[Mechanism of Chaenomelis Fructus in treatment of rheumatoid arthritis based on network pharmacology and experimental verification].

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1ß(IL-1ß). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1ß, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.

Electroclinical aspects and therapy of Han patients with juvenile myoclonic epilepsy in northern China.

OBJECTIVE: The objective of this study was to assess the electroclinical aspects and treatment of Han patients with juvenile myoclonic epilepsy (JME) in northern China. METHODS: One hundred fifty-six outpatients with JME from six epilepsy centers, between January 2011 and June 2012, were followed up for at least two years. They underwent twenty-four-hour video-EEG recording. Brain imaging was performed using magnetic resonance imaging (MRI). Clinical aspects, electroencephalographic (EEG) features, and antiepileptic drugs (AEDs) received were reviewed. RESULTS: Generalized tonic-clonic seizures (GTCS) were found in 150/156 patients. Delay of diagnosis was 4.60±9.92years. Photosensitivity was more common in eye closure condition during IPS in patients with JME; in addition, patients with JME with myoclonic seizures (MS) and GTCS as seizure types were likely to present photoparoxysmal responses (PPRs). The 82 nontreated patients showed a median latency to first interictal or ictal generalized spike-wave discharge (GSWD) of 50min (IQR: 22-102min). The first GSWDs were recorded in 63%, 76%, 90%, and 98% patients within one, two, three, and 4h, respectively; only 2% of patients had first GSWDs after 4h. One hundred eleven patients (111/156) chose extended-release valproate (VPA) at daily doses ≤1000mg. The percentages of seizure-free patients among MS, GTCS, and absence seizure (AS) groups were 88.3%, 99.0%, and 94.9%, respectively. CONCLUSION: Photoparoxysmal responses were more common in patients with JME with MS and GTCS and rare in patients with JME with MS and AS in northern Chinese Han patients. Most patients with JME in northern China chose VPA as first therapeutic choice, and low dose (500 to 1000mg daily) of extended-release VPA may be an optimal choice for them. Video-EEG monitoring for at least 4h may be helpful in detecting the first interictal or ictal GSWD in patients with potential JME. Moreover, video-EEG monitoring performed at about 9 o'clock in the morning with patients in the awake state might be useful to find the first GSWD. For JME diagnosis, Class II criteria are more helpful than Class I counterparts, the latter yielding more missed diagnoses.

Procedures and potential pitfalls for constructing a bee-infecting RNA virus clone.

Viruses are factors that can fluctuate insect populations, including honey bees. Most honey bee infecting viruses are single positive-stranded RNA viruses that may not specifically infect honey bees and can be hazardous to other pollinator insects. In addition, these viruses could synergize with other stressors to worsen the honey bee population decline. To identify the underlying detailed mechanisms, reversed genetic studies with infectious cDNA clones of the viruses are necessary. Moreover, an infectious cDNA clone can be applied to studies as an ideal virus isolate that consists of a single virus species with a uniform genotype. However, only a few infectious cDNA clones have been reported in honey bee studies since the first infectious cDNA clone was published four decades ago. This article discusses steps, rationales, and potential issues in bee-infecting RNA virus cloning. In addition, failed experiences of cloning a Deformed wing virus isolate that was phylogenetically identical to Kakugo virus were addressed. We hope the information provided in this article can facilitate further developments of reverse-genetic studies of bee-infecting viruses to clarify the roles of virus diseases in the current pollinator declines.

Structure of Industrial Sacrificial Fragile Cementitious Foams.

Sacrificial fragile cementitious foams (SFCFs) act as a core material of the engineered material arresting system (EMAS) installed in airports to enhance the safe take-offs and landings of aircrafts. The foam structures and foaming mechanisms that greatly impact the collapse strength, specific energy, and arresting efficiency of SFCFs, however, have not been fully addressed. Herein, the engineering properties, chemical characteristics, and pore-skeleton structures of three batches of industrial SFCFs were experimentally investigated. Penetration tests showed significant differences in collapse strength and specific energy among the SFCFs with a similar density. Three-dimensional (3D) pore-skeleton structures were resolved by microfocused X-ray computed tomography. The pore-skeleton anisotropy was investigated to uncover the stages of differences in the SFCFs' engineering properties. The results demonstrate that the pore anisotropy rather than the porosity dominates the collapse of cementitious foams. Viscosity-associated nucleation and growth mechanisms were proposed to account for the featured pore-skeleton structures of the SFCFs. The findings would contribute to better pore structure controls of SFCFs toward the improved quality of EMAS.

The Effect of a Multifaceted Intervention on Dietary Quality in Schoolchildren and the Mediating Effect of Dietary Quality between Intervention and Changes in Adiposity Indicators: A Cluster Randomized Controlled Trial.

Some studies have found associations between dietary quality and obesity and their concurrent changes were observed in a few interventions. The present study aimed to assess the effect of a multifaceted intervention for childhood obesity on dietary quality and examine the mediating effect of dietary quality between the intervention and changes in adiposity indicators. Based on the social ecological model, the cluster randomized controlled trial included five components (three targeted children and two targeted their environment). In total, 1176 children from three cities in China participated in a baseline (2018) and end-of-trial (2019) examination, including 605 children in the intervention group and 571 in the control group. Self-reported behavior and anthropometric measures were collected at both time points. The Diet Balance Index Revision (DBI-07) was calculated to assess dietary quality. Generalized linear mixed models were used to estimate the intervention effect on dietary quality and its mediating effects were examined. Compared to the controls, the proportion of sugar-sweetened beverage (SSB) intake (OR = 0.27, p < 0.001, corrected p < 0.001) decreased in the intervention group. Higher bound scores (HBS) of the DBI-07 indicating over-intake decreased in the intervention group compared to the controls (mean difference = −1.52, p = 0.005, corrected p = 0.015). Changes in the HBS partially mediated the associations between the intervention and changes in body mass index, waist circumference, and body fat percentage. Future intervention should promote knowledge, attitudes, and behaviors related to dietary quality.

Eight years follow-up of a generalized epilepsy patient with eating-induced late-onset epileptic spasms and atypical absence with myoclonic jerks.

PURPOSE: Eating epilepsy was previously known as a kind of focal reflex epilepsy. However, the development of eating-induced multiple generalized seizures and the associated EEG changes were rarely reported. Herein, we present a 13-year-old generalized epilepsy patient with eating-induced generalized seizures since the age of 5. CASE PRESENTATION: The 13-year-old male patient had suffered from late-onset eating-induced epileptic spasms during the meal since the age of 5. Meanwhile, he also experienced spontaneous epileptic spasms during the period of sleep. The seizure frequency and type gradually increased from 7 years of age. In addition to epileptic spasms, he started experiencing atypical absence with myoclonic jerks during the meal. Ictal EEG presented as the appearance of an irregular slow-wave mixed with generalized polyspike wave with the intake of food, and gradually evolved to bursts of generalized polyspike wave complexes. At the end of the meal, the EEG returned to normal. Nevertheless, at the age of 13, his seizure frequency increased and appeared new seizure type, and besides epileptic spasm and atypical absence, he began to experience myoclonic seizure during sleep and awaking-generalized tonic-clonic seizure in the morning. In this period he started taking valproic acid, topiramate and clonazepam, and his seizure frequency was reduced. CONCLUSION: In conclusion, this case demonstrated the variability of eating induced multiple generalized seizure types, and eight years follow-up also indicates that generalized epilepsy progressed with age. The EEG and clinical changes of our patient contribute to a better understanding of the electro-clinical features of eating-induced multiple generalized seizures and the course of generalized epilepsy with such seizures.

Radiological and clinical outcomes of balloon kyphoplasty for osteoporotic vertebral compression fracture in patients with rheumatoid arthritis.

BACKGROUND: This study was conducted to investigate the outcomes and complications of balloon kyphoplasty (KP) for the treatment of osteoporotic vertebral compression fracture (OVCF) in patients with rheumatoid arthritis (RA) and compare its radiological and clinical effects with OVCF patients without RA. METHODS: Ninety-eight patients in the RA group with 158 fractured vertebrae and 114 patients in the control group with 150 vertebrae were involved in this study. Changes in compression rate, local kyphotic angle, visual analog scale (VAS) and Oswestry disability index (ODI) scores, conditions of bone cement leakage, refracture of the operated vertebrae, and new adjacent vertebral fractures were examined after KP. In addition, patients in the RA group were divided into different groups according to the value of erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and whether they were glucocorticoid users or not to evaluate their influence on the outcomes of KP. RESULTS: KP procedure significantly improved the compression rate, local kyphotic angle, and VAS and ODI scores in both RA and control groups (p<0.05). Changes in compression rate and local kyphotic angle in the RA group were significantly larger than that in the control group (p<0.05), and patients with RA suffered more new adjacent vertebral fractures after KP. The outcomes and complications of KP from different ESR or CRP groups did not show significant differences. The incidence of cement leakage in RA patients with glucocorticoid use was significantly higher than those who did not take glucocorticoids. In addition, RA patients with glucocorticoid use suffered more intradiscal leakage and new adjacent vertebral fractures. CONCLUSIONS: OVCF patients with RA obtained more improvement in compression rate and local kyphotic angle after KP when compared to those without RA, but they suffered more new adjacent vertebral fractures. Intradiscal leakage and new adjacent vertebral fractures occurred more in RA patients with glucocorticoid use. TRIAL REGISTRATION: Retrospectively registered.

Balloon kyphoplasty combined with posterior pedicle screw fixation for the treatment of osteoporotic thoracolumbar burst fractures.

BACKGROUND: Osteoporotic thoracolumbar burst fracture (TLBF) is difficult to treat due to its high rate of postoperative implant failure. This study was designed to evaluate the clinical effect of balloon kyphoplasty with polymethylmethacrylate (PMMA) and posterior pedicle screw fixation for the treatment of osteoporotic TLBF. METHODS: Between February 2012 and May 2016, 24 consecutive patients with osteoporotic TLBFs were included in this study, all of whom suffered incomplete neurologic deficit. They were managed with transpedicular balloon kyphoplasty, PMMA augmentation, and posterior pedicle screw fixation. Scanning with X-ray and computed tomography (CT) were performed to evaluate the kyphotic deformity with the Cobb angle and vertebral body height loss (VBHL) of the injured vertebra. Visual analogue scale (VAS) and the Oswestry Disability Index (ODI) were adopted to assess the pain and dysfunction levels before and after the operation. RESULTS: All participants were followed up for an average of 18 months and those with incomplete neurologic deficit recovered completely. The Cobb angle significantly improved from a preoperative angle of 23.2°±3.6° to 5.3°±2° after operation and to 5.7°±2.2° at the last follow up (P<0.05). The VBHL improved from 56.8%±7.8% before operation to 9.1%±1.6% after operation and to 9.7%±1.9% at the last follow up (P<0.05). The visual analog scale (VAS) score decreased from 8.8±0.9 before operation to 2.5±0.4 after operation and to 1.4±0.4 at the last follow up (P<0.05). The ODI score decreased from 88.6%±3.5% before the operation to 32.3%±3.7% after operation and to 17.5%±1.8% at the last follow up (P<0.05). CONCLUSIONS: Balloon kyphoplasty combined with posterior pedicle screw fixation was an effective treatment for osteoporotic TLBFs. This procedure can reconstruct 3 spinal columns using a single approach with less blood loss, short operation time, and rapid recovery. Ruptures of the posterior vertebral wall should not be a contraindication of this procedure. TRIAL REGISTRATION: Chinese Clinical Trial Registry (NO.: ChiCTR1900026157).

SKA3 Promotes Cell Growth in Breast Cancer by Inhibiting PLK-1 Protein Degradation.

Breast cancer (Bca) remains the most common form of malignancy affecting females in China, leading to significant reductions in the mental and physical health of those with this condition. While spindle and kinetochore associated complex subunit 3 (SKA3) is known to be linked with cervical cancer progression, whether it is similarly associated with Bca progression remains unknown. Using shRNA, we specifically knocked down the expression of SKA3 in Bca cell lines and then assessed the resultant changes in cell proliferation using CCK-8 and colony formation assays. In addition, we used western blotting to quantify the expression levels of relevant proteins in these cells, and we assessed the interaction between SKA3 and polo-like kinase-1 (PLK-1) via co-immunoprecipitation.In this study, we observed elevated SKA3 expression in Bca tissues and cell lines. When we knocked down SKA3 expression in Bca cells, we were able to determine that it functions in an oncogenic manner so as to promote the growth and proliferation of these cells in vitro. From a mechanistic perspective, we were able to show that in Bca cells SKA functions at least in part via interacting with PLK-1 and preventing its degradation. In summary, we found that SKA3 is able to regulate PLK-1 degradation in Bca cells, thus controlling their growth and proliferation. These results highlight SKA3 as a potentially viable target for anti-cancer drug development aimed at combatting Bca.

Visualizing Sacbrood Virus of Honey Bees via Transformation and Coupling with Enhanced Green Fluorescent Protein.

Sacbrood virus (SBV) of honey bees is a picornavirus in the genus Iflavirus. Given its relatively small and simple genome structure, single positive-strand RNA with only one ORF, cloning the full genomic sequence is not difficult. However, adding nonsynonymous mutations to the bee iflavirus clone is difficult because of the lack of information about the viral protein processes. Furthermore, the addition of a reporter gene to the clones has never been accomplished. In preliminary trials, we found that the site between 3' untranslated region (UTR) and poly(A) can retain added sequences. We added enhanced green fluorescent protein (EGFP) expression at this site, creating a SBV clone with an expression tag that does not affect virus genes. An intergenic region internal ribosome entry site (IRES) from Black queen cell virus (BQCV) was inserted to initiate EGFP expression. The SBV-IRES-EGFP clone successfully infected Apis cerana and Apis mellifera, and in A. cerana larvae, it was isolated and passaged using oral inoculation. The inoculated larvae had higher mortality and the dead larvae showed sacbrood symptoms. The added IRES-EGFP remained in the clone through multiple passages and expressed the expected EGFP in all infected bees. We demonstrated the ability to add gene sequences in the site between 3'-UTR and poly(A) in SBV and the potential to do so in other bee iflaviruses; however, further investigations of the mechanisms are needed. A clone with a desired protein expression reporter will be a valuable tool in bee virus studies.

D-Serine Contributes to Seizure Development via ERK Signaling.

A seizure is one of the leading neurological disorders. NMDA receptor-mediated neuronal excitation has been thought to be essential for epileptogenesis. As an endogenous co-agonist of the NMDA receptor, D-serine has been suggested to play a role in epileptogenesis. However, the underlying mechanisms remain unclear. In the current study, we investigated the effects of antagonizing two key enzymes in D-serine metabolism on the development of seizures and the downstream signaling. Our results showed that serine racemase (SR), a key enzyme in regulating the L-to-D-serine conversion, was significantly up-regulated in hippocampal astrocytes in rats and patients who experienced seizure, in comparison with control rats and patients. L-aspartic acid ß-hydroxamate (LaaßH), an inhibitor of SR, significantly prolonged the latencies of seizures, shortened the durations of seizures, and decreased the total EEG power in rats. In contrast, D-amino acid oxidase inhibitor 5-chlorobenzo[d]isoxazol-3-ol (CBIO), which can increase D-serine levels, showed the opposite effects. Furthermore, our data showed that LaaßH and CBIO significantly affected the phosphorylation of Extracellular Signal-regulated Kinase (ERK). Antagonizing or activating ERK could significantly block the effects of LaaßH/CBIO on the occurrence of seizures. In summary, our study revealed that D-serine is involved in the development of epileptic seizures, partially through ERK signaling, indicating that the metabolism of D-serine may be targeted for the treatment of epilepsy.

Antidepressants for the treatment of narcolepsy: A prospective study of 148 patients in northern China.

Narcolepsy is a life-long neurological disorder characterized by excessive daytime sleepiness (EDS) and cataplexy. At present, Sodium oxybate, modafinil, methylphenidate and other stimulants are recommended first-line therapies for narcolepsy but are difficult to obtain in China. One hundred forty-eight patients with narcolepsy were treated with antidepressants and administered the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT) before and after treatment from August 2012 to August 2017. The subjects were followed for 1-6 years after treatment. Improvement in sleepiness, cataplexy, cataplexy-like episodes, and antidepressant side effects were assessed. There were significant differences in the mean sleep latency (MSL) and sleep onset rapid eye movement periods (SOREMPs) in MWT and ESS scores, cataplexy and cataplexy-like episodes before and after treatment (p < 0.01). Venlafaxine demonstrated significantly greater improvements in MSL in the MWT (p < 0.01). Early awakenings and dry mouth were the most common adverse effects.

Comparative study of mesenchymal stem cells from C57BL/10 and mdx mice.

BACKGROUND: Human mesenchymal stem cells (MSCs) have been studied and applied extensively because of their ability to self-renew and differentiate into various cell types. Since most human diseases models are murine, mouse MSCs should have been studied in detail. The mdx mouse - a Duchenne muscular dystrophy model - was produced by introducing a point mutation in the dystrophin gene. To understand the role of dystrophin in MSCs, we compared MSCs from mdx and C57BL/10 mice, focusing particularly on the aspects of light and electron microscopic morphology, immunophenotyping, and differentiation potential. RESULTS: Our study showed that at passage 10, mdx-MSCs exhibited increased heterochromatin, larger vacuoles, and more lysosomes under electron microscopy compared to C57BL/10-MSCs. C57BL/10-MSCs formed a few myotubes, while mdx-MSCs did not at the same passages. By passage 21, mdx-MSCs but not C57BL/10-MSCs had gradually lost their proliferative ability. In addition, a significant difference in the expression of CD34, not Sca-1 and CD11b, was observed between the MSCs from the 2 mice. CONCLUSION: Our current study reveals that the MSCs from the 2 mice, namely, C57BL/10 and mdx, exhibit differences in proliferative and myogenic abilities. The results suggest that the changes in mouse MSC behavior may be influenced by lack of dystrophin protein in mdx mouse.

Sleep-related hypermotor epilepsy activated by rapid eye movement sleep.

Most sleep-related seizures occur during non-rapid eye movement (NREM) sleep, particularly during stage changes. Sleep-related hypermotor epilepsy (SHE) is a rare epileptic syndrome characterized by paroxysmal motor seizures, mainly arising from NREM sleep. Here, we report a patient with SHE who had seven seizures captured on video-EEG-polysomnography during REM sleep. Ictal semiology of this patient ranged from brief paroxysmal arousals to hypermotor seizures. On EEG-polysomnography, the spontaneous arousals were more frequent during REM than NREM sleep, with a considerably higher arousal index in REM sleep (20/hour). While the reason for seizures during REM sleep in this patient is unclear, we speculate that the threshold and mechanisms of arousal during different sleep stages may be related to the occurrence of seizures. [Published with video sequences on www.epilepticdisorders.com].

The electroclinical features of idiopathic generalized epilepsy patients presenting with fixation-off sensitivity.

To determine the electroclinical features of fixation-off sensitivity (FOS) in patients with idiopathic generalized epilepsy (IGE). We searched the EEG database using the terms "fixation-off sensitivity" and "idiopathic generalized epilepsy" over a four-year period from March 2014 to April 2018 in the Xijing Hospital, Xi'an, China. FOS was evaluated according to the technique proposed by Panayiotopoulos. Photic stimulation procedure and neuropsychological testing were performed during video-EEG monitoring. FOS was observed in eight patients with several different IGE syndromes, including four with eyelid myoclonia/Jeavons syndrome, two with juvenile myoclonic epilepsy, one with photosensitivity epilepsy, and one with epilepsy with generalized tonic-clonic seizures only. FOS was associated with seizures in five patients manifesting with eyelid myoclonic, myoclonic, and myoclonic-tonic-clonic seizures, and eyelid myoclonic status. FOS coexisted with photosensitivity in six patients as independent EEG features. Neuropsychological testing revealed transitory cognitive impairments associated with FOS. FOS is associated with several different IGE syndromes and may coexist with photosensitivity in the same patient as independent EEG features. FOS may be associated with both clinical seizures and cognitive impairments. Intermittent photic stimulation and registration of different eye conditions with and without fixation will aid the study of the dynamics of the visual system in epilepsy patients. [Published with video sequences on www.epilepticdisorders.com].

Mechanism of Chaenomelis Fructus in treatment of rheumatoid arthritis based on network pharmacology and experimental verification / 中国中药杂志

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.

[Experimental studies on the existence and distribution characteristics of neural stem cells in adult human ciliary body and retina].

OBJECTIVE: To investigate the existence and distribution characteristics of neural stem cells in the eyes of adult human ciliary body and retina. METHODS: Eight eyes from 20 - 40 years old health adult and 3 infant eyes were obtained from Guangdong Eye Bank and were used in the present studies. The protein and mRNA expressions of neural progenitor cell-specific antigen nestin in the ciliary body and retina were detected by immunohistochemical staining and reverse RT-PCR assays, respectively. The ultrastructural and distribution characteristics of these cells were studied by transmission electron microscopy (TEM). RESULTS: Immunohistochemical staining showed that there were a few nestin-positive cells existed in pigment epithelium layer of ciliary body and inner nuclear layer (INL) of retina. mRNA expression of nestin gene was detected in both the ciliary body and retina of the infant and adult eyes by RT-PCR assays. The expression of nestin in the infant ciliary body was higher than that of the adult eye. By TEM, a few cells with the characteristic morphology of neural stem cells were identified and their location was consistent with the results of immunohistochemical staining. CONCLUSION: Cells with the features of neural stem cells are present in the pigment epithelium layer of ciliary body and the inner nuclear layer of retina in adult human eyes.

Postictal apnea as an important mechanism for SUDEP: A near-SUDEP with continuous EEG-ECG-EMG recording.

Sudden unexpected death in epilepsy (SUDEP) is one of the most frequent causes of death among patients with epilepsy. Most SUDEP or near-SUDEP are unwitnessed and not observed or recorded during video-EEG recording in epilepsy monitoring units. This report describes a young woman with post ictal apnea and generalized EEG suppression (PGES) after a secondary generalized tonic-clonic seizure (sGTCS). This was accompanied by bradycardia and then ventricular tachycardia (VT). But at the end of VT, the patient's breath recovered without any intervention, such as cardio-respiratory resuscitation. This case report with continuous EEG, EKG, EMG during near SUDEP may provide insights into the mechanism of action.

BRAFV600E mutation is not associated with central lymph node metastasis in all patients with papillary thyroid cancer: Different histological subtypes and preoperative lymph node status should be taken into account.

The association between central lymph node metastasis (LNM) and risk factors, including the presence of the BRAF mutation, BRAFV600E, in patients with papillary thyroid cancer (PTC) requires further investigation. A potent risk factor that can indicate LNM in different histological subtypes of PTC and in different preoperative central lymph node statuses also requires further research. A total of 287 patients with PTC who accepted thyroidectomy were included in the present study. Clinicopathological data of these patients were reviewed to examine the risk factors for central LNM through univariate and multivariate analyses. Overall, BRAFV600E in patients with cN0 (subclinical nodal disease) and cN1 (other than cN0) PTC was associated with central LNM. However, multivariate analyses demonstrated that BRAFV600E was not an independent risk factor in patients with cN1 or cN0 PTC. For patients with classical variant PTC (CVPTC), BRAFV600E was independently associated with central LNM. However, on further analysis, the association was only significant in patients with cN0 CVPTC. For patients with follicular variant PTC (FVPTC) or aggressive variant PTC (AVPTC), the BRAFV600E mutation rate was not significantly different between patients with and without central LNM. In conclusion, BRAFV600E was an independent risk factor for central LNM overall in patients with PTC and in patients with CVPTC, particularly in patients with cN0 CVPTC. However, BRAFV600E was not an independent risk factor for patients with FVPTC and AVPTC. Therefore, BRAFV600E provides varied clinical significance in different histological subtypes and preoperative central lymph node status.

Mitochondrial protective and anti-apoptotic effects of Rhodiola crenulata extract on hippocampal neurons in a rat model of Alzheimer's disease.

In our previous study, we found that the edible alcohol extract of the root of the medicinal plant Rhodiola crenulata (RCE) improved spatial cognition in a rat model of Alzheimer's disease. Another study from our laboratory showed that RCE enhanced neural cell proliferation in the dentate gyrus of the hippocampus and prevented damage to hippocampal neurons in a rat model of chronic stress-induced depression. However, the mechanisms underlying the neuroprotective effects of RCE are unclear. In the present study, we investigated the anti-apoptotic effect of RCE and its neuroprotective mechanism of action in a rat model of Alzheimer's disease established by intracerebroventricular injection of streptozotocin. The rats were pre-administered RCE at doses of 1.5, 3.0 or 6.0 g/kg for 21 days before model establishment. ATP and cytochrome c oxidase levels were significantly decreased in rats with Alzheimer's disease. Furthermore, neuronal injury was obvious in the hippocampus, with the presence of a large number of apoptotic neurons. In comparison, in rats given RCE pretreatment, ATP and cytochrome c oxidase levels were markedly increased, the number of apoptotic neurons was reduced, and mitochondrial injury was mitigated. The 3.0 g/kg dose of RCE had the optimal effect. These findings suggest that pretreatment with RCE prevents mitochondrial dysfunction and protects hippocampal neurons from apoptosis in rats with Alzheimer's disease.