Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.
ObjectiveTo evaluate the efficacy and safety of prompt phacoemulsification, intraocular lens implantation, visco-goniosynechialysis, combined with pseudo-pupilloplasty for refractory acute primary angle closure (APAC) with atonic dilated pupil and to describe a feasible method of pupilloplasty.MethodsA consecutive series of refractory APAC patients who had atonic dilated pupil and undergone prompt phacoemulsification combined with pseudo-pupilloplasty at our center were retrospectively analyzed. Pseudo-pupilloplasty referred to a method of pupilloplasty which included 4.5-mm capsulorhexis, postoperative opacification of anterior capsule residue, and ultimate pseudo-pupil formation. Preoperative and postoperative measurements included intraocular pressure (IOP), best corrected visual acuity (BCVA), and anterior chamber depth (ACD). Intraoperative and postoperative complications were documented. The process of pseudo-pupil formation was also observed.ResultsA total of 20 eyes of 19 APAC patients were followed up for 19.7 ± 9.8 months. IOP was lowered from preoperative 44.0 ± 9.8 mmHg to 15.5 ± 2.6 mmHg at final visit (t = 11.945, P < 0.001). ACD was deepened from preoperative 1.77 ± 0.21 mm to 3.40 ± 0.20 mm at final visit (t = –27.711, P < 0.001). Twelve of 20 eyes had residual angle synechiae, whereas only 3 eyes needed anti-glaucoma medications. No severe complication was observed. All eyes had pseudo-pupil gradually formed within 3 months, accompanied with the gradual improvement of BCVA from preoperative 1.18 ± 0.55 to 0.58 ± 0.22, 0.26 ± 0.09, 0.11 ± 0.09, and 0.11 ± 0.09 at postoperative day 1, month 1, month 3, and last visit.ConclusionsPrompt phacoemulsification-goniosynechialysis is effective and safe for refractory APAC with atonic dilated pupil. Pseudo-pupilloplasty is a feasible procedure for pupil reconstruction. 相似文献
Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity. 相似文献