BMSC-derived Exosomes Ameliorate Peritoneal Dialysis-associated Peritoneal Fibrosis via the Mir-27a-3p/TP53 Pathway

Objective:Peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on PF in response to PD.Methods:Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing.C57BL/6J mice were infused with 4.25%glucose-based peritoneal dialysis fluid(PDF)for 6 consecutive weeks to establish a PF model.A total of 36 mice were randomly divided into 6 groups:control group,1.5%PDF group,2.5%PDF group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF.HE and Masson staining were performed to evaluate the extent of PF.The therapeutic potential of BMSC-Exos for PF was examined through pathological examination,RT-qPCR,Western blotting,and peritoneal function analyses.Epithelial-mesenchymal transition(EMT)of HMrSV5 was induced with 4.25%PDF.Cells were divided into control group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Cell Counting Kit-8 assay was used to measure cell viability,and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells.Results:Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs.The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos,but decreased in PD mice.We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice.Compared with the control mice,the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response,with markedly increased peritoneal thickness and higher expression ofα-SMA,collagen-I,fibronectin,and ECM1.The mice with PD showed decreased miR-27a-3p.Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment,while PF and mesothelial damage were significantly ameliorated.Additionally,markers of fibrosis(α-SMA,collagen-I,fibronectin,ECM1)and profibrotic cytokines(TGF-β1,PDGF)were downregulated at the mRNA and protein levels after BMSC-Exos treatment.In HMrSV5 cells,BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF.Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin(epithelial marker)and decreased expression ofα-SMA,Snail,and vimentin(mesenchymal markers)compared to those of the 4.25%PDF-treated cells.Importantly,a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p.TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos.Conclusion:The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53.

Salvage of venoarterial extracorporeal membrane oxygenation following prolonged cardiopulmonary resuscitation and failure of catheter-directed thrombectomy for massive pulmonary embolism in a young patient

Dear editor,Acute massive pulmonary embolism(PE) is a common life-threatening disease with high mortality of up to 30%–50%.[1,2]Potential heterogeneous reasons for PE remain controversial, and its treatment strategies mainly include antithrombotics, fibrinolytics, and embolectomy.

体重管理干预对肥胖型PCOS患者糖脂代谢的影响

目的探讨体重管理干预对肥胖型多囊卵巢综合征(PCOS)患者糖脂代谢的影响。方法选取肥胖型PCOS患者70例,按照患者是否愿意接受体重管理,将其分为干预组和对照组,分别测定并分析两组患者0、15、30及45 d干预糖脂代谢指标。结果 (1)干预后不同时间点的TG、TC、FPG、2 h PPG、FINS及PINS比较有差异(P<0.05);(2)两组患者干预后的TG、TC、2 h PPG、FINS及PINS比较有差异(P<0.05);(3)两组患者的TG、TC、2 h PPG及PINS变化趋势比较有差异(P<0.05)。结论肥胖型PCOS患者在药物治疗的基础上实施体重管理,能更有效地改善患者糖脂代谢异常,增强药物疗效。

3D Face Similarity Measure by Frechet Distances of Geodesics

3D face similarity is a critical issue in computer vision, computer graphics and face recognition and so on. Since Fr@chet distance is an effective metric for measuring curve similarity, a novel 3D face similarity measure method based on Fr^chet distances of geodesics is proposed in this paper. In our method, the surface similarity between two 3D faces is measured by the similarity between two sets of 3D curves on them. Due to the intrinsic property of geodesics, we select geodesics as the comparison curves. Firstly, the geodesics on each 3D facial model emanating from the nose tip point are extracted in the same initial direction with equal angular increment. Secondly, the Fr@chet distances between the two sets of geodesics on the two compared facial models are computed. At last, the similarity between the two facial models is computed based on the Fr6chet distances of the geodesics obtained in the second step. We verify our method both theoretically and practically. In theory, we prove that the similarity of our method satisfies three properties： reflexivity, symmetry, and triangle inequality. And in practice, experiments are conducted on the open 3D face database GavaDB, Texas 3D Face Recognition database, and our 3D face database. After the comparison with iso-geodesic and Hausdorff distance method, the results illustrate that our method has good discrimination ability and can not only identify the facial models of the same person, but also distinguish the facial models of any two different persons.

A homozygous protein-truncating mutation in ACTL7A causes male infertility characterized by fertilization failure

Objective:This study aimed to screen for novel mutations in ACTL7A and expand the spectrum of known mutations responsible for recurrent fertilization failure.Methods:Whole-exome sequencing was performed on samples from couples who experienced recurrent assisted reproductive technology failure and visited the General Hospital of Ningxia Medical University.Western blotting and quantitative Real-time PCR were used to investigate the effects of the mutation on HEK293T cells.Results:Samples from 12 couples with total fertilization failure or poor fertilization(fertilization rate<20%)were subjected to whole-exome sequencing,and a novel homozygous protein-truncating mutation(c.1101dupC,p.S368Qfs*5)in ACTL7A was identified in a patient with recurrent poor fertilization.The mutant resulted in a truncated protein as well as decreased protein expression level in HEK293T cells.Conclusions:Our findings expand the mutational and phenotypic spectrum of ACTL7A,thus providing a potential diagnostic marker for fertilization failure due to male factors.