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Purpose: Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN. Patients and Methods: The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus. Results: The mean follow-up period was 27.3 (19.3-41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids. Conclusion: Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.
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Purpose: To investigate the deficits in contrast sensitivity in patients with Fuchs uveitis syndrome (FUS) and to explore the potential relationship between contrast sensitivity and ocular structure. Methods: In this prospective study, 25 patients with FUS and 30 healthy volunteers were recruited. Eyes were divided into three groups: FUS-affected eyes (AE), fellow eyes (FE), and healthy eyes. The contrast sensitivity function (CSF) of all participants was evaluated using the quick CSF (qCSF) method. Fundus photographs were collected for the analysis of refractive media, and vascular density (VD) was assessed using optical coherence tomography angiography (OCTA). Data were analyzed and compared using the generalized estimating equation (GEE). Results: The CSF of AE was significantly lower than that of FE and controls, while no significant difference was observed between FE and controls. Contrast sensitivity was negatively correlated with the grade of haze. No significant correlation was found between visual function and VDs in FUS eyes. Conclusions: We found that the CSF of FUS-affected eyes was significantly reduced, and the visual impairment was predominantly caused by the refractive media turbidity.
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MicroRNAs (miRNAs) play important roles in the fibrosis of systemic sclerosis (SSc). However, the underlying miRNA-mRNA regulatory network is not fully understood. A systemic investigation of the role of miRNAs would be very valuable for increasing our knowledge of the pathogenesis of SSc. Here, we combined miRNA and mRNA expression profiles and bioinformatics analyses and then performed validation experiments. we identified 21 miRNAs and 2698 mRNAs that were differentially expressed in SSc. Among these, 17 miRNAs and their 33 target mRNAs (55 miRNA-mRNA pairs) were involved in Toll-like receptor, transforming growth factor ß and Wnt signalling pathways. Validation experiments revealed that miR-146b, miR-130b, miR-21, miR-31 and miR-34a levels were higher whereas miR-145 levels were lower in SSc skin tissues and fibroblasts, normal fibroblasts and endothelial cells that were stimulated with SSc serum. ACVR2B, FZD2, FZD5 and SOX2 levels were increased in SSc skin fibroblasts, normal fibroblasts and endothelial cells that were stimulated with SSc serum. We did not identify any negative correlations among these miRNA-mRNA pairs. miR-21 was specifically expressed at higher levels in SSc serum. Six miRNAs and 4 mRNAs appear to play important roles in the pathogenesis of SSc are worth investigating in future functional studies.
