51±98.80)mm 3) in the SCD group were smaller than the corresponding volumes in NC group ( F=9.139, 8.039, 11.207, 7.266, all P<0.05, FDR correction). Differences in structural covariance connectivity were found between the SCD and NC groups in the following pairs: right CA1-right subiculum, right CA1-left subiculum, right CA3-left parasubiculum and right hippocampus-amygdala transition area-left subiculum ( Z=-3.848, -3.896, -3.597, -3.895, all P<0.05, FDR correction).Partial correlation analysis revealed that in the SCD group, the volume of the left subiculum ( r=0.359, P=0.007), left CA1 ( r=0.430, P=0.001), right entorhinal cortex ( r=0.296, P=0.029), right middle temporal gyrus ( r=0.361, P=0.007), right parahippocampal gyrus ( r=0.313, P=0.021)were positively correlated with the total memory function score. Conclusion:Hippocampal subfields atrophy, as well as alterations in structural covariance network, have been found in SCD individuals. Furthermore, the decline in memory function may be closely associated with atrophy in hippocampal subfields and structurally covariant regions.
10.Interventional Treatment Strategy for Different Types of Pulmonary Artery Lesions in Chronic Thromboembolic Pulmonary Hypertension
Xin LI ; Tao YANG ; Yi ZHANG ; Qin LUO ; Qing ZHAO ; Qixian ZENG ; Sicheng ZHANG ; Zhihui ZHAO ; Zhihong LIU
Chinese Circulation Journal 2025;40(2):190-196
Chronic thromboembolic pulmonary hypertension is characterised by the persistent obstruction of the proximal pulmonary arteries by organized thrombi and peripheral microvascular disease,which can lead to right-sided heart failure and mortality.Pulmonary endarterectomy enables complete removal of visible obstructive elements within the pulmonary arteries and is recommended for operable patients.Nevertheless,over 40%of patients are precluded from pulmonary endarterectomy because of factors such as surgically inaccessible lesions,compromised general health status,or concurrent comorbidities or still with residual pulmonary hypertension after pulmonary endarterectomy.For inoperable patients or those with residual pulmonary hypertension after pulmonary endarterectomy,balloon pulmonary angioplasty is an effective therapeutic option,which could significantly improve the hemodynamic,exercise tolerance and outcome of the patients.With the emerging accumulation of clinical experience and evidence,2022 European Society of Cardiology/European Respiratory Society guidelines of pulmonary hypertension recommend balloon pulmonary angioplasty as an alternative therapeutic option for these patients.However,different types of lesions may have their own lesion characteristics,the strategy and device of balloon pulmonary angioplasty should thus be individually considered for different lesions,in fact,the success rate of treatment and the incidence rate of complications are varied significantly.Therefore,the aim of this review is to comprehensively summarize the existing studies on balloon pulmonary angioplasty treatment strategies for different types of lesions and the management of complications to provide guidance and reference for clinicians.

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