Neuron-specific enolase expression in a rat model of radiation-induced brain injury following vascular endothelial growth factor-modified neural stem cell transplantation

BACKGROUND： Previous studies have shown that transplantation of vascular endothelial growth factor （VEGF）-modified neural stem cells （NSC） provides better outcomes, compared with neural stem cells, in the treatment of brain damage. OBJECTIVE： To compare the effects of VEGF-modified NSC transplantation and NSC transplantation on radiation-induced brain injury, and to determine neuron-specific enolase （NSE） expression in the brain. DESIGN, TIME, AND SETTING： The randomized, controlled study was performed at the Linbaixin Experimental Center, Second Affiliated Hospital, Sun Yat-sen University, China from November 2007 to October 2008. MATERIALS： VEGF-modified C17.2 NSCs were supplied by Harvard Medical School, USA. Streptavidin-biotin-peroxidase-complex kit （Boster, China） and 5, 6-carboxyfluorescein diacetate succinimidyl ester （Fluka, USA） were used in this study. METHODS： A total of 84 Sprague Dawley rats were randomly assigned to a blank control group （n = 20）, model group （n = 20）, NSC group （n = 20）, and a VEGF-modified NSC group （n = 24）. Rat models of radiation-induced brain injury were established in the model, NSC, and VEGF-modified NSC groups. At 1 week following model induction, 10 pL （5 ×10^4 cells/μL） VEGF-modified NSCs or NSCs were respectively infused into the striatum and cerebral cortex of rats from the VEGF-modified NSC and NSC groups. A total of 10μL saline was injected into rats from the blank control and model groups. MAIN OUTCOME MEASURES： NSE expression in the brain was detected by immunohistochemistry following VEGF-modified NSC transplantation. RESULTS： NSE expression was significantly decreased in the brains of radiation-induced brain injury rats （P 〈 0.05）. The number of NSE-positive neurons significantly increased in the NSC and VEGF-modified NSC groups, compared with the model group （P 〈 0.05）. NSE expression significantly increased in the VEGF-modified NSC group, compared with the NSC group, at 6 weeks following transplantation （P 〈 0.05）. CONCLUSION： VEGF-modified NSC transplantation increased NSE expression in rats with radiation-induced brain injury, and the outcomes were superior to NSC transplantation.

Neuron-like differentiation of adult rat bone marrow stromal cells induced by transforming growth factor-beta and brain-derived neurotrophic factor

BACKGROUND： It has been demonstrated that transforming growth factor-β （TGF-β） and brain- derived neurotrophic factor （BDNF） can induce stem cell differentiation into neuron-like cells. OBJECTIVE： To investigate the efficacy of TGF-β and BDNF at inducing the differentiation of adult rat bone marrow stromal cells （BMSCs） into neuron-like cells, both in combination or alone. DESIGN, TIME AND SETTING： A comparative observation experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between October 2007 and January 2008. MATERIALS： TGF-~ and BDNF were purchased from Sigma, USA; mouse anti-rat neuron specific enolase, neurofilament and glial fibrillary acidic protein were purchased from Beijing HMHL Biochem Ltd., China. METHODS： BMSCs were isolated from rats aged 4 weeks and incubated with TGF-β（1μ g/L） and/or BDNF （50 μ g/mL）. MAIN OUTCOME MEASURES： Expression of neuron-specific enolase, neurofilament and glial fibrillary acidic protein were determined by immunocytochemistry. RESULTS： BMSCs differentiated into neuron-like cells following induction of TGF-β and BDNF, and expressed both neuron-specific enolase and neurofilament. The percent of positive cells was significantly greater in the combination group than those induced with TGF-β or BDNF alone （P 〈 0.01）. CONCLUSION： Treatment of BMSCs with a combination of TGF-β and BDNF induced differentiation into neuron-like cells, with the induction being significantly greater than with TGF-β or BDNF alone.

Basic flbroblast growth factor protects auditory neurons and hair cells from noise exposure and glutamate neurotoxicity

The purpose of the present study was to determine protectivie effects of basic fibroblast growth factor (bFGF) on cochlear neurons and hair cells in vitro and in vivo. In experiment I, cultured spiral ganglion neurons (SGNs) prepared from P3 mice were exposed to 20mM glutamate for 2 hours before the culture medium was replaced with fresh medium containing 0, 25, 50, and 100 ng/ml bFGF, respectively. Fourteen days later, all cultures were fixed with 4% paraformaldehyde, and stained with 1% toluidine blue. The number of surviving SGNs were counted and the length of SGNs neurites were measured. Exposure to 20 mM glutamate for 24 hours resulted in an inhibition on neurite outgrowth of SGNs and elevated cell death. Treatment of the cultures with bFGF led to promotion of neurite outgrowth and elevated number of surviving SGNs. Effects of bFGF were dose dependent with the highest potency at 100 ng/ml. In experiment Ⅱ, in vivo studies were carried out with guinea pigs in which bFGF or artificial perilymph was perfused into the cochlea to assess possible protective effects of bFGF on cochlear hair cells and compound action potentials(CAP). The CAPs were measured before, immediatly and 48 hours after exposure to noise. Significant differences in CAP were observed (p＜0. 05 ) among the bFGF perfused group, control group(t =3. 896 ) and artificial perilymph perfused group (t =2. 520) at 48 hours after noise exposure, Cochleae were removed and hair cell Loss was analyzed in surface preparations prepared from all experimental animals. Acoustic trauma caused loss of 651 and 687 inner hair cells in the control and artificial perilymph perfused group, respectively. In sharp contrast, only 31 inner hair cells were lost in the bFGF perfused ears. Similarly, more outer hair cells died in the control and perilymph perfuesed group (41830 and 41968, respectively) than in the group treated with bFGF (34258). Our results demonstrate that bFGF protected SGNs against glutmate neurotoxicity in vitro. In addition, treatment with bFGF also protected hair cells from acoustic trauma.

Role of neurotrophic factors in enhancing linear axonal growth of ganglionic sensory neurons in vitro

Neurotrophins play a major role in the regulation of neuronal growth such as neurite sprouting or regeneration in response to nerve injuries. The role of nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor in maintaining the survival of peripheral neurons remains poorly understood. In regenerative medicine, different modalities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. This study was to investigate the influence of nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor on the growth of neurites using two in vitro models of dorsal root ganglia explants and dorsal root ganglia-derived primary cell dissociated cultures. Quantitative data showed that the total neurite length and tortuosity were differently influenced by trophic factors. Nerve growth factor and, indirectly, brain-derived neurotrophic factor stimulate the tortuous growth of sensory fibers and the formation of cell clusters. Neurotrophin-3, however, enhances neurite growth in terms of length and linearity allowing for a more organized and directed axonal elongation towards a peripheral target compared to the other growth factors. These findings could be of considerable importance for any clinical application of neurotrophic factors in peripheral nerve regeneration. Ethical approval was obtained from the Regione Piemonte Animal Ethics Committee ASLTO1(file # 864/2016-PR) on September 14, 2016.

Directional induction of dopaminergic neurons from neural stem cells using substantia nigra homogenates and basic fibroblast growth factor

To date, complex components of available reagents have been used for directional induction of neural stem cells into dopaminergic neurons, resulting in a poor ability to repeat experiments. This study sought to investigate whether a homogenate of the substantia nigra of adult rats and/or basic fibroblast growth factor could directionally induce neural stem cells derived from the subventricular zone of embryonic rats to differentiate into dopaminergic neurons. Tyrosine hydroxylase-positive cells were observed exclusively after induction with the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor for 48 hours in vitro. However, in the groups treated with homogenate supernatant or basic fibroblast growth factor alone, tyrosine hydroxylase expression was not observed. Moreover, the content of dopamine in the culture medium of subventricular zone neurons was significantly increased at 48 hours after induction with the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor. Experimental findings indicate that the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor could directionally induce neural stem cells derived from the subventricular zone of embryonic rats to differentiate into dopaminergic neurons in the substantia nigra with the ability to secrete dopamine.

Recombinant human fibroblast growth factor-2 promotes nerve regeneration and functional recovery after mental nerve crush injury

Several studies have shown that fibroblast growth factor-2 （FGF2） can directly affect axon regeneration after peripheral nerve damage. In this study, we performed sensory tests and histological analyses to study the effect of recombinant human FGF-2 （rhFGF2） treatment on damaged mental nerves. The mental nerves of 6-week-old male Sprague-Dawley rats were crush-injured for 1 minute and then treated with 10 or 50 μg/mL rhFGF2 or PBS in crush injury area with a mini Osmotic pump. Sensory test using von Frey filaments at 1 week revealed the presence of sensory degeneration based on decreased gap score and increased difference score. However, at 2 weeks, the gap score and difference score were significantly rebounded in the mental nerve crush group treated with 10 μg/mL rhFGF2. Interestingly, treatment with 10 μg/mL rhFGF had a more obviously positive effect on the gap score than treatment with 50 μg/mL rhFGF2. In addition, retrograde neuronal tracing with Dil revealed a significant increase in nerve regeneration in the trigeminal ganglion at 2 and 4 weeks in the rhFGF2 groups （10 μg/mL and 50 μg/mL） than in the PBS group. The 10 μg/mL rhFGF2 group also showed an obviously robust regeneration in axon density in the mental nerve at 4 weeks. Our results demonstrate that 10 μg/mL rhFGF induces mental nerve regeneration and sensory recovery after mental nerve crush injury.

Beta-nerve growth factor gene therapy alleviates pyridoxine-induced neuropathic damage by increasing doublecortin and tyrosine kinase A in the dorsal root ganglion

Beta-nerve growth factor(β-NGF) is known to be a major leading cause of neuronal plasticity. To identify the possible action mechanisms of β-NGF gene therapy for sciatic nerve recovery, experimental dogs were randomly divided into control, pyridoxine, and pyridoxine + β-NGF groups. We observed chronological changes of morphology in the dorsal root ganglia in response to pyridoxine toxicity based on cresyl violet staining. The number of large neurons positive for cresyl violet was dramatically decreased after pyridoxine intoxication for 7 days in the dorsal root ganglia and the neuron number was gradually increased after pyridoxine withdrawal. In addition, we also investigated the effects of β-NGF gene therapy on neuronal plasticity in pyridoxine-induced neuropathic dogs. To accomplish this, tyrosine kinase receptor A(TrkA), βIII-tubulin and doublecortin(DCX) immunohistochemical staining was performed at 3 days after the last pyridoxine treatment. TrkA-immunoreactive neurons were dramatically decreased in the pyridoxine group compared to the control group, but strong TrkA immunoreactivity was observed in the small-sized dorsal root ganglia in this group. TrkA immunoreactivity in the dorsal root ganglia was similar between β-NGF and control groups. The numbers of βIII-tubulin-and DCX-immunoreactive cells decreased significantly in the pyridoxine group compared to the control group. However, the reduction of βIII-tubulin-and DCX-immunoreactive cells in the dorsal root ganglia in the β-NGF group was significantly ameliorated than that in the pyridoxine group. These results indicate that β-NGF gene therapy is a powerful treatment of pyridoxine-induced neuropathic damage by increasing the TrkA and DCX levels in the dorsal root ganglia. The experimental protocol was approved by the Institutional Animal Care and Use Committee(IACUC) of Seoul National University, South Korea(approval No. SNU-060623-1, SNU-091009-1) on June 23, 2006 and October 9, 2009, respectively.

Neuronal differentiation effects of vascular endothelial factor on bone marrow stromal cells

BACKGROUND：Studies have demonstrated that bone marrow stromal cells （BMSCs） undergo neuronal differentiation under certain in vitro conditions.However,very few inducers of BMSC differentiation have been used in clinical application.The effects of vascular endothelial growth factor （VEGF） on in vitro neuronal differentiation of BMSCs remain poorly understood.OBJECTIVE：To investigate the effect of VEGF on neuronal differentiation of BMSCs in vitro,and to determine the best VEGF concentration for experimental induction.DESIGN,TIME AND SETTING：In vitro comparative study was performed at the Central Laboratory and Laboratory of Male Reproductive Medicine,Shenzhen Hospital of Peking University from October 2008 to August 2009.MATERIALS：Recombinant human VEGF165 was purchased from Peprotech Asia,Rehovot,Israel.Neuron-specific enolase （NSE） was purchased from Beijing Biosynthesis Biotechnology,China.METHODS：BMSCs were harvested from adult Sprague Dawley rats.The passaged cells were pre-induced with 10 ng/mL basic fibroblast growth factor for 24 hours,followed by differentiation induction with 0,5,10,and 20 ng/mL VEGF,respectively.MAIN OUTCOME MEASURES：Morphological changes in BMSCs prior to and following VEGF induction.Expression of NSE following induction was determined by immunocytochemistry.RESULTS：Shrunken,round cells,with a strong refraction and thin bipolar or multipolar primary and secondary branches were observed 3 days after induction with 5,10,and 20 ng/mL VEGF.However,these changes were not observed in the control group.At 10 days after induction,the number of NSE-positive cells was greatest in the 10 ng/mL VEGF-treated group （P〈 0.05）.The number of NSE-positive cells was least in the control group at 3 and 10 days post-induction （P〈 0.05）.Moreover,the number of NSE-positive cells was greater at 10 days compared with at 3 days after induction （P〈 0.05）.CONCLUSION：Of the VEGF concentrations tested,10 ng/mL induced the greatest number of neuronal-like cells in vitro from BMSCs.

Dab2 attenuates brain injury in APP/PS1 mice via targeting transforming growth factor-beta/SMAD signaling

Transforming growth factor-beta （TGF-β） type II receptor （TβRⅡ） levels are extremely low in the brain tissue of patients with Alzheimer＇s disease. This receptor inhibits TGF-β1/SMAD signaling and thereby aggravates amyolid-beta deposition and neuronal injury. Dab2, a specific adapter protein, protects T RII from degradation and ensures the effective conduction of TGF-β 1/SMAD signaling. In this study, we used an adenoviral vector to overexpress the Dab2 gene in the mouse hippocampus and investigated the regulatory effect of Dab2 protein on TGF-β1/SMAD signaling in a mouse model of Alzheimer＇s disease, and the potential neuroprotective effect. The results showed that the TβRⅡ level was lower.in APP/PS1 mouse hippocampus than in normal mouse hippocampus. After Dab2 expression, hippocampal TβRⅡ and p-SMAD2/3 levels were signifi- cantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor- and interleulin-6 levels and neuronal loss were significantly attenuated in APP/PS1 mouse brain tissue. These results suggest that Dab2 can exhibit neuroprotective effects in Alzheimer＇s disease by regulating TGF-β1/SMAD signaling.

Distribution and localization of fibroblast growth factor-8 in rat brain and nerve cells during neural stem/progenitor cell differentiation

The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth factor-8 in brain activities and neural stem/progenitor cell differentiation.

Changes in expression and secretion patterns of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway molecules during murine neural stem/progenitor cell differentiation in vitro

In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differentiation from embryonic Sprague-Dawley rats or embryonic Kunming species mice, using fluorescent quantitative reverse transcription-PCR and western blot analyses. Results demonstrated that the dynamic expression of fibroblast growth factor 8 was similar to fibroblast growth factor receptor 1 expression but not to other fibroblast growth factor receptors. Enzyme-linked immunosorbent assay demonstrated that fibroblast growth factor 8 and Sonic Hedgehog signaling pathway protein factors were secreted by neural cells into the intercellular niche. Our experimental findings indicate that fibroblast growth factor 8 and Sonic Hedgehog expression may be related to the differentiation of neural stem/progenitor cells.

In vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity

Ciliary neurotrophic factor has neuroprotective effects mediated through signal transducer and Janus kinase（JAK） 2/activator of transcription 3（STAT3） and phosphatidylinositol 3-kinase（PI3 K）/Akt signaling pathways.Whether ciliary neurotrophic factor is neuroprotective for glutamate-induced excitotoxicity of dorsal root ganglion neurons is poorly understood.In the present study,the in vitro neuroprotective effects of ciliary neurotrophic factor against glutamate-induced excitotoxicity were determined in a primary culture of dorsal root ganglion neurons from Wistar rat embryos at embryonic day 15.Whether the JAK2/STAT3 and PI3 K/Akt signaling pathways were related to the protective effects of ciliary neurotrophic factor was also determined.Glutamate exposure inhibited neurite outgrowth,cell viability,and growth-associated protein 43 expression and promoted apoptotic neuronal cell death,all of which were reversed by the administration of exogenous ciliary neurotrophic factor.Additionally,preincubation with either JAK2 inhibitor AG490 or PI3 K inhibitor LY294002 blocked the neuroprotective effect of ciliary neurotrophic factor.These data indicate that the two pathways JAK2/STAT3 and PI3 K/Akt play major roles in mediating the in vitro neuroprotective effects of ciliary neurotrophic factor on dorsal root ganglion neurons with glutamate-induced neurotoxicity.

原花青素对大鼠背根神经节神经元突起生长的影响

目的探讨原花青素(proanthocyanidins,PC)对大鼠背根神经节(dorsal root ganglion,DRG)神经元突起生长的作用。方法在体外,培养原代大鼠DRG神经元细胞并检测不同浓度PC对其突起生长数量、长度及生长锥的影响;在体内,构建大鼠坐骨神经夹伤模型,检测损伤早期生长相关蛋白43(growth-associated protein 43,GAP43)的表达情况。最后在体外采用细胞免疫荧光和ELISA检测PC对DRG神经元中神经生长因子(nerve growth factor,NGF)的表达影响。结果PC可显著增加DRG神经元突起的数量、长度及生长锥伪足数量;促进大鼠坐骨神经损伤早期GAP43蛋白的表达;增强DRG神经元内NGF的表达。结论PC可能通过促进大鼠DRG神经元内NGF的表达,加快神经元突起生长。

子宫内膜异位症不同r-AFS分期患者血清Furin,TGF-β,VEGF,netrin-1水平表达及Furin基因P1启动区r2071410 C/T位点多态性分析

目的了解子宫内膜异位症(endometriosis,EMT)不同r-AFS分期患者血清弗林蛋白酶(Furin)、肿瘤生长因子-β(tumor growth factor-β,TGF-β)、血管生长因子(vascular endothelial growth factor,VEGF)及神经轴突导向因子-1(neuron towards axon guidance factor-1,netrin-1)水平表达及Furin基因P1启动区r2071410 C/T位点多态性,探讨其与深圳地区EMT发病的相关性。方法选取2021年5月~2023年1月深圳市龙华区人民医院确诊的EMT患者102例为EMT组,并根据r-AFs分期法将EMT组分为I~II期和III~IV期。同时收集同期非EMT患者78例为对照组。采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清Furin,TGF-β,VEGF及netrin-1水平,并采用反转录-实时荧光定量聚合酶链反应法(reverse transcription-real time quantitative polymerase chain reaction,RT-qPCR)分析Furin基因P1启动区r2071410 C/T位点多态性。结果EMT组患者血清Furin(140.84±47.02pg/ml),TGF-β(376.46±82.36ng/L)和VEGF水平(167.67±53.02ng/L)明显高于对照组(55.49±13.67pg/ml,216.37±15.04ng/L,102.27±8.45ng/L),而netrin-1水平(48.37±15.20pg/ml)明显低于对照组(165.85±15.63pg/ml),差异具有统计学意义(t=28.409,20.347,16.915,36.653,均P<0.05)。III~IV期患者血清Furin(192.41±20.62pg/ml),TGF-β(452.61±72.03ng/L)和VEGF水平(201.84±28.01ng/L)明显高于I~II期(78.05±16.54pg/ml,283.75±56.92ng/L,126.07±19.35ng/L),而netrin-1水平(37.95±11.34pg/ml)明显低于I~II期(61.05±9.52pg/ml),差异有统计学意义(t=31.071,18.054,19.183,21.625,均P<0.05)。经Pearson/Spearman相关性分析结果显示,Furin与TGF-β,VEGF水平及临床分期呈正相关(r=0.6149,0.7526,0.7905,均P<0.05),而与netrin-1水平呈负相关(r=-0.6701,均P<0.05)。EMT组患者Furin基因P1启动区r2071410 C/T位点TT基因型和T等位基因频率(42.16%,55.39%)明显高于对照组(7.69%,19.87%),且III~IV期TT基因型和T等位基因频率(51.79%,65.18%)比I~II期(30.43%,43.48%)明显升高,差异具有统计学意义(χ^(2)=26.500,46.472,4.721,9.626,均P<0.05)。EMT组不同基因型患者血清Furin水平差异具有统计学意义(F=51.286,P<0.001),其中TT基因型患者血清Furin水平(216.29±68.53pg/ml)明显高于CC(83.04±21.37pg/ml)和CT基因型(89.18±20.95pg/ml),差异具有统计学意义(t=27.146,25.719,均P<0.01),但CC与CT基因型之间差异无统计学意义(t=1.326,P>0.05)。结论EMT患者血清Furin水平明显升高,且与TGF-β,VEGF,netrin-1水平及临床分期呈一定相关性;同时Furin基因P1启动区r2071410 C/T位点呈多态性分布,其中TT基因型患者血清Furin水平升高更为明显,可能与深圳地区EMT发病有关。

醒脑静联合利巴韦林治疗病毒性脑炎患儿的疗效

目的 探讨醒脑静联合利巴韦林治疗病毒性脑炎(VE)患儿的疗效。方法 采用随机数字表法将该院2020年12月至2023年2月收治的124例VE患儿分为参照组、研究组,每组62例。参照组在常规治疗的基础上给予利巴韦林治疗,研究组在参照组的基础上给予醒脑静治疗。比较两组临床疗效、症状消失时间、治疗前后神经因子水平[神经生长因子(NGF)、神经元特异性烯醇化酶(NSE)、脑源性神经营养因子(BDNF)、髓鞘碱性蛋白(MBP)]、血浆细胞参数[辅助性T细胞17(Th17)/调节性T淋巴细胞(Treg)、Treg比例、Th17比例、微小RNA-125b(miR-125b)]、炎症因子水平[转化生长因子-β(TGF-β)、白细胞介素(IL)-17、肿瘤坏死因子-α(TNF-α)、IL-6]和不良反应总发生率。结果 研究组临床总有效率(91.94%)高于参照组(77.42%),差异有统计学意义(P<0.05);治疗后研究组临床症状消失时间均短于参照组(P<0.05);治疗后研究组NGF、MBP、NSE水平低于参照组,BDNF水平高于参照组,差异均有统计学意义(P<0.05);治疗后研究组Th17比例、miR-125b水平和Th17/Treg低于参照组,Treg比例高于参照组,差异均有统计学意义(P<0.05);治疗后研究组TNF-α、IL-6、IL-17水平低于参照组,TGF-β水平高于参照组,差异均有统计学意义(P<0.05);两组不良反应总发生率相比,差异无统计学意义(P>0.05)。结论 醒脑静联合利巴韦林治疗VE的效果显著,能改善患儿神经功能及临床症状,减轻炎症反应,提高免疫功能,用药较安全可靠。

贝伐珠单抗与GC化疗方案联合治疗晚期非小细胞肺癌的效果及药物经济学评价

目的 探究贝伐珠单抗联合GC化疗方案(顺铂+吉西他滨)治疗晚期非小细胞肺癌(NSCLC)的效果及药物经济学价值。方法 选取2020年7月—2022年7月收治的86例晚期NSCLC,依据治疗方案分为对照组和观察组,每组43例。对照组给予GC化疗方案,观察组给予贝伐珠单抗联合GC化疗方案。对比2组疗效、毒副反应发生情况以及治疗前后血生化指标,并进行成本-效果分析。结果 观察组客观缓解率58.14%(25/43)、疾病控制率93.02%(40/43)均高于对照组的32.56%(14/43)、72.09%(31/43)(P<0.05)。治疗2、4个疗程,观察组血清癌胚抗原、糖类抗原125、神经元特异性烯醇化酶、血管内皮生长因子、碱性成纤维细胞生长因子均低于对照组(P<0.05)。2组各项毒副反应总发生率比较无显著差异(P>0.05)。观察组总成本高于对照组(P<0.05)。观察组成本-效果比为790.67低于对照组的901.31,且敏感性分析显示,成本-效果分析稳定可靠。结论 贝伐珠单抗联合GC化疗方案治疗晚期NSCLC患者,可下调肿瘤标志物及血管内皮因子水平,提升疗效,且成本-效果优势明显。

左乙拉西坦与丙戊酸钠治疗癫痫患儿的效果比较

目的:比较左乙拉西坦与丙戊酸钠治疗癫痫患儿的效果。方法:选取2020年2月至2023年2月上蔡重阳医院儿科收治的80例癫痫患儿进行前瞻性研究,按照随机数字表法将其分为观察组和对照组各40例。对照组口服丙戊酸钠片治疗,观察组口服左乙拉西坦片治疗。比较两组临床疗效,治疗前后癫痫发作频率、发作持续时间、脑损伤指标[胶质纤维酸性蛋白(GFAP)、神经元特异性烯醇化酶(NSE)和胰岛素样生长因子1(IGF-1)]水平、生命质量[儿童生活质量普通适用核心量表4.0(PedsQL4.0)]评分,以及不良反应发生率。结果:观察组治疗总有效率为90.00%(36/40),高于对照组的72.50%(29/40),差异有统计学意义(P<0.05);治疗后,观察组癫痫发作频率及血清IGF-1、GFAP和NSE水平均低于对照组,PedsQL4.0评分高于对照组,癫痫发作持续时间短于对照组,差异有统计学意义(P<0.05);观察组不良反应发生率为10.00%(4/40),低于对照组的32.50%(13/40),差异有统计学意义(P<0.05)。结论:左乙拉西坦治疗小儿癫痫的效果显著,能够有效降低患儿癫痫发作频率,缩短癫痫发作持续时间,减轻神经损伤,改善生命质量,还能降低不良反应发生率,效果及安全性均优于丙戊酸钠。

血清CYFRA21-1、NSE、VEGF水平联合检测对肺癌患者淋巴结转移的诊断价值

目的:探讨血清细胞角蛋白19片段抗原21-1(CYFRA21-1)、神经元特异性烯醇化酶(NSE)、血管内皮生长因子(VEGF)水平联合检测对肺癌患者淋巴结转移的诊断价值。方法:回顾性分析2020年1月至2022年12月该院收治的150例肺癌患者的临床资料。根据是否发生淋巴结转移将其分为转移组(n=52)与未转移组(n=98)。比较两组患者的病理分型、临床分期和血清CYFRA21-1、NSE、VEGF水平,以及不同临床分期患者的血清CYFRA21-1、NSE、VEGF水平。采用受试者工作特征(ROC)曲线分析血清CYFRA21-1、NSE、VEGF水平单项及联合检测对肺癌淋巴结转移的诊断价值。结果:转移组小细胞肺癌占比、临床分期及血清CYFRA21-1、NSE、VEGF水平均高于未转移组,且患者临床分期越高,血清CYFRA21-1、NSE、VEGF水平越高,差异有统计学意义(P<0.05);ROC曲线分析结果显示,血清CYFRA21-1、NSE、VEGF水平单项及联合检测诊断肺癌淋巴结转移的曲线下面积分别为0.873、0.828、0.701、0.954,联合检测诊断价值高于单一指标检测。结论:血清CYFRA21-1、NSE、VEGF水平检测对肺癌淋巴结转移具有较高的诊断价值,且联合检测的诊断价值高于单项指标检测。

CT血管造影联合NSE及IGF-1在进展性脑梗死疾病评估中的应用价值

目的:探究CT血管造影联合神经元特异性烯醇化酶(NSE)、胰岛素样生长因子-1(IGF-1)在进展性脑梗死疾病评估中的应用价值。方法:选取2022年5月至2023年5月长征医院收治的110例疑似进展性脑梗死患者,均行CT血管造影检测,并按病情将其中63例进展性脑梗死患者纳入观察组[依据美国国立研究院卒中量表(NIHSS)评分,按神经功能缺损的状况分为轻度19例、中度25例、重度16例],47例非进展性脑梗死患者纳入对照组。分析两组患者的血管狭窄度,NSE、IGF-1水平的变化,分析神经功能缺损不同程度的NSE、IGF-1水平变化,探究CT血管造影与NSE、IGF-1之间的关系,以及CT血管造影、NSE及IGF-1联合检测对进展性脑梗死的评估价值。结果:与对照组比较,观察组患者的血管狭窄度、NSE水平有所上升,IGF-1水平有所降低,差异有统计学意义(t=20.893、24.156、40.209,P<0.05)。与轻度患者相比,中度和重度患者的IGF-1水平降低,NSE水平升高,差异有统计学意义(t中度=4.689、9.103,t重度=18.464、23.672,P<0.05);与中度患者相比,重度患者的NSE水平上升,IGF-1水平下降,差异有统计学意义(t=5.408、8.118,P<0.05)。NSE水平与血管狭窄度呈正相关(r=0.651,P<0.05),而IGF-1水平与其呈负相关(r=-0.617,P<0.05)。血管狭窄度、NSE与进展性脑梗死呈正相关(r=0.672,P<0.05),而IGF-1与其呈负相关(r=-0.629,P<0.05)。CT血管造影受试者工作特征曲线下面积(AUC)为0.688(95%CI:0.594~0.786)、NSE的AUC为0.710(95%CI:0.609~0.811)、IGF-1的AUC为0.676(95%CI:0.578~0.775),3项联合AUC为0.822(95%CI:0.734~0.910),3项联合对进展性脑梗死的评估价值较高。结论:NSE在进展性脑梗死患者体内的水平较高,IGF-1水平较低,且NSE、IGF-1与CT血管造影联合可有助于增强对进展性脑梗死的临床评估,为临床诊疗该病提供有利依据。

血清血管内皮生长因子及肿瘤标志物水平与肺癌患者临床分期的关系

目的探讨血清血管内皮生长因子(VEGF)及肿瘤标志物[癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、鳞状细胞癌抗原(SCC-Ag)、细胞角质蛋白19片段抗原21-1(CYFRA21-1)]水平与肺癌患者临床分期的关系。方法选取112例肺癌患者作为观察组,87例健康体检者作为对照组,比较两组受试者、不同临床分期肺癌患者血清VEGF、CEA、NSE、SCC-Ag、CYFRA21-1水平。相关性分析采用Spearman分析;绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评估VEGF、CEA、NSE、SCC-Ag、CYFRA21-1单独及联合检测对肺癌患者临床分期的诊断效能。结果观察组患者血清VEGF、CEA、NSE、SCC-Ag、CYFRA21-1水平均明显高于对照组,差异均有统计学意义(P﹤0.01)。Ⅲ~Ⅳ期肺癌患者血清VEGF、CEA、NSE、SCC-Ag、CYFRA21-1水平均明显高于Ⅰ~Ⅱ期患者,差异均有统计学意义(P﹤0.01)。ROC曲线显示,VEGF、CEA、NSE、SCC-Ag、CYFRA21-1联合检测诊断肺癌患者临床分期的AUC为0.952(95%CI:0.915~0.989),均高于各指标单独检测,此时的灵敏度为0.862,特异度为0.926。血清VEGF、CEA、NSE、SCC-Ag、CYFRA21-1与肺癌患者的临床分期均呈正相关(P﹤0.05)。结论肺癌患者血清VEGF、CEA、NSE、SCC-Ag、CYFRA21-1水平均明显升高,各指标联合检测对肺癌患者的临床分期有较高的诊断价值,且与临床分期均呈正相关。