陈小曦
中国医学科学院阜外医院 肺血管病中心
PURPOSE:To investigate the imaging characteristics and prognostic factors for the long-term survival of Behcet's disease (BD) with arterial involvement.METHODS:In this retrospective study, BD patients with arterial involvement were identified from January 2003 to January 2020. Arterial lesions were detected by ultrasonography, traditional arteriography, and/or computed tomography angiography (CTA). Cox proportional hazards regression analyses were performed to identify the prognostic factors.RESULTS:Totally, 84 BD patients with arterial involvement were identified (73.8 % males). The mean age at BD diagnosis was 39.1 ± 13.1 years. Arterial involvement was the initial manifestation in 33.3 % of the patients, and the median time from BD diagnosis to arterial involvement was 6 (IQR 1-15.5) years for the rest of patients. Systemic artery involvement and pulmonary artery involvement (PAI) were found in 64 and 27 patients, respectively. Approximately 94.0 % (79/84) of the patients had more than one artery involved concurrently or successively during the course of BD. Aneurysm/dilation was the most prevalent lesion in the aorta (76.0 %), while stenosis/occlusion was the main lesion of the coronary artery (90.9 %) and other aortic branches (74.5 %). Pulmonary hypertension was found in 70.4 % (19/27) of patients with PAI. The 5- and 10-year survival rates of BD patients with arterial involvement were 87.4 % and 84.1 %, respectively. Cardiac involvement (HR: 4.34) and pulmonary artery aneurysm/dilation (HR: 4.89) were independently associated with mortality.CONCLUSIONS:Arterial lesions associated with BD usually involve multiple arteries and manifest differently in different types of arteries. Cardiac involvement and pulmonary artery aneurysm/dilation are independent prognostic factors of BD patients with arterial involvement.
European journal of radiology 2024
Acute kidney injury (AKI), characterized by tissue inflammation and oxidative damage, is a common and potentially life-threatening complication in patients. Quercetin, a natural antioxidant, possesses diverse pharmacological properties. However, limited stability and bioavailability hinder its clinical utilization. Moreover, the application of nanotechnology in antioxidant strategies for AKI treatment faces significant knowledge gaps. These gaps stem from limited understanding of the therapeutic mechanisms and renal clearance pathways. To tackle these issues, this study aims to develop an anti-oxidation nanozyme through the coordination of quercetin (Que) with a ruthenium (Ru) doped platinum (Pt) nanozyme (RuPt nanozyme). Compared to using Que or the RuPt nanozyme alone, the combined use of Que and the nanozyme led to enhanced antioxidant activities, especially in ABTS and DPPH free radical scavenging activities. Moreover, the modified nanozyme showed remarkable efficacy in scavenging reactive oxygen species and inhibiting apoptosis in a H2O2-induced cellular model. Additionally, the in vivo study showed that the coordination-modified nanozyme effectively alleviated glycerol- and cisplatin-induced AKI by inhibiting oxidative stress. Furthermore, this nanozyme exhibited superior therapeutic efficacy when compared to free quercetin and the RuPt nanozyme. In conclusion, the findings of our study suggest that the quercetin modified RuPt nanozyme (QCN) exhibits remarkable biocompatibility and holds significant promise for the therapeutic management of AKI.
Nanoscale 2024
Background:Pulmonary arterial hypertension (PAH) leads to myocardial remodeling, manifesting as mechanical dyssynchrony (M-dys) and electrical dyssynchrony (E-dys), in both right (RV) and left ventricles (LV). However, the impacts of layer-specific intraventricular M-dys on biventricular functions and its association with E-dys in PAH remain unclear.Methods:Seventy-nine newly diagnosed patients with PAH undergoing cardiac magnetic resonance scanning were consecutively recruited between January 2011 and December 2017. The biventricular volumetric and layer-specific intraventricular M-dys were analyzed. The QRS duration z-scores were calculated after adjusting for age and sex.Results:77.22 % of patients were female (mean age 30.30 ± 9.79 years; median follow-up 5.53 years). Further, 29 (36.71 %) patients succumbed to all-cause mortality by the end of the study. At the baseline, LV layer-specific intraventricular M-dys had apparent transmural gradients compared with RV in the radial and circumferential directions. However, deceased patients lost the transmural gradients. The LV longitudinal strain rate time to late diastolic peak in the myocardial region (LVmyoLSRTTLDPintra) predicted long-term survival. The Kaplan-Meier curve revealed that patients with PAH with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. Larger right ventricle (RV) intraventricular M-dys resulted in worse RV ejection fraction. However, larger LV intraventricular M-dys in the late diastolic phase indicated remarkable exercise capacity and higher LV stroke volume index. E-dys and intraventricular M-dys had no direct correlations.Conclusions:The layer-specific intraventricular M-dys had varying impacts on biventricular functions in PAH. PAH patients with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. LV intraventricular M-dys in the late diastolic phase needs more attention to precisely evaluate LV function.
Heliyon 2024
OBJECTIVES:To report the 10-year survival rate and prognostic factors of pulmonary arterial hypertension associated with CTD (CTD-PAH) patients, to compare treatment and survival between patients enrolled before and after 2015, and to validate the discrimination of the recommended four-strata model in predicting 10-year survival at follow-up in Chinese CTD-PAH patients.METHODS:This study was derived from a Chinese national multicentre prospective registry study from 2009 to 2019. Medical records were collected at baseline and follow-up, including PAH-targeted therapy and binary therapy (both CTD and PAH-targeted therapy).RESULTS:A total of 266 CTD-PAH patients were enrolled and the 10-year survival rate was 59.9% (median follow-up time: 4.85 years). Underlying CTD (SSc), baseline 6-min walking distance and SaO2 were independent risk factors for 10-year survival. The proportion of patients receiving PAH-targeted combination therapy increased from 10.1% (2009-2014) to 26.5% (2015-2019) and that of binary therapy increased from 14.8% to 35%. The 1-year survival rate increased from 89.8% (2009-2014) to 93.9%, and the 3-year survival rate increased from 80.1% (2009-2014) to 86.5% (both P > 0.05). The four-strata strategy performed well in predicting 10-year survival at follow-up (C-index = 0.742).CONCLUSION:The 10-year survival rate of CTD-PAH patients was reported for the first time. The 10-year prognosis was poor, but there was a tendency for more standardized treatment and better survival in patients enrolled after 2015. The recommended four-strata model at follow-up can effectively predict 10-year survival in CTD-PAH patients.
Rheumatology (Oxford, England) 2023
Right heart thrombus (RHT) is a rare but life-threatening condition in acute pulmonary embolism (APE) without clear management guidelines. This study aimed to address the clinical characteristics and outcomes of RHT-APE in Chinese patients. In this study, 17 RHT-APE and 329 non-RHT-APE patients, who were diagnosed between September 2015 and August 2019, were retrospectively recruited with the median follow-up was 360 days. The overall prevalence of RHT was 4.91% in APE. Its prevalence increased along the increase of APE risk stratifications. Comparisons showed that with higher proportion of male gender and younger age, RHT-APE patients also had worse hemodynamic instability and heart function, and higher risk stratification levels than non-RHT-APE patients. After adjusting by age and gender, multivariate logistic regression analysis found high/intermediate-high risk stratification, decreased right ventricular (RV) motion, NT-proBNP >600 pg/mL, and RV dysfunction were risk factors for RHT. Kaplan-Meier analysis showed non-RHT had better prognosis than RHT patients (30-day survival: log-rank: p < 0.001; 90-day survival: log-rank: p = 0.002). The multivariate logistic regression analysis showed RHT was an independent risk factor for 30-day mortality in APE. The subgroup analysis showed RHT would result in worse outcomes in patients who already had higher APE early mortality risk. RHT would increase the risk of 30- and 90-day mortality in APE. More attention should be paid to young male APE patients with decreased RV motion, NT-proBNP >600 pg/mL, RV dysfunction, or high level of risk stratification, to exclude the coexistence of RHT.
Pulmonary circulation 2023
Background:Our objective was to clarify the characteristics and long-term survival of idiopathic pulmonary arterial hypertension (IPAH) patients with thyroid dysfunction and compare them with IPAH without thyroid dysfunction.Methods:A retrospective analysis was conducted using prospectively collected data. IPAH patients with thyroid dysfunction at baseline were included. Patients with other subgroups of PAH and Group 2-5 pulmonary hypertension were excluded. IPAH patients with euthyroid function were matched 1:1 to IPAH patients with thyroid dysfunction by age and sex.Results:In total, 148 IPAH patients with thyroid dysfunction were included. Patients with hyperthyroidism, hypothyroidism, subclinical hyperthyroidism and subclinical hypothyroidism accounted for 16.2%, 18.9%, 8.1% and 56.8%, respectively. IPAH patients with hyperthyroidism showed the highest mixed venous oxygen saturation (SvO2) and the lowest pulmonary vascular resistance (PVR) at baseline among subgroups, while patients with subclinical hypothyroidism had the lowest SvO2 and highest PVR (p<0.05). Compared with IPAH without thyroid dysfunction, patients with hyperthyroidism (9.14 versus 13.86 WU; p<0.05) and hypothyroidism (10.70 versus 13.86 WU; p<0.05) showed significantly lower PVR. The haemodynamic profiles of patients with subclinical hypothyroidism were similar to IPAH with euthyroid function except for lower right atrial pressure (6 versus 8 mmHg; p=0.009). The long-term survival of patients with clinical thyroid dysfunction was better than IPAH without thyroid dysfunction, while that of those with subclinical diseases was comparable to the latter, even after adjusting for baseline haemodynamics and treatment.Conclusion:IPAH patients with clinical hyper- and hypothyroidism had better haemodynamics and survival than those without thyroid dysfunction, while patients with subclinical hypothyroidism had similar haemodynamics and survival profiles to the latter.
ERJ open research 2023
BACKGROUND:Registry-based studies of pediatric pulmonary arterial hypertension (PPAH) are scarce in developing countries, including China. The PPAH risk assessment tool needs further evaluation and improvement.RESEARCH QUESTION:What are the characteristics and long-term survival of PPAH in China and what is the performance of the PPAH risk model in Chinese patients?STUDY DESIGN AND METHODS:Patients with PAH were enrolled in the national prospective multicenter registry from August 2009 through December 2019. Children 3 months to 18 years of age at the time of PAH diagnosis were analyzed.RESULTS:A total of 247 children with PAH were enrolled. The median patient age was 14.8 years, and 58.3% of patients were female. Most patients had a diagnosis of PAH associated with congenital heart disease (CHD; 61.5%) and idiopathic or heritable PAH (37.7%). The median time from symptom onset to PAH diagnosis was 24 months. The mean pulmonary artery pressure and pulmonary vascular resistance index were 70.78 ± 19.80 mm Hg and 21.82 ± 11.18 Wood Units·m2, respectively. Patients with CHD-associated PAH experienced a longer diagnostic delay and demonstrated higher pulmonary artery pressure, but better cardiac performance, than those with idiopathic or heritable PAH. An increased number of patients received targeted therapy at the last follow-up compared with baseline. The 5- and 10-year survival rates of the entire cohort were 74.9% and 55.7%, respectively, with better survival in patients with CHD-associated PAH than in those with idiopathic or heritable PAH. Patients with low risk had better survival than those with high risk according to the simplified noninvasive risk score model with weight, function class, and echocardiographic right ventricular size, both at baseline and follow-up.INTERPRETATION:Patients with PPAH in China showed severely compromised hemodynamics with marked diagnostic delay. The long-term survival of PPAH is poor despite the increased usefulness of targeted drugs. The simplified noninvasive risk model demonstrated good performance for predicting survival in Chinese children with PAH.TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT01417338; URL: www.CLINICALTRIALS:gov.
Chest 2023
Risk assessment for pulmonary arterial hypertension (PAH) utilizing noninvasive prognostic variables could be more practical in real-world scenarios, especially at follow-up reevaluations. Patients who underwent comprehensive evaluations both at baseline and at follow-up visits were enrolled. The primary endpoint was all-cause mortality. Predictive variables identified by Cox analyses were further incorporated with the French noninvasive risk prediction approach. A total of 580 PAH patients were enrolled. During a median follow-up time of 47.0 months, 112 patients (19.3%) died. By multivariate Cox analyses, tricuspid annular plane systolic excursion (TAPSE), TAPSE/pulmonary arterial systolic pressure (PASP), and cardiopulmonary exercise testing-derived peak oxygen consumption (VO2) remained independent predictors for survival. Regarding the French noninvasive risk prediction method, substituting N-terminal pro-b-type natriuretic peptide (NT-proBNP) with the newly derived low-risk criteria of a TAPSE ≥ 17 mm or a TAPSE/PASP > 0.17 mm/mmHg, or alternating 6-min walking distance with a peak VO2 ≥ 44 %predicted retained the discrimination power. When recombining the low-risk criteria, the combination of World Health Organization functional class (WHO FC), TAPSE and peak VO2 at baseline, and the combination of WHO FC, NT-proBNP, and peak VO2 at follow-up showed better discriminative ability than the other combinations. In conclusion, Peak VO2, TAPSE, and TAPSE/PASP are significant prognostic predictors for survival in PAH, with incremental prognostic value when incorporated with the French noninvasive risk prediction approach, especially at reevaluations. For better risk prediction, WHO FC, at least one measurement of exercise capacity and one measurement of right ventricular function should be considered.
Pulmonary circulation 2022
AIMS:Orchestrating the transition from reversible medial hypertrophy to irreversible plexiform lesions is crucial for pulmonary arterial hypertension related to congenital heart disease (CHD-PAH). Transgelin is an actin-binding protein that modulates pulmonary arterial smooth muscle cell (PASMC) dysfunction. In this study, we aimed to probe the molecular mechanism and biological function of transgelin in the pathogenesis of CHD-PAH.METHODS AND RESULTS:Transgelin expression was detected in lung tissues from both CHD-PAH patients and monocrotaline (MCT)-plus aortocaval (AV)-induced PAH rats by immunohistochemistry. In vitro, the effects of transgelin on the proliferation, migration, and apoptosis of human PASMCs (HPASMCs) were evaluated by the cell count and EdU assays, transwell migration assay, and TUNEL assay, respectively. And the effect of transgelin on the expression of HPASMC phenotype markers was assessed by the immunoblotting assay. (i) Compared with the normal control group (n = 12), transgelin expression was significantly overexpressed in the pulmonary arterioles of the reversible (n = 15) and irreversible CHD-PAH group (n = 4) (reversible group vs. control group: 18.2 ± 5.1 vs. 13.6 ± 2.6%, P < 0.05; irreversible group vs. control group: 29.9 ± 4.7 vs. 13.6 ± 2.6%, P < 0.001; irreversible group vs. reversible group: 29.9 ± 4.7 vs. 18.2 ± 5.1, P < 0.001). This result was further confirmed in MCT-AV-induced PAH rats. Besides, the transgelin expression level was positively correlated with the pathological grading of pulmonary arteries in CHD-PAH patients (r = 0.48, P = 0.03, n = 19). (ii) Compared with the normal control group (n = 12), TGF-β1 expression was notably overexpressed in the pulmonary arterioles of the reversible (n = 15) and irreversible CHD-PAH group (n = 4) (reversible group vs. control group: 14.8 ± 4.4 vs. 6.0 ± 2.5%, P < 0.001; irreversible group vs. control group: 20.1 ± 4.4 vs. 6.0 ± 2.5%, P < 0.001; irreversible group vs. reversible group: 20.1 ± 4.4 vs. 14.8 ± 4.4, P < 0.01). The progression-dependent correlation between TGF-β1 and transgelin was demonstrated in CHD-PAH patients (r = 0.48, P = 0.04, n = 19) and MCT-AV-induced PAH rats, which was further confirmed at sub-cellular levels. (iii) Knockdown of transgelin diminished proliferation, migration, apoptosis resistance, and phenotypic transformation of HPASMCs through repressing the TGF-β1 signalling pathway. On the contrary, transgelin overexpression resulted in the opposite effects.CONCLUSIONS:These results indicate that transgelin may be an indicator of CHD-PAH development via boosting HPASMC dysfunction through positive regulation of the TGF-β1 signalling pathway, as well as a potential therapeutic target for the treatment of CHD-PAH.
ESC heart failure 2022
BACKGROUND AND OBJECTIVE:Nationally representative reports on the characteristics and long-term survival of pulmonary arterial hypertension (PAH) from developing countries are scarce. The applicability of the current main risk stratifications and the longitudinal changes in goal-oriented treatments have yet to be elucidated in real-world settings. Therefore, we aimed to provide insights into the characteristics, goal-oriented treatments and survival of PAH in China and to explore the applicability of the main risk stratifications in our independent cohort.METHODS:PAH patients were consecutively enrolled from a national prospective multicentre registry. Data on baseline, follow-up re-evaluation and therapeutic changes were collected.RESULTS:A total of 2031 patients were enrolled, with congenital heart disease (CHD)-PAH (45.2%) being the most common aetiology. The mean age was 35 ± 12 years, and 76.2% were females. At baseline, approximately 20% of the patients with intermediate or high risk received combination treatment. At follow-up, approximately half of the re-evaluated patients did not achieve low-risk profiles, and even among patients who received combination therapy at baseline, 4% of them still worsened. The rate of combination therapy increased significantly from 6.7% before 2015 to 35.5% thereafter. The main risk assessment tools demonstrated good performance for predicting survival both at baseline and at follow-up.CONCLUSION:Chinese PAH patients show both similar and distinct features compared to other countries. Current main risk stratifications can significantly discriminate patients at different risk levels. There were still many patients not achieving low-risk profiles at follow-up, indicating more aggressive treatment should be implemented to optimize the goal-oriented treatment strategy.
Respirology (Carlton, Vic.) 2022
