Key elements determining the intestinal region-specific environment of enteric neurons in type 1 diabetes

Diabetes,as a metabolic disorder,is accompanied with several gastrointestinal(GI)symptoms,like abdominal pain,gastroparesis,diarrhoea or constipation.Serious and complex enteric nervous system damage is confirmed in the background of these diabetic motility complaints.The anatomical length of the GI tract,as well as genetic,developmental,structural and functional differences between its segments contribute to the distinct,intestinal region-specific effects of hyperglycemia.These observations support and highlight the importance of a regional approach in diabetes-related enteric neuropathy.Intestinal large and microvessels are essential for the blood supply of enteric ganglia.Bidirectional morpho-functional linkage exists between enteric neurons and enteroglia,however,there is also a reciprocal communication between enteric neurons and immune cells on which intestinal microbial composition has crucial influence.From this point of view,it is more appropriate to say that enteric neurons partake in multidirectional communication and interact with these key players of the intestinal wall.These interplays may differ from segment to segment,thus,the microenvironment of enteric neurons could be considered strictly regional.The goal of this review is to summarize the main tissue components and molecular factors,such as enteric glia cells,interstitial cells of Cajal,gut vasculature,intestinal epithelium,gut microbiota,immune cells,enteroendocrine cells,prooxidants,antioxidant molecules and extracellular matrix,which create and determine a gut region-dependent neuronal environment in diabetes.

Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

Neuron specific enolase,p53蛋白和proliferating-cell nuclear antigen在肺癌组织中的表达及意义

目的：研究神经元特异性烯醇化酶（neuronspecificenolase，NSE）的表达，与p53蛋白和增殖细胞核抗原（prolif－erating－cellnuclearantigen，PCNA）表达的关系及意义．方法：用特异性鼠抗人单克隆抗体，按LSAB免疫组织化学方法检测石蜡包埋的肺癌标本中NSE，p53蛋白和PCNA的表达．结果：在小细胞性肺癌（SmallCellLungCancer，SCLC）中，NSE阳性表达者，PCNA标记指数（LabellingIndex，LI）高于NSE阴性者，而p53蛋白的表达与NSE的表达无关．在非小细胞性肺癌（non－smallcelllungcancr，non－SCLC）中，p53蛋白的表达和PCNALI均与NSE的表达无关．结论：在SCLC的发生及发展过程中，神经内分泌功能可能起了部分作用．而p53抑癌基因在SCLC的发生中并不起着重要的作用．

Changes in plasma calcitonin gene-related peptide and serum neuron specific enolase in rats with acute cerebral ischemia after low-frequency electrical stimulation with different waveforms and intensities

Following acute cerebral ischemia in rats, plasma calcitonin gene-related peptide decreased and the level of serum neuron specific enolase and the volume of the infarction increased. Square-wave and triangular-wave electrical stimulation with low or high intensities could increase the plasma calcitonin gene-related peptide, decrease the serum neuron specific enolase and reduce the infarction volume in the brain in rats with cerebral ischemia. There was no significant difference between different wave forms and intensities. The experimental findings indicate that low-frequency electrical stimulation with varying waveforms and intensities can treat acute cerebral ischemia in rats.

Neuron-specific Enclose and Myelin Basic Protein in Cerebrospinal Fluid of Patients with First Episode Schizophrenia

In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase （NSE） and myelin basic protein （MBP）in cerebrospinal fluid （CSF） of 33 patients with first episode schizophrenia and 9 from the control group were determined by double antibody sandwich enzyme immunoassay method. The results showed that there was significant difference in the NSE contents between the experimental group and control group （P〈0.01）. The NSE contents in CSF in the experimental group were positively correlated with MBP in schizophrenia patients （P〈 0.05）. These findings suggested that patients with schizophrenia had cerebral injury.

Plasma level of neuron specific enolase in patients with acute cerebral infarction:A case-control study

BACKGROUND： The plasma level of neuron specific enolase （NSE） can be used to diagnose and evaluate neuronal injury and predict early prognosis. OBJECTIVE： To observe the dynamic changes in plasma levels of NSE in patients with acute cerebral infarction, and to investigate its correlations with disease severity and prognosis. DESIGN, TIME AND SETTING： This non-randomized, concurrent case-control experiment was performed at the Department of Neurology, First Hospital Affiliated to Heilongjiang University of Traditional Chinese Medicine between May and July 2007. PARTICIPANTS： Eighteen patients with acute cerebral infarction, who received treatment at the Department of Neurology, First Hospital Affiliated to Heilongjiang University of Traditional Chinese Medicine between May and July 2007, were recruited into the patient group. An additional 10 healthy individuals, who received health examinations simultaneously, were included as controls. METHODS： Following admission （within 3 days） and at days 6, 12, and 30 subsequent to acute cerebral infarction attack, 3 mL venous blood was taken from each patient before the morning meal to determine the plasma level of NSE by enzyme-labeled immunosorbent assay. One-time blood extraction was performed in each healthy subject during the health examination for the same purpose as in patients. At 6 and 30 days following acute cerebral infarction attack, CT examination was performed for calculation of cerebral infarction volume according to the Tada formula. Following admission and at 30 days of disease invasion, all patients were scored by the National Institutes of Health Stroke Scale （NIHSS, 13 items）. MAIN OUTCOME MEASURES： Comparison of NSE plasma level between acute cerebral infarction patients and healthy individuals; correlations of NSE plasma level in acute cerebral infarction patients with cerebral infarction volume, NIHSS score, and prognosis. RESULTS： Following admission and at days 6 and 12 of disease invasion, the plasma level of NSE was significantly higher in the patient group than in the control group （P 〈 0.05）. Following admission and at day 30 of disease invasion, the NIHSS scores of the patient group were 17.706 and 11.222, respectively. Following admission and at day 6 of disease invasion, the plasma level of NSE was positively correlated with cerebral infarction volume （r = 0.503, 0.435, P 〈 0.05）, but it was negatively correlated with NIHSS score （r = -0.571, 0.368, P 〈 0.05）. The plasma level of NSE was mostly correlated with cerebral infarction volume, followed by NIHSS score, and lastly prognosis, with regression coefficients of 0.386, 0.343, and 0.340, respectively. CONCLUSION： The plasma level of NSE is higher in patients with acute cerebral infarction than in the healthy population. It can reflect infarct severity and predict early prognosis of acute cerebral infarction.

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.

Flunarizine and lamotrigine prophylaxis effects on neuron-specific enolase, S-100, and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage

BACKGROUND： Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE： To investigate the neuroprotective effects of flunarizine （FNZ）, lamotrigine （LTG） and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING： This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People＇s Hospital, Guangdong Medical College. MATERIALS： Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ ＋ LTG, and model groups, with 10 rats in each group. METHODS： Rats in the FNZ, LTG, and FNZ ＋ LTG groups received intragastric injections of FNZ （0.5 mg/kg/d）, LTG （10 mg/kg/d）, and FNZ （0.5 mg/kg/d） ＋ LTG （10 mg/kg/d）, respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES： Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS： Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ ＋ LTG groups following ischemia, compared with the model group （P 〈 0.01）. However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ ＋ LTG group, following ischemia （P 〈 0.01）. CONCLUSION： Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.

龟羚帕安丸对帕金森病大鼠血清NSE、Cys-C、5-HT、5-HIAA及NE水平的影响

目的观察龟羚帕安丸对帕金森病(Parkinson’s disease,PD)大鼠血清神经元特异性烯醇化酶(Neuron-specific enolase,NSE)、胱抑素C(Cystatin C,Cys-C)、5-羟色胺(5-Hydroxytryptamine,5-HT)、5-羟基吲哚乙酸(5-Hydroxyindoleacetic acid,5-HIAA)及去甲肾上腺素(Norepinephrine,NE)水平的影响。方法采用6-羟基多巴胺(6-OHDA)立体定向注射法制作PD大鼠模型,造模成功的PD大鼠随机分为模型组,西药组,中药高、中、低剂量组,中西药合用组,每组15只,另设假手术组15只。模型组及假手术组给予等容积生理盐水灌胃,其余组给予相应药物灌胃,连续给药28 d。大鼠腹主动脉取血,用酶联免疫吸附测定法(Enzyme linked immunosorbent assay,ELISA)检测各组大鼠血清NSE、Cys-C、5-HT、5-HIAA及NE的水平。结果模型组大鼠血清NSE及Cys-C水平均明显升高,血清5-HT、5-HIAA及NE水平均明显降低;中药各剂量组、中西药合用组、西药组血清NSE及Cys-C水平均明显降低,5-HT、5-HIAA及NE水平均明显升高。结论龟羚帕安丸具有明显神经保护作用,作用机制与降低NSE及Cys-C水平,增加5-HT、5-HIAA及NE水平,降低脑实质损伤、神经炎症损伤及提高单胺类神经递质有关。

血清NSE、CYFRA21-1与CT影像联合检测区分肺结节良恶性的临床性能研究

目的探究血清肿瘤标志物神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段(CYFRA21-1)和计算机断层扫描(CT)在肺结节良、恶性诊断中的临床应用价值。方法回顾性研究2020年6月至2021年6月于我院经病理检查确诊的肺结节患者396例,比较患者肺部良、恶性结节的CT影像特征和血清肿瘤标志物NSE、CYFRA21-1水平的差异,分析血清NSE和CYFRA21-1水平与CT影像在区分肺结节良、恶性的临床性能。结果肺恶性结节患者的CT征象中磨玻璃或混合密度结节、分叶征、毛刺征的发生率明显高于良性结节,结节直径较大。肺恶性结节患者的血清肿瘤标志物NSE和CYFRA21-1水平显著升高(P<0.05)。NSE、CYFRA21-1与CT影像联合检测的灵敏度为78.60%,特异性为83.43%,明显高于肿瘤标志物性能。结论血清NSE、CYFRA21-1联合CT检测,对于良、恶性肺结节的诊断具有更高的临床诊断性能。

Electrophoretic Determination of Aqueous and Serum Neuron-specific Enolase in the Diagnosis of Retinoblastoma

Purpose: Neuron-specific enolase (NSE) of containing γ-enolase is considered valuable in the diagnosis of tumours of neuroectodermal origin.Method : We used rapid electrophoretic method on cellulose acetate plate to determine the pattern of enolase isoenzymes in 21 aqueous humor and 23 serum specimens from retinoblastoma (Rb) and 21 aqueous and 25 serum specimens from 25 control cases to evaluate NSE in the diagnosis of Rb. The assay allowed assessment of all three major isoenzymes (aa,aγ and γγ),and NSE relative activity and its percentage in the total relative activity of the three enolase isoenzymes were assessed by means of fluorometer.Result: Aqueous from all patients with Rb contained aa,ar and rr isoenzymes and presented strong postitive, the positive rate of NSE being 100% and its relative activity accounting for 45 ± 9% of the total relative activity of the 3 enolase isoenzymes; No enolase was detectable in control aqueous with cataract, glaucoma and Coats's diseases (4 cases),but in two

血清HIF-1α、NSE、GFAP及相关临床特征与新生儿缺氧缺血性脑病发生风险的关系分析

目的探讨血清低氧诱导因子-1α(HIF-1α)、神经元特异性烯醇化酶(NSE)、胶质纤维酸性蛋白(GFAP)及相关临床特征与新生儿缺氧缺血性脑病(HIE)发生风险的关系。方法选取2020年1月—2023年1月苏州大学附属儿童医院收治的85例HIE患儿作为HIE组,另选取同期在该院出生的120例健康新生儿作为对照组,分析两组的临床资料并检测新生儿出生后3 d血清HIF-1α、NSE、GFAP水平。绘制受试者工作特征(ROC)曲线分析血清HIF-1α、NSE、GFAP水平预测新生儿HIE发病的价值;多因素逐步Logistic回归模型分析新生儿HIE发病的影响因素。结果与对照组相比,HIE组宫内窘迫、脐带异常、羊水污染、1 min Apgar评分≤7分的患儿比例较高(P<0.05),并且血清HIF-1α、NSE、GFAP水平较高(P<0.05);两组孕妇年龄、孕妇文化程度、胎龄、新生儿性别、出生体重、产次、剖宫产、胎膜早破比较,差异均无统计学意义(P>0.05)。ROC曲线分析结果显示,HIF-1α、NSE、GFAP及三者联合预测新生儿HIE发病的敏感性分别为82.7%(95%CI:0.795,0.862)、78.7%(95%CI:0.705,0.849)、84.0%(95%CI:0.803,0.891)、85.3%(95%CI:0.788,0.922),特异性分别为85.3%(95%CI:0.816,0.907)、74.7%(95%CI:0.715,0.796)、72.0%(95%CI:0.692,0.771)、90.5%(95%CI:0.825,0.956),AUC分别为0.907(95%CI:0.884,0.930)、0.850(95%CI:0.816,0.884)、0.893(95%CI:0.827,0.959)、0.936(95%CI:0.905,0.967);多因素逐步Logistic回归分析显示,宫内窘迫[O^R=3.592(95%CI:2.017,6.397)]、脐带异常[O^R=4.905(95%CI:2.862,8.406)]、羊水污染[O^R=7.262(95%CI:3.603,14.637)]、1 min Apgar评分≤7分[O^R=3.139(95%CI:1.954,5.043)]、HIF-1α≥0.463 ng/mL[O^R=2.916(95%CI:1.422,5.980)]、NSE≥12.395μg/L[O^R=3.714(95%CI:1.955,7.056)]、GFAP≥3.962 ng/mL[O^R=3.556(95%CI:2.039,6.202)]均是新生儿HIE发病的危险因素(P<0.05)。结论宫内窘迫、脐带异常、羊水污染、出生后1 min Apgar评分低及血清HIF-1α、NSE、GFAP水平高是新生儿HIE发病的危险因素,临床通过检测血清HIF-1α、NSE、GFAP水平可为临床筛查HIE提供帮助,3项指标联合检测可进一步提高诊断价值。

血清CA125、CYFRA21-1、CEA、NSE及ALP联合检测对原发性肺癌患者骨转移的预测价值

目的探究血清糖类抗原125(CA125)、细胞角蛋白19片段抗原21-1(CYFRA21-1)、癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)及碱性磷酸酶(ALP)联合检测对原发性肺癌患者骨转移的预测价值。方法选取肺癌患者104例为观察组,并根据是否发生骨转移分为骨转移组(50例)和无骨转移组(54例)。同时选取100例肺部良性病变者为对照组。收集肺癌患者临床资料,检测所有受试者血清CA125、CYFRA21-1、CEA、NSE及ALP水平。采用受试者工作特征(ROC)曲线分析血清CA125、CYFRA21-1、CEA、NSE、ALP对肺癌患者骨转移的预测价值。采用多因素Logistic回归分析肺癌患者骨转移的影响因素。结果与对照组相比,观察组血清CA125、CYFRA21-1、CEA、NSE、ALP水平显著升高(P<0.05)。骨转移组中临床分期Ⅲ~Ⅳ期患者占比、有淋巴结转移患者占比及血清CA125、CYFRA21-1、CEA、NSE、ALP水平显著高于无骨转移组(P<0.05)。血清CA125、CYFRA21-1、CEA、NSE、ALP预测肺癌患者发生骨转移的AUC分别为0.818、0.816、0.739、0.770、0.771,5种肿瘤标志物联合检测的AUC为0.955,敏感度、特异度、AUC均显著高于各肿瘤标志物单独检测(P<0.05)。多因素Logistic回归分析显示,CA125、CYFRA21-1、CEA、NSE、ALP是影响肺癌患者发生骨转移的危险因素(P<0.05)。结论血清CA125、CYFRA21-1、CEA、NSE、ALP联合检测对原发性肺癌患者骨转移的预测具有较高的价值,联合诊断效能更高。

血清NSE、CYFRA21-1及Pro-GRP与肺癌病理特征及转移的关系

目的探讨血清神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段(CYFRA21-1)及胃泌素释放肽前体(Pro-GRP)与肺癌病理特征及转移的关系。方法选择100例肺癌患者设为肺癌组,50例肺部良性病变患者设为良性组和50例健康体检者设为对照组,采集3组受检者空腹静脉血5 mL,测定血清NSE、Pro-GRP、CYFRA21-1水平。对比3组NSE、Pro-GRP、CYFRA21-1水平差异,并分析NSE、Pro-GRP、CYFRA21-1与肺癌病理特征及转移的关系。结果肺癌组、良性组NSE、Pro-GRP、CYFRA21-1水平均高于对照组,有统计学差异(P<0.05)。肺癌Ⅲ~Ⅳ期者NSE、Pro-GRP、CYFRA21-1水平高于Ⅰ~Ⅱ期者,有统计学差异(P<0.05);小细胞癌NSE、Pro-GRP水平高于腺癌、鳞癌,CYFRA21-1水平低于腺癌,鳞癌Pro-GRP水平高于腺癌,CYFRA21-1水平低于腺癌,有统计学差异(P<0.05);有转移者NSE、Pro-GRP、CYFRA21-1水平均高于无转移者,有统计学差异(P<0.05)。结论肺癌患者NSE、Pro-GRP、CYFRA21-1呈高表达,其水平高低与TNM分期和转移有关。

THE EXTENSIVENESS AND SPECIFICITY OF EFFECT OF ELECTROACUPUNCTURE AT DIFFERENT ACUPOINTS ON NOCICEPTIVE RESPONSE OF CONVERGENT NEURONS IN TRIGEMINAL NUCLEUS CAUDALIS

Experiments were carried out on rats anaesthetized with uraethane. The sponta-neous discharges and nociceptive responses of convergent neurons in the right trigerninal nucleus cau-dalis(TNC) to noxious stimuli at receptive field (cheek) were recorded extracellularly with glass mi-cro-electrode. Electroacupuncture (EA ) was applied at bilateral " Xiaguan" (ST 7 on face ) or "Zusanli" (ST 36 on shank) acupoint with Iow (2V) and high (18V) intensity. The noclceptive re-sponse of convergent neurons in TNC could be inhihited by low intensity EA applied at "Xiaguan" butnot "Zusanlil", showing the specificity of acupoints. High intensity EA at either "Xiaguan" or "Zusan-li" also reduced the nociceptive responses, showing the analgesic extensiveness of acupoints. We sug-gest that "the gate of control" mechanism plays a main role in low intensity EA and "diffuse noxiousinhibitory controls" (DNIC) rnechanism does so in high intensity EA.The results suggest that we should pay attention to the location of acupoints,

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

Pivotal role of long non-coding ribonucleic acid-X-inactive specific transcript in regulating immune checkpoint programmed death ligand 1 through a shared pathway between miR-194-5p and miR-155-5p in hepatocellular carcinoma

BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.

急性腹泻伴良性惊厥患儿血清NSE、H_2S、UCH-L1水平变化及对预测复发的临床价值分析

目的 探讨急性腹泻伴良性惊厥患儿血清神经元特异性烯醇化酶(NSE)、硫化氢(H_(2)S)、泛素羧基末端水解酶L1(UCH-L1)水平变化及其对疾病复发的预测效能。方法 选择秦皇岛市第一医院2018年8月—2021年8月收治的急性腹泻伴良性惊厥的104例患儿进行前瞻性研究,另选同期于秦皇岛市第一医院行健康体检的30例健康儿童为对照组,所有儿童均取空腹静脉血检测血清NSE、H_(2)S、UCH-L1水平,并对比两组儿童及观察组不同病情患儿的血清NSE、H_(2)S、UCH-L1水平差异;观察组患儿随访2年以观察复发情况,对比有无复发患儿血清NSE、H_(2)S、UCH-L1水平差异,并采用受试者工作特征曲线(ROC)分析急性腹泻伴良性惊厥患儿血清NSE、H_(2)S、UCH-L1水平对复发的预测效能。结果 观察组血清NSE、UCH-L1水平明显高于对照组,H_(2)S水平明显低于对照组(P<0.05);相较于腹泻3~5次/d、惊厥发作1次、单次惊厥持续时间<5 min、惊厥局灶性发作的患儿,腹泻≥6次/d、惊厥发作≥2次、单次惊厥持续时间≥5 min、惊厥全面性发作患儿的血清NSE,UCH-L1水平均明显更高(P<0.05),血清H_(2)S水平明显更低(P<0.05);复发组患儿的血清NSE、UCH-L1水平明显高于未复发组(P<0.05),血清H_(2)S水平明显低于未复发组(P<0.05);ROC曲线分析显示,急性腹泻伴良性惊厥患儿血清NSE、H_(2)S、UCH-L1水平及联合检测均对复发有预测效能(P<0.05),其中单项检测时血清NSE对复发的预测效能较高,曲线下面积(AUC)为0.787,敏感为77.78%,特异度为81.05%;联合检测的预测效能最高,AUC为0.804,敏感性为88.89%,特异度为75.79%。结论 急性腹泻伴良性惊厥患儿的血清NSE、UCH-L1水平明显升高,血清H_(2)S水平降低,且与病情程度存在相关性,可用于预测惊厥复发。

血清神经元特异性烯醇化酶及肿瘤坏死因子-α水平与病毒性脑炎继发性癫痫患儿预后的关系

目的探讨血清神经元特异性烯醇化酶(NSE)、肿瘤坏死因子-α(TNF-α)水平与病毒性脑炎(VE)患儿继发性癫痫发作期及其与预后的关系。方法选择2015年1月至2020年1月内蒙古医科大学附属人民医院收治的96例VE患儿为研究对象,根据脑电图检查结果分为对照组(单纯VE患儿,n=30)和观察组(VE继发性癫痫患儿,n=66)。另选择同期在医院进行体检的30例健康儿童作为健康组。比较健康组、对照组、观察组受试者血清NSE、TNF-α水平。根据入院后24 h内是否再次发作将观察组患儿分为24 h内再发作组(n=48)和24 h内未再发作组(n=18),比较2组患儿血清NSE、TNF-α水平,并采用Pearson相关性分析NSE、TNF-α水平与VE继发性癫痫患儿发作期的关系。根据出院时儿童格拉斯哥预后量表评分将观察组患儿分为预后良好组(n=45)和预后不良组(n=21),比较2组患儿血清NSE、TNF-α水平及其他可能影响预后的因素,采用多因素logistic回归分析影响VE继发性癫痫患儿预后的相关因素,并绘制受试者操作特征曲线分析血清NSE、TNF-α对VE继发性癫痫患儿预后的预测价值。结果对照组患儿血清NSE水平显著高于健康组(P<0.05);对照组与健康组受试者血清TNF-α水平比较差异无统计学意义(P>0.05);观察组患儿血清NSE、TNF-α水平显著高于健康组和对照组(P<0.05)。24 h内再发作组患儿血清NSE、TNF-α水平显著高于24 h内未再发作组(P<0.05)。预后良好组患儿脑电图重度异常、头颅影像学重度异常、合并呼吸衰竭占比及血清C反应蛋白、NSE、TNF-α水平均低于预后不良组(P<0.05);2组患儿的性别、年龄、体质量、脑损伤部位、发热、低钾血症、低钠钾症、既往抽搐、应激性高血糖、合并脏器功能损伤、病毒感染情况、首发癫痫、入院时格拉斯哥昏迷量表评分、抽搐持续时间、住院时间、白细胞计数及天冬氨酸转氨酶、肌酸激酶、心肌肌钙蛋白水平比较差异均无统计学意义(P>0.05)。多因素logistic回归分析结果显示,合并呼吸衰竭、血清NSE、TNF-α水平升高是影响VE继发性癫痫患儿预后的相关因素(P<0.05)。血清NSE、TNF-α预测VE继发性癫痫患儿预后曲线下面积(AUC)分别为0.724(95%置信区间:0.672~0.776)、0.689(95%置信区间:0.637~0.734),敏感度分别为82.22%、75.56%,特异度分别为76.19%、71.43%,二者联合预测VE继发性癫痫患儿预后的AUC为0.826(95%置信区间:0.774~0.873),敏感度和特异度分别为73.33%、80.95%。结论VE继发癫痫患儿血清NSE、TNF-α水平呈异常高表达,是影响患儿预后的相关因素,对患儿预后具有良好预测价值。