Efficacy of roxadustat in treatment of peritoneal dialysis patients with renal anaemia.

BACKGROUND: There are no studies on the use of roxadustat in patients on regular peritoneal dialysis in China. AIM: To observe the efficacy and safety of roxadustat in treating renal anaemia in peritoneal dialysis patients. METHODS: Patients with renal anaemia who were regularly followed at the Peritoneal Dialysis Center of the First Affiliated Hospital of China Medical University from November 1, 2019 to June 30, 2020 were selected. A before-and-after self-control design was performed to retrospectively analyse the treatment effects on anaemia in patients treated with recombinant human erythropoietin (EPO) and roxadustat. RESULTS: A total of 31 patients with renal anaemia on long-term peritoneal dialysis treated with roxadustat were included. Haemoglobin (Hb) levels were maintained or increased in all patients (100%), and no patients had a decrease in Hb compared with the previous phase. Patients had a mean Hb of 86.2 ± 14.8 g/L with Hb compliance (Hb ≥ 110 g/L) of 16.1% during the EPO phase and a mean Hb of 112.4 ± 18.5 g/L with Hb compliance of 67.7% during the roxadustat phase. No major adverse cardiovascular events occurred in any patient. CONCLUSION: The application of roxadustat in peritoneal dialysis patients with renal anaemia can effectively improve the Hb compliance rate.

LncRNA ARAP1-AS2 promotes high glucose-induced human proximal tubular cell injury via persistent transactivation of the EGFR by interacting with ARAP1.

The persistent transactivation of epidermal growth factor receptor (EGFR) causes subsequent activation of the TGF-ß/Smad3 pathway, which is closely associated with fibrosis and cell proliferation in diabetic nephropathy (DN), but the exact mechanism of persistent EGFR transactivation in DN remains unclear. ARAP1, a susceptibility gene for type 2 diabetes, can regulate the endocytosis and ubiquitination of membrane receptors, but the effect of ARAP1 and its natural antisense long non-coding RNA (lncRNA), ARAP1-AS2, on the ubiquitination of EGFR in DN is not clear. In this study, we verified that the expression of ARAP1 and ARAP1-AS2 was significantly up-regulated in high glucose-induced human proximal tubular epithelial cells (HK-2 cells). Moreover, we found that overexpression or knockdown of ARAP1-AS2 could regulate fibrosis and HK-2 cell proliferation through EGFR/TGF-ß/Smad3 signalling. RNA pulldown assays revealed that ARAP1-AS2 directly interacts with ARAP1. Coimmunoprecipitation, dual-immunofluorescence and ubiquitination assays showed that ARAP1 may maintain persistent EGFR activation by reducing EGFR ubiquitination through competing with Cbl for CIN85 binding. Taken together, our results suggest that the lncRNA ARAP1-AS2 may promote high glucose-induced proximal tubular cell injury via persistent EGFR/TGF-ß/Smad3 pathway activation by interacting with ARAP1.

Caspase-3 Promotes Diabetic Kidney Disease Through Gasdermin E-Mediated Progression to Secondary Necrosis During Apoptosis.

BACKGROUND: Apoptosis has been repeatedly linked with diabetic kidney disease (DKD), which is a programmed cell death mediated by effector caspases-3, 6 and 7, targeting >600 substrates. However, the pathophysiologic correlations of this process remain obscure. As a putative tumor suppressor, gasdermin E (GSDME) was recently reported to be cleaved by caspase-3 to produce a GSDME-N fragment which targets the plasma membrane to switch apoptosis to secondary necrosis. However, it remains elusive whether GSDME is involved in the regulation of DKD. METHODS: To evaluate the therapeutic potential of caspase-3 inhibition in DKD, we administered caspase-3 inhibitor Z-DEVD-FMK to STZ-induced diabetic mice for eight weeks. Albuminuria, renal function, pathological changes, and indicators of secondary necrosis and fibrosis were evaluated. In vitro, human tubule epithelial cells (HK-2 cells) were subjected to high-glucose treatment. Secondary necrosis was determined by LDH release, GSDME cleavage, and morphological feature under confocal microscopy. Z-DEVD-FMK and GSDME inhibition by shRNA were administered to suppress the cleavage and expression of GSDME. Flow cytometry, cytotoxicity assay and immunoblot were used to assess cell death and fibrogenesis. RESULTS: Caspase-3 inhibition by Z-DEVD-FMK ameliorated albuminuria, renal function, and tubulointerstitial fibrosis in diabetic mice. The nephroprotection mediated by Z-DEVD-FMK was potentially associated with inhibition of GSDME. In vitro, molecular and morphological features of secondary necrosis were observed in glucose-stressed HK-2 cells, evidenced by active GSDME cleavage, ballooning of the cell membrane, and release of cellular contents. Here we showed that caspase-3 inhibition prevented GSDME activation and cell death in glucose-treated tubular cells. Specifically, knocking down GSDME directly inhibited secondary necrosis and fibrogenesis. CONCLUSION: These data suggest GSDME-dependent secondary necrosis plays a crucial role in renal injury, and provides a new insight into the pathogenesis of DKD and a promising target for its treatment.

Risk factors of periodontal disease in maintenance hemodialysis patients.

To explore the characteristics and relevant risk factors of periodontal disease (PD) among hemodialysis patients.Uremic patients on maintenance hemodialysis from November 2015 to March 2016 were retrospectively reviewed. Patients were divided into a PD group and a non-PD group. Demographic and laboratory data were collected and analyzed.In all, 136 uremic patients (79 males and 57 females, aged 50.8 ±â€Š15.3 years) on maintenance hemodialysis were included in this study. The incidence of PD increased with age. Hemodialysis patients most likely developed PD if they were male, smokers, or diabetic (P = .009, <.001, and <.001, respectively). Patients brushing their teeth twice daily had significantly less chance of developing PD as compared with those only brushing once daily (P < .001). Hemodialysis patients in the PD group had significantly higher levels of total cholesterol, high-sensitivity C-reactive protein, fasting blood glucose, and peripheral white blood cell counts, compared with the non-PD group (all P < .001). Logistic regression analysis revealed that diabetes, total cholesterol, high-sensitivity C-reactive protein, and peripheral white blood cell count were independent risk factors for developing PD, whereas teeth brushing twice daily and serum calcium were favorable factors for maintenance hemodialysis patients against PD.Identification of risk factors provides a theoretical basis for prevention and improvement of PD among maintenance hemodialysis patients.

Titanium alloy surface coatings using poly(sodium styrene sulfonate) and poly(acrylic acid).

BACKGROUND: Osseointegration of implant materials with surrounding tissues is crucial for their long-term success. OBJECTIVE: The aim of the present study was to investigate the extent of physisorption of polymers on a titanium alloy (Ti6Al4V) surface. In addition, the water contact angles on the physisorbed coatings were measured to compare the hydrophilicity of the modified surfaces. METHODS: Ti6Al4V disks (13-mm diameter) were prepared to evaluate polymer adsorption on the alloy surface. The surface hydrophilicity was evaluated by contact angle (Θ) measurement. Physisorption of polymers on the surface was evaluated quantitatively by a colorimetric method. RESULTS: The largest contact angles were recorded on samples polished with silicon carbide papers of 1200 and 500 grit (Poli1200 and Poli500 samples: 97.3 ± 4.8 and 84.8 ± 11.0, respectively). Treatment of polished samples with Kroll solution remarkable reduced the contact angles to 46.8 ± 11.6 and 58.6 ± 11.5 for Poli500+Kroll and Poli1200+Kroll, respectively. Contact angles were further reduced in response to PolyNaSS and PAA treatment. Regardless of surface treatment, there was no significant difference in the contact angles on surfaces after SiC 500 and 1200 grit polishing. CONCLUSIONS: Physisorbed polymer coatings (such as PAA) on the Ti6Al4V surface can reduce the contact angle and improve the hydrophilicity and wettability of the alloy surface. Moreover, physisorption is a simple technique that does not require any special equipment.

[Surveillance of schistosomiasis in Xixi National Wetland Park, 2012-2014].

OBJECTIVE: To understand the endemic dynamic and situation of schistosomiasis in the Xixi National Wetland Park. METHODS: The surveillances of Oncomelania hupensis snail situation and the schistosome infection status of the permanent residents and floating population in the Xixi National Wetland were conducted annually from 2012 to 2014 according to the Surveillance Programs of Schistosomiasis in Surveillance Sites of Zhejiang Province. RESULTS: From 2012 to 2014, accumulatively 12.31 hm2 of area, 4965 m2 of vegetation and 75,379 alien plants were surveyed in the Xixi National Wetland Park, and no Oncomelania snails were found. The seropositive rates in the permanent residents and floating population were 0.71% (5/706) and 1.36% (25/1 834), respectively, and 1 imported chronic schistosomiasis case was found in 2014. Totally 3 006 floating personnel were involved in the investigation of infection status and awareness on knowledge of schistosomiasis control in 2013, the sero-positive rate was 0.63% (19/3 006), and the rates of those from endemic and non-endemic areas were 1.00% (15/1 503) and 0.27% (4/1 503), respectively, and the difference was statistically significant ( χ2 = 6.41, P < 0.05). The results of the fecal examinations among the seropositive cases were all negative. The awareness rates on the Regulation of Schistosomiasis Control and Prevention as well as related knowledge about Oncomelania snails were low. The indoor survival experiment of Oncomelania snails showed the survival rates of Oncomelania snails were 58.33% and 1.25% after observing for 3 and 6 months respectively. CONCLUSIONS: The Xixi National Wetland Park is suitable for Oncomelania snails to inhabit and breed. The imported cases in floating population pose a serious threat to the endemic situation of schistosomiasis in local. In the future, the surveillance on snails and floating population as well as the health education should be strengthened.