Peritoneal dialysis effluent-derived exosomal miR-432-5p: an assessment tool for peritoneal dialysis efficacy.

Background: Ultrafiltration (UF) volume and peritoneal solute transport rate (PSTR) are common parameters used to evaluate the efficacy of peritoneal dialysis (PD) on individual patients. It is unclear whether the level of exosomal microRNA (miRNA) in peritoneal dialysis effluent (PDE) can predict UF or PSTR. This study was designed to investigate if there is a correlation between PDE exosomal miRNA (miR-432-5p) levels and various UF volumes and PSTRs in PD patients. It also aimed to explore the underlying mechanism of water and dialytic sodium removal (DSR). Methods: The PSTR was quantified using the 4-hour (4 h) 3.86% dialysate to plasma creatinine ratio. The PDE exosomes (PDE-exo) were isolated by ultracentrifugation. An miRNA assay was used to identify the different miRNA in the PDE-exo of patients in a high (H; PSTR >0.65, n=5) and low (L; PSTR <0.65, n=5) group. We focused on miR-432-5p as bioinformatic analysis had shown that it could be involved in sodium transport. We used mimic/inhibitor transfection and dual luciferase reporter assay to verify the target genes of miR-432-5p. We used PKH-67 stained PDE-exo to observe their interaction with human MeT-5A mesothelial cells. Results: Our results showed that the PDE-exo-miR-432-5p level was higher in group H than in group L. The levels of PDE-exo-miR-432-5p were positively correlated with PSTR (r=0.391; P<0.05; n=40) and negatively correlated with the 4 h UF volume (r=-0.376; P<0.05; n=40) and 4 h DSR (r=-0.535; P<0.01; n=24). Epithelial sodium channel α subunit (α-ENaC) was revealed as a direct target gene of miR-432-5p and expressed on both human peritoneum and MeT-5A cells. Furthermore, we found the PKH67 labeled-PDE-exo could be internalized into MeT-5A cells. Conclusions: A high PDE-exo-miR-432-5p level was associated with poor UF volume and DSR. It may be that PDE-exo-miR-432-5p affects DSR through downregulating α-ENaC expression.

Effect and Safety of Huannao Yicong Formula () in Patients with Mild-to-Moderate Alzheimer's Disease: A Randomized, Double-Blinded, Donepezil-Controlled Trial.

OBJECTIVE: To assess the effect and safety of Huannao Yicong Formula (, HYF) in the treatment of patients with mild-to-moderate Alzheimer's disease (AD). METHODS: Sixty patients with mild-tomoderate AD were evenly randomized into HYF group and donepezil group with the random number method. Patients in the HYF group took 5 g of HYF granules twice daily and 5 mg placebo of donepezil once daily. Patients in the donepezil group took 5 mg donepezil once daily and 5 g placebo of HYF granules twice daily. The intervention lasted for 6 months. Clinical researchers, participants and statisticians were blinded to the treatment assignment throughout the study. The primary outcomes were scores of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Montreal Cognitive Assessment (MoCA) test and Mini-Mental State Exam (MMSE). The serum levels of acetylcholinesterase (AchE) and amyloid-ß protein 42 (Aß42) were detected with enzymelinked immunosorbent assay kits. The scale assessments were conducted at baseline, the 3rd and 6th months of treatment, respectively. Biochemistry tests were conducted at baseline and the 6th month of treatment. RESULTS: A total of 52 patients completed the trial, 28 in HYF group and 24 in donepezil group. Compared with the baseline, HYF and donepezil signifificantly decreased the total scores of ADAS-Cog and CM-SS, and signifificantly increased the scores of MoCA and MMSE after 6-month treatment (all P<0.01). Both treatments remarkably reduced the serum levels of AchE and Aß42 (both P<0.05). The CM-SS total effective rate of HYF was signifificantly higher than donepezil [75.00% (21/28) vs. 54.17% (13/24), P<0.05]. No severe adverse events were observed in both groups. CONCLUSION: HYF is effective and safe for improving the cognitive function in mildto-moderate AD patients. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-IOR-17011746)].

Immunosuppression effects of bone marrow mesenchymal stem cells on renal interstitial injury in rats with unilateral ureteral obstruction.

We investigated the effects of intravenously administered bone marrow mesenchymal stem cells (BMSCs) on renal interstitial inflammation and fibrosis. In unilateral ureteral obstruction (UUO) rats, the CD4(+)CD25(+) regulatory T-cell (Treg) cell, macrophage population and some inflammation related cytokines were tested. In the BMSCs -treated rats, renal exhibited lower renal Masson scores, decreased macrophage infiltration and interferon gamma (IFNγ) expression, and increased forkhead transcription factor (Foxp3) and interleukin-10 (IL-10) expression. No significant differences in the CD4(+)CD25(+) Treg population and renal transforming growth factor-ß1 (TGFß1) expression were observed between BMSCs-treated group and control group (p>0.05). In conclusion, BMSCs infusion leads to an anti-inflammation response in the early stage of UUO which may related to paracine mechanism.

[Application and prospect on the resin-dentin adhesion in the root canal therapy].

The application of adhesive root canal filling materials is the tendency in root canal obturation. The orientation is to develop the adhesive core material and sealer making a whole structure. In this review, we summarized the researches on the resin-dentin adhesion in the root canal obturation.