血管内支架介入成形术对老年缺血性脑血管病患者的神经功能、动脉血流速度及预后的影响

摘要 目的：探讨血管内支架介入成形术对老年缺血性脑血管病（ICVD）患者的神经功能、动脉血流速度及预后的影响。方法：选取2018年3月~2019年4月期间我院收治的117例老年ICVD患者作为研究对象,根据随机数字表法分为对照组（n=58）和研究组（n=59）,其中对照组患者予以保守药物治疗,研究组患者予以血管内支架介入成形术治疗,比较两组患者疗效、神经功能、动脉血流速度、预后及并发症情况。结果：研究组治疗6个月后的临床总有效率为91.53%（54/59）,高于对照组的72.41%（42/58）（P<0.05）。两组患者治疗后1个月、治疗后3个月、治疗后6个月美国国立卫生研究院卒中量表（NIHSS）评分均下降（P<0.05）,且研究组低于对照组（P<0.05）。两组患者治疗后6个月大脑中动脉、基底动脉、颈内动脉血流速度均升高（P<0.05）,且研究组高于对照组（P<0.05）。两组患者治疗后1个月、治疗后3个月、治疗后6个月改良Rankin量表（mRS）评分呈下降趋势（P<0.05）,且研究组低于对照组（P<0.05）。两组患者并发症发生率对比未见统计学差异（χ²=2.261,P=0.133）。结论：老年ICVD患者经血管内支架介入成形术治疗后的疗效显著,可有效改善患者神经功能、动脉血流速度及预后,且不增加并发症发生率,具有较高的临床应用价值。     

免疫球蛋白联合磷酸肌酸钠对病毒性心肌炎患儿心肌重塑和心肌损伤的影响

摘要 目的：研究免疫球蛋白联合磷酸肌酸钠对病毒性心肌炎患儿心肌重塑和心肌损伤的影响。方法：选择2017年1月～2019年12月我院收治的143例病毒性心肌炎患儿,随机分为两组。对照组静脉输注磷酸肌酸钠治疗,每次0.5～1.0 g,每天1次,连用14 d。观察组联合静脉注射人免疫球蛋白,剂量1 g/(kg?d),每天1次,连用2 d。检测两组治疗前后的心肌重塑指标和心肌损伤指标变化情况。结果：观察组的有效率明显高于对照组（P<0.05）;治疗前,两组的血清血清转化生长因子β1(transforming growth factor-β1,TGFβ1）、I型前胶原氨基端肽(nitrogen terminal propeptide of type I procollagen,PINP）、基质金属蛋白酶(matrix metalloproteinase-2,MMP2）、I型胶原吡啶交联终肽(type I collagen carboxy terminal telopeptide,ICTP）、MMP9水平无明显差异（P>0.05）,治疗后,两组的血清TGFβ1、PINP、MMP2、ICTP、MMP9水平均明显降低（P<0.05）,且观察组的血清TGFβ1、PINP、MMP2、ICTP、MMP9水平明显低于对照组（P<0.05）;治疗前,两组的血清血清丙二醛(malondialdehyde,MDA）、心肌肌钙蛋白I(Cardiac troponini,cTnI）、脑利钠肽(B -type natriuretic peptide,BNP）、肌酸激酶同工酶(Creatine kinase isoenzyme,CK-MB）水平无明显差异（P>0.05）,治疗后,两组的血清MDA、CK-MB、BNP和cTnI水平均明显降低（P<0.05）,且观察组的血清MDA、CK-MB、BNP和cTnI水平明显低于对照组（P<0.05）。结论：免疫球蛋白联合磷酸肌酸钠对病毒性心肌炎患儿有显著的疗效,能有效抑制心肌重塑、减轻心肌损伤,值得进行推广。     

Charged multivesicular body protein 2B (CHMP2B) of the endosomal sorting complex required for transport-III (ESCRT-III) polymerizes into helical structures deforming the plasma membrane

The endosomal sorting complexes required for transport (ESCRT-0-III) allow membrane budding and fission away from the cytosol. This machinery is used during multivesicular endosome biogenesis, cytokinesis, and budding of some enveloped viruses. Membrane fission is catalyzed by ESCRT-III complexes made of polymers of charged multivesicular body proteins (CHMPs) and by the AAA-type ATPase VPS4. How and which of the ESCRT-III subunits sustain membrane fission from the cytoplasmic surface remain uncertain. In vitro, CHMP2 and CHMP3 recombinant proteins polymerize into tubular helical structures, which were hypothesized to drive vesicle fission. However, this model awaits the demonstration that such structures exist and can deform membranes in cellulo. Here, we show that depletion of VPS4 induces specific accumulation of endogenous CHMP2B at the plasma membrane. Unlike other CHMPs, overexpressed full-length CHMP2B polymerizes into long, rigid tubes that protrude out of the cell. CHMP4s relocalize at the base of the tubes, the formation of which depends on VPS4. Cryo-EM of the CHMP2B membrane tubes demonstrates that CHMP2B polymerizes into a tightly packed helical lattice, in close association with the inner leaflet of the membrane tube. This association is tight enough to deform the lipid bilayer in cases where the tubular CHMP2B helix varies in diameter or is closed by domes. Thus, our observation that CHMP2B polymerization scaffolds membranes in vivo represents a first step toward demonstrating its structural role during outward membrane deformation.     

The protease allergen Pen c 13 induces allergic airway inflammation and changes in epithelial barrier integrity and function in a murine model

Fungal allergens are associated with the development of asthma, and some have been characterized as proteases. Here, we established an animal model of allergic airway inflammation in response to continuous exposure to proteolytically active Pen c 13, a major allergen secreted by Penicillium citrinum. In functional analyses, Pen c 13 exposure led to increased airway hyperresponsiveness, significant inflammatory cell infiltration, mucus overproduction, and collagen deposition in the lung, dramatically elevated serum levels of total IgE and Pen c 13-specific IgE and IgG1, and increased production of the Th2 cytokines IL-4, IL-5, and IL-13 by splenocytes stimulated in vitro with Pen c 13. To examine the mechanisms involved in the regulation of allergenicity by Pen c 13, we performed two-dimensional fluorescence difference gel electrophoresis analysis combined with nano-LC-MS/MS, followed by bioinformatics analysis to identify potential targets that associated with allergic inflammation, which suggested that galectin-3 and laminin might be involved in novel pathogenic mechanisms. Finally, we focused on junctional proteins between cells, because, in addition to opening of the epithelial barrier by environmental proteases possibly being the initial step in the development of asthma, these proteins are also associated with actin rearrangement. Taken together, our findings indicate that Pen c 13 exposure causes junctional structure alterations and actin cytoskeletal rearrangements, resulting in increased permeability and airway structural changes. These effects probably change the lung microenvironment and foster the development of allergic sensitization.     

Contractile forces contribute to increased glycosylphosphatidylinositol-anchored receptor CD24-facilitated cancer cell invasion

The malignancy of a tumor depends on the capability of cancer cells to metastasize. The process of metastasis involves cell invasion through connective tissue and transmigration through endothelial monolayers. The expression of the glycosylphosphatidylinositol-anchored receptor CD24 is increased in several tumor types and is consistently associated with increased metastasis formation in patients. Furthermore, the localization of β1-integrins in lipid rafts depends on CD24. Cell invasion is a fundamental biomechanical process and usually requires cell adhesion to the extracellular matrix (ECM) mainly through β1 heterodimeric integrin receptors. Here, we studied the invasion of A125 human lung cancer cells with different CD24 expression levels in three-dimensional ECMs. We hypothesized that CD24 expression increases cancer cell invasion through increased contractile forces. To analyze this, A125 cells (CD24 negative) were stably transfected with CD24 and sorted for high and low CD24 expression. The invasiveness of the CD24(high) and CD24(low) transfectants was determined in three-dimensional ECMs. The percentage of invasive cells and their invasion depth was increased in CD24(high) cells compared with CD24(low) cells. Knockdown of CD24 and of the β1-integrin subunit in CD24(high) cells decreased their invasiveness, indicating that the increased invasiveness is CD24- and β1-integrin subunit-dependent. Fourier transform traction microscopy revealed that the CD24(high) cells generated 5-fold higher contractile forces compared with CD24(low) cells. To analyze whether contractile forces are essential for CD24-facilitated cell invasion, we performed invasion assays in the presence of myosin light chain kinase inhibitor ML-7 as well as Rho kinase inhibitor Y27632. Cell invasiveness was reduced after addition of ML-7 and Y27632 in CD24(high) cells but not in CD24(neg) cells. Moreover, after addition of lysophosphatidic acid or calyculin A, an increase in pre-stress in CD24(neg) cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase or STAT3 strongly reduced the invasiveness of CD24(high) cells, slightly reduced that of CD24(low) cells, and did not alter the invasiveness of CD24(neg) cells. Taken together, these results suggest that CD24 enhances cell invasion through increased generation or transmission of contractile forces.     

Periostin promotes atrioventricular mesenchyme matrix invasion and remodeling mediated by integrin signaling through Rho/PI 3-kinase

Recent evidence suggests that extracellular matrix components may play a signaling role in embryonic valve development. We have previously identified the spatiotemporal expression patterns of periostin in developing valves, but its function during this process is largely unknown. To evaluate the functional role periostin plays during valvulogenesis, two separate three-dimensional culture assay systems, which model chick atrioventricular cushion development, were employed. These assays demonstrated that cushion mesenchymal cells adhered and spread on purified periostin in a dose-responsive manner, similar to collagen I and fibronectin via alpha(v)beta(3) and beta(1) integrin pairs. Periostin overexpression resulted in enhanced mesenchyme invasion through 3D collagen gels and increased matrix compaction. This invasion was dependent on alpha(v)beta(3) more than beta(1) integrin signaling, and was mediated differentially by Rho kinase and PI 3-kinase. Both matrix invasion and compaction were associated with a colocalization of periostin and beta(1) integrin expression to migratory cell phenotype in both surface and deep cells. The Rho/PI 3-kinase pathway also differentially mediated matrix compaction. Both Rho and PI 3-kinase were involved in normal cushion mesenchyme matrix compaction, but only PI 3-kinase was required for the enhanced matrix compaction due to periostin. Taken together, these results highlight periostin as a mediator of matrix remodeling by cushion mesenchyme towards a mature valve structure.