Assessment of electroencephalography and event-related potentials in unresponsive patients with brain injury.

OBJECTIVE: To investigate the predictors of clinical outcomes in unresponsive patients with acquired brain injuries. METHODS: Patients with coma or disorders of consciousness were enrolled from August 2019 to March 2021. A retrospective analysis of demographics, etiology, clinical score, diagnosis, electroencephalography (EEG), and event-related potential (ERP) data from 1 week to 2 months after coma onset was conducted. Findings were assessed for predicting favorable outcomes at 6 months post-coma, and functional outcomes were determined using the Glasgow Outcome Scale-Extended (GOS-E). RESULTS: Of 68 patients, 22 patients had a good neurological outcome at 6 months, while 11 died. Univariate analysis showed that motor response (Motor-R; p < 0.001), EEG pattern (p = 0.015), sleep spindles (p = 0.018), EEG reactivity (EEG-R; p < 0.001), mismatch negativity (MMN) amplitude at electrode Fz (FzMMNA; p = 0.001), P3a latency (p = 0.044), and P3a amplitude at electrode Cz (CzP3aA; p < 0.001) were significantly correlated with patient prognosis. Multivariable logistic regression analysis showed that FzMMNA, CzP3aA, EEG-R, and Motor-R were significant independent predictors of a favorable outcome. The sensitivity and specificity of FzMMNA (dichotomized at 1.16 µV) were 86.4% and 58.5%, and of CzP3aA (cut-off value 2.76 µV) were 90.9% and 70.7%, respectively. ERP amplitude (ERP-A), a combination of FzMMNA and CzP3aA, improved prediction accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.884. A model incorporating Motor-R, EEG-R, and ERP-A yielded an outstanding predictive performance (AUC=0.921) for a favorable outcome. CONCLUSION: ERP-A and the prognostic model resulted in the efficient prediction of a favorable outcome in unresponsive patients.

Hemgn Protects Hematopoietic Stem and Progenitor Cells Against Transplantation Stress Through Negatively Regulating IFN-γ Signaling.

Hematopoietic stem and progenitor cells (HSPCs) possess the remarkable ability to regenerate the whole blood system in response to ablated stress demands. Delineating the mechanisms that maintain HSPCs during regenerative stresses is increasingly important. Here, it is shown that Hemgn is significantly induced by hematopoietic stresses including irradiation and bone marrow transplantation (BMT). Hemgn deficiency does not disturb steady-state hematopoiesis in young mice. Hemgn-/- HSPCs display defective engraftment activity during BMT with reduced homing and survival and increased apoptosis. Transcriptome profiling analysis reveals that upregulated genes in transplanted Hemgn-/- HSPCs are enriched for gene sets related to interferon gamma (IFN-γ) signaling. Hemgn-/- HSPCs show enhanced responses to IFN-γ treatment and increased aging over time. Blocking IFN-γ signaling in irradiated recipients either pharmacologically or genetically rescues Hemgn-/- HSPCs engraftment defect. Mechanistical studies reveal that Hemgn deficiency sustain nuclear Stat1 tyrosine phosphorylation via suppressing T-cell protein tyrosine phosphatase TC45 activity. Spermidine, a selective activator of TC45, rescues exacerbated phenotype of HSPCs in IFN-γ-treated Hemgn-/- mice. Collectively, these results identify that Hemgn is a critical regulator for successful engraftment and reconstitution of HSPCs in mice through negatively regulating IFN-γ signaling. Targeted Hemgn may be used to improve conditioning regimens and engraftment during HSPCs transplantation.

Atorvastatin combined with dexamethasone in chronic subdural haematoma (ATOCH II): study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. METHODS: The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days. DISCUSSION: This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. TRIAL REGISTRATION: ChiCTR, ChiCTR1900021659 . Registered on 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157 .

Trans-base and trans-vault low-velocity penetrating brain injury: A retrospective comparative study of characteristics, treatment, and outcomes.

PURPOSE: Low-velocity penetrating brain injury (LVPBI) caused by foreign bodies can pose life-threatening emergencies. Their complexity and lack of validated classification data have prevented standardization of clinical management. We aimed to compare the trans-base and trans-vault phenotypes of LVPBI to help provide guidance for clinical decision-making of such injury type. METHODS: A retrospective study on LVPBI patients managed at our institution from November 2013 to March 2020 was conducted. We included LVPBI patients admitted for the first time for surgery, and excluded those with multiple injuries, gunshot wounds, pregnancy, severe blunt head trauma, etc. Patients were categorized into trans-base and trans-vault LVPBI groups based on the penetration pathway. Discharged patients were followed up by outpatient visit or telephone. The data were entered into the Electronic Medical Record system by clinicians, and subsequently derived by researchers. The demography and injury characteristics, treatment protocols, complications, and outcomes were analyzed and compared between the two groups. A t-test was used for analysis of normally distributed data, and a Mann-Whitney U test for non-parametric data. A generalized linear model was further established to determine whether the factors length of stay and performance scale score were influenced by each factor. RESULTS: A total of 27 LVPBI patients were included in this analysis, comprised of 13 (48.1%) trans-base cases and 14 (51.9%) trans-vault cases. Statistical analyses suggested that trans-base LVPBI was correlated with deeper wounds; while the trans-vault phenotype was correlated with injury by metal foreign bodies. There was no difference in Glasgow Coma Scale score and the risk of intracranial hemorrhage between the two groups. Surgical approaches in the trans-base LVPBI group included subfrontal (n = 5, 38.5%), subtemporal (n = 5, 38.5%), lateral fissure (n = 2, 15.4%), and distal lateral (n = 1, 7.7%). All patients in the trans-vault group underwent a brain convex approach using the foreign body as reference (n = 14, 100%). Moreover, the two groups differed in application prerequisites for intracranial pressure monitoring and vessel-related treatment. Trans-base LVPBI was associated with higher rates of cranial nerve and major vessel injuries; in contrast, trans-vault LVPBI was associated with lower functional outcome scores. CONCLUSION: Our findings suggest that trans-base and trans-vault LVPBIs differ in terms of characteristics, treatment, and outcomes. Further understanding of these differences may help guide clinical decisions and contribute to a better management of LVPBIs.

Clinical significance of mismatch negativity in predicting the awakening of comatose patients after severe brain injury.

We assessed the clinical significance of mismatch negativity (MMN) in predicting the awakening of comatose patients with severe brain injury. The clinical data of patients with severe brain injury, admitted to the neurosurgical intensive care unit of Xiangya Hospital of Central South University from July 2018 to March 2020, who underwent auditory MMN examinations within 28 days after coma onset, were reviewed. Correlations between clinical factors and prognosis [Glasgow Outcome Scale (GCS) for 3 mo] were analyzed. Fifty-three patients were included; 37 (69.8%) had favorable outcomes. A univariate analysis revealed the Glasgow Coma Scale (GCS) and absolute MMN amplitudes at electrodes Fz and Cz were significantly correlated with prognosis. Only GCS scores and MMN amplitude at Fz were independent predictors in multivariate logistic regression analysis (area under the curve 0.744 vs. 0.753, respectively); both combined, improved accuracy to 84.6%. MMN amplitudes at Fz were dichotomized at a value of 1.08 µV with a sensitivity and specificity of 81.1% and 68.7%, respectively, for predicting comatose patients' awakening. In conclusion, MMN amplitude at Fz is a reliable prognostic indicator for comatose patients with severe brain injury; the prediction value improved when combined with GCS. Thus, an event-related potential component with a clear site and cutoff value may support prognostication in severe brain injury.NEW & NOTEWORTHY Mismatch negativity (MMN) can assess the prognosis of comatose patients after severe brain injury, especially for MMN amplitude. In addition, MMN analysis at electrode Fz best predicts recovery of consciousness in patients with severe brain injury. Importantly, a quantitative approach (cutoff value of 1.08 µV) may improve the use of MMN for prognostication.

MiRNA-873-5p Acts as a Potential Novel Biomarker and Promotes Cervical Cancer Progression by Regulating ZEB1 via Notch Signaling Pathway.

OBJECTIVE: Our group aimed to investigate the expression pattern of miRNA-873-5p in cervical cancer (CC) patients and its association with CC progression. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied for the examination of the expressions of miRNA-873-5p in both CC specimens and cell lines. The clinical significance of miRNA-873-5p was statistically analyzed. MTT, colony formation, Transwell and flow cytometry assays were used to detect cell proliferation, metastasis, and apoptosis changes of Hela and Siha cell line. Luciferase reporter assays and Western blots were utilized to identify the target genes of miRNA-873-5p. Western blot and RT-PCR were used to judge the dysregulation of Notch signaling. RESULTS: Our results indicated that miRNA-873-5p expression was distinctly reduced in CC patients. Low miRNA-873-5p expressions were distinctly correlated with positively distant metastasis, The International Federation of Gynecology and Obstetrics (FIGO) stage and poor prognosis of CC patients. A functional assay using miRNA-873-5p mimics indicated that overexpression of miRNA-873-5p distinctly suppressed CC cells proliferation and metastasis, and promoted apoptosis. Bioinformatic assays revealed that miRNA-873-5p may target the 3'-UTR of ZEB1 and lead to the suppression of its translation, which was verified by the use of luciferase assays. Finally, overexpression of miRNA-873-5p suppressed the expressions of Jag1, Maml2 and Hey1. CONCLUSION: Taken together, we firstly provided evidence that miRNA-873-5p expression was a poor favorable factor for CC patients, and the use of miRNA-873-5p may represent a and potential biomarker and promising therapeutic approach for CC.

LncRNA NEAT1 promotes malignant phenotypes and TMZ resistance in glioblastoma stem cells by regulating let-7g-5p/MAP3K1 axis.

Glioblastoma multiforme (GBM) is one of the most malign brain tumors in adults. Temozolomide (TMZ) is an oral chemotherapy drug constituting the backbone of chemotherapy regimens utilized as first-line treatment of GBM. However, resistance to TMZ often leads to treatment failure. In the present study, we explored the expression and related mechanisms of nuclear enriched abundant transcript 1 (NEAT1) in glioma stem cells (GSCs). Quantitative real-time PCR (qRT-PCR) showed that NEAT1 was up-regulated in serum samples of GBM patients and GSCs isolated from U87, U251 cell lines. Functional experiments showed that NEAT1 knockdown restrained malignant behaviors of GSC, including proliferation, migration and invasion. Dual-luciferase assays identified let-7g-5p was a downstream target and negatively adjusted by NEAT1. Restoration of let-7g-5p impeded tumor progression by inhibiting proliferation, migration and invasion. Mitogen-activated protein kinase kinase kinase 1 (MAP3K1), as a direct target of let-7g-5p, was positively regulated by NEAT1 and involved to affect the regulation of NEAT1 on GSCs' behaviors. In conclusion, our results suggested that NEAT1 promoted GSCs progression via NEAT1/let-7g-5p/MAP3K1 axis, which provided a depth insight into TMZ resistance mechanism.

EDAG mediates Hsp70 nuclear localization in erythroblasts and rescues dyserythropoiesis in myelodysplastic syndrome.

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients.

[Dynamics of Proliferation and Differentiation after Transplantation of Hematopoietic Cells in Mouse].

OBJECTIVE: To investigate the effects of Listeria monocytogenes infection on hematopoietic stem and progenitor cell (HSPC) composition, cell cycle and cell colony-forming ability in mouse bone marrow. METHODS: The C57BL/6J mice were divided into infected group and control group. The mice in injected group were infected intraperitoneally with 6.7×106 CFU Listeria monocytogenes,while the mice in control group were injecfed with PBS of same volume.The serum levels of IFNγ were detected at different time points. After 24 hours, the HS/PC composition, cell cycle and cell colony-forming ability in bone marrow of mice were measured, and the difference between the control group and the infected group was statistically analyzed. RESULTS: Serum IFNγ levels peaked at 24 hours after infection with Listeria monocytogenes. After 24 h, the proportion of LSK, LSK in S phase, and short-term hematopoietic stem cells (ST-HSC) in the infected group were significantly higher than those in the control group (P＜0.001), long-term hematopoietic stem cells (LT-HSC) and the proportion of LT-HSC in S phase were significantly increased (P＜0.01), and the cell colony-forming ability of bone marrow significantly decreased (P＜0.01). [WTHZ]Conclusion: [WTB1]After infection with Listeria monocytogenes, bone marrow hematopoietic stem cells enter the proliferative state from rest, the cell colony-forming ability decreases, suggesting that Listeria monocytogenes infection can cause hematopoietic stem cell depletion.

Traumatic brain injury in China.

China has more patients with traumatic brain injury (TBI) than most other countries in the world, making this condition a major public health concern. Population-based mortality of TBI in China is estimated to be approximately 13 cases per 100 000 people, which is similar to the rates reported in other countries. The implementation of various measures, such as safety legislation for road traffic, establishment of specialised neurosurgical intensive care units, and the development of evidence-based guidelines, have contributed to advancing prevention and care of patients with TBI in China. However, many challenges remain, which are augmented further by regional differences in TBI care. High-level care, such as intracranial pressure monitoring, is not universally available yet. In the past 30 years, the quality of TBI research in China has substantially improved, as evidenced by an increasing number of clinical trials done. The large number of patients with TBI and specialised trauma centres offer unique opportunities for TBI research in China. Furthermore, the formation and development of research collaborations between China and international groups are considered essential to advancing the quality of TBI care and research in China, and to improve quality of life in patients with this condition.

Effects of Brain Temperature on the Outcome of Patients with Traumatic Brain Injury: A Prospective Observational Study.

A prospective observational study collected temperature data from 51 patients in 11 neurosurgical centers and follow-up outcome information at 6 months in 49 patients. Brain temperature (Tbr) was measured directly by an intraventricular temperature sensor. Axillary temperature (Tax) and rectal temperature (Tre) were measured by electric thermometers. Tbr was 0.4 to 1.5°C higher than body temperature. Tre correlated well with the Tbr (coefficient: 0.7378; p < 0.05). Among all patients, Glasgow Coma Scale (GCS) scores on admission were significantly lower in the patients with post-operatively extreme peak temperature (Tpeak, < 37°C or >39°C in first 24 h) and major temperature variation (Tvari > 1°C in first 12 h; p < 0.05, p < 0.01, respectively). Among the patients with no temperature intervention, the extreme Tpeak group showed a lower Glasgow Outcome Scale-Extended (GOS-E) score at 6 months (p < 0.05) with lower GCS scores on admission (p < 0.01), compared with the moderate Tpeak group. Remarkably, the major Tvari group showed significantly lower GOS-E scores (p < 0.05) with the same GCS scores as the minor Tvari group. Thus, Tre is the better candidate to estimate Tbr. Spontaneously extreme Tpeak in TBI represents both more serious injury on admission and worse prognosis, and Tvari might be used as a novel prognostic parameter in TBI. Brain temperature is therefore one of the critical indicators evaluating injury severity, prognostication, and monitoring in the management of TBI. This prospective observational study has been registered in ClinicalTrials.gov ( https://clinicaltrials.gov ), and the registration number is NCT03068143.

EDAG promotes the expansion and survival of human CD34+ cells.

EDAG is multifunctional transcriptional regulator primarily expressed in the linloc-kit+Sca-1+ hematopoietic stem cells (HSC) and CD34+ progenitor cells. Previous studies indicate that EDAG is required for maintaining hematopoietic lineage commitment balance. Here using ex vivo culture and HSC transplantation models, we report that EDAG enhances the proliferative potential of human cord blood CD34+ cells, increases survival, prevents cell apoptosis and promotes their repopulating capacity. Moreover, EDAG overexpression induces rapid entry of CD34+ cells into the cell cycle. Gene expression profile analysis indicate that EDAG knockdown leads to down-regulation of various positive cell cycle regulators including cyclin A, B, D, and E. Together these data provides novel insights into EDAG in regulation of expansion and survival of human hematopoietic stem/progenitor cells.

Fibroblasts play a potential role in bone destruction via osteopontin related caldesmon expression and polymerization in human non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. The elucidation of the mechanisms of aggressive NFPAs in bone destruction is required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, we investigated the differential proteomics of fibroblasts isolated from clinical specimens of NFPAs with or without bone destruction. Proteomic analysis revealed a group of molecules associated with cytoskeleton organization, including caldesmon, were differentially expressed between fibroblasts isolated from bone destruction NFPAs (BD-NFPAs) and fibroblasts isolated from non-bone destruction NFPAs (NBD-NFPAs). The secreted proteins analysis found that osteopontin was significantly upregulated in BD-NFPAs fibroblasts. Furthermore, immunohistochemical staining of the NFPAs clinical samples showed that the expression of caldesmon in stromal cells and the expression of osteopontin in both tumor cells and stroma were significantly increased in BD-NFPAs. Taken together, our results indicate a possible way that osteopontin secreted from both NFPA cells and surrounding fibroblasts modify caldesmon expression and polymerization in fibroblasts, which may contribute to bone destruction in NFPA patients.

The role of Dickkopf family in cancers: from Bench to Bedside.

Numerous epidemiological studies indicate that cancer will be responsible for millions of deaths in one year. Although multiple therapeutic strategies exist, and vast research efforts are being focused on developing newer and better regimens, cancer-related morbidity and mortality remain high. Metastasis and recurrence are prominent causes of treatment failure in cancers. Moreover, early diagnosis and treatment initiation are difficult to achieve in clinical practice. Fortunately, targeted therapy, which exerts its function at the molecular level, has proved to be greatly beneficial in several human diseases including cancers. The Wnt signaling pathway is a crucial regulator of embryogenesis and development in humans, and its dysfunction has been implicated in the incidence and development of cancers and other diseases. The Dickkopf family (Dkks) is a widely studied Wnt signaling pathway antagonist and plays multiple roles in human physiological and pathological process through both Wnt pathway-dependent and -independent manners. However, the precise roles of Dkks in tumorigenesis and the causal mechanisms have not been clearly elucidated. We discuss the pleiotropic roles of Dkks, with a specific focus on the underlying mechanisms, in cancer biology. We review recent literature to explore the potential use of Dkks as a tumor diagnosis biomarker and therapeutic target.

Bleomycin Suppresses the Proliferation and the Mobility of Human Gastric Cancer Cells Through the Smad Signaling Pathway.

BACKGROUND/AIMS: Extensive studies have demonstrated that Bleomycin (BLM) is a glycopeptide antibiotic that has been used as an anticancer chemotherapeutic reagent. It can induce both single- and double-strand DNA damage, inhibit synthesis of DNA, suppress proliferation, and induce apoptosis in cancer cells. Smad signaling transducers are considered as important molecules in tumor development and progression, and may closely be related to the biological behaviors of some malignant carcinomas, including gastric cancer. METHODS: The effects of different concentrations of BLM on the proliferation, cell cycle, apoptosis, migration, and invasion on gastric cancer cell lines MKN45 and AGS were assayed by using CCK-8 assay, Annexin V/PI double staining, PI staining, and transwell assay. Western blot and Immunohistochemistry were applied to analyze the potential mechanism(s). RESULTS: BLM treatment resulted in a low proliferation, high apoptosis, low migration and invasion in MKN45 and AGS cells. Furthermore, the possible mechanisms underlying that Smad3 activity could be changed after binding with BLM, and subsequently the Smad signaling pathway had a cascade response. CONCLUSION: These results highlight BLM as an exciting theme for gastric cancer treatment, which may represent an effective clinical therapeutic reagent for gastric cancer patients.

Aldehyde dehydrogenase 1 expression correlates with clinicopathologic features of patients with breast cancer: a meta-analysis.

A number of studies have investigated the relationship between aldehyde dehydrogenase 1 (ALDH1) expression and the clinical pathological features of the patients with breast cancer. However, conclusions reported by different parties seem to be inconsistent. We have reviewed published studies and carried out this meta-analysis to provide credible results. We searched PubMed for articles published in English until September 12, 2014. Our main analyses were focused on the association between ALDH1 and the clinical pathological features, such as age, tumor size, nodal status, lymphovascular invasion, histological grade, and the expression of ER, PR, and HER2 by meta-analysis methods. If heterogeneity was observed, we used random effects model to calculate the overall odds ratios, otherwise fixed effects model was used. Twenty-one eligible studies were included in the present meta-analysis. From the pooled analyses, there was significant association between ALDH1 expression and histological grade (low vs. intermediate: pooled OR = 1.51, 95% CI: 1.09-2.10, P = 0.01; intermediate vs. high: pooled OR = 1.86, 95% CI: 1.12-3.07, P = 0.02), ER expression (pooled OR = 0.41, 95% CI: 0.29-0.58, P < 0.00001), and PR expression (pooled OR = 0.56, 95% CI: 0.40-0.77, P = 0.0004). No clear correlation was found between ALDH1 expression and age, tumor size, lymph node (LN) metastasis, lynphovascular invasion, and HER2 expression (P > 0.05). Despite the inconsistency in the published reports, this meta-analysis provides credible evidence to support the association between ALDH1 and breast cancer. However, it is necessary to conduct large sample studies using standardized and well-matched controls.

Common variants of KCNJ10 are associated with susceptibility and anti-epileptic drug resistance in Chinese genetic generalized epilepsies.

To explore genetic mechanism of genetic generalized epilepsies (GGEs) is challenging because of their complex heritance pattern and genetic heterogeneity. KCNJ10 gene encodes Kir4.1 channels and plays a major role in modulating resting membrane potentials in excitable cells. It may cause GGEs if mutated. The purpose of this study was to investigate the possible association between KCNJ10 common variants and the susceptibility and drug resistance of GGEs in Chinese population. The allele-specific MALDI-TOF mass spectrometry method was used to assess 8 single nucleotide polymorphisms (SNPs) of KCNJ10 in 284 healthy controls and 483 Chinese GGEs patients including 279 anti-epileptic drug responsive patients and 204 drug resistant patients. We found the rs6690889 TC+TT genotypes were lower frequency in the GGEs group than that in the healthy controls (6.7% vs 9.5%, p = 0.01, OR = 0.50[0.29-0.86]). The frequency of rs1053074 G allele was lower in the childhood absence epilepsy (CAE) group than that in the healthy controls (28.4% vs 36.2%, p = 0.01, OR = 0.70[0.53-0.93]). The frequency of rs12729701 G allele and AG+GG genotypes was lower in the CAE group than that in the healthy controls (21.2% vs 28.4%, p = 0.01, OR = 0.74[0.59-0.94] and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72-0.96], respectively). The frequency of rs12402969 C allele and the CC+CT genotypes were higher in the GGEs drug responsive patients than that in the drug resistant patients (9.3% vs 5.6%, OR = 1.73[1.06-2.85], p = 0.026 and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72-0.96], respectively). This study identifies potential SNPs of KCNJ10 gene that may contribute to seizure susceptibility and anti-epileptic drug resistance.

Prognostic value of circulating CD133(+) cells in patients with gastric cancer.

OBJECTIVES: Gastric cancer is an important cause of cancer-related mortality worldwide (1). There is increasing evidence that the existence of cancer stem cells (CSC) is responsible for tumour formation and maintenance. MATERIALS AND METHODS: The present study was designed to recognise circulating CSCs from blood samples of patients with gastric cancer, using CD133 and ABCG2 as potential markers. CD133(-) , CD133(+)  ABCG2(-) and CD133(+)  ABCG2(+) cells lines were analysed by flow cytometry, immunofluorescence staining, western blotting and real-time PCR. Furthermore, functional assays (clonogenic assay in vitro and tumourigenic assay in vivo) were also performed using these cell lines. RESULTS: Higher percentages of CD133(+) cells were identified in blood samples from gastric cancer patients compared to normal controls. In addition, we found by using Kaplan-Meier analysis, that numbers of CD133(+) cells correlated with poor prognosis gastric cancer patients. Finally, tumourigenic properties of CD133(+)  ABCG2(+) cells were determined in vitro and in vivo. CONCLUSIONS: Our in vitro and in vivo experiments demonstrated that CD133(+)  ABCG2(+) cells exhibited well-known CSC characteristics; thus when circulating they could be used as a prognostic marker for gastric cancer.

4-Di-phenyl-phosphanyl-8-methyl-1,5-naphthyridine.

In the title compound, C21H17N2P, the dihedral angles between the 1,5-naphthyridine ring system (r.m.s. deviation = 0.005 Å) and the phenyl rings are 89.18 (8) and 77.39 (8)°. The phenyl rings are almost perpendicular, making a dihedral angle of 88.12 (8)°. The only possible inter-molecular inter-action is a very weak aromatic π-π stacking inter-action [centroid-centroid separation = 3.898 (2) Å].

The relation between persistent coma and brain ischemia after severe brain injury.

AIM: To investigate the relation between brain ischemia and persistent vegetative state after severe traumatic brain injury. METHODS: The 66 patients with severe brain injury were divided into two groups: The persistent coma group (coma duration ≥10 d) included 51 patients who had an admission Glasgow Coma Scale (GCS) of 5-8 and were unconscious for more than 10 d. There were 15 patients in the control group, their admission GCS was 5-8, and were unconscious for less than 10 d. The brain areas, including frontal, parietal, temporal, occipital lobes and thalamus, were measured by Single Photon Emission Computed Tomography (SPECT). RESULTS: In the first SPECT scan, multiple areas of cerebral ischemia were documented in all patients in both groups, whereas bilateral thalamic ischemia were presented in all patients in the persistent coma group and were absented in the control group. In the second SPECT scan taken during the period of analepsia, with an indication that unilateral thalamic ischemia were persisted in 28 of 41 patients in persistent coma group(28/41,68.29%). CONCLUSION: Persistent coma after severe brain injury is associated with bilateral thalamic ischemia.