Fibrosis mediated by transforming growth factor-beta (TGF-beta) is a common cause of peritoneal dialysis (PD) failure. In a model of peritoneal fibrosis, we tested the effect of Smad7, an inhibitor of TGF-beta signaling, using an ultrasound-microbubble-mediated delivery system. Rats were given daily PD for 4 weeks and received Smad7 or control plasmid transfer. The ultrasound technique enhanced Smad7 expression in a dose-dependent manner in more than 80% of the peritoneal cells after 3 days. The expression decreased by 14 days, but this was corrected by a second gene transfer. The overexpression of Smad7 substantially inhibited Smad2/3 activation, TGF-beta, plasminogen activator inhibitor-1, extracellular matrix, and myofibroblast mRNA, and protein expression in the peritoneal cells. The decreased peritoneal injury included the rise of mass transfer of glucose, a reduction of the ultrafiltration rate, and fibrotic thickening. Our studies suggest that ultrasound-mediated Smad7 gene delivery may be useful in the prevention or treatment of dialysis-induced peritoneal fibrosis.

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Background The benefit of IVIG (Intravenous Immunoglobulin) therapy for COVID-19 remains controversial. We performed a meta-analysis to investigate the efficacy of IVIG treatment in patients with COVID-19. Methods We searched articles from Web of Science, PubMed, Embase, the Cochrane Library, MedRxiv between 1 January 2020 and February 17, 2021. We selected randomized clinical trials and observational studies with a control group to assess the efficiency of IVIG in treating patients with COVID-19. Subjects were divided into ‘non-severe’, ‘severe’ and ‘critical’ three subgroups based on the information of the study and the World Health Organization (WHO) definition of severity. We pooled the data of mortality and other outcomes using either a fixed-effect model or a random-effects model. Results Our meta-analysis retrieved 4 clinical trials and 3 cohort studies including 825 hospitalized patients. The severity of COVID-19 is associated with the efficiency of IVIG. In critical subgroup, IVIG could reduce the mortality compared with the control group [RR=0.63 (0.45-0.88,I 2 =25%). But there was no significant difference in the severe or non-severe subgroups. Conclusion IVIG has demonstrated clinical efficacy on critical ill patients with COVID-19. There may be a relationship between the efficacy of IVIG and the COVID-19 disease severity. Well-designed clinical trials to identify the clinical and biochemical characteristics in COVID-19 patients’ population that could benefit from IVIG are warranted in the future.