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Simple febrile convulsion (SFC) is a common disease that is mainly caused by fever from extracranial infections. In this study, we used proteomic approaches involving discovery and validation cohorts to examine the proteomes of serum from children who were diagnosed with SFC, children with fever but without convulsion, and healthy children (normal controls). We identified 86 proteins involved in different biological pathways that were significantly different between the SFC and normal control groups. Of these 86 proteins, 35 had higher expression in the SFC group compared with the normal control group, whereas 51 had lower expression. Notably, fibrinogen-related proteins involved in the coagulation system pathway were markedly decreased in the SFC group. Targeted and absolute quantification of fibrinogen-related proteins was performed and validated the potential of these proteins as biomarkers. Thus, fibrinogen-related proteins may participate in the pathophysiological process of SFC and may be potential biomarkers for the diagnosis of SFC.

Asthma is marked by chronic irritation in the airway lumen of the lungs due to the accretion of inflammatory cells that influence the regular inhalation process. An extended buildup of inflammation leads to oxidative pressure and the repression of antioxidant functions. In the current study, a potential compound, boldine, was tested for the containment of provocative markers along the path of antiasthmatic activity in an ovalbumin (OVA)-induced asthmatic mice model. As an effect, the boldine (10 and 20 mg/kg) treatment suppressed inflammatory cells such as eosinophil, macrophage, neutrophil, lymphocyte, and other inflammatory markers in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. Likewise, immunoglobulin E (IgE) levels were drastically condensed in the serum of boldine-treated animals. Levels of enzymatic and nonenzymatic antioxidants, such as superoxide dismutase (SOD) and glutathione (GSH), were upregulated in the boldine treatment group compared to the asthmatic control group, which displays the antioxidant effects of boldine on asthmatic animals. Interestingly, the reactive oxygen species (ROS) and malonaldehyde (MDA) levels were repressed in the BALF of boldine-treated mice groups. Therefore, the effects of boldine are significant for the management of asthma, reducing the accrual of inflammatory cells, along with other inflammatory markers, while improving antioxidant markers and containing ROS. Hence, boldine may be an option for clinical trials of chronic asthma management.

Objective: This study investigated whether pre-operative interictal discharge patterns detected by electroencephalogram (EEG) and magnetic resonance imaging (MRI) findings affect the surgical prognosis in temporal lobe epilepsy (TLE) patients. Methods: A retrospective analysis of 115 cases of patients with refractory TLE was carried out from October 2010 to 2014 based on the classification of pre-operative interictal discharge patterns in EEG and MRI findings. The patients were followed up for 4 years after surgery. The ILAE method was used to assess differences in seizure-free rate among different types of interictal discharge pattern as well as in MRI findings. Results: A total of 115 cases were classified according to interictal discharge patterns in EEG, including normal cases, unilateral anterior discharge, unilateral multi-region discharge, and bilateral discharge. MRI findings were classified into negative results and positive results. Unilateral anterior and bilateral discharges showed statistically significant differences in post-operative seizure-free rates (p< 0.001). MRI-positive cases showed good overall post-operative outcome, irrespective of interictal discharge pattern in the EEG, whereas MRI-negative cases showed good overall prognosis if the interictal discharge pattern in EEG occurred in the unilateral anterior region. Conclusion: If the pre-operative interictal discharge pattern in EEG is confined to the unilateral anterior region, prognosis is good. If there are abnormalities in MRI findings, post-operative prognosis is good, regardless of pre-operative interictal discharge patterns in EEG. Surgical intervention is highly recommended for TLE patients with normal MRI findings and interictal discharge confined to the unilateral anterior region.

Temporal lobe epilepsy (TLE) is one of the most common and intractable neurological disorders in adults. Dysfunctional PKA signaling is causally linked to the TLE. However, the mechanism underlying PKA involves in epileptogenesis is still poorly understood. In the present study, we found the autophosphorylation level at serine 114 site (serine 112 site in mice) of PKA-RIIβ subunit was robustly decreased in the epileptic foci obtained from both surgical specimens of TLE patients and seizure model mice. The p-RIIβ level was negatively correlated with the activities of PKA. Notably, by using a P-site mutant that cannot be autophosphorylated and thus results in the released catalytic subunit to exert persistent phosphorylation, an increase in PKA activities through transduction with AAV-RIIβ-S112A in hippocampal DG granule cells decreased mIPSC frequency but not mEPSC, enhanced neuronal intrinsic excitability and seizure susceptibility. In contrast, a reduction of PKA activities by RIIβ knockout led to an increased mIPSC frequency, a reduction in neuronal excitability, and mice less prone to experimental seizure onset. Collectively, our data demonstrated that the autophosphorylation of RIIβ subunit plays a critical role in controlling neuronal and network excitabilities by regulating the activities of PKA, providing a potential therapeutic target for TLE., Jingliang Zhang et al. examine how dysfunctional PKA signaling impacts neuronal activity and seizure susceptibility in a mouse model of temporal lobe epilepsy. Their data suggest that autophosphorylation of the RIIβ subunit regulates neuronal excitability, and may act as a future therapeutic target.

Background Lumbar cisterna drainage (LCD) is widely used in neurosurgery as an effective treatment for postoperative meningitis, vasospasm of subarachnoid hemorrhage and ventricular system hemorrhage, and for reducing intracranial pressure in patients with severe craniocerebral trauma. The purpose of this work was two-fold: to analyze the dynamic curve of cerebrospinal fluid (CSF) related indices in cases of postoperative meningitis after selective craniotomy and to provide reference data for the clinical treatment with LCD. Methods We conducted a retrospective study of LCD placement in patients who underwent either supratentorial craniotomy (n=23) or subtentorial craniotomy (m=28). Primary outcomes measured included pre-intervention and post-intervention dynamic changes of body temperature, and CSF biochemical parameters (white blood cell (WBC) count, polykaryocyte percentage, protein, glucose and chloride) over the course of 13 days of catheter placement. We also assessed the bivariate correlation between WBC count changes, polykaryocyte percentage, body temperature and daily CSF drainage volume. Finally, we analyzed the effect of average daily drainage volume, antibiotic choice, and surgical site on the WBC count change curves. Results After LCD, a trend of increased WBC count was observed on the first day of drainage, followed by an overall decrease in WBC count. There was a statistically significant ( P 0.05 ). Conclusions LCD is an effective method for the treatment of postoperative meningitis. The WBC count can decrease significantly by the fourth day after drainage, and placement of the LCD for six to seven days is ideal. An average drainage volume of 250-300 ml/d is safe and effective.

Purpose The aim of the study was to investigate factors which may predispose patients to early neurological deterioration (END) and explore peripheral biomarkers for the prediction of END in cardiogenic cerebral embolism (CCE) patients. Methods Patients diagnosed with CCE within 24 hr of onset between January 2017 and January 2019 were included in this study. END was defined as an increase of ≥2 on the National Institutes of Health Stroke Scale (NIHSS) or the emergence of new neurological symptoms within 3 days of admission. Binary logistic regression was used to investigate the factors associated with END. Receiver operating characteristic (ROC) curves were then generated to determine the predictive value of the potential biomarkers and the optimal cutoff values. Results Of the 129 (male, 55.81%; mean age 71.85 ± 11.99 years) CCE patients, 55 patients with END were identified. Hemorrhage transformation (HT), coronary heart disease (CHD), diastolic blood pressure, cystatin C levels, NIHSS score, and platelet‐to‐lymphocyte ratio (PLR) at admission were independently associated with END. A peripheral cystatin C level ≥ 1.41 mg/L and a PLR ≥ 132.97 were predictive factors for END in CCE patients. The lymphocyte‐to‐monocyte ratio (LMR) was negatively independently associated with HT, and LMR, Early neurological deterioration (END) in the early phase of acute ischemic stroke (AIS) generally leads to a marked increase in poor prognosis due to diverse mechanisms. Cystatin C levels (cutoff value 1.41 mg/L, AUC 0.635, 95% CI 0.537–0.733, p = .009) and PLR (cutoff value 132.97, AUC 0.619, 95% CI 0.518–0.719, p = .02) were predictive of END, with high specificity and sensitivity. Hemorrhage transformation (HT) was independently associated with END, the lymphocyte‐to‐monocyte ratio (LMR) was negatively independently associated with HT, and LMR

Endothelial monocyte-activating polypeptide II (EMAP II) is a sensitive marker of neurotoxic injury, the expression of which increases significantly under conditions of stress, such as hypoxia or apoptosis. Studies have confirmed the extensive apoptosis of nerve cells in the brain following status epilepticus (SE), and the occurrence of SE can confer a hypoxic state on cells. The purpose of the present study was to observe the changes in the expression of EMAP II, and in the numbers and tight junction protein levels of micro-vascular endothelial cells in the hippocampus of rats with pilocarpine-induced SE. The protein expression levels of EMAP II, CD31, zonula occludens 1 (ZO-1) and occludin in the hippocampus were determined by immunofluorescence and western blot analyses. It was found that almost 75.6% of the rats in the SE group developed Racine stage IV-V seizures at approximately 44.7±18.8 min after the pilocarpine administration, and the 24-h mortality rate was almost 10.4%. The weight of the rats in the SE group was significantly decreased within 24 h following SE. Immunofluorescence staining revealed a low EMAP II expression in the hippo-campus of the rats in the control group; however, the numbers of EMAP II-positive cells were significantly increased in the SE group from 2 h to 21 days. The trend of EMAP II protein expression was consistent with that obtained with immunofluorescence staining. The numbers of CD31-positive microvascular endothelial cells were significantly increased from 24 h to 21 days compared with the levels in the control group. The protein expression of ZO-1 and occludin was most significantly decreased in the SE group. On the whole, the present study demonstrated that the expression of EMAP II in the rat hippocampus was upregulated in the SE model, which may promote angiogenesis and alter the TJ integrity of brain microvascular endothelial cells, with an increased number of CD31-positive microvascular endothelial cells and a decreased expression of ZO-1 and occludin.

Impairment of intrinsic plasticity is involved in a range of neurological disorders such as epilepsy. However, how intrinsic excitability is regulated is still not fully understood. Here we report that the epigenetic factor Chromodomain Y-like (CDYL) protein is a critical regulator of the initiation and maintenance of intrinsic neuroplasticity by regulating voltage-gated ion channels in mouse brains. CDYL binds to a regulatory element in the intron region of SCN8A and mainly recruits H3K27me3 activity for transcriptional repression of the gene. Knockdown of CDYL in hippocampal neurons results in augmented Nav1.6 currents, lower neuronal threshold, and increased seizure susceptibility, whereas transgenic mice over-expressing CDYL exhibit higher neuronal threshold and are less prone to epileptogenesis. Finally, examination of human brain tissues reveals decreased CDYL and increased SCN8A in the temporal lobe epilepsy group. Together, our findings indicate CDYL is a critical player for experience-dependent gene regulation in controlling intrinsic excitability., Alterations in intrinsic plasticity are important in epilepsy. Here the authors show that the epigenetic factor CDYL regulates the gene expression of the voltage gated sodium channel, Nav1.6, which contributes to seizures in a rat model of epilepsy.

The purposes of this study were to determine the cause of avascular hypoechoic lesions detected at scrotal ultrasound and to assess usefulness of sonographic and clinical features in differentiating benign from malignant etiologic factors.This retrospective study included 58 patients with avascular hypoechoic lesions detected at testicular ultrasound. The sonographic features recorded were lesion size and margins and presence of peripheral vascularity and focal calcifications. Also recorded were patient age, symptoms, risk factors, lesion palpability, and levels of serum tumor markers. The reference standard was pathologic results or at least 2-year stability documented with serial follow-up ultrasound studies. Features associated with malignant, including burnt-out, lesions and benign lesions were examined by Fisher exact test, Wilcox-on rank sum test, and the generalized estimating equations method for multivariable models.Sixty-three lesions were identified in 58 patients; 40 of the 63 (63.5%) were benign. Patients with malignant lesions had elevated serum tumor marker levels more often than patients who had benign lesions (26.1% versus 5.7%, p = 0.043). The clinical palpability of lesions and history of testicular cancer were not statistically significantly different between patients with malignant and those with benign lesions. Poorly defined margins of a lesion and focal calcification within the lesion were more often found in malignant lesions. Maximal size of a lesion and peripheral vascularity were not associated with either the benign or the malignant nature of a lesion.Although most avascular hypoechoic testicular lesions are benign, a substantial proportion are malignant. The ultrasound characteristics of a lesion, the patient's clinical presentation, and serum tumor marker status may be useful in differentiating malignant from benign lesions.

KEY POINTS: ERG3 channels have a high expression level in the central nervous system. Knockdown of ERG3 channels enhances neuronal intrinsic excitability (caused by decreased fast afterhyperpolarization, shortened delay time to the generation of an action potential and enhanced summation of somatic excitatory postsynaptic potentials) in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. The expression of ERG3 protein is reduced in human and mouse hippocampal epileptogenic foci. Knockdown of ERG3 channels in hippocampus enhanced seizure susceptibility, while mice treated with the ERG channel activator NS‐1643 were less prone to epileptogenesis. The results provide strong evidence that ERG3 channels have a crucial role in the regulation of neuronal intrinsic excitability in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells and are critically involved in the onset and development of epilepsy. . ABSTRACT: The input–output relationship of neuronal networks depends heavily on the intrinsic properties of their neuronal elements. Profound changes in intrinsic properties have been observed in various physiological and pathological processes, such as learning, memory and epilepsy. However, the cellular and molecular mechanisms underlying acquired changes in intrinsic excitability are still not fully understood. Here, we demonstrate that ERG3 channels are critically involved in the regulation of intrinsic excitability in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. Knock‐down of ERG3 channels significantly increases neuronal intrinsic excitability, which is mainly caused by decreased fast afterhyperpolarization, shortened delay time to the generation of an action potential and enhanced summation of somatic excitatory postsynaptic potentials. Interestingly, the expression level of ERG3 protein is significantly reduced in human and mouse brain tissues with temporal lobe epilepsy. Moreover, ERG3 channel knockdown in hippocampus significantly enhanced seizure susceptibility, while mice treated with the ERG channel activator NS‐1643 were less prone to epileptogenesis. Taken together, our results suggest ERG3 channels play an important role in determining the excitability of hippocampal neurons and dysregulation of these channels may be involved in the generation of epilepsy. ERG3 channels may thus be a novel therapeutic target for the prevention of epilepsy.

Glioblastoma is the most common and most aggressive malignant primary brain tumor in humans, accounting for 52 % of all functional tissue brain tumor cases and 20 % of all intracranial tumors. The typical treatment involves a combination of chemotherapy, radiation, and surgery, whereas it still achieves fairly poor patient survival. Ginsenoside Rh2 has been reported to have a therapeutic effect on some tumors, but its effect on glioblastoma has not been extensively evaluated. Here, we show that ginsenoside Rh2 can substantially inhibit the growth of glioblastoma in vitro and in vivo in a mouse model. Moreover, the inhibition of the tumor growth appears to result from combined effects on decreased tumor cell proliferation and increased tumor cell apoptosis. Further analyses suggest that ginsenoside Rh2 may have its antiglioblastoma effect through inhibition of the epidermal growth factor receptor (EGFR) signaling pathway in tumor cells. In a lose-of-function experiment, recombinant EGFR was given together with ginsenoside Rh2 to the tumor cells in vitro and in vivo, which completely blocked the antitumor effects of ginsenoside Rh2. Thus, our data not only reveal an anti-glioblastoma effect of ginsenoside Rh2 but also demonstrate that this effect may function via inhibition of EGFR signaling in glioblastoma cells.

The role of atherosclerosis in ischemic stroke has been intensively investigated in recent years, and lipoprotein (a) [Lp(a)] is found to have roles during the process. The aim of this study was to investigate the relationship between acute ischemic stroke (AIS) and serum Lp(a) levels in the Chinese population. All consecutive patients with first-ever acute ischemic stroke during 2011–2012 were recruited to participate in the study. Serum Lp(a) levels and routine tests were examined in both groups. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to Lp(a) levels. In this study, 181 patients with acute ischemic stroke were included. There was a significant difference in median serum Lp(a) levels between acute ischemic stroke patients and control cases (328 [IQR, 173–554] vs. 145 [IQR, 66–254] mg/L, respectively; P = 0.000). Lp(a) levels increased with increasing severity of stroke as defined by the NIHSS score (P = 0.000). For the entire group, when adjusting for other possible risk factors, an elevated Lp(a) level was an independent risk factor for stroke, and a serum Lp(a) level ≥300 mg/L was associated with a 2.23-fold increase in AIS (P = 0.015). In addition, this association was stronger in male than in female patients. High Lp(a) levels are significantly related to stroke, independent from other traditional and emerging risk factors, suggesting that they may play a role in its pathogenesis. It should be considered as a routine risk factor for stroke in the Chinese population.

OBJECTIVE. The purpose of our study is to present the radiographic findings in a series of 16 patients with complications associated with intravesical bacille Calmette-Guerin (BCG) treatment of bladder cancer.CONCLUSION. Intravesical BCG-related complications such as granulomatous disease may show imaging findings mimicking primary or metastatic tumors in patients with bladder cancer. Radiologists should consider this possibility when imaging abnormalities are encountered in bladder cancer patients treated with intravesical BCG so that appropriate management can be administered and unnecessary procedures avoided.