RESUMO
Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.
RESUMO
1. The purpose of the present study was to examine lung water transport properties and the expression and regulation of the alveolar endothelial water channel aquaporin (AQP)-1 and the epithelial water channel AQP-5 in aged mouse lung using gene expression analysis and water permeability measurements. 2. In aged (20-24-month-old) mice, AQP-1 and AQP-5 mRNA expression decreased by 55.5 and 50.3%, respectively, compared with that in young (8-10-week-old) mice (P < 0.01). In addition, AQP-1 and AQP-5 protein expression decreased in aged mice by 36.9 and 44.6%, respectively, compared with that in young mice (P < 0.01). 3. The osmotically driven water transport rate between the airspace and capillary compartments was reduced by 31.7% in aged mice compared with young mice (2.8 +/- 0.3 vs 4.1 +/- 0.3 mg/s, respectively; P < 0.01). The hydrostatically driven lung water accumulation rate in response to a 10 cmH(2)O increase in pulmonary artery pressure was also reduced in aged mice by 21.9% compared with young mice (0.32 +/- 0.06 vs 0.41 +/- 0.04 mg/s, respectively; P < 0.01). 4. There was a 62.7% decrease in serum glucocorticoids in aged mice compared with young mice (67.6 +/- 26.8 vs 181.3 +/- 44.4 nmol/L, respectively; P < 0.01). In vivo administration of dexamethasone (4 mg/kg) for 5 consecutive days to aged mice increased lung AQP-1 mRNA and protein expression by 2.1 +/- 0.1 fold (P < 0.01) and 1.8 +/- 0.2 fold (P < 0.01), respectively. Accordingly, osmotically and hydrostatically driven water transport rates increased by 35.6% (P < 0.01) and 31.2% (P < 0.01), respectively. 5. The present study provides the first evidence of altered lung water transport associated with downregulation of AQPs in aged lung. Blood glucocorticoid hormone levels are important to maintain normal AQP-1 expression in the lung microvascular endothelium. Corticosteroid-induced AQP-1 upregulation may contribute to the role of corticosteroids in accelerating oedema clearance in aged lung.
