法舒地尔、疏血通联合治疗糖尿病合并脑梗死44例疗效观察

的:研究疏血通联合法舒地尔对于糖尿病并发脑梗死的治疗价值。方法:选择在我院就诊的糖尿病合并脑梗死患者作为研究对象,随机分为给予法舒地尔、疏血通联合治疗的观察组和法舒地尔治疗的对照组,观察治疗效果、神经功能、精神状态及其相关的血清细胞因子水平。结果:观察组治疗总有效率95.5%、MMSE皮肤以及外周血中NTF、NGF以及VEGF的含量均明显高于对照组;CSS评分、NIHSS评分均明显低于对照组。结论:疏血通联合法舒地尔治疗能够提高治疗效果、改善神经功能和精神状态,具有积极的临床价值。     

尤瑞克林联合依达拉奉治疗急性脑梗死的临床疗效及对血清VEGF和NO的影响

目的:观察尤瑞克林联合依达拉奉治疗急性脑梗死的临床疗效及对血清血管内皮生长因子(vascular endothelial growth factor,VEGF)和一氧化氮(nitric oxide,NO)的影响。方法:将2015年1月至2016年12月期间在我院神经内科住院治疗的急性脑梗死患者70例随机分成观察组和对照组。两组患者均采用常规治疗方式,如抗血小板、脑保护、活血化瘀等。在此基础上,给予观察组患者依达拉奉和尤瑞克林治疗,而对照组仅给予依达拉奉治疗,两组患者均持续治疗10 d。随后,分别观察两组患者的临床疗效以及治疗前后的血清VEGF和NO水平变化。结果:观察组的总有效率明显高于对照组,且差异具有统计学意义(P0.05);治疗后,两组患者的血清VEGF和NO水平均较治疗前明显升高,NIHSS评分明显下降(P0.05),且观察组的血清VEGF和NO水平均显著高于对照组,NIHSS评分明显低于对照组差异(P0.05)。结论:采用尤瑞克林联合依达拉奉治疗急性脑梗死的临床疗效优于依达拉奉单药治疗,可能与其明显提高血清血清VEGF、NO水平,有助于改善患者的血管内皮细胞功能和神经功能缺损有关。     

覆膜支架腔内修复术对Stanford B型主动脉夹层动脉瘤患者术后血清血管内皮生长因子、核因子-κB水平的影响

目的:分析覆膜支架腔内修复术对Stanford B型主动脉夹层动脉瘤患者术后血清血管内皮生长因子(VEGF)、核因子-κB(NF-κB)水平的影响。方法:选取2015年6月～2017年6月空军军医大学第一附属医院收治的150例Stanford B型主动脉夹层动脉瘤患者,根据治疗方法不同分为两组。对照组(75例)采用药物治疗,观察组(75例)采用覆膜支架腔内修复术治疗,对比两组治疗前后血清血管内皮生长因子(VEGF)、核因子-KB(NF-κB)、白细胞介素-1β(IL-1β)、干扰素-γ(IFN-γ)、急性生理和慢性健康状况(Acute physiology and chronic health evaluation,APACHEⅡ)评分、SF-36量表评分的变化,并发症(内漏、动脉栓塞、左上肢乏力、支架后移等)发生情况,再次手术或介入治疗发生率及病死率。结果:治疗后,观察组血清VEGF、NF-κB、IL-1β、IFN-γ水平显著低于对照组(P0.05);两组治疗后APACHEⅡ评分均较治疗前降低,SF-36量表评分均较治疗前升高,且观察组APACHEⅡ与SF-36量表评分改善程度大于对照组(P0.05);观察组并发症总发生率4%、再次手术或介入治疗发生率为5.33%,病死率为1.33%,均显著低于对照组(17.33%、21.33%、10.67%,P0.05)。结论:覆膜支架腔内修复术能显著提高Stanford B型主动脉夹层动脉瘤患者生活质量与生存率,并发症与再治疗发生率,改善其病情,可能降低VEGF、NF-κB水平有关。     

Rt-PA静脉溶栓治疗急性脑梗死的疗效及对血清IL-6，IL-17及VEGF水平的影响

目的:探讨重组组织纤溶酶原激活剂(Rt-PA)静脉溶栓治疗急性脑梗死的疗效及对血清白介素-6(IL-6)、IL-17及血管内皮生长因子(VEGF)水平的影响。方法:选择2014年8月至2016年8月我院接诊的86例急性脑梗死患者,通过随机数表法分为观察组(n=43)和对照组(n=43)。对照组给予常规治疗,观察组在对照组基础上进行Rt-PA静脉溶栓。比较两组的治疗效果、不良反应的发生情况、治疗前后美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数、血清IL-6、IL-17及VEGF水平的变化。结果:治疗14 d后,观察组NIHSS评分显著低于对照组,Barthel指数明显高于对照组(P0.05);观察组在治疗后1 d、3 d、7 d、14 d时血清IL-6、IL-17水平均显著低于对照组(P0.05),治疗后1 d、3 d、7 d时血清VEGF水平明显高于对照组,治疗后14 d时血清VEGF水平显著低于对照组(P0.05)。观察组治疗后总有效率显著高于对照组(P0.05)。结论:在急性脑梗死患者中早期采用Rt-PA治疗的效果显著,可有效促进神经功能恢复,且安全性高,可能与其降低血清IL-6、IL-17、VEGF水平有关。     

高压氧联合神经节苷脂对高血压脑出血患者术后的影响

目的:分析高压氧联合神经节苷脂对高血压脑出血患者微创血肿清除术后的临床疗效。方法:选择2012年1月-2016年10月我院收治的高血压脑出血患者100例,根据随机数字表法分成观察组、对照组,每组各50例。所有患者均先行微创血肿清除术,对照组患者术后24 h内确定体征平稳,病情稳定后给予高压氧治疗,观察组在对照组治疗方法的基础之上加用神经节苷脂。比较两组患者的临床疗效、治疗前后神经功能缺损评分(NIHSS)、脑水肿体积、血清基质金属蛋白酶-9(MMP-9)、S100β蛋白及神经生长因子(NGF)的水平的变化及术后3个月时的日常生活活动能力。结果:治疗后,观察组的基本痊愈率显著高于对照组(P0.05),两组NIHSS评分都较治疗前显著降低,且观察组NIHSS评分显著低于对照组(P均0.05)。两组手术后第7 d、14 d及28 d的脑水肿体积均显著低于治疗前(P0.05),且观察组各时间点的脑水肿体积均显著低于对照组(P0.05)。两组血清MMP-9、S100β均较治疗前降低(P0.05),NGF较治疗前升高(P0.05),且观察组治疗后的血清MMP-9、S100β水平显著低于、血清NGF水平显著高于对照组(P0.05)。观察组患者术后3个月时的日常生活活动能力总良好率显著高于对照组(P0.05)。结论:高压氧联合神经节苷脂辅助微创血肿清除术治疗高血压脑出血临床疗效显著,有利于改善患者预后。     

黄芪当归汤联合莫沙比利治疗功能性便秘的疗效及对血清胃肠激素水平的影响

目的:研究黄芪当归汤联合莫沙比利治疗功能性便秘的临床疗效及对血清胃肠激素水平的影响。方法:选择2015年3月至2016年5月我院接受治疗的功能型便秘患者86例。按照随机数字表法分为观察组与对照组,各43例。对照组患者给予莫沙比利治疗,观察组同时加用黄芪当归汤治疗,对比两组临床疗效、不良反应;检测患者治疗前后血清胃动素(MTL)、P物质(SP)水平;采用SF-36生活质量量表对患者治疗后的生活质量进行评价。结果:观察组治疗总有效率为95.35%(41/43),显著高于对照组的81.40%(35/43),差异有统计学意义(P0.05)。两组腹痛、皮疹、稀便发生率对比,均无统计学意义(均P0.05)。治疗前两组血清胃肠激素水平对比无显著差异,治疗后两组MTL均降低,而SP均上升,且治疗后观察组MTL水平显著低于对照组,SP水平显著高于对照组(均P0.05)。治疗后观察组患者饮食、精神、睡眠以及心理四个维度的生活质量评分均显著高于对照组,差异均有统计学意义(均P0.05)。结论:黄芪当归汤联合莫沙比利治疗功能性便秘具有显著的临床疗效,能有效改善患者血清胃肠激素水平,提高患者生活质量,且安全可靠,值得推广应用。     

盐酸米诺环素软膏联合布洛芬对慢性牙周炎患者龈沟液TNF-α、IL-1β、IL-8水平及生活质量的影响

目的:探讨盐酸米诺环素软膏联合布洛芬对慢性牙周炎患者龈沟液肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-8(IL-8)水平及生活质量的影响。方法:选取成都医学院第一附属医院于2016年3月至2018年3月期间收治的84例慢性牙周炎患者,按照数表法随机分为观察组(n=42)和对照组(n=42)。对照组患者予以盐酸米诺环素软膏治疗,观察组患者则在对照组的基础上联合布洛芬治疗,比较两组临床治疗总有效率,比较治疗前、后龈沟液TNF-α、IL-1β、IL-8水平,治疗前后菌斑指数(PLI)、牙龈指数(GI)水平,采用健康检查简表(SF-36)评价两组患者生活质量。结果:观察组临床治疗总有效率明显高于对照组(P0.05)。治疗后观察组患者龈沟液TNF-α、IL-1β、IL-8水平均明显低于对照组(P0.05)。治疗后观察组患者PLI、GI水平均明显低于对照组(P0.05)。治疗后观察组SF-36量表各维度评分均显著高于对照组(P0.05)。结论:盐酸米诺环素软膏联合布洛芬治疗慢性牙周炎的疗效确切,且有效降低患者龈沟液TNF-α、IL-1β、IL-8水平,有利于牙周组织的重建和恢复,提高患者生活质量。     

功能性鼻内窥镜手术治疗鼻窦炎与鼻息肉的疗效分析

目的:探讨功能性鼻内窥镜手术治疗鼻窦炎与鼻息肉的疗效。方法:选取350例鼻窦炎与鼻息肉患者,按随机数字表法分为两组,对照组(164例)给予综合疗法,观察组(186例)给予功能性鼻内窥镜手术联合综合疗法。通过观察并记录疗效,治疗前,治疗后3个月患者体内IL-1,IL-8水平,SF-36量表评分,评价功能性鼻内窥镜手术治疗鼻窦炎与鼻息肉的疗效。结果:经手术和药物治疗,观察组有效率明显高于对照组(P0.05),治疗前,两组IL-1和IL-8水平无统计学差异(P0.05),治疗后3个月,两组IL-1和IL-8水平均明显下降,且观察组IL-1和IL-8水平低于对照组(P0.05),治疗前,两组SF-36各项评分无统计学差异,治疗后3个月,两组SF-36评分均明显增加(P0.05)。观察组在躯体疼痛和总体健康2项评分明显高于对照组(P0.05),其余6项评分相比无统计学差异(P0.05)。结论:功能性鼻内窥镜手术对鼻窦炎与鼻息肉具有较好的疗效,能显著减轻炎症反应,改善患者生活质量,值得临床推广使用。     

前列地尔与常规治疗对急性脑梗死血清学指标的影响

目的分析前列地尔与常规治疗对急性脑梗死患者血清学指标的影响。方法对我院收治的100例急性脑梗死患者根据治疗方法的不同进行分组,对照组50例患者采用常规药物治疗,观察组50例患者给予前列地尔与常规治疗联合应用,观察比较两组患者的血清学指标变化情况。结果治疗后1天,两组患者的BDNF、NGF、S100β、NSE水平无显著统计学意义(P0.05);治疗后第3、5、7天,两组患者的BDNF、NGF、S100β、NSE指标均有所下降,且观察组患者的下降幅度显著优于对照组,差异有统计学意义(P0.05)。治疗后,两组患者的PPARγ、CD62p、YKL-40、sCD40L、Fibulin水平均有所下降,且观察组患者的下降幅度显著优于对照组,差异有统计学意义(P0.05)。结论前列地尔联合常规治疗急性脑梗死的临床应用价值高,能有效改善患者血清学水平,提高患者的临床治疗效果,且安全性高,是治疗急性脑梗死的理想治疗方法,值得推广使用     

治疗性沟通结合肉毒素治疗氯胺酮相关性膀胱炎的疗效观察

目的探讨治疗性沟通结合肉毒素治疗氯胺酮相关性膀胱炎的疗效。方法选取60例氯胺酮相关性膀胱炎患者,按随机数字表法分为观察组(n=30)和对照组(n=30)。对照组给予常规术后护理,观察组给予治疗性沟通系统,并比较两组简明健康调查量表(Short-Form-36Health Survey,SF-36)评分、中文版Herth希望量表(Herth hope index,HHI)评分及膀胱功能。结果观察组患者SF-36评分及HHI评分均显著高于对照组,差异具有统计学意义(P0.05)。而且观察组患者的膀胱功能指标改善明显优于对照组,差异具有统计学意义(P0.05)。结论对氯胺酮相关性膀胱炎患者进行治疗性沟通,可显著提高其希望水平和生活质量,改善膀胱功能。     

Model analysis of difference between EGF pathway and FGF pathway

The difference in time course of Ras and mitogen activated protein kinase (MAPK) cascade by different growth factors is considered to be the cause of different cellular responses. We have developed the computer simulation of Ras-MAPK signal transduction pathway containing newly identified negative feedback system, Sprouty, and adaptor molecules. Unexpectedly, negative feedback system did not profoundly affect time course of MAPK activation. We propose the key role of fibroblast growth factor receptor substrate 2 (FRS2) in NGF/FGF pathway for sustained MAPK activation. More Grb2-SOS complexes were recruited to the plasma membrane by binding to membrane-bound FRS2 in FGF pathway than in EGF pathway and caused sustained activation of ERK. The EGF pathway with high concentration of EGF receptor also induced sustained MAPK activation, which is consistent with the results in the PC12 cell overexpressing the EGF receptors. The simulated time courses of FRS2 knock-out cells were consistent with those of the reported experimental results.     

Acute Regulation of the Epidermal Growth Factor Receptor in Response to Nerve Growth Factor

PC12 cells possess specific receptors for both nerve growth factor and epidermal growth factor, and by an unknown mechanism, nerve growth factor is able to attenuate the propagation of a mitogenic response to epidermal growth factor. The differentiation response of PC12 cells to nerve growth factor, therefore, predominates over the proliferative response to epidermal growth factor. We have observed that the addition of nerve growth factor to PC12 cells rapidly produces a decrease in surface 125I-epidermal growth factor binding capacity. Unlike previously described nerve growth factor effects on 125I-epidermal growth factor binding capacity, which required several days of nerve growth factor exposure, the decreases we report occur within minutes of nerve growth factor addition: A 50% decrease in 125I-epidermal growth factor binding capacity is evident at 10 min. This rapid nerve growth factor response is concentration dependent; inhibition of 125I-epidermal growth factor binding is detectable at nerve growth factor levels as low as 0.2 ng/ml and is maximal at approximately 50 ng/ml, consistent with known ranges of biological activity. No demonstrable differences in the rate of epidermal growth factor receptor synthesis or degradation were observed in cells acutely exposed to nerve growth factor. Scatchard analysis revealed that acute nerve growth factor treatment decreased the number of both high- and low-affinity 125I-epidermal growth factor binding sites, while the receptor affinity remained unchanged. We have also investigated the involvement of various potential intracellular mediators of nerve growth factor action and of known intracellular modulatory systems of the epidermal growth factor receptor for their capacity to participate in this nerve growth factor activity.     

pp42/44MAP Kinase Is a Component of the Neurogenic Pathway Utilized by Nerve Growth Factor in PC12 Cells

Nerve growth factor-stimulated mitogen-activated protein kinase (pp42/44MAP) kinase was characterized by sequential column chromatography on DEAE-Sephacel, phenyl-Sepharose CL4B, and S-200. The kinase displayed an apparent molecular mass of 42 kDa and reacted with an antiphosphotyrosine antibody. Peptide mapping of myelin basic protein revealed the presence of one phosphopeptide that was phosphorylated on Thr-97. pp42/44MAP kinase activity was dependent on Mg2+ and inhibited by K252a both in vitro and in vivo. Nerve growth factor-stimulated kinase activation was diminished by down-regulation of protein kinase C with 200 nM 12-phorbol 13-myristate acetate or with staurosporine (1 nM), a protein kinase C inhibitor. Genistein, a protein tyrosine kinase inhibitor, blocked nerve growth factor-mediated neurite extension as well as diminished activation of pp42/44MAP kinase. Our data demonstrate that activation of this kinase system by nerve growth factor displays a requirement for both protein kinase C as well as protein tyrosine kinase. In addition, other agents that are capable of promoting neurite outgrowth in PC12 cells, such as fibroblast growth factor or dibutyryl cyclic AMP, do so independently of activating this kinase system.     

Defined medium for normal adult human prostatic stromal cells

Summary Stromal-epithelial interactions are pivotal in many aspects of prostatic biology. A defined culture system is critical for the investigation of factors that regulate the growth and differentiation of human prostatic stromal cells. We have identified conditions which promote stromal cell attachment and proliferation in serum-free medium. MCDB 201, originally developed for the clonal growth of chick embryo fibroblasts, proved to be a superior basal medium of those that we tested. Supplementation of MCDB 201 with basic fibroblast growth factor (FGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF) permitted attachment and exponential growth of cells throughout a 7-d period with an initial inoculum as low as 10³ cells per well of a 96-well microtiter dish. Using these assay conditions, we subsequently verified that basic FGF and IGF, but not PDGF, were required for optimal growth. No activity was found for heparin, transferrin, or the androgen R1881. Epidermal growth factor (EGF) didn’t stimulate growth when added to medium containing basic FGF and IGF, but was moderately stimulatory when added to basal medium alone. Cholera toxin inhibited growth. This simple and efficient culture medium provides a suitable assay system for more extensive studies of growth regulation and differentiation of human prostatic stromal cells, and will provide the basis for future development of a defined medium that supports clonal growth. Characterization of stromal-epithelial interactions will be facilitated by the use of this defined culture system for stromal cells in conjunction with the serum-free culture systems previously developed for human prostatic epithelial cells.     

Heterologous regulation of EGF receptors in fibroblastic cells

Platelet-derived growth factor (PDGF) increases the mitogenic activity of epidermal growth factor (EGF) in several cells lines, including BALB/C-3T3. PDGF-treated BALB/C-3T3 cells manifest a reduced capacity to bind 125I-labeled EGF due to a loss of high affinity EGF receptors. Cholera toxin potentiates the ability of PDGF to both decrease EGF binding and initiate mitogenesis. Whether PDGF increases EGF sensitivity via its effects on EGF receptors is not known and requires a more complete understanding of the mechanism by which PDGF decreases EGF binding. 12-O-tetradecanoylphorbol 13-acetate (TPA) also reduces EGF binding in BALB/C-3T3 and other cells, presumably by activating protein kinase C and, consequently, inducing the phosphorylation of EGF receptors at threonine-654. PDGF indirectly activates protein kinase C, and EGF receptors in PDGF-treated WI-38 cells are phosphorylated at threonine-654. Thus, the effects of PDGF on EGF binding may also be mediated by protein kinase C. We investigated this hypothesis by comparing the actions of PDGF and TPA on EGF binding in density-arrested BALB/C-3T3 cells. Both PDGF and TPA caused a rapid, transient, cycloheximide-independent loss of 125I-EGF binding capacity. The actions of both agents were potentiated by cholera toxin. However, whereas TPA allowed EGF binding to recover, PDGF induced a secondary and cycloheximide-dependent loss of binding capacity. Most importantly, PDGF effectively reduced binding in cells refractory to TPA and devoid of detectable protein kinase C activity. These findings indicate that PDGF decreases EGF binding by a mechanism that involves protein synthesis and is distinct from that of TPA.     

Inhibition of FGF‐FGFR and VEGF‐VEGFR signalling in cancer treatment

The sites of targeted therapy are limited and need to be expanded. The FGF‐FGFR signalling plays pivotal roles in the oncogenic process, and FGF/FGFR inhibitors are a promising method to treat FGFR‐altered tumours. The VEGF‐VEGFR signalling is the most crucial pathway to induce angiogenesis, and inhibiting this cascade has already got success in treating tumours. While both their efficacy and antitumour spectrum are limited, combining FGF/FGFR inhibitors with VEGF/VEGFR inhibitors are an excellent way to optimize the curative effect and expand the antitumour range because their combination can target both tumour cells and the tumour microenvironment. In addition, biomarkers need to be developed to predict the efficacy, and combination with immune checkpoint inhibitors is a promising direction in the future. The article will discuss the FGF‐FGFR signalling pathway, the VEGF‐VEGFR signalling pathway, the rationale of combining these two signalling pathways and recent small‐molecule FGFR/VEGFR inhibitors based on clinical trials.     

Mass production of human epidermal growth factor using fed-batch cultures of recombinant Escherichia coli

Fed-batch cultures of recombinant E. coli HB101 harboring expression plasmid pTRLBT1 or pTREBT1, with acetate concentration monitoring, are investigated to obtain high cell density and large amounts of human epidermal growth factor (hEGF). The expression plasmid pTRlBT1 contains a synthetic hEGF gene attached downstream of the N-terminal fragment of the trp L gene preceded by the trp promoter. The expression plasmid pTREBT1 contains the same coding sequence attached downstream of the N-terminal fragment of the trp E gene preceded by the trp promoter, trp L gene, and attenuator region. E. coli harboring pTREBT1 produces 0.56 mg/L hEGE and immediately degrades it. On the other hand E. coli harboring pTRLBT1 produces 6.8 mg/L hEGF and does not decompose it. Prominent inclusion bodies are observed in E. coli cells harboring pTRLBT1 using an election microscope. To Cultivate E. coli harboring pTRLBT1, a fed-batch culture system, divided into a cell growth step and an hEGF production step, is carried out. The cells grow smoothly without acetate-induced inhibition. Cell concentration and hEGF quantity reach the high values of 21 g/L and 60 mg/L, respectively.     

Production of a monoclonal antibody directed against the nerve growth factor receptor from sympathetic membranes

Spleen cells from BALB/c mice immunized with a plasma membrane-enriched fraction from rabbit sympathetic ganglia were fused with the mouse myeloma NS1. A hybrid clone was obtained that produced monoclonal antibody directed against the receptor for nerve growth factor (NGF). The antibody, identified as IgG, was able to immunoprecipitate solubilized NGF receptor in the presence or absence of bound NGF. The antibody bound specifically to sympathetic membranes with high affinity but did not affect the binding of 125I-NGF to its receptor in sympathetic or sensory neurons or PC12 cells.