Effect of transcranial direct current stimulation on neurological injury markers and prognosis in patients with acute and severe carbon monoxide poisoning / 中华劳动卫生职业病杂志

Objective: To observe the effects of transcranial direct current stimulation (tDCS) on nerve injury markers and prognosis in patients with acute severe carbon monoxide poisoning (ASCOP) . Methods: In May 2021, 103 ASCOP patients were treated in the emergency department of Harrison International Peace Hospital of Hebei Medical University from November 2020 to January 2021. The patients were divided into two groups according to whether they received tDCS treatment. The control group (50 cases) were given oxygen therapy (hyperbaric oxygen and oxygen inhalation) , reducing cranial pressure, improving brain circulation and cell metabolism, removing oxygen free radicals and symptomatic support, and the observation group (53 cases) was treated with 2 weeks of tDCS intensive treatment on the basis of conventional treatment. All patients underwent at least 24 h bispectral index (BIS) monitoring, BIS value was recorded at the hour and the 24 h mean value was calculated. Neuron-specific enolase (NSE) and serum S100B calcium-binding protein (S100B) were detected after admission, 3 d, 7 d and discharge. Follow-up for 60 days, the incidence and time of onset of delayed encephalopathy (DEACMP) with acute carbon monoxide poisoning in the two groups were recorded. Results: The NSE and S100B proteins of ASCOP patients were significantly increased at admission, but there was no significant difference between the two groups (P=0.711, 0.326) . The NSE and S100B proteins were further increased at 3 and 7 days after admission. The increase in the observation group was slower than that in the control group, and the difference was statistically significant (P(3 d)=0.045, 0.032, P(7 d)=0.021, 0.000) ; After 14 days, it gradually decreased, but the observation group decreased rapidly compared with the control group, with a statistically significant difference (P=0.009, 0.025) . The 60 day follow-up results showed that the incidence of DEACMP in the observation group was 18.87% (10/53) , compared with 38.00% (19/50) in the control group (P=0.048) ; The time of DEACMP in the observation group[ (16.79±5.28) d] was later than that in the control group[ (22.30±5.42) d], and the difference was statistically significant (P=0.013) . Conclusion: The early administration of tDCS in ASCOP patients can prevent the production of NSE and S100B proteins, which are markers of nerve damage. and can improve the incidence and time of DEACMP.

Aerobic glycolysis in colon cancer is repressed by naringin via the HIF1Α pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.

Clinical features of neuroblastoma: an analysis of 44 children / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of neuroblastoma (NB) and the factors influencing survival rate.@*METHODS@#A total of 44 children with NB who were admitted from April 2016 to February 2020 were enrolled as research subjects. A retrospective analysis was performed on their medical data and follow-up data.@*RESULTS@#The common clinical symptoms of these 44 children were fever (10/44, 23%), mass (9/44, 20%), abdominal pain (8/44, 18%), cough (7/44, 16%), pale complexion (3/44, 7%), claudication (2/44, 5%), and abnormal activity (2/44, 5%). According to the INSS stage, 2 children (4%) had stage I NB, 5 children (11%) had stage II NB, 5 children (11%) had stage III NB, and 32 children (73%) had stage IV NB. The mean follow-up time was (15.3±1.5) months, with a recurrence rate of 20% and an overall survival rate of 82%. Among the 44 children, 29 (66%) achieved event-free survival and 7 (16%) had survival with tumor. The univariate analysis showed that a pathological type of NB and an increase in serum neuron-specific enolase (NSE) decreased the overall survival rate of children with NB (P<0.05).@*CONCLUSIONS@#The clinical symptoms of children with NB are not specific at the first visit. Fever, abdominal pain, and mass are common symptoms, and there is a high proportion of children in the advanced stage. The pathological type of NB and an increase in serum NSE may be associated with a reduction in the overall survival rate of children with NB.

Could cerebrospinal fluid biomarkers offer better predictive value for spinal cord ischaemia than current neuromonitoring techniques during thoracoabdominal aortic aneurysm repair - a systematic review

Abstract Objective: Cerebrospinal fluid (CSF) drainage is a technique that has significantly reduced the incidence of spinal cord ischaemia (SCI). We present results of a systematic review to assess the literature on this topic in relation to thoracoabdominal aortic aneurysm repair (TAAR). Methods: Major medical databases were searched to identify papers related to CSF biomarkers measured during TAAAR. Results: Fifteen papers reported measurements of CSF biomarkers with 265 patients in total. CSF biomarkers measured included S-100ß, neuron-specific endolase (NSE), lactate, glial fibrillary acidic protein A (GFPa), Tau, heat shock protein 70 and 27 (HSP70, HSP27), and proinflammatory cytokines. Lactate and S-100ß were reported the most, but did not correlate with SCI, which was also the case with NSE and TAU. GFPa showed significant CSF level rises, both intra and postoperative in patients who suffered SCI and warrants further investigation, similar results were seen with HSP70, HSP27 and IL-8. Conclusions: Although there is significant interest in this topic, there still remains a significant lack of high-quality studies investigating CSF biomarkers during TAAR to detect SCI. A large and multicentre study is required to identify the significant role of each biomarker.

Neuron-specific enolase as biomarker for possible neuronal damage in dogs with distemper vírus / Enolase neuronal específica como um possível biomarcador para lesão neuronal em cães com cinomose

Neuron-specific enolase (NSE) is a biomarker of neuronal cell lysis, which demonstrates stability in extracellular fluids such as blood and cerebrospinal fluid. To the authors knowledge there is no research information comparing the use of NSE in dogs with and without encephalitis, putting in evidence the importance of that biomarker to detect neuronal damage in dogs. The objective was to compare the serum NSE levels in dogs with and without encephalitis, and to determine the serum NSE levels in normal dogs. Thirty eight dogs were evaluated, 19 dogs with encephalitis (EG Group) and 19 dogs without encephalitis (CG Group). The criteria for inclusion in the EG Group were presence of neurological signs in more than one part of the CNS (multifocal syndrome) and positive molecular diagnosis for canine distemper virus; for the CG Group were an age between 1 to 7 years and be clinically normal; NSE were measured in serum using an ELISA assay, and the results were compared. In the EG Group the NSE values were higher with significant difference (P=0.0053) when compared with the CG Group. NSE is a biomarker that can be measured in serum samples of dogs to monitor neuronal lesions in encephalitis.(AU)

Enolase neuronal específica (NSE) é um biomarcador de lise de neurônios, que demonstra estabilidade em fluidos extracelulares como sangue e líquido cerebrospinal. Para o conhecimento dos autores, não há informações de pesquisa que comparem o uso de NSE em cães com e sem encefalite, evidenciando a importância desse biomarcador para detectar danos neuronais em cães. O objetivo foi comparar os níveis séricos de NSE em cães com e sem encefalites, e determinar os níveis séricos de NSE em cães saudáveis. Trinta e oito cães foram avaliados, 19 cães com encefalites (Grupo EG) e 19 cães sem encefalite (Grupo CG). O critério para inclusão no Grupo EG foi presença de sinais neurológicos em mais de uma estrutura do SNC (síndrome multifocal) e positividade no diagnóstico molecular para o vírus da cinomose canina; para o Grupo CG foi idade entre 1 e 7 anos e ser clinicamente normal; NSE foram mensuradas em amostras séricas usando o método de ELISA, e os resultados comparados. No Grupo EG os valores de NSE foram altos com diferença significativa (P=0.0053) quando comparado com o Grupo CG. NSE é um biomarcador que pode ser mensurado em amostras séricas de cães para monitorar lesões neuronais em encefalites.(AU)

Effect of modified Buyang Huanwu Decoction on hemorrhagic transformation after rt-PA intravenous thrombolysis in patients with super early cerebral infarction / 中国中药杂志

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.

Clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates / 中国当代儿科杂志

OBJECTIVE@#To study the clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates.@*METHODS@#A total of 100 neonates with hypoglycemia were enrolled as subjects. According to amplitude-integrated EEG (aEEG) findings and/or clinical manifestations, they were divided into symptomatic hypoglycemic brain injury group (n=22), asymptomatic hypoglycemic brain injury group (n=37) and hypoglycemic non-brain injury group (n=41). The three groups were compared in terms of blood glucose, duration of hypoglycemia, levels of neuroglobin and neuron-specific enolase (NSE), and modified aEEG score. The correlation of neuroglobin with NSE and modified aEEG score was analyzed. The receiver operating characteristic (ROC) curve was plotted.@*RESULTS@#Compared with the asymptomatic hypoglycemic brain injury and hypoglycemic non-brain injury groups, the symptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Compared with the hypoglycemic non-brain injury group, the asymptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Neuroglobin was positively correlated with NSE and duration of hypoglycemia (r=0.922 and 0.929 respectively; P<0.05) and negatively correlated with blood glucose and modified aEEG score (r=-0.849 and -0.968 respectively; P<0.05). The areas under the ROC curve of neuroglobin, NSE and modified aEEG score were 0.894, 0.890 and 0.941 respectively, and neuroglobin had a sensitivity of 80.8% and a specificity of 95.8% at the optimal cut-off value of 108 mg/L.@*CONCLUSIONS@#Like NSE and modified aEEG score, serum neuroglobin can also be used as a specific indicator for the assessment of brain injury in neonates with hypoglycemia and has a certain value in clinical practice.

Use of neuron-specific enolase to predict mild brain injury in motorcycle crash patients with maxillofacial fractures: A pilot study / 中华创伤杂志(英文版)

PURPOSE@#Mild traumatic brain injury (TBI) is common but accurate diagnosis and its clinical consequences have been a problem. Maxillofacial trauma does have an association with TBI. Neuron-specific enolase (NSE) has been developed to evaluate neuronal damage. The objective of this study was to investigate the accuracy of NSE serum levels to detect mild brain injury of patients with sustained maxillofacial fractures during motor vehicle accidents.@*METHODS@#Blood samples were drawn from 40 healthy people (control group) and 48 trauma patients who had sustained isolated maxillofacial fractures and mild brain injury in motor vehicle accidents. Brain injuries were graded by Glasgow Coma Scale. In the trauma group, correlations between the NSE serum value and different facial fracture sites were also assessed.@*RESULTS@#The NSE serum level (mean ± SD, ng/ml) in the 48 patients with maxillofacial fractures and mild TBI was 13.12 ± 9.68, significantly higher than that measured in the healthy control group (7.72 ± 1.82, p < 0.001). The mean NSE serum level (ng/ml) in the lower part of the facial skeleton (15.44 with SD 15.34) was higher than that in the upper facial part (12.42 with SD 7.68); and the mean NSE level (ng/ml) in the middle-and lower part (11.97 with SD 5.63) was higher than in the middle part (7.88 with SD 2.64).@*CONCLUSION@#An increase in NSE serum levels can be observed in patients sustained maxillofacial fractures and mild brain injury.

Assessment of serum biomarkers and coagulation/fibrinolysis markers for prediction of neurological outcomes of out of cardiac arrest patients treated with therapeutic hypothermia

OBJECTIVE: Despite increased survival in patients with cardiac arrest, it remains difficult to determine patient prognosis at the early stage. This study evaluated the prognosis of cardiac arrest patients using brain injury, inflammation, cardiovascular ischemic events, and coagulation/fibrinolysis markers collected 24, 48, and 72 hours after return of spontaneous circulation (ROSC).METHODS: From January 2011 to December 2016, we retrospectively observed patients who underwent therapeutic hypothermia. Blood samples were collected immediately and 24, 48, and 72 hours after ROSC. Neuron-specific enolase (NSE), S100-B protein, procalcitonin, troponin I, creatine kinase-MB, pro-brain natriuretic protein, D-dimer, fibrin degradation product, antithrombin-III, fibrinogen, and lactate levels were measured. Prognosis was evaluated using Glasgow-Pittsburgh cerebral performance categories and the predictive accuracy of each marker was evaluated. The secondary outcome was whether the presence of multiple markers improved prediction accuracy.RESULTS: A total of 102 patients were included in the study: 39 with good neurologic outcomes and 63 with poor neurologic outcomes. The mean NSE level of good outcomes measured 72 hours after ROSC was 18.50 ng/mL. The area under the curve calculated on receiver operating characteristic analysis was 0.92, which showed the best predictive power among all markers included in the study analysis. The relative integrated discrimination improvement and category-free net reclassification improvement models showed no improvement in prognostic value when combined with all other markers and NSE (72 hours).CONCLUSION: Although biomarker combinations did not improve prognostic accuracy, NSE (72 hours) showed the best predictive power for neurological prognosis in patients who received therapeutic hypothermia.

Virulence genes of Streptococcus mutans and dental caries

Streptococcus mutans is one of the important bacteria that forms dental biofilm and cause dental caries. Virulence genes in S. mutans can be classified into the genes involved in bacterial adhesion, extracellular polysaccharide formation, biofilm formation, sugar uptake and metabolism, acid tolerance, and regulation. The genes involved in bacterial adhesion are gbps (gbpA, gbpB, and gbpC) and spaP. The gbp genes encode glucan-binding protein (GBP) A, GBP B, and GBP C. The spaP gene encodes cell surface antigen, SpaP. The genes involved in extracellular polysaccharide formation are gtfs (gtfB, gtfC, and gtfD) and ftf, which encode glycosyltransferase (GTF) B, GTF C, and GTF D and fructosyltransferase, respectively. The genes involved in biofilm formation are smu630, relA, and comDE. The smu630 gene is important for biofilm formation. The relA and comDE genes contribute to quorum-sensing and biofilm formation. The genes involved in sugar uptake and metabolism are eno, ldh, and relA. The eno gene encodes bacterial enolase, which catalyzes the formation of phosphoenolpyruvate. The ldh gene encodes lactic acid dehydrogenase. The relA gene contributes to the regulation of the glucose phosphotransferase system. The genes related to acid tolerance are atpD, aguD, brpA, and relA. The atpD gene encodes F1F0-ATPase, a proton pump that discharges H⁺ from within the bacterium to the outside. The aguD gene encodes agmatine deiminase system and produces alkali to overcome acid stress. The genes involved in regulation are vicR, brpA, and relA.

Marcadores moleculares de la asfixia perinatal / Molecular markers of perinatal asphyxia

Introducción: la asfixia perinatal es un problema de salud que puede acarrear alteraciones del neurodesarrollo en los recién nacidos. Las determinaciones en suero de enolasa específica de neurona, lactato deshidrogenasa y aspartato amino transferasa han sido utilizadas como marcadores de asfixia perinatal. Objetivos: evaluar el valor de las determinaciones en suero de lactato deshidrogenasa, aspartato amino transferasa y enolasa específica de neurona como marcadores moleculares de la asfixia perinatal. Métodos: se realizó un estudio observacional descriptivo de corte transversal. Se trabajó con una muestra intencional de 41 recién nacidos asfícticos, clasificados con distintos grados de encefalopatía hipóxico-isquémica según los criterios de Sarnat. Se tomaron muestras de suero al momento del nacimiento y a las 72 horas siguientes. Las determinaciones en suero de enolasa específica de neurona se realizaron por ELISA. Se cuantificó lactato deshidrogenasa y aspartato amino transferasa por espectrofotometría. Resultados: todos los pacientes presentaron valores elevados en suero, de los tres analitos, a las 24 y 72 horas de nacidos. Los valores enzimáticos no variaron significativamente entre las 24 y 72 horas de nacidos sin tomar en cuenta el grado de encefalopatía hipóxico-isquémica. Existe correlación positiva entre los valores enzimáticos a las 24 y a las 72 horas de enolasa específica de neurona y lactato deshidrogenasa. No fue posible diferenciar el grado de encefalopatía hipóxico-isquémica a través de los niveles en suero de estas enzimas. Conclusiones: los valores de estas determinaciones enzimáticas contribuyen a describir desde el punto de vista bioquímico el cuadro del neonato con asfixia perinatal(AU)

Introduction: perinatal asphyxia is a health problem which may cause neurodevelopmental alterations in newborns. Serum determinations of neuron-specific enolase, lactate dehydrogenase, and aspartate aminotransferase have been used as markers of perinatal asphyxia. Objectives: evaluate the value of serum determinations of lactate dehydrogenase, aspartate aminotransferase and neuron-specific enolase as molecular markers of perinatal asphyxia. Methods: a cross-sectional observational descriptive study was conducted of 41 asphyxiated newborns classified as different grades of hypoxic-ischemic encephalopathy according to Sarnat's scale. Serum samples were taken at birth and 72 hours later. Serum determinations of neuron-specific enolase were obtained by ELISA. Lactate dehydrogenase and aspartate aminotransferase were quantified by espectrophotometry. Results: all the patients had high serum values of the three analytes 24 and 72 hours after birth. Enzyme values did not vary significantly from 24 to 72 hours after birth, not considering the grade of hypoxic-ischemic encephalopathy. A positive correlation was found between enzyme values for neuron-specific enolase and lactate dehydrogenase at 24 and 72 hours. It was not possible to differentiate the grade of hypoxic-ischemic encephalopathy via the serum levels of these enzymes. Conclusions: the values of these enzyme determinations contribute to describe the status of neonates with perinatal asphyxia from a biochemical point of view(AU)

Identification of the alpha-enolase P46 in the extracellular membrane vesicles of Bacteroides fragilis

BACKGROUND Members of the Bacteroides fragilis group are the most important components of the normal human gut microbiome, but are also major opportunistic pathogens that are responsible for significant mortality, especially in the case of bacteraemia and other severe infections, such as intra-abdominal abscesses. Up to now, several virulence factors have been described that might explain the involvement of B. fragilis in these infections. The secretion of extracellular membrane vesicles (EMVs) has been proposed to play a role in pathogenesis and symbiosis in gram-negative bacteria, by releasing soluble proteins and other molecules. In B. fragilis, these vesicles are known to have haemagglutination and sialidosis activities, and also contain a capsular polysaccharide (PSA), although their involvement in virulence is still not clear. OBJECTIVE The aim of this study was to identify proteins in the EMV of the 638R B. fragilis strain by mass spectrometry, and also to assess for the presence of Bfp60, a surface plasminogen (Plg) activator, previously shown in B. fragilis to be responsible for the conversion of inactive Plg to active plasmin, which can also bind to laminin-1. METHODS B. fragilis was cultured in a minimum defined media and EMVs were obtained by differential centrifugation, ultracentrifugation, and filtration. The purified EMVs were observed by both transmission electron microscopy (TEM) and immunoelectron microscopy (IM). To identify EMV constituent proteins, EMVs were separated by 1D SDS-PAGE and proteomic analysis of proteins sized 35 kDa to approximately 65 kDa was performed using mass spectrometry (MALDI-TOF MS). FINDINGS TEM micrographs proved the presence of spherical vesicles and IM confirmed the presence of Bfp60 protein on their surface. Mass spectrometry identified 23 proteins with high confidence. One of the proteins from the B. fragilis EMVs was identified as an enolase P46 with a possible lyase activity. MAIN CONCLUSIONS Although the Bfp60 protein was not detected by proteomics, α-enolase P46 was found to be present in the EMVs of B. fragilis. The P46 protein has been previously described to be present in the outer membrane of B. fragilis as an iron-regulated protein.

Diagnostic value of α-enolase expression and serum α-enolase autoantibody levels in lung cancer / Valor diagnóstico da expressão de α-enolase e dos níveis séricos de autoanticorpos contra α-enolase no câncer de pulmão

ABSTRACT Objective: To investigate the diagnostic value of α-enolase (ENO1) and serum ENO1 autoantibody levels in lung cancer. Methods: Immunohistochemistry staining and ELISA were performed to detect ENO1 expression in lung tissue and serum ENO1 autoantibody levels, respectively. Results: The expression of ENO1 was higher in lung cancer tissues than in benign lung disease tissues (p < 0.001). The proportion of lung cancer samples expressing ENO1 was not significantly different among the various pathological classification groups. The proportion of samples expressing ENO1 was higher in lung cancer patients in stages I/II than in those in stages III/IV (χ2 = 5.445; p = 0.018). The expression of ENO1 in lung cancer tissues was not associated with age, gender, or smoking history. Serum ENO1 antibody levels were significantly higher in the lung cancer group than in the benign lung disease and control groups (p < 0.001). The differences among the pathological classification groups were not statistically significant. Serum ENO1 antibody levels were also in lung cancer patients in stages I/II than in those in stages III/IV (p < 0.01). Serum ENO1 antibody levels were not associated with age, gender, or smoking history in lung cancer patients. The ROC curve representing the diagnosis of lung cancer based on ENO1 antibody levels had an area under the curve of 0.806. Conclusions: Our results suggest that high levels of ENO1 are associated with the clinical stage of lung cancer and that ENO1 expression and its serum autoantibody levels show diagnostic value in lung cancer.

RESUMO Objetivo: Investigar o valor diagnóstico da α-enolase (ENO1) e dos níveis séricos de autoanticorpos contra ENO1 no câncer de pulmão. Métodos: Marcação imuno-histoquímica e ELISA foram realizados para detectar a expressão de ENO1 no tecido pulmonar e os níveis séricos de autoanticorpos contra ENO1, respectivamente. Resultados: A expressão de ENO1 foi maior nos tecidos de câncer de pulmão que nos tecidos de doença pulmonar benigna (p < 0,001). Não houve diferença significativa entre os diversos grupos de classificação patológica quanto à proporção de amostras de câncer de pulmão que expressaram ENO1. A proporção de amostras que expressaram ENO1 foi maior nos pacientes com câncer de pulmão nos estágios I/II que naqueles com câncer de pulmão nos estágios III/IV (χ2 = 5,445; p = 0,018). Não houve relação entre a expressão de ENO1 em tecidos de câncer de pulmão e idade, sexo ou histórico de tabagismo. Os níveis séricos de anticorpos contra ENO1 foram significativamente maiores no grupo câncer de pulmão que nos grupos doença pulmonar benigna e controle (p < 0,001). As diferenças entre os grupos de classificação patológica não foram estatisticamente significativas. Os níveis séricos de anticorpos contra ENO1 foram também significativamente maiores nos pacientes com câncer de pulmão nos estágios I/II que naqueles com câncer de pulmão nos estágios III/IV (p < 0,01). Nos pacientes com câncer de pulmão, não houve relação entre os níveis séricos de anticorpos contra ENO1 e idade, sexo ou histórico de tabagismo. A curva ROC do diagnóstico de câncer de pulmão baseado nos níveis de anticorpos contra ENO1 apresentou área sob a curva = 0,806. Conclusões: Nossos resultados sugerem que há relação entre níveis elevados de ENO1 e o estágio clínico do câncer de pulmão e que a expressão de ENO1 e os níveis séricos de autoanticorpos contra ENO1 têm valor diagnóstico no câncer de pulmão.

Analyzing the neuropsychological characteristics and changes in serum markers of patients with chronic cerebral circulation insufficiency

Summary Objective: To investigate the neuropsychological characteristics and changes in CRP, S100B, MBP, HSP-7, and NSE in serum. Method: Sixty-six (66) patients treated in our hospital as CCCI group were chosen for our study, and 90 patients with depression were selected as the depression group. The patients in both groups were examined with CT perfusion, depression, anxiety and cognition evaluation. Their serum CRP, S100B, MBP, HSP-70 and NSE levels were detected. Neuropsychological and serum markers characteristics were compared. Results: The CBF and CBV in bilateral basal ganglia, frontal lobes, greater oval center, brain stem, and left and right regions of occipital lobes of the patients in CCCI group were significantly lower than in the depression group. The HAMD and HAMA scores of CCCI group patients were significantly lower than in the depression group; CCCI group performed better regarding attention, memory, abstract terms and delayed recall. CCCI also had significantly higher total scores than the depression group. Serum CRP, S100B, MBP, HSP-70 and NSE levels in CCCI group were significantly higher than in the depression group. The differences reach statistical significance (p<0.05). Conclusion: CCCI patients who are accompanied by minor depressive disorder have different degrees of cognitive impairment and experience a significant rise in serum CRP, S100B, MBP, HSP-70 and NSE.

Relationship between Serum Neuron Specific Enolase Level and Seizure in Patients with Acute Glufosinate Ammonium Poisoning

PURPOSE: Glufosinate ammonium poisoning can cause seizures, even after a symptom-free period. This study was conducted to evaluate the relationship between serum neuron specific enolase (NSE) level and the occurrence of seizures in patients with acute glufosinate ammonium poisoning. METHODS: For this retrospective observational study, data from patients diagnosed with acute glufosinate ammonium poisoning were collected between January 2016 and June 2016. Serum NSE was measured within 2 hours of arrival at the emergency department. The patients were divided into a seizure group and a non-seizure group. RESULTS: The seizure group included eight of the 15 total patients (53.3%). The serum NSE level was significantly higher in the seizure group than in the non-seizure group (32.4±11.9 ng/mL vs. 19.5±5 ng/mL, p=0.019). The amount of glufosinate ingested and initial and peak serum ammonia levels were significantly higher in the seizure group than in the non-seizure group. There was no significant difference in the area under the curve of the serum NSE level or the initial and peak serum ammonia levels in terms of predicting the occurrence of seizures. CONCLUSION: In acute glufosinate poisoning, initial serum NSE levels may help in prediction of seizures.

Laminar Distribution of Neurochemically-Identified Interneurons and Cellular Co-expression of Molecular Markers in Epileptic Human Cortex / 神经科学通报·英文版

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the co-expression of molecular markers in epileptic human cortex. We found that parvalbumin (PV) and somatostatin (SST) neurons were distributed in all cortical layers except layer I, while tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were abundant in the deep layers and white matter. Cholecystokinin (CCK) neurons showed a high density in layers IV and VI. Neurons with these markers constituted ~7.2% (PV), 2.6% (SST), 0.5% (TH), 0.5% (NPY), and 4.4% (CCK) of the gray-matter neuron population. Double- and triple-labeling revealed that NPY neurons were also SST-immunoreactive (97.7%), and TH neurons were more likely to express SST (34.2%) than PV (14.6%). A subpopulation of CCK neurons (28.0%) also expressed PV, but none contained SST. Together, these results revealed the density and distribution patterns of different interneuron populations and the overlap between molecular markers in epileptic human cortex.

Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature

Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year-old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC.

Lentivirus-mediated microRNA-124 gene-modified bone marrow mesenchymal stem cell transplantation promotes the repair of spinal cord injury in rats

Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group. The mRNA expression of miR-124 and the mRNA and protein expression of pyridoxal kinase (PDXK) were detected by quantitative real-time polymerase chain reaction and western blotting. The locomotor capacity of the rats was evaluated using the Basso, Beattie and Bresnahan (BBB) scale. Brdu, neuron-specific enolase (NSE), neurofilament (NF) and microtubule-associated protein 2 (MAP2) were detected using immunohistochemistry. The expression levels of thyrotropin-releasing hormone (TRH), prostacyclin (PGI2) and gangliosides (GM) were measured using an enzyme-linked immunosorbent assay. PDXK was identified as the target gene of miR-124. The overexpressed miR-124 group exhibited higher miR-124 expression than the SCI, NC and si-PDXK groups. Compared with the SCI and NC groups, the PDXK expression was downregulated in the overexpressed miR-124 and si-PDXK groups, and the BBB scores were significantly increased 7, 21 and 35 days after transplantation. The double-labeled positive cell densities (Brdu+NSE/NF/MAP2) and the expression levels of TRH, PGI2 and GM in the overexpressed miR-124 group were significantly higher than those in the NC and SCI groups. These results indicated that miR-124 targeted PDXK to accelerate the differentiation of BMSCs into neurocytes and promote SCI repair.

Advances of circulating biomarkers in gastroenteropancreatic neuroendocrine neoplasms / 中华胃肠外科杂志

Gastroenteropancreatic neuroendocrine neoplam (GEP-NEN) is a rare group of tumors with its incidence rising significantly in recent decades. Because of the late presentation of the disease and limitations in conventional biomarkers, about 50% of GEP-NEN patients manifests advanced disease when diagnosed. Therefore, it is vital to identify circulating biomarkers which can not only be used for early diagnosis but also accurately evaluating the biological behavior of GEP-NEN. This review summarizes the advances of circulating biomarkers in diagnosing and evaluating efficacy of treatment in GEP-NEN. Well-known circulating biomarkers include chromogranin A (CgA), pancreastatin (PST), chromogranin B (CgB), neuron-specific enolase (NSE) and pancreatic peptide(PP). Novel biomarkers including circulating tumor cell(CTC), microRNA and NETest are promising biomarkers with potential clinical benefit, but further researches are needed before their clinical applications.

Clinical Significance of Pretreatment FDG PET/CT in MIBG-Avid Pediatric Neuroblastoma / 대한핵의학회잡지

PURPOSE: ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in ¹²³I- or ¹³¹I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated.METHODS: Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information—including histopathology, and serum markers—and several PET parameters—including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)—were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS).RESULTS: Total 20 patients (4.5 ± 3.5 years) were divided as two groups by disease progression. Six patients (30.0 %) experienced disease progression and one patient (5.0 %) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv (p = 0.017), TBR (p = 0.09), MTV (p = 0.02), and CV (p = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv (p = 0.021) and TBR (p = 0.023).CONCLUSIONS: FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma.