腰大池引流联合法舒地尔治疗动脉瘤性蛛网膜下腔出血的疗效及对血清sICAM-1、FABP、MCP-1水平和脑积水形成的影响

目的:分析腰大池引流联合法舒地尔治疗动脉瘤性蛛网膜下腔出血的疗效及对血清可溶性细胞间黏附分子-1(sICAM-1)、脂肪酸结合蛋白质(FABP)、核细胞趋化蛋白(MCP-1)水平和脑积水形成的影响。方法:选择我院2016年3月~2018年3月收治的112例动脉瘤性蛛网膜下腔出血患者,按随机数字表法分为对照组(n=48)和研究组(n=64)。对照组采用腰大池引流治疗,研究组基于对照组联合法舒地尔治疗。比较两组临床疗效,治疗前后血清sICAM-1、FABP、MCP-1水平、血压、大脑中动脉血流参数水平和神经功能的变化,脑积水发生率及不良反应发生情况。结果:治疗后,研究组总有效率显著高于对照组(89.02%vs.72.91%,P<0.05)。两组治疗后血清sICAM-1、FABP、MCP-1、血压、大脑中动脉血流参数水平和神经功能缺损评分量表(NIHSS)均较治疗前下降,格拉斯哥昏迷评分(GCS)均较治疗前上升,研究组以上指标较对照组改变更明显(均P<0.05)。两组不良反应发生情况比较差异无统计学意义(P>0.05)。结论:腰大池引流联合法舒地尔治疗动脉瘤性蛛网膜下腔出血的疗效明显优于单用腰大池引流治疗,其可显著降低血清sICAM-1、FABP、MCP-1水平,降低脑积水发生率,改善患者预后。     

椎间孔镜与开窗术对腰椎间盘突出患者远期治疗效果对比

目的:探究椎间孔镜与开窗术对腰椎间盘突出患者治疗远期效果对比。方法:选择2016年3月至2018年3月于我院接受治疗的腰椎间盘突出患者,按照其接受术式的不同将其分为孔镜组(108例)和开窗组(40例),对比两组手术出血量、术后卧床时间及切口长度,对比两组术前、术后3个月及术后12个月腰椎日本矫形外科学会(Japan Orthopaedic Assoctiation,JOA)评分、Odwestry功能障碍指数(Odwestris ability index, ODI)评分、视觉模拟评分(Visual analog scales,VAS)及生活质量评分,最后对比两组术后12个月椎间隙高度降低数值。结果:(1)孔镜组术中出血量、术后卧床时间及切口长度均小于开窗组,手术时间长于开窗组(P0.05);(2)术前两者JOA及ODI评分对比无统计学意义(P0.05),术后3个月及术后12个月孔镜组JOA及ODI评分优于开窗组(P0.05);(3)术前两组VAS及SF-36量表(the 36-item shot form health survey,SF-36)评分对比无统计学意义(P0.05),术后3个月及12个月两组VAS评分均有明显下降,SF-36评分有明显上升(P0.05),且术后3个月及12个月孔镜组SF-36评分高于开窗组(P0.05),VAS评分对比无统计学意义(P0.05);(4)术后12个月,孔镜组椎间隙高度降低率低于开窗组(P0.05)。结论:椎间孔镜在治疗腰椎间盘突出方面效果较好,相比于开窗术,孔镜术患者术中创伤小、术后恢复快、腰椎功能改善明显,且远期随访显示患者生活质量更高,值得进行临床推广。     

6-gingerol protects nucleus pulposus-derived mesenchymal stem cells from oxidative injury by activating autophagy

BACKGROUNDTo date, there has been no effective treatment for intervertebral disc degeneration (IDD). Nucleus pulposus-derived mesenchymal stem cells (NPMSCs) showed encouraging results in IDD treatment, but the overexpression of reactive oxygen species (ROS) impaired the endogenous repair abilities of NPMSCs. 6-gingerol (6-GIN) is an antioxidant and anti-inflammatory reagent that might protect NPMSCs from injury.AIMTo investigate the effect of 6-GIN on NPMSCs under oxidative conditions and the potential mechanism.METHODSThe cholecystokinin-8 assay was used to evaluate the cytotoxicity of hydrogen peroxide and the protective effects of 6-GIN. ROS levels were measured by 2´7´-dichlorofluorescin diacetate analysis. Matrix metalloproteinase (MMP) was detected by the tetraethylbenzimidazolylcarbocyanine iodide assay. TUNEL assay and Annexin V/PI double-staining were used to determine the apoptosis rate. Additionally, autophagy-related proteins (Beclin-1, LC-3, and p62), apoptosis-associated proteins (Bcl-2, Bax, and caspase-3), and PI3K/Akt signaling pathway-related proteins (PI3K and Akt) were evaluated by Western blot analysis. Autophagosomes were detected by transmission electron microscopy in NPMSCs. LC-3 was also detected by immunofluorescence. The mRNA expression of collagen II and aggrecan was evaluated by real-time polymerase chain reaction (RT-PCR), and the changes in collagen II and MMP-13 expression were verified through an immunofluorescence assay.RESULTS6-GIN exhibited protective effects against hydrogen peroxide-induced injury in NPMSCs, decreased hydrogen peroxide-induced intracellular ROS levels, and inhibited cell apoptosis. 6-GIN could increase Bcl-2 expression and decrease Bax and caspase-3 expression. The MMP, Annexin V-FITC/PI flow cytometry and TUNEL assay results further confirmed that 6-GIN treatment significantly inhibited NPMSC apoptosis induced by hydrogen peroxide. 6-GIN treatment promoted extracellular matrix (ECM) expression by reducing the oxidative stress injury-induced increase in MMP-13 expression. 6-GIN activated autophagy by increasing the expression of autophagy-related markers (Beclin-1 and LC-3) and decreasing the expression of p62. Autophagosomes were visualized by transmission electron microscopy. Pretreatment with 3-MA and BAF further confirmed that 6-GIN-mediated stimulation of autophagy did not reduce autophagosome turnover but increased autophagic flux. The PI3K/Akt pathway was also found to be activated by 6-GIN. 6-GIN inhibited NPMSC apoptosis and ECM degeneration, in which autophagy and the PI3K/Akt pathway were involved.CONCLUSION6-GIN efficiently decreases ROS levels, attenuates hydrogen peroxide-induced NPMSCs apoptosis, and protects the ECM from degeneration. 6-GIN is a promising candidate for treating IDD.     

Irregular chiasm-C-roughest, a member of the immunoglobulin superfamily, affects sense organ spacing on the Drosophila antenna by influencing the positioning of founder cells on the disc ectoderm

We describe a role for Irregular chiasmC-roughest (IrreC-rst), an immunoglobulin (Ig) superfamily member, in patterning sense organs on the Drosophila antenna. IrreC-rst protein is initially expressed homogeneously on apical profiles of ectodermal cells in regions of the antennal disc. During specification of founder cells (FCs), the intracellular protein distribution changes and becomes concentrated in regions where specific intercellular contacts presumably occur. Loss of function mutations as well as misexpression of irreC-rst results in an altered arrangement of FCs within the disc compared to wildtype. Sense organ development occurs normally, although spacing is affected. Unlike its role in interommatidial spacing, irreC-rst does not affect apoptosis during antennal development. We propose that IrreC-rst affects the spatial relationship between sensory and ectodermal cells during FC delamination. Received: 19 January 1999 / Accepted: 10 May 1999     

Regulation of Protrusion Shape and Adhesion to the Substratum during Chemotactic Responses of Mammalian Carcinoma Cells

We report here the first direct observation of chemotaxis to EGF by rat mammary carcinoma cells. When exposed to a gradient of EGF diffusing from a micropipette, MTLn3 cells displayed typical ameboid chemotaxis, extending a lamellipod-like protrusion and moving toward the pipette. Using a homogeneous upshift in EGF to model stimulated lamellipod extension (J. E. Segallet al.,1996,Clin. Exp. Metastasis14, 61–72), we analyzed the relationship between adhesion and chemoattractant-stimulated protrusion. Exposure to EGF led to a rapid remodeling of the adhesive contacts on adherent cells, in synchrony with extension of a flat lamellipod over the substratum. EGF-stimulated lamellipods still extended in the presence of adhesion-blocking peptides or over nonadhesive surfaces. They were, however, slightly shorter and retracted rapidly under those conditions. The major protrusive structure observed on well-spread, adherent cells, after EGF stimulation was a flat broad lamellipod, whether or not in contact with the substratum, while cells in suspension showed transient protrusive activity over the entire cell surface. We conclude that the initial adhesive status of the cell conditions the shape of the outcoming protrusion. Altogether our results suggest that, although adhesive contacts are not necessary for lamellipod extension, they play a role in stabilizing the protrusion as well as in the control of its final shape and amplitude.     

Positional information in imaginal discs transformed by homoeotic mutations

Summary Mutations of the bithorax complex result in segmental transformations in the thorax and abdomen ofDrosophila. The haltere discs from larvae homozygous forbx ³ orpbx are transformed so that the discs contain cells that will produce wing cuticle as well as cells that produce haltere cuticle. The pattern regulation behavior of these discs has been examined. The fate maps of the two discs were established, and then the regulative behavior of a number of fragments from both types of mutant discs was established by culturing the fragments in vivo prior to metamorphosis. The most important conclusion from this work is that the cells producing, haltere cuticle and wing cuticle within the same disc share the same positional information and that they communicate during pattern regulation.     

Analyses of deoxycytidylate deaminase molecular forms in human-mouse and monkey-mouse somatic cell hybrids

Disc polyacrylamide gel electrophoresis (disc PAGE) analyses have revealed that mouse, human, and monkey cytosol deoxycytidylate (dCMP) deaminases differ in electrophoretic mobility, so that mixtures of mouse and human, mouse and monkey, and human and monkey enzymes can be separated. To learn whether the genes for dCMP deaminase and thymidine (dT) kinase are genetically linked, disc PAGE analyses of cytosol fractions from human-mouse and monkey-mouse somatic cell hybrids were carried out. The interspecific somatic cell hybrids were derived from the fusion of cytosol dT kinase deficient mouse cells with cytosol dT kinase-positive human and monkey cells: they contained mostly mouse chromosomes and a few primate chromosomes, including the determinant for primate cytosol dT kinase. The disc PAGE analyses demonstrated that the human-mouse and monkey-mouse somatic cell hybrids contained a dCMP deaminase activity with an electrophoretic mobility characteristic of mouse dCMP deaminase. Enzymes with electrophoretic mobilities characteristic of human and monkey dCMP deaminases were not demonstrable. These findings suggest that primate cytosol dT kinase and dCMP deaminase are coded on different chromosomes, or that the formation in hybrid cells of an active primate dCMP deaminase is suppressed. Chick-mouse somatic cell hybrids containing chick but not mouse cytosol dT kinase were also analyzed. The chick-mouse hybrid cells contained cytosol dCMP deaminase activity, but it was not possible to establish whether the enzyme was of murine or avian origin because of the similarity in electrophoretic mobility between the chick and mouse enzymes. Human and mouse cells contained low levels of mitochondrial dCMP deaminase activity. In contrast to dT kinase isozymes, however, mitochondrial and cytosol dCMP deaminases were electrophoretically indistinguishable.This investigation was aided by Grant Q-163 from the Robert A. Welch Foundation and by USPHS Grants CA-06656-12 and 1-K6-AI 2352 from the National Cancer Institute and the National Institute of Allergy and Infectious Diseases.     

A combined passive and active musculoskeletal model study to estimate L4-L5 load sharing

A number of geometrically-detailed passive finite element (FE) models of the lumbar spine have been developed and validated under in vitro loading conditions. These models are devoid of muscles and thus cannot be directly used to simulate in vivo loading conditions acting on the lumbar joint structures or spinal implants. Gravity loads and muscle forces estimated by a trunk musculoskeletal (MS) model under twelve static activities were applied to a passive FE model of the L4-L5 segment to estimate load sharing among the joint structures (disc, ligaments, and facets) under simulated in vivo loading conditions. An equivalent follower (FL), that generates IDP equal to that generated by muscle forces, was computed in each task. Results indicated that under in vivo loading conditions, the passive FE model predicted intradiscal pressures (IDPs) that closely matched those measured under the simulated tasks (R² = 0.98 and root-mean-squared-error, RMSE = 0.18 MPa). The calculated equivalent FL compared well with the resultant force of all muscle forces and gravity loads acting on the L4-L5 segment (R² = 0.99 and RMSE = 58 N). Therefore, as an alternative approach to represent in vivo loading conditions in passive FE model studies, this FL can be estimated by available in-house or commercial MS models. In clinical applications and design of implants, commonly considered in vitro loading conditions on the passive FE models do not adequately represent the in vivo loading conditions under muscle exertions. Therefore, more realistic in vivo loading conditions should instead be used.