Topological properties and connectivity patterns in brain networks of patients with refractory epilepsy combined with intracranial electrical stimulation.

Objective: Although intracranial electrical stimulation has emerged as a treatment option for various diseases, its impact on the properties of brain networks remains challenging due to its invasive nature. The combination of intracranial electrical stimulation and whole-brain functional magnetic resonance imaging (fMRI) in patients with refractory epilepsy (RE) makes it possible to study the network properties associated with electrical stimulation. Thus, our study aimed to investigate the brain network characteristics of RE patients with concurrent electrical stimulation and obtain possible clinical biomarkers. Methods: Our study used the GRETNA toolbox, a graph theoretical network analysis toolbox for imaging connectomics, to calculate and analyze the network topological attributes including global measures (small-world parameters and network efficiency) and nodal characteristics. The resting-state fMRI (rs-fMRI) and the fMRI concurrent electrical stimulation (es-fMRI) of RE patients were utilized to make group comparisons with healthy controls to identify the differences in network topology properties. Network properties comparisons before and after electrode implantation in the same patient were used to further analyze stimulus-related changes in network properties. Modular analysis was used to examine connectivity and distribution characteristics in the brain networks of all participants in study. Results: Compared to healthy controls, the rs-fMRI and the es-fMRI of RE patients exhibited impaired small-world property and reduced network efficiency. Nodal properties, such as nodal clustering coefficient (NCp), betweenness centrality (Bc), and degree centrality (Dc), exhibited differences between RE patients (including rs-fMRI and es-fMRI) and healthy controls. The network connectivity of RE patients (including rs-fMRI and es-fMRI) showed reduced intra-modular connections in subcortical areas and the occipital lobe, as well as decreased inter-modular connections between frontal and subcortical regions, and parieto-occipital regions compared to healthy controls. The brain networks of es-fMRI showed a relatively weaker small-world structure compared to rs-fMRI. Conclusion: The brain networks of RE patients exhibited a reduced small-world property, with a tendency toward random networks. The network connectivity patterns in RE patients exhibited reduced connections between cortical and subcortical regions and enhanced connections among parieto-occipital regions. Electrical stimulation can modulate brain network activity, leading to changes in network connectivity patterns and properties.

Acute Cerebellitis Associated With Anti-homer 3 Antibodies: A Rare Case Report and Literature Review.

Acute cerebellitis associated with Homer-3 antibodies is very rare. Here we present a 20-year-old woman who suffered from uncontrollable head shaking quickly from side to side and an unsteady gait for 2 days after the cold. Antibodies were screened by cell-based assays. The indirect immunofluorescence technique results revealed anti-Homer-3 antibody titers of 1:3.2 in the CSF and 1:100 in the serum. The woman was obviously improved after antiviral and immunosuppression (immunoglobin, methylprednisolone and mycophenolate mofetil) treatment. Our report indicated immune-mediated causes should be considered in the acute cerebellitis. Immunotherapy can contribute to the improvement of cerebellar syndrome.

Altered Neuromagnetic Activity in Persistent Postural-Perceptual Dizziness: A Multifrequency Magnetoencephalography Study.

Objective: The aim of our study was to investigate abnormal changes in brain activity in patients with persistent postural-perceptual dizziness (PPPD) using magnetoencephalography (MEG). Methods: Magnetoencephalography recordings from 18 PPPD patients and 18 healthy controls were analyzed to determine the source of brain activity in seven frequency ranges using accumulated source imaging (ASI). Results: Our study showed that significant changes in the patterns of localization in the temporal-parietal junction (TPJ) were observed at 1-4, 4-8, and 12-30 Hz in PPPD patients compared with healthy controls, and changes in the frontal cortex were found at 1-4, 80-250, and 250-500 Hz in PPPD patients compared with controls. The neuromagnetic activity in TPJ was observed increased significantly in 1-4 and 4-8 Hz, while the neuromagnetic activity in frontal cortex was found increased significantly in 1-4 Hz. In addition, the localized source strength in TPJ in 1-4 Hz was positively correlated with DHI score (r = 0.7085, p < 0.05), while the localized source strength in frontal cortex in 1-4 Hz was positively correlated with HAMA score (r = 0.5542, p < 0.05). Conclusion: Our results demonstrated that alterations in the TPJ and frontal cortex may play a critical role in the pathophysiological mechanism of PPPD. The neuromagnetic activity in TPJ may be related to dizziness symptom of PPPD patients, while the neuromagnetic activity in frontal lobe may be related to emotional symptoms of PPPD patients. In addition, frequency-dependent changes in neuromagnetic activity, especially neuromagnetic activity in low frequency bands, were involved in the pathophysiology of PPPD.

Frequency-Dependent Dynamics of Functional Connectivity Networks During Seizure Termination in Childhood Absence Epilepsy: A Magnetoencephalography Study.

Objective: Our aim was to investigate the dynamics of functional connectivity (FC) networks during seizure termination in patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and graph theory (GT) analysis. Methods: MEG data were recorded from 22 drug-naïve patients diagnosed with CAE. FC analysis was performed to evaluate the FC networks in seven frequency bands of the MEG data. GT analysis was used to assess the topological properties of FC networks in different frequency bands. Results: The patterns of FC networks involving the frontal cortex were altered significantly during seizure termination compared with those during the ictal period. Changes in the topological parameters of FC networks were observed in specific frequency bands during seizure termination compared with those in the ictal period. In addition, the connectivity strength at 250-500 Hz during the ictal period was negatively correlated with seizure frequency. Conclusions: FC networks associated with the frontal cortex were involved in the termination of absence seizures. The topological properties of FC networks in different frequency bands could be used as new biomarkers to characterize the dynamics of FC networks related to seizure termination.

Altered functional connectivity in newly diagnosed benign epilepsy with unilateral or bilateral centrotemporal spikes: A multi-frequency MEG study.

OBJECTIVE: Rolandic epilepsy (RE) is one of the most common forms of epilepsy syndromes in children. The condition is usually accompanied with either unilateral or bilateral centrotemporal epileptic discharge. Despite the term "benign", many studies have reported that children with benign epilepsy with centrotemporal spikes (BECTS) display a range of pervasive cognitive difficulties. In addition, existing research suggests that unilateral and bilateral centrotemporal spikes may affect cognition through different mechanisms. Consequently, the present study aimed to investigate cognitive impairment and the resting-state network topology of children with benign epilepsy with unilateral centrotemporal spikes (U-BECTS) and with bilateral centrotemporal spikes (B-BECTS). METHODS: This study recruited 14 children with U-BECTS and 14 with B-BECTS. Thereafter, cognition was assessed in 28 children with BECTS and 14 healthy controls, using the fourth edition of the Wechsler Intelligence Scale (WISC-IV). Additionally, the functional network of the brain was constructed through magnetoencephalography (MEG) to record the resting-state brain magnetic signals of the brain and by computing virtual sensor waveforms at the source level. Moreover, graph theory (GT) analysis was used to assess the properties of the brain network. RESULTS: Children in the B-BECTS group had an earlier onset of epilepsy compared to those in the U-BECTS category. In addition, both the B-BECTS and U-BECTS groups had lower Full Scale Intelligence Quotient (FSIQ), Verbal Comprehension Index (VCI), and Working Memory Index (WMI) scores, compared to the healthy controls although only children in the B-BECTS category had lower Perceptual Reasoning Index (PRI) scores. The results also showed that both BECTS groups had increased frontal cortex connectivity in specific frequency bands. Notably, children with B-BECTS showed a more disorderly and randomized network in the 1-4-Hz and 80-250-Hz frequency bands. Moreover, GT analysis showed that children with B-BECTS had lower clustering coefficient and characteristic path length in the 80-250-Hz frequency bands and higher connection strength in the 4-8-Hz frequency bands. On the other hand, the U-BECTS group had a higher clustering coefficient in the 8-12-Hz frequency bands, compared to the healthy controls. Correlation analysis revealed that there were negative correlations between network parameters, clinical characteristics, and neuropsychological data in the U-BECTS category. CONCLUSION: The findings revealed that children with BECTS display a diffuse early cognitive deficit. In addition, resting-state suboptimal network topology may be the mechanism of cognitive impairment in children with BECTS. The study also showed that and children with B-BECTS may be at a higher risk of cognitive impairment.

Impact of Antiepileptic Drugs on Cognition and Neuromagnetic Activity in Childhood Epilepsy With Centrotemporal Spikes: A Magnetoencephalography Study.

Objective: Childhood epilepsy with centrotemporal spikes (CECTS), the most common childhood epilepsy, still lacks longitudinal imaging studies involving antiepileptic drugs (AEDs). In order to examine the effect of AEDs on cognition and brain activity. We investigated the neuromagnetic activities and cognitive profile in children with CECTS before and after 1 year of treatment. Methods: Fifteen children with CECTS aged 6-12 years underwent high-sampling magnetoencephalography (MEG) recordings before treatment and at 1 year after treatment, and 12 completed the cognitive assessment (The Wechsler Intelligence Scale for Children). Next, magnetic source location and functional connectivity (FC) were investigated in order to characterize interictal neuromagnetic activity in the seven frequency sub-bands, including: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), gamma (30-80 Hz), ripple (80-250 Hz), and fast ripple (250-500 Hz). Results: After 1 year of treatment, children with CECTS had increased scores on full-scale intelligence quotient, verbal comprehension index (VCI) and perceptual reasoning index (PRI). Alterations of neural activity occurred in specific frequency bands. Source location, in the 30-80 Hz frequency band, was significantly increased in the posterior cingulate cortex (PCC) after treatment. Moreover, FC analysis demonstrated that after treatment, the connectivity between the PCC and the medial frontal cortex (MFC) was enhanced in the 8-12 Hz frequency band. Additionally, the whole-brain network distribution was more dispersed in the 80-250 Hz frequency band. Conclusion: Intrinsic neural activity has frequency-dependent characteristic. AEDs have impact on regional activity and FC of the default mode network (DMN). Normalization of aberrant DMN in children with CECTS after treatment is likely the reason for improvement of cognitive function.

Pretreatment Source Location and Functional Connectivity Network Correlated With Therapy Response in Childhood Absence Epilepsy: A Magnetoencephalography Study.

Objective: This study aims to investigate the differences between antiepileptic drug (AED) responders and nonresponders among patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and to additionally evaluate whether the neuromagnetic signals of the brain neurons were correlated with the response to therapy. Methods: Twenty-four drug-naïve patients were subjected to MEG under six frequency bandwidths during ictal periods. The source location and functional connectivity were analyzed using accumulated source imaging and correlation analysis, respectively. All patients were treated with appropriate AED, at least 1 year after their MEG recordings, their outcome was assessed, and they were consequently divided into responders and nonresponders. Results: The source location of the nonresponders was mainly in the frontal cortex at a frequency range of 8-12 and 30-80 Hz, especially 8-12 Hz, while the source location of the nonresponders was mostly in the medial frontal cortex, which was chosen as the region of interest. The nonresponders showed strong positive local frontal connections and deficient anterior and posterior connections at 80-250 Hz. Conclusion: The frontal cortex and especially the medial frontal cortex at α band might be relevant to AED-nonresponsive CAE patients. The local frontal positive epileptic network at 80-250 Hz in our study might further reveal underlying cerebral abnormalities even before treatment in CAE patients, which could cause them to be nonresponsive to AED. One single mechanism cannot explain AED resistance; the nonresponders may represent a subgroup of CAE who is refractory to several antiepileptic drugs.

Functional reorganization of brain regions into a network in childhood absence epilepsy: A magnetoencephalography study.

OBJECTIVE: Epilepsy is considered as a network disorder. However, it is unknown how normal brain activity develops into the highly synchronized discharging activity seen in disordered networks. This study aimed to explore the epilepsy brain network and the significant re-combined brain areas in childhood absence epilepsy (CAE). METHODS: Twenty-two children with CAE were recruited to study the neural source activity during ictal-onset and interictal periods at frequency bands of 1-30 Hz and 30-80 Hz with magnetoencephalography (MEG) scanning. Accumulated source imaging (ASI) was used to analyze the locations of neural source activity and peak source strength. RESULTS: Most of the participants had more active source activity locations in the ictal-onset period rather than in the interictal period, both at 1-30 Hz and 30-80 Hz. The frontal lobe (FL), the temporo-parietal junction (T-P), and the parietal lobe (PL) became the main active areas of source activity during the ictal period, while the precuneus (PC), cuneus, and thalamus were relatively inactive. CONCLUSIONS: Some brain areas become more excited and have increased source activity during seizures. These significant brain regions might be re-combined to form an epilepsy network that regulates the process of absence seizures. SIGNIFICANCE: The study confirmed that important brain regions are reorganized in an epilepsy network, which provides a basis for exploring the network mechanism of CAE development. Imaging findings may provide a reference for clinical characteristics.

Changes of Ictal-Onset Epileptic Network Synchronicity in Childhood Absence Epilepsy: A Magnetoencephalography Study.

Objective: To further understand the mechanisms underlying epileptic network and the characteristics of individual specific network, we conducted a study on brain network by magnetoencephalography (MEG) focusing on patients with childhood absence epilepsy (CAE). Methods: The network connectivity of 22 patients was investigated with MEG at the source level. Network connectivity of spikes and slow waves was computed with accumulated source imaging (ASI) and correlation analysis. Time-frequency analysis was used to characterize the network changes during the ictal-onset period of each patient and the potential factors. Results: We found that spectral power increased at around 1 s and distributed at 2-4 Hz in all patients. Ictal spikes simultaneously showed elevation of network connectivity, predominantly excitatory connections, when generalized firing activity spread to the overall brain. High-frequency oscillations (HFOs) were prone to detect overexcited neuronal firing in certain focal areas. Conclusions: Personal network changes during ictal onset had unique features in the time range and parallel seizure rhythm uniformly in every patient. There was an important time point for generalized discharges of the epileptic network. Ictal spiking activity played an important role in the epileptic network synchronicity of childhood absence epilepsy. Frequency oscillations provided references for locating abnormal changes in neuromagnetic signals.

The relationship between epilepsy and cognitive function in benign childhood epilepsy with centrotemporal spikes.

INTRODUCTION: This study was aimed to explore the relationship between neural network changes in newly diagnosed children with Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) and cognitive impairment. METHODS: Children's cognition was evaluated using the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). Magnetoencephalographic (MEG) data of 18 healthy children and 22 BECTS patients were recorded in order to construct a functional connectivity (FC) network, which was quantified by graph theory (GT). RESULTS: The mean age of the control group was 7.94 ± 1.89 years, and the mean age of BECTS patients was 8.14 ± 1.73 years. Our results show that the WISC-IV index scores in the BECTS group were significantly lower than those in the control group. Besides, the FC network pattern of BECTS patients changed significantly in the 12-30, 30-80, and 250-500 Hz frequency band. The local functional connections between posterior cingulate cortex (PCC) and frontal lobe varied significantly in 12-30, 80-250, and 250-500 Hz. Our GT analysis shows that the connection strength of BECTS patients increases significantly in the 12-30 Hz frequency band, the path length decreases significantly in the 12-30 Hz and 30-80 Hz frequency bands, with the clustering coefficient decreasing significantly in the 12-30 Hz, 30-80 Hz, and 250-500 Hz frequency bands. Correlation analysis showed that the full-scale IQ (FSIQ) was positively correlated with the 12-30 Hz clustering coefficient, verbal comprehension index (VCI) was positively correlated with the 250-500 Hz clustering coefficient, perceptual reasoning index (PRI) was positively correlated with the 12-30 Hz clustering coefficient, and perceptual reasoning index (PSI) was negatively correlated with the 12-30 Hz path length. CONCLUSION: There is a trend of cognitive impairment in patients with early BECTS. This trend of cognitive impairment in early BECTS children may be related to the changes in the FC network pattern.

The relationship between neuromagnetic activity and cognitive function in benign childhood epilepsy with centrotemporal spikes.

PURPOSE: Our aim was to explore the pathophysiological mechanism of cognitive function changes in early untreated children with benign childhood epilepsy with centrotemporal spikes (BECTS). METHODS: Magnetoencephalography (MEG) was performed in 33 children with BECTS and 18 healthy children. Wechsler Intelligence Scale for Children, fourth edition (WISC-IV) was used to divide children with BECTS into two groups. Normal cognitive function was defined as a full-scale intelligence quotient (FSIQ) of >80, while decreased cognitive function was defined as a FSIQ of <80. Accumulated source imaging was used to evaluate the neuromagnetic source activity in multifrequency bands. RESULTS: Of the 33 patients with early untreated BECTS, a total of 17 had a FSIQ of <80 and 16 had FSIQ of >80. The course of epilepsy and number of seizures in the FSIQ <80 group were higher than that in the FSIQ >80 group. Our MEG results showed that in the 4-8 Hz frequency band, both patient groups had inactivation of the posterior cingulate cortex (PCC) region compared with the healthy control group. In the 30-80 Hz frequency band, the FSIQ <80 group showed inactivation of the PCC region compared with both the healthy control group and the FSIQ >80 group. In the 80-250 Hz frequency band, the FSIQ <80 group had inactivated of the medial frontal cortex (MFC) region compared with the healthy control group. In the 30-80 Hz frequency band, the strength of neuromagnetic source in patients with BECTS with FSIQ <80 was higher than that in the FSIQ >80 group and the healthy control group. CONCLUSIONS: The magnetic source inactivation of the MFC and PCC regions during the interictal time may be the reason for cognitive decline in early untreated children with BECTS. Children with BECTS with cognitive decline had a longer course of epilepsy and more seizures. The magnetic source localization in the 4-8 Hz frequency band may be a new imaging marker for the diagnosis of new BECTS.

Multifrequency Dynamics of Cortical Neuromagnetic Activity Underlying Seizure Termination in Absence Epilepsy.

PURPOSE: This study aimed to investigate the spectral and spatial signatures of neuromagnetic activity underlying the termination of absence seizures. METHODS: Magnetoencephalography (MEG) data were recorded from 18 drug-naive patients with childhood absence epilepsy (CAE). Accumulated source imaging (ASI) was used to analyze MEG data at the source level in seven frequency ranges: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), gamma (30-80 Hz), ripple (80-250 Hz), and fast ripple (250-500 Hz). RESULT: In the 1-4, 4-8, and 8-12 Hz ranges, the magnetic source during seizure termination appeared to be consistent over the ictal period and was mainly localized in the frontal cortex (FC) and parieto-occipito-temporal junction (POT). In the 12-30 and 30-80 Hz ranges, a significant reduction in source activity was observed in the frontal lobe during seizure termination as well as a decrease in peak source strength. The ictal peak source strength in the 1-4 Hz range was negatively correlated with the ictal duration of the seizure, whereas in the 30-80 Hz range, it was positively correlated with the course of epilepsy. CONCLUSION: The termination of absence seizures is associated with a dynamic neuromagnetic process. Frequency-dependent changes in the FC were observed during seizure termination, which may be involved in the process of neural network interaction. Neuromagnetic activity in different frequency bands may play different roles in the pathophysiological mechanism during absence seizures.

Differences Between Interictal and Ictal Generalized Spike-Wave Discharges in Childhood Absence Epilepsy: A MEG Study.

Purpose: To investigate the differences between interictal and ictal generalized spike-wave discharges (GSWDs) for insights on how epileptic activity propagates and the physiopathological mechanisms underlying childhood absence epilepsy (CAE). Methods: Twenty-five patients with CAE were studied using magnetoencephalography (MEG). MEG data were digitized at 6,000 Hz during the interictal and ictal GSWDs. GSWDs were analyzed at both neural magnetic source levels and functional connectivity (FC) in multifrequency bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), gamma (30-80 Hz), ripple (80-250 Hz), and fast ripple (250-500 Hz). Brain FC was studied with the posterior cingulate cortex/precuneus (PCC/pC) as the seed region. Results: The magnetic source of interictal GSWDs mainly locates in the PCC/pC region at 4-8 and 8-12 Hz, while that of ictal GSWDs mainly locates in the medial frontal cortex (MFC) at 80-250 Hz. There were statistically significant differences between interictal and ictal GSWDs (p < 0.05). The FC network involving the PCC/pC showed strong connections in the anterior-posterior pathways (mainly with the frontal cortex) at 80-250 Hz during ictal GSWDs, while the interictal GSWDs FC were mostly limited to the posterior cortex region. There was no significant difference in the magnetic source strength among interictal and ictal GSWDs at all bandwidths. Conclusions: There are significant disparities in the source localization and FC between interictal and ictal GSWDs. Low-frequency activation in the PCC/pC during inhibition of seizures possibly relates to the maintenance of consciousness during interictal GSWDs. High-frequency oscillations (HFOs) of the MFC during CAE may associate with the inducing or occurrence of GSWDs. Weakened network connections may be in favor of preventing overexcitability and relates to the termination of GSWDs.

[Comparison of Cookgas and Fastrach intubating laryngeal mask airway with fiberoptic bronchoscope in anticipated difficult airway management].

OBJECTIVE: To compare the clinical effectiveness of fiberoptic bronchoscope (FOB)-guided intubation through the Cookgas intubating laryngeal airway(CILA)and the Fastrach intubating laryngeal mask airway (FT-LMA) in the management of anticipated difficult airways. METHODS: Sixty patients with all three difficult intubation criterion (thyromental distance<60 mm, interincisor distance<35 mm, and Mallampati class 3 or 4) undergoing elective plastic surgery under general anesthesia were randomly allocated into CILA group (n=30) and FT-LMA group (n=30). After anesthesia being induced and CILA or FT-LMA being inserted, the patients were treated with FOB-guided intubation through CILA or FT-LMA. The success of the intubating laryngeal airway(ILA)insertion and FOB-guided intubation, the number of attempts, and the duration of the successful attempt were recorded. RESULTS: The ILA was inserted successfully in 30 patients from CILA group and 27 patients from FT-LMA group. Three failed cases in FT-LMA group were inserted successfully with CILA. In CILA group, the first FOB-guided intubation attempt succeeded in 26 patients, and 4 cases were intubated at the second attempt. In 27 patients of FT-LMA group, 20 cases were intubated successfully at the first attempt, 4 cases at the second attempt, and 3 cases failed; of these three failed patients, two patients were intubated smoothly with FOB through CILA at the first attempt, one was intubated by FOB via CILA at the second attempt. The duration of FT-LMA insertion [(35.3±12.8)s] was significantly longer when compared with CILA [(23.9±17.5)s] (P<0.05). However, the duration of FOB-guided intubation through CILA and FT-LMA [(48.6±13.5)s vs.(53.2±14.2)s] and the time of ILA removal [(40.4±10.2)s vs. (38.5±11.3)s] were not significantly different between these two groups (P>0.05). The adverse events during and after intubtion were not significantly different between these two groups. CONCLUSIONS: FOB-guided intubation through CILA and FT-LMA is safe and feasible for the management of anticipated difficult airways. However, in patients with severe scar contracture of face and neck and those with huge expander in neck, the CILA insertion and FOB-guided intubation via CILA is superior to FT-LMA.

CD105/Ki67 coexpression correlates with tumor progression and poor prognosis in epithelial ovarian cancer.

AIM: To analyze the expression patterns of CD105 and Ki67 in human epithelial ovarian cancer (EOC) and to evaluate the clinical significance of these two markers in the progression and prognosis in EOC. MATERIALS AND METHODS: The CD105 and Ki67 protein expression patterns in paraffin-embedded specimens gathered from 166 patients with EOC were detected by immunohistochemistry analysis. The association of CD105 and Ki67 protein expression with the prognosis in EOC was subsequently assessed. RESULTS: The CD105 and Ki67 proteins were positively expressed in 101/166 (60.8%) and 129/166 (77.7%) of EOC patients, respectively. The CD105 tumors are more likely to have higher tumor grade (P = 0.02). Patients with positive Ki67 staining are more likely to be at the advanced stage of the disease (P = 0.008). Marker CD105 was positively correlated with Ki67 (r = 0.66, P = 0.01). In addition, Ki67 (hazards ratio [HR], 4.8; confidence interval [CI], 1.2-16.6; P = 0.008) and CD105⁺ (HR, 4.1; CI, 1.0-15.2; P = 0.01) were both independent prognostic factors for poor overall survival in EOC patients. Furthermore, combined CD105/Ki67 expression was significantly related to unfavorable overall survival (HR, 16.6; CI, 1.2-128.9; P < 0.001). CONCLUSIONS: Our results suggest that the CD105 and Ki67 expressions might be involved in the progression of EOC and patient prognosis. A combined detection of CD105/Ki67 coexpression may benefit us in predicting the prognosis in EOC.

Serine/threonine kinase gene Stpk-V, a key member of powdery mildew resistance gene Pm21, confers powdery mildew resistance in wheat.

Powdery mildew resistance gene Pm21, located on the chromosome 6V short arm of Haynaldia villosa and transferred to wheat as a 6VS·6AL translocation (T6VS·6AL), confers durable and broad-spectrum resistance to wheat powdery mildew. Pm21 has become a key gene resource for powdery mildew resistance breeding all over the world. In China, 12 wheat varieties containing Pm21 have been planted on more than 3.4 million hectares since 2002. Pm21 has been intractable to molecular genetic mapping because the 6VS does not pair and recombine with the 6AS. Moreover, all known accessions of H. villosa are immune to powdery mildew fungus. Pm21 is still defined by cytogenetics as a locus. In the present study, a putative serine and threonine protein kinase gene Stpk-V was cloned and characterized with an integrative strategy of molecular and cytogenetic techniques. Stpk-V is located on the Pm21 locus. The results of a single cell transient expression assay showed that Stpk-V could decrease the haustorium index dramatically. After the Stpk-V was transformed into a susceptible wheat variety Yangmai158, the characterized transgenic plants showed high and broad-spectrum powdery mildew resistance similar to T6VS·6AL. Silencing of the Stpk-V by virus-induced gene silencing in both T6VS·6AL and H. villosa resulted in their increased susceptibility. Stpk-V could be induced by Bgt and exogenous H(2)O(2), but it also mediated the increase of endogenous H(2)O(2), leading to cell death and plant resistance when the plant was attacked by Bgt.

[Screening hv-S/TPK from TAC library of a Triticum aestivum-Haynaldia villosa translocation line].

Hv-S/TPK gene, a resistance related gene to powdery mildew, was cloned by using genechip, and its expression was upregulated after the inoculation of Blumeria graminis to Haynaldia villosa. Using the specific primers of Hv-S/TPK to screen a genomic TAC (Transformation-competent artificial chromosome) library of translocation line 6VS/6AL, a positive TAC was screened. A 5-kb fragment containing Hv-S/TPK was subcloned and identified. This 5160-bp fragment (GenBank Accession No. EU153366) was determined by specific primer walking. The analysis of Hv-S/TPK genomic sequence showed three introns and four extrons between start code and stop code. In the promoter region of Hv-S/TPK, there were W-box and OCS-like elements which were the elements related to disease resistance. In this study, the positive TAC clone was used to as probe in situ hybridized to mitotic metaphase chromosomes of translocation line. The result of fluorescence in situ hybridization (FISH) indicated that the TAC clone containing Hv-S/TPK was from Haynaldia villosa chromosome.

Expression level of wild-type survivin in gastric cancer is an independent predictor of survival.

AIM: Survivin is a novel antiapoptotic gene in which three splicing variants have been recently cloned and characterized. Survivin has been found to be abundantly expressed in a wide variety of human malignancies, whereas it is undetectable in normal adult tissues. We aimed to study the expression of three survivin splicing variants in gastric cancer, and to evaluate the prognostic significance of the expression of survivin variants in gastric cancer. METHODS: Real time quantitative RT-PCR was performed to analyze the expression of survivin variants in 79 paired tumors and normal gastric mucosa samples at the mRNA level. Proliferative and apoptotic activity was measured using Ki-67 immunohistochemical analysis and the TUNEL method, respectively. RESULTS: All the cases tested expressed wild-type survivin mRNA, which was not only the dominant transcript, but also a poor prognostic biomarker (P = 0.003). Non-antiapoptostic survivin-2B mRNA was correlated with tumor stage (P = 0.001), histological type (P = 0.004), and depth of tumor invasion (P = 0.041), while survivin-DeltaEx3 mRNA showed a significant association with apoptosis (P = 0.02). CONCLUSION: Wild-type survivin mRNA expression levels are of important prognostic value and significant participation of survivin-2B and survivin-DeltaEx3 is suggested in gastric cancer development.

[Elevated expression level of wild-type survivin in gastric cancer promotes in vitro docetaxel-resistance].

OBJECTIVE: To study the expression of three survivin splicing variants in gastric cancer and to evaluate the significant correlation between survivin variants' expression and chemoresistance in gastric cancer. METHODS: Real time quantitative RT-PCR was used to analyze the mRNA expression of survivin variants in 39 gastric tumor specimens resected during operation. The clinical resistance to anticancer agents [CDDP, MMC, 5-Fu, docetaxel (Taxotere TXT), and GEM] was analyzed by histoculture drug-response assay (HDRA). RESULTS: Among the 39 tumor samples, survivin expression was detected in all tumor samples (39/39); 79.5% (31/39) of the samples demonstrated survivin-2B expression and 66.7% (26/39) of the samples had survivin-Delta Ex3 expression. HDRA showed that the in vitro efficacy rates of CDDP, MMC, 5Fu, TXT, and GEM were 36.8% (14/38), 31.2% (10/32), 23.1% (9/39), 20.5% (8/39), and 12.5% (4/32) respectively, equivalent to the previous HDRA studies and historical clinical studies in gastric cancer patients. The expression rate of wild-type survivin was significantly higher in the group of chemoresistance to TXT than in the group sensitive to docetaxel (P = 0.021). CONCLUSION: Elevated expression level of wild-type survivin promotes docetaxel-resistance in patients with gastric cancer.