Abstract Background: Studies on the correlation between serum uric acid (SUA) and all-cause mortality in peritoneal dialysis (PD) patients were mainly based on the results of baseline SUA. We aimed to analyze the change of SUA level post PD, and the correlation between follow-up SUA and prognosis in PD patients. Methods: All patients who received PD catheterization and maintaining PD in our center from March 2, 2001 to March 8, 2017 were screened. Kaplan-Meier and Cox proportional-hazards regression models were used to analyze the effect of SUA levels on the risks of death. We graded SUA levels at baseline, 6 months, 12 months, 18 months and 24 months post PD by mean of SUA plus or minus a standard deviation as cut-off values, and compared all-cause and cardiovascular mortality among patients with different SUA grades. Results: A total of 1402 patients were included, 763 males (54.42%) and 639 females (45.58%). Their average age at PD start was 49.50±14.20 years. The SUA levels were 7.97±1.79mg/dl at baseline, 7.12±1.48mg/dl at 6 months, 7.05±1.33mg/dl at 12 months, 7.01±1.30mg/dl at 18 months, and 6.93±1.26mg/dl at 24 months. During median follow-up time of 31 (18, 49) months, 173 (12.34%) all-cause deaths occurred, including 68 (4.85%) cardiovascular deaths. There were no significant differences on all-cause mortality among groups with graded SUA levels at baseline, 12 months, 18 months and 24 months during follow-up or on cardiovascular mortality among groups with graded SUA levels at baseline, 6 months, 12 months, 18 months and 24 months during follow-up. At 6 months post PD，Kaplan Meier analysis showed there was significant difference on all-cause mortality among graded SUA levels (c 2 =11.315, P=0.010), and the all-cause mortality was lowest in grade of 5.65mg/dl≤SUA<7.13mg/dl. Conclusion : SUA level decreased during follow up post PD. At 6 months post PD, a grade of 5.65mg/dl≤SUA<7.13mg/dl was appropriate for better patients’ survival.
Introduction: Rituximab has proven effective and safe in pediatric and adult minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients with frequently relapsing nephrotic syndrome. However, its efficacy diminishes in several patients who experience nephrotic syndrome relapsing in short durations or failing to achieve remission. We aimed to explore the efficacy and safety of obinutuzumab, a novel anti-CD20 antibody, in these patients. Methods: A retrospective case series study at our center included 11 adult MCD or FSGS patients who presented with nephrotic syndrome characterized by short-duration relapses or lack of remission after multitarget therapy, including rituximab. Primary outcomes included the first relapse-free time, relapse rate during follow-up, and the use of immunosuppressants after obinutuzumab. All adverse events were recorded. Results: Eleven adult patients (median age 26.0 years, 81.9% males) received an average obinutuzumab dose of 2.0 (1.0, 2.0) g during a median follow-up period of 17.0 (12.0, 22.0) months. The first relapse-free time was 12.1 (10.8, 18.9) months. Two patients with FSGS experienced relapses, while the remaining maintained remission by the end of follow-up. Six patients (54.5%) achieved cessation of corticosteroids and immunosuppressants within 3 months after obinutuzumab. Adverse events were mostly mild. Conclusion: Obinutuzumab may be an efficient and safe option for inducing remission in adult MCD and FSGS patients who presented with nephrotic syndrome relapsing in short durations or failed to achieve remission after multitarget therapy, including rituximab. It was effective in maintaining remission in MCD patients, while its efficacy in maintaining remission in FSGS patients remained uncertain.
Introduction: ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) levels are increased in human descending thoracic aortic aneurysm and dissection (dTAAD) samples. Hypothesi...
Background: Thoracic aortic aneurysms associated with Marfan syndrome (MFS) carry a high risk of mortality; however, the molecular and cellular processes leading to aortopathy in this population remain poorly understood. We aimed to use single-cell RNA (scRNA) sequencing to define the non-immune cell populations present within the aortic wall in MFS, hypothesizing that these would differ from those of non-aneurysmal control tissue. Methods: We performed scRNA sequencing of ascending aortic aneurysm tissues from MFS patients (n=3) undergoing aneurysm repair and of age-matched, non-aneurysmal control tissue from cardiac transplant donors and recipients (n=4). The Seurat package in R was used for analysis. Differentially expressed genes were identified using edgeR. Results: Eighteen non-immune cell clusters were identified, with conserved gene expression of the largest of the clusters consistent with smooth muscle cells (SMCs; n=6), fibroblasts (n=3), and endothelial cells (n=3). The SMCs and fibroblasts exhibited graded changes in their expression of contractile and extracellular matrix protein genes, supportive of a phenotypic continuum. Additionally, we identified differences in the proportions of non-immune cells in MFS tissues compared to controls. In control tissues, the most common non-immune cells expressed markers of contractile SMC maturity including CNN1 , MYH11 , and SMTN . In contrast, the largest clusters in MFS tissue were most closely related to SMCs on correlation analysis, but displayed increased expression of cyclin genes as well as immune, endothelial, and fibroblast genes indicative of de-differentiated, proliferative SMCs. Additionally, expression of genes associated with SMC phenotypic maturity, including MYH11 and MYOCD , were significantly downregulated in several of the MFS SMC clusters. Conclusion: Our data demonstrate a phenotypic continuum between fibroblasts and SMCs, with aortas from patients with MFS exhibiting an increased proportion of de-differentiated, proliferative SMCs compared to controls. Additionally, markers of SMC maturity were downregulated in SMCs in MFS compared to controls. This may be due to disruption of signaling pathways that promote differentiation.
Objective To explore the value of transthoracic echocardiography in diagnosis of univentricle and analyze the sonogram typing. Methods The results of 66 patients with univentricle were reviewed retrospectively,and analayzed their typing connected with the reports in the literature. Results There were 3 ultrasonic types in 66 cases:①Type A(single left ventricle) 19 cases,single ventricle with left ventricular shape,residual cavity in front of it. ②Type B(single right ventricle) 38 cases, single ventricle with right ventricular form,and residual cavity in the rear.③Type C (solitary single-ventricle) 9 cases,there was only one ventricle. Thirty-one of them were treated surgically, 5 cases without operation had MRI or cardiac catheterization examination and the remaining 26 patients were only observed by echocardiography,the positive rate of diagnosis in type was 100%, the results were compared with cardiac catheterization or MRI examination and the operation: 1 cases of mixed type total anomalous pulmonary venous connection was misdiagnosed as heart-type total anomalous pulmonary venous drainage. But 1 case of descending aorta limitations narrow complicated patent ductus arteriosus(PDA), PDA was missed. The rest were completely correct diagnosis. Conclusions The transthoracic echocardiography can be used to evaluate types and all containing malformations of univentricle,and offers reliable information for operation.
Key words:
Echocardiograghy; Heart defects,congenital; Single ventricle
Background Aortic aneurysms and dissections are highly lethal diseases for which an effective treatment strategy is critically needed to prevent disease progression. The nucleotide‐binding oligomerization domain–like receptor pyrin domain containing 3 (NLRP3)–caspase‐1 inflammasome cascade was recently shown to play an important role in aortic destruction and disease development. In this study, we tested the effects of MCC950, a potent, selective NLRP3 inhibitor, on preventing aortic destruction and aortic aneurysm and dissection formation. Methods and Results In a model of sporadic aortic aneurysm and dissection induced by challenging wild‐type mice with a high‐fat, high‐cholesterol diet and angiotensin II infusion, MCC950 treatment significantly inhibited challenge‐induced aortic dilatation, dissection, and rupture in different thoracic and abdominal aortic segments in both male and female mice. Aortic disease reduction by MCC950 was associated with the prevention of NLRP3–caspase‐1 upregulation, smooth muscle cell contractile protein degradation, aortic cell death, and extracellular matrix destruction. Further investigation revealed that preventing matrix metallopeptidase 9 (MMP‐9) expression and activation in macrophages is an important mechanism underlying MCC950's protective effect. We found that caspase‐1 directly activated MMP‐9 by cleaving its N‐terminal inhibitory domain. Moreover, the genetic knockdown of Nlrp3 or Casp‐1 in mice or treatment of mice with MCC950 diminished the challenge‐induced N‐terminal cleavage of MMP‐9, MMP‐9 activation, and aortic destruction. Conclusions Our findings suggest that the NLRP3–caspase‐1 inflammasome directly activates MMP‐9. Targeting the inflammasome with MCC950 is a promising approach for preventing aortic destruction and aortic aneurysm and dissection development.
Rationale: Aortic aneurysm and dissection (AAD) are major diseases of the adult aorta caused by progressive medial degeneration of the aortic wall. Although the overproduction of destructive factors promotes tissue damage and disease progression, the role of protective pathways is unknown. Objective: In this study, we examined the role of AKT2 in protecting the aorta from developing AAD. Methods and Results: AKT2 and phospho-AKT levels were significantly downregulated in human thoracic AAD tissues, especially within the degenerative medial layer. Akt2- deficient mice showed abnormal elastic fibers and reduced medial thickness in the aortic wall. When challenged with angiotensin II, these mice developed aortic aneurysm, dissection, and rupture with features similar to those in humans, in both thoracic and abdominal segments. Aortas from Akt2 -deficient mice displayed profound tissue destruction, apoptotic cell death, and inflammatory cell infiltration that were not observed in aortas from wild-type mice. In addition, angiotensin II–infused Akt2- deficient mice showed significantly elevated expression of matrix metalloproteinase-9 (MMP-9) and reduced expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). In cultured human aortic vascular smooth muscle cells, AKT2 inhibited the expression of MMP-9 and stimulated the expression of TIMP-1 by preventing the binding of transcription factor forkhead box protein O1 to the MMP-9 and TIMP-1 promoters. Conclusions: Impaired AKT2 signaling may contribute to increased susceptibility to the development of AAD. Our findings provide evidence of a mechanism that underlies the protective effects of AKT2 on the aortic wall and that may serve as a therapeutic target in the prevention of AAD.
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