ABSTRACT
Objective To investigate the effect of complement C3a on mouse podocytes phenotype transformation.Methods Purified C3a recombinant protein was used to stimulate mature mouse podocytes.The expression of the mature podocyte markers synaptopodin,podocin,nephrin,CD2-associated protein (CD2AP) and the mesenchymal cell markers fibroblast specific protein 1 (FSP-1),α-smooth muscle actin (α-SMA) were detected by RT-PCR,Western blotting,immunochemistry and immunofluorescence,respectively.Some podocytes were transfected with integrin-linked kinase (ILK) siRNA before the administration of C3a,the expression of nephrin and α-SMA were accessed by Western blotting,and the expression of Snail and α-actinin 4 were accessed by Western blotting and immunochemical method.The migration ability of podocytes was observed by scratch test.Results Immunocytochemistry and immunofluorescence analysis showed that synaptopodin,podocin,nephrin,CD2AP were highly expressed by mature mouse podocytes.The expression of these podocyte markers could be markedly inhibited after 24 h of C3a (0.1 μmol/L) treatment,and accompanied by the induction of mesenchymal markers FSP-1 and α-SMA.Compared with control group,the mRNA levels of synaptopodin,podocin,CD2AP and nephrin were significantly repressed by the administration of C3a in a dose-dependent manner,whereas the transcription of FSP-1 and α-SMA were remarkably up-regulated by C3a treatment (P ＜ 0.05,respectively).Western blotting analysis also confirmed the decrease of synaptopodin,podocin,nephrin and CD2AP protein and the increase of FSP-1 and α-SMA protein were closely depend on the C3a concentration (P ＜ 0.05,respectively).To further assess the downstream of C3a,some podocytes were transfected with ILK siRNA before the administration of C3a.Compared with C3a group,the protein levels of nephrin and α-SMA were significantly changed by the administration of ILK siRNA (P ＜ 0.05,respectively).The expression of α-actinin 4 and Snail induced by C3a were inhibited by ILK knockdown (P ＜ 0.05,respectively),accompanied by a decline of cell migration potency.Conclusion Complement fragment C3a can induce transformation of mouse podocytes to mesenehymal cells,and ILK signaling pathway is involved in this cell type transformation.
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Objective To explore the risk factors of bone density disorder and vascular calcification in non-dialysis chronic kidney disease (CKD) patients.Methods Clinical data of nondialysis CKD patients who were admitted to the First Affiliated Hospital of Fujian Medical University between January 2013 and June 2014 were retrospectively analyzed.Using dual energy X-ray absorptiometry to evaluate their bone mineral density (BMD) and T value.Patients were divided into normal BMD group (T≥-1),osteopenia group (-2.5 ＜ T ＜-1) and osteoporosis group (T≤-2.5).The vascular calcification was evaluated by pectoral computed tomography.Multi-factor stepwise logistic regression analysis was used to assess the risk factors for low bone density and vascular calcification in non-dialysis CKD patients.Results A total of 337 non-dialysis CKD patients were enrolled.There were 110 (32.6％) patients with normal BMD,and 146(43.3％) patients with osteopenia,and 81(24.0％) patients with osteoporosis.Gender,history of hypertension,25-hydroxy vitamin D and N-terminal osteocalcin shown statistical differences among three groups (all P ＜ 0.05).The incidence rate of 25-hydroxy vitamin D deficiency shown statistical difference among three groups (P=0.012).Further,the rates were increased with the decreased bone mass (x2=7.100,P=0.008).The other mineral bone disorders,such as hypocalcemia,hyperphosphatemia,low intact parathyroid hormone (iPTH) and high iPTH had no statistical difference among three groups (all P ＞ 0.05).Multi-factor stepwise logistic regression analysis revealed that increased iPTH (OR=1.938),and low bone density (OR=1.724) were independent risk factors for CKD patients with vascular calcification (all P ＜ 0.05),while women (OR=3.312) and vascular calcification (OR=1.742) were independent risk factors for CKD patients with low bone density (all P ＜ 0.05).Conclusion Increased iPTH and low bone density are independent risk factors for non-dialysis CKD patients with vascular calcification,while women and vascular calcification are independent risk factors for non-dialysis CKD patients with low bone density.
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OBJECTIVE:To systematically review the efficacy and safety of mizolastine combined with H2 recepter antagonists in the treatment of chronic urticaria,and provide evidence-based reference for the clinical treatment. METHODS:Retrieved from PubMed,Cochrane Library,EMBase,CBM,CJFD,etc.,randomized controlled trials (RCT) or QRCT about mizolastine com-bined with H2 recepter antagonists(test group)versus mizolastine alone(control group)in the treatment of chronic urticaria. After quality evaluation and data extract,Meta-analysis was conducted by using Stata 12.0 statistics software. RESULTS:A total of 12 RCT were included,involving 1 188 patients. Results of Meta-analysis showed the effective rate [RR=1.23,95%CI(1.16,1.31), P0.05]. CONCLUSIONS:The effective rate of mizo-lastine combined with H2 recepter antagonists is significantly higher than mizolastine in the treatment of chronic urticaria,with bet-ter safety. Due to the limit of methodological quality and sample size,it remains to be further verified with more rigorously de-signed and long-term follow-up of large-scale RCT.